
1: Ann N Y Acad Sci. 2009 Jan;1151:133-56.

Genetic calcium signaling abnormalities in the central nervous system: seizures, 
migraine, and autism.

Gargus JJ.

Department of Physiology & Biophysics, Section of Human Genetics, School of
Medicine, University of California-Irvine, Irvine, CA 92697, USA.
jjgargus@uci.edu

The calcium ion is one of the most versatile, ancient, and universal of
biological signaling molecules, known to regulate physiological systems at every 
level from membrane potential and ion transporters to kinases and transcription
factors. Disruptions of intracellular calcium homeostasis underlie a host of
emerging diseases, the calciumopathies. Cytosolic calcium signals originate
either as extracellular calcium enters through plasma membrane ion channels or
from the release of an intracellular store in the endoplasmic reticulum (ER) via 
inositol triphosphate receptor and ryanodine receptor channels. Therefore, to a
large extent, calciumopathies represent a subset of the channelopathies, but
include regulatory pathways and the mitochondria, the major intracellular calcium
repository that dynamically participates with the ER stores in calcium signaling,
thereby integrating cellular energy metabolism into these pathways, a process of 
emerging importance in the analysis of the neurodegenerative and neuropsychiatric
diseases. Many of the calciumopathies are common complex polygenic diseases, but 
leads to their understanding come most prominently from rare monogenic
channelopathy paradigms. Monogenic forms of common neuronal disease
phenotypes-such as seizures, ataxia, and migraine-produce a constitutionally
hyperexcitable tissue that is susceptible to periodic decompensations. The gene
families and genetic lesions underlying familial hemiplegic migraine,
FHM1/CACNA1A, FHM2/ATP1A2, and FHM3/SCN1A, and monogenic mitochondrial migraine
syndromes, provide a robust platform from which genes, such as CACNA1C, which
encodes the calcium channel mutated in Timothy syndrome, can be evaluated for
their role in autism and bipolar disease.

Publication Types: 
    Review

PMID: 19154521 [PubMed - indexed for MEDLINE]

2: Cephalalgia. 2009 Feb;29(2):269-78.

Body mass index, migraine, migraine frequency and migraine features in women.

Winter AC, Berger K, Buring JE, Kurth T.

Institute of Epidemiology and Social Medicine, University of Münster, Münster,
Germany.

We evaluated the association of body mass index (BMI) with migraine and migraine 
specifics in a cross-sectional study of 63 467 women aged > or = 45 years, of
whom 12,613 (19.9%) reported any history of migraine and 9195 had active
migraine. Compared with women without migraine and a BMI < 23 kg/m(2), women with
a BMI > or = 35 kg/m(2) had adjusted odds ratios (ORs) (95% confidence intervals)
of 1.03 (0.95, 1.12) for any history of migraine. Findings were similar for
active migraineurs. Women with a BMI of > or = 35 kg/m(2) had increased risk for 
low and high migraine frequency, with the highest estimate for women who reported
daily migraine. Compared with women with the lowest associated risk (migraine
frequency < 6 times/year; BMI between 27.0 and 29.9 kg/m(2)), women with a BMI > 
or = 35 kg/m(2) had an OR of daily migraine of 3.11 (1.12, 8.67). Among the women
with active migraine, a BMI > or = 35 kg/m(2) was associated with increased risk 
of phonophobia and photophobia and decreased risk of a unilateral pain
characteristic and migraine aura. Our data confirm previous findings that the
association between BMI with migraine is limited to migraine frequency and
specific migraine features.

Publication Types: 
    Research Support, N.I.H., Extramural

PMID: 19143772 [PubMed - indexed for MEDLINE]

3: Indian J Pediatr. 2008 Nov;75(11):1139-48. Epub 2009 Jan 7.

Management of pediatric migraine: Current concepts and controversies.

Hung RM, MacGregor DL.

Division of Neurology, Department of Pediatrics, The Hospital for Sick Children, 
Toronto, Ontario, Canada.

Migraine in children and adolescents is a common condition. Emerging knowledge
about the pathophysiology of migraine is leading to new targeted treatments
toward specific mechanisms of migraine. This review explores the evidence for
different treatments for pediatric migraine including the periodic syndromes of
childhood that commonly represent precursors to migraine.

Publication Types: 
    Review

PMID: 19132316 [PubMed - indexed for MEDLINE]

4: AAOHN J. 2008 Dec;56(12):495-500; quiz 501-502.

Working through a migraine: addressing the hidden costs of workplace headaches.

Weiss MD, Bernards P, Price SJ.

Weiss Health Group, LLC, Neenah, WI, USA.

The financial and personal impact of migraines in the workplace is substantial.
Effective management of workplace migraines includes screening, prevention, and
effective treatment. Worksite screeners are available to detect the burden of
undiagnosed migraine in the workplace. Decreasing the personal and financial
impact of migraines in the workplace requires a variety of strategies predicated 
on collaborative efforts among workers, occupational health nurses, other
providers, and management.

Publication Types: 
    Review

PMID: 19119716 [PubMed - indexed for MEDLINE]

5: Headache. 2008 Nov-Dec;48 Suppl 3:S131-41.

Menstrual migraine: case studies of women with estrogen-related headaches.

Hutchinson SL, Silberstein SD.

Orange County Migraine and Headache Center, University of California, Irvine, CA,
USA.

This paper presents 2 case scenarios that illustrate the complexity of diagnosing
and managing migraine associated with hormonal changes. Migraine is commonly
associated with comorbidies such as depression, anxiety, obesity, cardiovascular 
disease, as well as other conditions, thereby making management more challenging 
for the physician and the patient. The first case is a 35-year-old woman who has 
migraine almost exclusively during menstruation. She is under a physician's care 
for long-term management of premenstrual dysphoric disorder (PMDD). Achieving a
differential diagnosis of pure menstrual migraine is illustrated, and a detailed 
treatment plan including use of a migraine miniprophylaxis protocol, management
of her PMDD, and prescription of acute treatment medications is reviewed. The
second case scenario describes the diagnosis of menstrually associated migraine
in a woman who suffers from a frequent disabling migraine along with work-related
anxiety and depression. This paper reviews her differential diagnosis, laboratory
testing, treatment plan, including management of her comorbid anxiety and
depressive symptoms.

Publication Types: 
    Case Reports
    Review

PMID: 19076659 [PubMed - indexed for MEDLINE]

6: Headache. 2008 Nov-Dec;48 Suppl 3:S124-30.

Epidemiology and biology of menstrual migraine.

Martin VT, Lipton RB.

Department of Internal Medicine, University of Cincinnati, Cincinnati, OH, USA.

Migraine is frequently associated with menstruation in female migraineurs, and
consequently it is commonly referred to as menstrually associated migraine. The
trigger thought to be partially responsible for menstrually associated migraine
is a significant drop in circulating estrogen that is noted during 2-3 days prior
to onset of menses. It is estimated that approximately 50% of women have an
increased risk of experiencing migraine during the premenstrual phase of
decreasing estrogen levels. Understanding the biological basis of migraine
associated with menses will facilitate an accurate diagnosis and help patients
recognize time susceptible to migraine exacerbations. This paper will review the 
biological bases for the hormonal changes that occur during the menstrual cycle
and review the prevalence and burden of menstrual migraine among female headache 
sufferers.

Publication Types: 
    Review

PMID: 19076658 [PubMed - indexed for MEDLINE]

7: Headache. 2008 Nov-Dec;48 Suppl 3:S115-23.

Diagnosis and treatment of the menstrual migraine patient.

Silberstein SD, Hutchinson SL.

Thomas Jefferson University, Philadelphia, PA, USA.

Women presenting with recurrent disabling headache frequently have migraine; but 
physicians need to rule out other headache disorders before they reach a
diagnosis of migraine with or without aura. Many women who experience migraine in
close association to their menstrual cycle may meet the diagnostic criteria for
either menstrually related migraine (MRM), or pure menstrual migraine (PMM). Once
an accurate diagnosis is made, treatment may be established to best suit the
individual needs of that patient. Most women will find that migraine associated
with hormone fluctuations respond well to standard treatment approaches including
pharmacological and nonpharmacological treatments. Pharmacological approaches
include acute, preventive, and short-term prophylaxis. Herein we review the
difference between non-menstrual migraine, PMM, and MRM and identify effective
treatment strategies for appropriate management of migraine associated with
hormonal fluctuations.

Publication Types: 
    Review

PMID: 19076657 [PubMed - indexed for MEDLINE]

8: Am J Med Sci. 2008 Dec;336(6):458-61.

Migraine-patent foramen ovale connection: role of prominent eustachian valve and 
large Chiari network in migrainous patients.

Rigatelli G, Dell'avvocata F, Cardaioli P, Giordan M, Braggion G, Aggio S, Roncon
L, Chinaglia M.

Section of Adult Congenital and Adult Heart Disease, Cardiovascular Diagnosis and
Endoluminal Interventions, and Neuroscience Department, Division of Neurology,
Rovigo General Hospital, Rovigo, Italy. jackyheart@hotmail.com

BACKGROUND: We postulated that eustachian valve (EV) and Chiari network (CN) play
a role in the pathophysiology of both migraine and paradoxical embolism. We
sought to prospectively investigate the potential role of EV/CN in
migraine-patent foramen ovale (PFO) connection assessing their prevalence by
intracardiac echocardiography (ICE) in patients with migraine submitted to PFO
transcatheter closure. METHODS: Over a 24-month period, we prospectively enrolled
50 consecutive patients (mean age 37+/-12.5 years, 38 females) with previous
stroke and migraine referred to our centre for PFO catheter-based closure.
Migraine with aura (MwA) and migraine without aura (MwoA) were diagnosed
according to the International Headache Society criteria and Migraine Disability 
Assessment Score (MIDAS). Patients who met the inclusion criteria for closure
underwent ICE study and closure attempt. RESULTS: After ICE study, a prominent EV
or CN were diagnosed on ICE in 41 patients (82%): 100% in MwA patients, 60% in
MwoA patients (p<0.001) and in 55.5% of patients with no migraine. Patients with 
EV and CN had more frequently a curtain pattern on TC Doppler, a larger
right-to-left shunt, more recurrent cerebral paradoxical embolism before closure,
and a higher preoperative MIDAS score. Patients with EV/CN had a larger decrease 
in MIDAS score after closure. CONCLUSIONS: This study suggests that EV and CN
have a deep impact on MwA and paradoxical embolism pathophysiology: EV, CN, and
MwA should be considered as adjunctive risk factors for paradoxical embolism in
the work-up of both symptomatic and asymptomatic PFO patients.

PMID: 19092317 [PubMed - indexed for MEDLINE]

9: BMC Med Genet. 2008 Dec 16;9:109.

Investigation of gamma-aminobutyric acid (GABA) A receptors genes and migraine
susceptibility.

Fernandez F, Esposito T, Lea RA, Colson NJ, Ciccodicola A, Gianfrancesco F,
Griffiths LR.

Genomics Research Centre, Griffith Institute for Health and Medical Research,
Griffith University, Gold Coast, Queensland, Australia.
f.fernandez@griffith.edu.au

BACKGROUND: Migraine is a neurological disorder characterized by recurrent
attacks of severe headache, affecting around 12% of Caucasian populations. It is 
well known that migraine has a strong genetic component, although the number and 
type of genes involved is still unclear. Prior linkage studies have reported
mapping of a migraine gene to chromosome Xq 24-28, a region containing a cluster 
of genes for GABA A receptors (GABRE, GABRA3, GABRQ), which are potential
candidate genes for migraine. The GABA neurotransmitter has been implicated in
migraine pathophysiology previously; however its exact role has not yet been
established, although GABA receptors agonists have been the target of therapeutic
developments. The aim of the present research is to investigate the role of the
potential candidate genes reported on chromosome Xq 24-28 region in migraine
susceptibility. In this study, we have focused on the subunit GABA A receptors
type epsilon (GABRE) and type theta (GABRQ) genes and their involvement in
migraine. METHODS: We have performed an association analysis in a large
population of case-controls (275 unrelated Caucasian migraineurs versus 275
controls) examining a set of 3 single nucleotide polymorphisms (SNPs) in the
coding region (exons 3, 5 and 9) of the GABRE gene and also the I478F coding
variant of the GABRQ gene. RESULTS: Our study did not show any association
between the examined SNPs in our test population (P>0.05). CONCLUSION: Although
these particular GABA receptor genes did not show positive association, further
studies are necessary to consider the role of other GABA receptor genes in
migraine susceptibility.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 19087248 [PubMed - indexed for MEDLINE]

10: Eur J Neurol. 2008 Dec;15(12):1279-85.

Migraine, allodynia, and implications for treatment.

Schürks M, Diener HC.

Division of Preventive Medicine, Department of Medicine, Brigham and Womens
Hospital, Harvard Medical School, Boston, MA 02215-1204, USA.
mschuerks@rics.bwh.harvard.edu

Allodynia--perception of pain from non-noxious stimuli--is a common clinical
feature in various pain syndromes. The significance for migraine has increasingly
been recognized and the pathophysiology has been investigated in detail.
Allodynia is a marker for sensitization of central trigeminal neurons. Intensity 
and persistence of allodynic symptoms are a function of duration of migraine
attacks, frequency of attacks, and migraine history. It has been hypothesized
that treatment success with triptans may be severely impaired in the presence of 
allodynia. However, randomized controlled trials did not confirm that. Treatment 
with cyclooxygenase inhibitors and dihydroergotamine does not seem to be limited 
by allodynia; these medications may be able to reverse allodynia. Data on the new
class of calcitonin-gene related-peptide antagonists are not yet available.
Additional and more refined randomized controlled trials, focusing on
methodological issues pertaining to the determination of allodynia, are warranted
to resolve the true relationship between allodynia and treatment response.
Regardless--based on available randomized controlled trials--the recommendation
prevails to initiate abortive treatment as soon as possible after attack onset
when pain is still mild.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 19068510 [PubMed - indexed for MEDLINE]

11: Psychiatry Clin Neurosci. 2008 Dec;62(6):738-40.

Severity of depressive symptoms as predictor of impairment of quality of life in 
chronic migraine: comparison with episodic migraine.

Canuet L, Ishii R, Fernandez-Concepcion O, Iwase M, Takeda M.

Department of Psychiatry, Osaka University Graduate School of Medicine, Osaka,
Japan. leo@psy.med.osaka-u.ac.jp

To identify predictors of quality of life (QoL) in episodic migraine (EM) and
chronic migraine (CM), 116 migraineurs were evaluated using the Headache Needs
Assessment (HANA). QoL was significantly more impaired in patients with CM.
Disability was a predictor of QoL in both EM and CM. Severity of depressive
symptoms emerged as a predictor of QoL in CM. QoL was also poorer in women and in
those with greater headache intensity and nausea associated with headache in the 
total sample. The present findings suggest a specific role for depressive
symptoms in impaired QoL in CM sufferers.

Publication Types: 
    Comparative Study

PMID: 19068012 [PubMed - indexed for MEDLINE]

12: Eur J Neurol. 2008 Dec;15(12):1421-3.

Comorbidity of migraine and epilepsy in a Norwegian community.

Brodtkorb E, Bakken IJ, Sjaastad O.

Department of Neuroscience, Norwegian University of Science and Technology,
Trondheim, Norway. eylert.brodtkorb@ntnu.no

BACKGROUND AND PURPOSE: Studies on the comorbidity of migraine and epilepsy have 
shown conflicting results. We wanted to explore the epidemiological association
between migraine and seizure disorders in a population-based material where case 
ascertainment was enhanced by individual specialist assessments. METHODS:
Information concerning migraine and seizure disorders was collected from 1793
participants in an interview-based survey in a circumscribed community. Mixed
headache, with features both of migraine without aura and tension-type headache, 
was excluded from further analyses because of its ambiguous character (n = 137). 
Thus, data from 1656 participants were included in the study. RESULTS: The number
of subjects with epilepsy was small, and a statistically significant association 
between migraine and the diagnosis of epilepsy was not found. There was a
tendency to more active epilepsy in subjects with migraine (1.0%, 5/524),
particularly for migraine with aura (1.8%, 3/168), compared with subjects without
migraine (0.5%, 6/1132). Migraine was present in five of 11 subjects with active 
epilepsy (45%) and in four of 28 (14%) with epilepsy in remission (P = 0.09).
CONCLUSIONS: An overall association between migraine and seizure disorders could 
not be demonstrated, but there was a tendency to more migraine in individuals
with active epilepsy.

PMID: 19049567 [PubMed - indexed for MEDLINE]

13: Acta Clin Belg. 2008 Jul-Aug;63(4):262-8.

New-onset and persistent migraine early after percutaneous atrial septal defect
closure disappear at follow-up.

Voet A, Luermans JG, Thijs V, Herroelen L, Post MC, Troost E, Budts W.

Department of Cardiology, University Hospital Leuven, Belgium.

AIMS: Recently we reported that percutaneous atrial septal defect (ASD) closure
had no influence on the prevalence of migraine during a short followup period. 12
% of patients however developed a new-onset migraine after the ASD closure. As it
has been suggested that the closing device might induce or maintain migraine
temporarily, we were interested in the prevalence of migraine at longer
follow-up. METHODS: All 75 patients included in the previous study, received the 
same structured headache questionnaire. A neurologist, blinded to previous data, 
diagnosed migraine with or without aura (MA+ or MA-) according to the
International Headache Criteria. McNemar paired X2 test was used to evaluate
changes in the occurrence of migraine. RESULTS: Seventy-one patients (94.7%)
answer the questionnaire (55 women, mean age at closure 51 +/- 18 years). Mean
follow-up time was 52 +/- 13 months. The overall migraine prevalence decreased
from 30.7% before to 22.5% after closure (P=0.21). A significant reduction was
noted in patients with new-onset migraine early after closure (n=7), where
migraine disappeared in 6 patients (P=0.031). In the group with persistent
migraine early after closure (n=13), another 6 patients became migraine-free
(P=0.031). CONCLUSION: Percutaneous ASD closure was not related to a significant 
decrease in overall migraine prevalence. However, new-onset and persistent
migraine early after closure disappeared.

PMID: 19048705 [PubMed - indexed for MEDLINE]

14: Lancet. 2008 Dec 20;372(9656):2115-23. Epub 2008 Nov 25.

Comment in:
    Lancet. 2008 Dec 20;372(9656):2089-90.

Efficacy and tolerability of MK-0974 (telcagepant), a new oral antagonist of
calcitonin gene-related peptide receptor, compared with zolmitriptan for acute
migraine: a randomised, placebo-controlled, parallel-treatment trial.

Ho TW, Ferrari MD, Dodick DW, Galet V, Kost J, Fan X, Leibensperger H, Froman S, 
Assaid C, Lines C, Koppen H, Winner PK.

Merck Research Laboratories, North Wales, PA 19454-1099, USA. tony_ho@merck.com

BACKGROUND: Calcitonin gene-related peptide (CGRP) probably has a role in
migraine pathophysiology, and antagonism of its receptors might provide treatment
without the vasoconstrictor effects of triptans. We aimed to assess the clinical 
profile of MK-0974 (telcagepant), an orally bioavailable antagonist of CGRP
receptor. METHODS: In a randomised, parallel-treatment, placebo-controlled,
double-blind, trial at 81 sites in the Europe and the USA, adults with migraine
diagnosed by International Headache Society criteria treated moderate or severe
attacks with either oral telcagepant 150 mg or 300 mg, zolmitriptan 5 mg, or
placebo. The five co-primary endpoints were pain freedom, pain relief, or absence
of photophobia, phonophobia, or nausea at 2 h after treatment. Analysis was by
the full analysis set and multiplicity was controlled for with a step-down
closed-testing procedure. This trial is registered with ClinicalTrials.gov,
number NCT00442936. FINDINGS: 1380 patients were randomly assigned to receive
telcagepant 150 mg (n=333) or 300 mg (354), zolmitriptan (345), or placebo (348).
Telcagepant 300 mg was more effective than placebo for pain freedom (95 [27%] of 
353 patients vs 33 [10%] of 343 [p<0.0001]), pain relief (194 [55%] of 353 vs 95 
[28%] of 343 [p<0.0001]), and absences of phonophobia (204 [58%] of 353 vs 126
[37%] of 342 [p<0.0001]), photophobia (180 [51%] of 353 vs 99 [29%] of 342
[p<0.0001]), and nausea (229 [65%] of 352 vs 189 [55%] of 342 [p=0.0061]).
Efficacy of telcagepant 300 mg and zolmitriptan 5 mg were much the same, and both
were more effective than telcagepant 150 mg. Adverse events were recorded for 31%
taking telcagepant 150 mg, 37% taking telcagepant 300 mg, 51% taking zolmitriptan
5 mg, and 32% taking placebo. INTERPRETATION: Telcagepant 300 mg is effective as 
an acute treatment for migraine with efficacy comparable to that of zolmitriptan 
5 mg, but with fewer associated adverse effects. FUNDING: Merck Research
Laboratories.

Publication Types: 
    Clinical Trial, Phase III
    Comparative Study
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 19036425 [PubMed - indexed for MEDLINE]

15: Headache. 2008 Oct;48(9):1356-65.

Migraine disability awareness campaign in Asia: migraine assessment for
prophylaxis.

Wang SJ, Chung CS, Chankrachang S, Ravishankar K, Merican JS, Salazar G, Siow C, 
Cheung RT, Phanthumchinda K, Sakai F.

Neurological Institute, Taipei Veterans General Hospital, National Yang-Ming
University School of Medicine, Taipei, Taiwan.

OBJECTIVES: This study aimed to survey the headache diagnoses and consequences
among outpatients attending neurological services in 8 Asian countries. METHODS: 
This survey recruited patients who consulted neurologists for the first time with
the chief complaint of headache. Patients suffering from headaches for 15 or more
days per month were excluded. Patients answered a self-administered
questionnaire, and their physicians independently completed a separate
questionnaire. In this study, the migraine diagnosis given by the neurologists
was used for analysis. The headache symptoms collected in the physician
questionnaire were based on the diagnostic criteria of migraine proposed by the
International Classification of Headache Disorders, second edition (ICHD-2).
RESULTS: A total of 2782 patients (72% females; mean age 38.1 15.1 years)
finished the study.Of them, 66.6% of patients were diagnosed by the neurologists 
to have migraine, ranging from 50.9% to 85.8% across different countries.Taken as
a group, 41.4% of those patients diagnosed with migraine had not been previously 
diagnosed to have migraine prior to this consultation. On average, patients with 
migraine had 4.9 severe headaches per month with 65% of patients missing
school,work, or household chores. Most (87.5%) patients with migraine took
medications for acute treatment. Thirty-six percent of the patients had at least 
one emergency room consultation within one year. Only 29.2% were on prophylactic 
medications. Neurologists recommended pharmacological prophylaxis in 68.2% of
patients not on preventive treatment. In comparison, migraine prevalence was the 
highest with ICHD-2 "any migraine" (ie, migraine with or without migraine and
probable migraine) (73.3%) followed by neurologist-diagnosed migraine (66.6%) and
ICHD-2 "strict migraine" (ie, migraine with or without aura only) (51.3%). About 
88.6% patients with neurologist-diagnosed migraine fulfilled ICHD-2 any migraine 
but only 67.1% fulfilled the criteria of ICHD-2 strict migraine. CONCLUSIONS:
Migraine is the most common headache diagnosis in neurological services in Asia. 
The prevalence of migraine was higher in countries with higher referral rates of 
patients to neurological services. Migraine remains underdiagnosed and
under-treated in this region even though a high disability was found in patients 
with migraine. Probable migraine was adopted into the migraine diagnostic
spectrum by neurologists in this study.

Publication Types: 
    Multicenter Study
    Research Support, Non-U.S. Gov't

PMID: 19031500 [PubMed - indexed for MEDLINE]

16: Headache. 2008 Oct;48(9):1337-42.

Memantine in the preventive treatment of refractory migraine.

Bigal M, Rapoport A, Sheftell F, Tepper D, Tepper S.

Merck Research Laboratories and the Albert Einstein College of
Medicine-Neurology, Bronx, New York, NY, USA.

OBJECTIVES: To assess the efficacy and tolerability of memantine(MEM)in the
preventive treatment of refractory migraine. BACKGROUND: Glutamate is of
importance in migraine pathophysiology and may be related to progression from
episodic to chronic migraine. Furthermore, individuals with chronic pain often
report cognitive problems. MEM has the potential to address both issues,
justifying this pilot study. METHODS: We included subjects with refractory
migraine (episodic migraine with 8-14 days of headache per month or transformed
migraine, who had previously failed at least 2 trials of adequate preventive
therapy). Other preventive drugs were allowed if the patient had been on a stable
dose for more than 30 days. MEM dose ranged from 10 mg to 20 mg per day. The
treatment phase lasted 3 months. The primary endpoint was number of days with
headache at month 3. Cognitive performance was assessed with the trail making
tests A and B (TMT-A and B). Statistical analyses were performed on the
intent-to-treat (ITT) population, using data subjected to the last observation
carried forward algorithm.We also conducted per protocol analyses. RESULTS: In
the ITT population (n = 28), monthly headache frequency was reduced from 21.8
days at baseline to 16.1 (P < .01) at 3 months. The mean number of days with
severe pain was reduced from 7.8 to 3.2 at 3 months (P < .01). The mean
disability scores were significantly reduced at 3 months, compared with baseline 
(36.6 vs 54.9, P < .01). There was a significant reduction in the time to
complete TMT-A at termination vs baseline (28.4 vs 23.2,P = .02) and also TMT-B
(70.1 vs 50.4,P = .04). Side effects were present in 37.5% of the patients; 5.5% 
dropped out the study because of poor tolerability. Most adverse events were
mild. CONCLUSION: This study offers preliminary evidence for the use of MEM in
the prevention of refractory migraine.Double-blind studies are now required.

Publication Types: 
    Clinical Trial

PMID: 19031499 [PubMed - indexed for MEDLINE]

17: Headache. 2008 Oct;48(9):1311-25.

Lay trainers with migraine for a home-based behavioral training: a 6-month
follow-up study.

Mérelle SY, Sorbi MJ, van Doornen LJ, Passchier J.

Department of Medical Psychology and Psychotherapy, Erasmus University Medical
Center, Rotterdam, the Netherlands.

OBJECTIVE: To evaluate the changes at 6-month follow-up after a home-based
behavioral training (BT) provided by lay trainers with migraine to small groups
of fellow patients. BACKGROUND: The need for self-management programs and
cost-effective treatments gave rise to this study. METHODS: In a previous
randomized controlled trial, we compared the BT group with a waitlist-control
group, receiving usual care. The control group was trained directly after their
waitlist period. The present study examined the follow-up results in both groups 
and measurements were held pre BT, post BT, and at 6-month follow-up. RESULTS:
Six months after BT, 42% was categorized as responders (>or=-50% decrease in
attack frequency), 42% did not change (-49 to 49%), and 16% responded adversely
(>or=50% increase). In the group as a whole (n = 95), attack frequency
significantly decreased from 3.0 attacks at baseline to 2.5 post BT and to 2.3 at
6-month follow-up (-23%, medium effect size 0.6). The strong improvements of
perceived control over and self-confidence in attack prevention were maintained
at follow-up. Disability and health status were unchanged but quality of life
significantly improved over time (P = .007). BT was more beneficial for patients 
who entered the training with a high attack frequency. Linear regression analysis
demonstrated that a stronger belief at baseline that the occurrence of migraine
is due to chance (external control) significantly predicted a lower attack
frequency at follow-up. CONCLUSION: Lay trainers with migraine can train small
groups of fellow patients at home in behavioral attack prevention. At 6-month
follow-up, attack frequency and quality of life were significantly but modestly
improved and feelings of control and self-confidence remained strongly improved.

Publication Types: 
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 19031498 [PubMed - indexed for MEDLINE]

18: Neurology. 2008 Nov 25;71(22):1821-8.

Excessive acute migraine medication use and migraine progression.

Bigal ME, Lipton RB.

Merck Research Laboratories, Whitehouse Station, NJ 08889, USA.
marcelo_bigal@merck.com

Long considered a chronic disorder with a stable course, recent research
demonstrates that, in a subgroup, migraine progresses to chronic migraine. Among 
the risk factors for migraine progression, acute symptomatic medication overuse
(SMO) is regarded as one of the most important. Though SMO and chronic migraine
are associated, several questions remain unanswered. First, the causal path is
controversial (SMO as a cause or consequence). Second, it is unclear if specific 
classes of medication, as well as critical doses of exposures, are necessary.
Herein we review this topic in the light of recent conducted research. Although
several caveats exist and the data should be taken with caution, important
findings are as follows: 1) Opiates are associated with migraine progression;
critical dose of exposure is around 8 days per month, and the effect is more
pronounced in men. 2) Barbiturates are also associated with migraine progression.
Critical dose of exposure is around 5 days per month and the effect is more
pronounced in women. 3) Triptans induced migraine progression in those with high 
frequency of migraine at baseline (10-14 days per month), but not overall. 4)
Anti-inflammatory medications were protective in those with <10 days of headache 
at baseline, and, as triptans, induced migraine progression in those with high
frequency of headaches. Accordingly, specific classes of medications are
associated with migraine progression, and high frequency of headaches seems to be
a risk factor for chronic migraine regardless of medication exposure.

Publication Types: 
    Review

PMID: 19029522 [PubMed - indexed for MEDLINE]

19: Cephalalgia. 2009 Feb;29(2):244-9. Epub 2008 Nov 18.

Are cortical spreading depression and headache in migraine causally linked?

Wolthausen J, Sternberg S, Gerloff C, May A.

Department of Neurology, University of Hamburg, Hamburg, Germany.

During the past few decades, much controversy has surrounded the pathophysiology 
of migraine. Cortical spreading depression (CSD) is widely accepted as the
neuronal process underlying visual auras. It has been proposed that CSD can also 
cause the headaches, at least in migraine with aura. We describe three patients, 
each fulfilling the International Headache Society criteria for migraine with
aura, who suffered from headaches 6-10 days per month. Two patients were treated 
with flunarizine and the third patient with topiramate for the duration of 4
months. All patients reported that aura symptoms resolved completely, whereas the
migraine headache attacks persisted or even increased. These observations
question the theory that CSD (silent or not) is a prerequisite for migraine
headaches.

Publication Types: 
    Case Reports

PMID: 19025548 [PubMed - indexed for MEDLINE]

20: Acta Cardiol. 2008 Oct;63(5):571-7.

Closure of a patent foramen ovale is associated with a decrease in prevalence of 
migraine: a prospective observational study.

Luermans JG, Post MC, Temmerman F, Thijs V, Schonewille WJ, Plokker HW, Suttorp
MJ, Budts WI.

Department of Cardiology, St. Antonius Hospital, Nieuwegein, The Netherlands.

BACKGROUND: A causal relationship between migraine and a right-to-left shunt, due
to a patent foramen ovale (PFO), has been suggested. In mainly retrospective
studies, percutaneous closure of a PFO has been associated with a decrease in the
prevalence of migraine. OBJECTIVE: In this prospective observational study we
evaluated whether percutaneous closure of a PFO is associated with a decrease in 
the prevalence of migraine. METHODS: Between November 2003 and August 2005, we
included 92 patients (age >16 years) who underwent a percutaneous closure of a
symptomatic PFO, which was considered to be related to a paradoxical
embolism.They received a headache questionnaire before and six months after
closure.Two neurologists diagnosed migraine, according to the International
Headache Criteria. RESULTS: Eighty-nine of 92 patients (97%, mean age 51.6 +/-
12.3 years, 63 men) completed the questionnaire immediately before PFO
closure.The overall prevalence of migraine was 27.0%, for migraine without aura
(MA-) 15.7%, and for migraine with aura (MA+) 11.2%. After more than six months
of follow-up 84 of 89 patients (94%, mean age 52.1 +/- 12.0 years, 60 men)
returned the questionnaire. The overall prevalence of migraine in this group
decreased from 28.6% to 10.7% (P = 0.001), for MA-from 16.7% to 8.3% (P = 0.07), 
and for MA+ from 11.9% to 2.4% (P = 0.02). CONCLUSIONS: Percutaneous PFO closure 
is related to a decrease in the prevalence of migraine in this prospective
observational study. However, randomized placebo controlled trials have to
confirm these findings.

PMID: 19013999 [PubMed - indexed for MEDLINE]

21: Neurol Sci. 2008 Oct;29 Suppl 3:336-8.

Headache and migraine.

Filippi M, Rocca MA.

Neuroimaging Research Unit, Department of Neurology, Scientific Institute and
University Ospedale San Raffaele, Via Olgettina 60, 20132 Milan, Italy.
filippi.massimo@hsr.it

The application of modern imaging techniques to the study of patients with
headache/migraine has dramatically changed our understanding of these conditions.
Several studies of these patients have demonstrated not only the occurrence of
abnormalities of function, but also relevant and diffuse structural changes of
the brain white and grey matter. More recently, it has been suggested that the
different forms of headache/migraine might have specific functional and
structural MRI correlates, which, in the future, is likely to result in new
therapeutic scenarios.

Publication Types: 
    Review

PMID: 18941726 [PubMed - indexed for MEDLINE]

22: Headache. 2008 Oct;48(9):1411-4.

The neurogenic basis of migraine.

Cutrer FM, Charles A.

Mayo Clinic, Rochester, MN 55902, USA.

There is accumulating evidence of a neurogenic basis of migraine. This evidence
arises from both the clinical and experimental domains. Many of the well known
clinical features of migraine attacks including the prodrome are not explained by
changes in vascular caliber. Despite the fact that ergotamines and triptans are
vasoactive does not provide substantive proof that vasoconstriction is their most
important mechanism of action. Several effective treatments for migraine, both
old and new, do not affect vascular caliber. Experimental evidence from
investigation of both the aura and headache phases of migraine clearly supports a
neural basis of migraine. All genes thus far conclusively associated with
hemiplegic migraine code for neural proteins.

Publication Types: 
    Review

PMID: 19006559 [PubMed - indexed for MEDLINE]

23: Headache. 2008 Oct;48(9):1409-10.

"Outside-in" vs "inside-out": revisiting migraine's vascular hypothesis.

Rothrock JF.

Department of Neurology, University of Alabama at Birmingham, Birmingham, AL
35233, USA.

The neurovascular contribution to migraine biogenesis should not be overlooked in
the rush to embrace a central "generator."

Publication Types: 
    Review

PMID: 19006558 [PubMed - indexed for MEDLINE]

24: Headache. 2008 Oct;48(9):1399-405.

Refractory migraine and chronic migraine: pathophysiological mechanisms.

Goadsby PJ, Hargreaves R.

Department of Neurology, University of California, San Francisco, San Francisco, 
CA, USA.

Despite increased understanding of primary headaches and their treatment, the
underlying causes of refractory migraine remain unknown. This note considers
potential genetic, structural, functional and pharmacological factors that could 
contribute to this relatively intractable condition. Further understanding of
refractory migraine will require the use of medical imaging technologies,
clinical experimental medicine studies on novel pharmacological agents and astute
observations in clinical practice to direct potential novel therapeutic
approaches.

Publication Types: 
    Review

PMID: 19006557 [PubMed - indexed for MEDLINE]

25: Ann Pharmacother. 2008 Dec;42(12):1804-13. Epub 2008 Nov 11.

Pharmaceutical care for migraine and headache patients: a community-based,
randomized intervention.

Hoffmann W, Herzog B, Mühlig S, Kayser H, Fabian R, Thomsen M, Cramer M, Fiss T, 
Gresselmeyer D, Janhsen K.

Institute of Community Medicine, University of Greifswald, Greifswald, Germany.
wolfgang.hoffmann@uni-greifswald.de

BACKGROUND: Despite the high prevalence of headache and migraine in the general
population, many people do not receive adequate medical attention and treatment. 
OBJECTIVE: To evaluate the effects of pharmaceutical care (defined as intensified
structured counseling between patient and pharmacist, including the use of drug
databases), for patients with headache or migraine, on both clinical and
psychological endpoints. METHODS: A prospective, randomized, controlled
intervention study was conducted using pharmacies in Northern Germany. A total of
112 pharmacies (26% of all pharmacies in the study region) recruited 410 patients
with headaches. Pharmacies were randomly assigned to an intervention or control
group. Patients were interviewed by telephone prior to the intervention and again
after 4 months. Primary endpoints were number of days with headache, number and
severity of headaches, self-efficacy, and the patients' perceptions of their
health-related quality of life. RESULTS: Each pharmacy treated an average of 4.6 
patients (total time effort 9 h). The intervention group consisted of 201
patients who received pharmaceutical care, whereas the control group comprised
209 patients who received standard counseling. In both groups, the number of
headache attacks and intensity of pain in treated headache attacks did not change
significantly between the first and second interviews. However, a statistically
significant improvement in mental health and self-efficacy was shown in the
intervention group. Intensity of pain in untreated headache attacks and the
number of days with headache decreased in both groups. Most participants
described this intervention as helpful and effective and 90% reported that they
would recommend pharmaceutical care to other patients with headache. CONCLUSIONS:
A short-term pharmaceutical care intervention improved patients' mental health
and self-efficacy, although it did not significantly change the number and
severity of headaches. The increase in self-efficacy and mental health associated
with pharmaceutical care may be instrumental in improving long-term
pharmacotherapy of patients with migraine and headache. To fully assess the
effects of pharmaceutical care, a longer study may be required.

Publication Types: 
    Randomized Controlled Trial

PMID: 19001531 [PubMed - indexed for MEDLINE]

26: Curr Top Med Chem. 2008;8(16):1468-79.

The tortuous road to an ideal CGRP function blocker for the treatment of
migraine.

Davis CD, Xu C.

Department of Pharmacokinetics and Drug Metabolism, Amgen Inc., One Amgen Center 
Drive, Thousand Oaks, CA 91320-1799, USA.

The critical role of Calcitonin Gene-Related Peptide (CGRP) in migraine has been 
validated, with two small molecule CGRP antagonists BIBN4096BS and MK-0974
demonstrating efficacy in the reversal of acute migraine attack. Multiple
approaches have been taken to find the ideal agent that most effectively inhibits
CGRP's function. Here, we have summarized the progress made in recent years,
including the identification and optimization of an orally bioavailable small
molecule CGRP receptor antagonist. We also describe other interventions such as
scavenging of CGRP itself. The advantages and disadvantages of these distinct
approaches are discussed.

Publication Types: 
    Review

PMID: 18991732 [PubMed - indexed for MEDLINE]

27: Cancer Epidemiol Biomarkers Prev. 2008 Nov;17(11):3116-22.

Migraine in postmenopausal women and the risk of invasive breast cancer.

Mathes RW, Malone KE, Daling JR, Davis S, Lucas SM, Porter PL, Li CI.

Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, 1100 
Fairview Avenue North, M4-C308, P. O. Box 19024, Seattle, WA 98109-1024, USA.
rmathes@u.washington.edu

BACKGROUND: The frequency of migraine headache changes at various times of a
woman's reproductive cycle. Menarche, menses, pregnancy, and perimenopause may
carry a different migraine risk conceivably because of fluctuating estrogen
levels, and in general, migraine frequency is associated with falling estrogen
levels. Given the strong relationship between endogenous estrogen levels and
breast cancer risk, migraine sufferers may experience a reduced risk of breast
cancer. METHODS: We combined data from two population-based case-control studies 
to examine the relationship between migraine and risk of postmenopausal invasive 
breast cancer among 1,199 ductal carcinoma cases, 739 lobular carcinoma cases,
and 1,474 controls 55 to 79 years of age. Polytomous logistic regression was used
to estimate odds ratios (OR) and 95% confidence intervals (95% CI). RESULTS:
Women who reported a clinical diagnosis of migraine had reduced risks of ductal
carcinoma (OR, 0.67; 95% CI, 0.54-0.82) and lobular carcinoma (OR, 0.68; 95% CI, 
0.52-0.90). These associations were primarily limited to hormone
receptor-positive tumors as migraine was associated with a 0.65-fold (95% CI,
0.51-0.83) reduced risk of estrogen receptor-positive (ER+)/progesterone
receptor-positive (PR+) ductal carcinoma. The reductions in risk observed were
seen among migraine sufferers who did and did not use prescription medications
for their migraines. CONCLUSIONS: These data suggest that a history of migraine
is associated with a decreased risk of breast cancer, particularly among ER+/PR+ 
ductal and lobular carcinomas. Because this is the first study to address an
association between migraine history and breast cancer risk, additional studies
are needed to confirm this finding.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 18990752 [PubMed - indexed for MEDLINE]

28: Can J Neurol Sci. 2008 Sep;35(4):448-51.

Insulin resistance and high sensitivity C-reactive protein in migraine.

Guldiken B, Guldiken S, Demir M, Turgut N, Kabayel L, Ozkan H, Ozcelik E, Tugrul 
A.

Department of Neurology, Medical Faculty of Trakya University, Turkey.

BACKGROUND: A relationship between migraine and vascular disorders such as
hypertension, stroke, and coronary ischemia has been recently reported. Insulin
resistance and endothelial dysfunction, which commonly underlies these disorders,
have not been widely investigated in migraine patients. In this study, we aimed
to investigate the existence of insulin resistance and endothelial dysfunction,
and their relationship to vascular risk factors in patients with migraine.
METHODS: We evaluated insulin resistance and high-sensitivity C-reactive protein 
(hs-CRP), a marker of endothelial dysfunction, in 60 migraine patients and 25
healthy control subjects. Multiple analysis of covariance test was used to adjust
for known confounding factors that can influence insulin metabolism and
endothelial function, such as obesity, blood pressure, and lipid parameters.
RESULTS: Insulin resistance, as measured homeostasis model assessment (HOMA)-R
levels, was significantly higher in the migraine group (p<0.001). After
adjustment for confounding variables, the relationship between migraine and the
HOMA-R levels remained significant (p<0.001). The hs-CRP levels did not differ
between the migraine and control groups. CONCLUSIONS: Our data show that insulin 
resistance is present in migraine patients. Endothelial dysfunction is not found 
during the headache-free period. Further studies are needed to explain the role
of insulin resistance in migraine pathogenesis.

PMID: 18973061 [PubMed - indexed for MEDLINE]

29: J Neurol. 2008 Sep;255(9):1290-301. Epub 2008 Sep 30.

Migraine-associated risks and comorbidity.

Diener HC, Küper M, Kurth T.

Dept. of Neurology and Headache Center, University Duisburg-Essen, Hufelandstr.
55, 45147, Essen, Germany. hans.diener@uni.duisburg-essen.de

This review reports important co-morbid conditions of migraine and resulting
consequences for the choice of acute and preventive treatments of migraine.
Comorbidity in this context means the occurrence of two diseases in an individual
beyond chance. The basis of comorbidity can be genetic and/or based on common
environmental factors. In some cases, the temporal relationship is unclear and
one disease can cause another disease. In order to prove a real comorbidity,
large-scale and well-performed epidemiological studies are required.

Publication Types: 
    Review

PMID: 18958572 [PubMed - indexed for MEDLINE]

30: Childs Nerv Syst. 2009 Feb;25(2):257-61. Epub 2008 Oct 29.

Superficial temporal artery-middle cerebral artery bypass surgery in a pediatric 
giant intracranial aneurysm presenting as migraine-like episodes.

Goedee HS, Depauw PR, vd Zwam B, Temmink AH.

Department of Neurology, Elisabeth Hospital Tilburg, Tilburg, The Netherlands.

INTRODUCTION: Aneurysms of the intracranial arteries in the pediatric population 
are reportedly rare. There is a male predominance, association with connective
tissue disorders, as well as bacterial, mycotic infections, and trauma. RESULTS
AND DISCUSSION: Common sites of presentation are the internal carotid artery
bifurcation, posterior circulation, and distal segment of middle cerebral artery.
Clinical manifestations can vary from seizures and subarachnoidal hemorrhage to
headache, irritability, lethargy, vomiting, or focal motor deficits. Current
treatment modalities encompass endovascular or surgical approach. CONCLUSION: We 
present a case report on an 11-year-old girl with migraine-like episodes due to
an underlying giant fusiform middle cerebral artery aneurysm treated successfully
with two superficial temporal artery-middle cerebral artery bypasses.

Publication Types: 
    Case Reports

PMID: 18958477 [PubMed - indexed for MEDLINE]

31: Dis Markers. 2008;25(2):107-13.

The C677T polymorphism in MTHFR is not associated with migraine in Portugal.

Ferro A, Castro MJ, Lemos C, Santos M, Sousa A, Pereira-Monteiro J, Sequeiros J, 
Maciel P.

UnIGENe-IBMC, Instituto de Biologia Molecular e Celular, Universidade do Porto,
Porto, Portugal.

Migraine is a debilitating disorder affecting a large proportion of the
population. The effect of methylenetetrahydrofolate reductase (GeneID: 4524)
polymorphisms in migraine etiology and development has been a theme of great
interest. Several populations were evaluated with contradictory results. In this 
case-control study, we investigated the effect of the C677T polymorphism in
MTHFR, as a genetic risk factor for migraine, in the Portuguese population. We
observed that, overall, there was no significant difference in the frequencies of
MTHFR C677T genotypes or of the T-allele among the Portuguese migraineurs when
compared to controls. There was also no association of migraine with aura with
MTHFR genotypes or with the T-allele, in contrast with previous studies.
Regarding the risk of the T-allele homozygote carriers, there was an equal
probability to develop migraine with aura over migraine without aura in our
patients. Thus, we conclude that the C677T MTHFR polymorphism, responsible for a 
reduction of the MTHFR activity in folate metabolism, is not a major genetic
susceptibility factor for migraine in the Portuguese population.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 18957721 [PubMed - indexed for MEDLINE]

32: Laryngoscope. 2008 Dec;118(12):2235-9.

Treatment of sinus headache as migraine: the diagnostic utility of triptans.

Kari E, DelGaudio JM.

Department of Otolaryngology, Emory University School of Medicine, Atlanta, GA
30322, USA.

OBJECTIVE: To determine the response rate to triptans in alleviating "sinus
headache" in patients with endoscopy- and computed tomography (CT)-negative sinus
examinations. STUDY DESIGN: Prospective clinical trial. METHODS: Patients who
presented to a tertiary care center Otolaryngology Department with primary
complaints of facial pain, pressure, or headache localized over the area of the
sinuses, and a self- or physician-diagnosis of "sinus headache" were enrolled.
Patients underwent directed history, physical examination, rigid nasal endoscopy,
a sinus CT scan, and completed a headache questionnaire. Those patients that had 
negative findings were treated empirically with triptans. Patients completed a
headache diary for each headache, using a visual analogue scale to rate the
headache before and after triptan use. Response was considered as significant
improvement (greater than 50% reduction of pain), partial (25-50% reduction), and
no response. RESULTS: Fifty-four patients were enrolled. Thirty-eight (69%)
completed follow-up, 63% were women. The mean age was 41 years (23-70).
Thirty-one patients (82%) had significant reduction of headache pain with triptan
use. Thirty-five patients (92%) had a significant reduction in headache pain in
response to migraine-directed therapy. Seventeen patients (31%) withdrew or
failed to follow-up, often reluctant to accept a diagnosis of migraine.
CONCLUSIONS: This study demonstrated that the demographics of patients with
self-described "sinus headaches" who did not have findings of sinusitis on
endoscopy and CT scan closely reflected the demographics of patients afflicted
with migraines. It also showed that 82% of these patients had a significant
response to empiric treatment for sinus headaches with triptans. These findings
support that "sinus headaches" may represent migraines, and response to triptans 
may aid in diagnosis.

PMID: 18948830 [PubMed - indexed for MEDLINE]

33: Popul Health Manag. 2008 Aug;11(4):203-8.

Assessing quality of care for migraineurs: a model health plan measurement set.

Leas BF, Gagne JJ, Goldfarb NI, Rupnow MF, Silberstein S.

Department of Health Policy, Jefferson Medical College, Philadelphia,
Pennsylvania, 19107, USA. brian.leas@jefferson.edu

Quality of care measures are increasingly important to health plans, purchasers, 
physicians, and patients. Appropriate measures can be used to assess quality and 
evaluate improvement and are necessary components of pay-for-performance
programs. Despite the broad scope of activity in the development of quality
measures, migraine headache has received little attention. Given the enormous
costs associated with migraine, especially in terms of lost productivity and
preventable health care utilization, health plans could gain from a structured
approach to measuring the quality of migraine care their beneficiaries receive. A
potential migraine quality measurement set was developed through a review of
migraine care literature and guidelines, interviews with leaders in migraine
care, health care purchasing, and managed care, and the assembly of an advisory
board. The board discussed candidate measures and established consensus on a
testable measurement set. Twenty measures were developed, focused primarily on
diagnosis and utilization. Areas of utilization include physician visits,
emergency department visits, hospitalizations, and imaging. Use of both acute and
preventive medications is included. More complex aspects of migraine care are
also addressed, including triptan overuse, the relationship between acute and
preventive medications, and follow-up after emergency department visits. The
measures are currently being tested in health plans to assess their feasibility
and value. A compelling case can be made for the development of migraine-specific
quality measures for health plans. This effort to develop and test a starter set 
of measures should lead to new and innovative efforts to assess and improve
quality of care for migraineurs.

PMID: 18942925 [PubMed - indexed for MEDLINE]

34: BMC Health Serv Res. 2008 Oct 10;8:211.

Are migraineur women really more vulnerable to stress and less able to cope?

Gunel MK, Akkaya FY.

Hacettepe University, Faculty of Health Sciences, Department of Physical Therapy 
and Rehabilitation, 06100, Ankara, Turkey. mintaze@hacettepe.edu.tr

BACKGROUND: In this study, we aimed to investigate the differences between a
sample of migraineurs and non-migraineurs with regard to their stress symptoms,
tendency to stress, coping styles and life satisfaction. METHODS: This study was 
carried out on a migraineur group (n = 62, mean age: 37.5 +/- 11.3, range: 18 to 
61 years) and a non-migraineur group (n = 58, mean age: 32.0 +/- 11.2, range: 18 
to 61 years). Stress Audit (Symptoms), Stress Audit (Vulnerability), Turkish
version of Ways of Coping Inventory Scales and Life Satisfaction were applied to 
the migraineur and non-migraineur groups. RESULTS: No significant differences
were found between the groups in the scores of the stress symptoms except in the 
sub scores of the sympathetic system. There was no significant difference between
the groups in the tendency to stress and life satisfaction (p > .05). For scores 
of the coping styles, the mean scores of the seeking social support subscale was 
higher in the control group than that of the migraineur group. However,
migraineur women had higher mean scores in the submissive and the optimistic
subscales. CONCLUSION: We consider that, these outcomes may emphasize the
necessity to be careful when using negative expressions about stress relating to 
migraineurs. Further comprehensive studies are required considering the multiple 
triggers of the disease in various cultural contexts.

PMID: 18847471 [PubMed - indexed for MEDLINE]

35: J Am Pharm Assoc (2003). 2008 Sep-Oct;48(5):e107-20; quiz e121-4.

Migraine-preventive medications: ensuring their appropriate use.

Wenzel RG.

Diamond Headache Clinic Inpatient Unit, Saint Joseph Hospital, Chicago, IL 60657,
USA. rwenz@hotmail.com

OBJECTIVES: To emphasize the magnitude and burden of migraine, the need for
greater use of migraine-preventive medications in patients who could most benefit
from them, and the role that pharmacists can play in migraine prevention. DATA
SOURCES: PubMed and Medline-based literature searches were conducted to determine
the need for migraine-preventive medications, the treatment of migraine, and how 
pharmacists can assist patients in preventing and treating migraines. The
literature search included articles from the previous 6 years, as well as earlier
articles for historical perspective. DATA SYNTHESIS: Migraine is a prevalent,
chronic, neurologic condition that imposes substantial disability on affected
patients, leading to a poor quality of life. However, migraine remains
underrecognized, underdiagnosed, and under- or suboptimally treated. In
particular, migraine-preventive medications are greatly underused, which
contributes to avoidable disability. Community pharmacists can play important
roles in identifying these and other patients with headache who are in need of
medical care, referring appropriate patients to a health care provider, and
educating and counseling patients with respect to abortive and preventive
medications. CONCLUSION: Pharmacists are in a unique position to assist in
migraine management, particularly with regard to migraine-preventive medications,
because many patients may not be familiar with the benefits and use of these
agents. Pharmacist involvement can have a measurable effect on patient care and
improve the lives of migraine patients.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 18826892 [PubMed - indexed for MEDLINE]

36: Neurol Res. 2008 Oct;30(8):801-12.

Migraine and stroke: current perspectives.

Elliott D.

Department of Neurology, Louisiana State University Health Sciences Center,
Shreveport, LA 71130-3932, USA. delli1@Isuhsc.edu

OBJECTIVE: The purpose of this article is to review the latest concepts regarding
migraine and ischemic stroke. In addition, focal neurological deficits and MRI
changes in migraine patients will be reviewed. METHODS: A PubMed search of
neurological literature pertaining to this study was conducted using specific
keyword search terms pertaining to migraine and ischemic stroke. RESULTS:
Migraine, especially with aura, is a relative risk factor for stroke.
Neuroimaging demonstrates the posterior circulation as being most vulnerable,
although the reason for this distribution is unclear. Factors that may contribute
to stroke in migraine include changes during cortical spreading depression with
hyper- or hypoperfusion of neural tissue, vasospasm and endothelial dysfunction. 
Estrogen affects migraine expression as well as cerebral circulation, yet most
women with migraine without aura are not at increased risk. Co-morbidity with
patent foramen ovale can be mechanism of both disorders via presumed lack of
filtration of microemboli or toxic substances; however, closure with reversal of 
right to left shunt seems to be more beneficial for cryptogenic stroke than
migraine. Migraine and stroke are found in specific genetic disorders such as
CADASIL, HERNS and MELAS giving clues to genetic factors. Stroke associated with 
migraine treatments such as ergots or triptans is rare, and usually associated
with special circumstances such as overuse or concomitant thrombogenic
conditions. CONCLUSION: Although true migrainous infarction is rare, our
understanding of the subtle associations between migraine and cerebrovascular
behavior is expanding.

Publication Types: 
    Review

PMID: 18826806 [PubMed - indexed for MEDLINE]

37: Ann Neurol. 2008 Sep;64(3):315-24.

Enhanced circadian phase resetting in R192Q Cav2.1 calcium channel migraine mice.

van Oosterhout F, Michel S, Deboer T, Houben T, van de Ven RC, Albus H,
Westerhout J, Vansteensel MJ, Ferrari MD, van den Maagdenberg AM, Meijer JH.

Laboratory for Neurophysiology, Department of Molecular Cell Biology, Leiden
University Medical Center, Leiden, the Netherlands.

OBJECTIVE: Mammalian circadian rhythms are driven by the circadian pacemaker of
the suprachiasmatic nucleus (SCN) and are synchronized to the external 24-hour
light/dark cycle. After advance time zone transitions (eastbound jet lag), overt 
circadian rhythms require several days to adjust. The retarded adaptation may
protect against acute imbalance of different brain systems. Abrupt circadian
rhythm changes may trigger migraine attacks, possibly because migraineurs have an
inadequate adaptation mechanism. The novel R192Q knock-in migraine mouse model
carries mutated Ca(v)2.1 calcium channels, causing increased presynaptic calcium 
influx and neurotransmitter release. We investigated whether these mice have an
abnormal adjustment to phase advance shifts. METHODS: We examined phase resetting
to 6-hour advance shifts of the light/dark cycle with behavioral and
electroencephalographic recordings in R192Q and wild-type mice. We recorded
excitatory postsynaptic currents in the SCN, and electrical impulse frequency in 
vitro and in vivo. RESULTS: R192Q mice showed a more than twofold enhanced
adjustment of behavioral wheel-running activity and electroencephalographic
patterns, as well as enhanced shifts of electrical activity of SCN neurons in
vivo. No differences were found for in vitro recordings of the electrical impulse
frequency in SCN slices. INTERPRETATION: R192Q migraine mice lack the
physiological retardation in circadian adaptation to phase advance shifts. The
opposite findings in vivo and in vitro exclude involvement of the retinal input
pathway or the phase-shifting capacity of the SCN. Thus, the physiological
inhibitory process appears to be mediated by Ca(v)2.1 channel-dependent afferent 
signaling from extra-SCN brain areas to the SCN.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 18825664 [PubMed - indexed for MEDLINE]

38: Cephalalgia. 2009 Feb;29(2):204-13. Epub 2008 Sep 24.

Correlation between abnormal brain excitability and emotional symptomatology in
paediatric migraine.

Valeriani M, Galli F, Tarantino S, Graceffa D, Pignata E, Miliucci R, Biondi G,
Tozzi A, Vigevano F, Guidetti V.

Headache Centre, Division of Neurology, Ospedale Pediatrico Bambino Gesu, IRCCS, 
Rome Italy. m.valeriani@tiscali.it

We investigated a possible correlation between brain excitability in children
with migraine and tension-type headache (TTH) and their behavioural
symptomatology, assessed by using the Child Behaviour Checklist (CBCL). The
mismatch negativity (MMN) and P300 response were recorded in three successive
blocks to test the amplitude reduction of each response from the first to the
third block (habituation). MMN and P300 habituation was significantly lower in
migraineurs and TTH children than in control subjects (two-way ANOVA: P < 0.05). 
In migraineurs, but not in TTH patients, significant positive correlations
between the P300 habituation deficit and the CBCL scores were found (P < 0.05),
meaning that the migraineurs with the most reduced habituation showed also the
worst behavioural symptomatology. To the best of our knowledge, this is the first
study showing a correlation between neurophysiological abnormality and emotional 
symptomatology in migraine, suggesting a role of the latter in producing the
migrainous phenotype.

PMID: 18823365 [PubMed - indexed for MEDLINE]

39: Cephalalgia. 2009 Feb;29(2):214-20. Epub 2008 Sep 24.

Medication overuse headache and chronic migraine in a specialized headache
centre: field-testing proposed new appendix criteria.

Zeeberg P, Olesen J, Jensen R.

Danish Headache Centre, Department of Neurology, University of Copenhagen,
Glostrup Hospital, Glostrup, Denmark.

The classification subcommittee of the International Headache Society (IHS) has
recently suggested revised criteria for medication overuse headache (MOH) and
chronic migraine (CM). We field tested these revised criteria by applying them to
the headache population at the Danish Headache Centre and compared the results
with those using the current criteria. For CM we also tested two alternative
criteria, one requiring > or = 4 migraine days/month and > or = 15 headache
days/month, the second requiring > or = 15 headache days/month and > or = 50%
migraine days. We included 969 patients with migraine or tension-type headache
(TTH) among 1326 patients treated and dismissed in a 2-year period. Two hundred
and eighty-five patients (30%) had TTH, 265 (27%) had migraine and 419 (43%) had 
mixed migraine and TTH. The current criteria for MOH classified 86 patients (9%) 
as MOH, 98 (10%) as probable MOH and 785 (81%) as not having MOH after a 2-month 
drug-free period. Using the appendix criteria, 284 patients (29%) were now
classified as MOH, no patients as probable MOH and 685 (71%) as not having MOH.
For CM only 16 patients (3%) fulfilled the current diagnostic criteria. This
increased to 42 patients (7%) when we applied the appendix criteria. Using the
less restrictive criteria of > or = 4 migraine days and > or = 15 headache days, 
88 patients (14%) had CM, whereas the more restrictive criteria of > or = 15
headache days and > or = 50% migraine days resulted in 24 patients (4%) with CM. 
Our data suggest that the IHS has succeeded in choosing new criteria for CM which
are neither too strict, nor too loose. For MOH, a shift to the appendix criteria 
will increase the number of MOH patients, but take into account the possibility
of permanent changes in pain perception due to medication overuse and the
possibility of a renewed effect of prophylactic drugs due to medication
withdrawal. We therefore recommend the implementation of the appendix criteria
for both MOH and CM into the main body of the International Classification of
Headache Disorders.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 18823364 [PubMed - indexed for MEDLINE]

40: Cephalalgia. 2009 Feb;29(2):221-32. Epub 2008 Sep 24.

Management of medication overuse headache: 1-year randomized multicentre
open-label trial.

Hagen K, Albretsen C, Vilming ST, Salvesen R, Grønning M, Helde G, Gravdahl G,
Zwart JA, Stovner LJ.

Department of Neuroscience, Faculty of Medicine, Norwegian University of Science 
and Technology, Trondheim, Norway. knut.hagen@ntnu.no

It is a general belief that patients with medication overuse headache (MOH) need 
withdrawal of acute headache medication before they respond to prophylactic
medication. In this 1-year open-labelled, multicentre study intention-to-treat
analyses were performed on 56 patients with MOH. These were randomly assigned to 
receive prophylactic treatment from the start without detoxification, undergo a
standard out-patient detoxification programme without prophylactic treatment from
the start, or no specific treatment (5-month follow-up). The primary outcome
measure, change in headache days per month, did not differ significantly between 
groups. However, the prophylaxis group had the greatest decrease in headache days
compared with baseline, and also a significantly more pronounced reduction in
total headache index (headache days/month x headache intensity x headache hours) 
at months 3 (P = 0.003) and 12 (P = 0.017) compared with the withdrawal group. At
month 12, 53% of patients in the prophylaxis group had > or = 50% reduction in
monthly headache days compared with 25% in the withdrawal group (P = 0.081).
Early introduction of preventive treatment without a previous detoxification
programme reduced total headache suffering more effectively compared with abrupt 
withdrawal. (ClinicalTrials.gov number, NCT00159588).

Publication Types: 
    Multicenter Study
    Randomized Controlled Trial

PMID: 18823363 [PubMed - indexed for MEDLINE]

41: Cephalalgia. 2009 Feb;29(2):188-93. Epub 2008 Sep 24.

Headache classification by history has only limited predictive value for headache
episodes treated in controlled trials with OTC analgesics.

Diener HC, Pfaffenrath V, Pageler L, Peil H, Aicher B, Lipton RB.

Department of Neurology, University Duisburg-Essen, Essen, Germany.
hans.diener@uni-duisburg-essen.de

We investigated the consistency between the headache diagnosis based on medical
history and three treated headache episodes diagnosed based on a diary. In a
randomized double-blind study including individuals with either migraine or
tension-type headache (TTH) we showed significant superiority of the fixed
combination of acetylsalicylic acid + paracetamol + caffeine over the combination
without caffeine, the single preparations, and placebo in the treatment of
headache. A neurologist performed a classification of the usual headache episodes
and each of the three treated ones in a blinded fashion based on a structured
questionnaire. This was done for the 1734 patients included in the efficacy
analysis who usually treated their episodic TTH or migraine attacks with
non-prescription analgesics. The overall percentage of patients with migraine and
TTH remained relatively stable. The treated headache episodes were between 75 and
77% migraine, 18-20% were TTH and 5-7% could not be classified. We observed some 
shift in headache type within patients from prior history and in treated attacks.
In 60% of patients all three treated episodes were of the type initially
diagnosed by the neurologist by history (56% migraine and 4% episodic TTH). Of
those with an initial diagnosis of migraine, 24% had at least one attack meeting 
criteria for TTH. Of patients with an initial diagnosis of TTH, 54% had at least 
one attack meeting the diagnostic criteria for migraine. Our results demonstrate 
that an initial headache diagnosis does not accurately predict the headache type 
treated in a randomized trial. Symptom features of treated headaches should be
captured to ensure that the attack is of the type targeted by the clinical trial.
The International Headache Society Guidelines for controlled clinical trials
should be updated accordingly.

Publication Types: 
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 18823361 [PubMed - indexed for MEDLINE]

42: Cephalalgia. 2009 Feb;29(2):194-203. Epub 2008 Sep 24.

Ictal headache and visual sensitivity.

Piccioli M, Parisi P, Tisei P, Villa MP, Buttinelli C, Kasteleijn-Nolst Trenité
DG.

Department of Neurology, II Faculty of Medicine, La Sapienza University, Rome
Italy.

Migrainous headache is reported by patients with photosensitive epilepsy, whereas
their relatives complain more often about headache than the relatives of patients
with other types of epilepsy. We therefore investigated whether headache itself
could be an epileptic symptom related to photosensitivity. Four probands with
headache and photosensitive epilepsy were selected. Their first-degree family
members were studied using video-EEG with extensive intermittent photic
stimulation and pattern stimulation. Nine of the 12 subjects (10 female and two
male, mean age 30 years, range 14-46 years) proved to be photosensitive with
either focal (n = 5) or generalized (n = 4) epileptiform discharges. In two
subjects an ictal recording of headache occurred after visual stimulation. We
found evidence that, in specific patients, headache could be an ictal sign of
epilepsy. Photic stimulation during EEG recording can contribute to correct
diagnosis and lead to the best care and management of the patient.

Publication Types: 
    Case Reports
    Research Support, Non-U.S. Gov't

PMID: 18823360 [PubMed - indexed for MEDLINE]

43: J Pak Med Assoc. 2008 Aug;58(8):453-5.

Migraine and patent foramen ovale: exploring the association and a possible
treatment option.

Hasan MY.

Department of Biological and Biomedical Sciences, Aga Khan University Hospital,
Karachi, Pakistan.

Migraine is a very common type of headache. With a prevalence of 10-12%, migraine
ranks 19th among diseases causing worldwide morbidity. Number of studies have
shown a high prevalence of patent foramen ovale (PFO) in patients with migraine, 
especially migraine with aura. The right to left shunting of blood in a PFO could
serve as a conduit for chemicals that would exert a trigger effect on hyper
excitable neurons leading to the development of migraine. Furthermore patients
with PFO and migraine also show a marked improvement in their symptoms after
percutaneous closure of the PFO. This review is a close look at this association 
and also explores whether subsequent closure of the shunt can be looked upon as a
viable treatment option.

Publication Types: 
    Review

PMID: 18822645 [PubMed - indexed for MEDLINE]

44: Minerva Cardioangiol. 2008 Oct;56(5):461-5.

Early post-procedural migraine attack predicts migraine resolution after patent
foramen ovale transcatheter closure.

Rigatelli G, Cardaioli P, Dell'Avvocata F, Braggion G, Giordan M, Chinaglia M.

Unit of Adult Congenital and Structural Heart Disease, Cardiovascular Diagnosis
and Interventions, Department of Neurosciences, Rovigo General Hospital, Rovigo, 
Italy. jackyheart@hotmail.com

AIM: In patients with patent foramen ovale-related migraine, the procedure of
transcatheter closure itself is likely to cause a migraine attack. Our study is
aimed to evaluate the incidence of migraine attacks immediately after closure
procedure and their clinical and potential prognostic significance. METHODS: We
reviewed our database from January 2005 to April 2007 searching for patients with
severe disabling migraine despite anti-headache therapy who were submitted to
transcatheter closure of patent foramen ovale (PFO). Medical records of these
patients were carefully reviewed in order to record migraine episodes immediately
(0 to 6 h) after closure procedure. RESULTS: Twenty-one patients with previous
stroke and migraine underwent PFO closure: the procedure was successful in all of
the patients with no perioperative and in-hospital complications. Ten patients
(47.6%) experienced a migraine attack of mean duration 3.5+/-2.4 h immediately
after the closure procedure. Those patients had the same procedure time compared 
with other patients, but had larger PFO: patients with migraine attack
immediately after closure had higher rate of complete abolition of migraine in
the follow-up. CONCLUSION: Although more larger studies are needed to evaluate
the exact relationships between migraine and PFO, in patients with a tight
correlation between migraine and PFO, a prolonged opening of the PFO, as during
closure procedure, may cause a migraine attack immediately after the closure.
This fact can be considered a positive prognostic factor for migraine abolishment
in the follow-up.

PMID: 18813181 [PubMed - indexed for MEDLINE]

45: Neurol Sci. 2008 Sep;29(4):285-7. Epub 2008 Sep 20.

Melatonin to prevent migraine or tension-type headache in children.

Miano S, Parisi P, Pelliccia A, Luchetti A, Paolino MC, Villa MP.

Child Neurology, Paediatric Sleep Centre and Paediatric Headache Centre, La
Sapienza University - II Faculty c/o Sant' Andrea Hospital, Rome, Italy.

We designed a 3-month open label trial of melatonin prophylaxis in children with 
primary headache. After a one month baseline period without receiving preventive 
drugs, all children received a 3-month course of melatonin, 3 mg, administered
orally, at bedtime. A total of 22 children were enrolled (10 boys, mean age
12.2+/-2.6 years, age range 6-16 years), 13 had recurrent migraine without aura, 
1 with aura and 8 had chronic tension-type headache. When the trial ended, 14 of 
the 21 subjects reported that the headache attacks had decreased by more than 50%
in respect to baseline and 4 of them reported having no headache attacks. After
receiving melatonin for one month one subject dropped out because of excessive
daytime sleepiness. Our promising results warrant randomized placebo-controlled
trials in children to assess the real effectiveness of melatonin in preventing
primary headache.

Publication Types: 
    Clinical Trial

PMID: 18810607 [PubMed - indexed for MEDLINE]

46: Am J Cardiol. 2008 Oct 1;102(7):916-20. Epub 2008 Jul 18.

Frequency of migraine headache relief following patent foramen ovale "closure"
despite residual right-to-left shunt.

Jesurum JT, Fuller CJ, Kim CJ, Krabill KA, Spencer MP, Olsen JV, Likosky WH,
Reisman M.

Department of Cardiovascular Scientific Development, Swedish Medical Center,
Seattle, Washington, USA. jill.jesurum@swedish.org

Retrospective studies have shown improvement in migraines after patent foramen
ovale (PFO) closure. To date, no study has evaluated whether the completeness of 
closure affects headache status; therefore, the objective of this study was to
evaluate the impact of residual right-to-left shunt (RLS) on migraine symptoms
after transcatheter PFO closure in migraineurs with and without aura. This was a 
small-series, single-center, retrospective analysis of late follow-up data on 77 
patients with presumed paradoxical embolism and migraine who underwent PFO
closure for secondary stroke prevention. Power M-mode transcranial Doppler was
used to assess RLS at baseline and 6 and 12 months after closure. A standardized 
migraine questionnaire was administered at baseline and 6, 12, and 24 months
after closure. Fifty-five (71%) patients had migraine with aura. Final closure
and migraine status were available for 67 patients; 23 (34%) had incomplete PFO
closure, defined as 30 embolic tracks detected at final power M-mode transcranial
Doppler examination (median 366 days, 95% confidence interval 332 to 474).
Migraine relief (> or = 50% reduction in frequency) was independent of closure
status (77% complete closure vs 83% incomplete closure, p = 0.76) at late
follow-up (540 days, 95% confidence interval 537 to 711). Migraineurs with aura
were 4.5 times more likely to experience migraine relief than migraineurs without
aura. In conclusion, migraine relief may occur despite residual RLS after
transcatheter PFO closure, which may suggest a reduction in RLS burden below a
neuronal threshold that triggers migraine; however, this warrants further
investigation. Migraine with aura may be an independent predictor of relief after
PFO closure.

PMID: 18805122 [PubMed - indexed for MEDLINE]

47: Expert Opin Pharmacother. 2008 Oct;9(15):2565-73.

Treatment of migraine with prophylactic drugs.

Evers S.

University of Münster, Department of Neurology, Albert-Schweitzer-Street 33,
48129 Münster, Germany. everss@uni-muenster.de

BACKGROUND: Migraine is among the 10 most disabling disorders worldwide. Besides 
acute attack treatment, drug prophylaxis of migraine is important in order to
improve the quality of life. OBJECTIVE: The aim of this paper is to describe the 
indications, principles and appropriate drugs with published evidence for the
prophylaxis of migraine in general and in specific situations. METHODS: Based on 
the American and European guidelines for the treatment of migraine, the evidence 
for different drugs in the prophylaxis of migraine was evaluated. In addition,
all trials on migraine drug prophylaxis published since the publication of the
guidelines were included in the evaluation. These trials were identified by a
literature search in MedLine, Embase and the Cochrane library. RESULTS: The drugs
of first choice are beta-blockers, flunarizine, valproic acid and topiramate and,
in the US, amitriptyline is also grouped among the first-choice drugs. Drugs of
second choice, with less efficacy or poorer evidence, are venlafaxine,
gabapentin, naproxen, butterbur root, vitamin B(2) and magnesium. The potential
side effects are considered when choosing the appropriate prophylactic drug. All 
drugs used in migraine prophylaxis have been detected by chance and not by
pathophysiological considerations. In the future, drugs developed on the basis of
the current knowledge of migraine pathophysiology will hopefully be more
effective.

Publication Types: 
    Review

PMID: 18803445 [PubMed - indexed for MEDLINE]

48: Pharmacol Rep. 2008 Jul-Aug;60(4):542-8.

Serum and intraerythrocyte antioxidant enzymes and lipid peroxides in children
with migraine.

Boćkowski L, Sobaniec W, Kułak W, Smigielska-Kuzia J.

Department of Pediatric Neurology and Rehabilitation, Medical University of
Białystok, Waszyngtona 17, PL 15-274 Białystok, Poland. bockow@kki.pl

The oxidant-antioxidant balance disorders underlie a number of acute and chronic 
diseases of the central nervous system (CNS). It is believed that oxidative
stress plays a role in the pathogenesis of migraine. The study objective was to
assess the processes of lipid peroxidation with malondialdehyde (MDA) as its
major indicator and to determine the activities of antioxidant enzymes:
superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and glutathione
reductase (GSSG-R) in the serum and erythrocytes of patients at developmental age
with migraine with and without aura. The study group consisted of 34 patients at 
the age of 10-18 years (mean +/- standard deviation: 14.04 +/- 2.29 years),
suffering from migraine. The control group included 38 patients, aged 4-17 years 
(mean age 12.11 +/- 3.46). MDA concentration and activities of SOD, GSH-Px and
GSSG-R were determined in serum and erythrocytes of all the patients. In the
migraine group, the MDA levels in serum and erythrocytes were statistically
significantly lower than in control subjects (p < 0.001). In the migraine group, 
serum GSH-Px activity was significantly higher (p < 0.05). The GSSG-R activity in
the erythrocytes of migraine children was significantly higher compared to
controls (p < 0.001). SOD activity was decreased and GSH-Px was increased
(non-significantly) in erythrocytes of migraineurs. Our results confirm the
disturbances of lipid peroxidation processes in migraine and suggest the
activation of antioxidant mechanisms. Its important indicator seems to be the
increase in the GSSG-R activity in the erythrocytes and the GSH-Px activity in
serum between migraine attacks. Further studies are necessary.

Publication Types: 
    Clinical Trial

PMID: 18799823 [PubMed - indexed for MEDLINE]

49: Cephalalgia. 2008 Dec;28(12):1327-38. Epub 2008 Sep 16.

Binocular rivalry in migraine.

Wilkinson F, Karanovic O, Wilson HR.

Centre for Vision Research, York University, Toronto, ON, Canada. franw@yorku.ca

Cortical hyperexcitability in migraine could arise from abnormally weak
inhibition or from strengthened intracortical excitatory mechanisms. The present 
study employed binocular rivalry to differentiate between these possibilities.
Rivalry between static oriented grating patterns was examined in migraine with
aura (MA), migraine without aura (MoA) and headache-free control participants. A 
non-significant trend toward elevated mean dominance intervals (monocular
percepts, in seconds) was seen in both migraine groups at all contrasts. Second, 
significant interocular differences in rivalry dominance durations were seen in
the MoA group compared with controls; this difference also approached
significance in the MA group. Finally, both MA and MoA exhibited significantly
greater visual discomfort than the control group in the presence of both static
stripes and flickering visual stimuli. The rivalry results provide no support for
weakened intracortical inhibition in migraine. Optical or neural precortical
differences in the eyes' input strengths paired with enhanced recurrent cortical 
excitation can explain these findings.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 18798842 [PubMed - indexed for MEDLINE]

50: Curr Opin Otolaryngol Head Neck Surg. 2008 Oct;16(5):412-5.

Migraine-associated vestibulopathy.

Honaker J, Samy RN.

Division of Audiology, Mayo Clinic, Rochester, Minnesota, USA.

PURPOSE OF REVIEW: In the past few years, otologists have been seeing an
increasing number of patients with vestibular disorders due to
migraine-associated vestibulopathy. This article reviews some of the latest
developments in the understanding of this disease process, specifically its
incidence, symptoms, diagnosis, and treatment. RECENT FINDINGS:
Migraine-associated vestibular symptoms may include episodic true vertigo,
movement-provoked dysequilibrium, imbalance/unsteadiness, and complaints of
lightheadedness. The pathophysiology of migraine-associated vestibulopathy is not
completely understood; however, both peripheral and central deficits have been
observed. Although the International Headache Society classification does not
include migraine-associated vestibulopathy as a subclassification of migraine,
there is emerging evidence to support this development, which should then lead
toward improved diagnosis and treatment. Currently, migraine-associated
vestibulopathy is still considered a diagnosis of exclusion. SUMMARY: Treatment
of migraine-associated vestibulopathy is effective and includes lifestyle
changes, such as reducing triggers that increase susceptibility to migraines
(e.g. stress, poor diet, nicotine, or irregular sleep patterns), prophylactic and
abortive medications, vestibular therapy, or a combination of these. Further
research is needed to better understand migraine-associated vestibulopathy and
improve treatment.

Publication Types: 
    Review

PMID: 18797281 [PubMed - indexed for MEDLINE]

51: Eur J Neurol. 2008 Nov;15(11):1199-205. Epub 2008 Sep 13.

Thermal pain thresholds are decreased in the migraine preattack phase.

Sand T, Zhitniy N, Nilsen KB, Helde G, Hagen K, Stovner LJ.

Department of Neuroscience, Norwegian University of Science and Technology, St
Olavs University Hospital, Trondheim, Norway. trond.sand@ntnu.no

BACKGROUND AND PURPOSE: Migraine patients may have cutaneous allodynia during
attacks. In order to investigate if pain physiology changes in the preattack
phase we estimated heat pain and cold pain detection threshold (HPT and CPT) on
three different days in 41 migraine patients and 28 controls. METHODS: A thermode
was applied at four sites bilaterally: forehead, face, neck, and hand. A subgroup
of 11 migraine patients had been tested within 24 h before their next attack and 
in the interictal phase. RESULTS: In the preattack phase, HPT was lower compared 
with the paired interictal recording for the hand (44.8 degrees C vs. 45.9
degrees C, P = 0.009), neck (46.8 degrees C vs. 48.2 degrees C, P = 0.02), and
forehead (45.1 degrees C vs. 46.3 degrees C, P = 0.02). Neck and hand CPT were
higher in the preattack phase than interictally (10 degrees C vs. 7.3 degrees C, 
P = 0.01 and 11.6 degrees C vs. 9.4 degrees C, P = 0.06, respectively). Preattack
forehead changes were most apparent on the headache side of the subsequent
attack. DISCUSSION: Subclinical preattack thermal pain hypersensitivity seems to 
be a feature of the process that leads to a migraine attack.

PMID: 18795945 [PubMed - indexed for MEDLINE]

52: Acta Cardiol. 2008 Aug;63(4):431-5.

Migraine and coarctation of the aorta: prevalence and risk factors.

Borin C, Troost E, Thijs V, Moons P, Budts W.

Division of Cardiology, University Hospital Gasthuisberg, Leuven, Belgium.

OBJECTIVES: We previously described a potential relationship between the presence
of migraine and congenital heart defects. It has been hypothesized that a genetic
substrate might determine for congenital heart defects and migraine. Therefore,
we wanted to study the prevalence of migraine in female patients with coarctation
of the aorta (CA) and to determine predictive variables for migraine in this
specific population. METHODS: All patients with CA, previously selected for the
ZAHARA trial to evaluate pregnancies and outcome, were recruited from the
database of congenital heart disease of the University Hospital of Leuven. These 
patients were contacted by phone and asked to complete a structured headache
questionnaire. Based on this questionnaire, a neurologist blinded to the
patients' files, diagnosed migraine without or with aura (MA- and MA+,
respectively), according to the international headache criteria. Demographic,
clinical, and technical data were obtained by reviewing the patients' records.
RESULTS: Thirty-four female patients (age 32.2 +/- 6.3 y) were included in the
study. The overall prevalence of migraine in female CA patients was 38%, of which
12% were MA- and 26% MA+. No significant relationship between demographic,
clinical, and technical variables and migraine could be determined, except for
migraine and the number of pregnancies and smoking behaviour (univariate logistic
regression; B = 1.2 and 1.9, P = 0.039 and 0.027, respectively). CONCLUSION: In
this study, we found a relatively high prevalence of migraine in female adult CA 
patients. We could also demonstrate a positive relationship between migraine,
smoking behaviour, and the number of pregnancies. Therefore, we should pay more
attention to these findings in daily practice.

PMID: 18795579 [PubMed - indexed for MEDLINE]

53: Neurology. 2008 Sep 16;71(12):937-43.

Burden of atherosclerosis and risk of venous thromboembolism in patients with
migraine.

Schwaiger J, Kiechl S, Stockner H, Knoflach M, Werner P, Rungger G, Gasperi A,
Willeit J.

Department of Neurology, Innsbruck Medical University, Austria.

BACKGROUND: Previous studies have yielded evidence of an enhanced risk of
cardiovascular disease, especially stroke, among patients with migraine. Our
understanding of the underlying mechanisms is far from complete. The aims of the 
present study were to investigate the potential association between migraine and 
atherosclerosis and to assess the risk of venous thromboembolism as a clinical
surrogate for a procoagulant state in patients with migraine. METHODS: The
examination was part of the population-based Bruneck Study. During the 2005
evaluation, 574 participants aged 55-94 years underwent neurologic and laboratory
examinations involving a standardized headache interview and scanning of the
carotid and femoral arteries to evaluate presence, severity, and progression
(2000-2005) of atherosclerosis. RESULTS: A large number of well-founded and
putative cardiovascular risk factors have emerged as being unrelated to migraine 
status. Prevalence, severity, and 5-year progression of carotid and femoral
atherosclerosis did not differ significantly between migraineurs with and without
aura and nonmigraineurs. In fact, there was even a tendency for atherosclerosis
to be less pronounced among patients with migraine, and for the intima-media
thickness to be lower (p = 0.029). As a novel finding migraineurs faced a
significantly enhanced risk of venous thromboembolism (18.9% vs 7.6% in
nonmigraineurs, age/sex-adjusted p = 0.031). CONCLUSION: This study is the first 
to compare the burden of atherosclerosis as quantified by high-resolution duplex 
ultrasound between migraineurs and nonmigraineurs in the general community, and
provides solid evidence against the view that migraine predisposes to
atherosclerosis. The higher risk for venous thromboembolism among migraineurs
(prothrombotic state) awaits confirmation and elaboration in future research.

PMID: 18794497 [PubMed - indexed for MEDLINE]

54: Circulation. 2008 Sep 30;118(14):1419-24. Epub 2008 Sep 15.

Erratum in:
    Circulation. 2008 Oct 28;118(18):e682.

Comment in:
    Circulation. 2008 Sep 30;118(14):1405-7.

Patent foramen ovale and migraine: a cross-sectional study from the Northern
Manhattan Study (NOMAS).

Rundek T, Elkind MS, Di Tullio MR, Carrera E, Jin Z, Sacco RL, Homma S.

Department of Neurology, Miller School of Medicine, University of Miami, Miami,
FL 33136, USA. trundek@med.miami.edu

BACKGROUND: A causal relationship between patent foramen ovale (PFO) and migraine
has been hypothesized, and improvement of migraine frequency and severity after
percutaneous PFO closure has been reported. Population-based data on the
relationship between PFO and migraine are sparse, however. The objective of this 
study was to examine the association between PFO and migraine among stroke-free
individuals in an urban, population-based, multiethnic cohort. METHODS AND
RESULTS: As a part of the ongoing Northern Manhattan Study (NOMAS), 1101
stroke-free subjects were assessed for self-reported history of migraine. The
presence of PFO was assessed by transthoracic echocardiography. The mean age of
the group was 69+/-10 years; 58% were women. Forty-eight percent were Caribbean
Hispanic, 24% were white, 26% were black, and 2% were another race/ethnicity. The
prevalence of self-reported migraine was 16% (13% migraine with aura). The
prevalence of PFO was 15%. Migraine was significantly more frequent among younger
subjects, women, and Hispanics. The prevalence of PFO was not significantly
different between subjects who had migraine (26/178, or 14.6%) and those who did 
not (138/923, or 15.0%; P=0.9). In an adjusted multivariate logistic regression
model, the presence of PFO was not associated with increased prevalence of
migraine (odds ratio 1.01, 95% confidence interval 0.63 to 1.61). Increasing age 
was associated with lower prevalence of migraine in both subjects with a PFO
(odds ratio 0.94, 95% confidence interval 0.90 to 0.99 per year) and those
without PFO (odds ratio 0.97, 95% confidence interval 0.95 to 0.99 per year). The
observed lack of association between PFO and migraine (with or without aura) was 
not modified by diabetes mellitus, hypertension, cigarette smoking, or
dyslipidemia. CONCLUSIONS: In this multiethnic, elderly, population-based cohort,
PFO detected with transthoracic echocardiography and agitated saline was not
associated with self-reported migraine. The causal relationship between PFO and
migraine remains uncertain, and the role of PFO closure among unselected patients
with migraine remains questionable.

Publication Types: 
    Comparative Study
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 18794393 [PubMed - indexed for MEDLINE]

55: Pharmacol Ther. 2008 Nov;120(2):157-71. Epub 2008 Aug 23.

The role of nitric oxide (NO) in migraine, tension-type headache and cluster
headache.

Olesen J.

University of Copenhagen, Department of Neurology, Glostrup Hospital, Ndr.
Ringvej 57, DK - 2600 Glostrup, Copenhagen, Denmark. jeol@glo.regionh.dk

The most important primary headaches (i.e. independent disorders that are not
caused by another disease) are migraine, tension-type headache and cluster
headache. All primary headaches are in need of better treatments. Migraine has a 
prevalence of 10% in the general population and its societal costs are high.
Although the precise mechanisms underlying the pathophysiology of migraine are
still elusive, the last decades have witnessed some progress (e.g. involvement of
serotonin, calcitonin gene-related peptide, nitric oxide, etc). Nitric oxide (NO)
is a very important molecule in the regulation of cerebral and extra cerebral
cranial blood flow and arterial diameters. It is also involved in nociceptive
processing. Glyceryl trinitrate (GTN), a pro-drug for NO, causes headache in
normal volunteers and a so called delayed headache that fulfils criteria for
migraine without aura in migraine sufferers. Blockade of nitric oxide synthases
(NOS) by L-NMMA effectively treats attacks of migraine without aura. Similar
results have been obtained for chronic tension-type headache and cluster
headache. Inhibition of the breakdown of cGMP also provokes migraine in
sufferers, indicating that cGMP is the effector of NO-induced migraine. Several
relationships exist between NO, calcitonin gene-related peptide and other
molecules important in migraine. Also ion channels, particularly the K(ATP)
channels, are important for the action of NO. In conclusion, inhibition of NO
production or blockade of steps in the NO-cGMP pathway or scavenging of NO may be
targets for new drugs for treating migraine and other headaches. Indeed,
selective n-NOS and i-NOS inhibitors are already in early clinical development.

Publication Types: 
    Review

PMID: 18789357 [PubMed - indexed for MEDLINE]

56: CNS Drugs. 2008;22(10):877-86.

Oral zolmitriptan in the short-term prevention of menstrual migraine: a
randomized, placebo-controlled study.

Tuchman MM, Hee A, Emeribe U, Silberstein S.

Palm Beach Neurological Center, Palm Beach Gardens, Florida 33418, USA.
mmtuchman@aol.com

OBJECTIVE: To evaluate the efficacy and tolerability of oral zolmitriptan as a
short-term preventative therapy for menstrual migraine. METHODS: This was a
randomized, double-blind, parallel group, placebo-controlled, multicentre,
two-phase study. The results of the second phase are reported here (the first
phase evaluated zolmitriptan in the acute treatment of menstrual migraine and is 
reported elsewhere). Women who successfully completed phase I (with either a
positive or negative outcome, and who still fulfilled the inclusion criteria)
were randomized to zolmitriptan 2.5 mg oral tablet three times daily,
zolmitriptan 2.5 mg twice daily or placebo three times daily. Patients were
treated for three consecutive menstrual cycles, starting 2 days prior to the
expected onset of menses, for 7 days in total. RESULTS: Two hundred and
fifty-three patients completed phase I and were eligible for phase II. The
intention-to-treat population comprised 244 patients (zolmitriptan three times
daily [n = 83]; zolmitriptan twice daily [n = 80]; placebo [n = 81]). Both
zolmitriptan regimens demonstrated superior efficacy versus placebo, as measured 
by the proportion of patients with a >or=50% reduction in the frequency of
menstrual migraine attacks (zolmitriptan three times daily [58.6%], p = 0.0007 vs
placebo; zolmitriptan twice daily [54.7%], p = 0.002 vs placebo; placebo three
times daily [37.8%]). The mean frequency of breakthrough migraine attacks per
menstrual cycle was reduced accordingly. Fewer breakthrough attacks were treated 
with escape medication in the zolmitriptan three times daily (61.6% of attacks; p
= 0.0004 vs placebo) and twice daily (60.7%; p = 0.0055 vs placebo) treatment
groups than in the placebo group (74.4%). Short-term preventative therapy with
zolmitriptan was well tolerated. CONCLUSION: Zolmitriptan 2.5 mg oral tablet is
effective and well tolerated as a short-term preventative therapy for menstrual
migraine attacks.

Publication Types: 
    Clinical Trial, Phase I
    Clinical Trial, Phase II
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 18788838 [PubMed - indexed for MEDLINE]

57: Intern Emerg Med. 2008 Oct;3 Suppl 1:S17-24.

Acute migraine in the Emergency Department: extending European principles of
management.

Martelletti P, Farinelli I, Steiner TJ; Working Group for Specialist Education,
WHO's Global Campaign to Reduce the Burden of Headache Worldwide (Lifting The
Burden).

Department of Medical Sciences, Internal Medicine, Regional Referral Headache
Centre, 2nd School of Medicine, Sapienza University of Rome, Sant'Andrea
Hospital, Via di Grottarossa 1035, 00189 Rome, Italy.
paolo.martelletti@uniroma1.it

The World Health Organization (WHO) placed migraine 19th among all causes of
disability (12th in women) measured in years of healthy life lost to disability
(YLD). The importance of headache disorders, particularly of the primary forms,
is established by their distribution worldwide, their duration (the majority
being life-long conditions) and their imposition of both disability and
life-style restrictions among large numbers of people. For these reasons,
headache disorders should represent a public-health priority. In the Emergency
Department (ED), as elsewhere, migraine is often under-diagnosed-and
under-treated when it is diagnosed. The result is likely to be failure of
treatment. Particular attention to diagnosis is needed in ED patients with acute 
headache, since there is a higher probability of secondary headache due to
underlying pathologies. According to European principles of management, acute
migraine treatment generally is stepwise. Of the two main steps, the first relies
on symptomatic medication, preferably NSAIDs with or without antiemetics. The
second step uses specific therapies, usually triptans. Modifications to routine
practice are appropriate in the ED. Parenteral administration of symptomatic
therapies is a preferred first choice, whilst immediate resort to triptans may be
appropriate, and achieve better outcomes, in patients with severe headache and
diagnostic confirmation of migraine.

Publication Types: 
    Review

PMID: 18785015 [PubMed - indexed for MEDLINE]

58: Intern Emerg Med. 2008 Oct;3 Suppl 1:S9-16.

From migraine to stroke.

Katsarava Z, Rabe K, Diener HC.

Department of Neurology, University of Essen, Hufelandstrasse 55, 45122 Essen,
Germany. zaza.katsarava@uni-essen.de

An association between migraine and ischemic stroke has been observed for many
years but the exact mechanisms by which migraine can lead to stroke are currently
still under investigation. Migraine seems to affect neurovascular factors and
substances that increase the risk of stroke during and in between migraine
attacks. Ischemic stroke can occur as a complication of an attack of migraine
with aura. Epidemiological studies suggest that vascular risk factors are
increased in migraineurs, thus increasing the incidence of stroke. Another
important issue is a patent foramen ovale (PFO), which is a well-known risk
factor for stroke and which, on the other hand, seems to be more frequent in
migraineurs than in people without. The purpose of this review is to summarize
the current literature linking the two neurological diseases: migraine and
stroke.

Publication Types: 
    Review

PMID: 18781406 [PubMed - indexed for MEDLINE]

59: Neurology. 2008 Sep 9;71(11):848-55.

Clinical course in migraine: conceptualizing migraine transformation.

Bigal ME, Lipton RB.

Department of Neurology, Albert Einstein College of Medicine, Bronx, NY, USA.
marcelo_bigal@merck.com

Migraine is currently conceptualized as a chronic disease with episodic
manifestations, with attacks that increase in frequency in a subgroup (migraine
transformation or progression). Transformation of migraine may be subdivided in
three partially overlapping forms, although research in this area is still in
infancy, and evidence is sometimes weak. Typically, transformation refers to
increases in attack frequency over time leading to chronic migraine; this process
is termed clinical transformation. Additionally, in some patients with migraine, 
physiologic changes in the CNS manifest themselves through alterations in
nociceptive thresholds (allodynia) and alterations in pain pathways (physiologic 
transformation). Finally, in some individuals, definitive brain lesions including
stroke and deep white matter lesions emerge (anatomic transformation). Herein we 
discuss the evidence that migraine may transform and then consider potential
mechanisms as well as risk factors. We close with a brief discussion of clinical 
strategies that arise based on this perspective on migraine.

Publication Types: 
    Review

PMID: 18779513 [PubMed - indexed for MEDLINE]

60: Neurology. 2008 Sep 9;71(11):841-7.

Calcitonin gene-related peptide does not cause the familial hemiplegic migraine
phenotype.

Hansen JM, Thomsen LL, Olesen J, Ashina M.

Danish Headache Center and Department of Neurology, Glostrup Hospital, Faculty of
Health Sciences, University of Copenhagen, Nordre Ringvej 57, Bolig 23-24,
DK-2600 Glostrup, Copenhagen, Denmark. jmh@dadlnet.dk

OBJECTIVE: The neuropeptide calcitonin gene-related peptide (CGRP) is a migraine 
trigger that plays a crucial role in migraine pathophysiology, and CGRP
antagonism is efficient in the treatment of migraine attacks. Familial hemiplegic
migraine (FHM) is a dominantly inherited subtype of migraine with aura associated
with several gene mutations. FHM shares many phenotypical similarities with
common types of migraine, indicating common neurobiological pathways. We tested
the hypothesis that the FHM genotype confers a CGRP hypersensitive phenotype.
METHODS: We included 9 FHM patients with known mutations in the CACNA1A and
ATP1A2 genes and 10 healthy controls. All subjects received i.v. infusion of CGRP
(1.5 microg/min). We recorded headache intensity on a verbal rating scale and
vascular changes in the middle cerebral artery and the superficial temporal
artery. RESULTS: CGRP infusion did not induce an aura in any of the participants.
The incidences of reported migraine and migraine-like headache were not different
in the two groups, with 22% (2 of 9) reporting migraine in the patient group and 
10% (1 of 10) reporting migraine-like headache in the control group (95% CI -0.31
to 0.55; p = 0.58). Headache severity and intensity were not different between
the groups. CONCLUSIONS: Familial hemiplegic migraine (FHM) patients do not show 
hypersensitivity of the calcitonin gene-related peptide (CGRP)-cyclic adenosine
3',5'-monophosphate pathway, as characteristically seen in migraine patients
without aura. This indicates that the pathophysiologic pathways underlying
migraine headache in FHM may be different from the common types of migraine and
questions whether CGRP antagonists would be effective in the treatment of FHM
patients.

Publication Types: 
    Comparative Study
    Controlled Clinical Trial
    Research Support, Non-U.S. Gov't

PMID: 18779512 [PubMed - indexed for MEDLINE]

61: Curr Pain Headache Rep. 2006 Jun;10(3):231-8.

Cutaneous allodynia and migraine: another view.

Dahlöf C.

Gothenburg Migraine Clinic, c/o Läkarhuset, Södra vägen 27, S-411 35 Gothenburg, 
Sweden. carl.dahlof@migraineclinic.se

The paradigm of early treatment of the migraine attack at mild pain intensity has
become one alternative to circumventing the problem of compromised oral
absorption of symptomatic drugs due to migraine-induced gastrointestinal
dysmotility. Early treatment also has been proposed to be advantageous because
most migraineurs could be less responsive to delayed treatment, owing to the
development of central sensitization of the trigeminal pain transmission. Ranking
the underlying principles, it seems that the improved response to an oral triptan
formulation at mild migraine symptom intensity has more to do with less impaired 
gastrointestinal absorption in the early stage of the attack than decreasing the 
time and preventing chances for central sensitization and development of
cutaneous allodynia. Furthermore, parenteral administration of a triptan is
always more likely to provide relief of symptoms than conventional tablets, even 
when it is used later in the course of the migraine attack. Individually tailored
use of the available triptan formulations will increase, without any doubt, the
within-migraineur consistency of response. It also will reduce the overall
proportion of migraine attacks or migraineurs not responding to triptan
treatment. Notwithstanding, the recommendation of early treatment during the
migraine attack when the pain is mild remains valid.

Publication Types: 
    Review

PMID: 18778579 [PubMed - indexed for MEDLINE]

62: Curr Pain Headache Rep. 2006 Jun;10(3):225-30.

Insights from experimental studies into allodynia and its treatment.

Oshinsky ML.

Department of Neurology, Thomas Jefferson University, 1020 Locust Street, Suite
398 JAH, Philadelphia, PA 19107, USA. michael.oshinsky@jefferson.edu

Migraine is a common disorder that often is accompanied by cutaneous allodynia.
Cutaneous allodynia on the head has been linked to sensitization of neurons in
the trigeminal nucleus caudalis in animal models of migraine. In addition,
migraine with allodynia is refractory to acute treatment with triptans.
Understanding the mechanisms of allodynia, preventing its development, and
finding effective treatments have become a priority in headache research. This
paper reviews recent research on the pathogenesis of headache and the generation 
of allodynia. We discuss the regions of the nervous system that are involved in
generating and maintaining headache pain and allodynia. We also discuss recent
advances in the treatment of migraine based on translation research.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 18778578 [PubMed - indexed for MEDLINE]

63: Curr Pain Headache Rep. 2006 Jun;10(3):221-4.

Neuroimaging of migraine.

Afridi SK, Goadsby PJ.

Institute of Neurology, Queen Square, London, WC1N 3BG, UK.

Neuroimaging of migraine recently has provided us with further information
regarding the pathophysiology of the disorder and posed important questions as to
whether migraine is a progressive disorder. This article provides the background 
of imaging in migraine and discusses recent advances in the field.

Publication Types: 
    Review

PMID: 18778577 [PubMed - indexed for MEDLINE]

64: Curr Pain Headache Rep. 2006 Jun;10(3):214-20.

Current views of the risk of stroke for migraine with and migraine without aura.

Kurth T, Diener HC.

Division of Aging, Brigham and Women's Hospital, 1620 Tremont Street, Boston, MA 
02120, USA. tkurth@rics.bwh.harvard.edu

The association between migraine and stroke is complex and is a continued focus
of attention. Several observational studies have identified migraine as an
independent risk factor for ischemic stroke. However, a distinction should be
made between migraine with and migraine without aura. The migraine-stroke
association is mostly apparent for young women with migraine with aura. The
association between migraine with aura and stroke is weaker in older age groups, 
which may be due to the fact that traditional cardiovascular risk factors are
more prominent with increasing age. Most studies have not found an association
between migraine without aura and ischemic stroke. Although there are several
hypotheses about the biologic link between migraine with aura and ischemic
stroke, the precise mechanisms remain unclear. However, because the absolute risk
of stroke is low in patients with migraine with aura, and migraine without aura
is likely not associated with ischemic stroke, most migraine patients will not
experience a stroke event.

Publication Types: 
    Review

PMID: 18778576 [PubMed - indexed for MEDLINE]

65: Curr Pain Headache Rep. 2006 Jun;10(3):207-13.

Migraine at all ages.

Bigal ME, Lipton RB.

Albert Einstein College of Medicine, Department of Neurology, 1165 Morris Park
Avenue, Bronx, NY 10451, USA. mbigal@aecom.yu.edu

Although the influence of age on the prevalence of migraine is well known, the
clinical characterization of migraine across the lifespan remains poorly studied.
Limited evidence suggests that migraine attacks get shorter and less typical with
advancing age. Similar results were found for transformed migraine at different
ages. In this article, we first discuss the prevalence and clinical features of
episodic migraine. We then discuss the epidemiology and profile of transformed
migraine across the lifespan. Clarifying the influence of age on migraine is of
importance for clinical diagnosis and treatment. It also may contain clues to
evolving disease biology.

Publication Types: 
    Review

PMID: 18778575 [PubMed - indexed for MEDLINE]

66: Curr Pain Headache Rep. 2006 Jun;10(3):167-78.

Is migraine a neuropathic pain syndrome?

Biondi DM.

Headache Management Program, Spaulding Rehabilitation Hospital, 125 Nashua
Street, Boston, MA 02114, USA. dbiondi@partners.org

The understanding of migraine pathophysiology has evolved from the belief that
migraine is a vascular disorder, to evidence that better defines migraine as a
neurogenic disorder associated with secondary changes in brain perfusion. There
is evidence to suggest that the early phase of migraine pain results from
neurogenic inflammation affecting cranial blood vessels and dura. Allodynia,
hyperalgesia, and expansion of nociceptive fields occur during most
well-established migraine attacks. These clinical features of migraine are
evocative of those traditionally associated with neuropathic pain. A hypothesis
that defines migraine pain as a unique neuropathic pain disorder can imply the
potential for neural plasticity and may provide insight into the mechanisms that 
underlie the transformation of episodic to chronic forms of migraine. The
neuropathic pain model of migraine pathophysiology not only paves the way for
mechanism-based treatment strategies that can improve the acute and preventive
management of migraine attacks, but also opens the door for the discovery of
novel therapeutic targets. It also lends momentum to an understanding of
clinically intriguing topics such as opiate-induced hyperalgesia and
medication-overuse headache (rebound headache), opioid resistance in the
treatment of chronic headache, and disease modification in defending against the 
potential for migraine transformation.

Publication Types: 
    Review

PMID: 18778570 [PubMed - indexed for MEDLINE]

67: Br J Pharmacol. 2008 Dec;155(7):967-9. Epub 2008 Sep 8.

Comment on:
    Br J Pharmacol. 2008 Dec;155(7):1093-103.

CGRP blockers in migraine therapy: where do they act?

Edvinsson L.

Department of Medicine, Institute of Clinical Sciences, Lund University Hospital,
Lund, Sweden. lars.edvinsson@med.lu.se

Calcitonin gene-related peptide (CGRP) is expressed throughout the CNS and
peripheral nervous system, consistent with control of vasodilatation,
nociception, motor function, secretion and olfaction. AlphaCGRP is prominently
localized in primary afferent C and Adelta fibres of spinal and trigeminal
ganglia. Activation of the trigeminal nerve results in antidromic release of
CGRP, acting through a CGRP1 receptor. Antagonists of CGRP1 receptors reduce
signalling in the trigeminovascular pathway at multiple sites, putatively inside 
the blood-brain barrier. Other ways of interacting with CGRP mechanisms have
appeared limiting the availability of CGRP in the circulation with a specific
CGRP antibody or with a CGRP-binding RNA-Spiegelmer. Either way reduces
neurogenic inflammation and attenuates signalling within the trigeminovascular
pathway. Specific CGRP receptor blockade has been shown to reduce the effect of
released CGRP and to abort acute migraine attacks. The novel approach of reducing
available CGRP is limited by the blood-brain barrier; its usefulness may be more 
as prophylaxis rather than as acute treatment of migraine.

Publication Types: 
    Comment

PMID: 18776915 [PubMed - indexed for MEDLINE]

68: J Pharmacol Sci. 2008 Sep;108(1):89-94. Epub 2008 Sep 6.

Goshuyuto, a traditional Japanese medicine for migraine, inhibits platelet
aggregation in guinea-pig whole blood.

Hibino T, Yuzurihara M, Terawaki K, Kanno H, Kase Y, Takeda A.

Tsumura Research Laboratories, Tsumura & Co., 3586 Yoshiwara, Ami-machi,
Inashiki-gun, Ibaraki, Japan. hibino_tomoko@mail.tsumura.co.jp

The effects of goshuyuto and chotosan, traditional Japanese medicines, on
collagen-induced platelet aggregation were examined using guinea-pig blood.
Goshuyuto at the concentration of 1,000 mug/mL inhibited collagen-induced
platelet hyper-aggregation to the same degree as aspirin at the concentration of 
100 mumol/L, but chotosan did not. Goshuyuto is composed of four medicinal herbs.
Of them, aqueous extracts of Evodiae Fructus and Zingiberis Rhizoma inhibited
platelet aggregation, but aqueous extracts of Zizyphi Fructus and Ginseng Radix
did not. Two components of Zingiberis Rhizoma, 6-shogaol and 6-gingerol, also
inhibited platelet aggregation. These results suggest that Evodiae Fructus and
Zingiberis Rhizoma may play important roles in the anti-aggregation effects of
goshuyuto and that 6-shogaol and 6-gingerol are among the active ingredients.
Therefore, goshuyuto may ameliorate migraine by preventing the hyper-aggregation 
of platelets in migraine with aura.

PMID: 18776713 [PubMed - indexed for MEDLINE]

69: Cephalalgia. 2008 Dec;28(12):1292-7. Epub 2008 Sep 11.

Physical activity and headache: results from the Nord-Trøndelag Health Study
(HUNT).

Varkey E, Hagen K, Zwart JA, Linde M.

Cephalea Headache Centre, Gothenburg, Sweden. emma.varkey@cephalea.se

The aim of this study was to evaluate, using a prospective and a cross-sectional 
design, the relationship between level of physical activity and migraine and
non-migraine headache. In the prospective part, 22,397 participants, not likely
to have headache, answered questions about physical activity at baseline
(1984-1986) and responded to a headache questionnaire at follow-up. In the
cross-sectional part (1995-1997), 46,648 participants answered questions about
headache and physical activity. Physically inactive individuals at baseline were 
more likely than active individuals to have non-migraine headache 11 years later 
(odds ratio 1.14, 95% confidence interval 1.02, 1.28). In the cross-sectional
analyses, low physical activity was associated with higher prevalence of migraine
and non-migraine headache. In both headache groups, there was a strong linear
trend (P < 0.001) of higher prevalence of 'low physical activity' with increasing
headache frequency. The result may indicate that physical inactivity among
headache-free individuals is a risk factor for non-migraine headache and that
individuals with headache are less physically active than those without headache.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 18771495 [PubMed - indexed for MEDLINE]

70: Cephalalgia. 2008 Dec;28(12):1315-26. Epub 2008 Sep 2.

Antiepileptic drugs on calcium currents recorded from cortical and PAG neurons:
therapeutic implications for migraine.

Martella G, Costa C, Pisani A, Cupini LM, Bernardi G, Calabresi P.

Clinica Neurologica, Dipartimento di Neuroscienze, Università di Roma Tor Vergata
Rome, Italy.

Cortex and periaqueductal grey (PAG) play a major role in the pathophysiology of 
migraine. Some antiepileptic drugs (AEDs) influence the activity of these
structures by modulating high-voltage-activated (HVA) Ca(2+) channels and are
effective in migraine prevention. The aim of the present study was to investigate
the expression of total HVA Ca(2+) channels in cortical and PAG neurons and to
study the differential action of AEDs on these channels. Isolated neurons were
visually identified based on morphological criteria. HVA currents were recorded
by whole-cell patch-clamp technique. The distribution ratio of L-, N-, P-, Q- and
R-type HVA Ca(2+) channels was different between cortical and PAG neurons. In
particular, we found that P- and Q-type HVA Ca(2+) channels were more expressed
in PAG neurons than in cortical cells, whereas L- and R-type HVA Ca(2+) channels 
showed an opposite distribution. Interestingly, N-type HVA Ca(2+) channels were
equally distributed in these two neuronal populations. A differential sensitivity
to AEDs of HVA Ca(2+) channels located on cortical and PAG neurons was observed
for topiramate (TPM), but not for lamotrigine (LTG) or levetiracetam (LEV). In
fact, whereas both LTG and LEV were equally effective and potent in inhibiting
HVA Ca(2+) currents in the two neuronal populations, TPM showed a much higher
potency and efficacy in blocking these currents in PAG neurons than in cortical
pyramidal cells. TPM, in fact, inhibited N-, P- and L-type channels in PAG
neurons, whereas in cortical neurons this AED modulated only P- and L-type
channels. Unlike the other AEDs investigated, valproic acid did not affect HVA
Ca(2+) currents in cortical and PAG neurons. The negative modulation of specific 
subtypes of HVA Ca(2+) channels by various AEDs can restore normal electrical
activity in target brain areas such as cortex and PAG, providing interesting
therapeutic approaches in migraine prevention.

PMID: 18771493 [PubMed - indexed for MEDLINE]

71: Cephalalgia. 2008 Sep;28 Suppl 2:42-9.

Applying the benefits of the AwM study in the clinic.

Dodick DW.

Mayo Clinic, Scottsdale, AZ, USA. dodick.david@mayo.edu

The Act when Mild (AwM) Study has illustrated the benefits to migraineurs of
taking triptan medication when their migraine pain is still mild and within 1 h
of the onset of symptoms. Yet many patients wait until the attack has fully
developed before taking their medication, with potentially inferior outcomes. In 
order to reproduce the benefits of early intervention using the AwM paradigm in
daily practice, a number of key barriers need to be addressed at both the
physician and patient level. Notable physician-related barriers to be overcome,
particularly at the primary care level, include accuracy of an early diagnosis of
migraine in newly presenting patients, communication skills that generate a
therapeutic engagement with migraine patients and enhance patient confidence, the
application of knowledge about up-to-date strategies to optimize treatment
outcomes, and the setting of achievable goals to avoid unrealistic expectations. 
Patient-related obstacles that need to be identified and overcome encompass
patient attitude, expectations, and behaviour. Migraine patients may be reluctant
to consult their physician, and, of those who do, many stop consulting because
they perceive that physicians can do little to improve their situation. For this 
reason, migraine patients need to be counselled about the most appropriate
medication for their level of symptoms. Moreover, patients need to be confident
before they will adhere routinely to the advice they receive, and high in the
priority of advice is the use of medication, particularly triptans, at the first 
sign of a migraine attack, rather than waiting until their attack has progressed 
to moderate or severe intensity. Patients who adhere to this advice are likely to
experience a notable reduction in the pain, disability and time lost that they
would otherwise suffer. The beneficial effects of early triptan intervention
illustrated in the AwM Study can therefore be best reproduced in the clinic if
the correct advice given to patients is not only accepted and applied by them,
but also followed up by their physician.

Publication Types: 
    Case Reports
    Research Support, Non-U.S. Gov't
    Review

PMID: 18715332 [PubMed - indexed for MEDLINE]

72: Cephalalgia. 2008 Sep;28 Suppl 2:36-41.

The 'Act when Mild' (AwM) study: a step forward in our understanding of early
treatment in acute migraine.

Goadsby PJ.

Headache Group, Department of Neurology, University of California, San Francisco,
San Francisco, CA, USA. peter.goadsby@ucsf.edu

An important issue in the management of migraine is the advice given to patients 
as to when to take their treatment in the course of the attack. While it seems
common sense almost to take treatment early in the attack, the evidence base for 
that advice is not as robust as could be expected. The 'Act when Mild' (AwM)
Study was a randomized, four-arm, multicentre, multinational, double-blind,
placebo-controlled trial of almotriptan (12.5 mg) to compare outcomes after
administration of treatment when pain intensity was mild and within 1 h of
headache onset (mild/early) with outcomes when pain had become moderate or
severe. Of 491 migraineurs enrolled, 403 were evaluable with an
intention-to-treat population (ITT) of 404. At the primary end-point, 2 h pain
free, on the ITT analysis 49% of patients in the almotriptan 12.5 mg treat
early/mild group and 40% in the treat moderate/severe group had responded (P =
0.21). Of these patients, 43 did not take medication according to their randomly 
allocated baseline pain intensity (mild or moderate/severe) and were subsequently
reassigned, prior to study unblinding, to the appropriate group (AwM population) 
for re-analysis of the primary outcome measure: 2-h pain-free rates. In the
almotriptan arms, 53% of the mild/early group and 37.5% of the moderate/severe
group were pain free at 2 h (P = 0.02; AwM population). The corresponding
proportions in the placebo groups were 24.7% and 17.5% (significantly lower than 
the respective almotriptan arms; P </= 0.01). Considering the ITT population,
secondary end-points were also significantly in favour of treatment with
almotriptan in the mild/early vs. the moderate/severe stage, including: sustained
pain-free, 45.6% vs. 30.5% (P = 0.02); headache recurrence at 24 h, 6% vs. 24% (P
= 0.0124). Adverse events were reported in < 5% of patients, with no significant 
differences between almotriptan and placebo and no serious events in any group.
Treatment with almotriptan while migraine pain is still mild and within 1 h of
onset provides statistically significant and clinically relevant enhancements in 
efficacy compared with waiting until pain has reached higher severity levels.

Publication Types: 
    Review

PMID: 18715331 [PubMed - indexed for MEDLINE]

73: Cephalalgia. 2008 Sep;28 Suppl 2:28-35.

Early treatment in migraine: how strong is the current evidence?

Gendolla A.

Klinik für Neurologie, Universitätsklinik Essen, Essen, Germany.
astrid.gendolla@uni-due.de

Over the last 10 years, triptans (serotonin 5-HT(1B/1D) receptor agonists) have
proved to be efficacious in treating migraine pain. However, recent evidence
suggests that patients are still not receiving optimal pain management,
particularly in clinical trials, where triptan treatment is generally not
initiated until pain has reached moderate intensity. Pathophysiological evidence 
indicates that if treatment is initiated at an early stage, while pain is still
mild and before the onset of central sensitization, outcomes for patients may be 
improved. In addition, a small number of clinical trials have been reported in
which triptans were taken early (within 1 h of pain onset) or while pain was
still mild; although constraints of trial design and data analysis limit definite
conclusions, overall the results suggest that this early/mild approach results in
more rapid and sustained pain relief. New studies are therefore needed to clarify
the clinical benefits of early treatment, whilst taking into account potential
risks, such as medication overuse. Ultimately, migraine treatment strategies
require optimization in order to meet patient expectations and to reduce the
current burden of migraine-associated disability.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 18715330 [PubMed - indexed for MEDLINE]

74: Cephalalgia. 2008 Sep;28 Suppl 2:21-7.

Pathways to the best fit of triptans for migraine patients.

Buzzi MG.

IRCCS Fondazione Santa Lucia, Rome, Italy. mg.buzzi@hsantalucia.it

Variability in drug response is a major barrier to the successful treatment of
migraine, and most treatments are only optimal in a subset of patients. Although 
triptans provide the best therapeutic option for the treatment of acute migraine,
it has not previously been possible to predict how well patients will respond to 
a specific triptan or whether they will experience unpleasant adverse events.
Hence, it has been difficult for physicians to match individual patients with the
most suitable agent to treat their migraine pain. Intrapatient variability has
been associated with polymorphisms in genes encoding drug-metabolizing enzymes,
drug transporters and drug targets. Pharmacogenetics provides the possibility of 
tailoring the therapeutic approach to individual patients, in order to maximize
treatment efficacy while minimizing the potential for unwanted side-effects. This
review demonstrates how almotriptan may overcome genetically determined responses
by utilizing diverse metabolic pathways to provide therapeutic benefit to many
migraineurs.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 18715329 [PubMed - indexed for MEDLINE]

75: Cephalalgia. 2008 Sep;28 Suppl 2:14-20.

Almotriptan in triptan-naïve patients: new evidence of benefits.

Pascual J.

University Hospital of Salamanca, Salamanca, Spain. juliopascual@telefonica.net

Although triptans represent the standard of care for migraine that is severe,
disabling and/or suboptimally responsive to migraine non-specific analgesia, they
are often underused in clinical practice. Simple analgesics and non-steroidal
anti-inflammatory drugs (NSAIDs) may provide effective treatment in some
patients, but it is an inadequate response to these drugs that drives the
therapeutic progression to triptans at the end of the traditional 'step-care'
approach. However, there are several disadvantages to this approach. It may cause
patients to lose confidence in their physician during this hierarchical
'trial-and-error' search for optimal treatment when prescribed medications are
ineffective, leading them to cease consulting before triptans are tried. It may
also result in a protracted time interval of suboptimal treatment, with
unnecessary suffering in patients who are triptan candidates. The alternative
approach of 'stratified care', in which medication is prescribed according to the
severity of symptoms, enables triptans to be used earlier in the treatment plan, 
especially when triptan candidates are given a choice between simple
analgesic/NSAID and triptan medication from the start. This raises the question
about the efficacy of triptans in triptan-naïve (TN) patients. A recent
exploratory post-hoc analysis compared the effect of almotriptan 12.5 mg in TN
patients (n = 342) with that in triptan-experienced patients (n = 237).
Almotriptan was effective in both cohorts with a consistent trend in favour of
the efficacy of almotriptan in TN patients, notably for sustained pain freedom
(SPF) and SPF plus no adverse events. Moreover, both headache recurrence at 24 h 
and the use of rescue medication was lower in the TN patients, whereas
tolerability was equally good in both cohorts. These findings indicate that TN
patients can expect excellent symptom control when they progress from
non-specific analgesia to treatment with almotriptan and support the earlier use 
of triptans in line with the stratified care paradigm.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 18715328 [PubMed - indexed for MEDLINE]

76: Cephalalgia. 2008 Sep;28 Suppl 2:9-13.

Emergency treatment of migraine.

Ducros A.

Centre d'Urgences Céphalées, Hôpital Lariboisière, Paris, France.
anne.ducros@lrb.aphp.fr

During the past few years, several surveys have highlighted the high prevalence
of migraine amongst the general French population and the large healthcare burden
associated with suboptimal treatment. Since it opened, the Centre d'Urgences
Céphalées (EHC) has treated more than 55 000 patients, the majority of whom were 
suffering from migraine. Expert diagnosis of the type and causes of the headache,
followed by immediate medication, allows patient stabilization. Detailed
assessments can then determine the most appropriate treatment for each patient to
improve outcomes and reduce the necessity for further emergency admissions.
Triptans are generally recommended, and for those patients who currently have
ineffective migraine control with one triptan, individual evaluation allows
prescription of an alternative triptan which will better suit their needs.
Follow-up is crucial to ensure that treatment remains optimal and that patient
expectations are being met. Although a minority of patients with severe headache 
will continue to require repeated emergency treatment, more than 90% of patients 
seen at the EHC can be successfully managed with this combination of accurate
diagnosis, effective treatment and individualized follow-up care.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 18715327 [PubMed - indexed for MEDLINE]

77: Cephalalgia. 2008 Sep;28 Suppl 2:1-8.

The role of general practitioners in migraine management.

Lantéri-Minet M.

Département d'Evaluation et Traitement de la Douleur, Pôle Neurosciences
Cliniques, Hôpital Pasteur, Nice, France. lanteri-minet.m@chu-nice.fr

General practitioners (GPs) play a pivotal role in managing migraine and ensuring
that patients have a positive first experience when seeking treatment. A large
proportion of migraineurs do not consult a GP, preferring to rely on
over-the-counter remedies to reduce pain and disability. For those who do
consult, receiving a satisfactory outcome at their first consultation is
important for ensuring subsequent effective management of their migraine. If
patient expectations are not met at their first visit (prescribed treatment is
ineffective or GP does not empathize with their suffering), patients may not
return for further consultation. There remains a need to improve migraine
diagnosis and treatment, and GPs require continuing medical education and
neurologist support to ensure that they are providing the best migraine
treatments and outcomes. More widespread use of diagnostic tools, standardized
management guidelines and individualized treatment regimens will help GPs
successfully manage both migraine symptoms and patient expectations.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 18715326 [PubMed - indexed for MEDLINE]

78: Rom J Intern Med. 2007;45(4):355-63.

Antiphospholipid antibodies and migraine: a retrospective study of 428 patients
with inflammatory connective tissue diseases.

Tănăsescu R, Nicolau A, Caraiola S, Ticmeanu M, Cojocaru IM, Frăsineanu A,
Ionescu R, Hristea A, Ene A, Anghel D, Tănăsescu R, Băicuş C.

Carol Davila University of Medicine and Pharmacy, Department of Neurology,
Colentina Hospital, Bucharest, Romania neuradutanasescu@yahoo.com

The antiphospholipid syndrome (APS) is defined by the presence of
antiphospholipid antibodies (aPL), associated with thrombosis or recurrent
spontaneous abortions. APS can occur alone or secondary to other conditions,
especially associated to inflammatory systemic autoimmune diseases. Among the
neurological manifestations associated with aPL, only ischemic stroke is
recognized by the actual classification criteria for APS. Other neurological
manifestations have been, however, repeatedly reported in case studies of APS
patients. Headache, and especially migraine, was commonly reported in APS
patients and is one of the classical features described by Hughes as related to
aPL, but studies failed to confirm this association. We studied retrospectively
the association between headache syndromes and aPL in 428 patients with
inflammatory connective tissue diseases admitted in the Neurology and Internal
Medicine Departments of Colentina Hospital-Bucharest. We found that migraine
alone, not headache of all types, is significantly associated with aPL in
patients with systemic immune disease. We studied the presence of cerebral
ischemia in patients with headache and aPL. In SLE patients, headache (all types)
is significantly associated with positive titers of aPL, and cerebral ischemic
lesions are significantly encountered. Even if both migraine and aPL are
conditions with high frequency in patients with immune systemic disease and their
association may be coincidental, the presence of ischemic lesions in patients
showing this association suggests the need to define a sub-group at risk, for
whom headache can be a marker and anticoagulants can be discussed.

PMID: 18767411 [PubMed - indexed for MEDLINE]

79: Ophthalmic Physiol Opt. 2008 Sep;28(5):404-21.

The content of optometric eye examinations for a young myope with headaches.

Shah R, Edgar DF, Rabbetts R, Blakeney SL, Charlesworth P, Harle DE, Evans BJ.

The Neville Chappell Research Clinic, The Institute of Optometry, 56-62 Newington
Causeway, London SE1 6DS. rakhee19@gmail.com

BACKGROUND: A recent review found standardised patient (SP) methodology to be the
gold standard methodology for evaluating clinical care. We used this to
investigate the content of optometric eye care for a young myopic patient with
headaches suggestive of migraine. METHODS: We recruited 100 community
optometrists who consented to be visited by an unannounced actor for an eye
examination and to have that eye examination recorded. The actor received
extensive training to enable accurate reporting of the content of the eye
examinations, via an audio recording and a checklist completed for each clinical 
encounter. The actor presented as a 20-year-old student seeking a private eye
examination and complaining of symptoms suggestive of migraine headaches. The
results of each clinical encounter were recorded on a pre-designed checklist
based on evidence-based reviews on headaches, clinical guidelines and the views
of an expert panel of optometrists. RESULTS: The presence of headache was
detected in 98% of cases. Eight standard headache questions were considered to be
the gold standard for primary care headache investigation. Although none of the
optometrists asked all of these questions, 22% asked at least four of the eight
questions. Sixty-nine per cent of practitioners asked the patient to seek a
medical opinion regarding the headaches. The proportion of the tests recommended 
by the expert panel that was carried out varied from 33% to 89% and the durations
of the eye examination varied from 5 to 50 min. CONCLUSION: SP encounters are an 
effective way of measuring clinical care within optometry and should be
considered for further comparative measurements of quality of care. As in
research using SPs in other healthcare disciplines, our study has highlighted
substantial differences between different practitioners in the duration and depth
of their clinical investigations. This highlights the fact that not all eye
examinations are the same and that there is no such thing as a 'standard sight
test'. We recommend that future optometric continuing education could usefully
focus on migraine diagnosis and assessment.

Publication Types: 
    Evaluation Studies
    Research Support, Non-U.S. Gov't

PMID: 18761478 [PubMed - indexed for MEDLINE]

80: Med J Aust. 2008 Sep 1;189(5):283-8.

Migraine prophylaxis.

Stark RJ, Stark CD.

Alfred Hospital, Monash University, Melbourne, VIC, Australia.
richard.stark@med.monash.edu.au

There is a wide array of options for migraine prophylaxis; many of the available 
drugs are clearly proven to be effective and yet are underused in Australia.
"New" drugs which are gaining favour for migraine prophylaxis include topiramate,
candesartan, gabapentin and botulinum toxin. The evidence for efficacy is
excellent for topiramate and reasonably good but limited for candesartan and
gabapentin. The use of botulinum toxin is controversial and has gained
substantial popularity through anecdotal experience rather than convincing
published evidence. Transformed or chronic migraine with medication overuse is a 
particularly difficult problem. New strategies to aid in medication withdrawal
are reviewed. The approach to menstrual migraine and migraine with prominent aura
may differ from that for typical migraine. Novel approaches are being explored
for these problems.

Publication Types: 
    Review

PMID: 18759728 [PubMed - indexed for MEDLINE]

81: Expert Rev Neurother. 2008 Sep;8(9):1347-54.

Proinflammatory mediators and migraine pathogenesis: moving towards CGRP as a
target for a novel therapeutic class.

Farinelli I, Missori S, Martelletti P.

Department of Medical Sciences, 2nd School of Medicine, Sapienza University,
Sant'Andrea Hospital, Via di Grottarossa 1035, I-00189 Rome, Italy.
ivano.farinelli@uniroma1.it

Migraine is a complex neurological disorder in which genetic and environmental
factors interact. At present, frontline therapies in migraine's acute treatment
include the use of NSAIDS and triptans. Restrictions in the use of frontline
drugs for migraine treatment and evidence concerning CGRP's key role led research
towards new pathways involved in migraine pathophysiology. CGRP is a strong
vasodilatory neuropeptide released from activated trigeminal sensory nerves. The 
development of CGRP antagonists has also been driven by the fact that triptans
are vasoconstrictive and cannot be used in patients with vascular risk factors.
BIBN4096 (olcegepant) is the first CGRP antagonist for the treatment of migraine 
which has been tested in clinical trials, but its principal limitation is that
BIBN4096 presents low oral bioavailability and has only been tested through
intravenous formulation. The first oral nonpeptide CGRP antagonist, MK-0974
(telcagepant), has recently been shown to be highly effective in the treatment of
migraine attacks. This development can be considered the most important
pharmacological breakthrough for migraine treatment since the introduction of
sumatriptan in the early 1990s. These results are important since they confirm
the current pathophysiological concept of migraine. The future introduction of
CGRP antagonists in clinical practice could represent a progress for migraine
therapy.

Publication Types: 
    Review

PMID: 18759547 [PubMed - indexed for MEDLINE]

82: Expert Rev Neurother. 2008 Sep;8(9):1331-7.

Migraine and patent foramen ovale: connecting flight or one-way ticket?

Rigatelli G.

Adult Congenital Heart Disease, Cardiovascular Diagnosis & Endoluminal
Interventions, Roligo General Hospital, Roligo, Italy. jackyheart@libero.it

CONTEXT: The genesis of migraine in patients with patent foramen ovale (PFO) and 
its relationship with paradoxical stroke is still debated. Some authors agree
that migraine with aura and PFO have higher coincidences than would be expected
by chance and that it is possible that both conditions are inherited together.
OBJECTIVE: The present review aims to make a comprehensive attempt at clarifying 
the PFO-migraine connection in light of recent evidence from literature. EVIDENCE
ACQUISITION: A Medline search using both OVID and PubMed was performed by
searching for literature in English regarding randomized trials, prospective
cohort studies, meta-analyses, reviews and editorials about PFO and migraine
between 1998 and 2008. Search key words were 'migraine' and 'patent foramen
ovale' matched with 'prevalence', 'echocardiography', 'transcranial Doppler
ultrasound', 'magnetic resonance imaging', 'coagulation abnormalities' and
'transcatheter closure treatment'. Additional reference material was obtained
from the proceedings of relevant conferences on PFO and migraine, and the
author's personal experience. EVIDENCE SYNTHESIS: Echocardiographic, transcranial
Doppler and MRI studies suggest that migraine patients are at higher risk of
stroke compared with the normal population and often have white matter brain
lesions on MRI. A large proportion of PFO patients have migraine, in particular
migraine with aura, and migraine with aura patients plus PFO have larger shunts
compared with migraine-free patients. It has been suggested that patients with
migraine and large PFO have an increased risk of paradoxical embolism. Most
patients with PFO and migraine respond well to transcatheter closure and this
fact is unlikely to be caused just by a placebo effect. CONCLUSIONS: Although
many gray areas are still present, migraine with aura and large PFO seem to be
strictly related to both anatomic and functional states at least in a proportion 
of patients.

Publication Types: 
    Review

PMID: 18759545 [PubMed - indexed for MEDLINE]

83: Expert Rev Neurother. 2008 Sep;8(9):1321-30.

Migraine genetics.

Montagna P.

Department of Neurological Sciences, University of Bologna Medical School, Via U.
Foscolo 7, 40123 Bologna, Italy. pasquale.montagna@unibo.it

Migraine with aura (MA) and migraine without aura (MO) are primary headaches
prevalent in the general population that carry a substantial familial liability. 
Based on the model of migraine as a complex disease, a multifactorial type of
inheritance has been suggested, but familial hemiplegic migraine (FHM),
classified as a subtype of MA, shows an autosomal dominant transmission pattern
and is due to mutations in three genes encoding for neural channel subunits.
These FHM mutations, however, account for a minority of the FHM families and are 
not usually found in sporadic HM or in the typical migraines MA/MO. This implies 
that the genetic predisposition to the typical migraines may be different and
that FHM could be better classified as a type of syndromic migraine rather than a
MA subtype. Linkage and genome-wide scans have disclosed several chromosomal
liability loci in selected families with MA/MO. It is likely that typical
migraine genes will be discovered in the future. Epigenetic mechanisms,
especially those acting in the early stages of neural development, are here
proposed to be involved in the genetics of the typical migraines, especially if
the typical migraines are modeled as evolutionarily conserved behaviors (sickness
behavior) enacted out of a genetic repertoire.

Publication Types: 
    Review

PMID: 18759544 [PubMed - indexed for MEDLINE]

84: Expert Rev Neurother. 2008 Sep;8(9):1307-11.

Migraine and epilepsy: genetically linked?

Haan J, van den Maagdenberg AM, Brouwer OF, Ferrari MD.

Department of Neurology K5Q, Leiden University Medical Centre, PO Box 9600, 2300 
RC Leiden, The Netherlands. jhaan@rijnland.nl

Most molecular genetic knowledge in migraine so far comes from the study of a
rare subtype, familial hemiplegic migraine (FHM). The three known FHM genes
(CACNA1A, ATP1A2 and SCN1A) are ion transporter genes. Mutations in all three FHM
genes can also be associated with epilepsy. Of the many epilepsy genes that have 
been discovered, an association with migraine has been reported only for SCN1A.
There is probably a lack of systematic studies of migraine in epilepsy families. 
A genetically determined dysfunction of ion transporters seems to point, at least
to certain extent, at a common underlying mechanism for both paroxysmal
disorders. The effect of ion channel mutations on neuronal neurotransmitter
release is probably of major importance. In this article, we will discuss the
arguments for a genetic relationship between migraine and epilepsy. A possible
genetic link could give insight into the pathophysiology of both syndromes, and
offer possibilities to develop specific preventive treatment aimed at the
underlying ion transporter dysfunction and its consequences.

Publication Types: 
    Review

PMID: 18759542 [PubMed - indexed for MEDLINE]

85: Expert Rev Neurother. 2008 Sep;8(9):1289-97.

Sumatriptan/naproxen sodium combination for the treatment of migraine.

Cleves C, Tepper SJ.

Department of Pediatric Neurology, Center for Headache and Pain, Neurological
Institute, Cleveland Clinic Foundation, 778 Long Ridge Rd, Stamford, CT 06902,
USA. clevesc@ccf.org

Sumatriptan 85 mg with naproxen sodium 500 mg, a combination tablet for the acute
treatment of migraine, is approved in the USA. It is likely that triptan/NSAID
combination benefits are a class effect, although the majority of data are on
sumatriptan and naproxen sodium. The combination tablet demonstrated superior
effectiveness over its individual components or placebo in two Phase III
regulatory trials on six coprimary end points. The pharmacokinetic shifts in the 
combination tablet result in an earlier T(max) for sumatriptan, a later T(max)
for naproxen sodium and a reduction of the C(max) by 36% for naproxen sodium
compared with the components alone. In addition, the 85 mg dose of sumatriptan in
the combination tablet has an area under the curve similar to 100 mg of
sumatriptan alone. The clinical advantage of the sumatriptan and naproxen sodium 
combination is likely to be prolonged benefit per attack, that is, a sustained
pain-free response.

Publication Types: 
    Review

PMID: 18759540 [PubMed - indexed for MEDLINE]

86: J Biol Chem. 2008 Nov 7;283(45):31097-106. Epub 2008 Aug 26.

Diverse functional consequences of mutations in the Na+/K+-ATPase alpha2-subunit 
causing familial hemiplegic migraine type 2.

Tavraz NN, Friedrich T, Dürr KL, Koenderink JB, Bamberg E, Freilinger T, Dichgans
M.

Technical University of Berlin, Institute of Chemistry, D-10623 Berlin, Germany.

Mutations in ATP1A2, the gene coding for the Na(+)/K(+)-ATPase alpha(2)-subunit, 
are associated with both familial hemiplegic migraine and sporadic cases of
hemiplegic migraine. In this study, we examined the functional properties of 11
ATP1A2 mutations associated with familial or sporadic hemiplegic migraine,
including missense mutations (T263M, T376M, R383H, A606T, R763H, M829R, R834Q,
R937P, and X1021R), a deletion mutant (del(K935-S940)ins(I)), and a frameshift
mutation (S966fs). According to the Na(+)/K(+)-ATPase crystal structure, a subset
of the mutated residues (Ala(606), Arg(763), Met(829), and Arg(834)) is involved 
in important interdomain H-bond networks, and the C terminus of the enzyme, which
is elongated by the X1021R mutation, has been implicated in voltage dependence
and formation of a third Na(+)-binding site. Upon heterologous expression in
Xenopus oocytes, the analysis of electrogenic transport properties, Rb(+) uptake,
and protein expression revealed pronounced and markedly diverse functional
alterations in all ATP1A2 mutants. Abnormalities included a complete loss of
function (T376M), impaired plasma membrane expression (del(K935-S940)ins(I) and
S966fs), and altered apparent affinities for extracellular cations or reduced
enzyme turnover (R383H, A606T, R763H, R834Q, and X1021R). In addition, changes in
the voltage dependence of pump currents and the increased rate constants of the
voltage jump-induced redistribution between E(1)P and E(2)P states were observed.
Thus, mutations that disrupt distinct interdomain H-bond patterns can cause
abnormal conformational flexibility and exert long range consequences on apparent
cation affinities or voltage dependence. Of interest, the X1021R mutation
severely impaired voltage dependence and kinetics of Na(+)-translocating partial 
reactions, corroborating the critical role of the C terminus of Na(+)/K(+)-ATPase
in these processes.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 18728015 [PubMed - indexed for MEDLINE]

87: Cephalalgia. 2008 Oct;28(10):1012-6. Epub 2008 Aug 22.

Tolerability of acute migraine medications: influence of methods of assessment
and relationship with headache attributes.

Feleppa M, Apice G, D'Alessio A, Fucci S, Bigal ME.

Department of Neurology, Hospital 'G. Rummo', Benevento, Italy.
michele.feleppa@ao-rummo.it

Tolerability is an important attribute of patient satisfaction with, and
consequence adherence to, migraine acute treatment. Nevertheless, the
determinants of tolerability are poorly explored. Accordingly, our objectives
were: (i) in subjects receiving triptans, to contrast two methods of assessing
adverse events (AEs); and (ii) to explore the relationship between migraine
features and treatment attributes with tolerability. We surveyed 365 migraineurs 
who had been using the same triptan for at least 3 months. After prospectively
treating an attack, headache characteristics and treatment response were assessed
using headache calendars. Subjects also completed a standardized questionnaire,
first asking about any AE and then prompting patients with a list of possible
AEs. We contrasted both sets of answers and conducted logistic regression to
assess if headache attributes or response to therapy influenced tolerability.
Using the unprompted method, AEs occurred in 11.5-36.4% of patients, depending on
the triptan used. Using the prompted method, they ranged from 26.9 to 64.3%.
Chest and neck tightness were spontaneously reported by 3.5% of the sample, vs.
7.4% when prompted (P < 0.05). Chest pain was not spontaneously reported and was 
elicited in nine patients (2.5%, P = 0.002). Feeling groggy occurred in 5.7 and
17.5% (P < 0.001). AEs were not a function of headache severity, disability,
efficacy of the drug, time to meaningful relief with the drug or recurrence of
pain. The report of AEs varies dramatically with the methods of assessment.
However, tolerability is not influenced by the severity of the attacks or by
medication efficacy.

PMID: 18727650 [PubMed - indexed for MEDLINE]

88: Cephalalgia. 2008 Nov;28(11):1196-200. Epub 2008 Aug 22.

Medication overuse headache: predictors and rates of relapse in migraine patients
with low medical needs. A 1-year prospective study.

Rossi P, Faroni JV, Nappi G.

Headache Clinic INI Grottaferrata, IRCCS C. Mondino Institute of Neurology
Foundation, Pavia, Italy. paolo.rossi90@alice.it

The aim of this study was to evaluate the rates and predictors of relapse, after 
successful drug withdrawal, in migraine patients with medication overuse headache
(MOH) and low medical needs. The study population, study design, inclusion
criteria and short-term effectiveness of the medication withdrawal strategies
have been described elsewhere (Rossi et al., Cephalalgia 2006; 26:1097).
Relapsers were defined as those patients fulfilling, at follow-up, the new
International Classification of Headache Disorders, 2nd edn, appendix criteria
for MOH. Complete datasets were available for 83 patients. At 1 year's follow up,
the relapse rate was 20.5%. Univariate analysis showed that patients who relapsed
had a longer duration of migraine with more than eight headache days/month, a
longer duration of drug overuse, had tried a greater number of preventive
treatments in the past, had a lower reduction of headache frequency after
withdrawal, and had previously consulted a greater number of specialists. Binary 
logistic regression analysis was performed, and three variables emerged as
significant predictors of relapse: duration of migraine with more than eight
headache days/month [odds ratio (OR) 1.57, P = 0.01], a higher frequency of
migraine after drug withdrawal (OR 1.48, P = 0.04) and a greater number of
previous preventive treatments (OR 1.54, P = 0.01). In patients with migraine
plus MOH and low medical needs, relapse seems to depend on a greater severity of 
baseline migraine.

Publication Types: 
    Randomized Controlled Trial

PMID: 18727648 [PubMed - indexed for MEDLINE]

89: Cephalalgia. 2008 Oct;28(10):1003-11. Epub 2008 Aug 22.

The importance of placebo in headache research.

Diener HC, Schorn CF, Bingel U, Dodick DW.

Department of Neurology, University Duisburg-Essen, Essen, Germany.
hans.diener@uni-duisburg-essen.de

The best way to appreciate the efficacy of drug and behavioural therapy in the
acute and prophylactic treatment of headache is to perform placebo-controlled
randomized trials. In order to plan and conduct these studies in the most
appropriate way, it is desirable to know which factors influence the placebo
response. This paper reviews factors which influence the placebo response in
clinical trials, such as expectation, blinding, route of application of drugs and
age, gender and geographical distribution. Response rates of placebo in the
treatment of acute headache episodes are higher than in headache prophylaxis.
Invasive procedures such as injections have a higher placebo response compared
with oral drugs. Variables known to influence the placebo response have to be
taken into consideration to calculate properly the power of planned randomized
trials.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 18727647 [PubMed - indexed for MEDLINE]

90: Cephalalgia. 2008 Nov;28(11):1179-87. Epub 2008 Aug 22.

Differential effects of corticosteroids on the expression of cyclooxygenase-2,
tumour necrosis factor-alpha and matrix metalloproteinase-9 in an animal model of
migraine.

Kim GM, Jin KS, Chung CS.

Department of Neurology, Samsung Medical Centre, Sungkyunkwan University School
of Medicine, Seoul, Korea. kimgm@skku.edu

Nitric oxide (NO) directly activates trigeminal afferents innervating the dura
mater and up-regulates inflammatory mediators. We evaluated NO-mediated
up-regulation of cyclooxygenase-2 (COX-2), tumour necrosis factor-alpha
(TNF-alpha) and matrix metalloproteinase-9 (MMP-9), and the effect of
glucocorticoid administration in an experimental animal model of migraine. COX-2 
and TNF-alpha expression and MMP-9 activity were increased after continuous
intravenous infusion of glyceryl trinitrate (GTN), a NO donor. Immunofluorescence
staining demonstrated strong expression of these inflammatory mediators in the
meningeal blood vessels. Methylprednisolone (MP) down-regulated MMP-9, which was 
reversed by RU486, a glucocorticoid receptor antagonist. COX-2 and TNF-alpha
expression was not affected by MP or RU486 administration. These results suggest 
proinflammatory mediators are involved in the NO-mediated cascade of migraine
pathogenesis. Further understanding of the activation of these inflammatory
mediators at the transcriptional level may have therapeutic implications for
future migraine treatments.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 18727644 [PubMed - indexed for MEDLINE]

91: Cephalalgia. 2008 Dec;28(12):1259-63. Epub 2008 Aug 22.

Symptoms of migraine in the paediatric population by age group.

Eidlitz-Markus T, Gorali O, Haimi-Cohen Y, Zeharia A.

Department of Paediatrics E/Ambulatory Day Care, Schneider Children's Medical
Centre of Israel, Petah Tiqwa, Israel. eidlitz@post.tau.ac.il

The revised criteria of the International Headache Society (IHS) for paediatric
headache do not differentiate among age groups. This study aims to determine if
different symptoms of migraine are specific or typical of different age groups of
children. The files of 160 children (79 boys, 81 girls, mean age 10.39 +/- 3.71
years) with migraine treated at the paediatric headache clinic of a tertiary
centre were reviewed. The diagnosis was based on the criteria of the IHS
(ICHD-II). The patients were divided by age into three groups according to
educational status, < or =6 years (preschool, group 1), >6 to < or =12 years
(elementary school, group 2) and >12 to < or =18 years (secondary school, group
3), and compared by symptoms and signs. Symptoms of migraine with and without
aura were also compared. There was no significant difference among the groups in 
rates of unilateral headache, phonophobia, photophobia, awakening pain, nausea or
worsening of pain during physical activity. The parameters found to be
statistically significant were dizziness and duration of migraine, and aura which
increased with time. Frequency of attacks increased with age. The single
statistically significant parameter found to be more frequent in younger age was 
vomiting. The statistically significant parameters of nausea and duration of
migraine were more frequent in migraine with aura compared with migraine without 
aura. In conclusion, most of the migraine symptoms included in the 2004
recommendations of the IHS are not typical for specific paediatric age groups,
probably because brain maturity is a continuous process. A familial history of
migraine is a frequent finding among all age groups and should be considered in
the paediatric criteria, especially in younger children in whom diagnosis is more
difficult. Vomiting may help the diagnosis of migraine in young children with a
familial history of migraine.

Publication Types: 
    Comparative Study

PMID: 18727643 [PubMed - indexed for MEDLINE]

92: Cephalalgia. 2008 Oct;28(10):1069-80. Epub 2008 Aug 22.

Olfactory hypersensitivity in migraineurs: a H(2)(15)O-PET study.

Demarquay G, Royet JP, Mick G, Ryvlin P.

Service de Neurologie, Hôpital de la Croix-Rousse; INSERM, U821, Université
Claude-Bernard, Institut Fédératif des Neurosciences de Lyon, Lyon, France.
genevieve.demarquay@chu-lyon.fr

Olfactory hypersensitivity (OHS) may occur during migraine attacks and seems to
be very specific to this form of headache. OHS is also observed during
migraine-free periods and is associated with the presence of odour-triggered
attacks. Yet the pathophysiology of OHS remains unknown. The aim of our study was
to evaluate olfactory processing in migraineurs with OHS and to investigate
whether regional cerebral blood flow (rCBF) associated with olfactory stimulation
is modified in these patients compared with controls. Eleven migraineurs with OHS
and 12 controls participated in a H(2)(15)O-positron emission tomography study,
including three scans in which odours were delivered and three scans where only
odourless air was delivered. rCBF during olfactory condition was compared with
that for the odourless baseline condition. Between-group analyses were performed 
using voxel-based and region-of-interest analyses. During both olfactory and
non-olfactory conditions, we observed higher rCBF in the left piriform cortex and
antero-superior temporal gyrus in migraineurs compared with controls. During
odour stimulation, migraineurs also showed significantly higher activation than
controls in the left temporal pole and significantly lower activation in the
frontal (left inferior as well as left and right middle frontal gyri) and
temporo-parietal (left and right angular, and right posterior superior temporal
gyri) regions, posterior cingulate gyrus and right locus coeruleus. These results
could reflect a particular role of both the piriform cortex and antero-superior
temporal gyrus in OHS and odour-triggered migraine. Whether these rCBF changes
are the cause or a consequence of odour-triggered migraines and interictal OHS
remains unknown. Further comparisons between migraineurs with and without OHS are
warranted to address this issue. The abnormal cerebral activation patterns during
olfactory stimulation might reflect altered cerebrovascular response to olfactory
stimulation due to the migraine disease, or an abnormal top-down regulation
process related to OHS.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 18727640 [PubMed - indexed for MEDLINE]

93: Cephalalgia. 2008 Dec;28(12):1245-58. Epub 2008 Aug 22.

The blood-brain barrier in migraine treatment.

Edvinsson L, Tfelt-Hansen P.

Department of Internal Medicine, University Hospital, Lund, Sweden.
lars.edvinsson@med.lu.se

Salient aspects of the anatomy and function of the blood-barrier barrier (BBB)
are reviewed in relation to migraine pathophysiology and treatment. The main
function of the BBB is to limit the access of circulating substances to the
neuropile. Smaller lipophilic substances have some access to the central nervous 
system by diffusion, whereas other substances can cross the BBB by
carrier-mediated influx transport, receptor-mediated transcytosis and
absorptive-mediated transcytosis. Studies of drugs relevant to migraine
pathophysiology and treatment have been examined with the pressurized
arteriography method. The drugs, given both luminally and abluminally, provide
important notions regarding antimigraine site of action, probably abluminal to
the BBB. The problems with the BBB in animal models designed to study the
pathophysiology, acute treatment models and preventive treatments are discussed
with special emphasize on the triptans and calcitonin gene-related peptide
(CGRP). The human experimental headache model, especially the use of glycerol
trinitrate (the nitric oxide model), and experiences with CGRP administrations
utilize the systemic administration of the agonists with effects on other
vascular beds also. We discuss how this can be related to genuine migraine
attacks. Our view is that there exists no clear proof of breakdown or leakage of 
the BBB during migraine attacks, and that antimigraine drugs need to pass the BBB
for efficacy.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 18727638 [PubMed - indexed for MEDLINE]

94: Cephalalgia. 2008 Dec;28(12):1277-81. Epub 2008 Aug 22.

Lack of seasonal variation in menstrually-related migraine.

Bekkelund SI, Alstadhaug KB, Salvesen R.

Department of Neurology, University Hospital of North Norway, Tromsø, Norway.
svein.ivar.bekkelund@unn.no

The aim of the study was to study seasonal variation in migraine headache in a
group of women with menstrually-related migraine (MRM) compared with
non-menstrual migraine. Via newspaper advertisement, women with migraine living
in North Norway were invited. The patients were included by questionnaire and
telephone interview. We prospectively recorded migraine attacks from a 12-month
headache diary performed by a group of 62 women with a mean age of 36.0 years
(range 16-46 years), who fulfilled the criteria of migraine without aura. Of
these, 29 had MRM and 33 non-menstrual migraine. Mean ratio between number of
attacks in the light arctic season (May-June-July) divided with total number of
migraine attacks during 12 months was 0.24 (9.4/38.4) in the group of MRM
compared with 0.25 (5.6/22.1) in others (confidence interval -4.2, 6.3, P =
0.84). Nor were there more migraine attacks in the dark season in an arctic area 
(November-December-January) in any group. We found a higher migraine attack rate 
in those with MRM, but no indication of more or less frequency of attacks during 
the bright arctic season. These findings support the assumption that MRM and
seasonal variation of migraine are due to different mechanisms.

Publication Types: 
    Comparative Study

PMID: 18727637 [PubMed - indexed for MEDLINE]

95: Cephalalgia. 2008 Dec;28(12):1282-91. Epub 2008 Aug 22.

Interictal brain 5-HT1A receptors binding in migraine without aura: a
18F-MPPF-PET study.

Lothe A, Merlet I, Demarquay G, Costes N, Ryvlin P, Mauguière F.

Université de Lyon, Lyon, Inserm, U821, Bron, Institut Fédératif des
Neurosciences de Lyon, France.

In this study we aimed to assess the brain distribution of 5-HT(1A) receptors in 
migraine patients without aura. Ten female migraine patients and 24 female
healthy volunteers underwent magnetic resonance imaging and positron emission
tomography using a radioligand antagonist of 5-HT(1A) receptors
[4-(2'-methoxyphenyl)-1-[2'-(N-2-pirydynyl)-p-fluorobenzamido]-ethylpiperazine
((18)F-MPPF)]. A simplified reference tissue model was used to generate
parametric images of 5-HT(1A) receptor binding potential (BP) values. Statistical
Parametrical Mapping (SPM) analysis showed increased MPPF BP in posterior
cortical areas and hippocampi bilaterally in patients compared with controls.
Region of interest (ROI) analysis showed a non-significant trend in favour of a
BP increase patients in cortical regions identified by the SPM analysis except in
hippocampi, left parietal areas and raphe nuclei. During the interictal period of
migraine patients without aura, the increase of MPPF BP in posterior cortical and
limbic areas could reflect an increase in receptor density or a decrease of
endogenous serotonin, which could explain their altered cortical excitability.

PMID: 18727636 [PubMed - indexed for MEDLINE]

96: Cephalalgia. 2008 Dec;28(12):1298-304. Epub 2008 Aug 22.

The visual aura rating scale as an outcome predictor for persistent visual aura
without infarction.

Wang YF, Fuh JL, Chen WT, Wang SJ.

Neurological Institute, Taipei Veterans General Hospital, Taipei, Taiwan.

Persistent visual aura without infarction is rare. Its pathogenic mechanism is
unknown, and the response to migraine prophylactic agents varies. A systematic
analysis of 29 patients (23 from the literature and six in the present report;
6M/23F, mean age 37.6 years) was carried out in terms of demographics, headache
and visual symptom profiles, treatment regimens and outcomes. Patterns of visual 
disturbances (VDs) were re-assessed with the Visual Aura Rating Scale (VARS,
score 0-10). Even though the majority of patients had headache improvement, only 
eight (27.6%) had complete resolution of persistent VD, without definite
relevance to any specific agent. Patients with complete resolution of VD tended
to have scotoma (50.0% vs. 0%; P = 0.003), unilateral/homonymous involvement
(62.5% vs. 9.5%; P = 0.008), higher VARS scores (1.88 +/- 1.73 vs. 0.10 +/- 0.30;
P < 0.001) and shorter duration of illness (10.0 +/- 12.9 vs. 60.2 +/- 90.9
months, P = 0.008) compared with those without. These findings remained even when
the six current patients were not included for analyses. In conclusion, the
prognosis of persistent VD was poor, and higher VARS scores, i.e. more typical of
migraine visual aura, predicted a better outcome. For those with a potential for 
complete resolution, improvement would occur early in the course.

Publication Types: 
    Case Reports
    Research Support, Non-U.S. Gov't

PMID: 18727635 [PubMed - indexed for MEDLINE]

97: Appl Psychophysiol Biofeedback. 2008 Sep;33(3):125-40. Epub 2008 Aug 26.

Biofeedback treatment for headache disorders: a comprehensive efficacy review.

Nestoriuc Y, Martin A, Rief W, Andrasik F.

Department of Psychiatry, Brigham and Women's Hospital, Harvard Medical School,
Boston, MA 02120, USA. ynestoriuc@partners.org

The aim of the present review was to critically evaluate the documented evidence 
regarding the efficacy of biofeedback for the two most prevalent headache
conditions--migraine and tension-type headache. Drawing upon two recently
published meta-analyses, data from 150 outcome studies, including randomized
controlled trials as well as uncontrolled quasi-experimental designs, were
screened. Of these, 94 studies were selected for inclusion according to
predefined criteria. Meta-analytic integrations were carried out separately for
the two conditions of interest. The main results were medium-to-large mean effect
sizes for biofeedback in adult migraine and tension-type headache patients.
Treatment effects remained stable over an average follow-up period of 14 months, 
both in completer and intention-to-treat analyses. Headache frequency was the
primary outcome variable and showed the largest improvements. Further significant
effects were shown for perceived self-efficacy, symptoms of anxiety and
depression, and medication consumption. Reduced muscle tension in pain related
areas was observed in electromyographic feedback for tension-type headache.
Biofeedback was more effective than waiting list and headache monitoring
conditions in all cases, while electromyographic feedback for tension-type
headache showed additional significant effects over placebo and relaxation
therapies. Levels of efficacy (migraine: efficacious, level 4; tension-type
headache: efficacious and specific, level 5) and recommendations for future
research are provided.

Publication Types: 
    Meta-Analysis

PMID: 18726688 [PubMed - indexed for MEDLINE]

98: Am J Otolaryngol. 2008 Sep-Oct;29(5):295-9. Epub 2008 Mar 19.

Migraine and audiovestibular dysfunction: is there a correlation?

Dash AK, Panda N, Khandelwal G, Lal V, Mann SS.

Department of Otolaryngology, Postgraduate Institute of Medical Education and
Research, Chandigarh, India.

PURPOSE: To study the audiovestibular functions in cases of migraine with or
without vertigo. MATERIALS AND METHODS: This was a prospective study involving 50
cases of migraine who were divided into 2 groups: patients with vertigo and those
without. All patients underwent a detailed otological and neurootological
examination followed by full audiological and vestibular investigation including 
pure tone audiometry, speech reception threshold, speech discrimination score,
tone decay, short increment sensitivity index, auditory brainstem-evoked
responses, and electronystagmography (ENG). RESULTS: Thirty-eight (76%) of 50
patients had vertigo on presentation, of which rotatory nonpositional vertigo
(22/38) was the most common. Phonophobia was the most common auditory symptom
(35/50, 70%) followed by tinnitus (25/50, 50%). Only 17 patients (34%) reported
hearing loss, of whom only 7 had documented hearing loss on pure tone audiometry.
However, the auditory brainstem-evoked responses of all these patients showed
some abnormalities in the form of prolonged absolute latency or prolonged
interwave peak latencies or both. Electronystagmography revealed canal paresis in
13 patients (26%), although there was no statistical difference between patients 
with or without vertigo on various electronystagmographic parameters. CONCLUSION:
Auditory brainstem-evoked response abnormalities may be the earliest indicator of
impending auditory involvement in migraine.

Publication Types: 
    Comparative Study

PMID: 18722884 [PubMed - indexed for MEDLINE]

99: Eur J Neurol. 2008 Oct;15(10):1071-4. Epub 2008 Aug 19.

Adapted Finnish Migraine-Specific Questionnaire for family studies (FMSQ(FS)): a 
validation study in two languages.

Facheris MF, Vogl FD, Hollmann S, Sixt G, Pattaro C, Schönhuber R, Pramstaller
PP.

Institute of Genetic Medicine, EURAC Research, Bolzano, Italy.

BACKGROUND AND PURPOSE: The hypothesis of a genetic component in the etiology of 
migraine is getting a foothold. However, to explore genetic associations,
precision in clinical phenotypization is crucial. For this reason,
migraine-specific questionnaires, well discriminating between primary headaches, 
are required when large numbers of individuals need to be assessed. METHODS: We
adapted and translated in two languages, German and Italian, the Finnish
Migraine-Specific Questionnaire for use in family studies. RESULTS AND
CONCLUSIONS: This adaptation proved to be reliable when differentiating from
primary headaches, and to be in very good agreement with the standard for
comparison. However, discriminating between migraine with and without aura still 
relays on a specialist evaluation. This article describes the validation of this 
questionnaire.

Publication Types: 
    Validation Studies

PMID: 18715259 [PubMed - indexed for MEDLINE]

100: Can J Neurol Sci. 2008 Jul;35(3):335-41.

Diagnostic accuracy of neurological problems in the emergency department.

Moeller JJ, Kurniawan J, Gubitz GJ, Ross JA, Bhan V.

Division of Neurology, Department of Medicine, Queen Elizabeth II Health Sciences
Centre and Dalhousie University, Halifax, Nova Scotia, Canada.

BACKGROUND: Previous studies describe significant rates of misdiagnosis of
stroke, seizure and other neurological problems, but there are few studies
examining diagnostic accuracy of all emergency referrals to a neurology service. 
This information could be useful in focusing the neurological education of
physicians who assess and refer patients with neurological complaints in
emergency departments. METHODS: All neurological consultations in the emergency
department at a tertiary-care teaching hospital were recorded for six months. The
initial diagnosis of the requesting physician was recorded for each patient. This
was compared to the initial diagnosis of the consulting neurologist and to the
final diagnosis, as determined by retrospective chart review. RESULTS: Over a
six-month period, 493 neurological consultations were requested. The initial
diagnosis of the requesting physician agreed with the final diagnosis in 60.4%
(298/493) of cases, and disagreed or was uncertain in 35.7% of cases (19.1% and
16.6% respectively). In 3.9% of cases, the initial diagnosis of both the
referring physician and the neurologist disagreed with the final diagnosis.
Common misdiagnoses included neurocardiogenic syncope, peripheral vertigo,
primary headache and psychogenic syndromes. Often, these were initially diagnosed
as stroke or seizure. CONCLUSIONS: Our data indicate that misdiagnosis or
diagnostic uncertainty occurred in over one-third of all neurological
consultations in the emergency department setting. Benign neurological
conditions, such as migraine, syncope and peripheral vertigo are frequently
mislabeled as seizure or stroke. Educational strategies that emphasize emergent
evaluation of these common conditions could improve diagnostic accuracy, and may 
result in better patient care.

PMID: 18714802 [PubMed - indexed for MEDLINE]

101: Biostatistics. 2009 Jan;10(1):187-200. Epub 2008 Aug 19.

Gamma frailty model for linkage analysis with application to interval-censored
migraine data.

Jonker MA, Bhulai S, Boomsma DI, Ligthart RS, Posthuma D, Van der Vaart AW.

Department of Mathematics, Faculty of Sciences, Vrije Universiteit, De Boelelaan 
1081 a, 1081 HV Amsterdam, The Netherlands. majonker@few.vu.nl

For many diseases, it seems that the age at onset is genetically influenced.
Therefore, the age-at-onset data are often collected in order to map the disease 
gene(s). The ages are often (right) censored or truncated, and therefore, many
standard techniques for linkage analysis cannot be used. In this paper, we
present a correlated frailty model for censored survival data of siblings. The
model is used for testing heritability for the age at onset and linkage between
the loci and the gene(s) that influence(s) the survival time. The model is
applied to interval-censored migraine twin data. Heritability (obtained from the 
frailties rather than actual onset times) was estimated as 0.42; this value was
highly significant. The highest lod score, a score of 1.9, was found at the end
of chromosome 19.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Twin Study

PMID: 18714083 [PubMed - indexed for MEDLINE]

102: Neurology. 2008 Aug 19;71(8):559-66.

Chronic migraine in the population: burden, diagnosis, and satisfaction with
treatment.

Bigal ME, Serrano D, Reed M, Lipton RB.

Merck Research Laboratories, 1 Merck Drive, Whitehouse Station, NJ 08889, USA.
marcelo_bigal@merck.com

OBJECTIVE: To evaluate the disability profile and patterns of treatment and
health care use for chronic migraine (CM) in the general population, in contrast 
to episodic migraine. METHODS: We identified 24,000 headache sufferers, drawn
from more than 165,000 individuals representative of the US population. This
sample has been followed up with annual surveys using validated questionnaires
for the diagnosis of episodic migraine and CM. As a part of the survey, subjects 
were asked to report the specific medications currently used for their most
severe headaches, as well as level of satisfaction with treatment. RESULTS: Our
sample consisted of 520 individuals with CM and 9,424 with episodic migraine.
Over a 3-month period, more than half of the individuals with CM missed at least 
5 days of household work, compared with 24.3% of those with episodic migraine (p 
< 0.001). Reduced productivity in household work for at least 5 days over 3
months was reported by 58.1% and 18.2% (p < 0.001); at least 5 days of missed
family activities was reported by 36.9% and 9.5% (p < 0.001). The majority of the
CM sufferers (87.6%) had previously sought care to discuss their headaches with a
health professional. Migraine-specific acute treatments were used by 31.6% of
respondents with CM and 24.8% with episodic migraine. Around 48% of the
individuals with CM were satisfied with their acute therapies. Just 33.3% of
those with CM were currently using preventive medications. CONCLUSION: Chronic
migraine (CM) is more disabling than episodic migraine in the population.
Although most individuals with CM sought medical care for this disorder, the
majority did not receive specific acute or preventive medications.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 18711108 [PubMed - indexed for MEDLINE]

103: Curr Atheroscler Rep. 2008 Oct;10(5):427-33.

Migraine with and without aura and risk for cardiovascular disease.

Vargas BB, Dodick DW, Wingerchuk DM, Demaerschalk BM.

Department of Neurology, Mayo Clinic Hospital, 5777 East Mayo Boulevard, Phoenix,
AZ 85054, USA. bvargas@neurotucson.com

Migraine, cardiovascular disease, and stroke are three highly prevalent and
disabling conditions that exert a significant socioeconomic impact. The
association between migraine and a twofold risk of stroke and myocardial
infarction has been the topic of much debate. The mechanism underlying this link 
is largely unknown but may be the result of an increased prevalence of other
conditions such as vasculopathies, hypercoagulable states, and patent foramen
ovale seen in migraine with aura. Although many prior studies have demonstrated
increased risks in women with migraine with aura, an emerging body of evidence is
showing similar risks in men. These risks are further compounded with increased
migraine frequency, smoking, and the use of oral contraceptive pills. Because the
overall risk for stroke and myocardial infarction in migraineurs remains
relatively low, recommendations at this time are limited to the modification of
cardiovascular risk factors, such as smoking cessation and the avoidance of oral 
contraceptive pills, especially in women suffering from migraine with aura.

Publication Types: 
    Review

PMID: 18706284 [PubMed - indexed for MEDLINE]

104: Magnes Res. 2008 Jun;21(2):101-8.

The effects of magnesium prophylaxis in migraine without aura.

Köseoglu E, Talaslioglu A, Gönül AS, Kula M.

Erciyes University, Medicine Faculty, Neurology Department, Kayseri, Turkey.
emelk@erciyes.edu.tr

There are inconsistent findings about the efficacy of magnesium in the
prophylaxis of migraine attacks and there is no study of magnesium prophylaxis
focused on migraine subtypes without aura. In this double blind, randomized,
placebo controlled study; we tried to evaluate the prophylactic effects of oral
magnesium in migraine patients without aura. The prophylactic effects of 600
mg/day oral magnesium citrate supplementation were assessed by means of clinical 
evaluation, visual evoked potential and statistical parametric mapping of brain
single photon emission computerized tomography before and after a 3 month
treatment period. The results of 30 patients with migraine without aura (20-55
years old with 2-5 migraine attacks per month) on magnesium treatment were
compared with those of 10 patients with similar properties on placebo treatment. 
Migraine attack frequency, severity and P1 amplitude in visual evoked potential
examination decreased after magnesium treatment with respect to pretreatment
values (p < 0.001). In a comparison of the effects of magnesium treatment with
those of placebo, post/pretreatment ratios of migraine attack frequency, severity
and P1 amplitude in Mg treatment group were found to be significantly lower than 
those in placebo treatment group (attack frequency p = 0.005, attack severity p <
0.001, P1 amplitude p < 0.05). Cortical blood flow in inferolateral frontal (p < 
0.001), inferolateral temporal (p = 0.001) and insular regions (p < 0.01)
increased significantly after magnesium treatment with respect to the
pretreatment; while such significant changes of cortical blood flow were not
observed with placebo treatment. These results have made us think that magnesium 
is a beneficial agent in prophylaxis of migraine without aura and might work with
both vascular and neurogenic mechanisms.

Publication Types: 
    Randomized Controlled Trial

PMID: 18705538 [PubMed - indexed for MEDLINE]

105: Ann Behav Med. 2008 Aug;36(1):21-32. Epub 2008 Aug 12.

Relaxation training and written emotional disclosure for tension or migraine
headaches: a randomized, controlled trial.

D'Souza PJ, Lumley MA, Kraft CA, Dooley JA.

Department of Psychology, Wayne State University, 5057 Woodward Avenue, 7th
Floor, Detroit, MI 48202, USA.

BACKGROUND AND PURPOSE: Behavioral medicine interventions that directly reduce
arousal and negative emotions, such as relaxation training (RT), are conceptually
different from interventions that temporarily increase negative emotions, such as
written emotional disclosure (WED), but no studies have directly compared their
efficacy. We compared the effects of RT and WED on people with tension or
migraine headaches. METHODS: College students with either tension (n = 51) or
migraine (n = 90) headaches were randomized to one of three groups: RT, WED, or a
neutral writing control condition; four sessions were held over 2 weeks. Mood was
measured before and after each session, and outcomes (headache frequency,
severity, disability, and general physical symptoms) were assessed at baseline
and at 1-month and 3-month follow-ups. RESULTS: As expected, RT led to an
immediate increase in calmness, whereas WED led to an immediate increase in
negative mood, for both headache samples. Intent-to-treat analyses showed that,
for the tension headache sample, RT led to improved headache frequency and
disability compared to both WED and the control group, but WED had no effect. For
migraine headaches, RT improved pain severity relative to the control group, but 
WED again had no effect. CONCLUSIONS: A brief RT protocol was effective for
tension headaches, but WED had no effect on health status for either tension or
migraine headaches. Modifications to WED, such as targeting people with
unresolved stress, providing guidance to enhance the potency of the writing, or
including additional at-home writing and exposure exercises, may improve its
efficacy for people with headaches and other health problems.

Publication Types: 
    Comparative Study
    Randomized Controlled Trial
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 18696172 [PubMed - indexed for MEDLINE]

106: Neuroreport. 2008 Aug 27;19(13):1351-3.

Is migraine a lateralization defect?

Kaaro J, Partonen T, Naik P, Hadjikhani N.

AV-Torppa Oy, Lohja bNational Public Health Institute, Helsinki, Finland.

Migraine often co-occurs with patent foramen ovale (PFO), and some people have
suggested surgical closure as an efficient treatment for migraine. Prospective
studies, however, do not report radical effect of PFO surgery on migraine. Here, 
we examined the hypothesis that PFO and migraine may cooccur as two independent
manifestations of lateralization defect during embryonic development. We measured
the absolute displacement of a midline structure, the pineal gland, on brain
scans of 39 migraineurs and 26 controls. We found a significant asymmetry of the 
pineal gland in migraineurs compared with controls. Our data suggest that
migraine's circadian component and its association with PFO may be linked to a
lateralization defect during embryogenesis, which could be a result from abnormal
serotonin regulation.

Publication Types: 
    Research Support, N.I.H., Extramural

PMID: 18695522 [PubMed - indexed for MEDLINE]

107: J Occup Environ Med. 2008 Aug;50(8):895-903.

Labor productivity in migraine patients: primary care contribution to
occupational medicine.

Castillo J, Láinez MJ, Domínguez M, Palacios G, Díaz S, Rejas J.

Primary Care Health Center of Camargo, Muriedas, Cantabria, Spain.
Jcastilloo25@hotmail.com

OBJECTIVE: To estimate the impact of migraine on labor productivity and health
resources utilization in an active population attending Primary Care settings in 
Spain. METHODS: An observational, cross-sectional, and multicenter study was
designed. Productivity, loss workdays equivalents and previous 3-months health
resources utilization were calculated. RESULTS: Four thousand four hundred twenty
six patients were evaluated. The migraine group showed the lowest productivity,
highest loss workdays equivalents and health resources utilization compared with 
non-migraine headaches and subjects without headaches (P < 0.05 in all cases).
Within the migraine group, lower productivity values were observed in female
patients compared to male (64.04 vs 59.69; P < 0.05), while emergency room visits
were more frequent for male patients (0.71 vs 076; P < 0.05). CONCLUSIONS:
Subjects with migraine showed higher impact on health resources utilization and
productivity when evaluated at Primary care level.

Publication Types: 
    Multicenter Study
    Research Support, Non-U.S. Gov't

PMID: 18695448 [PubMed - indexed for MEDLINE]

108: Rev Alerg Mex. 2007 Sep-Oct;54(5):162-8.

Food allergy mediated by IgG antibodies associated with migraine in adults.

Arroyave Hernández CM, Echevarría Pinto M, Hernández Montiel HL.

Centro de Inmunología y Alergias, Querétaro, Querétaro, México.

BACKGROUND: Migraine occurs with a high prevalence of 18 per cent. Management
requires a tailored regimen of pharmacological and other measures based on
individual clinical history. In some patients, allergen-specific IgG has been
suspected to be involved in their mechanism, however, serological methods to
investigate such possibility, are seldomly used. OBJECTIVE: The aim of this study
was to investigate allergen-specific IgG in serum of patients with migraine
refractory to traditional treatment. MATERIAL AND METHODS: Serum antibodies to
specific 108 food allergens were measured by enzyme immunoassay from 56 patients 
with migraine and a control group without migraine. RESULTS: In addition to
statistical significant differences in the number of positives for IgG food
allergens between patients with migraine and a controlled group, elimination
diets successfully control the migraine without the need of medications.
CONCLUSION: According to the results obtained, serum IgG antibodies to common
food should be investigated in patients with migraine.

PMID: 18693538 [PubMed - indexed for MEDLINE]

109: BMJ. 2008 Aug 7;337:a636. doi: 10.1136/bmj.a636.

Comment in:
    BMJ. 2008;337:a745.

Migraine, vascular risk, and cardiovascular events in women: prospective cohort
study.

Kurth T, Schürks M, Logroscino G, Gaziano JM, Buring JE.

Division of Preventive Medicine, Department of Medicine, Brigham and Women's
Hospital, Harvard Medical School, Boston, MA, USA. tkurth@rics.bwh.harvard.edu

OBJECTIVES: To evaluate whether the association between migraine with aura and
increased risk of cardiovascular disease is modified by vascular risk groups as
measured by the Framingham risk score for coronary heart disease. DESIGN:
Prospective cohort study. SETTING: Women's health study, United States.
PARTICIPANTS: 27 519 women who were free from cardiovascular disease at baseline 
with available information on the Framingham risk score and migraine status. MAIN
OUTCOME MEASURES: Time to major cardiovascular disease event (non-fatal
myocardial infarction, non-fatal ischaemic stroke, death from ischaemic
cardiovascular disease), myocardial infarction, and ischaemic stroke. RESULTS: At
baseline, 3577 (13.0%) women reported active migraine, of whom 1418 (39.6%)
reported migraine with aura. During 11.9 years of follow-up, there were 697
cardiovascular disease events. We stratified participants based on 10 year risk
of coronary heart disease estimated from the Framingham risk score (<or=1%, 2-4%,
5-9%, and >or=10%). Compared with women without migraine, the age adjusted hazard
ratios in women with active migraine with aura were 1.93 (95% confidence interval
1.45 to 2.56) for major cardiovascular disease, 1.80 (1.16 to 2.79) for ischaemic
stroke, and 1.94 (1.27 to 2.95) for myocardial infarction. When stratified by
Framingham risk score, the association between migraine with aura and major
cardiovascular disease was strongest in the lowest risk score group. There was a 
diametric association pattern for ischaemic stroke and myocardial infarction.
Compared with women without migraine, the age adjusted hazard ratios in women who
reported migraine with aura in the lowest Framingham risk score group were 3.88
(1.87 to 8.08) for ischaemic stroke and 1.29 (0.40 to 4.21) for myocardial
infarction. Hazard ratios in women with migraine with aura in the highest
Framingham risk score group were 1.00 (0.24 to 4.14) for ischaemic stroke and
3.34 (1.50 to 7.46) for myocardial infarction. Women with migraine without aura
were not at increased risk of ischaemic stroke or myocardial infarction in any of
the Framingham risk score groups. CONCLUSION: The association between migraine
with aura and cardiovascular disease varies by vascular risk status. Information 
on history of migraine and vascular risk status might help to identify women at
increased risk for specific future cardiovascular disease events. TRIAL
REGISTRATION: Clinical trials NCT00000479.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 18687721 [PubMed - indexed for MEDLINE]

110: Brain Topogr. 2008 Sep;21(1):36-42. Epub 2008 Aug 5.

Three-dimensional localization of abnormal EEG activity in migraine: a low
resolution electromagnetic tomography (LORETA) study of migraine patients in the 
pain-free interval.

Clemens B, Bánk J, Piros P, Bessenyei M, Veto S, Tóth M, Kondákor I.

Department of Neurology, Kenézy Hospital, Bartók Béla út 3, 4031, Debrecen,
Hungary. clemensdr@freemail.hu

Investigating the brain of migraine patients in the pain-free interval may shed
light on the basic cerebral abnormality of migraine, in other words, the
liability of the brain to generate migraine attacks from time to time. Twenty
unmedicated "migraine without aura" patients and a matched group of healthy
controls were investigated in this explorative study. 19-channel EEG was recorded
against the linked ears reference and was on-line digitized. 60 x 2-s epochs of
eyes-closed, waking-relaxed activity were subjected to spectral analysis and a
source localization method, low resolution electromagnetic tomography (LORETA).
Absolute power was computed for 19 electrodes and four frequency bands (delta:
1.5-3.5 Hz, theta: 4.0-7.5 Hz, alpha: 8.0-12.5 Hz, beta: 13.0-25.0 Hz). LORETA
"activity" (=current source density, ampers/meters squared) was computed for 2394
voxels and the above specified frequency bands. Group comparison was carried out 
for the specified quantitative EEG variables. Activity in the two groups was
compared on a voxel-by-voxel basis for each frequency band. Statistically
significant (uncorrected P < 0.01) group differences were projected to cortical
anatomy. Spectral findings: there was a tendency for more alpha power in the
migraine that in the control group in all but two (F4, C3) derivations. However, 
statistically significant (P < 0.01, Bonferroni-corrected) spectral difference
was only found in the right occipital region. The main LORETA-finding was that
voxels with P < 0.01 differences were crowded in anatomically contiguous cortical
areas. Increased alpha activity was found in a cortical area including part of
the precuneus, and the posterior part of the middle temporal gyrus in the right
hemisphere. Decreased alpha activity was found bilaterally in medial parts of the
frontal cortex including the anterior cingulate and the superior and medial
frontal gyri. Neither spectral analysis, nor LORETA revealed statistically
significant differences in the delta, theta, and beta bands. LORETA revealed the 
anatomical distribution of the cortical sources (generators) of the EEG
abnormalities in migraine. The findings characterize the state of the cerebral
cortex in the pain-free interval and might be suitable for planning forthcoming
investigations.

PMID: 18679787 [PubMed - indexed for MEDLINE]

111: Hum Mol Genet. 2008 Nov 1;17(21):3318-31. Epub 2008 Aug 2.

A high-density association screen of 155 ion transport genes for involvement with
common migraine.

Nyholt DR, LaForge KS, Kallela M, Alakurtti K, Anttila V, Färkkilä M, Hämaläinen 
E, Kaprio J, Kaunisto MA, Heath AC, Montgomery GW, Göbel H, Todt U, Ferrari MD,
Launer LJ, Frants RR, Terwindt GM, de Vries B, Verschuren WM, Brand J, Freilinger
T, Pfaffenrath V, Straube A, Ballinger DG, Zhan Y, Daly MJ, Cox DR, Dichgans M,
van den Maagdenberg AM, Kubisch C, Martin NG, Wessman M, Peltonen L, Palotie A.

Genetic Epidemiology Laboratory, Queensland Institute of Medical Research, PO
Royal Brisbane Hospital, Brisbane4029, Queensland, Australia.
dale.nyholt@qimr.edu.au

The clinical overlap between monogenic Familial Hemiplegic Migraine (FHM) and
common migraine subtypes, and the fact that all three FHM genes are involved in
the transport of ions, suggest that ion transport genes may underlie
susceptibility to common forms of migraine. To test this leading hypothesis, we
examined common variation in 155 ion transport genes using 5257 single nucleotide
polymorphisms (SNPs) in a Finnish sample of 841 unrelated migraine with aura
cases and 884 unrelated non-migraine controls. The top signals were then tested
for replication in four independent migraine case-control samples from the
Netherlands, Germany and Australia, totalling 2835 unrelated migraine cases and
2740 unrelated controls. SNPs within 12 genes (KCNB2, KCNQ3, CLIC5, ATP2C2,
CACNA1E, CACNB2, KCNE2, KCNK12, KCNK2, KCNS3, SCN5A and SCN9A) with promising
nominal association (0.00041 < P < 0.005) in the Finnish sample were selected for
replication. Although no variant remained significant after adjusting for
multiple testing nor produced consistent evidence for association across all
cohorts, a significant epistatic interaction between KCNB2 SNP rs1431656
(chromosome 8q13.3) and CACNB2 SNP rs7076100 (chromosome 10p12.33) (pointwise P =
0.00002; global P = 0.02) was observed in the Finnish case-control sample. We
conclude that common variants of moderate effect size in ion transport genes do
not play a major role in susceptibility to common migraine within these European 
populations, although there is some evidence for epistatic interaction between
potassium and calcium channel genes, KCNB2 and CACNB2. Multiple rare variants or 
trans-regulatory elements of these genes are not ruled out.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 18676988 [PubMed - indexed for MEDLINE]

112: Neurology. 2008 Aug 12;71(7):505-13. Epub 2008 Jul 30.

Interrelationships among the MTHFR 677C>T polymorphism, migraine, and
cardiovascular disease.

Schürks M, Zee RY, Buring JE, Kurth T.

Department of Medicine, Division of Preventive Medicine, Brigham and Women's
Hospital, Boston, MA 02215-1204, USA.

BACKGROUND: Interrelationships among the MTHFR 677C>T polymorphism (rs1801133),
migraine, and cardiovascular disease (CVD) are plausible but remain
controversial. METHODS: Association study among 25,001 white US women,
participating in the Women's Health Study, with information on MTHFR 677C>T
polymorphism. Migraine and migraine aura status were self-reported. Incident CVD 
events were confirmed after medical record review. We used logistic regression to
investigate the genotype-migraine association and proportional hazards models to 
evaluate the interrelationships of genotype and migraine on incident CVD.
RESULTS: At baseline, 4,577 (18.3%) women reported history of migraine; 39.5% of 
the 3,226 women with active migraine indicated aura. During a mean of 11.9 years 
of follow-up, 625 CVD events occurred. Carriers of the TT genotype were less
likely to have migraine with aura. The multivariable-adjusted relative risk (RR) 
in the recessive model was 0.79 (95% CI = 0.65-0.96; p = 0.02). The TT genotype
did not increase the risk for CVD. In contrast, migraine with aura doubled the
risk for CVD (multivariable-adjusted RR = 2.06; 95% CI = 1.53-2.78; p < 0.0001). 
Coexistence of migraine with aura and the TT genotype selectively raised this
risk (RR = 3.66; 95% CI = 1.69-7.90; p = 0.001). This pattern was driven by a
fourfold increased risk for ischemic stroke (multivariable-adjusted RR = 4.19;
95% CI = 1.38-12.74; p = 0.01) and was not apparent for myocardial infarction.
CONCLUSIONS: Data from this large cohort of women suggest a modest protective
effect of the MTHFR 677TT genotype on migraine with aura. The increased risk for 
cardiovascular disease among migraineurs with aura was magnified for TT genotype 
carriers, which was driven by a substantially increased risk of ischemic stroke.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 18672474 [PubMed - indexed for MEDLINE]

113: Funct Neurol. 2008 Apr-Jun;23(2):83-6.

Cerebral blood flow changes in patients with probable medication-overuse
headache.

Savrun FK, Goksan B, Savrun M, Sahin R, Sahin S.

Department of Neurology, University of Istanbul, Turkey.

Transcranial Doppler (TCD) is a non-invasive method for measuring blood flow
velocity (BFV), and a marker of vessel diameter. In this study, intracranial BFV 
was investigated, by means of TCD, in patients suffering from probable
medication-overuse headache (PMOH). Twenty-three female patients with probable
ergotamine- overuse headache (PEOH), 23 female patients with probable
analgesic-overuse headache (PAOH), and 15 healthy female controls participated in
the study. The mean BFVs of the bilateral middle and anterior cerebral arteries
(MCA and ACA) and basilar artery (BA) were measured by TCD. The mean BFVs of the 
BA and MCA were found to be significantly increased in the PEOH group when
compared with those of the PAOH and control groups (p<0.05). No significant
differences in BFV of the ACA were observed between any groups (p>0.05). The mean
BFV of all the vessels in the PAOH group was found to be lower than that of the
control group but no statistical significance was found (p>0.05). Our results
show that ergotamine increases BFV via vasoconstriction, especially of the BA and
MCA. We also suggest that 5HT1B/1D receptors are mainly localized in the BA and
MCA, and that analgesic overuse results in a functional disorder of neuronal
receptor and neurovascular reflexes and may cause a reduction of intracerebral
vessel tone, leading to vasodilatation.

Publication Types: 
    Comparative Study

PMID: 18671908 [PubMed - indexed for MEDLINE]

114: Funct Neurol. 2008 Apr-Jun;23(2):77-81.

Plasma melatonin pattern in chronic and episodic headaches: evaluation during
sleep and waking.

Bruera O, Sances G, Leston J, Levin G, Cristina S, Medina C, Barontini M, Nappi
G, Figuerola MA.

Department of Neurology, Clinical Hospital, University of Buenos Aires,
Argentina.

To look for a relationship between pineal function in chronic migraine (CM),
cluster headache (CH) (during active and remission periods), chronic tension-type
headache (CTTH) patients and controls during NREM sleep, REM sleep and waking, we
performed serial sampling of plasma melatonin in the different sleep stages
during the first half of the night, in order to avoid chronobiological
interferences. Plasma melatonin levels did not show a normal curve either in the 
CTTH or in the CM patients and no significant differences between these groups
were found in any of the sleep stages studied. Plasma melatonin values of CH
patients during the cluster period showed an abnormal pattern. The curve showed a
pathological lack of peaks during the active period, melatonin levels remaining
within normal daytime range throughout the study. A trend to normalization of the
curve during the remission period was observed. On the basis of these different
melatonin secretion patterns, it might be hypothesized that the involvement of
the hypothalamus in chronic-type headaches differs from that displayed in
episodic forms.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 18671907 [PubMed - indexed for MEDLINE]

115: Funct Neurol. 2008 Apr-Jun;23(2):71-6.

Tension-type headache: comparison with migraine without aura and cervicogenic
headache. The Vågå study of headache epidemiology.

Sjaastad O, Bakketeig L.

Department of Neurology, St.Olavs Hospital, Trondheim University Hospitals,
Trondheim, Norway. eylert.brodtkorb@ntnu.no

The aim of the present study was to describe the prevalence of tension-type
headache (T-TH) in rural Norway, and 1838 citizens aged 18-65 years were
included. Features indicating neck involvement were also looked for. T-TH was
compared with migraine without aura and with cervicogenic headache (CEH)
considering both these features and typical migraine traits. Face-to-face
interviews were carried out, based on an elaborate questionnaire. The IHS
criteria, first version, were used for T-TH diagnosis. A T-TH prevalence of 34%
was found. In T-TH and migraine without aura, typical CEH features, such as
reduced range of motion in the neck and mechanical provocation of pain, were far 
less prominent than in CEH. Typical migraine traits, e.g. photophobia, were much 
less frequently present in T-TH and CEH than in migraine without aura. T-TH is,
in all probability, not a CEH variant and vice versa.

PMID: 18671906 [PubMed - indexed for MEDLINE]

116: Funct Neurol. 2008 Apr-Jun;23(2):63-9.

Acute treatment of migraine in children and adolescents.

Termine C, Ferri M, Balottin U.

Department of Clinical and Biological Sciences, University of Insubria, Italy.
cristiano.terminea@uninsubria.it

The management of headaches with juvenile onset presents several problems,
related not only to appropriate drug selection but also to the specific features 
distinguishing headache disorders in children and adolescents: a child is not a
"little adult". Many age-related factors influence the clinical expression of
headache and these should be taken into account not only in the treatment, but
also in the diagnosis, of juvenile headache. Few randomised placebo-controlled
clinical trials of acute or preventive drugs have been conducted in paediatric
headache patients, and those that have show a high placebo response rate in
children (e.g. up to 55% for prophylactic drugs and up to 69% for symptomatic
ones). The available data on symptomatic drugs are presented and discussed,
focusing, in particular, on mechanisms of action, evidence of efficacy, and
tolerability.

Publication Types: 
    Review

PMID: 18671905 [PubMed - indexed for MEDLINE]

117: J Neurol. 2008 Oct;255(10):1541-4. Epub 2008 Jul 28.

Downbeat positioning nystagmus is a common clinical feature despite variable
phenotypes in an FHM1 family.

Yabe I, Kitagawa M, Suzuki Y, Fujiwara K, Wada T, Tsubuku T, Takeichi N,
Sakushima K, Soma H, Tsuji S, Niino M, Saitoh S, Sasaki H.

Department of Neurology, Hokkaido University Graduate School of Medicine, N15 W7 
Kita-ku, Sapporo 060-8638, Japan. yabe@med.hokudai.ac.jp

Clinical examinations and mutational analyses were carried out in three patients 
of a Japanese familial hemiplegic migraine (FHM) pedigree. Each affected member
demonstrated a broad clinical spectrum that included hemiplegic migraine with
progressive cerebellar ataxia, migraine without aura, and episodic ataxia.
Despite this variability, all members exhibited marked downbeat positioning
nystagmus, and magnetic resonance images (MRI) all showed cerebellar atrophy
predominantly of the cerebellar vermis. All affected members had a T666M missense
mutation in the protein encoded by the CACNA1A gene (calcium channel,
voltage-dependent, P/Q type, alpha 1A subunit). Although clinical features
associated with the T666M CACNA1A mutation are highly variable, downbeat
positioning nystagmus may be an important clinical feature of this disease.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 18670797 [PubMed - indexed for MEDLINE]

118: Clin Neuropharmacol. 2008 Jul-Aug;31(4):238-40.

Remission of migraine attacks in a patient with depression who is taking
pregabalin.

Masdrakis VG, Oulis P, Karakatsanis NA, Potagas C, Kouzoupis AV, Soldatos CR.

Department of Psychiatry, Athens University Medical School, Eginition Hospital,
Athens, Greece. vmasdrakis@med.uoa.gr

Antiepileptic drugs (AED) are increasingly used in the treatment of migraine.
Pregabalin (PGB) is an AED that has been used in the treatment of partial
seizures, of various types of pain, and of certain anxiety disorders, but to the 
best of our knowledge, there has been no report on the use of PGB in the
treatment of migraine. We report the case of a 60-year-old female inpatient with 
depression, long experiencing migraine, whose migraine symptoms improved markedly
after receiving PGB in combination with escitalopram administered for her
depression. The PGB mechanism of action in conjunction with its structural
similarity with gabapentin, already successfully tested in the treatment of
migraine, provide additional supportive evidence, theoretical and clinical,
respectively, for PGB potential to alleviate migraine symptoms. However, only
carefully randomized, controlled studies, or at the very least, open-label series
of large patient samples treated in a similar fashion could establish the
efficacy of PGB in migraine treatment.

Publication Types: 
    Case Reports

PMID: 18670248 [PubMed - indexed for MEDLINE]

119: J Med Chem. 2008 Aug 28;51(16):4858-61. Epub 2008 Jul 30.

Discovery of
(R)-4-(8-fluoro-2-oxo-1,2-dihydroquinazolin-3(4H)-yl)-N-(3-(7-methyl-1H-indazol-5
-yl)-1-oxo-1-(4-(piperidin-1-yl)piperidin-1-yl)propan-2-yl)piperidine-1-carboxami
de (BMS-694153): a potent antagonist of the human calcitonin gene-related peptide
receptor for migraine with rapid and efficient intranasal exposure.

Degnan AP, Chaturvedula PV, Conway CM, Cook DA, Davis CD, Denton R, Han X, Macci 
R, Mathias NR, Moench P, Pin SS, Ren SX, Schartman R, Signor LJ, Thalody G,
Widmann KA, Xu C, Macor JE, Dubowchik GM.

Department of Neuroscience Chemistry, Bristol-Myers Squibb Research &
Development,Wallingford, Connecticut 06492, USA. andrew.degnan@bms.com

Calcitonin gene-related peptide (CGRP) has been implicated in the pathogenesis of
migraine. Early chemistry leads suffered from modest potency, significant CYP3A4 
inhibition, and poor aqueous solubility. Herein, we describe the optimization of 
these leads to give 4 (BMS-694153), a molecule with outstanding potency, a
favorable predictive toxicology profile, and remarkable aqueous solubility.
Compound 4 has good intranasal bioavailability in rabbits and shows
dose-dependent activity in validated in vivo and ex vivo migraine models.

PMID: 18665579 [PubMed - indexed for MEDLINE]

120: Drug Dev Ind Pharm. 2008 Oct;34(10):1100-10.

Elastic liposomal formulation for sustained delivery of antimigraine drug: in
vitro characterization and biological evaluation.

Garg T, Jain S, Singh HP, Sharma A, Tiwary AK.

Department of Pharmaceutical Sciences and Drug Research, Punjabi University,
Patiala, India.

The aim of this study was to prepare and characterize a topical formulation for
sustained delivery of rizatriptan. Elastic liposomal formulation of rizatriptan
was prepared and characterized for different characteristics by evaluating in
vitro and in vivo parameters. The in vivo performance of optimized formulation
was evaluated for antimigraine activity in mice using morphine withdrawal-induced
hyperalgesia. The in vitro skin permeation study across rat skin suggested
carrier-mediated transdermal permeation for different elastic liposomal
formulation to range between 18.1 +/- 0.6 and 42.7 +/- 2.3 microg/h/cm(2), which 
was approximately 8-19 times higher than that obtained using drug solution. The
amount of drug deposited was 10-fold higher for elastic liposome (39.9 +/- 3.2%) 
than using drug solution (3.8 +/- 1%); similarly the biological activity of
optimized elastic liposome formulation was found to be threefold higher than the 
drug solution. On the basis of the results, it can be concluded that the elastic 
liposomal formulation provided sustained action of rizatriptan due to depot
formation in the deeper layer of skin.

PMID: 18663655 [PubMed - indexed for MEDLINE]

121: Radiat Med. 2008 Jun;26(5):313-7. Epub 2008 Jul 27.

Migrainous infarction in an adult: evaluation with serial diffusion-weighted
images and cerebral blood flow studies.

Arai S, Utsunomiya H, Arihiro S, Arakawa S.

Department of Neuroradiology, Hakujyuji Hospital, Fukuoka, Japan.
s.arai@hakujyujikai.or.jp

We report the case of a 64-year-old man with migrainous infarction, giving
special attention to chronological changes in neuroimaging findings. Five days
after the onset, diffusion-weighted imaging showed slightly high intensity, and
the apparent diffusion coefficient map showed increased diffusion in the right
occipital lobe, which indicated vasogenic edema. Perfusion magnetic resonance
imaging (MRI) and MR angiography demonstrated hyperperfusion of the ipsilateral
hemisphere. Follow-up MRI showed irreversible brain damage. These images may
reflect chronological changes in cerebral edema due to prolonged hyperperfusion
with migraine.

Publication Types: 
    Case Reports

PMID: 18661217 [PubMed - indexed for MEDLINE]

122: J Psychosom Res. 2008 Aug;65(2):135-42.

The impacts of migraine, anxiety disorders, and chronic depression on quality of 
life in psychiatric outpatients with major depressive disorder.

Hung CI, Wang SJ, Yang CH, Liu CY.

Department of Psychiatry, Chang Gung Memorial Hospital and Chang Gung University 
College of Medicine, Taoyuan, Taiwan.

OBJECTIVE: Our purpose was to determine if migraine, anxiety comorbidities, and
chronic depression were independently related to health-related quality of life
(HRQoL) in outpatients with major depressive disorder (MDD). METHOD: Consecutive 
psychiatric outpatients with MDD in a medical center were enrolled. MDD, chronic 
depression, and seven anxiety disorders were diagnosed using the Structured
Clinical Interview for DSM-IV-TR. Migraine was diagnosed based on the
International Classification of Headache Disorders, 2nd edition. The acute
version of the Short-Form 36 and the Hamilton Depression Rating Scale (HAMD) were
used to evaluate the HRQoL and the severity of depression, respectively. Multiple
linear regressions were used to determine the independent factors related to
HRQoL. RESULTS: There were 135 participants (34 men, 101 women) with MDD.
Subjects with migraine, anxiety comorbidities, or chronic depression had higher
HAMD scores and poor HRQoL. Migraine, specific phobia, and panic disorder were
important and independent comorbidities predicting HRQoL. The impact of migraine 
on HRQoL, especially on bodily pain, was not inferior to those of some anxiety
comorbidities or chronic depression. CONCLUSION: Future studies related to HRQoL 
of MDD should consider migraine and anxiety comorbidities simultaneously.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 18655858 [PubMed - indexed for MEDLINE]

123: Cochrane Database Syst Rev. 2008 Jul 16;(3):CD005219.

Normobaric and hyperbaric oxygen therapy for migraine and cluster headache.

Bennett MH, French C, Schnabel A, Wasiak J, Kranke P.

Diving and Hyperbaric Medicine, Prince of Wales Hospital, Barker Street,
Randwick, NSW, Australia, 2031. m.bennett@unsw.edu.au

BACKGROUND: Migraine and cluster headaches are severe and disabling. Migraine
affects up to 18% of women, while cluster headaches are much less common (0.2% of
the population). A number of acute and prophylactic therapies are available.
Hyperbaric oxygen therapy (HBOT) is the therapeutic administration of 100% oxygen
at environmental pressures greater than one atmosphere, while normobaric oxygen
therapy (NBOT) is oxygen administered at one atmosphere. OBJECTIVES: To assess
the safety and effectiveness of HBOT and NBOT for treating and preventing
migraine and cluster headaches. SEARCH STRATEGY: We searched the following in May
2008: CENTRAL, MEDLINE, EMBASE, CINAHL, DORCTIHM and reference lists from
relevant articles. Relevant journals were hand searched and researchers
contacted. SELECTION CRITERIA: Randomised trials comparing HBOT or NBOT with one 
another, other active therapies, placebo (sham) interventions or no treatment in 
patients with migraine or cluster headache. DATA COLLECTION AND ANALYSIS: Three
reviewers independently evaluated study quality and extracted data. MAIN RESULTS:
Nine small trials involving 201 participants were included. Five trials compared 
HBOT versus sham therapy for acute migraine, two compared HBOT to sham therapy
for cluster headache and two evaluated NBOT for cluster headache.Pooling of data 
from three trials suggested that HBOT was effective in relieving migraine
headaches compared to sham therapy (relative risk (RR) 5.97, 95% confidence
interval (CI) 1.46 to 24.38, P = 0.01). There was no evidence that HBOT could
prevent migraine episodes, reduce the incidence of nausea and vomiting or reduce 
the requirement for rescue medication. There was a trend to better outcome in a
single trial evaluating HBOT for the termination of cluster headache (RR 11.38,
95% CI 0.77 to 167.85, P = 0.08), but this trial had low power.NBOT was effective
in terminating cluster headache compared to sham in a single small study (RR
7.88, 95% CI 1.13 to 54.66, P = 0.04), but not superior to ergotamine
administration in another small trial (RR 1.17, 95% CI 0.94 to 1.46, P = 0.16).
Seventy-six per cent of patients responded to NBOT in these two trials.No serious
adverse effects of HBOT or NBOT were reported. AUTHORS' CONCLUSIONS: There was
some evidence that HBOT was effective for the termination of acute migraine in an
unselected population, and weak evidence that NBOT was similarly effective in
cluster headache. Given the cost and poor availability of HBOT, more research
should be done on patients unresponsive to standard therapy. NBOT is cheap, safe 
and easy to apply, so will probably continue to be used despite the limited
evidence in this review.

Publication Types: 
    Meta-Analysis
    Review

PMID: 18646121 [PubMed - indexed for MEDLINE]

124: Pract Neurol. 2008 Aug;8(4):211-21.

A practical approach to acute vertigo.

Seemungal BM, Bronstein AM.

Neuro-otology Unit, Department of Clinical Neuroscience, Imperial College London,
Charing Cross Hospital, London, UK. b.seemungal@imperial.ac.uk

Patients complaining of symptoms of acute vertigo present a diagnostic challenge 
for the clinician; the main differential diagnoses are acute unilateral
peripheral vestibulopathy ("vestibular neuritis"), cerebellar stroke or migraine.
The head impulse test is useful in the acute situation because, of these three
diagnostic alternatives, it will only be positive in patients with vestibular
neuritis. A history of acute vertigo and hearing loss suggests Ménière's disease 
but the clinician must be wary of anterior inferior cerebellar artery strokes
which may cause audiovestibular loss due to peripheral vestibulocochleal
ischaemia, although the accompanying brainstem signs should remove diagnostic
ambiguity. We also discuss other less common vertigo diagnoses that may be
referred to the neurologist from the acute general hospital take. As ever in
neurology, a careful history and focussed examination is necessary in the
evaluation and management of acute vertigo.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 18644907 [PubMed - indexed for MEDLINE]

125: J Neurol Sci. 2008 Oct 15;273(1-2):123-6. Epub 2008 Jul 21.

A novel de novo nonsense mutation in ATP1A2 associated with sporadic hemiplegic
migraine and epileptic seizures.

Gallanti A, Tonelli A, Cardin V, Bussone G, Bresolin N, Bassi MT.

Dino Ferrari Center, IRCCS Ospedale Maggiore Policlinico, Mangiagalli e Regina
Elena Foundation, Dept. of Neurological Sciences, University of Milan, 20129
Milan, Italy.

Familial hemiplegic migraine (FHM) is a severe dominant form of migraine with
aura associated with transient hemiparesis. Several other neurological signs and 
symptoms can be associated with FHM such as cerebellar abnormalities, cerebral
edema and coma after minor head trauma, epileptic seizures and mental
retardation. The sporadic form of hemiplegic migraine named SHM, presents with
identical clinical symptoms. Here we report a case of a young hemiplegic migraine
patient, 11 years old, who had the first hemiplegic attack at the age of 10
years. This patient has a clinical history of epileptic seizures in the childhood
successfully controlled with drug therapy. No familiarity for any type of
migraine or seizures can be observed within the paternal or maternal line. The
patient who can therefore be considered a sporadic case, carries a novel de novo 
nonsense mutation p.Tyr1009X in the ATP1A2 gene (FHM2), leading to a truncated
alpha-2 subunit of the Na+/K+-ATPase pump thus lacking the last 11 amino acids.
The novel mutation identified confirms the role of FHM2 gene in forms of
hemiplegic migraine associated with epilepsy with both familial and sporadic
occurrence, and expands the spectrum of mutations related to these forms of the
disease.

Publication Types: 
    Case Reports
    Research Support, Non-U.S. Gov't

PMID: 18644608 [PubMed - indexed for MEDLINE]

126: Cephalalgia. 2008 Nov;28(11):1115-25. Epub 2008 Jul 15.

Anxiety, stress and coping behaviours in primary care migraine patients: results 
of the SMILE study.

Radat F, Mekies C, Géraud G, Valade D, Vivès E, Lucas C, Joubert JM,
Lantéri-Minet M.

Department of Treatment of Chronic Pain Patients, Pellegrin University Teaching
Hospital, Bordeaux, France. francoise.radat@chu-bordeaux.fr

The objectives of the SMILE study were to assess anxiety, stress, depression,
functional impact and coping behaviours in migraine patients consulting in
primary care in France. General practitioners (n = 1467) and 83 neurologists
included 5417 consulting migraine patients. Of these patients, 67% were found
anxious, of whom 59% were also depressive. Patients with both anxiety and
depressive dimensions showed a profile similar to that of chronic migraine
patients (severe attacks, poor treatment effectiveness and pronounced stress,
functional impact and maladaptive behaviours). A quantitative progression in the 
levels of stress, maladaptive coping behaviours and functional impact was noted
from patients with neither dimension to those with both anxious and depressive
dimensions. Stress and maladaptive coping strategies were found to be major
determinants of anxiety. Anxious and depressive dimensions were associated with
elevated consumption of acute treatments for migraine and low treatment
effectiveness. Stress and anxiety should be looked for carefully in migraine
patients.

PMID: 18644041 [PubMed - indexed for MEDLINE]

127: Cephalalgia. 2008 Oct;28(10):1039-47. Epub 2008 Jul 17.

Genetic analysis of 27 Spanish patients with hemiplegic migraine, basilar-type
migraine and childhood periodic syndromes.

Cuenca-León E, Corominas R, Fernàndez-Castillo N, Volpini V, Del Toro M, Roig M, 
Macaya A, Cormand B.

Grup de Recerca en Neurologia Infantil i Psiquiatria Genètica, Hospital
Universitari Vall d'Hebron, Barcelona, Spain.

Familial hemiplegic migraine (FHM) is a rare type of migraine with aura.
Mutations in three genes have been described in FHM patients: CACNA1A (FHM1),
ATP1A2 (FHM2) and SCN1A (FHM3). We screened 27 Spanish patients with hemiplegic
migraine (HM), basilar-type migraine or childhood periodic syndromes (CPS) for
mutations in these three genes. Two novel CACNA1A variants, p.Val581Met and
p.Tyr1245Cys, and a previously annotated change, p.Cys1534Ser, were identified in
individuals with HM, although they have not yet been proven to be pathogenic.
Interestingly, p.Tyr1245Cys was detected in a patient displaying a changing,
age-specific phenotype that began as benign paroxysmal torticollis of infancy,
evolving into benign paroxysmal vertigo of childhood and later becoming HM. This 
is the first instance of a specific non-synonymous base change being described in
a subject affected with CPS. The fact that the molecular screen identified
non-synonymous changes in < 15% of our HM patients further stresses the genetic
heterogeneity underlying the presumably monogenic forms of migraine.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 18644040 [PubMed - indexed for MEDLINE]

128: Cephalalgia. 2008 Nov;28(11):1126-35. Epub 2008 Jul 15.

History of methysergide in migraine.

Koehler PJ, Tfelt-Hansen PC.

Department of Neurology, Atrium Medical Centre, Heerlen, The Netherlands.

Harold Wolff's theory of vasodilation in migraine is well-known. Less known is
his search for a perivascular factor that would damage local tissues and increase
pain sensitivity during migraine attacks. Serotonin was found to be among the
candidate agents to be included. In the same period, serotonin was isolated
(1948) and, because of its actions, an anti-serotonin drug was needed.
Methysergide was synthesized from lysergic acid (LSD) by adding a methyl group
and a butanolamid group. This resulted in a compound with selectivity and high
potency as a serotonin (5-HT) inhibitor. Based on the possible involvement of
serotonin in migraine attacks, it was introduced in 1959 by Sicuteri as a
preventive drug for migraine. The clinical effect was often excellent, but 5
years later it was found to cause retroperitoneal fibrosis after chronic intake. 
Consequently, the use of the drug in migraine declined considerably, but it was
still used as a 5-HT antagonist in experimental studies. In 1974 Saxena showed
that methysergide had a selective vasoconstrictor effect in the carotid bed and
in 1984 he found an atypical receptor. This finding provided an incentive for the
development of sumatriptan. Bredberg et al. showed that methysergide is probably 
a prodrug for its active metabolite methylergometrine. Whereas methysergide is 'a
clean drug', methylergometrine is 'a relatively dirty drug' with additional
dopaminergic activity. The mechanism for the preventive effect of methysergide
(methylergometrine) in migraine remains elusive. We describe the rise, fall and
subsequent use as a third-choice drug of the first effective migraine
prophylactic, methysergide.

Publication Types: 
    Historical Article
    Review

PMID: 18644039 [PubMed - indexed for MEDLINE]

129: Cephalalgia. 2008 Nov;28(11):1136-44. Epub 2008 Jul 15.

Sickness absence among female employees with migraine and co-existing conditions.

Mäki K, Vahtera J, Virtanen M, Elovainio M, Pentti J, Keltikangas-Järvinen L,
Kivimäki M.

Department of Psychology, University of Helsinki, Finland.

This prospective cohort study examined the risk of sickness absence among 27,127 
female public-sector employees by status of migraine and co-existing conditions. 
A baseline survey was used to assess chronic disorders and demographic factors.
Information on sickness absence in the 3 years following the survey was obtained 
from employers' registers. Migraine was related to 5.4 extra sickness absence
days per person-year, with the corresponding figures being 14.6 and 6.1 for
depression and respiratory disorders, respectively. After adjusting for age,
marital status, socioeconomic status and presence of depression or respiratory
disorders, employees with migraine had a 1.21 (95% confidence interval 1.18,
1.24) times higher risk of self-certified sickness absence episodes (< or = 3
days) than did those without migraine. The corresponding excess risk for
medically certified absence episodes (> 3 days) was 1.15 (1.12, 1.19). Among
employees with depression or respiratory disorders, secondary migraine was
associated with an increased risk of sickness absence episode of 1.15 to 1.23.
These findings suggest that migraine is associated with increased risk of
recorded sickness absence independent of depression and respiratory disorders.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 18644038 [PubMed - indexed for MEDLINE]

130: Cephalalgia. 2008 Oct;28(10):1095-105. Epub 2008 Jul 17.

Almotriptan and its combination with aceclofenac for migraine attacks: a study of
efficacy and the influence of auto-evaluated brush allodynia.

Schoenen J, De Klippel N, Giurgea S, Herroelen L, Jacquy J, Louis P, Monseu G,
Vandenheede M; Belgian Headache Society.

Department of Neurology and Headache Research Unit, Liège University, Liège,
Belgium. jschoenen@ulg.ac.be

Early treatment and combining a triptan with a non-steroidal anti-inflammatory
drug (NSAID) are thought to improve outcome during migraine attacks, possibly by 
counteracting the negative influence of cutaneous allodynia. The aim of this
multicentre, double-blind pilot study was to evaluate the prevalence of brush
allodynia and its relative influence on the efficacy of a triptan-NSAID
combination compared with headache intensity at the time of treatment. In a
randomized, cross-over design, 112 migraineurs treated two moderate or severe
attacks with almotriptan 12.5 mg combined with either aceclofenac 100 mg or
placebo. Patients used a 2-cm brush to assess cutaneous allodynia. Allodynia was 
reported in 34.4% of attacks. The almotriptan-aceclofenac combination was
numerically superior to triptan-placebo on 2-24-h sustained pain-free (P = 0.07),
2-h pain-free (P = 0.07) and headache recurrence (P = 0.05) rates, but not on 1-h
headache relief. Allodynia numerically reduced treatment success overall, but
this effect was not significant for the primary outcome measures. Headache
intensity had a significant negative influence on 1-h relief in both attacks (P =
0.0001 and 0.0008, chi(2)) and on 2-24-h sustained pain-free rates in
triptan-placebo-treated attacks (P = 0.013). Multivariate logistic regression
analysis confirmed that headache intensity at treatment intake, rather than
allodynia, significantly influenced most outcome measures, predominantly so in
attacks treated with almotriptan and aceclofenac. In the latter, severe compared 
with moderate headache intensity reduced the likelihood of achieving the primary 
efficacy end-points [odds ratios (OR) 0.12 and 0.33], whereas allodynia was not a
significant explanatory variable (OR 0.76 and 0.65). The results apply to the
protocol used here and need to be confirmed in larger studies using quantitative 
sensory testing.

Publication Types: 
    Multicenter Study
    Randomized Controlled Trial

PMID: 18644036 [PubMed - indexed for MEDLINE]

131: Cephalalgia. 2008 Oct;28(10):1061-8. Epub 2008 Jul 17.

Selective diffusion changes of the visual pathways in patients with migraine: a
3-T tractography study.

Rocca MA, Pagani E, Colombo B, Tortorella P, Falini A, Comi G, Filippi M.

Neuroimaging Research Unit, Department of Neurology, University Ospedale San
Raffaele, Milan, Italy.

Using diffusion tensor (DT) tractography, we quantified optic radiation (OR)
structural changes in seven migraine patients with (MA) and eight without visual 
aura (MoA) and their relation to clinical manifestations and T2-visible burden.
The corticospinal tract and the corpus callosum were studied as 'control' white
matter (WM). No difference was found for any of the WM fibre bundles metrics
between controls and MoA patients. MA patients had reduced average fractional
anisotropy (FA) of both OR compared with controls and reduced average FA of the
right OR compared with MoA patients. They also showed higher right OR mean
diffusivity than controls. OR metrics were not correlated with clinical and
magnetic resonance imaging (MRI) metrics. DT tractography reveals OR changes in
MA patients that might represent a phenotypic biomarker of the disease given the 
lack of correlation with clinical and structural MRI metrics.

PMID: 18644035 [PubMed - indexed for MEDLINE]

132: Cephalalgia. 2008 Nov;28(11):1170-8. Epub 2008 Jul 15.

Cumulative lifetime migraine incidence in women and men.

Stewart WF, Wood C, Reed ML, Roy J, Lipton RB; AMPP Advisory Group.

Collaborators: Lipton RB, Bigal ME, Reed ML, Stewart W, Diamond M, Freitag F,
Hazard E, Tierce J, Loder E, Winner P, Silberstein S, Simons S, Diamond S.

Geisinger Clinic, Center for Health Research, Danville, PA 17822, USA.
wfstewart@geisinger.edu

The aim was to estimate lifetime sex and age-specific incidence of migraine. Data
are from the American Migraine Prevalence and Prevention study, a mailed survey
sent to 120,000 US households. Age-specific incidence was estimated using
self-reported data relevant to identification of migraine cases, age of onset of 
migraine and age at interview. Migraine incidence peaked between the ages of 20
and 24 years in women (18.2/1000 person-years) and the ages of 15 and 19 years in
men (6.2/1000 person-years). Cumulative incidence was 43% in women and 18% in
men. Median age of onset was 25 years among women and 24 years among men. Onset
in 50% of cases occurred before age 25 and in 75% before age 35 years. Four of
every 10 women and two of every 10 men will contract migraine in their lifetime, 
most before age 35 years. The incidence estimates from this analysis are
consistent with those reported in previous longitudinal studies.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 18644028 [PubMed - indexed for MEDLINE]

133: Clin Ther. 2008 Jun;30(6):1069-80.

Weight change associated with the use of migraine-preventive medications.

Taylor FR.

Park Nicollet Headache Clinic & Research Center and the University of Minnesota
School of Medicine, Minneapolis, Minnesota 55426, USA.
Frederick.Taylor@ParkNicollet.com

BACKGROUND: Medications administered long term, such as those used for migraine
prophylaxis, are often associated with weight change as a side effect. Such
effects may compromise general health status, exacerbate coexisting medical
conditions, and affect medication adherence. Weight gain should be of particular 
concern in patients with migraine, as there is evidence that overweight and obese
patients with migraine are at risk for an increased frequency and severity of
migraine attacks. OBJECTIVE: This article reviews weight-change data from recent 
clinical studies of migraine-preventive medications in children, adolescents, and
adults with migraine. METHODS: A PubMed search was conducted for English-language
articles published between January 1970 and November 2007. Among the search terms
were migraine prevention, migraine prophylaxis, migraine treatment,
antidepressant drug, beta-adrenergic-receptor blockers, antiepileptic drug,
anticonvulsant drug, weight gain, and weight loss. Studies that reported
weight-change data (gain, loss, or neutral) were included. When available,
double-blind, placebo-controlled studies were selected for review. Open-label,
retrospective or prospective trials may also have been included. RESULTS: Most of
the migraine-preventive medications classified by the United States Headache
Consortium as group 1 based on the high level of evidence for their efficacy--for
instance, amitriptyline, propranolol, and divalproex sodium-have been associated 
with varying degrees of weight gain. The exceptions are timolol, which is weight 
neutral, and topiramate, which is associated with weight loss. Among the drugs
that have been associated with weight gain, a higher incidence of weight gain was
observed with amitriptyline and divalproex sodium than with propranolol.
CONCLUSION: Weight-change effects require careful consideration when selecting
migraine-preventive medications, and weight should be monitored carefully over
the course of any migraine treatment plan.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 18640463 [PubMed - indexed for MEDLINE]

134: J Neurosci. 2008 Jul 16;28(29):7273-83.

Self-limited hyperexcitability: functional effect of a familial hemiplegic
migraine mutation of the Nav1.1 (SCN1A) Na+ channel.

Cestèle S, Scalmani P, Rusconi R, Terragni B, Franceschetti S, Mantegazza M.

Department of Neurophysiopathology, Besta Neurological Institute, 20133 Milan,
Italy.

Familial hemiplegic migraine (FHM) is an autosomal dominant inherited subtype of 
severe migraine with aura. Mutations causing FHM (type 3) have been identified in
SCN1A, the gene encoding neuronal voltage-gated Na(v)1.1 Na(+) channel alpha
subunit, but functional studies have been done using the cardiac Na(v)1.5
isoform, and the observed effects were similar to those of some epileptogenic
mutations. We studied the FHM mutation Q1489K by transfecting tsA-201 cells and
cultured neurons with human Na(v)1.1. We show that the mutation has effects on
the gating properties of the channel that can be consistent with both
hyperexcitability and hypoexcitability. Simulation of neuronal firing and long
depolarizing pulses mimicking promigraine conditions revealed that the effect of 
the mutation is a gain of function consistent with increased neuronal firing.
However, during high-frequency discharges and long depolarizations, the effect
became a loss of function. Recordings of firing of transfected neurons showed
higher firing frequency at the beginning of long discharges. This self-limited
capacity to induce neuronal hyperexcitability may be a specific characteristic of
migraine mutations, able to both trigger the cascade of events that leads to
migraine and counteract the development of extreme hyperexcitability typical of
epileptic seizures. Thus, we found a possible difference in the functional
effects of FHM and familial epilepsy mutations of Nav1.1.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 18632931 [PubMed - indexed for MEDLINE]

135: Ann Emerg Med. 2008 Dec;52(6):705-13. Epub 2008 Jul 16.

The relative efficacy of meperidine for the treatment of acute migraine: a
meta-analysis of randomized controlled trials.

Friedman BW, Kapoor A, Friedman MS, Hochberg ML, Rowe BH.

Department of Emergency Medicine, Albert Einstein College of Medicine, Bronx, NY 
10467, USA. befriedm@montefiore.org

STUDY OBJECTIVE: Despite guidelines recommending against opioids as first-line
treatment for acute migraine, meperidine is the agent used most commonly in North
American emergency departments. Clinical trials performed to date have been small
and have not arrived at consistent conclusions about the efficacy of meperidine. 
We performed a systematic review and meta-analysis to determine the relative
efficacy and adverse effect profile of opioids compared with nonopioid active
comparators for the treatment of acute migraine. METHODS: We searched multiple
sources (Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, CINAHL,
and LILACS, emergency and headache medicine conference proceedings) for
randomized controlled trials comparing parenteral opioid and nonopioid active
comparators for the treatment of acute migraine headache. Our primary outcome was
relief of headache. If this was unavailable, we accepted rescue medication use or
we transformed visual analog scale change scores by using an established
procedure. We grouped studies by comparator: a regimen containing
dihydroergotamine, antiemetic alone, or ketorolac. For each study, we calculated 
an odds ratio (OR) of headache relief and then assessed clinical and statistical 
heterogeneity for the group of studies. We then pooled the ORs of headache relief
with a random-effects model. RESULTS: From 899 citations, 19 clinical trials were
identified, of which 11 were appropriate and had available data. Four trials
involving 254 patients compared meperidine to dihydroergotamine, 4 trials
involving 248 patients compared meperidine to an antiemetic, and 3 trials
involving 123 patients compared meperidine to ketorolac. Meperidine was less
effective than dihydroergotamine at providing headache relief (OR=0.30; 95%
confidence interval [CI] 0.09 to 0.97) and trended toward less efficacy than the 
antiemetics (OR=0.46; 95% CI 0.19 to 1.11); however, the efficacy of meperidine
was similar to that of ketorolac (OR=1.75; 95% CI 0.84 to 3.61). Compared to
dihydroergotamine, meperidine caused more sedation (OR=3.52; 95% CI 0.87 to
14.19) and dizziness (OR=8.67; 95% CI 2.66 to 28.23). Compared to the
antiemetics, meperidine caused less akathisia (OR=0.10; 95% CI 0.02 to 0.57).
Meperidine and ketorolac use resulted in similar rates of gastrointestinal
adverse effects (OR=1.27; 95% CI 0.31 to 5.15) and sedation (OR=1.70; 95% CI 0.23
to 12.72). CONCLUSION: Clinicians should consider alternatives to meperidine when
treating acute migraine with injectable agents.

Publication Types: 
    Meta-Analysis
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't
    Review

PMID: 18632186 [PubMed - indexed for MEDLINE]

136: Headache. 2008 Oct;48(9):1372-4. Epub 2008 Jul 8.

Ophthalmoplegic migraine and infundibular dilatation of a cerebral artery.

Vieira JP, Castro J, Gomes LB, Jacinto S, Dias A.

Ophthalmoplegic migraine (OM) is a childhood disorder of uncertain etiology
manifesting recurrent unilateral headache associated with a transitory oculomotor
(usually IIIrd nerve) palsy. Recent publications emphasize the finding on MRI of 
contrast enhancement in the IIIrd nerve suggesting that OM may be a recurrent
inflammatory neuropathy. We report the case of a 7-year-old boy with typical
symptoms of this disorder. Angio MR and Angio CT revealed the presence of an
infundibular dilatation of a perforating branch of the posterior cerebral artery 
adjacent to the symptomatic IIIrd nerve. We speculate that this and perhaps other
cases of OM may have a different pathophysiology related to compression of the
IIIrd nerve by an adjacent vascular structure that could activate the
trigeminovascular system and produce migrainous pain.

Publication Types: 
    Case Reports
    Letter

PMID: 18631189 [PubMed - indexed for MEDLINE]

137: Dermatitis. 2008 May-Jun;19(3):E10-1.

Formaldehyde, aspartame, and migraines: a possible connection.

Jacob SE, Stechschulte S.

Department of Dermatology and Cutaneous Surgery, University of Miami, Miami, FL, 
USA.

Aspartame is a widely used artificial sweetener that has been linked to pediatric
and adolescent migraines. Upon ingestion, aspartame is broken, converted, and
oxidized into formaldehyde in various tissues. We present the first case series
of aspartame-associated migraines related to clinically relevant positive
reactions to formaldehyde on patch testing.

Publication Types: 
    Case Reports

PMID: 18627677 [PubMed - indexed for MEDLINE]

138: Neurol Sci. 2008 May;29 Suppl 1:S186-90.

Oral contraceptive-induced menstrual migraine. Clinical aspects and response to
frovatriptan.

Allais G, Bussone G, Airola G, Borgogno P, Gabellari IC, De Lorenzo C, Pavia E,
Benedetto C.

Women's Headache Center Department of Gynecology and Obstetrics, University of
Turin, Via Ventimiglia 3, 10126 Turin, Italy. gb.allais@tiscali.it

Oral contraceptive-induced menstrual migraine (OCMM) is a poorly defined migraine
subtype mainly triggered by the cyclic pill suspension. In this pilot, open-label
trial we describe its clinical features and evaluate the efficacy of frovatriptan
in the treatment of its acute attack. During the first 3 months of the study 20
women (mean age 32.2+/-7.0, range 22-46) with a 6-month history of pure OCMM
recorded, in monthly diary cards, clinical information about their migraine.
During the 4th menstrual cycle they treated an OCMM attack with frovatriptan 2.5 
mg. The majority of attacks were moderate/severe and lasted 25-72 h or more, in
the presence of usual treatment. Generally an OCMM attack appeared within the
first 5 days after the pill suspension, but in 15% of cases it started later.
After frovatriptan administration, headache intensity progressively decreased
(2.4 at onset, 1.6 after 2 h, 1.1 after 4 h and 0.8 after 24 h; p=0.0001). In 55%
of patients pain relief was reported after 2 h. Ten percent of subjects were
pain-free subjects after 2 h, 35% after 4 h and 60% after 24 h (p=0.003 for
trend); 36% relapsed within 24 h. Rescue medication was needed by 35% of
patients; 50% of frovatriptan-treated required a second dose. Concomitant nausea 
and/or vomiting, photophobia and phonophobia decreased significantly after drug
intake. OCMM is a severe form of migraine; actually its clinical features are not
always exactly identified by the ICHD-II classification. However, treatment with 
frovatriptan 2.5 mg might be effective in its management.

Publication Types: 
    Clinical Trial
    Research Support, Non-U.S. Gov't

PMID: 18545931 [PubMed - indexed for MEDLINE]

139: Neurol Sci. 2008 May;29 Suppl 1:S182-5.

Patent foramen ovale detected by near-infrared spectroscopy in patients suffering
from migraine with aura.

Liboni W, Molinari F, Allais GB, Mana O, Negri E, D'Andrea G, Bussone G,
Benedetto C.

Department of Neuroscience, Gradenigo Hospital, Turin, Italy.

There is an increased prevalence of patent foramen ovale (PFO) in women with
migraine with aura (MwA) compared to controls, but the role of PFO in triggering 
aura is still debated. The aim of this study was to test a group of women
suffering from MwA with near-infrared spectroscopy (NIRS), to assess the NIRS
capability of discriminating between subjects with and without PFO. Eighty-eight 
MwA patients (mean age 37.4+/-10.7 years, range 16-62 years) underwent NIRS
measurement of the cerebral variations of the oxygenated (O2Hb) and reduced
haemoglobin (HHb) during breath-holding. The prevalence of O2Hb vs. HHb was used 
to assess the presence of PFO. As a gold standard, the presence of PFO was
assessed by transcranial Doppler sonography (TCD). At the TCD analysis 48
patients (55%) showed PFOs, 32 of which were permanent. NIRS correctly detected
36 subjects out of 40 without PFO, and 38 subjects out of 48 having PFO:
sensitivity was 79%; specificity was 90%. All the false negatives were permanent 
shunts. MwA patients with PFO showed a delayed increase in the O2Hb concentration
and a reduced oxygenation with respect to subjects without PFO. NIRS is effective
in identifying the presence of PFO in a MwA population, but TCD achieves better
diagnostic performances. The NIRS provides additional information about the
cerebral vasoreactivity and highlights substantial differences between patients
with latent and permanent shunts that warrant further studies.

PMID: 18545930 [PubMed - indexed for MEDLINE]

140: Neurol Sci. 2008 May;29 Suppl 1:S179-81.

Association between plasma lipid levels and migraine in subjects aged > or =50
years: preliminary data from the Zabùt Aging Project.

Monastero R, Pipia C, Cefalù AB, Liveri ET, Rosano R, Camarda R, Camarda C.

Adult Headache Center Department of Clinical Neuroscience, University of Palermo,
Via La Loggia 1, 90129 Palermo, Italy. roberto.monastero@unipa.it

We evaluated the association between lipid levels and migraine using
cross-sectional, population-based data of 1809 subjects aged > or =50 years; 151 
subjects with migraine and 1658 nonmigraineurs were included. Diagnosis of
migraine was carried out using the criteria of the International Headache
Society. The following plasma lipids were collected: total cholesterol (TC), low 
density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol
(HDL-C) and triglycerides (TG). Only TC (p<0.003) and LDL-C levels (p<0.004) were
significantly higher in migraineurs than nonmigraineurs. After multiple
adjustments, only elevated TC (> or =220 mg/dl) was significantly associated with
migraine (OR [95% CI]=1.6 [1.1-2.3]); this association increased in elderly males
with migraine (OR [95% CI]=3.8 [1.4-9.9]). According to our results, TC plasma
levels should be closely monitored in elderly males with migraine.

PMID: 18545929 [PubMed - indexed for MEDLINE]

141: Neurol Sci. 2008 May;29 Suppl 1:S173-5.

Homocysteine plasma levels in patients with migraine with aura.

Moschiano F, D'Amico D, Usai S, Grazzi L, Di Stefano M, Ciusani E, Erba N,
Bussone G.

L. Mandic Hospital, Via L. Mandic 1, Merate (LC), Italy.
f.moschiano@ospedale.lecco.it

We investigated homocysteine plasma levels in 136 MA sufferers and in 117 sex-and
age-matched controls. Mean homocysteine plasma levels - as well as the proportion
of subjects with hyperhomocysteinaemia - were significantly higher in patients
with MA than in healthy controls. Hyperhomocysteinaemia may be a link between MA 
and ischaemic stroke.

PMID: 18545927 [PubMed - indexed for MEDLINE]

142: Neurol Sci. 2008 May;29 Suppl 1:S166-8.

High prevalence of Dopaminergic Premonitory Symptoms in migraine patients with
Restless Legs Syndrome: a pathogenetic link?

Cologno D, Cicarelli G, Petretta V, d'Onofrio F, Bussone G.

Clinical Neurophysiology Department of Neuroscience, Ospedali Riuniti, Viale L.
Pinto 1, 71100 Foggia, Italy. danielacologno@virgilio.it

In order to assess the prevalence of Dopaminergic Premonitory Symptoms (DPS) in
migraine patients with Restless Legs Syndrome (RLS), we chose migraine patients
from a large Italian clinical headache population previously investigated for an 
association between primary headaches and RLS. We evaluated a total sample of 164
patients with migraine, in particular 114 with migraine without aura (MO), 10
with migraine with aura (MA) and 40 with MO and MA in various combinations
between them or with episodic tension-type headache (ETTH), defined as a "mixed
group". About 20% of all migraine patients referred at least one of the following
DPS: yawning, nausea, somnolence or food craving, confirming data already
indicated in the literature. Among migraine patients with RLS (25.6%), DPS were
referred from about half of the patients (47.6%) compared to those without RLS
(47.6% vs. 13.1%; p<0.001). Based on migraine subtype, patients with MO referred 
DPS (26.3%) more frequently compared to the MA group and "mixed group" (12.0%,
p<0.05), particularly in the presence of RLS (63.0% vs. 20.0%, p<0.01). No
statistical differences were found between clinical and demographic data of the
subgroups or related to medical conditions investigated (anxiety, depression,
sleep disorders, body mass index). It is interesting that the chances of having
RLS in migraine patients were more than 5 times higher in the presence of DPS.
These results could support a hypothetical dopaminergic imbalance in RLS and
migraine, as the dopamine is involved in the pathogenesis of both disorders and
it is responsible for the migraine DPS reported above.

PMID: 18545925 [PubMed - indexed for MEDLINE]

143: Neurol Sci. 2008 May;29 Suppl 1:S155-7.

Quality of life, eating and mood disorders in menstrual migraine: a case-control 
study.

Nicodemo M, Vignatelli L, Grimaldi D, Sancisi E, Fares JE, Zanigni S, Pierangeli 
G, Cortelli P, Montagna P, Cevoli S.

Department of Neurological Science, University of Bologna, Via U. Foscolo 7,
40123 Bologna (BO), Italy. centro.cefalee@unibo.it

The aim of this study was to evaluate the prevalence of mood and eating disorders
in patients with menstrual migraine. Quality of life and disability were also
assessed. The study confirmed the presence of significant disability and poor
quality of life due to migraine even in a selected subgroup of patients affected 
with menstrual migraine. In contrast with the previous literature we did not find
any difference in the prevalence of mood and eating disorders.

PMID: 18545921 [PubMed - indexed for MEDLINE]

144: Neurol Sci. 2008 May;29 Suppl 1:S152-4.

Personality profile and allodynic migraine.

Lovati C, D'Amico D, Brambilla A, Mariani C, Bussone G.

Department of Neurology, L. Sacco Hospital, Via GB Grassi 74, 20157 Milan, Italy.
carlo.lovati@tiscali.it

Migraine is known to be associated to particular psychological features.
Cutaneous allodynia is a painful sensation or discomfort induced by a non-noxious
stimulus, and is a frequent complaint during migraine attacks. The aim of this
study was to compare the personality profile of allodynic and non-allodynic
migraineurs to identify possible relationships between psychological aspects and 
the presence of allodynia. The Symptom Check List 90-R (SCL90R), a 90-item
self-report psychological symptom inventory, was used to investigate the
psychological profile of our patients. The presence of allodynia was assessed by 
a set of semi-structured questions that investigated if the patient experienced
abnormal scalp sensitiveness and/or discomfort during headache episodes.
Twenty-five nonallodynic patients and 38 allodynic migraineurs were studied. No
significant difference was found between the two groups in any area of the
personality profile. The psychological profile seems not to affect the
presence/absence of cutaneous allodynia in migraine patients. This reinforces the
hypothesis that allodynia is a "somatic" symptom, not modified by psychological
aspects.

PMID: 18545920 [PubMed - indexed for MEDLINE]

145: Neurol Sci. 2008 May;29 Suppl 1:S149-51.

Comorbidity between depressive symptoms and migraine: preliminary data from the
Zabút Aging Project.

Camarda C, Pipia C, Taglialavori A, Di Fiore P, Camarda R, Monastero R.

Adult Headache Centre Department of Clinical Neuroscience, University of Palermo,
Via La Loggia 1, 90129 Palermo, Italy. ceca72@hotmail.com

We evaluated the association between depressive symptoms and migraine using
cross-sectional data from the Zabút Aging Project, a population-based study
including subjects aged > or =50 years. A total of 1285 nonmigraineurs and 151
migraineurs were included. Diagnosis of migraine was carried out using the
criteria of the International Headache Society. The Center for Epidemiologic
Studies Depression scale (CES-D) was used to score depressive symptoms.
Depressive symptoms were clustered in four groups: depressed and positive
affects, somatic activity and intrapersonal feelings. Migraineurs showed higher
total and specific depressive symptoms than controls (p from 0.005 to <0.0001).
Mild-to-moderate depressive symptoms (CES-D score of > or =16) were present in
47.2% of migraineurs compared to 15.8% of controls (p<0.0001). After adjustment
for demographics, mild-to-moderate depressive symptoms were strongly associated
with migraine (OR [95% CI]=4.7 [3.1-7.0]). This association significantly
increased in males (OR [95% CI]=6.2 [2.8-14.6]). Depressive features represent
highly frequent comorbid symptoms of adult-to-elderly migraineurs.

PMID: 18545919 [PubMed - indexed for MEDLINE]

146: Neurol Sci. 2008 May;29 Suppl 1:S144-5.

Cerebrovascular risk factors and MRI abnormalities in migraine.

Rao R, Rosati A, Liberini P, Gipponi S, Venturelli E, Sapia E, Ambrosi C,
Padovani A.

Department of Neurology, University of Study of Brescia, Piazzale Spedali Civili 
1, 25123 Brescia, Italy. centrocefalee@spedalicivili.brescia.it

Case series have demonstrated an increased incidence of white matter lesions
(WMLs) in patients with migraine. It is controversial whether the evidence of
subclinical brain lesions relates to a higher risk of cerebrovascular disease.
The objective of this study was to evaluate the association between magnetic
resonance imaging (MRI) subclinical brain lesions and cerebrovascular risk
factors (hyperhomocysteinaemia, MTHFR genotype, patent foramen ovale,
hypertension, smoking and hypercholesterolaemia). From our database of 1201
patients followed at our Headache Clinic since September 2003 we analysed the MRI
findings of 253 individuals. All MRI were blindly analysed by a second
neuroradiologist (C.A.) and patients with WMLs (study group) were evaluated. In
order to assess the association of WMLs with specific vascular risk factors,
patients with WMLs were matched, according to age, sex and ICHD II diagnosis,
with an equal number of individuals with normal MRI (control group). Headache was
classified by the International Classification of Headache Disorders (ICHD 2004) 
criteria. We did not find any statistically significant difference between the
two groups with regard to the presence of the cerebrovascular disease risk
factors considered. Our results confirm that the WMLs are not related to the
cerebrovascular disease risk factors.

PMID: 18545917 [PubMed - indexed for MEDLINE]

147: Neurol Sci. 2008 May;29 Suppl 1:S141-3.

A functional MRI study of language disturbances in subjects with migraine
headache during treatment with topiramate.

De Ciantis A, Muti M, Piccolini C, Principi M, Di Renzo A, De Ciantis R, Frondizi
D, Iannone G, Ottaviano P, Piccirilli M.

Department of Neuroscience (Neurophysiopathology, Neurorehabilitation,
Neurology), Terni, Italy. alessiodec1982@libero.it

Topiramate (TPM) is a new antiepileptic drug approved for the prevention of
migraine headache. However its use is limited by treatment-emergent adverse
events; in particular, therapy can exert profound impact on language function. In
this investigation, we used functional magnetic resonance imaging (fMRI) to study
the anatomofunctional correlates of language disturbances in TPM patients
experiencing subjective cognitive impairment. Ten right-handed individuals
receiving therapy (five with and five without language disfluency) and five
matched healthy control subjects took part in this study. During fMRI subjects
alternately rested and performed a word-generating task. The task comprised the
silent generation of words beginning with a different input letter visually
presented. The activation paradigm consisted of six activation blocks alternating
with six baseline rest blocks. The main fMRI measure was the pattern activation
of the prefrontal regions (Brodmann's areas 44, 45, and 46) in both left and
right hemispheres. Patients receiving TPM (50-100 mg/day) significantly reduced
mean monthly migraine frequency. However several differences in fMRI activation
were evident in the subject group comparison. Notably, changes in brain activity 
were observed during the phonemic task in patients with language disturbances. It
is likely that TPM therapy is associated with a "remapping" of the language
cerebral network.

Publication Types: 
    Controlled Clinical Trial

PMID: 18545916 [PubMed - indexed for MEDLINE]

148: Neurol Sci. 2008 May;29 Suppl 1:S127-30.

Peripheral mechanism of action of antimigraine prophylactic drugs.

Frediani F, Villani V, Casucci G.

Neurological Department and Headache Center, Policlinico S. Pietro, via Forlanini
15, 24036 Ponte San Pietro (BG), Italy. fabio_frediani@yahoo.it

Migraine is a visceral pain. According to current theories, activation of
trigeminocervical nerve endings releases calcitonin gene-related peptide and
substance P, inducing vasodilation and plasma protein extravasation, leading to
'neurogenic' inflammation. Activation of the trigeminovascular system is followed
by sensitisation of trigeminocervical fibres, maintaining a condition of
hypersensitivity to non-noxious stimuli that support persistent pain during
migraine attack. Other neurotransmitters (nitric oxide, bradykinins, 5-HT, etc.) 
play a role in regulating this complex mechanism. In this brief review, we
consider the effect of drugs that, acting on the different transmitters involving
in pain perception, can stop or inhibit these pathogenetic mechanisms.

Publication Types: 
    Review

PMID: 18545913 [PubMed - indexed for MEDLINE]

149: Neurol Sci. 2008 May;29 Suppl 1:S123-6.

Central mechanism of action of antimigraine prophylactic drugs.

Casucci G, Villani V, Frediani F.

Casa di Cura S. Francesco, Viale Europa 21, 82036 Telese Terme (BN), Italy.
gerardocasucci@tin.it

The pathogenesis of migraine is obscure. A hyperexcitable brain state has been
postulated. Cortical spreading depression (CSD) is the most suggestive argument
for the brain hyperexcitability. It has been showed that valproate, topiramate,
amitriptyline and propranolol inhibit CSD in rats, which suggests that most
preventative treatments of migraine act by normalising neuronal firing and
increasing a genetically lowered and environmentally modified threshold for
neuronal discharge. It has also been suggested that some antimigraine
prophylactic drugs (i.e., amitriptyline, candesartan and magnesium) may act by
restoring central nociceptive dysmodulation.

Publication Types: 
    Review

PMID: 18545912 [PubMed - indexed for MEDLINE]

150: Neurol Sci. 2008 May;29 Suppl 1:S110-22.

Acute and prophylactic treatments for migraine: present and future.

Rapoport AM.

The David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
alanrapoport@gmail.com

Herein I will present general principles of acute-care and preventive therapy of 
migraine, both in the present and the future. Details of currently used migraine 
acute-care therapies with their contraindications, drug-drug interactions and
adverse events will be presented. Details of migraine preventive therapies with
their adverse events and drug-drug interactions will be discussed. Some
over-the-counter vitamins, minerals and herbs, used as preventive therapy in
migraine, will be discussed. Future treatments in the pipeline will be briefly
detailed.

Publication Types: 
    Review

PMID: 18545911 [PubMed - indexed for MEDLINE]

151: Neurol Sci. 2008 May;29 Suppl 1:S96-8.

Behavioural approach to the "difficult" patient.

Grazzi L.

Department of Clinical Neurosciences, C. Besta Neurological Institute, Via
Celoria 11, 20133 Milan, Italy. liciagrazzi@mac.com

The challenges in managing the more complicated headache patients are discussed
and reviewed in this article. These patients often have chronic daily headache or
high-frequency disabling headache. Some of these patients have problems adhering 
to treatment regimens, which may reduce treatment efficacy and sometimes lead to 
medication overuse. Medication overuse itself may induce a transformation of
headache to daily by reducing the effectiveness of acute and preventive
therapies. Biobehavioral factors are important in the assessment and treatment of
headache patients. Also the biobehavioral aspects involved in headache patients
will provide a model for integration of behavioural therapies into clinical
practice. The purpose of this article is to highlight behavioural/psychological
factors important to consider for clinicians managing this particular category of
patients.

Publication Types: 
    Review

PMID: 18545907 [PubMed - indexed for MEDLINE]

152: Neurol Sci. 2008 May;29 Suppl 1:S88-92.

Study of tyrosine metabolism in eating disorders. Possible correlation with
migraine.

D'Andrea G, Ostuzzi R, Bolner A, Francesconi F, Musco F, d'Onofrio F, Colavito D.

Headache Center of Villa Margherita Neurology Clinic, Via Costacolonna 20, 36057 
Arcugnano, Vicenza, Italy. giovinavi@virgilio.it

In order to understand the possible role of tyrosine metabolism and in particular
that of elusive amines in the pathogenesis of eating disorders (ED), we measured 
the plasma levels of dopamine, noradrenaline, tyramine (Tyr) and octopamine (Oct)
in a large group of anorexic and bulimic patients. In comparison to the control
group, the levels of nordrenaline were significantly lower and those of dopamine 
and Tyr higher in the ED patients. The plasma levels of Oct were in the same
range in both subject groups. However when comparing the bulimic vs. the anorexic
group, the Oct levels were significantly lower in the anorexic group, whereas
those of Tyr were significantly higher in the bulimic patients, suggesting that
different activation in the metabolism of elusive amines may underlie the shift
from the anorexic into the bulimic state. These biochemical findings raise the
possibility that abnormalities of the limbic and hypothalamic circuitries play a 
role in the pathogenesis of ED. In addition, the very high prevalence of migraine
(>75%) in our group of ED sufferers, and the biochemical profile(s) reported in
migraine, which appear similar to that found in ED patients, suggest that
migraine constitutes a risk factor for the occurrence of ED in young females.

PMID: 18545905 [PubMed - indexed for MEDLINE]

153: Neurol Sci. 2008 May;29 Suppl 1:S55-8.

When should "chronic migraine" patients be considered "refractory" to
pharmacological prophylaxis?

D'Amico D, Leone M, Grazzi L, Bussone G.

Department of Clinical Neurosciences, C. Besta Neurological Institute, Via
Celoria 11, 20133 Milan, Italy. damicodo@tiscali.it

Patients with chronic headache forms evolving from a previous episodic migraine
('chronic migraine') are often difficult to treat. In this paper we focus
attention on aspects we believe important for producing a definition of
"refractory" in relation to this headache form. We propose a "chronic migraine"
patient should be considered "refractory" to pharmacological prophylaxis when
adequate trials of preventive therapies at adequate doses have failed to reduce
headache frequency and improve headache-related disability and, in patients with 
medication overuse, reduce the consumption of symptomatic drugs. However before a
definition of "refractory" chronic migraine can become established, generally
accepted diagnostic criteria and treatment guidelines for this condition need to 
be developed.

Publication Types: 
    Review

PMID: 18545898 [PubMed - indexed for MEDLINE]

154: Neurol Sci. 2008 May;29 Suppl 1:S52-4.

Is migraine a genetic illness? The various forms of migraine share a common
genetic cause.

Russell MB.

Head and Neck Research Group, Akershus University Hospital, Dr. Kobros vei 39,
1474 Nordbyhagen, Oslo, Norway. m.b.russell@medisin.uio.no

Is migraine a genetic illness? This question was previously controversial, but
today the answer yes is generally accepted. The scientific evidence is the
significantly increased familial risk of migraine, and the significantly higher
concordance rate of migraine in monozygotic than dizygotic twin pairs. Finally,
the three identified ion-channel genes that can cause familial hemiplegic
migraine provide very strong evidence of genetics. Mutations in these genes can
also cause sporadic hemiplegic migraine. The next question is whether the
different types of migraine, i.e. migraine without aura, migraine with aura,
sporadic hemiplegic migraine and familial hemiplegic migraine share a common
genetic cause. This question is at present controversial. However, the fact that 
all types of migraine are paroxystic in nature suggest that a common genetic
cause could be mutations in ion channels, although a common mutation has not yet 
been identified in the more common types of migraine: migraine without aura and
migraine with aura.

Publication Types: 
    Review

PMID: 18545897 [PubMed - indexed for MEDLINE]

155: Neurol Sci. 2008 May;29 Suppl 1:S47-51.

Migraine: a genetic disease?

Montagna P.

Department of Neurological Sciences, University of Bologna Medical School, Via U.
Foscolo 7, 40123 Bologna, Italy. pasquale.montagna@unibo.it

Migraines carry a substantial genetic liability, and in families affected with
the typical migraines (migraine with, MA, and without aura, MO) linkage to some
chromosomal loci has been reported. As yet however, no genes are known for MA/MO,
while the three genes discovered as responsible for familial hemiplegic migraine 
(FHM) are not involved in the typical migraines. Accordingly, we propose to
consider FHM as a syndromic migraine and not as a variety of MA. Moreover, we
suggest that epigenetic mechanisms play a role in the determination of the
typical migraines, and that the primary headaches represent behavioural responses
(sickness behaviour, fight-or-flight responses), having adaptive advantage and
having been evolutionary conserved, in which pain represents a signal of
homeostatic imbalance. Epigenetic mechanisms and this proposed genetic
behavioural model could be usefully incorporated into headache genetic research.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 18545896 [PubMed - indexed for MEDLINE]

156: Neurol Sci. 2008 May;29 Suppl 1:S44-6.

Migraine with and without aura share the same pathogenic mechanisms.

Purdy RA.

Department of Medicine, Dalhousie University, Halifax, Canada. a.purdy@dal.ca

Migraine with aura and without aura share the same clinical features with respect
to the headache, and differ nosologically in the presence or absence of aura. The
mechanisms of aura generation are now becoming clearer, based on imaging studies,
and a common migraine pathophysiology for all subtypes of migraine headaches now 
seems reasonable, as it would seem implausible that all of these neurological
events have different pathogenic mechanisms. Both major subtypes of migraine
clearly represent a perturbation of normal physiology and employ normal anatomic 
pathways to generate the aura and headache, similar to aura and a seizure. So
what is the mechanism of migraine aura? Do migraine without aura patients have
clinically silent aura? Migraine is after all defined as a clinical disorder and 
is the prototypic primary headache and thus its uniform pathogenesis must
underlie all that we know about migraine clinically. This presentation will take 
the resolve that the migraine with and without aura share the same pathogenic
mechanisms.

Publication Types: 
    Review

PMID: 18545895 [PubMed - indexed for MEDLINE]

157: Neurol Sci. 2008 May;29 Suppl 1:S40-3.

Migraine with and without aura: a single entity?

Manzoni GC, Torelli P.

Headache Centre, Section of Neurology, Department of Neuroscience, University of 
Parma, c/o Ospedale Maggiore, Via Gramsci 14, 43100 Parma, Italy.
giancamillo.manzoni@unipr.it

A debate has been going on for many years about whether migraine with aura and
migraine without aura are part of the same disorder or should instead be
considered as two separate disorders. Although no final consensus has yet been
reached on this issue, many clinical and pathogenetic elements suggest that the
second option is true. Clinically, migraine with aura and migraine without aura
are differentiated by epidemiological features, the characteristics of the
headache phase, patient behaviour during attacks, natural history, age at onset
and age at resolution, the recurrence pattern of attacks, favouring circumstances
and trigger factors, correlation to female reproductive events, comorbidity and
preventive therapies. Moreover, several literature reports suggest a possible
different pathogenetic basis for the two forms of migraine.

Publication Types: 
    Review

PMID: 18545894 [PubMed - indexed for MEDLINE]

158: Neurol Sci. 2008 May;29 Suppl 1:S37-9.

Migraine and hypertension.

Agostoni E, Aliprandi A.

Department of Neurosciences Division of Neurology, Alessandro Manzoni Hospital,
Lecco, Italy. elioagostoni@ospedale.lecco.it

Although the possibility of a comorbidity between migraine and hypertension has
long been suspected, the epidemiologic evidence is controversial, with studies
demonstrating positive, negative or no correlation between the two diseases. A
unifying view that takes into account the most recent evidence suggests that
there might be a different effect of diastolic and systolic pressure, with the
former having a positive and the latter a negative correlation with migraine. In 
this paper, the methodologic and clinical reasons for the discrepancies in
epidemiologic studies are discussed, together with the possible biological
mechanisms that might account for the migraine-hypertension correlation. One such
mechanisms may be the renin angiotensin system, which is certainly involved in
hypertension and has activities in the CNS that may be relevant for migraine
pathogenesis. Despite the uncertainty still present in this field, the control of
hypertension in migraine patients is an important factor for the success of
migraine treatment and to lower cerebrovascular risk.

Publication Types: 
    Review

PMID: 18545893 [PubMed - indexed for MEDLINE]

159: Neurol Sci. 2008 May;29 Suppl 1:S23-7.

Does closure of a patent foramen ovale have a role in the treatment of migraine
with aura?

D'Amico D, Usai S, Caputi L, Bussone G.

Department of Clinical Neurosciences Department, C. Besta Neurological Institute,
Via Celoria 11, 20133 Milan, Italy. damicodo@tiscali.it

Patent foramen ovale (PFO) is associated with ischaemic stroke and migraine with 
aura (MA), and has been proposed as a cause of both. Numerous studies indicate
that percutaneous PFO closure can improve MA, but they all suffer from
methodological problems. It is recommended that the advantages and risks of PFO
closure be carefully assessed in each individual, bearing in mind that effective 
prophylactic medications are available for MA patients with high attack
frequency.

Publication Types: 
    Review

PMID: 18545890 [PubMed - indexed for MEDLINE]

160: Neurol Sci. 2008 May;29 Suppl 1:S19-22.

The diagnostic iter of patent foramen ovale in migraine patients: an update.

Liboni W, Molinari F, Chiribiri A, Allais G, Mana O, Negri E, Grippi G, Giacobbe 
M, Badalamenti S, Benedetto C.

Department of Neuroscience, Gradenigo Hospital, Turin, Italy.

Patent foramen ovale (PFO) is a frequent finding in migraine patients. The
standard technique for PFO diagnosis is actually trans-oesophageal
echocardiography (TEE). It requires the injection of a contrast agent unable to
pass the pulmonary filter; hence, it is possible to detect a right-to-left shunt 
by observing the presence of the contrast medium in the cardiac left compartment.
The transcranial Doppler (TCD) device accurately measures the blood flow
velocities in different cerebral arteries. It can record microembolic signals
(MES) backscattered by microbubbles travelling in the cerebral circulation, and
distinguish cardiac shunts from pulmonary shunts. The number of MES is correlated
to the entity of the shunt. The near-infrared spectroscopy (NIRS) technique
tracks the changes in the concentration of oxygenated and reduced haemoglobin in 
the brain tissue. PFO is revealed by an alteration of the normal vasoreactivity
pattern of the subject during functional stimuli. Magnetic resonance imaging
(MRI) provides, at the same time, detailed anatomical information and functional 
measurements. MRI dynamic perfusion sequences can be used to reliably detect PFO 
either by visual assessment or by signal-time curves in the pulmonary artery and 
in the left atrium. A good correlation between TEE and MRI grading scores has
been demonstrated, even though the interindividual variability of performing the 
Valsalva manoeuvre could greatly reduce the sensitivity of the method. Further
prospective studies are needed to confirm the PFO MRI grading and to assess the
sensitivity and specificity of the method.

Publication Types: 
    Review

PMID: 18545889 [PubMed - indexed for MEDLINE]

161: Neurol Sci. 2008 May;29 Suppl 1:S15-8.

The patent foramen ovale-migraine connection: a new perspective to demonstrate a 
causal relation.

Anzola GP, Mazzucco S.

Service of Neurology, S. Orsola Hospital FBF, Via Vittorio Emanuele II 27, 25100 
Brescia, Italy. gpanzola@fatebenefratelli.it

In the last ten years a considerable bulk of evidence has accumulated on the
relationship between migraine, particularly migraine with aura, and atrial septal
defects, particularly patent foramen ovale (PFO). The increased frequency of PFO 
in migraine with aura, which almost parallels that found in stroke of unknown
cause, the fact that in migraine patients PFO tends to be larger than in
non-migraine controls and some positive results on migraine severity obtained
after PFO closure have spurred speculation on a possible causal relationship. By 
applying the criteria proposed by Bradford-Hill to establish causality between
associated phenomena, we try to demonstrate that PFO is not just a further
example of migraine comorbidity but exerts a causal effect at least in the
triggering of aura.

Publication Types: 
    Historical Article
    Review

PMID: 18545888 [PubMed - indexed for MEDLINE]

162: Neurol Sci. 2008 May;29 Suppl 1:S12-4.

Migraine and stroke: the role of oral contraceptives.

Allais G, Gabellari IC, Mana O, Schiapparelli P, Terzi MG, Benedetto C.

Women's Headache Center Department of Gynecology and Obstetrics, University of
Turin, Via Ventimiglia 3, 10126 Turin, Italy. gb.allais@tiscali.it

The use of oral contraceptives (OCs) confers an increased risk for ischaemic
stroke (IS). This risk slightly decreases, but remains significant, if low-dose
formulations are used, particularly if other risk factors, such as hypertension
or smoking, are associated. Some inherited prothrombotic conditions (e.g., Factor
V Leiden, G20210A prothrombin or methylenetetrahydrofolate reductase C677T
polymorphism) could also greatly increase the IS risk if present in OC users.
Migraine, particularly with aura, is an independent risk factor for IS, and the
patient's IS risk is probably affected by other individual risk factors (e.g.,
age, genetic predisposition to thrombosis, presence of patent foramen ovale or
enhanced platelet aggregation) which seem to be over-represented in migraine
patients. IS risk among migraineurs is further increased when OCs are currently
used and can become very high if associated with smoking. Consequently, in 2004
the WHO stated in its 'Medical Eligibility Criteria for Contraceptive Use' that
women suffering from migraine with aura at any age should never use OCs.
Moreover, since the exposure to the effects of OCs may greatly increase the IS
risk in some migraine subpopulations with specific personal characteristic,
testing for these risk factors may allow for more accurate stratification of the 
population at risk before long-term use of OCs is prescribed.

Publication Types: 
    Historical Article
    Review

PMID: 18545887 [PubMed - indexed for MEDLINE]

163: Neurol Sci. 2008 May;29 Suppl 1:S7-11.

Migraine and stroke: from a questioned relationship to a supported comorbidity.

Narbone MC, Gangemi S, Abbate M.

Department of Neurosciences, Psychiatric and Anaesthesiological Sciences, AOU G. 
Martino, Via C. Valeria-Contesse, 98124 Messina, Italy. mcnarbone@yahoo.it

Migraine and stroke are two common and prevalent diseases. The relationship
between them is an ongoing, intriguing matter of debate. About 40 years ago, some
different reports on this topic raised the question of the existence of a
relationship between the two diseases. To date the existence of a comorbidity
between migraine and ischaemic stroke is supported by population and clinical
series studies. Literature data on this subject are reviewed in this report.

Publication Types: 
    Historical Article
    Review

PMID: 18545886 [PubMed - indexed for MEDLINE]

164: Naunyn Schmiedebergs Arch Pharmacol. 2008 Oct;378(4):371-94. Epub 2008 Jul
15.

Current and prospective pharmacological targets in relation to antimigraine
action.

Mehrotra S, Gupta S, Chan KY, Villalón CM, Centurión D, Saxena PR,
MaassenVanDenBrink A.

Division of Vascular Pharmacology, Department of Internal Medicine, Erasmus MC,
University Medical Center Rotterdam, P.O. Box 2040, 3000 CA, Rotterdam, The
Netherlands.

Migraine is a recurrent incapacitating neurovascular disorder characterized by
unilateral and throbbing headaches associated with photophobia, phonophobia,
nausea, and vomiting. Current specific drugs used in the acute treatment of
migraine interact with vascular receptors, a fact that has raised concerns about 
their cardiovascular safety. In the past, alpha-adrenoceptor agonists
(ergotamine, dihydroergotamine, isometheptene) were used. The last two decades
have witnessed the advent of 5-HT(1B/1D) receptor agonists (sumatriptan and
second-generation triptans), which have a well-established efficacy in the acute 
treatment of migraine. Moreover, current prophylactic treatments of migraine
include 5-HT(2) receptor antagonists, Ca(2+) channel blockers, and
beta-adrenoceptor antagonists. Despite the progress in migraine research and in
view of its complex etiology, this disease still remains underdiagnosed, and
available therapies are underused. In this review, we have discussed
pharmacological targets in migraine, with special emphasis on compounds acting on
5-HT (5-HT(1-7)), adrenergic (alpha(1), alpha(2,) and beta), calcitonin
gene-related peptide (CGRP(1) and CGRP(2)), adenosine (A(1), A(2), and A(3)),
glutamate (NMDA, AMPA, kainate, and metabotropic), dopamine, endothelin, and
female hormone (estrogen and progesterone) receptors. In addition, we have
considered some other targets, including gamma-aminobutyric acid, angiotensin,
bradykinin, histamine, and ionotropic receptors, in relation to antimigraine
therapy. Finally, the cardiovascular safety of current and prospective
antimigraine therapies is touched upon.

Publication Types: 
    Review

PMID: 18626630 [PubMed - indexed for MEDLINE]

165: Curr Pain Headache Rep. 2008 Aug;12(4):285-91.

Ophthalmoplegic migraine: still a diagnostic dilemma?

Ravishankar K.

The Headache and Migraine Clinic, Jaslok Hospital and Research Centre, Lilavati
Hospital and Research Centre; A-64, Kalpataru Residency, Sion, Mumbai - 400 022, 
India. dr.k.ravishankar@gmail.com

The term ophthalmoplegic migraine (OM) was first coined by Charcot in 1890. This 
condition was included as a migraine variant in the first Headache Classification
of the International Headache Society in 1988. Based on postcontrast enhancement 
seen on MRI in some patients who were diagnosed with OM, there was a suggestion
that this could be an inflammatory/demyelinating disorder; therefore, it was
moved out of the "migraine" group and repositioned as a "neuralgia" in the
revised 2004 classification. However, there have been subsequent reports in the
literature in which there was no enhancement on postcontrast MRI. Based on a
survey of literature on OM in the post-imaging era, this article highlights the
fact that enhancement on magnetic resonance is not a sine qua non for the
diagnosis of OM. Some diagnostic dilemmas are discussed, and a protocol is
included for documentation of clinical findings in future case reports on a
prospective basis. Hopefully, this will help in modification of the criteria,
better understanding the etiology, correct diagnosis, and determining appropriate
treatment for OM.

Publication Types: 
    Review

PMID: 18625106 [PubMed - indexed for MEDLINE]

166: Cephalalgia. 2008 Sep;28(9):945-9.

Increased risk for coeliac disease in paediatric patients with migraine.

Alehan F, Ozçay F, Erol I, Canan O, Cemil T.

Divisions of Child Neurology, Baskent University of Medicine, Ankara, Turkey.
falehan@hotmail.com

The aim was to determine the prevalence of coeliac disease (CD) in paediatric
patients with migraine. Serum tissue transglutaminase IgA (tTGA) antibodies and
IgA concentrations were measured in 73 patients with migraine (age range 6-17
years) and the control group (n = 147). Patients having positive tTGA antibodies 
underwent duodenal biopsy. Four patients (5.5%) from the study group and one
(0.6%) from the control group had positive tTGA antibody titres (P < 0.05). Three
patients with migraine had normal duodenal histology and were considered as
potential CD. One patient from the study group and one from the control group
declined to have biopsy. tTGA antibody is considered as a reliable indicator for 
the presence of CD. However, some patients with positive antibodies may have
normal biopsy initially and are classified as having potential CD. Our finding of
a higher prevalance of tTGA antibodies in paediatric migraine patients suggests
that an association between migraine and CD might exist.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 18624809 [PubMed - indexed for MEDLINE]

167: Cephalalgia. 2008 Sep;28(9):960-8. Epub 2008 Jul 8.

Quantitative EEG power and asymmetry increase 36 h before a migraine attack.

Bjørk M, Sand T.

Department of Neuroscience, Norwegian University of Science and Technology, St.
Olav University Hospital, Trondeim, Norway. marte.bjork@ntnu.no

The aim was to estimate ictal, pre- and postictal brain function changes in
migraine in a blinded paired quantitative EEG (QEEG) study. EEG recordings (n =
119) from 40 migraineurs were retrospectively classified as ictal, interictal,
preictal or postictal. delta, theta, alpha and beta power, and hemispheric
asymmetry in frontocentral, temporal and occipitoparietal regions were calculated
from artefact-free EEG. Power and power asymmetry were calculated for two
time-windows, 36 and 72 h before/after the attack, and compared with the
interictal values. Frontocentral delta power increased (P = 0.03), whereas
frontocentral theta and alpha power tended to increase (P < 0.09) within 36 h
before the next attack compared with the interictal period. Occipitoparietal
(alpha and theta) and temporal (alpha) power were more asymmetric before the
attack compared with the interictal baseline (P < 0.04). Ictal posterior alpha
power increased slightly (P = 0.01). Postictal power and power asymmetry were not
significantly different from interictal baseline. EEG activity seems to change
shortly before the attack. This suggests that migraineurs are most susceptible to
attack when anterior QEEG delta power and posterior alpha and theta asymmetry
values are high. Changed activity patterns in cholinergic brainstem or basal
forebrain nuclei and thalamo-cortical connections before the migraine attack are 
hypothesized.

Publication Types: 
    Comparative Study

PMID: 18624805 [PubMed - indexed for MEDLINE]

168: Cephalalgia. 2008 Oct;28(10):1023-30. Epub 2008 Jul 8.

The usefulness and applicability of a basic headache diary before first
consultation: results of a pilot study conducted in two centres.

Tassorelli C, Sances G, Allena M, Ghiotto N, Bendtsen L, Olesen J, Nappi G,
Jensen R.

University Centre for the Study of Adaptive Disorders and Headache (UCADH), IRCCS
'C. Mondino Institute of Neurology' Foundation, Pavia, Italy.
cristina.tassorelli@mondino.it

We tested the usefulness and applicability of a simplified headache diary in the 
diagnosis of migraine (M), tension-type headache (TTH) and medication overuse
headache (MOH). The diary was given to headache patients before their first
consultation at the headache centre. Seventy-six naive headache patients
completed the study. Their understanding of the diary proved highly satisfactory.
The patients' level of compliance was also good, with 71% returning the diary
completely filled in. The data entered in the diary were deemed complete for the 
diagnostic purpose in 93% of cases. The level of agreement between headache
information gathered through clinical interview and the headache diary was
satisfactory. When comparing the diary with the clinical interview, sensitivity
was 92% for M, 75% for TTH and MOH. Specificity was 58% for M and TTH, 87% for
MOH. Combined use of a diagnostic diary and clinical interview is recommended
from the first consultation for headache.

Publication Types: 
    Clinical Trial
    Multicenter Study
    Research Support, Non-U.S. Gov't

PMID: 18624804 [PubMed - indexed for MEDLINE]

169: Cephalalgia. 2008 Sep;28(9):988-90. Epub 2008 Jul 8.

Abnormalities of the vestibulo-collic reflex are similar in migraineurs with and 
without vertigo.

Roceanu A, Allena M, De Pasqua V, Bisdorff A, Schoenen J.

Headache Research Unit, Department of Neurology and Universitty of Liège, Liège, 
Belgium.

The amplitude and habituation of the click-evoked vestibulo-collic reflex (VCR)
was found reduced between attacks in migraineurs without complaints of ictal or
interictal vertigo or dizziness, compared with healthy subjects. As a next step
we recorded VCR in 17 migraine patients (eight with migraine without aura and
nine with migraine with aura) who presented ictal migrainous vertigo according to
the criteria defined by Neuhauser et al., using a method described previously.
Migraineurs with migrainous vertigo have similar VCR abnormalities as patients
without vertigo, i.e. a decreased global amplitude and absence of habituation.
Potentiation seemed more pronounced in migraineurs with vertigo (7.46 +/- 18.6), 
but the difference was not significant.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 18624802 [PubMed - indexed for MEDLINE]

170: Cephalalgia. 2008 Oct;28(10):1031-8. Epub 2008 Jul 9.

Difference in triptan effect in patients with migraine and early allodynia.

Lampl C, Huber G, Haas S, Rittberger E, Diener HC.

Department of Neurology and Pain Medicine, Konventhospital Barmherzige Brüder,
Linz, Austria. christian.lampl@bblinz.at

The aim of this study was to determine whether in migraine patients with and
without aura early treatment with various triptans leads to differences in pain
reduction after 1 h and in modulating cutaneous allodynia. Thirty-six patients
with early manifestation of a clinically recognizable allodynia of the face and
non-responders to earlier treatment with sumatriptan 100 mg were included.
Patients were randomized to six triptan treatment groups. Significant pain
reduction was seen only in the group receiving zolmitriptan nasal spray 5 mg with
a mean visual analogue scale (VAS) score of 3.8 (s.d. 1.2) at baseline and 2.4
(s.d. 1.3; P = 0.015) at 1 h after using the triptan and was thus a predictor of 
a VAS score 3 within 1 h. The study results indicate that migraine headache
intensity can be reduced within 1 h by using zolmitriptan 5 mg nasal spray in
spite of the presence of early cutaneous allodynia.

Publication Types: 
    Comparative Study
    Randomized Controlled Trial

PMID: 18624801 [PubMed - indexed for MEDLINE]

171: Cephalalgia. 2008 Oct;28(10):1048-52. Epub 2008 Jul 9.

Migraine and antiphospholipid antibodies: no association found in
migraine-discordant monozygotic twins.

Williams FM, Cherkas LF, Bertolaccini ML, Murru V, Surdulescu GL, Hughes GR,
Khamashta MA, Spector TD, MacGregor AJ.

Twin Research and Genetic Epidemiology Unit, King's College London, London, UK.

Migraine headache (with and without aura) is common in the general population and
is known to be influenced by genetic factors with heritability estimates between 
34-57%. Antiphospholipid syndrome (APS) is a hypercoagulable state characterized 
by clinical features including venous and arterial thromboses, pregnancy loss and
migraine, and by association with antiphospholipid antibodies (aPL). Numerous
small studies have investigated whether aPL are associated with migraine in the
general population--with contradictory results. In this study, the question was
addressed by studying the prevalence of aPL in members of monozygotic (MZ) twin
pairs differing in their migraine status. Such twins provide a unique natural
experiment, matched as they are for age, sex and genetic factors, and allow the
role of environmental factors, such as aPL, to be determined. Despite 95% power
to detect a difference of 0.59 IgG units per litre in anticardiolipin antibody
IgG titres, no difference in prevalence of aPL could be detected in
migraine-discordant MZ twins.

Publication Types: 
    Twin Study

PMID: 18624800 [PubMed - indexed for MEDLINE]

172: Cephalalgia. 2008 Oct;28(10):1053-60. Epub 2008 Jul 8.

Effects of pregnancy on slow cortical potentials in migraine patients and healthy
controls.

Darabaneanu S, Kropp P, Niederberger U, Strenge H, Gerber WD.

Institute of Medical Psychology and Medical Sociology, University Clinic of Kiel,
Kiel, Germany. darabaneanu@med-psych.uni-kiel.de

Increased negative amplitudes and lack of habituation of contingent negative
variation (CNV) in migraine are well established and are supposed to reflect an
altered cortical excitability level. Migraine attacks occur less during pregnancy
but often relapse after delivery. We investigated the effect of pregnancy on slow
cortical potentials and reaction time in migraine patients and healthy controls. 
Four groups were examined: 14 pregnant migraine patients, 12 non-pregnant
migraine patients, 15 pregnant healthy women and 16 non-pregnant healthy women
aged 19-38 years. Two recordings were performed in the pregnant subjects: in the 
36th week of gestation and 4 weeks after delivery. The non-pregnant subjects were
recorded at the same time interval of 8 weeks. Pregnant migraine patients showed 
significantly fewer migraine days during the third trimester of pregnancy and
returned to nearly the former level 4 weeks post delivery. Non-pregnant migraine 
patients demonstrated a significant reduction of migraine days at the second
measurement. There was no effect of pregnancy on CNV amplitudes, but there was an
effect of pregnancy on the habituation coefficient and reaction time of migraine 
patients. Faster habituation from a higher preactivation level was found. As an
explanation for the changed habituation level we favour the model of correlation 
between preactivation level and habituation level, the so-called law of initial
value. We found a correlation between preactivation level and habituation. Our
study confirms a specific effect of pregnancy on slow cortical potentials in
migraine patients.

Publication Types: 
    Comparative Study

PMID: 18624798 [PubMed - indexed for MEDLINE]

173: Proc Natl Acad Sci U S A. 2008 Jul 15;105(28):9799-804. Epub 2008 Jul 9.

Divergent sodium channel defects in familial hemiplegic migraine.

Kahlig KM, Rhodes TH, Pusch M, Freilinger T, Pereira-Monteiro JM, Ferrari MD, van
den Maagdenberg AM, Dichgans M, George AL Jr.

Departments of Medicine and Pharmacology, Vanderbilt University, Nashville, TN
37240, USA.

Familial hemiplegic migraine type 3 (FHM3) is a severe autosomal dominant
migraine disorder caused by mutations in the voltage-gated sodium channel
Na(V)1.1 encoded by SCN1A. We determined the functional consequences of three
mutations linked to FHM3 (L263V, Q1489K, and L1649Q) in an effort to identify
molecular defects that underlie this inherited migraine disorder. Only L263V and 
Q1489K generated quantifiable sodium currents when coexpressed in tsA201 cells
with the human beta(1) and beta(2) accessory subunits. The third mutant, L1649Q, 
failed to generate measurable whole-cell current because of markedly reduced cell
surface expression. Compared to WT-Na(V)1.1, Q1489K exhibited increased
persistent current but also enhanced entry into slow inactivation as well as
delayed recovery from fast and slow inactivation, thus resulting in a
predominantly loss-of-function phenotype further demonstrated by a greater loss
of channel availability during repetitive stimulation. In contrast, L263V
exhibited gain-of-function features, including delayed entry into, as well as
accelerated recovery from, fast inactivation; depolarizing shifts in the
steady-state voltage dependence of fast and slow inactivation; increased
persistent current; and delayed entry into slow inactivation. Notably, the two
mutations (Q1489K and L1649Q) that exhibited partial or complete loss of function
are linked to typical FHM, whereas the gain-of-function mutation L263V occurred
in a family having both FHM and a high incidence of generalized epilepsy. We
infer from these data that a complex spectrum of Na(V)1.1 defects can cause FHM3.
Our results also emphasize the complex relationship between migraine and epilepsy
and provide further evidence that both disorders may share common molecular
mechanisms.

Publication Types: 
    Research Support, N.I.H., Extramural

PMID: 18621678 [PubMed - indexed for MEDLINE]

174: Clin Neurol Neurosurg. 2008 Dec;110(10):979-84. Epub 2008 Jul 11.

A double-blind randomized controlled trial of topiramate and amitriptyline either
alone or in combination for the prevention of migraine.

Keskinbora K, Aydinli I.

Pain Clinic, Department of Anesthesiology, Cerrahpasa Faculty of Medicine,
Istanbul University, Istanbul 34303, Turkey. kader@istanbul.edu.tr

OBJECTIVE: Effectiveness of antidepressants and antiepileptic drugs has already
been demonstrated for migraine prophylaxis as monotherapy. In the present study, 
the efficacy and tolerability of amitriptyline and topiramate combination is
examined in the prevention of migraine attacks, in comparison to the monotherapy 
of each drug. METHODS: A total of 73 patients with migraine headache with or
without aura are included in this single-center, double-blind, randomized, and
controlled trial. Patients were assigned to receive topiramate alone,
amitriptyline alone or a combination of these drugs. Frequency, duration and
severity of migraine attacks, accompanied symptoms, depressive state, consumption
of medications, side effects and patient satisfaction were evaluated. RESULTS:
All treatments resulted in significant improvements in all efficacy measures
(p<0.001 for all comparisons). However, patients receiving combination treatment 
had higher patient satisfaction compared with other groups both at 8 and 12 weeks
(p=0.006 and p<0.001, respectively). Patients receiving amitriptyline and
combination treatments had better depression scores compared with the topiramate 
group. Combination group had fewer side effects with a less amount of
amitriptyline consumption. CONCLUSION: Amitriptyline and topiramate combination
may be beneficial for patients with migraine and comorbid depression,
particularly in terms of side effects and associated displeasure due to
monotherapy.

Publication Types: 
    Randomized Controlled Trial

PMID: 18620801 [PubMed - indexed for MEDLINE]

175: J Neurol Sci. 2008 Oct 15;273(1-2):127-9. Epub 2008 Jul 14.

Ataxia and migraine-like headache in a girl with a cerebellar developmental
venous anomaly.

Fenzi F, Rizzuto N.

Department of Neurological and Visual Sciences, Section of Neurology, University 
of Verona, Verona, Italy. flavio.fenzi@univr.it

Cerebral developmental venous anomalies (DVAs) are generally considered as
anatomical variants of the venous system without clinical importance. We report
the case of a 15-year-old girl with recurrent episodes of migraine-like headache 
who presented with subacute vertigo and ataxia associated with intense occipital 
pain. Magnetic resonance imaging (MRI) showed a DVA with signal modifications of 
the surrounding brain parenchyma in the left cerebellar hemisphere. The patient's
ataxia regressed completely within about 2 months. On a follow-up MRI 4 years
later the venous malformation and the parenchymal abnormalities were unchanged.
We attribute the patient's focal neurological dysfunction to regional changes in 
the brain parenchyma, possibly secondary to venous hypertension. Our report
provides evidence that also uncomplicated DVAs can become symptomatic and
supports the role of the venous congestion within the DVA territory in
pathogenesis of some brain parenchymal abnormalities associated with DVAs.

Publication Types: 
    Case Reports

PMID: 18620709 [PubMed - indexed for MEDLINE]

176: Neurosci Lett. 2008 Sep 12;442(2):81-5. Epub 2008 Jul 3.

Effects of topiramate and levetiracetam vs placebo on habituation of contingent
negative variation in migraine patients.

de Tommaso M, Guido M, Sardaro M, Serpino C, Vecchio E, De Stefano G, Di Claudio 
T, Specchio LM, Livrea P.

Department of Neurological and Psychiatric Sciences, University of Bari, Italy.
m.detommaso@neurol.uniba.it

Migraine is characterized by reduced habituation of multimodal evoked potentials,
which in turn reflects an abnormal pattern of cortical excitability. We assessed 
the effects of a 2-month treatment with topiramate or levetiracetam vs placebo on
contingent negative variation (CNV) habituation and amplitude in a cohort of
migraine without aura (MO) patients. Forty-five MO patients were selected from a 
university-based outpatient clinic and randomly assigned to 100mg topiramate or
1000mg levetiracetam or placebo in a double-blind design. Twenty-four control
subjects were also recruited. The initial CNV (iCNV) amplitude and habituation
were assessed by Cz/A1-A2 derivation recordings in the basal condition (T0) and
after 2 months of treatment (T1). Both topiramate and levetiracetam produced a
significant reduction in migraine frequency compared to placebo, they also
reversed the abnormal iCNV habituation pattern which characterized the MO
patients in the basal condition and which was not present in controls. For
migraine patients, the reduced migraine frequency and habituation index following
treatment were significantly correlated. A lack of habituation of evoked
responses is an interictal endophenotypic marker in migraine, the reversion of
which may improve disease outcome. These results suggest a role for
neurophysiological methods in the management of migraine.

Publication Types: 
    Randomized Controlled Trial

PMID: 18620023 [PubMed - indexed for MEDLINE]

177: J Occup Environ Med. 2008 Jul;50(7):736-45.

Work impact of migraine headaches.

Stewart WF, Wood GC, Razzaghi H, Reed ML, Lipton RB.

Geisinger Clinic, Center for Health Research, MC 44-00,100 N. Academy Ave,
Danville, PA 17822, USA. wfstewart@geisinger.edu

OBJECTIVE: To estimate work impact of headache among migraineurs. METHODS: Data
were from a U.S. nationwide mailed questionnaire of 193,477 participants in the
American Migraine Prevalence and Prevention study. Lost Productive Time (LPT) was
the sum of missed hours plus reduced productivity hour equivalents. The cause of 
LPT was self-reported. RESULTS: The mean LPT per week was 1.8 hours for headache 
and 2.8 for all health related causes; 76.5% of the headache-related LPT was
explained by reduced performance (ie, presenteeism). The 29% of migraine cases
with 11+ headaches-d/mo accounted for 49% of overall LPT; the 19% of those with
pain score of 9 to 10 on a 0 to 10 scale accounted for 33% of the overall LPT.
CONCLUSIONS: Individuals with frequent and severe headaches account for a
disproportionate share of the headache-related LPT.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 18617829 [PubMed - indexed for MEDLINE]

178: Clin J Sport Med. 2008 Jul;18(4):363-5.

Aerobic exercise with relaxation: influence on pain and psychological well-being 
in female migraine patients.

Dittrich SM, Günther V, Franz G, Burtscher M, Holzner B, Kopp M.

Center of Psychiatry and Psychotherapy, Department of General and Social
Psychiatry, Innsbruck Medical University, Innsbruck, Austria.

OBJECTIVE: The objective of this pilot study was to address the influence of an
aerobic exercise program combined with relaxation on pain and psychological
variables in migraine patients. DESIGN: Controlled, randomised design with half
of the group receiving an intervention (aerobic exercise group) in addition to
standard medical care received by all patients. SETTING/PATIENTS/OUTCOME
MEASUREMENT: Thirty female migraine outpatients completed a range of
psychological questionnaires measuring sensational and affective dimensions of
pain, body image, depression, and quality of life. INTERVENTION: The aerobic
exercise group (n = 15) participated in a 6-week, twice-weekly, indoor exercise
program (45 minutes of gymnastics with music and 15 minutes of progressive muscle
relaxation). RESULTS/CONCLUSION: The program led to a significant reduction of
self-rated migraine pain intensity. Although there was an improvement in
depression-related symptoms within the aerobic exercise group, no significant
differences in psychological variables between groups were found.

Publication Types: 
    Randomized Controlled Trial

PMID: 18614890 [PubMed - indexed for MEDLINE]

179: Br J Ophthalmol. 2008 Aug;92(8):1069-75. Epub 2008 Jul 9.

Retinal nerve fibre layer thickness measurements using optical coherence
tomography in migraine patients.

Martinez A, Proupim N, Sanchez M.

Instituto Gallego de Oftalmología, La Coruña, Spain. tontxu_1999@yahoo.com

AIM: To compare the retinal nerve fibre layer (RNFL) thickness in eyes of
migraine patients with age-matched healthy subjects using optical coherence
tomography. METHODS: The study was designed as an observational cross-sectional
study. 70 eyes of 70 patients (mean age 28.2 (SD 7.9) years) with migraine with
or without aura according to the criteria of the Headache International Society
and 53 eyes of 53 age-matched healthy controls (mean age 28.0 (8.1) years) were
included. Optical coherence tomography was performed with the Stratus OCT (model 
3000, software ver. 4.0.2; Carl Zeiss Meditec, Dublin, CA) after pupillary
dilation. The fast RNFL thickness (3.4) scan acquisition protocol was used.
RESULTS: In the migraine group, the mean Migraine Disability Assessment Score
(MIDAS), the mean number of attacks per 3 months, and the length of migraine
history were 34.3 (15.2), 17.0 (6.7) and 14.8 (5.6), respectively. The RNFL
average thickness in the migraine was within the normal range, but the temporal
quadrant RNFL thickness in the migraine patients was significantly lower than
that of the control group, 62.2 (10.8) mum vs 70.8 (12.4) mum, respectively (p = 
0.0001). However, there was no difference between migraineurs and controls in the
superior, inferior, and nasal quadrants, p = 0.8810, p = 0.1531, and p = 0.8300, 
respectively. Within the migraine group, the average RNFL thickness was
significantly correlated with the MIDAS disability score (r = -0.93, p<0.0001)
and the frequency of migraine attacks (r = -0.86, p<0.0001). There were no
statistically significant differences, between study groups, in disc area or
cup/disc area ratio, p = 0.8102 and p = 0.7236, respectively. Considering the
clinical examination, RNFL, and optic disc parameters, no one in the migraine
group was qualified as having glaucomatous damage. CONCLUSION: The RNFL in the
temporal quadrant was found to be thinner in migraine patients. In addition, we
found a strong correlation between migraine severity and the RNFL average
thickness parameters.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 18614573 [PubMed - indexed for MEDLINE]

180: Scand J Gastroenterol. 2008;43(9):1076-81.

Patients with cyclic vomiting pattern and diabetic gastropathy have more
migraines, abnormal electrogastrograms, and gastric emptying.

Christensen CJ, Johnson WD, Abell TL.

Gastrointestinal Division, University of Mississippi Medical Center, Jackson,
Mississippi, USA.

OBJECTIVE: Some patients with diabetic gastroparesis exhibit cyclical symptoms.
The purpose of this work was to study the subset of patients with cyclic vomiting
characteristics, described as a cyclic vomiting pattern, in a population of
patients with symptoms of diabetic gastroparesis. MATERIAL AND METHODS:
Sixty-seven patients with symptoms of diabetic gastroparesis were investigated.
The patients were divided into two groups based on the presence or lack of cyclic
symptoms, and stratified by demographics, medical history, hemoglobin A1C, total 
symptom score (TSS), standardized gastric emptying test (GET), and
electrogastrography (EGG). RESULTS: Of these 67 patients, 38 (56%) had cyclic
symptoms. The two groups were similar in age, gender, illness duration, insulin
use, hemoglobin A1C values, and TSS. There were noteworthy differences regarding 
migraine headache (47.4% versus 20.7%, p=0.02), gastric emptying study (GES) at 1
h (84.1% versus 59.9%, p=0.02), EGG frequency (4.9 versus 3.6 cpm, p=0.05), and
gastric emptying area under the curve (p=0.06). CONCLUSIONS: A sizeable
percentage of patients have cyclic symptom patterns and have a higher incidence
of migraine headaches, a greater delay in gastric emptying, and more abnormal EGG
frequencies than other patients with symptoms of diabetic gastroparesis.

Publication Types: 
    Comparative Study

PMID: 18609160 [PubMed - indexed for MEDLINE]

181: Neurosci Behav Physiol. 2008 Jun;38(5):501-5.

The role of serotonin in the pathogenesis and clinical presentations of migraine 
attacks.

Izzati-Zade KF.

Department of Neurology, Therapeutic Faculty, Perm State Medical Academy of the
Federal Agency for Health and Social Development, Perm, Russia.

The Fontana-Masson method was used in 63 migraine patients to stain peripheral
blood thrombocytes and measure the numbers of serotonin granules within them
during the interictal period and, in 33 patients, during and 24, 48, and 72 h
after migraine attacks. Enzyme-linked immunosorbent assay (ELISA) was used in 19 
patients during attacks to study dissolved serotonin concentrations in serum.
During the interictal period, high contents of serotonin granules per 100 blood
thrombocytes were found (469.3 +/- 22.4), which was not significantly different
from the level in healthy subjects (447.9 +/- 19.6). At the peak of attacks,
serotonin contents decreased to 47.7 +/- 7.4, while the dissolved serotonin
concentration, conversely, increased to 345.5 +/- 39.1 ng/ml (compared with serum
serotonin levels of 184.2 +/- 12.3 ng/ml in healthy subjects). During the first
and subsequent time points after migraine attacks, thrombocyte serotonin levels
returned to baseline. These data provide evidence of impairment of serotonin
stored in thrombocytes during migraine attacks and its release into the plasma,
which may provide a laboratory method for monitoring the development of migraine 
attacks.

PMID: 18607750 [PubMed - indexed for MEDLINE]

182: J Headache Pain. 2008 Aug;9(4):207-13. Epub 2008 Jul 8.

Meeting patient expectations in migraine treatment: what are the key endpoints?

Antonaci F, Sances G, Guaschino E, De Cillis I, Bono G, Nappi G.

University Centre for Adaptive Disorders and Headache (UCADH), Section of Varese,
Pavia, Italy. fabio.antonaci@unipv.it

Clinical outcomes of migraine treatment are generally based on two major
endpoints: acute pain resolution and effects on quality of life (QOL). Resolution
of acute pain can be evaluated in a number of ways, each increasingly challenging
to achieve; pain relief, pain freedom at 2 h, sustained pain-freedom, and SPF
plus no adverse events (SNAE, the most challenging). QOL questionnaires help
assess the burden of migraine and identify optimal treatments. Pain resolution
and improved QOL form the basis of the ultimate target-meeting patient
expectations, to achieve patient satisfaction. To achieve this, it is crucial to 
choose appropriate endpoints that reflect realistic treatment goals for
individual patients. Moreover, SNAE can help discriminate between triptans, with 
almotriptan having the highest SNAE score. Kaplan-Meier plots are also relevant
when evaluating migraine treatments. The use of symptomatic medication may lead
to the paradoxical development of medication-overuse headache. In general
practice, patients should use simple tools for pain measurement (e.g. headache
diary) and a QOL questionnaire. A composite endpoint of pain resolution and QOL
restoration would constitute a step forward in migraine management.

Publication Types: 
    Review

PMID: 18607535 [PubMed - indexed for MEDLINE]

183: Neurology. 2008 Jul 8;71(2):114-21.

Multimechanistic (sumatriptan-naproxen) early intervention for the acute
treatment of migraine.

Silberstein SD, Mannix LK, Goldstein J, Couch JR, Byrd SC, Ames MH, McDonald SA, 
Lener SE.

Jefferson Headache Center, 111 South 11th Street, Suite 8130, Philadelphia, PA
19107, USA. stephen.silberstein@jefferson.edu

BACKGROUND: Research suggests treating a migraine at the first sign of pain
increases the likelihood of the best clinical outcome. OBJECTIVE: To investigate 
the efficacy and tolerability of a fixed-dose, single-tablet formulation of
sumatriptan 85 mg, formulated with RT Technology, and naproxen sodium 500 mg
(sumatriptan/naproxen) as early intervention acute therapy for migraine. METHODS:
Patients (aged 18 to 65 years) with International Headache Society-defined
migraine with or without aura were enrolled in one of two identically designed,
randomized, double-blind, parallel group, placebo-controlled studies. Patients
treated a single migraine within 1 hour of onset of migraine head pain and while 
the pain was mild with either sumatriptan/naproxen or placebo. The primary
efficacy measure was the percentage of patients who became pain-free 2 hours
postdose. RESULTS: Intent-to-treat analyses consisted of 576 and 535 migraineurs.
At 2 hours, 52% and 51% of sumatriptan/naproxen-treated patients were pain free, 
as compared to 17% and 15% of placebo-treated patients (p < 0.001). Significant
pain-free responses in favor of sumatriptan/naproxen were demonstrated as early
as 30 minutes, maintained at 1 hour, and sustained from 2 to 24 hours. At 2 and 4
hours, sumatriptan/naproxen provided significantly lower rates of traditional
migraine-associated symptoms (nausea, photophobia, and phonophobia) and
nontraditional migraine-associated symptoms (neck pain/discomfort and sinus
pain/pressure). The most commonly reported adverse events were nausea (< or =4%) 
and dizziness (< or =2%). CONCLUSION: The fixed-dose single-tablet formulation of
sumatriptan/naproxen was effective and well tolerated in an early intervention
paradigm for the acute treatment of migraine, including traditional and
nontraditional symptoms.

Publication Types: 
    Randomized Controlled Trial

PMID: 18606965 [PubMed - indexed for MEDLINE]

184: Neurology. 2008 Jul 8;71(2):101-7.

Right-to-left shunt does not increase white matter lesion load in migraine with
aura patients.

Adami A, Rossato G, Cerini R, Thijs VN, Pozzi-Mucelli R, Anzola GP, Del Sette M, 
Finocchi C, Meneghetti G, Zanferrari C; SAM Study Group.

Collaborators: Pascazio L, Anzola GP, Morandi E, Gamba M, Del Sette M, Finocchi
C, Dinia L, Sivori G, Caputi L, Parati E, Carriero MR, Adami A, Rossato G,
Marchioretto F, Meneghetti G, Santarello G, Zanferrari C, Manzoni GC, Torelli P, 
Devetak A, Tanzi A, Bosone D, Diomedi M, Leone G, Vernieri F, Altamura C, Tiburzi
F, Mazzucco S, Inchingolo E.

Stroke Center, Neurology Department, Ospedale Sacro Cuore, via Sempreboni 6,
37024 Negrar-Verona, Italy. alessandro.adami@sacrocuore.it

BACKGROUND: White matter lesions (WMLs) are commonly found on brain MRI of
migraine patients. Migraine with aura (MA+) is associated with an increased
frequency of right-to-left shunt (RLS) mostly due to patent foramen ovale. The
relationship between WML load and RLS in MA+ is currently unknown. METHODS: MA+
patients were consecutively enrolled as part of the Shunt Associated Migraine
(SAM) study. Patients underwent a standardized headache and vascular risk factors
questionnaire, contrast-enhanced transcranial Doppler, blood coagulation tests,
and brain MRI. RLS was categorized into four grades: no shunt, <10 microbubbles
(mb), >10 mb single spikes pattern, and >10 mb shower/curtain pattern. Standard
and fluid-attenuated inversion recovery T2-weighted MRI sequences were inspected 
for WMLs by three independent raters blinded to RLS grade. WML load was scored in
the periventricular areas (PV-WMLs) with the Fazekas scale and in the deep white 
matter (D-WMLs) with the Scheltens scale. Interobserver agreement was good to
excellent (kappa = 0.64 to 0.96, p < 0.0001). WML load was then correlated
between patients with and without RLS. RESULTS: One hundred eighty-five patients 
(77% women) were included. PV-WML load was similar between patients with and
without RLS. D-WML load decreased in patients with RLS (p = 0.045). On logistic
regression analysis, only age was associated with WMLs (p < 0.001). CONCLUSIONS: 
The presence of right-to-left shunt does not increase white matter lesion load in
patients who have migraine with aura.

Publication Types: 
    Multicenter Study

PMID: 18606963 [PubMed - indexed for MEDLINE]

185: Clin Neurol Neurosurg. 2008 Sep;110(8):818-22. Epub 2008 Jul 7.

Chronic migraine associated with the Chiari type 1 malformation.

Kaplan Y, Oksuz E.

Inonu University, Turgut Ozal Medical Center, Department of Neurology, Malatya,
Turkey. yukselkablan@yahoo.com

OBJECTIVE: Our objective was to assess the frequency and clinical characteristics
of migraine in the patients with CM-1. METHODS: We analyzed migraine in 73
patients with CM-1. Migraine was classified according to the new International
Headache Society criteria. We did not include patients who had intracranial,
parenchymal, or cervical lesions other than CM-1 on brain and cervical magnetic
resonance imaging. RESULTS: Of the 73 patients diagnosed as having CM-1, 11
(15.06%) had migraines; of them, 8 (10.95%) had chronic migraines, 2 (2.73%) had 
migraines with auras, and 1 (1.36%) had migraines without auras. The patients who
had both migraines and CM-1 (group 1) were compared regarding clinical
characteristics and demographic features to the control group having chronic
migraines. The control group comprised subjects free of CM-1. Onset age of pain
was earlier and the frequency of headache days per month, baseline pain
intensity, exacerbation of pain intensity, nausea, vomiting, and pain aggravated 
by physical activity were significantly higher in group 1. CONCLUSIONS: Although 
we found the frequency of migraine to be similar to that in population-based
studies, we detected a threefold increased frequency of chronic migraine in this 
special population. We believe that CM-1 may be a factor associated with chronic 
migraine.

PMID: 18603356 [PubMed - indexed for MEDLINE]

186: J Neurol Sci. 2008 Sep 15;272(1-2):194-5. Epub 2008 Jul 7.

Topiramate-associated worsening symptoms in a patient with familial hemiplegic
migraine.

Striano P, Zara F, Santorelli FM, Striano S.

Department of Neurological Sciences, Federico II University, Napoli, Italy.
pstriano@email.it

Topiramate has been shown to be highly effective for preventive treatment of
migraine and its use has been significantly increased in the last few years.
However, around 10% of migraineurs develop a worsening of their symptoms while on
topiramate. We report a 33-year-old woman with familial hemiplegic migraine (FHM)
who experienced worsening of her symptoms following repeated topiramate intake.
Withdrawal of the drug rapidly constantly induced resolution of the symptoms.
This is the first report of topiramate-associated worsening symptoms in FHM. It
is important to be aware of this phenomenon, as topiramate is worldwide-used drug
for migraine treatment.

Publication Types: 
    Case Reports

PMID: 18603263 [PubMed - indexed for MEDLINE]

187: Chaos. 2008 Jun;18(2):026110.

Failure of feedback as a putative common mechanism of spreading depolarizations
in migraine and stroke.

Dahlem MA, Schneider FM, Schöll E.

Institut für Theoretische Physik, Technische Universität Berlin,
Hardenbergstrasse 36, D-10623 Berlin, Germany.

The stability of cortical function depends critically on proper regulation. Under
conditions of migraine and stroke a breakdown of transmembrane chemical gradients
can spread through cortical tissue. A concomitant component of this emergent
spatio-temporal pattern is a depolarization of cells detected as slow voltage
variations. The propagation velocity of approximately 3 mm/min indicates a
contribution of diffusion. We propose a mechanism for spreading depolarizations
(SD) that rests upon a nonlocal or noninstantaneous feedback in a
reaction-diffusion system. Depending upon the characteristic space and time
scales of the feedback, the propagation of cortical SD can be suppressed by
shifting the bifurcation line, which separates the parameter regime of pulse
propagation from the regime where a local disturbance dies out. The optimization 
of this feedback is elaborated for different control schemes and ranges of
control parameters.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 18601512 [PubMed - indexed for MEDLINE]

188: J Headache Pain. 2008 Aug;9(4):237-48. Epub 2008 Jul 4.

Comorbid neuropathologies in migraine: an update on cerebrovascular and
cardiovascular aspects.

Sacco S, Cerone D, Carolei A.

Department of Neurology, University of L'Aquila, Piazzale Salvatore Tommasi,
L'Aquila, Italy.

Several conditions are comorbid with migraine; our review is focused on the
relation between migraine, and cerebrovascular and cardiovascular diseases.
Despite many studies showed an association between migraine and patent foramen
ovale, it is still not known whether its presence might be causal for the
migraine pathogenesis and currently its closure cannot be recommended for
migraine prevention. On the contrary, conflicting epidemiological data link
migraine to arterial hypertension and the use of antihypertensive agents acting
on the renin-angiotensin system sounds promising in migraine prevention. A
complex bidirectional relation exists between migraine and stroke, and new
evidences show a clear association between migraine and coronary heart disease.
In both conditions, migraine represents a defined risk factor although the
magnitude of the risk varies across the different studies. However, since the
risk is low in the general population, it is not possible to identify which
migraineurs will develop a cardiovascular or a cerebrovascular event making
difficult to apply preventive measures.

Publication Types: 
    Review

PMID: 18600300 [PubMed - indexed for MEDLINE]

189: Clin Neurol Neurosurg. 2008 Sep;110(8):850-1. Epub 2008 Jul 3.

Seizure after use of almotriptan.

Mazzoleni R, Kreisler A, Lucas C, Kwiatkowski A, Gautier S, Destee A, Defebvre L.

Department of Neurology A, Hôpital Roger Salengro, Rue Emile Laine, 59037 Lille, 
France.

We report the case of a young woman who suffered from a seizure after use of
almotriptan. There was a recurrence with ergotamine. We discuss possible link
with susceptibility genes.

Publication Types: 
    Case Reports

PMID: 18599194 [PubMed - indexed for MEDLINE]

190: J Manag Care Pharm. 2008 Jun;14(5):442-50.

Comment in:
    J Manag Care Pharm. 2008 Jun;14(5):465-7.

Humanistic, utilization, and cost outcomes associated with the use of botulinum
toxin for treatment of refractory migraine headaches in a managed care
organization.

Mitchell MP, Schaecher K, Cannon HE, Speckman M.

Pharmacy Services, SelectHealth, 4646 West Lake Park, Suite N3, Salt Lake City,
UT 84107, USA. Matt.Mitchell@selecthealth.org

BACKGROUND: Few patients with migraine syndrome receive treatment with preventive
medication regimens, and some of these patients fail to gain adequate migraine
relief. Botulinum toxin has been suggested to be effective in the treatment of
migraine for a select population. An integrated health system created a medical
policy and a supporting preauthorization form that permits coverage of botulinum 
toxin for the off-label treatment of migraine for patients who (1) fail at least 
3 drug classes for acute treatment, (2) fail at least 4 different preventive
medication classes, and (3) receive consultation from a neurologist. OBJECTIVES: 
To (1) evaluate the impact of botulinum toxin therapy on quality-of-life (QOL)
measures evaluated by direct member survey results, and (2) assess the use and
cost of migraine-related medications and overall medical and pharmacy services
pre- and post-botulinum toxin therapy. METHODS: The study was a retrospective
analysis of administrative claims data from a 500,000-member integrated health
system for the time period January 1, 2003, to October 31, 2007. Administrative
claims data were used to identify members with a billing code (International
Classification of Diseases, Ninth Revision, Clinical Modification [ICD-9-CM]) for
migraine (346.xx), tension headache (307.81), or headache (784.0) diagnosed by a 
neurologist. Administrative claims data for these patients were then queried for 
the use of botulinum toxin for dates of service from January 1, 2003, through
October 31, 2006. A survey was sent to the identified patients (N=54) to assess 6
QOL measures associated with the use of botulinum toxin. Self-reported
symptomatic improvement was assessed using a 5-point Likert scale for 6 questions
regarding headache severity, headache frequency, use of rescue medications,
productivity/absenteeism, recreational activities, and life enjoyment. For the
subset of patients (n = 32) who maintained health plan eligibility from 18 months
before through 18 months after the first botulinum toxin therapy claim (index
date), medical and pharmacy claims data were used to assess the utilization and
cost of specific medications and overall pharmacy and medical costs for the
18-month pre-index and post-index periods. Cost was defined as allowed charge,
which is the sum of plan cost and member cost. RESULTS: Of 54 surveys sent to all
patients identified as having used botulinum toxin for the treatment of migraine 
from January 1, 2003, to October 31, 2006, 34 surveys were returned (63%). Almost
3 of 4 respondents (73%) reported moderate or better improvement in overall
migraine or headache QOL measures, and 27% reported little or no improvement. For
the 32 patients with continuous eligibility for the total observation period of
36 months, the average migraine-related pharmacy utilization, excluding botulinum
toxin, increased by 50.5%, from 1.84 claims per patient per month (PPPM) in the
18-month pre-index period to 2.77 claims PPPM in the 18-month post-index period
(P = 0.011) and by 59.5% by mean days supply (42.58 days to 67.93, P=0.008).
Total migraine-related pharmacy cost increased by 80.9%, from $142.08 PPPM to
$256.97 PPPM (P=0.013). Acute-treatment migraine-related pharmacy utilization
increased from 1.23 claims PPPM to 1.92 claims PPPM (P=0.004). There was no
significant change in either the number of claims for migraine prophylaxis
medications (0.61 PPPM to 0.85 PPPM, P=0.121) or the use of hospital emergency
room services related to migraine or headache (0.07 PPPM vs. 0.10 PPPM, P=0.449).
The mean migraine-related and nonmigraine-related (i.e., all-cause) combined
medical/hospital and pharmacy expense, including botulinum toxin, increased by
111.3%, from $651.13 PPPM in the pre-index period to $1,376.05 PPPM in the
post-index period (P<0.001). CONCLUSION: The majority of patients who received
botulinum toxin for refractory migraine reported improvement in disease-specific 
symptoms and overall QOL, but total medical and pharmacy costs were higher in the
period after treatment, and there was no reduction in the use of other
migraine-related medications.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 18597573 [PubMed - indexed for MEDLINE]

191: J Headache Pain. 2008 Aug;9(4):221-4. Epub 2008 Jul 2.

Low urinary 6-sulphatoxymelatonin concentrations in acute migraine.

Masruha MR, de Souza Vieira DS, Minett TS, Cipolla-Neto J, Zukerman E, Vilanova
LC, Peres MF.

Department of Neurology and Neurosurgery, Federal University of São Paulo, São
Paulo, Brazil.

Substantial evidence points to melatonin as playing a role in the regulation of
circadian rhythms, sleep, and headache disorders. The objective of the study was 
to assess 6-sulphatoxymelatonin (aMT6s) levels in a large consecutive series of
patients with migraine, comparing with controls. A total of 220 subjects were
evaluated-146 had migraine and 74 were control subjects. Urinary samples were
collected into the same plastic container since 8:00 p.m. to 8:00 a.m. of the
next day (12-h period) and aMT6s was measured with quantitative ELISA technique. 
Among patients with migraine, 53% presented pain on the day of the urine samples 
collection. Their urinary aMT6s concentration was significantly lower than in the
urine of patients without pain [14.0 +/- 7.3 vs. 49.4 +/- 19.0; t(143) = -15.1;
95% CI = -40.0 to -30.8; P < 0.001]. There was no significant difference in the
aMT6s concentration of patients with migraine without pain on the day of their
urine samples collection and controls [49.4 +/- 19.0 vs. 42.5 +/- 27.9; t(140) = 
1.7; 95% CI = -1.2 to 14.8; P = 0.094]. To our knowledge, this is the first study
to demonstrate reduction in melatonin levels during attacks in episodic and
chronic migraine.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 18594760 [PubMed - indexed for MEDLINE]

192: Plast Reconstr Surg. 2008 Jul;122(1):115-22; discussion 123-4.

Confirmation of surgical decompression to relieve migraine headaches.

Poggi JT, Grizzell BE, Helmer SD.

Department of Surgery, The University of Kansas School of Medicine-Wichita,
Wichita, Kan, USA. poggiplasticsurgery@yahoo.com

BACKGROUND: Surgical decompression of various trigger sites has been shown by two
authors to relieve migraine headaches. The purpose of this study was to evaluate 
the effectiveness of surgical decompression of multiple migraine trigger sites in
a clinical practice setting, and to compare the results to those previously
published. METHODS: A retrospective, descriptive analysis was performed on 18
consecutive patients who had undergone various combinations of surgical
decompression of the supraorbital, supratrochlear, and greater occipital nerves
and zygomaticotemporal neurectomy performed by a single surgeon. All patients had
been diagnosed with migraine headaches according to neurologic evaluation and had
undergone identification of trigger sites by botulinum toxin type A injections.
RESULTS: The number of migraines per month and the pain intensity of migraine
headaches decreased significantly. Three patients (17 percent) had complete
relief of their migraines, and 50 percent of patients (nine of 18) had at least a
75 percent reduction in the frequency, duration, or intensity of migraines.
Thirty-nine percent of patients have discontinued all migraine medications. Mean 
follow-up was 16 months (range, 6 to 41 months) after surgery. One hundred
percent of participants stated they would repeat the surgical procedure.
CONCLUSIONS: This study confirms prior published results and supports the theory 
that peripheral nerve compression triggers a migraine cascade. The authors have
verified a reduction in duration, intensity, and frequency of migraine headaches 
by surgical decompression of the supraorbital, supratrochlear,
zygomaticotemporal, and greater occipital nerves. A significant amount of patient
screening is required for proper patient selection and trigger site
identification for surgical success.

PMID: 18594393 [PubMed - indexed for MEDLINE]

193: Optom Vis Sci. 2008 Jul;85(7):566-73.

Topographical analysis of the optic nerve in migraine patients.

Moehnke TD, Sowka J, Shallo-Hoffmann J, Hardigan P, Woods AD.

College of Optometry, Nova Southeastern University, Fort Lauderdale, FL, USA.
moehnke@nova.edu

PURPOSE: Vascular dysfunction appears related to the development of migraines and
has been associated with pressure-independent glaucoma. The purpose of this study
is to investigate possible topographical differences in the optic nerve between
migraine sufferers and normal age-matched control subjects. The identification of
optic disc topographical differences between migraine and non-migraine sufferers 
may help clinicians determine if the presence of migraine influences the
development and progression of glaucoma. METHODS: Sixty consecutively seen
patient-volunteers (30 subjects in migraine group: mean age 37.7 years, range
from 19 to 66 years, 28 females and 2 males; 30 subjects in the control group:
mean age 37.6 years, range from 19 to 61 years, 29 females and 1 male) were
categorized as either migraine patients or control group subjects. All migraine
subjects had been medically diagnosed with a migraine syndrome and were being
treated with prophylactic medication. Optic nerve head topographical analysis was
performed using a confocal scanning laser ophthalmoscope. The data was evaluated 
using generalized estimating equations, a priori and post hoc power analysis.
RESULTS: No significant differences were found in any of the optic nerve
parameters examined between the two groups. CONCLUSIONS: This study indicates
that the optic nerve parameters as measured by the Heidelberg retinal tomograph
II do not differ between migraine sufferers and age-matched control subjects.

PMID: 18594350 [PubMed - indexed for MEDLINE]

194: J Stroke Cerebrovasc Dis. 2008 Jul-Aug;17(4):246-7.

The syndrome of headache with neurologic deficits and cerebrospinal fluid
lymphocytosis mimicking acute ischemic stroke.

Ariës MJ, van Oostrom JC, de Keyser J.

Department of Neurology, University Medical Centre Groningen, University of
Groningen, The Netherlands. m.j.h.aries@neuro.umcg.nl

Headache with neurologic deficits and cerebrospinal fluid lymphocytosis is a
benign condition with a transient ischemic attack-like presentation. We present a
case of a 22-year-old man with episodes of right-sided weakness, global
dysphasia, and right-sided homonymous hemianopsia associated with frequent
vomiting. Systemic thrombolytic therapy was considered. A subsequent magnetic
resonance image with diffusion-weighted images revealed normal findings. A
diagnosis of headache with neurologic deficits and cerebrospinal fluid
lymphocytosis was made based mainly on clinical symptoms and cerebrospinal fluid 
analysis. With the current pressure on "door-to-needle" time for thrombolysis, it
is important to keep an open eye to stroke mimics and exclude them if possible.
We, therefore, strongly advise considering noninvasive magnetic resonance
diffusion-weighted imaging in patients with unusual presentations (e.g., the
vomiting in our patient) before thrombolysis.

Publication Types: 
    Case Reports

PMID: 18589348 [PubMed - indexed for MEDLINE]

195: J Formos Med Assoc. 2008 Jun;107(6):485-94.

Diagnosis and development of screening items for migraine in neurological
practice in Taiwan.

Wang SJ, Fuh JL, Huang SY, Yang SS, Wu ZA, Hsu CH, Wang CH, Yu HY, Wang PJ;
Taiwan MAP Study Group.

Collaborators: Fu CH, Chen CH, Chen JJ, Fang SC, Wang GQ, Wang JH, Chen JT,
Chiang TR, Huang CC, Lan MY, Lai SL, Lee LH, Lin HS, Lin KL, Lin TK, Liou SR, Lu 
YC, Ro LS, Tsai YT, Wu YL, Chen TC, Chen YY, Liou CS, Sun MC, Yeh CH, Hsieh LP,
Lai DC, Lin HJ, Lin KC, Ke DS, Lin KH, Jhou SB, Guo CJ, Chou MC, Guo YC, Hsu HY, 
Lu SR, Wang YJ, Pan YC, Liang CY, Fong CS, Hung TY, Tan JG, Tang S, Chen JC, Yè
BS, Chen SM, Wei CY, Lin YF, Chen CF, Lai CL, Liou LM, Chen JJ, Li JY, Lin YT, Lo
YK, Ho YT, Shih CS, Lin KW, Wang PJ, Cheng SH, Chiu NC, Dai D, Ho CS, Hsueh IH,
Lin JH, Fan BJ, Yang JC, Yang SS, Chang SF, Hwang SR, Chen WH, Tseng KY, Chen CS,
Ye SB, Wang SC, Su SH, Lee YC, Hu CJ, Huang CS, Su YC, Chen WT, Yuan RY, Chen C, 
Chen WK, Chern CM, Fuh JL, Hsu LC, Tsai CP, Wang KC, Wang PS, Wang SJ, Hu HY, Wu 
ZA, Shyu HY, Liu YC, Lin SL, Tseng YF, Hsu CH, Lee JT, Peng JS, Lee SY.

Neurological Institute, Taipei Veterans General Hospital and National Yang-Ming
University School of Medicine, 201 Section 2 Shih-Pai Road, Taipei, Taiwan.
sjwang@vghtpe.gov.tw

BACKGROUND/PURPOSE: The objectives of this study were to: (1) survey migraine
diagnoses among neurological outpatients in Taiwan; (2) compare neurologists'
migraine diagnoses with the International Classification of Headache Disorders
2nd Edition (ICHD-2) criteria; and (3) evaluate the diagnostic ability of
screening items on a patient migraine questionnaire. METHODS: This prospective
study surveyed patients who consulted neurologists for the first time with a
chief complaint of headache, excluding those experiencing headaches for > or = 15
days/month. Each neurologist interviewed a maximum of 10 patients. Patients were 
asked to complete a self-administered questionnaire and their physicians
completed another questionnaire. The physicians were asked if patients could be
diagnosed with migraine. In addition, a diagnosis of ICHD-2 migraine was made by 
the physician's questionnaire through a computer-generated algorithm. In this
study, migraine without aura (code 1.1) or migraine with aura (code 1.2) were
designated as "strict migraine", and the combination of strict migraine and
ICHD-2 probable migraine (code 1.6) as "any migraine". RESULTS: Among 755
patients who were eligible for analysis, 537 (71%) were diagnosed as having "any 
migraine", 363 (48%) with "strict migraine", and 451 (60%) with
physician-diagnosed migraine. Among the 537 patients diagnosed as having "any
migraine", 308 patients (57%) had not been diagnosed by any physician before. A
moderate agreement (kappa statistic around 0.5) was found between the physicians'
diagnoses and ICHD-2 "strict migraine" or "any migraine". In patients with ICHD-2
probable migraine (n = 174), only 52% were diagnosed with migraine by our
physicians. Nausea was the best single item for predicting migraine diagnosis,
while any combination of two items among nausea/vomiting, moderate or severe pain
and photophobia, provided the optimum screening tool. CONCLUSION: Migraine was
the most common headache diagnosis in the neurologists' clinics. Probable
migraine was not completely adopted as a migraine spectrum among neurologists. In
contrast to ID Migraine(TM), moderate or severe headache intensity replaced
headache-related disability as one screening item for migraine in Taiwan.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 18583220 [PubMed - indexed for MEDLINE]

196: Ann N Y Acad Sci. 2008;1135:219-29.

Menstrual cycle dysfunction associated with neurologic and psychiatric disorders:
their treatment in adolescents.

Joffe H, Hayes FJ.

Perinatal and Reproductive Psychiatry, Department of Psychiatry, Harvard Medical 
School, Boston, Massachusetts, USA. hjoffe@partners.org

Epilepsy, bipolar disorder, and migraines are common disorders that are often
associated with disturbances in menstrual function in adolescent girls. Women
with untreated epilepsy are more likely to have irregular menstrual cycles than
are nonepileptic controls, indicating that the disease itself plays a role in the
etiology of these reproductive abnormalities. In addition, many girls with these 
disorders require chronic maintenance treatment with agents that may perturb the 
hypothalamic-pituitary-ovarian axis. Valproate is a highly effective
antiepileptic drug used widely to treat epilepsy, bipolar disorder, and
migraines. Valproate induces features of the polycystic ovary syndrome (PCOS) in 
approximately 7% of women. Girls with epilepsy, and possibly bipolar disorder,
appear particularly susceptible to developing PCOS features on valproate, perhaps
on account of the relative immaturity of their hypothalamic-pituitary-ovarian
axes. Antipsychotics are highly effective drugs used widely to treat adolescents 
with bipolar disorder, psychotic disorders, and behavioral disturbances. Some,
but not all of the antipsychotic, induce hyperprolactinemia, which may result in 
oligo- or amenorrhea. Prolonged amenorrhea in association with hyperprolactinemia
incurs significant risks for bone health in adolescent girls. Because of the
potential reproductive health risks associated with use of specific antiepileptic
drugs and selective antipsychotics, these agents are vital treatments for
adolescents with severe illnesses. Use of these agents should be considered and
weighed against the risk of using alternative agents, which have their own side
effects, or not treating these serious neurologic and psychiatric disorders.

Publication Types: 
    Review

PMID: 18574228 [PubMed - indexed for MEDLINE]

197: Headache. 2008 Jun;48(6):921-30.

Efficacy and tolerability of coadministration of rizatriptan and acetaminophen vs
rizatriptan or acetaminophen alone for acute migraine treatment.

Freitag F, Diamond M, Diamond S, Janssen I, Rodgers A, Skobieranda F.

Diamond Headache Clinic, Chicago, IL, USA.

OBJECTIVE: To evaluate the efficacy and tolerability of coadministration of
rizatriptan and acetaminophen in the acute treatment of migraine. BACKGROUND:
Rizatriptan is a selective 5-HT1B/1D agonist approved for the acute treatment of 
migraine. Acetaminophen has been studied for acute migraine treatment. In
consideration of the prominent central and peripheral mechanisms in migraine, the
use of "multi-mechanism therapy" is gaining momentum in the treatment of acute
migraine attacks. STUDY DESIGN: This was a randomized, double-blind,
placebo-controlled trial conducted at 10 centers. Eligible patients with migraine
according to International Headache Society criteria treated a single migraine
attack of moderate or severe intensity within 4 h from pain onset. Patients were 
randomized into 1 of 4 groups (rizatriptan 10 mg + acetaminophen 1000 mg [RA],
rizatriptan alone [R], acetaminophen alone [A], and placebo [P]). There were 3
co-primary hypotheses tested sequentially for 2-h pain relief: (1) RA would be
superior to P; (2) if the first was fulfilled, RA would be superior to A; and (3)
if the first 2 were fulfilled, RA would be superior to R. RESULTS: Of 173
patients who treated a migraine, 123 patients (71.5%) achieved pain relief within
2 h. RA (90%) was significantly better than P (46%) and A (70%), but only
numerically better than R (77%) for 2-h pain relief. No significant differences
were seen between the active treatment groups in adverse events. CONCLUSION:
Rizatriptan coadministered with acetaminophen achieved 2 of the 3 primary
hypotheses, proving superior to both acetaminophen and placebo for 2-h pain
relief, but failing to achieve superiority to rizatriptan alone. RA was as well
tolerated as each of the individual agents.

Publication Types: 
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 18572432 [PubMed - indexed for MEDLINE]

198: Headache. 2008 Jun;48(6):890-9.

Exercise in migraine therapy--is there any evidence for efficacy? A critical
review.

Busch V, Gaul C.

University for Regensburg-Neurology, Regensburg, Germany.

BACKGROUND: Some migraine patients find that regular exercise helps in reducing
the frequency of headache attacks. In addition, exercise in migraine is
recommended from many headache experts. However, most of these recommendations
refer to some anecdotal reports or observational studies in literature stating
that regular exercise can reduce the frequency and severity of migraine.
OBJECTIVE: The purpose of this review is to investigate whether recommendations
for exercise in migraine are based on sufficient data to cope with requirements
of an evidence-based modern migraine therapy. The review summarizes and discusses
all available trials on this topic. RESULTS: Eight studies und 4 case reports
investigated the therapeutic role of aerobic exercise on migraine headache. Some 
results are controversial regarding the efficacy of sports intervention in
migraine. The majority of studies did not find a significant reduction of
headache attacks or headache duration and only indicate a reduction of pain
intensities in migraine patients due to regular exercise. The grade of
recommendation of exercise in migraine based on evidence based medicine
(EBM)-criteria is presently B-C. But due to methodological limitations, the
available data are insufficient for a final statement on this topic. CONCLUSIONS:
To further recommend exercise in migraine based on EBM-criteria, more studies are
imperative. Future studies should adhere to the rules for randomized clinical
trials in pharmacological migraines prophylaxis. Implications for further studies
are given.

Publication Types: 
    Review

PMID: 18572431 [PubMed - indexed for MEDLINE]

199: Ophthalmic Physiol Opt. 2008 Jul;28(4):295-309.

The Pattern Glare Test: a review and determination of normative values.

Evans BJ, Stevenson SJ.

Neville Chappell Research Clinic, Institute of Optometry, 56-62 Newington
Causeway, London, SE1 6DS, UK. bruce.evans@virgin.net

Pattern glare is characterised by symptoms of visual perceptual distortions and
visual stress on viewing striped patterns. People with migraine or Meares-Irlen
syndrome (visual stress) are especially prone to pattern glare. The literature on
pattern glare is reviewed, and the goal of this study was to develop clinical
norms for the Wilkins and Evans Pattern Glare Test. This comprises three test
plates of square wave patterns of spatial frequency 0.5, 3 and 12 cycles per
degree (cpd). Patients are shown the 0.5 cpd grating and the number of
distortions that are reported in response to a list of questions is recorded.
This is repeated for the other patterns. People who are prone to pattern glare
experience visual perceptual distortions on viewing the 3 cpd grating, and
pattern glare can be quantified as either the sum of distortions reported with
the 3 cpd pattern or as the difference between the number of distortions with the
3 and 12 cpd gratings, the '3-12 cpd difference'. In study 1, 100 patients
consulting an optometrist performed the Pattern Glare Test and the 95th
percentile of responses was calculated as the limit of the normal range. The
normal range for the number of distortions was found to be <4 on the 3 cpd
grating and <2 for the 3-12 cpd difference. Pattern glare was similar in both
genders but decreased with age. In study 2, 30 additional participants were given
the test in the reverse of the usual testing order and were compared with a
sub-group from study 1, matched for age and gender. Participants experienced more
distortions with the 12 cpd grating if it was presented after the 3 cpd grating. 
However, the order did not influence the two key measures of pattern glare. In
study 3, 30 further participants who reported a medical diagnosis of migraine
were compared with a sub-group of the participants in study 1 who did not report 
migraine or frequent headaches, matched for age and gender. The migraine group
reported more symptoms on viewing all gratings, particularly the 3 cpd grating.
The only variable to be significantly different between the groups was the 3-12
cpd difference. In conclusion, people have an abnormal degree of pattern glare if
they have a Pattern Glare Test score of >3 on the 3 cpd grating or a score of >1 
on the 3-12 cpd difference. The literature suggests that these people are likely 
to have visual stress in everyday life and may therefore benefit from
interventions designed to alleviate visual stress, such as precision tinted
lenses.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 18565084 [PubMed - indexed for MEDLINE]

200: Mult Scler. 2008 May;14(4):514-21.

Lifetime and actual prevalence of pain and headache in multiple sclerosis.

Boneschi FM, Colombo B, Annovazzi P, Martinelli V, Bernasconi L, Solaro C, Comi
G.

Department of Neuro-rehabilitation, San Raffaele Scientific Institute, Milan,
Italy.

The aim of the present study is to assess the actual and lifetime frequency of
neuropathic (trigeminal neuralgia, L'Hermitte's sign, dysesthesic pain) and
somatic (painful muscle spasms and low back pain) pain and headache (tensive
headache and migraine) in a cross-sectional sample of 428 consecutive multiple
sclerosis (MS) outpatients followed-up in an Italian University MS center over a 
3-month period. The impact of demographic and disease-related variables on pain
and headache risk is also studied. A semi-structured questionnaire was
administered during a face-to-face interview with MS patients and a multivariate 
logistic regression model is applied to obtain crude and adjusted risk measures. 
The mean age of the sample was 38.4 years, and female/male ratio was 1.65. The
mean disease duration was 9.6 years and the median Expanded Disability Status
Scale was 2.0, with most of the patients (74.8%) being affected by the
relapsing-remitting form. Lifetime prevalence at the date of examination of at
least one type of neuropathic or somatic pain was 39.8% in MS patients, with
58.5% also including headache, while the actual prevalence was 23.8% and 39.9%,
respectively. After multivariate analysis, a progressive course of disease was
shown to increase the risk of dysesthesic pain and painful muscle spasms, while
greater disability was responsible for a higher risk of back pain. L'Hermitte's
sign was more frequent in younger patients, while females had a higher risk of
headache. Pain and headache in MS are not negligible symptoms and a neurological 
examination should not miss the assessment of risk factors for specific types of 
pain for a more specific and individualized treatment.

PMID: 18562506 [PubMed - indexed for MEDLINE]

201: Cephalalgia. 2008 Sep;28(9):933-44. Epub 2008 Jun 28.

Serotonin type 1D receptors (5HTR) are differentially distributed in nerve fibres
innervating craniofacial tissues.

Harriott AM, Gold MS.

Department of Biomedical Sciences and Medical Sciences Training Program,
University of Maryland, Baltimore, MD, USA.

We tested the hypothesis that the 5HT(1D)R, the primary antinociceptive target of
triptans, is differentially distributed in tissues responsible for migraine pain.
The density of 5HT(1D)R was quantified in tissues obtained from adult female rats
with Western blot analysis. Receptor location was assessed with
immunohistochemistry. The density of 5HT(1D)R was significantly greater in
tissues known to produce migraine-like pain (i.e. circle of Willis and dura) than
in structures in which triptans have no antinociceptive efficacy (i.e. temporalis
muscle). 5HT(1D)R-like immunoreactivity was restricted to neuronal fibres, where 
it colocalized with calcitonin gene-related peptide and tyrosine hydroxylase
immunoreactive fibres. These results are consistent with our hypothesis that the 
limited therapeutic profile of triptans could reflect its differential peripheral
distribution and that the antinociceptive efficacy reflects inhibition of
neuropeptide release from sensory afferents. An additional site of action at
sympathetic efferents is also suggested.

Publication Types: 
    Research Support, N.I.H., Extramural

PMID: 18557979 [PubMed - indexed for MEDLINE]

202: Neurosci Lett. 2008 Aug 1;440(2):92-6. Epub 2008 May 16.

Frontal lobe structure and executive function in migraine patients.

Schmitz N, Arkink EB, Mulder M, Rubia K, Admiraal-Behloul F, Schoonman GG, Kruit 
MC, Ferrari MD, van Buchem MA.

Department of Radiology, Leiden University Medical Centre, Albinusdreef 2, 2300
RC, Leiden, The Netherlands.

Neuroimaging studies have identified frontal lobe brain abnormalities in
migraineurs. Neuropsychological investigations highlighted frontal lobe related
cognitive impairments in migraineurs, including working memory and executive
function deficits. The relationship between brain anatomy and cognitive function 
in migraine, however, is unclear. The aim of this study was to simultaneously
investigated cortex structure and executive function (EF) in patients with
migraine and control subjects. Thus, we assessed grey matter (GM) density in 25
adult patients with migraine, compared to age and sex-matched control subjects,
using magnetic resonance imaging (MRI) and voxel-based-morphometry (VBM), and we 
measured EF in the same population, employing three EF tasks of the Maudsley
attention and response suppression (MARS) battery. Migraineurs, compared to
control subjects, showed decreased frontal and parietal lobe GM density and
slower response time to task set-shifting and, the delayed response time
correlated significantly with reduced GM density of the frontal lobes in
migraineurs. Frontal and parietal lobe abnormalities in migraineurs could be an
underlying cause of significantly slower response time during cognitive
set-shifting.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 18556120 [PubMed - indexed for MEDLINE]

203: J Behav Med. 2008 Aug;31(4):351-66. Epub 2008 Jun 13.

Migraines and meditation: does spirituality matter?

Wachholtz AB, Pargament KI.

Department of Psychiatry, University of Mass Medical Center, Worcester, MA 01655,
USA. WachholA@ummhc.org

Migraine headaches are associated with symptoms of depression and anxiety (Waldie
and Poulton Journal of Neurology, Neurosurgery, and Psychiatry 72: 86-92, 2002)
and feelings of low self-efficacy (French et al. Headache, 40: 647-656, 2000).
Previous research suggests that spiritual meditation may ameliorate some of the
negative traits associated with migraine headaches (Wachholtz and Pargament
Journal of behavioral Medicine, 30: 311-318, 2005). This study examined two
primary questions: (1) Is spiritual meditation more effective in enhancing pain
tolerance and reducing migraine headache related symptoms than secular meditation
and relaxation? and, (2) Does spiritual meditation create better mental,
physical, and spiritual health outcomes than secular meditation and relaxation
techniques? Eighty-three meditation naïve, frequent migraineurs were taught
Spiritual Meditation, Internally Focused Secular Meditation, Externally Focused
Secular Meditation, or Muscle Relaxation which participants practiced for 20 min 
a day for one month. Pre-post tests measured pain tolerance (with a cold pressor 
task), headache frequency, and mental and spiritual health variables. Compared to
the other three groups, those who practiced spiritual meditation had greater
decreases in the frequency of migraine headaches, anxiety, and negative affect,
as well as greater increases in pain tolerance, headache-related self-efficacy,
daily spiritual experiences, and existential well being.

Publication Types: 
    Comparative Study
    Randomized Controlled Trial

PMID: 18551362 [PubMed - indexed for MEDLINE]

204: Eur J Neurol. 2008 Aug;15(8):817-21. Epub 2008 Jun 28.

Assessing migraine disability by diary-based measurement: relationship to the
characteristics of individual headache attacks.

Park JW, Shin HE, Kim JS, Lee KS.

Department of Neurology, The Catholic University of Korea, Seoul, Korea.

BACKGROUND AND PURPOSE: Information on headache-related disability helps
clinicians create the optimal treatment plan for migraine sufferers. The
estimation of disability must be determined by gathering the individual effects
of multiple headache attacks within a given period of time. This study was aimed 
to examine migraine-related disability from diary-based assessment and to
determine which elements of the headache characteristics are associated with
disability. METHODS: Ninety-two migraine patients were enrolled and contributed
data on a total of 422 diary days of headache attacks. Each diary booklet was
comprised of questions on headache features and disability comprising five items 
that originated from Migraine Disability Assessment (MIDAS). RESULTS: The average
days recorded with disability for one or more of the three aspects of activities 
per headache attack was 0.55. Amongst the headache variables, pain intensity,
nausea/vomiting, photophobia, type of abortive treatment and the employment
status were significantly correlated with disability. On regression analysis,
pain intensity, nausea/vomiting and employed work status were identified as
significant predicting factors for migraine-related disability. CONCLUSION: These
results demonstrated that a considerable amount of disability could occur during 
migraine attack and there are specified elements that act on the development of
disability.

PMID: 18549394 [PubMed - indexed for MEDLINE]

205: Headache. 2008 Jun;48(6):961-4.

Ophthalmoplegic migraine: a case with recurrent palsy of the abducens nerve.

Vasconcelos LP, Stancioli FG, Leal JC, da Silva A, Gómez RS, Teixeira AL.

Federal University of Minas Gerais (UFMG)-Internal Medicine/Clínica Médica, Belo 
Horizonte, Brazil.

Ophthalmoplegic migraine (OM) is a rare disorder characterized by recurrent
episodes of migraine-like headaches associated with extrinsic ocular musculature 
palsy. In this article, we report a patient with OM that presented recurrent
palsy of the abducens nerve and other atypical features. Case reports of OM with 
abducens nerve palsy were also reviewed.

Publication Types: 
    Case Reports
    Research Support, Non-U.S. Gov't
    Review

PMID: 18549374 [PubMed - indexed for MEDLINE]

206: Headache. 2008 Jun;48(6):939-43.

Examining the utility of in-clinic "rescue" therapy for acute migraine.

Morey V, Rothrock JF.

Department of Neurology, University of South Alabama, Mobile, AL, USA.

BACKGROUND: Management options currently are limited for patients with acute
migraine whose symptoms prove refractory to self-administered therapy. OBJECTIVE:
To evaluate the clinical utility and cost-effectiveness of a management program
offering in-clinic "rescue" treatment for patients with acute migraine. METHODS: 
Two hundred consecutive migraine patients presenting to a university-based
headache clinic were randomized to receive either optimal self-administered
medical therapy for acute migraine ("standard therapy") or similar therapy plus
the option of in-clinic parenteral drug administration should self-administered
therapy prove ineffective ("rescue therapy"). Patients randomized to the latter
group were restricted to a maximum of 2 "rescue visits" per month, and all
patients were followed for one year. Patients "rescued" in clinic were contacted 
by telephone 24 hours following treatment to evaluate their treatment response.
The primary analysis involved a comparison of the number of emergency department 
(ED) visits for headache recorded within each group over the one-year period of
study. For all ED visits in the rescue group and for a randomly selected and
equal number of ED visits within the standard group, the direct costs associated 
with those visits were assessed, and the direct costs of all in-clinic rescue
visits also were recorded and analyzed. RESULTS: The 2 groups studied were
similar in terms of age, gender ratio, migraine subtype, migraine-related
disability status at baseline and type/extent of medical insurance coverage. Over
the one-year study period, the rescue group recorded 423 in-clinic rescue visits 
and reported 27 ED visits for headache treatment. The standard therapy group
reported 73 ED visits (27 vs 73 visits; P < .01). The total direct costs
associated with ED visits were $45,330 for the rescue group (mean $1690 per ED
visit) and (by extrapolation from the sample selected) $147,971 for the standard 
therapy group (mean $2027 per ED visit). The total direct cost of the 423 "rescue
visits" was $33,647 (mean $80 per visit). In 79% of the 423 rescue encounters,
the patients involved reported no residual functional disability 24 hours
following treatment. Of those in the rescue group who sought in-clinic rescue,
89% reported themselves "very satisfied" with such management. CONCLUSION:
Providing the alternative of in-clinic "rescue" for acute migraine refractory to 
self-administered therapy offers an attractive alternative for patients and
appears to substantially lower use of an ED for headache treatment and the cost
associated with that use.

Publication Types: 
    Randomized Controlled Trial

PMID: 18549372 [PubMed - indexed for MEDLINE]

207: Headache. 2008 Jun;48(6):876-82.

Prevalence and impact of migraine among US Army soldiers deployed in support of
Operation Iraqi Freedom.

Theeler BJ, Mercer R, Erickson JC.

Department of Neurology, Madigan Army Medical Center, Tacoma, WA, USA.

OBJECTIVES: To assess the prevalence and impact of migraine headaches in US Army 
soldiers deployed in support of Operation Iraqi Freedom. METHODS: A brigade of US
Army soldiers stationed at Ft. Lewis, Washingtion was given a self-administered
headache questionnaire within 10 days of return from a 1-year combat tour in
Iraq. Soldiers who screened positive for migraine were surveyed again by phone 3 
months after return from Iraq. RESULTS: In total, 19% of soldiers screened
positive for migraine and 17% for possible migraine. Soldiers with a positive
migraine screen had a mean of 3.1 headache days per month, a mean headache
duration of 5.2 hours, and a mean of 2.4 impaired duty days per month due to
headache. Soldiers with migraine made a total of 490 sick call visits for
headache over a 3-month period compared with 90 sick call visits among those with
possible migraine. In all, 75% of the soldiers with migraine used
over-the-counter analgesics and only 4% used triptans. Soldiers with migraine
contacted 3 months after returning from Iraq had a mean of 5.3 headache days per 
month and 36% had a Migraine Disability Assessment Scale grade of 3 or 4.
CONCLUSIONS: Migraine headaches are common in deployed US Army soldiers exceeding
the expected prevalence. These headaches result in impaired duty performance and 
are a frequent cause of sick call visits. Migraine headaches tend to persist
after deployment in many soldiers.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 18549370 [PubMed - indexed for MEDLINE]

208: Headache. 2008 Jun;48(6):828-37.

Reflections and speculations on refractory migraine: why do some patients fail to
improve with currently available therapies?

Dodick DW.

Department of Neurology, Mayo Clinic Arizona, Phoenix, AZ, USA.

This review considers current debate surrounding refractory migraine and poses
the question, why do some patients fail to improve with currently available
therapies?

Publication Types: 
    Review

PMID: 18549360 [PubMed - indexed for MEDLINE]

209: Headache. 2008 Jun;48(6):820-7.

Pearls from an inpatient headache unit.

Saper JR.

Michigan Head Pain and Neurological Institute, Ann Arbor, MI, USA.

Much can be learned from treating over 15,000 headache hospitalized patients over
the course of 30 years. By the very need to be admitted, these individuals are
complicated, both physiologically and often psychologically. Founded in 1978, the
Michigan Head Pain and Neurological Institute and its hospital unit developed a
set of criteria for admission and a growing staff of professionals to serve this 
complex population of patients. Experience has taught us many lessons; several
are considered in this review. Among the important topics discussed are:
admission criteria to the hospital unit; treatment protocols and other
hospital-based strategies; integration of behavioral therapy and therapists into 
the treatment system; diagnostic testing of patients with intractable headache;
identifying the "problem patient" and "medication misuse" early in the course of 
therapy; approaching the headache patient with cluster B personality disorder;
and the use of interventional and anesthesiological treatment for intractable
headache. Outcome data and a review of recent publications are presented.

Publication Types: 
    Review

PMID: 18549359 [PubMed - indexed for MEDLINE]

210: Headache. 2008 Jun;48(6):805-19.

Rational combination therapy in refractory migraine.

Peterlin BL, Calhoun AH, Siegel S, Mathew NT.

Department of Neurology, Drexel University College of Medicine, Philadelphia, PA,
USA.

Refractory migraine (RM) headaches pose important treatment challenges to the
patients who live with them and the clinicians who try to treat them. Defined
based on the lack of response to acute, preventive, and nonpharmacologic
treatment, RM is often treated with a combination of treatments. Although
combination therapy for RM has not been systematically studied in randomized
trials, clinical experience suggests that a rational approach to RM treatment,
utilizing a combination of treatments, may be effective where monotherapy has
failed. In this article we briefly identify patient populations appropriate for
more aggressive migraine prevention with combination therapy. We then discuss
modifiable risk factors and comorbidities in migraine and then focus on the use
of rational combination therapy, as well as the duration migraine preventatives
should be considered for use. Future research is needed to evaluate the full
potential of rational combination treatment as a strategy for treating and
ultimately preventing RM.

PMID: 18549358 [PubMed - indexed for MEDLINE]

211: Headache. 2008 Jun;48(6):799-804.

Refractory migraine and chronic migraine: pathophysiological mechanisms.

Goadsby PJ, Hargreaves R.

Headache Group, Department of Neurology, University of California, San Francisco,
San Francisco, CA, USA.

Migraine is a complex disorder of the brain whose mechanisms are only now being
unravelled. It is common, disabling, and economically costly. Brain imaging has
suggested a role for the brainstem. While the disorder is almost certainly
inherited, the degree to which this contributes to a treatment refractory state
is not clear. Indeed, no specific structural or pharmacological explanation can
be seen from the data as they have been generated. It is clear that patients with
more frequent headache are very likely to go on to even more frequent headache,
but again these data are complex. A challenge going forward is to establish the
biology of these very challenging patients who undoubtedly have substantial
disability.

PMID: 18549357 [PubMed - indexed for MEDLINE]

212: Headache. 2008 Jun;48(6):783-90.

Refractory headache: classification and nomenclature.

Levin M.

Dartmouth Hitchcock Medical Center-Neurology, Lebanon, NH, USA.

There are a number of reasons to attempt to define and classify refractory
headache disorders. Particularly important are the potential benefits in the
areas of research, treatment, and medical cost reimbursement. There are
challenges in attempting to classify refractory forms of headaches, including the
lack of biological or other objective markers and a lack of consensus among
practitioners as to what qualifies as refractoriness, or even if a separate
category for refractory migraine and other refractory headaches needs to be
established. A definition of refractory migraine has been proposed by Schulman et
al in this issue ("Defining Refractory Migraine [RM] and Refractory Chronic
Migraine [RCM]: Proposed Criteria for the Refractory Headache Special Interests
Section of the American Headache Society"), which should be tested for validity
and usefulness. It seems reasonable to consider adding this defined syndrome to
the International Classification of Headache Disorders, second edition (ICHD-II).
In this article, options for adding refractory headache syndromes to the ICHD are
discussed with pros and cons for each. Two "best" options for adding the disorder
"refractory migraine" to the ICHD are presented along with an illustrative case
example.

PMID: 18549356 [PubMed - indexed for MEDLINE]

213: Cephalalgia. 2008 Jul;28 Suppl 1:18-20.

Cervicogenic headache: comparison with migraine without aura; Vågå study.

Sjaastad O.

Department of Neurology, St Olavs Hospital, Trondheim, Norway. tora.rui@ntnu.no

The prevalence of cervicogenic headache (CEH) is only vaguely known. Furthermore,
it is a common belief that in migraine without aura (MwoA), neck symptoms
frequently occur and that MwoA and CEH may pathogenetically be intimately
related. In the Vågå study, 1838 18-65-year-old citizens (88.6% of that age
group) were studied with face-to-face interviews and a thorough neck examination.
For CEH, the Cervicogenic Headache International Study Group criteria were used, 
and for MwoA, the IHS criteria. The extent of cervical involvement was assessed
by the 'CF' ('features indicative of cervical abnormality'). CEH prevalence was
4.1%. 'CF' was 2.37 in CEH vs 0.93 in M-A. CEH criteria, e.g. mechanical attack
provocation, were present many times more frequently in CEH than in MwoA.
Conversely, migraine criteria, e.g. photophobia, were >/= 2.6 times higher in
MwoA than in CEH. CEH is unlikely to be a subgroup of MwoA.

Publication Types: 
    Comparative Study

PMID: 18494988 [PubMed - indexed for MEDLINE]

214: Cephalalgia. 2008 Jul;28(7):767-8.

Maximum effect of triptans in migraine? A comment.

Tfelt-Hansen P.

Danish Headache Centre, Department of Neurology, University of Copenhagen,
Glostrup Hospital, Glostrup, Denmark. tfelt@inet.uni2.dk

The efficacy of triptans in the treatment of migraine was recently contested. How
high is then the maximum effect of a triptan? After subcutaneous naratriptan 10
mg a 88% pain-free response was observed. This result was obtained despite the
fact that more half of the patients had a migraine duration of > 4 h. These
results indicate that subcutaneous naratriptan in a high dose can overcome
central sensitization that occurs in migraine attacks.

Publication Types: 
    Comparative Study

PMID: 18547214 [PubMed - indexed for MEDLINE]

215: Arq Neuropsiquiatr. 2008 Jun;66(2A):216-20.

Lysine clonixinate versus dipyrone (metamizole) for the acute treatment of severe
migraine attacks: a single-blind, randomized study.

Krymchantowski AV, Carneiro H, Barbosa J, Jevoux C.

Headache Center of Rio, Rio de Janeiro, RJ, Brazil. abouchkrym@globo.com

BACKGROUND AND OBJECTIVE: Nonsteroidal anti-inflammatory drugs (NSAID) are
effective to treat migraine attacks. Lysine clonixinate (LC) and dipyrone
(metamizol) have been proven effective to treat acute migraine. The aim of this
study was to evaluate the efficacy and tolerability of the intravenous
formulations of LC and dipyrone in the treatment of severe migraine attacks.
METHOD: Thirty patients (28 women, 2 men), aged 18 to 48 years with migraine
according the International Headache Society (IHS) (2004) were studied. The
patients were randomized into 2 groups when presenting to an emergency department
with a severe migraine attack. The study was single-blind. Headache intensity,
nausea, photophobia and side effects were evaluated at 0, 30, 60 and 90 minutes
after the drug administration. Rectal indomethacin as rescue medication (RM) was 
available after 2 hours and its use compared between groups. RESULTS: All
patients completed the study. At 30 minutes, 0% of the dipyrone group 13% of the 
LC group were pain free (p=0.46). At 60 and 90 minutes, 2 (13%) and 5 (33%)
patients from the dipyrone group and 11 (73%) and 13 (86.7%) patients from the LC
group were pain free (p<0.001). At 60 minutes, significantly more patients from
the LC group were nausea-free (p<0.001). Regarding photophobia, there were no
differences between groups at 60 minutes (p=0.11). The use of RM at 2 hours did
not differ among groups (p=0.50). Pain in the site of the injection was reported 
by more patients of the LC group compared to the dipyrone group (p<0.0001).
CONCLUSION: LC is significantly superior to dipyrone in treating severe migraine 
attacks. LC promotes significantly more burning at the site of the injection.

Publication Types: 
    Comparative Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 18545786 [PubMed - indexed for MEDLINE]

216: Arch Neurol. 2008 Jun;65(6):709-14.

Comment in:
    Arch Neurol. 2008 Nov;65(11):1546; author reply 1546-7.

Common pathophysiologic mechanisms in migraine and epilepsy.

Rogawski MA.

Department of Neurology, University of California Davis School of Medicine, 4860 
Y St, Ste 3700, Sacramento, CA 95817, USA. rogawski@ucdavis.edu

Migraine and epilepsy are comorbid episodic disorders that have common
pathophysiologic mechanisms. Migraine attacks, like epileptic seizures, may be
triggered by excessive neocortical cellular excitability; in migraine, however,
the hyperexcitability is believed to transition to cortical spreading depression 
rather than to the hypersynchronous activity that characterizes seizures. Some
forms of epilepsy and migraine are known to be channelopathies. Mutations in the 
same genes can cause either migraine or epilepsy or, in some cases, both. Given
the likely commonalities in the underlying cellular and molecular mechanisms, it 
is not surprising that some antiepileptic drugs, including valproate, topiramate,
and gabapentin, are effective antimigraine agents. Ionotropic glutamate receptors
play roles in both migraine and epilepsy, with NMDA receptors that are critical
to cortical spreading depression of particular importance in migraine. Greater
understanding of the shared mechanisms of epilepsy and migraine can provide a
basis for the development of improved treatment approaches that may be applicable
to both conditions.

Publication Types: 
    Review

PMID: 18541791 [PubMed - indexed for MEDLINE]

217: BMJ. 2008 Jun 14;336(7657):1359-61. Epub 2008 Jun 9.

Comment in:
    BMJ. 2008 Jun 14;336(7657):1320.

Parenteral dexamethasone for acute severe migraine headache: meta-analysis of
randomised controlled trials for preventing recurrence.

Colman I, Friedman BW, Brown MD, Innes GD, Grafstein E, Roberts TE, Rowe BH.

School of Public Health, University of Alberta, Edmonton, AB, Canada.

OBJECTIVE: To examine the effectiveness of parenteral corticosteroids for the
relief of acute severe migraine headache and prevention of recurrent headaches.
DESIGN: Meta-analysis. DATA SOURCES: Electronic databases (Cochrane Central
Register of Controlled Trials, Medline, Embase, LILACS, and CINAHL), conference
proceedings, clinical practice guidelines, contacts with industry, and
correspondence with authors. SELECTION CRITERIA: Randomised controlled trials in 
which corticosteroids (alone or combined with standard abortive therapy) were
compared with placebo or any other standard treatment for acute migraine in
adults. REVIEW METHODS: Two reviewers independently assessed relevance,
inclusion, and study quality. Weighted mean differences and relative risks were
calculated and are reported with 95% confidence intervals. RESULTS: From 666
potentially relevant abstracts, seven studies met the inclusion criteria. All
included trials used standard abortive therapy and subsequently compared single
dose parenteral dexamethasone with placebo, examining pain relief and recurrence 
of headache within 72 hours. Dexamethasone and placebo provided similar acute
pain reduction (weighted mean difference 0.37, 95% confidence interval -0.20 to
0.94). Dexamethasone was, however, more effective than placebo in reducing
recurrence rates (relative risk 0.74, 95% confidence interval 0.60 to 0.90). Side
effect profiles between dexamethasone and placebo groups were similar.
CONCLUSION: When added to standard abortive therapy for migraine headache, single
dose parenteral dexamethasone is associated with a 26% relative reduction in
headache recurrence (number needed to treat=9) within 72 hours.

Publication Types: 
    Meta-Analysis
    Research Support, Non-U.S. Gov't
    Review

PMID: 18541610 [PubMed - indexed for MEDLINE]

218: BMC Complement Altern Med. 2008 Jun 9;8:28.

Craniosacral therapy for migraine: protocol development for an exploratory
controlled clinical trial.

Mann JD, Faurot KR, Wilkinson L, Curtis P, Coeytaux RR, Suchindran C, Gaylord SA.

Department of Neurology, School of Medicine, University of North Carolina at
Chapel Hill, Chapel Hill, NC, USA. mannj@neurology.unc.edu

BACKGROUND: Migraine affects approximately 20% of the population. Conventional
care for migraine is suboptimal; overuse of medications for the treatment of
episodic migraines is a risk factor for developing chronic daily headache. The
study of non-pharmaceutical approaches for prevention of migraine headaches is
therefore warranted. Craniosacral therapy (CST) is a popular non-pharmacological 
approach to the treatment or prevention of migraine headaches for which there is 
limited evidence of safety and efficacy. In this paper, we describe an ongoing
feasibility study to assess the safety and efficacy of CST in the treatment of
migraine, using a rigorous and innovative randomized controlled study design
involving low-strength static magnets (LSSM) as an attention control
intervention. METHODS: The trial is designed to test the hypothesis that,
compared to those receiving usual care plus a treatment with low-strength static 
magnets (attention-control complementary therapy), subjects receiving usual
medical care plus CST will demonstrate significant improvement in:
quality-of-life as measured by the Headache Impact Test (HIT-6); reduced
frequency of migraine; and a perception of clinical benefit. Criteria for
inclusion are either gender, age > 11, English or Spanish speaking, meeting the
International Classification of Headache Disorders (ICHD) criteria for migraine
with or without aura, a headache frequency of 5 to 15 per month over at least two
years. After an 8 week baseline phase, eligible subjects are randomized to either
CST or an attention control intervention, low strength static magnets (LSSM). To 
evaluate possible therapist bias, videotaped encounters are analyzed to assess
for any systematic group differences in interactions with subjects. RESULTS: 169 
individuals have been screened for eligibility, of which 109 were eligible for
the study. Five did not qualify during the baseline phase because of inadequate
headache frequency. Nineteen have withdrawn from the study after giving consent. 
CONCLUSION: This report endorses the feasibility of undertaking a rigorous
randomized clinical trial of CST for migraine using a standardized CST protocol
and an innovative control protocol developed for the study. Subjects are able and
willing to complete detailed headache diaries during an 8-week baseline period,
with few dropouts during the study period, indicating the acceptability of both
interventions. TRIAL REGISTRATION: ClinicalTrials.gov NCT00665236.

Publication Types: 
    Randomized Controlled Trial
    Research Support, N.I.H., Extramural

PMID: 18541041 [PubMed - indexed for MEDLINE]

219: Cephalalgia. 2008 Aug;28(8):847-55. Epub 2008 Jun 6.

Prediction of attack frequency in migraine treatment.

Maas HJ, Snelder N, Danhof M, Della Pasqua O.

Division of Pharmacology, Leiden/Amsterdam Center for Drug Research, the
Netherlands.

Usually limited information about the frequency of migraine episodes is derived
from acute migraine trials. However, the design of some studies is such that they
also provide relevant information about the attack frequency without the bias
associated with patient expectations of treatment effect between attacks during
prophylaxis trials. Using clinical data from repeated migraine attacks treated
with placebo, naratriptan 2.5 mg or sumatriptan 100 mg, we show that attack and
interictal periods can be described by a random probability distribution. Based
on a gamma distribution, the mean interval between attacks was estimated to be 24
(17-34) days for placebo, 23 (18-29) days for naratriptan 2.5 mg and 22 (17-28)
for sumatriptan 100 mg. These findings suggest that the interictal interval is
not affected by abortive treatment with triptans. Interpretation of these results
may be limited by the study type, yet the method represents a new tool for the
evaluation of disease dynamics and treatment effect in the prophylaxis of
migraine.

Publication Types: 
    Controlled Clinical Trial

PMID: 18540870 [PubMed - indexed for MEDLINE]

220: J Womens Health (Larchmt). 2008 Jun;17(5):879-91.

Menstrual-related pain conditions: dysmenorrhea and migraine.

Mannix LK.

Headache Associates, West Chester, Ohio 45069, USA. LKMannixMD@aol.com

Menstrual disorders affect millions of women in the United States and represent
an important health burden. The most common menstrual disorders are dysmenorrhea 
and headache; these conditions are leading causes of work or school absenteeism
and substantially impact quality of life. Headache associated with menses is
often migraine and referred to as menstrual migraine. Although the pathogenesis
of menstrual-related pain conditions is not fully understood, menstrual-related
overproduction of prostaglandins is implicated in the pathophysiology of both
menstrual migraine and dysmenorrhea. In clinical practice, nonsteroidal
anti-inflammatory drugs (NSAIDs) are considered the first-line therapeutic option
for managing pain associated with dysmenorrhea. NSAIDs also play a role in the
acute treatment and intermittent prophylaxis of migraine. Triptans, a class of
highly selective serotonin receptor agonists, represent the gold standard for
acute treatment of migraine. In addition, hormone therapy is effective in many
cases for treating dysmenorrhea and may be beneficial in the management of
menstrual migraine. Thus, overlapping treatment regimens may be advantageous in
treating the coexisting menstrual-related pain conditions of dysmenorrhea and
migraine.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 18537489 [PubMed - indexed for MEDLINE]

221: Stroke. 2008 Aug;39(8):2377-9. Epub 2008 Jun 5.

Postpartum cervicocephalic artery dissection.

Arnold M, Camus-Jacqmin M, Stapf C, Ducros A, Viswanathan A, Berthet K, Bousser
MG.

BACKGROUND AND PURPOSE: Cervicocephalic artery dissection (CAD) after childbirth 
is rare. The objective of this study was to determine differences between
postpartum and nonpostpartum CAD. METHODS: We compared consecutive patients with 
postpartum CAD with a control group of women with nonpostpartum CAD. RESULTS: Of 
245 patients with CAD, 102 women <50 years (6 with postpartum CAD and 96 with
nonpostpartum CAD) were identified. Vascular risk factors and presenting
characteristics did not differ significantly between postpartum CAD and
nonpostpartum CAD women. By contrast, patients with postpartum CAD had more often
coexisting conditions such as reversible cerebral vasoconstriction syndrome (2 of
6 versus 2 of 96; P=0.017), reversible posterior leukoencephalopathy syndrome (2 
of 6 versus one of 96; P=0.009), and subarachnoid hemorrhage without signs of
intracranial extension of CAD (2 of 6 versus zero of 96; P=0.003). CONCLUSIONS:
CAD and associated conditions should be looked for in women with unusual headache
after childbirth.

Publication Types: 
    Comparative Study
    Letter

PMID: 18535274 [PubMed - indexed for MEDLINE]

222: Curr Med Res Opin. 2008 Jul;24(7):1977-85. Epub 2008 Jun 4.

Randomized, double-blind, placebo-controlled study of the safety, tolerability
and pharmacokinetics of MAP0004 (orally-inhaled DHE) in adult asthmatics.

Shrewsbury SB, Kori SH, Miller SD, Pedinoff A, Weinstein S.

MAP Pharmaceuticals Inc., Mountain View, CA 94043, USA.

BACKGROUND: MAP0004 (a proprietary formulation of dihydroergotamine mesylate
[DHE]) for inhaled delivery is being developed for acute migraine treatment.
Because asthma and migraine often occur as co-morbid conditions, it is considered
important to study the safety of MAP0004 in a population of asthmatic adults and 
to confirm that the pharmacokinetics of DHE, when inhaled by asthmatic subjects, 
were comparable to a population of healthy volunteers. The safety, tolerability, 
and pharmacokinetics of orally-inhaled MAP0004 administered by the Tempo inhaler 
were studied in adult asthmatics. SCOPE: This was a randomized, double-blind,
placebo-controlled study of two doses of inhaled MAP0004. Eligible subjects were 
randomized in a 2 : 1 ratio to MAP0004 or placebo and observed for 4 h after each
dose. Pharmacokinetic parameters were determined pre-dose and up to 36 h
post-dose. FINDINGS: Among 19 subjects, geometric mean AUC(0-36) was 6754 pg.h/mL
and geometric mean AUC(0-inf) was 7483 pg.h/mL. Geometric mean t(max) was 9.6
min, geometric mean C(max) was 3174 pg/mL, and geometric mean t((1/2)) was 9.5 h.
Overall, 13 of 19 (68%) subjects reported at least one adverse event, most
commonly nausea, vomiting, dysgeusia, and headache. CONCLUSION: MAP0004 results
in rapid and efficient systemic absorption in asthmatic subjects. Systemic DHE
concentrations were similar to those previously reported in healthy subjects, and
no clinically relevant safety issues were observed. While this small study was
suitable for pharmacokinetic analysis and conclusions, MAP0004 use in migraineurs
with concomitant stable asthma should be supported by larger studies of longer
duration to confirm that it does not present additional safety risks compared to 
non-asthmatic migraineurs.

Publication Types: 
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 18534051 [PubMed - indexed for MEDLINE]

223: Acta Neurol Scand. 2008 Dec;118(6):367-72. Epub 2008 May 27.

Influence of disease features on adherence to prophylactic migraine medication.

Linde M, Jonsson P, Hedenrud T.

Cephalea Headache Centre, Gothenburg, Sweden. mattias.linde@neuro.gu.se

OBJECTIVES: Randomized controlled trials of prophylactic treatments for migraine 
focus on the effects in an ideal situation and underestimate the impact of
non-adherence, which in this study was examined in a natural setting. MATERIALS
AND METHODS: A sample of 174 adult migraineurs with a current prescription of
pharmacological prophylaxis were consecutively recruited at a specialist clinic. 
Logistic regression analysis was performed to analyse the association between
adherence (self-reported with the Medication Adherence Report Scale) and number
of years with migraine, frequency of attacks, number of days with migraine per
month, attack duration, presence of cardinal features, mean intensity of pain,
and recovery between attacks. RESULTS: One third (35%) were non-adherent. Neither
demographic characteristics nor any of the disease specific variables were
significantly associated with adherence. CONCLUSION: Characteristics of the
disease per se did not predict non-adherence which was also observed among
patients with severe migraine. The full benefit of drugs cannot be realized at
currently achieved levels of adherence.

PMID: 18513346 [PubMed - indexed for MEDLINE]

224: Cephalalgia. 2008 Aug;28(8):805-12. Epub 2008 May 30.

Combining proof-of-concept with dose-finding: utilization of adaptive designs in 
migraine clinical trials.

Sagkriotis A, Scholpp J.

Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim, Germany.

There is an obvious need to improve clinical trial designs with respect to
efficiency, duration and the number of patients recruited. Adaptive (flexible)
designs may be valuable in this respect. We simulated the properties of a
two-stage adaptive proof-of-concept and dose-finding trial design in adult
migraine patients with moderate to severe headache, with or without aura. We also
assessed the usefulness of a combined Bayesian and frequentist approach in the
estimation of the probability of success of subsequent Phase III studies.
Applying such an innovative approach would result in a reduction of the required 
sample size by 30 patients and no prolongation of the trial duration. The
probability of success in Phase III is > 81%. An innovative adaptive design can
facilitate testing of investigational migraine medications by reducing patient
numbers and improving predictivity of success in Phase III.

Publication Types: 
    Review

PMID: 18513264 [PubMed - indexed for MEDLINE]

225: Cephalalgia. 2008 Sep;28(9):914-21. Epub 2008 May 30.

Screen for CACNA1A and ATP1A2 mutations in sporadic hemiplegic migraine patients.

Thomsen LL, Oestergaard E, Bjornsson A, Stefansson H, Fasquel AC, Gulcher J,
Stefansson K, Olesen J.

Danish Headache Centre, University of Copenhagen, Department of Neurology,
Glostrup Hospital, Glostrup, Denmark. llt@dadlnet.dk

The aim of this study was to investigate the involvement of the CACNA1A and
ATP1A2 gene in a population-based sample of sporadic hemiplegic migraine (SHM).
Patients with SHM (n = 105) were identified in a nationwide search in the Danish 
population. We sequenced all exons and promoter regions of the CACNA1A and ATP1A2
genes in 100 patients with SHM to search for possible SHM mutations. Novel DNA
variants were discovered in eight SHM patients, four in exons of the CACNA1A gene
and four in exons of the ATP1A2 gene. Six of the variants were considered
non-pathogenic. The causal role of the two remaining DNA variants is unknown
until functional studies have been made or independent genetic evidence is
discovered. Only very few DNA variants were identified in 100 SHM patients, and
regardless of whether the identified variants are causal the CACNA1A and ATP1A2
genes are not major genes in SHM.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 18513263 [PubMed - indexed for MEDLINE]

226: Cephalalgia. 2008 Aug;28(8):856-62. Epub 2008 May 30.

Posterior cerebral hypoperfusion in migraine without aura.

Denuelle M, Fabre N, Payoux P, Chollet F, Geraud G.

Department of Neurology, Rangueil Hospital, France. denuelle.m@chu-toulouse.fr

In cerebral blood flow studies, migraine aura is characterized by a posterior
cortical hypoperfusion. In contrast, only rare and mild changes in brain
perfusion have been demonstrated in migraine without aura, suggesting two
different haemodynamic patterns in migraine with and without aura. Our aim was to
study hypoperfusion with positron emission tomography (PET) as early as possible 
during spontaneous migraine without aura attacks. We used H(2) (15)O PET to
investigate seven patients (six female, one male) with migraine without aura
(International Classification of Headache Diseases-II code 1.1) in three
situations: during the headache phase, after headache relief following
sumatriptan injection, and during an attack-free interval. Statistical analysis
was performed with SPM2. Within 4 h after the attack onset, significant relative 
bilateral posterior cortical hypoperfusion was found and persisted after headache
relief following sumatriptan injection. A posterior cortical hypoperfusion
demonstrated in migraine without aura could suggest a common pathogenesis in
migraine with and without aura. The significance of relative posterior
hypoperfusion in migraine without aura is discussed according to the current
knowledge of migraine pathogenesis.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 18513260 [PubMed - indexed for MEDLINE]

227: Brain. 2008 Aug;131(Pt 8):2192-200. Epub 2008 May 23.

Migraine headache is not associated with cerebral or meningeal vasodilatation--a 
3T magnetic resonance angiography study.

Schoonman GG, van der Grond J, Kortmann C, van der Geest RJ, Terwindt GM, Ferrari
MD.

Department of Neurology (K5-Q), Leiden University Medical Centre, PO Box 9600,
2300 RC Leiden, The Netherlands. g.g.schoonman@lumc.nl

Migraine headache is widely believed to be associated with cerebral or meningeal 
vasodilatation. Human evidence for this hypothesis is lacking. 3 Tesla magnetic
resonance angiography (3T MRA) allows for repetitive, non-invasive, sensitive
assessment of intracranial vasodilatation and blood flow. Nitroglycerine (NTG)
can faithfully induce migraine attacks facilitating pathophysiological studies in
migraine. Migraineurs (n = 32) randomly received NTG (IV 0.5 microg/kg/min for 20
min; n = 27) or placebo (n = 5; for blinding reasons). Using 3T MRA, we measured:
(i) blood flow in the basilar (BA) and internal carotid arteries (ICA) and (ii)
diameters of the middle meningeal, external carotid, ICA, middle cerebral, BA and
posterior cerebral arteries at three timepoints: (a) at baseline, outside an
attack; (b) during infusion of NTG or placebo and (c) during a provoked attack
or, if no attack had occurred, at 6 h after infusion. Migraine headache was
provoked in 20/27 (74%) migraineurs who received NTG, but in none of the five
patients who received placebo. The headache occurred between 1.5 h and 5.5 h
after infusion and was unilateral in 18/20 (90%) responders. During NTG (but not 
placebo) infusion, there was a transient 6.7-30.3% vasodilatation (P < 0.01) of
all blood vessels. During migraine, blood vessel diameters were no different from
baseline, nor between headache and non-headache sides. There were no changes in
BA and ICA blood flow during either NTG infusion or migraine. In contrast to
widespread belief, migraine attacks are not associated with vasodilatation of
cerebral or meningeal blood vessels. Future anti-migraine drugs may not require
vasoconstrictor action.

Publication Types: 
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 18502781 [PubMed - indexed for MEDLINE]

228: AJNR Am J Neuroradiol. 2008 Sep;29(8):1494-7. Epub 2008 May 22.

Migraine associated cerebral hyperperfusion with arterial spin-labeled MR
imaging.

Pollock JM, Deibler AR, Burdette JH, Kraft RA, Tan H, Evans AB, Maldjian JA.

Department of Radiology, Wake Forest University School of Medicine,
Winston-Salem, NC, USA. jeffmpollock@gmail.com

We present a case series demonstrating abnormal regional cerebral hyperperfusion 
associated with migraine headache using arterial spin-labeling (ASL). In 3 of 11 
patients, regional cortical hyperperfusion was demonstrated during a headache
episode that corresponded to previous aura symptoms.

Publication Types: 
    Case Reports
    Research Support, N.I.H., Extramural

PMID: 18499796 [PubMed - indexed for MEDLINE]

229: Anesth Analg. 2008 Jun;106(6):1844-6.

Migraine with atypical aura in the recovery room: a sometimes complicated
diagnosis!

Pianezza A, Barthélémy R, Minville V, Martin F, Faggianelli M.

Department of Anesthesiology and Intensive Care, University Hospital of Toulouse,
University Paul Sabatier, Toulouse, France. a.pianezza@wanadoo.fr

Migraine is a frequent neurological pathology. However, the diagnosis can be
difficult to establish, especially when it is accompanied with an atypical aura
that can be confounded with a stroke. We describe a case of 38-yr-old patient who
presented just after general anesthesia with a perioperative acute migraine with 
atypical aura which was wrongly treated as a serious cerebral stroke. The patient
had not mentioned migraine in her history before the surgery. This lack of
information led to unnecessary therapy.

Publication Types: 
    Case Reports

PMID: 18499620 [PubMed - indexed for MEDLINE]

230: Cephalalgia. 2008 Jul;28(7):723-33. Epub 2008 May 21.

Tactile-induced ultrasonic vocalization in the rat: a novel assay to assess
anti-migraine therapies in vivo.

Martino G, Perkins MN.

AstraZeneca Research and Development Montreal, Ville St Laurent, Montreal,
Quebec, Canada. john.martino@astrazeneca.com

A pharmacological model of migraine is described using ultrasound vocalization
(USV) of rats following central inflammation-induced sensitization to tactile
stimulation. Central inflammation induced by intracerebroventricular injection of
lipopolysaccharide (LPS) increased USV induced by an air current focused on the
head and this was abolished by morphine and ketorolac, suggesting a nociceptive
component. USV in naive rats were unaffected. Diazepam reduced USV in both
inflamed and naive rats. The triptans, zolmitriptan and sumatriptan, both reduced
USV in inflamed but not in naive rats, as did dihydroergotamine, and the
calcitonin gene-related peptide (CGRP) antagonists alphaCGRP(8-37) and
BIBN4096BS. The neurokinin-1 antagonist L-733-060 had no effect in either
inflamed or naive rats when given after induction of inflammation, but when given
with the LPS it prevented the augmentation of USV. This profile of activity of
agents proven to be effective in the clinic suggests this model can be used to
predict novel therapeutic agents for migraine.

Publication Types: 
    Comparative Study

PMID: 18498397 [PubMed - indexed for MEDLINE]

231: Cephalalgia. 2008 Aug;28(8):825-31. Epub 2008 May 21.

Osmophobia in juvenile primary headaches.

Corletto E, Dal Zotto L, Resos A, Tripoli E, Zanchin G, Bulfoni C, Battistella
PA.

Department of Paediatrics, Juvenile Headache Centre, Paediatric Neurology and
Psychiatry Unit, University of Padua Medical School, Padua, Italy.

This study was planned to investigate the prevalence of osmophobia in juvenile
headache sufferers and to analyse the diagnostic utility of osmophobia in order
to distinguish migraine without aura from episodic tension-type headache. We
examined 305 consecutive patients presenting at our Paediatric Headache Centre. A
semistructured questionnaire was given to 275 selected patients affected by
migraine or tension-type headache. The prevalence of osmophobia during attacks
was 18.5%, mainly in migraine patients (25.1%) vs. those with tension-type
headache (8.3%). Osmophobia showed more specificity than phonophobia or
photophobia in the differential diagnosis between migraine and tension-type
headache. In conclusion, this study demonstrates that osmophobia resulted in a
symptom with poor sensitivity (27.1%) but high specificity (92%) that could
become a supportive diagnostic criterion even in children for the differential
diagnosis between migraine without aura and tension-type headache.

PMID: 18498394 [PubMed - indexed for MEDLINE]

232: Cephalalgia. 2008 Aug;28(8):887-91. Epub 2008 May 21.

CACNA1A mutation linking hemiplegic migraine and alternating hemiplegia of
childhood.

de Vries B, Stam AH, Beker F, van den Maagdenberg AM, Vanmolkot KR, Laan L,
Ginjaar IB, Frants RR, Lauffer H, Haan J, Haas JP, Terwindt GM, Ferrari MD.

Department of Human Genetics, Leiden University Medical Centre, Leiden, Germany.

Familial hemiplegic migraine (FHM) and alternating hemiplegia of childhood (AHC) 
are severe neurological disorders that share clinical features. Therefore, FHM
genes are candidates for AHC. We performed mutation analysis in the CACNA1A gene 
in a monozygotic twin pair with clinical features overlapping with both AHC and
FHM and identified a novel de novo CACNA1A mutation. We provide the first
evidence that a CACNA1A mutation can cause atypical AHC, indicating an overlap of
molecular mechanisms causing AHC and FHM. These results also suggest that CACNA1A
mutation scanning is indicated in patients with a severe neurological phenotype
that includes paroxysmal (alternating) hemiplegia.

Publication Types: 
    Case Reports
    Research Support, Non-U.S. Gov't

PMID: 18498393 [PubMed - indexed for MEDLINE]

233: Cephalalgia. 2008 Jul;28(7):683-8. Epub 2008 May 21.

Evaluation and registration of adverse events in clinical drug trials in
migraine.

Tfelt-Hansen P, Bjarnason NH, Dahlöf C, Derry S, Loder E, Massiou H; Task Force
on Adverse Events in Migraine Trials of Subcommittee on Clinical Trial of
International Headache Society.

Danish Headache Centre, Department of Neurology, University of Copenhagen,
Glostrup Hospital, Copenhagen, Denmark. ptha@glo.regionh.dk

Tolerability of a drug should be regarded as important as its efficacy. In all
four phases of drug development evaluation of adverse events is important.
Recommendations for assessment of adverse events in acute and prophylactic
clinical drug trials in migraine are given. Tolerability may be indirectly
assessed using measures of general well-being and eight such tools are presented.
Finally, recommendations for reporting of adverse events are given.

Publication Types: 
    Evaluation Studies
    Research Support, Non-U.S. Gov't
    Review

PMID: 18498392 [PubMed - indexed for MEDLINE]

234: Cephalalgia. 2008 Jul;28(7):774-7. Epub 2008 May 21.

Severe attacks of familial hemiplegic migraine, childhood epilepsy and ATP1A2
mutation.

Lebas A, Guyant-Maréchal L, Hannequin D, Riant F, Tournier-Lasserve E, Parain D.

Departments of Paediatrics, Rouen University Hospital, Rouen, France.
axel.lebas@gmail.com

We studied four members of a family suffering from typical attacks of familial
hemiplegic migraine (FHM) caused by a new mutation, R548C, of ATP1A2 gene in exon
12. One individual had also childhood absence epilepsy and generalized
tonic-clonic seizures (GTCS). GTCS were followed by a severe attack of hemiplegic
migraine at four times. Sodium valproate enabled control of both the epileptic
seizures and the most severe FHM attacks. This association of FHM and epileptic
seizures and their control with the same treatment suggest similar
pathophysiological mechanisms.

PMID: 18498390 [PubMed - indexed for MEDLINE]

235: Pediatr Emerg Care. 2008 May;24(5):321-30.

Treatment of children with migraine in the emergency department: a qualitative
systematic review.

Bailey B, McManus BC.

Division of Emergency Medicine, Department of Pediatrics, Centre Hospitalier
Universitaire Ste-Justine, Montréal, Quebec, Canada. benoit.bailey@umontreal.ca

OBJECTIVE: To evaluate which treatment could be effective in the emergency
department (ED) for children with migraine and status migrainosus, we carried out
a qualitative systematic review of randomized controlled trials (RCTs) that
evaluated treatment that could be used for those conditions. METHODS: Databases
(Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of
Effects, Cochrane Controlled Trials Register, MedLine, and EMBASE) were searched 
for RCTs that evaluated treatment of migraine in children (<18 years of age).
Guidelines published on the subject were checked for missed references.
Characteristics of the identified studies as well as primary outcome (headache
relief), other recognized primary outcomes, and adverse events were abstracted.
Quality of the RCTs was evaluated using the Jadad score. RESULTS: Of the 14
trials included in the review, only 1 was performed in an ED after other
treatments have failed. In that situation, prochlorperazine was more effective
than ketorolac in relieving pain at 1 hour. Other treatments were evaluated by
neurologists on their outpatients who started the studied drugs early at the
beginning of the migraine without previous treatment. In that situation,
ibuprofen (n = 3) and acetaminophen (n = 1) were better than placebo for pain
relief. The efficacy of intranasal sumatriptan (n = 4), oral rizatriptan (n = 3),
and oral zolmitriptan (n = 2) for pain relief was unclear. Oral sumatriptan (n = 
1) and oral dihydroergotamine (n = 1) were not effective. CONCLUSIONS: There is a
lack of studies addressing the question of treatment in the ED for children
experiencing migraine. Although other treatments were found effective in children
with migraine, none was evaluated in the ED except prochlorperazine and
ketorolac.

Publication Types: 
    Review

PMID: 18496120 [PubMed - indexed for MEDLINE]

236: J Neurol Sci. 2008 Aug 15;271(1-2):119-26. Epub 2008 May 20.

Abnormal visual processing in migraine with aura: a study of steady-state visual 
evoked potentials.

Shibata K, Yamane K, Otuka K, Iwata M.

Department of Medicine, Tokyo Women's Medical University, Medical Center East,
2-1-10 Nishiogu, Arakawa-ku, Tokyo, 116-8567, Japan. kshbtgm@dnh.twmu.ac.jp

BACKGROUND: Although a number of studies reported different interictal findings
between migraine with aura (MA) and migraine without aura (MO), the
pathophysiology of the visual aura in migraine remains unclear. OBJECTIVE: To
investigate the visual processing in patients who experience MA between attacks
using steady-state visual evoked potentials (SSVEPs). METHODS: SSVEPs to high
(98%) and low (29%) contrast black and white checkerboard gratings with two
spatial frequencies (0.5 and 2.0 cpd) at 5 and 10 Hz (10 and 20 reversal/s) were 
recorded binocularly from 10 patients with MA, 10 patients with MO between
attacks and 20 healthy controls (HC). The SSVEPs were Fourier analyzed to obtain 
the amplitude and phase of the second (2F) and fourth (4F) harmonic response.
RESULTS: In the amplitude of 2F, at 0.5 cpd, there was significant increased
amplitude in both MA and MO in comparison to HC at 5 Hz in high and low contrast.
However, no significant differences were detected at 2.0 cpd in both 5 and 10 Hz 
in high and low contrast. In the amplitude of 4F, at 2.0 cpd, there was
significant increased amplitude in MA in comparison to MO and HC at 10 Hz in high
contrast. However, there were no significant differences at 0.5 cpd at both 5 and
10 Hz in high and low contrast. There were no significant phase differences
between MA, MO, and HC. CONCLUSION: The high amplitude of the SSVEPs suggests
that interictally migraine patients have abnormal excitability in the primary
visual cortex, and this change in excitability may exist, at least partially, in 
the visual association cortex in MA.

PMID: 18495160 [PubMed - indexed for MEDLINE]

237: Respiration. 2008;76(2):228-33. Epub 2008 May 20.

Pulmonary arteriovenous malformations and migraine: a new vision.

Post MC, van Gent MW, Snijder RJ, Mager JJ, Schonewille WJ, Plokker HW,
Westermann CJ.

Department of Cardiology, St Antonius Hospital, Nieuwegein, The Netherlands.
m.post@antonius.net

Migraine is a common neurological disorder with a great impact on the quality of 
life and social activities. Pulmonary arteriovenous malformations (PAVMs) are
mostly congenital, with a prevalence of 5-50% in patients with hereditary
hemorrhagic telangiectasia (HHT). A high prevalence of PAVMs is found in patients
with HHT and migraine. Embolization of PAVMs seems to decrease the prevalence of 
migraine. Different pathophysiological hypotheses have been proposed to explain
the association between migraine and the different right-to-left shunts. This
review article describes the association between a pulmonary right-to-left shunt 
and the occurrence of migraine. Copyright 2008 S. Karger AG, Basel.

Publication Types: 
    Review

PMID: 18493115 [PubMed - indexed for MEDLINE]

238: Headache. 2008 Jun;48(6):778-82. Epub 2008 May 14.

Defining refractory migraine and refractory chronic migraine: proposed criteria
from the Refractory Headache Special Interest Section of the American Headache
Society.

Schulman EA, Lake AE 3rd, Goadsby PJ, Peterlin BL, Siegel SE, Markley HG, Lipton 
RB.

Lankenau Hospital, Wynnewood, PA, USA.

Certain migraines are labeled as refractory, but the entity lacks a well-accepted
operational definition. This article summarizes the results of a survey sent to
American Headache Society members to evaluate interest in a definition for RM and
what were considered necessary criteria. Review of the literature, collaborative 
discussions and results of the survey contributed to the proposed definition for 
RM. We also comment on our considerations in formulating the criteria and any
issues in making the criteria operational. For the proposed definition for RM and
refractory chronic migraine, patients must meet the International Classification 
of Headache Disorders, Second Edition criteria for migraine or chronic migraine, 
respectively. Headaches need to cause significant interference with function or
quality of life despite modification of triggers, lifestyle factors, and adequate
trials of acute and preventive medicines with established efficacy. The
definition requires that patients fail adequate trials of preventive medicines,
alone or in combination, from at least 2 of 4 drug classes including:
beta-blockers, anticonvulsants, tricyclics, and calcium channel blockers.
Patients must also fail adequate trials of abortive medicines, including both a
triptan and dihydroergotamine (DHE) intranasal or injectable formulation and
either nonsteroidal anti-inflammatory drugs (NSAIDs) or combination analgesic,
unless contraindicated. An adequate trial is defined as a period of time during
which an appropriate dose of medication is administered, typically at least 2
months at optimal or maximum-tolerated dose, unless terminated early due to
adverse effects. The definition also employs modifiers for the presence or
absence of medication overuse, and with or without significant disability.

PMID: 18484982 [PubMed - indexed for MEDLINE]

239: Headache. 2008 Oct;48(9):1326-36. Epub 2008 May 14.

Efficacy and tolerability of almotriptan in adolescents: a randomized,
double-blind, placebo-controlled trial.

Linder SL, Mathew NT, Cady RK, Finlayson G, Ishkanian G, Lewis DW.

Dallas Pediatric Neurology Associates, Dallas, TX 75230-8601, USA.

OBJECTIVES: To assess the efficacy and safety of almotriptan 6.25 mg, 12.5 mg,
and 25 mg vs placebo for acute migraine treatment in adolescents. PATIENTS AND
METHODS: In this double-blind, placebo-controlled, parallel-group, multicenter
trial, 866 patients aged 12 to 17 years with a >1 year history of migraine (per
International Headache Society criteria) were randomized to treat one migraine
headache with almotriptan 6.25 mg, 12.5 mg, 25 mg, or placebo. The primary
efficacy endpoint was headache pain relief 2 hours after dosing, adjusted for
baseline severity, with absence of nausea, photophobia, and phonophobia 2 hours
after dosing as coprimary endpoints. RESULTS: The 2-hour pain-relief rate was
significantly higher with almotriptan 25 mg compared with placebo (66.7% vs
55.3%; P = .022). The incidence of nausea, photophobia, and phonophobia at 2
hours (adjusted for baseline pain intensity) for the almotriptan 25 mg and
placebo groups was not significantly different. The 2-hour pain-relief rates
(unadjusted) were significantly higher with almotriptan 6.25 mg (71.8%), 12.5 mg 
(72.9%), and 25 mg (66.7%) than with placebo (55.3%; P = .001, P < .001, and P = 
.028, respectively). Rates for sustained pain relief also were significantly
greater with almotriptan 6.25 mg (67.2%), 12.5 mg (66.9%), and 25 mg (64.5%) than
with placebo group (52.4%), P < .01 for the 6.25- and 12.5-mg doses and P < .05
for the 25-mg dose. Age group subanalysis demonstrated significantly greater
2-hour pain-relief rates with all 3 doses of almotriptan compared with placebo
for patients aged 15 to 17 years, a significantly lower incidence of photophobia 
and phonophobia at 2 hours with almotriptan 12.5 mg compared with placebo for
patients aged 15 to 17 years, and a significantly lower incidence of photophobia 
with almotriptan 12.5 mg compared with placebo for those aged 12 to 14 years.
Almotriptan treatment was well tolerated, with the most common adverse events
(>2%) of nausea, dizziness, and somnolence. CONCLUSIONS: Oral almotriptan was
efficacious for relieving migraine headache pain in adolescents, with the 12.5-mg
dose associated with the most favorable efficacy profile with respect to
relieving headache pain and associated symptoms of migraine (photophobia and
phonophobia). Almotriptan treatment was well tolerated in this adolescent
population.

Publication Types: 
    Multicenter Study
    Randomized Controlled Trial

PMID: 18484981 [PubMed - indexed for MEDLINE]

240: Neurol Sci. 2008 Apr;29(2):113-5. Epub 2008 May 16.

ATP1A2 gene mutations are not present in two sisters with basilar-type migraine
associated with menses.

Cologno D, d'Onofrio F, Esposito T, Gianfrancesco F, Petretta V, Casucci G,
Frediani F, Buzzi MG, Bussone G.

Institute of Clinical Neurophysiology Department of Neuroscience, Azienda
Ospedaliero-Universitaria Ospedali Riuniti, Foggia, Italy.
danielacologno@virgilio.it

Basilar-type migraine (BM) and hemiplegic migraine are clinically distinct
subtypes of migraine with aura, however they do share clinical features and it is
possible they may share genetic bases. In recent years, ATP1A2 and other gene
mutations have been discovered in familial and sporadic hemiplegic migraine. More
recently, an ATP1A2 mutation has been identified in an Italian family with BM. In
this study we document the absence of ATP1A2 mutations in two Italian sisters
with menstrual BM, suggesting that other genes are involved in the condition.

Publication Types: 
    Case Reports

PMID: 18483709 [PubMed - indexed for MEDLINE]

241: Cephalalgia. 2008 Jul;28(7):714-22. Epub 2008 May 13.

Comment in:
    Cephalalgia. 2008 Jul;28(7):681-2.

Involvement of corticotrophin-releasing factor and orexin-A in chronic migraine
and medication-overuse headache: findings from cerebrospinal fluid.

Sarchielli P, Rainero I, Coppola F, Rossi C, Mancini M, Pinessi L, Calabresi P.

Neurologic Clinic, University of Perugia, Perugia, Italy. neuro.pg@tiscalinet.it

The study set out to investigate the role of corticotrophin-releasing factor
(CRF) and orexin-A in chronic migraine (CM) and medication-overuse headache
(MOH). Twenty-seven patients affected by CM and 30 with MOH were enrolled.
Control CSF specimens were obtained from 20 age-matched subjects who underwent
lumbar puncture for diagnostic purposes, and in all of them CSF and blood tests
excluded central nervous system or systemic diseases. Orexin-A and CRF were
determined by radioimmunoassay methods. Significantly higher levels of orexin-A
and CRF were found in the CSF of MOH and to a lesser extent in patients with CM
compared with control subjects (orexin-A: P < 0.001 and P < 0.02; CRF: P < 0.002 
and P < 0.0003). A significant positive correlation was also found between CSF
orexin-A values and those of CRF (R = 0.71; P < 0.0008), monthly drug intake
group (R = 0.39; P < 0.03) and scores of a self-completion 10-item instrument to 
measure dependence upon a variety of substances, the Leeds Dependence
Questionnaire (LDQ) in the MOH group (R = 0.68; P < 0.0003). The significantly
higher orexin-A levels found in CM and MOH can be interpreted as a compensatory
response to chronic head pain or, alternatively, as an expression of hypothalamic
response to stress due to chronic pain. A potential role for orexin-A in driving 
drug seeking in MOH patients through activation of stress pathways in the brain
can also be hypothesized.

PMID: 18479471 [PubMed - indexed for MEDLINE]

242: Headache. 2008 Jun;48(6):959-61. Epub 2008 May 9.

Rebound abdominal pain: noncephalic pain in abdominal migraine is exacerbated by 
medication overuse.

Newman LC, Newman EB.

Headache Institute, Roosevelt Hospital Center, New York, NY, USA.

Abdominal migraine usually has its onset during childhood or adolescence and
resolves in adulthood, often being replaced by typical migraine headaches.
Rarely, migraine headache and recurrent abdominal pain coexist in some patients
during adulthood. We report a patient who developed abdominal migraine without
headaches beginning for the first time at the age of 22 years. The abdominal
symptoms increased in frequency coincident with medication overuse and resolved
after the overuse was treated. Analgesic overuse may cause a worsening of
noncephalic pain in patients with extra-cephalic variants of migraine.

Publication Types: 
    Case Reports

PMID: 18479426 [PubMed - indexed for MEDLINE]

243: Headache. 2008 Jun;48(6):791-8. Epub 2008 May 9.

Toward an epidemiology of refractory migraine: current knowledge and issues for
future research.

Lipton RB, Bigal ME.

Departments of Neurology & Epidemiology and Population Health, Albert Einstein
College of Medicine, and The Montefiore Headache Center, Bronx, NY, USA.

The proposed definitions for refractory migraine (RM) and refractory chronic
migraine (R-CM) comprise 5 key components that must be operationalized for
epidemiologic research. Persons with RM or R-CM must meet the second edition of
the International Classification of Headache Disorders criteria for migraine or
chronic migraine. They must experience significant interference with function or 
quality of life due to headaches. This interference must be present despite
adequate treatment in 3 domains: modification of triggers and lifestyle factors, 
acute medication, and preventive medicines. The epidemiologic data which address 
these 5 components will be reviewed herein though specifically designed studies
will be required to fully explore RM and R-CM. In addition, 2 "modifiers" of RM
and R-CM have been proposed; one addresses medication overuse and the other
considers disability based on a Migraine Disability Assessment score of 11 or
greater. The epidemiology of these modifiers is discussed.

PMID: 18479422 [PubMed - indexed for MEDLINE]

244: Headache. 2008 Jun;48(6):770-7. Epub 2008 May 9.

Refractory headache: historical perspective, need, and purposes for an
operational definition.

Schulman EA, Brahin EJ.

Lankenau Institute for Medical Research, Wynnewood, PA, USA.

The study of migraine has yielded many benefits for headache patients. Little
research, however, has been performed on refractory migraine (RM) headache, a
term often used interchangeably with intractable migraine. This may be a
consequence of a lack of a well-accepted definition. In a survey performed by the
Refractory Headache Special Interest Section (RHSIS) on the American Headache
Society (AHS) in 2006, 58% of the members agreed that a definition for refractory
headache should be added to the International Classification of Headache
Disorders-2. A PubMed search identified 21 articles that defined refractory or
intractable headache/migraine. Sixteen (76%) defined the term "refractory" and 5 
(24%) defined the term "intractable." Many of these definitions did not address
the need for an adequate trial of a preventive medicine, disability, and
medication overuse. An operational definition will allow us to better
characterize the disorder, address unmet medical needs, and identify the most
effective treatments. RHSIS of the AHS has proposed a definition of RM. It is our
hope that this definition will spur interest in this entity and will lead to
further research in the area.

Publication Types: 
    Historical Article

PMID: 18479419 [PubMed - indexed for MEDLINE]

245: J Neural Transm. 2008 Sep;115(9):1321-5. Epub 2008 May 14.

Investigation of the functional brain-derived neurotrophic factor gene variant
Val66MET in migraine.

Marziniak M, Herzog A, Mössner R, Sommer C.

Department of Neurology, University of Würzburg, Würzburg, Germany.
marzinia@uni-muenster.de

Experimental studies and investigations of the cerebrospinal fluid in migraineurs
have suggested an involvement of brain-derived neurotrophic factor (BDNF) in
migraine pathophysiology. In a case-control study approach, the functional
Val66MET polymorphism (rs6265) of the BDNF gene was investigated in 265 migraine 
patients and 153 controls. Genotype and allele frequencies did not differ between
healthy subjects and migraineurs. A subgroup analysis for the occurrence of aura 
or clinical characteristics, including the number of attacks, did not reveal a
positive association for the investigated polymorphism. Our data argue against a 
role of this well characterized BDNF gene variant as a risk factor in migraine.

PMID: 18478177 [PubMed - indexed for MEDLINE]

246: Curr Opin Otolaryngol Head Neck Surg. 2008 Jun;16(3):265-9.

Allergy and migraine: is there a connection?

Mehle ME.

Northeastern Ohio Universities College of Medicine, Rootstown, Ohio, USA.
dr.m.mehle@att.net

PURPOSE OF REVIEW: In the last 10 years, otolaryngologists and allergists have
become increasingly aware of migraine headaches in their practices. This is
partially due to a better understanding of the high incidence of migraine and a
realization that the majority of patients presenting as 'sinus headache' are
actually suffering from migraine headaches. Considering that the incidence of
migraine is approximately 20% in women and 6% in men and that 10-30% of people
have allergies (US Department of Health and Human Services. Evidence
Report/Technology Assessment No. 54; May 2002. AHRQ Publication No. 02-E024. pp. 
1-198), there is obviously a large population of patients who suffer from both
conditions. The question then arises that are migraine and allergy comorbid
conditions, or is any association between the two a random occurrence? RECENT
FINDINGS: The present study addresses this association, which has remained
controversial for over 100 years. Newer studies focusing on familial trends,
shared biochemical pathways and underlying mechanisms are presented. RELEVANCE:
This study will provide a foundation to support future clinical studies.

Publication Types: 
    Review

PMID: 18475083 [PubMed - indexed for MEDLINE]

247: Curr Med Res Opin. 2008 Jun;24(6):1711-8. Epub 2008 May 7.

Healthcare provider-patient communication and migraine assessment: results of the
American Migraine Communication Study, phase II.

Hahn SR, Lipton RB, Sheftell FD, Cady RK, Eagan CA, Simons SE, Nelson MR.

Albert Einstein College of Medicine, Bronx, NY, USA.

OBJECTIVE: The American Migraine Communication Study I (AMCS I) revealed
communication deficits illustrated by differing healthcare professional (HCP) and
patient reports about issues such as impairment and frequency. AMCS II was
designed to assess an intervention using open-ended questions about impairment
and 'ask-tell-ask' sequences to confirm headache frequency in days versus
attacks. RESEARCH DESIGN AND METHODS: HCPs who participated in AMCS I completed
an internet-based intervention. Researchers were sent to HCPs' offices, and
patients likely to discuss migraine were recruited immediately prior to
normally-scheduled appointments. Post-consent, visits were recorded without a
researcher present. Separate post-visit interviews were conducted with all
parties. All interactions were transcribed. MAIN OUTCOME MEASURES: Transcripts
were analyzed using validated sociolinguistic techniques, and study results were 
compared to AMCS I. RESULTS: HCPs assessed impairment in 90% of interactions
compared to 10% in AMCS I (p<0.0001) and used open-ended questions to assess
impairment in 55% of visits (95% CI: 0.4261-0.6598). Impairment between attacks
was discussed in 37% of visits vs. 0% in AMCS I (p<0.0001). HCPs completed full
ask-tell-ask sequences in 29% of visits (95% CI: 0.1921-0.4070). AMCS II
contained more discussions of migraine preventive therapy with appropriate
candidates compared to AMCS I (74 vs. 50%; p=0.069) without statistically
increasing median visit length (9:36 vs. 11:00; p=0.668). Post-visit, HCPs and
patients were often aligned about impairment and frequency and reported high
levels of satisfaction. CONCLUSIONS: Although further research with a larger
sample is needed, a brief, internet-based intervention appears to promote
positive communication changes not associated with increased visit length.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 18471346 [PubMed - indexed for MEDLINE]

248: Headache. 2008 May;48(5):730-1; discussion 732.

A pivotal moment in 50 years of headache history: the first American Migraine
Study.

Tepper SJ.

Yale University School of Medicine.

OBJECTIVE: To describe the magnitude and distribution of the public health
problem posed by migraine in the United States by examining migraine prevalence, 
attack frequency, and attack-related disability by gender, age, race, household
income, geographic region, and urban vs rural residence. DESIGN: In 1989, a
self-administered questionnaire was sent to a sample of 15,000 households. A
designated member of each household initially responded to the questionnaire.
Each household member with severe headache was asked to respond to detailed
questions about symptoms, frequency, and severity of headaches. SETTING: A sample
of households selected from a panel to be representative of the US population in 
terms of age, gender, household size, and geographic area. PARTICIPANTS: After a 
single mailing, 20,468 subjects (63.4% response rate) between 12 and 80 Years of 
age responded to the survey. Respondents and nonrespondents did not differ by
gender, household income, region of the country, or urban vs rural status. Whites
and the elderly were more likely to respond. Migraine headache cases were
identified on the basis of reported symptoms using established diagnostic
criteria. RESULTS: In total, 17.6% of females and 5.7% of males were found to
have 1 or more migraine headaches per year. The prevalence of migraine varied
considerably by age and was highest in both men and women between the ages of 35 
to 45 years. Migraine prevalence was strongly associated with household income;
prevalence in the lowest-income group (less than $10,000) was more than 60%
higher than in the 2 highest-income groups (greater than or equal to $30,000).
The proportion of migraine sufferers who experienced moderate to severe
disability was not related to gender, age, income, urban vs rural residence, or
region of the country. In contrast, the frequency of headaches was lower in
higher-income groups. Attack frequency was inversely related to disability.
CONCLUSIONS: A projection to the US population suggests that 8.7 million females 
and 2.6 million males suffer from migraine headache with moderate to severe
disability. Of these, 3.4 million females and 1.1 million males experience 1 or
more attacks per month. Females between ages 30 and 49 years from lower-income
households are at especially high risk of having migraines and are more likely
than other groups to use emergency care services for their acute condition.

PMID: 18471125 [PubMed - indexed for MEDLINE]

249: Headache. 2008 May;48(5):726-7.

A knockout punch: C. Miller Fisher's migraine accompaniments.

Young WB.

Department of Neurology and Jefferson Headache Center, Thomas Jefferson
University, Philadelphia, Pennsylvania, USA.

Occasionally patients in the stroke age-bracket over 40 years have unexplained
transient cerebral ischemic attacks in association with normal cerebral
angiograms. From this group, 120 have been collected in whom the transient
episodes resembled the neurological accompaniments of migraine. According to
symptoms, the patients were categorized as follows: visual accompaniments
(patients with only ordinary scintillating scotoma were excluded), 25; visual and
paresthesias, 18; visual and speech disturbance, 7; visual, and brain stem
symptoms, 14; visual, paresthesias, and speech disturbance, 7; visual,
paresthesias, speech disturbance, and paresis, 25; recurrence of old stroke
deficit, 9; miscellaneous, 8. In establishing the diagnosis, angiography is
advisable in all but classical cases. Typical of migrainous accompaniments are
the build-up and migration of visual scintillations, the march of paresthesia,
and progression from one accompaniment to another, characteristics that do not
occur in thrombosis and embolism. Diagnosis facilitated when 2 or more similar
episodes have occurred or migraine-like scintillations are present. Headache
occurred in 50% of cases. Other cerebrovascular processes, coagulation disorders,
and cerebral seizures must be ruled out.

PMID: 18471122 [PubMed - indexed for MEDLINE]

250: Headache. 2008 May;48(5):697-700.

Migraine genetics: a fascinating journey towards improved migraine therapy.

Ferrari MD.

Leiden Centre for Translational Neuroscience, Leiden University Medical Centre,
The Netherlands.

The study of migraine genetics promises to deliver significant changes to
migraine therapy. Dr. Ferrari explores the emergence of the field and its
importance to headache medicine.

Publication Types: 
    Historical Article

PMID: 18471114 [PubMed - indexed for MEDLINE]

251: Headache. 2008 May;48(5):688-90.

Defining a pathway to discovery from bench to bedside: the trigeminovascular
system and sensitization.

Moskowitz MA.

Neuroscience Center and the Stroke and Neurovascular Regulation Laboratory,
Department of Radiology, Massachusetts General Hospital, Harvard Medical School, 
Boston, MA, USA.

Over the past 50 years, investigations into the pathophysiology of migraine have 
yielded discoveries that both illuminate the various components of the "migraine 
process" and lend promise to the identification of new therapies unheralded in
their specificity and effectiveness.

Publication Types: 
    Historical Article

PMID: 18471111 [PubMed - indexed for MEDLINE]

252: Headache. 2008 May;48(5):685-7.

The discovery and development of the triptans, a major therapeutic breakthrough.

Humphrey PP.

Theravance Inc., South San Francisco, California, USA.

The drug discovery programs that led to the development of the triptans were
determined by the membership of the American Headache Society to be the most
important breakthrough in headache medicine in the last 50 years. Dr. Humphrey,
who spearheaded the drug discovery, recounts the pioneering work that took place 
and examines its therapeutic impact.

Publication Types: 
    Historical Article

PMID: 18471110 [PubMed - indexed for MEDLINE]

253: Headache. 2008 May;48(5):678-9.

Headache progress in Canada over the decades.

Becker WJ.

Department of Clinical Neurosciences, University of Calgary, Calgary, Canada.

As elsewhere in the world, migraine and other headache disorders have always
produced very significant disability amongst Canadians. Over the last 50 years,
progress has been made by health professionals to improve the care received by
patients with headache, and to reduce the headache-related burden carried by
patients and their families. Milestones in this progress have included programs
for better education for the public, for neurologists, and for other physicians
about migraine. Highlights in the Canadian battle against migraine and other
headaches include those listed below.

Publication Types: 
    Historical Article

PMID: 18471108 [PubMed - indexed for MEDLINE]

254: J Cereb Blood Flow Metab. 2008 Aug;28(8):1399-421. Epub 2008 May 7.

Migraine and ischemic stroke: a debated question.

Del Zotto E, Pezzini A, Giossi A, Volonghi I, Padovani A.

Dipartimento di Scienze Biomediche e Biotecnologie, Università degli Studi di
Brescia, Brescia, Italy. betty.delzotto@tin.it

Numerous epidemiologic observations reporting high prevalence of migraine among
young individuals with stroke as well as dysfunction of cerebral arteries during 
migraine attacks prompt speculation on the existence of a comorbidity between the
two disorders. The recent finding of silent infarct-like brain lesions in
migraineurs reinforced this hypothesis and raised questions on whether migraine
may be a progressive disorder rather than simply an episodic disorder. Stroke can
occur during the course of migraine attacks with aura, supporting the assumption 
of a causal relation between the two diseases. Migraine may accentuate other
existing risk factors for stroke, and both jointly increase the risk of cerebral 
ischemia outside of migraine attacks. In this regard, the role of migraine might 
be that of predisposing condition for cerebral ischemia. Migraine and ischemic
stroke may be the end phenotype of common pathogenic mechanisms. Evidence of a
migraine-stroke relation in cases of specific disorders, such as CADASIL
(cerebral autosomal-dominant arteriopathy with subcortical infarcts and
leukoencephalopathy) and MELAS (mitochondrial myopathy, encephalopathy, lactic
acidosis, and stroke-like episodes), strongly supports this concept. Finally,
acute focal cerebral ischemia can trigger migraine attacks, and, thus, migraine
may be the consequence of stroke. In this paper, we will review contemporary
epidemiologic studies, discuss potential mechanisms of migraine-induced stroke
and comorbid ischemic stroke, and pose new research questions.

Publication Types: 
    Review

PMID: 18461080 [PubMed - indexed for MEDLINE]

255: Curr Neurol Neurosci Rep. 2008 Mar;8(2):100-7.

Chronic daily headache: transformational migraine, chronic migraine, and related 
disorders.

Saper JR.

Michigan Head Pain & Neurological Institute, 3120 Professional Drive, Ann Arbor, 
MI 48104, USA. jrsaper@aol.com

Chronic daily headache is an important category of headache illness that affects 
4% of the general population. Within this classification are four chronic
headache entities: chronic migraine/transformational migraine, chronic
tension-type headache, hemicrania continua, and new daily persistent headache.
Chronic migraine/transformational migraine is the most common of these entities
and is frequently accompanied by medication overuse, neurobehavioral comorbidity,
and disability. The terminology and classification of this entity continue to be 
confounding. Current research is directed at identifying factors that might
promote the progression of this disorder from episodic migraine to daily or
almost daily headache, and at identifying the best approaches to treatment, which
include both pharmacotherapeutic and non-medicinal interventions. Patients with
intractable cases are often hospitalized as a consequence of the convergence of
several factors that make outpatient management unlikely to succeed.

Publication Types: 
    Review

PMID: 18460277 [PubMed - indexed for MEDLINE]

256: Cephalalgia. 2008 Jul;28(7):696-704. Epub 2008 May 5.

Sympathetic skin responses from frontal region in migraine headache: a pilot
study.

Yildiz SK, Yildiz N, Korkmaz B, Altunrende B, Gezici AR, Alkoy S.

Department of Neurology, Izzet Baysal Medical Faculty, Abant Izzet Baysal
University, Turkey. serpilkuyucu@hotmail.com

Frontal sympathetic skin responses (F-SSRs) were recorded to investigate
sympathetic nervous system activity in migraine headache (MH). Thirty-five
patients with unilateral MH and 10 healthy volunteers were studied by evoking
bilateral F-SSRs with electrical stimulation of the median nerve in attack,
post-attack and interictal periods. The mean latencies were longer and the
maximum amplitudes were smaller on the symptomatic side compared with the
asymptomatic side (P < 0.05 for both amplitude and latency) in attack and in
interictal periods. In five patients, F-SSRs were absent bilaterally, in four
patients the responses were absent only on the symptomatic side during the attack
period. In the post-attack period, F-SSRs on the symptomatic side had higher
amplitudes and shorter latencies compared with the asymptomatic side (P < 0.01
for both amplitude and latency). There is an asymmetric sympathetic hypofunction 
on the symptomatic side in attack and interictal periods, whereas there is a
hyperfunction in the post-attack period.

PMID: 18460010 [PubMed - indexed for MEDLINE]

257: Cephalalgia. 2008 Aug;28(8):877-86. Epub 2008 May 5.

History of the use of ergotamine and dihydroergotamine in migraine from 1906 and 
onward.

Tfelt-Hansen PC, Koehler PJ.

Danish Headache Centre, Department of Neurology, University of Copenhagen,
Glostrup Hospital, Glostrup, Denmark. tfelt@inet.uni2.dk

Dale showed in 1906 in a seminal work that ergot inhibits the pressor effect of
adrenaline. Stoll at Sandoz isolated ergotamine from ergot in 1918. Based on the 
belief that migraine was due to increased sympathetic activity, ergotamine was
first used in the acute treatment of migraine by Maier in Switzerland in 1925. In
1938 Graham and Wolff demonstrated the parallel decrease of temporal pulsations
and headache after ergotamine i.v. This inspired the vascular theory of Wolff: an
initial cerebral vasoconstriction followed by an extracranial vasodilation.
Dihydroergotamine (DHE) was introduced as an adrenolytic agent in 1943. It is
still in use parenterally and by the nasal route. Before the triptan era
ergotamine and DHE had widespread use as the only specific antimigraine drugs.
From 1950 the world literature on ergotamine was dominated by two adverse events:
ergotamine overuse headache and the relatively rare overt ergotism. Recently,
oral ergotamine, which has an oral bioavailability of < 1%, has been inferior to 
oral triptans in randomized clinical trials. A European Consensus in 2000
concluded that ergotamine is not a drug of first choice. In an American review of
2003 it was suggested that ergotamine may be considered in the treatment of
selected patients with moderate to severe migraine.

Publication Types: 
    Historical Article

PMID: 18460007 [PubMed - indexed for MEDLINE]

258: Cephalalgia. 2008 Jul;28(7):689-95. Epub 2008 May 5.

Increased cerebral vasomotor reactivity in migraine with aura: an autoregulation 
disorder? A transcranial Doppler and near-infrared spectroscopy study.

Vernieri F, Tibuzzi F, Pasqualetti P, Altamura C, Palazzo P, Rossini PM,
Silvestrini M.

Neurologia Clinica, Università Campus Bio-Medico di Roma, Via Alvaro del Portillo
200, Roma 00128, Italy. f.vernieri@unicampus.it

Migraine with aura (MA) is associated with changes in cerebral blood flow (CBF), 
whereas the role of cerebral autoregulation is uncertain. This study aimed to
evaluate basal CBF, cerebral blood volume (CBV) and vasomotor reactivity (VMR) in
MA patients. Twenty-one controls and 16 MA patients (eight with side
predominance) underwent simultaneous examination of flow velocity in the middle
cerebral arteries by transcranial Doppler (TCD) and of near-infrared spectroscopy
(NIRS) parameters [oxygen haemoglobin saturation: oxygen%, and total haemoglobin 
content (THC)] at rest and after hypercapnia. Cerebral VMR, THC and oxygen%
increases were significantly greater on the predominant compared with the
non-predominant migraine side, with both sides of patients without side
predominance and with controls. These findings suggest altered autoregulation in 
MA patients, possibly secondary to impaired cerebrovascular autonomic control.
Simultaneous TCD and NIRS investigation could represent a non-invasive approach
to evaluate cerebral haemodynamics at the cortical and subcortical level.

PMID: 18460006 [PubMed - indexed for MEDLINE]

259: Cephalalgia. 2008 Jul;28(7):734-43. Epub 2008 May 5.

Friendships and social interactions of school-aged children with migraine.

Vannatta K, Getzoff EA, Gilman DK, Noll RB, Gerhardt CA, Powers SW, Hershey AD.

Center for Biobehavioral Health, The Research Institute at Nationwide Children's 
Hospital and Department of Pediatrics, Ohio State University College of Medicine,
Columbus, OH 43205, USA. Kathryn.Vannatta@nationwidechildrens.org

We set out to evaluate the friendships and social behaviour of school-aged
children with migraine. Concern exists regarding the impact of paediatric
migraine on daily activities and quality of life. We hypothesized that children
with migraine would have fewer friends and be identified as more socially
sensitive and isolated than comparison peers. Sixty-nine children with migraine
participated in a school-based study of social functioning. A comparison sample
without migraine included classmates matched for gender, race and age. Children
with migraine had fewer friends at school; however, this effect was limited to
those in elementary school. Behavioural difficulties were not found.
Middle-school students with migraine were identified by peers as displaying
higher levels of leadership and popularity than comparison peers. Concern may be 
warranted about the social functioning of pre-adolescent children with migraine; 
however, older children with migraine may function as well as or better than
their peers.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 18460004 [PubMed - indexed for MEDLINE]

260: Mol Neurobiol. 2008 Feb;37(1):83-90. Epub 2008 May 6.

Molecular mechanisms of sensitization of pain-transducing P2X3 receptors by the
migraine mediators CGRP and NGF.

Giniatullin R, Nistri A, Fabbretti E.

Neurobiology Sector and Italian Institute of Technology Unit, International
School for Advanced Studies (SISSA), 34014 Trieste, Italy.

Migraine headache originates from the stimulation of nerve terminals of
trigeminal ganglion neurons that innervate meninges. Characteristic features of
migraine pain are not only its delayed onset but also its persistent duration.
Current theories propose that endogenous substances released during a migraine
attack (the neuropeptide calcitonin gene-related peptide [CGRP] and the
neurotrophin nerve growth factor [NGF]) sensitize trigeminal neurons to transmit 
nociceptive signals to the brainstem, though the mechanisms remain poorly
understood. Recent studies indicate that acute, long-lasting sensitization of
trigeminal nociceptive neurons occurs via distinct processes involving enhanced
expression and function of adenosine triphosphate (ATP)-gated P2X3 receptors
known to play a role in chronic pain. In particular, on cultured trigeminal
neurons, CGRP (via protein kinase A-dependent signaling) induces a slowly
developing upregulation of the ionic currents mediated by P2X3 receptors by
enhancing receptor trafficking to the neuronal membrane and activating their gene
transcription. Such upregulated receptors acquire the ability to respond
repeatedly to extracellular ATP, thus enabling long-lasting signaling of painful 
stimuli. In contrast, NGF induces rapid, reversible upregulation of P2X3 receptor
function via protein kinase C phosphorylation, an effect counteracted by anti-NGF
antibodies. The diverse intracellular signaling pathways used by CGRP and NGF
show that the sensitization of P2X3 receptor function persists if the action of
only one of these migraine mediators is blocked. These findings imply that
inhibiting a migraine attack might be most efficient by a combinatorial approach.
The different time domains of P2X3 receptor modulation by NGF and CGRP suggest
that the therapeutic efficacy of novel antimigraine drugs depends on the time of 
administration.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 18459072 [PubMed - indexed for MEDLINE]

261: Expert Rev Neurother. 2008 May;8(5):759-68.

Translational imaging studies of cortical spreading depression in experimental
models for migraine aura.

Smith JM, James MF, Fraser JA, Huang CL.

Physiological Laboratory, University of Cambridge, Downing Street, Cambridge CB2 
3EG, UK. justin@justin-smith.co.uk

This perspective discusses cortical spreading depression (CSD) phenomena and
their translational significance for human migraine aura and the peri-infarct
events following cerebral ischemia and injury. They begin with interstitial K(+) 
release and accumulation following neuronal stimulation, and a buffering
astrocytic K(+) influx and remote liberation propagating waves of neuronal
hyperexcitability and depression. Diffusion-weighted echoplanar MRI demonstrates 
CSD features in gyrencephalic brains recapitulating human migraine aura, spatial 
and temporal features of single primary events and multiple secondary events,
their stimulus dependence, pharmacological properties, and their relationship to 
blood oxygenation level-dependent signals and late cerebrovascular changes. The
article finally explores prospects for physiological studies of CSD gaining
fuller insights both into mechanisms underlying the pathology of the
corresponding human condition and possible approaches to management.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 18457533 [PubMed - indexed for MEDLINE]

262: Expert Rev Neurother. 2008 May;8(5):723-36.

Frovatriptan for the acute treatment of migraine and prevention of predictable
menstrual migraine.

Elkind AH, MacGregor EA.

Elkind Headache Center, 12 North Seventh Avenue, Mount Vernon, NY 10550, USA.
arthur.elkind@verizon.net

Frovatriptan is a 5-HT(1B/1D) receptor agonist that belongs to the triptan
therapeutic class. Relative to other triptans, frovatriptan has a long half-life 
(26 h) and a low incidence of migraine recurrence (17%). Frovatriptan is
indicated for the acute treatment of migraine with or without aura, and has a
relatively good safety and tolerability profile. Recent studies have also shown
that a 6-day regimen of frovatriptan scheduled during the perimenstrual period
significantly reduced the incidence and severity of menstrual migraine (MM;
attacks that regularly start day -2 to +3 relative to menses). Prevention may be 
important because MM attacks have been characterized as being of longer duration,
more severe and more refractory to treatment than non-MM attacks.

Publication Types: 
    Review

PMID: 18457529 [PubMed - indexed for MEDLINE]

263: Genomics. 2008 Jun;91(6):503-7. Epub 2008 May 2.

Replication study of the insulin receptor gene in migraine with aura.

Netzer C, Freudenberg J, Heinze A, Heinze-Kuhn K, Goebel I, McCarthy LC, Roses
AD, Göbel H, Todt U, Kubisch C.

Institute of Human Genetics, University of Cologne, 50931 Cologne, Germany.

We performed the first replication study for the reported association of the
insulin receptor gene (INSR) with migraine with aura (MA). Two of 35 SNPs
(rs1052371 and rs2860174) reached borderline significance (best uncorrected
allelic p value of 0.052 for rs2860174) in stage 1 of our study (270 MA patients,
280 controls). As rs2860174 was 1 of the 5 SNPs with prior evidence of
association, we also genotyped this SNP in our stage 2 sample (679 MA patients,
368 controls), and it was nonsignificant (allelic p value 0.478). The combined
analysis of our samples showed just a nonsignificant trend for rs2860174 (p=0.1).
However, the joint analysis of our study and the initial study reporting an
association-including 1278 Caucasian MA patients and 1337 Caucasian controls
altogether-displayed a significant allelic p value of 0.005. In conclusion,
further association studies for rs2860174 with even larger numbers of individuals
are required to exclude or confirm definitely a small effect of this SNP on
migraine susceptibility.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 18455362 [PubMed - indexed for MEDLINE]

264: Cephalalgia. 2008 Jun;28(6):640-52.

Cortico-NRM influences on trigeminal neuronal sensation.

Lambert GA, Hoskin KL, Zagami AS.

Institute of Neurological Sciences, University of New South Wales & Prince of
Wales Hospital, Randwick, Australia. g.lambert@unsw.edu.au

We tested the idea that migraine triggers cause cortical activation, which
disinhibits craniovascular sensation through the nucleus raphe magnus (NRM) and
thus produces the headache of migraine. Stimulation of the dura mater and facial 
skin activated neurons in the NRM and the trigeminal nucleus. Stimulation of the 
NRM caused suppression of responses of trigeminal neurons to electrical and
mechanical stimulation of the dura mater, but not of the skin. This suppression
was antagonized by the iontophoretic application of the 5-HT(1B/1D) receptor
antagonist GR127935 to trigeminal neurons. Migraine trigger factors were
simulated by cortical spreading depression (CSD) and light flash. Activity of
neurons in the NRM was inhibited by these stimuli. Multiple waves of CSD
antagonized the inhibitory effect of NRM stimulation on responses of trigeminal
neurons to dural mechanical stimulation but not to skin mechanical stimulation.
The cortico-NRM-trigeminal neuraxis might provide a target for a more universally
effective migraine prophylactic treatment.

PMID: 18454788 [PubMed - indexed for MEDLINE]

265: Cephalalgia. 2008 Jun;28(6):585-97.

Anticonvulsants in migraine prophylaxis: a Cochrane review.

Mulleners WM, Chronicle EP.

Department of Neurology, Canisius Wilhelmina Ziekenhuis, Nijmegen, The
Netherlands. w.mulleners@cwz.nl

Several trials have asserted that some anticonvulsant drugs seem to be useful for
the prophylaxis of migraine, but systematic reviews are sparse. We independently 
searched PubMed, EMBASE and the Cochrane Central Register of Controlled Trials
until 2005, as well as Headache and Cephalalgia through April 2006, for
prospective, controlled trials of anticonvulsant drugs. Data were calculated and 
pooled across studies and expressed as standardized mean differences, odds ratios
and numbers-needed-to-treat. Anticonvulsants, considered as a class, reduce
migraine frequency by about 1.3 attacks per 28 days compared with placebo, and
more than double the number of patients for whom migraine frequency is reduced by
> or = 50% relative to placebo. Sodium valproate/divalproex sodium and topiramate
were better than placebo, whereas acetazolamide, clonazepam, lamotrigine and
vigabatrin were not; gabapentin, in particular, needs further evaluation. Trials 
designed with sufficient power to compare different drugs are also necessary.

Publication Types: 
    Meta-Analysis
    Review

PMID: 18454787 [PubMed - indexed for MEDLINE]

266: Curr Opin Neurol. 2008 Jun;21(3):331-7.

Acute migraine therapy: recent evidence from randomized comparative trials.

Mett A, Tfelt-Hansen P.

Wolters Kluwer Health | Adis, Auckland, New Zealand.

(1) A wide array of data regarding acute migraine treatment are available, but
few trials strictly adhere to International Headache Society guidelines for
patient inclusion criteria.(2) Triptans appear to have similar efficacy profiles,
but among newer triptans, almotriptan offers improved tolerability over
sumatriptan.(3) Combination indomethacin/caffeine/prochlorperazine most likely
has similar therapeutic efficacy to triptan therapy, with further research needed
to complete understanding of any potential differences between these
treatments.(4) Multi-targeted combination therapy with a triptan plus a
non-steroidal anti-inflammatory (NSAID), such as sumatriptan/naproxen sodium, is 
more effective in acute migraine treatment than monotherapy with either agent
alone.(5) It is unclear whether triptans offer clinically relevant benefits over 
aspirin or NSAIDs in migraine patients. Thus NSAIDs, particularly effervescent
aspirin, should be considered the first-line treatment of migraine attacks.

Publication Types: 
    Comparative Study
    Review

PMID: 18451718 [PubMed - indexed for MEDLINE]

267: Curr Opin Neurol. 2008 Jun;21(3):316-22.

Pediatric headache.

Winner P.

Palm Beach Headache Center, Nova Southeastern University, West Palm Beach,
Florida 33407, USA. eneuro@aol.com

PURPOSE OF REVIEW: Headaches occur frequently in the pediatric population and
have a significant impact on both the patient and their family. Migraine, the
most common headache disorder for which patients see a physician, still remains
underdiagnosed and undertreated. Recent studies have revealed the increasing
incidence of migraine and chronic migraine in the pediatric population. RECENT
FINDINGS: Limitations of the present diagnostic criteria for migraine are
presented, and the proposed modifications to these criteria may assist you with
early recognition and ultimate treatment. New acute and preventive migraine
treatment data demonstrating statistically significant benefit for the primary
endpoints will be reviewed in detail. The clinically relevant impact of migraine 
on the pediatric patient documented by the use of the Pediatric Migraine
Disability Assessment and the Pediatric Quality of Life Inventory will be
discussed. SUMMARY: A comprehensive management approach blending the most current
acute, preventive, and biobehavioral treatments will be reviewed. Further
research, with novel study designs, in pediatric headaches is needed to help
reveal additional pathophysiological mechanisms, improve diagnostic criteria, and
advance optimal treatment. Prospective studies are needed to fully evaluate the
efficacy of preventive management in this population and to establish whether
early intervention might slow this disease progression.

Publication Types: 
    Review

PMID: 18451716 [PubMed - indexed for MEDLINE]

268: Curr Opin Neurol. 2008 Jun;21(3):309-15.

Menstrual migraine.

MacGregor EA.

The City of London Migraine Clinic, London, UK. anne.macgregor@sinoragram.co.uk

PURPOSE OF REVIEW: Menstrual migraine is prevalent but it is only recently that
research has specifically addressed the pathophysiology and management of this
disabling condition. RECENT FINDINGS: For many years, menstrual migraine was a
loose term used to describe an undefined association between migraine and
menstruation. The introduction of recognized criteria has improved the diagnosis 
and enabled the study of a more homogenous population of women with this
condition. As a consequence, studies have addressed putative mechanisms,
particularly the association between oestrogen 'withdrawal' and migraine. It is
recognised that other mechanisms have yet to be identified. Studies have
confirmed the efficacy of perimenstrual prophylaxis with triptans and
physiological doses of oestrogen. Despite robust data from randomized
placebo-controlled studies, no treatments are licensed specifically for this
indication at the time of writing. SUMMARY: Recognition of menstrual migraine as 
a specific entity has resulted in improved diagnosis and increased research into 
the condition. However, our understanding of the pathophysiology and the
consequent development of effective management strategies remain limited.

Publication Types: 
    Review

PMID: 18451715 [PubMed - indexed for MEDLINE]

269: Curr Opin Neurol. 2008 Jun;21(3):301-8.

The prognosis of migraine.

Bigal ME, Lipton RB.

Department of Neurology, Albert Einstein College of Medicine, Bronx, New York,
USA. mbigal@aecom.yu.edu

PURPOSE OF THE REVIEW: The prognosis of migraine is poorly studied and research
in this regard is in its infancy. Migraine is a chronic disorder with episodic
attacks with a highly variable long-term prognosis. In many, migraine may have a 
very benign (complete remission) or relatively benign (partial remission)
prognosis. In some, migraine persists and in others, it progresses. RECENT
FINDINGS: A recent population study showed that, over a 1-year period, 84% of the
patients with migraine persisted with this diagnosis (migraine persistence);
around 10% had 1-year complete clinical remission, and 3% had partial remission; 
the other 3% developed chronic migraine. Long-term studies support the concept
that remission increases with age and also that risk factors for progression have
been identified (e.g. medication overuse, obesity, etc.). SUMMARY: Identifying
predictors of migraine prognosis is, therefore, of great scientific and clinical 
interest. Herein we review the prognosis of migraine and risk factors for the
above-mentioned nonexclusive possibilities.

Publication Types: 
    Review

PMID: 18451714 [PubMed - indexed for MEDLINE]

270: Curr Opin Neurol. 2008 Jun;21(3):294-300.

Animal models of migraine headache and aura.

Eikermann-Haerter K, Moskowitz MA.

Stroke and Neurovascular Regulation Laboratory, Department of Radiology,
Massachusetts General Hospital, Harvard Medical School, Charlestown,
Massachusetts 02129, USA.

PURPOSE OF REVIEW: Over the past 30 years, animal models of migraine have led to 
the identification of novel drug targets and drug treatments as well as helped to
clarify a mechanism for abortive and prophylactic drugs. Animal models have also 
provided translational knowledge and a framework to think about the impact of
hormones, genes, and environmental factors on migraine pathophysiology. Although 
most acknowledge that these animal models have significant shortcomings,
promising new drugs are now being developed and brought to the clinic using these
preclinical models. Hence, it is timely to provide a short overview examining the
ways in which animal models inform us about underlying migraine mechanisms.
RECENT FINDINGS: First generation migraine models mainly focused on events within
pain-generating intracranial tissues, for example, the dura mater and large
vessels, as well as their downstream consequences within brain. Upstream events
such as cortical spreading depression have also been modeled recently and provide
insight into mechanisms of migraine prophylaxis. Mouse mutants expressing human
migraine mutations have been genetically engineered to provide an understanding
of familial hemiplegic migraine and possibly, by extrapolation, may reflect on
the pathophysiology of more common migraine subtypes. SUMMARY: Animal models of
migraine reflect distinct facets of this clinically heterogeneous disorder and
contribute to a better understanding of its pathophysiology and pharmacology.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't
    Review

PMID: 18451713 [PubMed - indexed for MEDLINE]

271: Curr Opin Neurol. 2008 Jun;21(3):288-93.

Genetics of migraine: an update with special attention to genetic comorbidity.

Stam AH, van den Maagdenberg AM, Haan J, Terwindt GM, Ferrari MD.

Department of Neurology, Leiden University Medical Centre, Leiden, The
Netherlands.

PURPOSE OF REVIEW: To highlight recent genetic findings in migraine and discuss, 
new mutations in hemiplegic migraine genes in familial and sporadic cases and
relevant candidate gene association studies. Special attention will be given to
comorbid diseases of migraine. RECENT FINDINGS: Familial hemiplegic migraine
(FHM) is genetically heterogeneous with mutations in the CACNA1A (FHM1), ATP1A2
(FHM2) and SCN1A (FHM3) genes. Nineteen novel ATP1A2 mutations were identified
last year, eleven of them in FHM2 families. A systematic genetic analysis of
patients with sporadic hemiplegic migraine revealed five mutations in this gene, 
which has implications for genetic counselling. The identification of a second
FHM3 SCN1A mutation definitely established SCN1A as a migraine gene. The
identification of TREX1 mutations in families with retinal vasculopathy and
associated diseases such as migraine may provide new insights in migraine
pathophysiology. SUMMARY: Many novel ATP1A2 mutations were identified in patients
with familial and sporadic hemiplegic migraine. In sporadic patients, ATP1A2
screening has the highest chance of finding a causal mutation. A second FHM3
mutation definitely established the epilepsy SCN1A gene as a migraine gene. The
discovery of genes in monogenic diseases in which migraine is prominent may lead 
to new insights in the molecular pathways involved in migraine pathophysiology.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 18451712 [PubMed - indexed for MEDLINE]

272: J Headache Pain. 2008 Jun;9(3):151-7. Epub 2008 Apr 25.

Involvement of calcitonin gene-related peptide in migraine: regional cerebral
blood flow and blood flow velocity in migraine patients.

Lassen LH, Jacobsen VB, Haderslev PA, Sperling B, Iversen HK, Olesen J,
Tfelt-Hansen P.

Department of Neurology, Glostrup Hospital, University of Copenhagen, Glostrup,
Denmark.

Calcitonin gene-related peptide (CGRP)-containing nerves are closely associated
with cranial blood vessels. CGRP is the most potent vasodilator known in isolated
cerebral blood vessels. CGRP can induce migraine attacks, and two selective CGRP 
receptor antagonists are effective in the treatment of migraine attacks. It is
therefore important to investigate its mechanism of action in patients with
migraine. We here investigate the effects of intravenous human alpha-CGRP
(halphaCGRP) on intracranial hemodynamics. In a double-blind, cross-over study,
the effect of intravenous infusion of halphaCGRP (2 mug/min) or placebo for 20
min was studied in 12 patients with migraine without aura outside attacks.
Xenon-133 inhalation SPECT-determined regional cerebral blood flow (rCBF) and
transcranial Doppler (TCD)-determined blood velocity (V (mean)) in the middle
cerebral artery (MCA), as well as the heart rate and blood pressure, were the
outcome parameters. No change of rCBF was observed at the end of infusion [1.2%
+/- 1.7 with halphaCGRP, vs. -1.6% +/- 3.1 with placebo (mean +/- SD)] (P =
0.43). V (mean) in MCA decreased to 13.5% +/- 3.6 with halphaCGRP versus 0.6% +/-
1.8 with placebo (P < 0.005). Since rCBF was unchanged, this indicates a dilation
of the MCA. halphaCGRP induced a decrease in MAP (12%) (P < 0.005) and an
increase in heart rate (58%) (P < 0.0001). CGRP dilates cerebral arteries, but
the effect is so small that it is unlikely to be the only mechanism of
CGRP-induced migraine.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial

PMID: 18437288 [PubMed - indexed for MEDLINE]

273: Semin Ophthalmol. 2008 May-Jun;23(3):169-77.

Neuro-ophthalmologic manifestations of primary headache disorders.

Shareef AH, Dafer RM, Jay WM.

Loyola University Medical Center, Maywood, IL 60153, USA.

Headaches are the most common disorders of the central nervous system affecting
46% of the adult population worldwide. Headaches may be lifelong illnesses, often
associated with substantial disability for the individual and the population as a
whole. The International Classification of Headache Disorders (ICHD-II) codifies 
headache disorders into fourteen categories, predominantly primary headaches and 
secondary headache disorders. Primary headache disorders, mainly migraine and
trigeminal autonomic cephalgias (TACs), are frequently associated with
neuro-ophthalmologic manifestations. Ophthalmologists are often the first
physicians to be involved in the deciphering of headache-related visual
disturbances. This article reviews two major primary headache disorders, migraine
and trigeminal autonomic cephalgias, and discusses their neuro-ophthalmic
complications, clinical presentation, and treatment.

Publication Types: 
    Review

PMID: 18432543 [PubMed - indexed for MEDLINE]

274: Curr Protoc Neurosci. 2001 May;Chapter 9:Unit9.1.

Dural inflammation model of migraine pain.

Phebus LA, Johnson KW.

Eli Lilly and Company, Indianapolis, Indiana, USA.

The cause of migraine pain is controversial. One recently proposed theory is that
migraine pain may originate from inflammation of the meninges, particularly the
dural membranes that surround the brain. This theory proposes that, during a
migraine, there is an idiopathic activation of trigeminal sensory afferents,
resulting in nociceptive transmission to the CNS as well as the release of
pro-inflammatory substances in the periphery, particularly the dura. Dural
inflammation is thought to lower the nociceptive threshold of dural afferents and
facilitate nociceptive transmission to the central nervous system. In the
procedure described in this unit, trigeminal sensory afferents are activated by
electrically stimulating the trigeminal ganglion. This stimulation causes
trigeminal peripheral sensory afferents to depolarize, inflammatory substances to
be released from these afferents, and dural inflammation to appear. Dural
inflammation is quantified by measuring plasma protein extravasation. The basic
protocol describes this model in rats, and the alternate protocol describes the
analogous procedure in guinea pigs.

PMID: 18428550 [PubMed - indexed for MEDLINE]

275: J Headache Pain. 2008 Jun;9(3):159-63. Epub 2008 Apr 22.

Prevalence of migraine diagnosis using ID Migraine among university students in
southern Turkey.

Bicakci S, Bozdemir N, Over F, Saatci E, Sarica Y.

Department of Neurology, School of Medicine, University of Cukurova, Adana,
Turkey. sebnemb@cu.edu.tr

In this prospective study, we aimed to determine the prevalence of migraine and
non-migraine headaches using a questionnaire, including ID Migraine, for
university students. The study was designed cross-sectionally and a questionnaire
consisting of 43 questions was applied to 1,256 students. The questionnaire
consisted of questions related to demographic, social, curriculum, housing and
headache characteristics of the subjects. Three-item screening questions of the
ID Migraine test were included at the end of the questionnaire aimed at migraine 
diagnosis. The mean age of 1,256 students (529 females and 727 males) enrolled in
this study was 21.9 +/- 2.1 years (17-31 years). Migraine-type headache was
detected in 265 subjects (21.9%) based on the ID Migraine evaluation. Of these,
145 (54.7%) were female and 120 (45.3%) were male (female/male ratio: 1.2/1).
Non-migraine-type headache was identified in 864 subjects, with 357 females and
507 males. As a conclusion, ID Migraine screening test might be practical and
beneficial when a face-to-face interview is not possible or to pre-determine the 
subjects for a face-to-face interview for migraine diagnosis in larger
populations.

PMID: 18427728 [PubMed - indexed for MEDLINE]

276: J Headache Pain. 2008 Jun;9(3):185-8. Epub 2008 Apr 22.

Headaches related to triptans therapy in patients of migrainous vertigo.

Prakash S, Chavda BV, Mandalia H, Dhawan R, Padmanabhan D.

Department of Neurology, Medical College, SSG Hospital, Gujarat, India.
drprakashs@yahoo.co.in

Dizziness and vertigo are frequently reported by patients with migraine. In
migrainous vertigo (MV), vertigo is causally related to migraine. Patients of MV 
usually have an attenuated or absent headache with their vertigo as compared with
their usual headache of migraine. Here we report three female patients of MV in
which administration of triptan was associated with induction (two patients) or
exacerbation (one patient) of headache with disappearance of vertigo. We suggest 
that headache and vertigo of migraine may be inversely related to each other and 
suppression of one may induce or aggravate the other.

Publication Types: 
    Case Reports

PMID: 18427727 [PubMed - indexed for MEDLINE]

277: Neurology. 2008 Apr 22;70(17):1555-63.

Acute treatment and prevention of menstrually related migraine headache:
evidence-based review.

Pringsheim T, Davenport WJ, Dodick D.

Division of Neurology, University of Toronto, Toronto, Canada.
tamara.pringsheim@utoronto.ca

Menstrually related migraine (MRM) headache is common in women and associated
with substantial disability. Compared to nonmenstrual migraine, MRM attacks are
more severe, longer in duration, and have a poorer response to analgesics. The
purpose of this guideline is to provide a systematic review and meta-analysis of 
the existing therapy trials for MRM and evidence-based recommendations for acute 
and short-term preventive treatment of MRM headache. Prospective, double-blind,
randomized controlled trials of any pharmacologic agent for the symptomatic
relief or prevention of MRM headache were included in the guideline. The main
outcomes considered were the pain response and pain-free response at 2 hours for 
acute treatment trials, and the incidence of MRM or the number of days on which
MRM attacks occurred for short-term prevention trials. Nineteen trials were
included in the analysis. The US Preventive Services Task Force quality criteria 
were used to assess trial quality and to grade recommendations. Based on the
evidence, grade B recommendations can be made for the use of sumatriptan 50 and
100 mg, mefenamic acid 500 mg, and rizatriptan 10 mg for the acute treatment of
MRM. For the preventive treatment of MRM, there are grade B recommendations for
the perimenstrual use of transcutaneous estrogen 1.5 mg, frovatriptan 2.5 mg
twice daily, and naratriptan 1 mg twice daily. Choosing among treatment
strategies must be based on clinical considerations.

Publication Types: 
    Review

PMID: 18427072 [PubMed - indexed for MEDLINE]

278: Am J Hum Genet. 2008 May;82(5):1051-63.

Consistently replicating locus linked to migraine on 10q22-q23.

Anttila V, Nyholt DR, Kallela M, Artto V, Vepsäläinen S, Jakkula E, Wennerström
A, Tikka-Kleemola P, Kaunisto MA, Hämäläinen E, Widén E, Terwilliger J,
Merikangas K, Montgomery GW, Martin NG, Daly M, Kaprio J, Peltonen L, Färkkilä M,
Wessman M, Palotie A.

Biomedicum Helsinki, Research Program in Molecular Medicine, University of
Helsinki, 00290 Helsinki, Finland.

Here, we present the results of two genome-wide scans in two diverse populations 
in which a consistent use of recently introduced migraine-phenotyping methods
detects and replicates a locus on 10q22-q23, with an additional independent
replication. No genetic variants have been convincingly established in migraine, 
and although several loci have been reported, none of them has been consistently 
replicated. We employed the three known migraine-phenotyping methods (clinical
end diagnosis, latent-class analysis, and trait-component analysis) with robust
multiple testing correction in a large sample set of 1675 individuals from 210
migraine families from Finland and Australia. Genome-wide multipoint linkage
analysis that used the Kong and Cox exponential model in Finns detected a locus
on 10q22-q23 with highly significant evidence of linkage (LOD 7.68 at 103 cM in
female-specific analysis). The Australian sample showed a LOD score of 3.50 at
the same locus (100 cM), as did the independent Finnish replication study (LOD
score 2.41, at 102 cM). In addition, four previously reported loci on 8q21,
14q21, 18q12, and Xp21 were also replicated. A shared-segment analysis of
10q22-q23 linked Finnish families identified a 1.6-9.5 cM segment, centered on
101 cM, which shows in-family homology in 95% of affected Finns. This region was 
further studied with 1323 SNPs. Although no significant association was observed,
four regions warranting follow-up studies were identified. These results support 
the use of symptomology-based phenotyping in migraine and suggest that the
10q22-q23 locus probably contains one or more migraine susceptibility variants.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 18423523 [PubMed - indexed for MEDLINE]

279: Eur J Pharmacol. 2008 May 13;585(2-3):313-9. Epub 2008 Mar 15.

Neurovascular pharmacology of migraine.

Maassenvandenbrink A, Chan KY.

Division of Vascular Pharmacology and Metabolic Diseases, Department of Internal 
Medicine, Erasmus MC, University Medical Center Rotterdam, P.O. Box 2040, 3000 CA
Rotterdam, The Netherlands. a.vanharen-maassenvandenbrink@erasmusmc.nl

Migraine is a paroxysmal neurovascular disorder, which affects a significant
proportion of the population. Since dilation of cranial blood vessels is likely
to be responsible for the headache experienced in migraine, many experimental
models for the study of migraine have focussed on this feature. The current
review discusses a model that is based on the constriction of carotid
arteriovenous anastomoses in anaesthetized pigs, which has during the last
decades proven of great value in identifying potential antimigraine drugs acting 
via a vascular mechanism. Further, the use of human isolated blood vessels in
migraine research is discussed. Thirdly, we describe an integrated neurovascular 
model, where dural vasodilatation in response to trigeminal perivascular nerve
stimulation can be studied. Such a model not only allows an in-depth
characterization of directly vascularly acting drugs, but also of drugs that are 
supposed to act via inhibition of vasodilator responses to endogenous
neuropeptides, or of drugs that inhibit the release of these neuropeptides. We
discuss the use of this model in a study on the influence of female sex hormones 
on migraine. Finally, the implementation of this model in mice is considered.
Such a murine model allows the use of genetically modified animals, which will
lead to a better understanding of the ion channel mutations that are found in
migraine patients.

Publication Types: 
    In Vitro
    Review

PMID: 18423447 [PubMed - indexed for MEDLINE]

280: Cephalalgia. 2008 Jun;28(6):598-604. Epub 2008 Apr 16.

Regional grey matter changes in patients with migraine: a voxel-based morphometry
study.

Kim JH, Suh SI, Seol HY, Oh K, Seo WK, Yu SW, Park KW, Koh SB.

Department of Neurology, Korea University Medical Centre, Korea University
College of Medicine, Seoul, Korea.

We used voxel-based morphometry (VBM) to compare grey matter volume (GMV) between
20 migraine patients (five with aura and 15 without aura) with normal
conventional magnetic resonance imaging findings and 33 healthy controls matched 
for age and sex. A separate analysis was also performed to delineate a possible
correlation between the GMV changes and the headache duration or lifetime
headache frequency. When compared with controls, migraine patients had
significant GMV reductions in the bilateral insula, motor/premotor, prefrontal,
cingulate cortex, right posterior parietal cortex, and orbitofrontal cortex (P < 
0.001, uncorrected for multiple comparisons at a voxel level; corrected P < 0.05 
after small volume corrections). All regions of the GMV changes were negatively
correlated with headache duration and lifetime headache frequency (P < 0.05,
Pearson's correlation test). We found evidence for structural grey matter changes
in patients with migraine. Our findings of progressive GMV reductions in relation
to increasing headache duration and increasing headache frequency suggest that
repeated migraine attacks over time result in selective damage to several brain
regions involved in central pain processing.

PMID: 18422725 [PubMed - indexed for MEDLINE]

281: Cephalalgia. 2008 Jun;28(6):626-30. Epub 2008 Apr 16.

Unilateral photophobia or phonophobia in migraine compared with trigeminal
autonomic cephalalgias.

Irimia P, Cittadini E, Paemeleire K, Cohen AS, Goadsby PJ.

Headache Group, Institute of Neurology, The National Hospital for Neurology and
Neurosurgery, London, UK.

Our objective was to compare the presence of self-reported unilateral photophobia
or phonophobia, or both, during headache attacks comparing patients with
trigeminal autonomic cephalalgias (TACs)--including cluster headache,
short-lasting unilateral neuralgiform headache attacks with conjunctival
injection and tearing (SUNCT) and paroxysmal hemicrania--or hemicrania continua, 
and other headache types. We conducted a prospective study in patients attending 
a referral out-patient clinic over 5 months and those admitted for an
intramuscular indomethacin test. Two hundred and six patients were included. In
episodic migraine patients, two of 54 (4%) reported unilateral photophobia or
phonophobia, or both. In chronic migraine patients, six of 48 (13%) complained of
unilateral photophobia or phonophobia, or both, whereas none of the 24 patients
with medication-overuse headache reported these unilateral symptoms, although
these patients all had clinical symptoms suggesting the diagnosis of migraine.
Only three of 22 patients (14%) suffering from new daily persistent headache
(NDPH) experienced unilateral photophobia or phonophobia. In chronic cluster
headache 10 of 21 patients (48%) had unilateral photophobia or phonophobia, or
both, and this symptom appeared in four of five patients (80%) with episodic
cluster headache. Unilateral photophobia or phonophobia, or both, were reported
by six of 11 patients (55%) with hemicrania continua, five of nine (56%) with
SUNCT, and four of six (67%) with chronic paroxysmal hemicrania. Unilateral
phonophobia or photophobia, or both, are more frequent in TACs and hemicrania
continua than in migraine and NDPH. The presence of these unilateral symptoms may
be clinically useful in the differential diagnosis of primary headaches.

PMID: 18422722 [PubMed - indexed for MEDLINE]

282: Cephalalgia. 2008 Jun;28(6):658-63. Epub 2008 Apr 16.

Acute convexity subarachnoid haemorrhage: a cause of aura-like symptoms in the
elderly.

Kleinig TJ, Kiley M, Thompson PD.

Department of Neurology, Royal Adelaide Hospital, Adelaide, SA, Australia.
timothy.kleinig@adelaide.edu.au

Late-life onset aura-like symptoms are not rare and can be potentially
misdiagnosed as transient ischaemic attacks. The cause is often obscure. Four
cases of recurrent aura-like symptoms are presented in whom acute convexity
subarachnoid haemorrhage (SAH) contralateral to symptoms was demonstrated. Three 
experienced subsequent events or groups of events triggered by recurrent SAH.
Negative diffusion-weighted imaging, normal electroencephalography and slow
symptom march with complete resolution argued against ischaemic and epileptic
causes. Aura-like symptoms in the elderly should be investigated with imaging
modalities most sensitive for detecting subarachnoid blood, in particular
gradient echo magnetic resonance imaging.

Publication Types: 
    Case Reports

PMID: 18422720 [PubMed - indexed for MEDLINE]

283: J Hist Neurosci. 2008;17(2):147-59.

Migraine in Gilbertus Anglicus' Compendium medicinae. The cases of MS Sloane 3486
and Wellcome MS 537.

González-Hernández A, Domínguez-Rodríguez MV.

Dept. of Neurology, Hospital Universitario de Gran Canaria Dr. Negrín, Las Palmas
de Gran Canaria (Canary Islands), Spain. ayozegonzalez@eresmas.net

Migraine is a common neurological disorder that has deserved attention since
Antiquity. The English physician Gilbertus Anglicus dedicated a separate chapter 
of his thirteenth-century Compendium medicinae to it, which was then reproduced
in some medical manuscripts from the later Middle Ages. MS Sloane 3486 and
Wellcome MS 537 are two extant Middle English translations of the Latin exemplar 
composed by the end of the fifteenth century. This work will analyze how their
copyists reduced Anglicus' long theoretical dissertations on the aetiology and
semiology of migraine, in order to emphasize the real therapeutic needs of a
nonuniversity-trained audience.

Publication Types: 
    Historical Article

PMID: 18421633 [PubMed - indexed for MEDLINE]

284: Curr Pain Headache Rep. 2008 Jan;12(1):56-61.

Obesity and chronic daily headache.

Bigal ME, Lipton RB.

Department of Neurology, Albert Einstein College of Medicine, 1165 Morris Park
Avenue, Bronx, NY 10461, USA. mbigal@aecom.yu.edu

Population studies suggest that obesity is associated with migraine progression
from episodic to chronic daily headaches. Although not a risk factor for episodic
migraine, obesity is associated with frequent and severe headaches among
migraineurs. We suggest that obesity is an exacerbating factor for migraine. This
association seems to be specific to migraine and does not apply to tension-type
headache. We review the clinical evidence that links obesity and migraine
progression. We then review the potential pathophysiologic mechanisms to support 
this relationship. We close by briefly discussing clinical interventions related 
to obesity and migraine.

Publication Types: 
    Review

PMID: 18417025 [PubMed - indexed for MEDLINE]

285: Neurology. 2008 Apr 15;70(16):1337-45.

Validity of the ID-Migraine screener in the workplace.

Siva A, Zarifoglu M, Ertas M, Saip S, Karli HN, Baykan B, Keskinaslan A, Senocak 
M.

Istanbul University Cerrahpasa School of Medicine, Department of Neurology,
Istanbul, Turkey. asiva@tnn.net

OBJECTIVE: The impact of migraine on physical, social, and emotional performance 
is considerable, yet it remains an underdiagnosed disorder. ID-Migraine is a
validated migraine-screening tool developed to facilitate diagnosis. This study
evaluated the validity and use of the Turkish version of the ID-Migraine screener
(ID-Ms) in the workplace, and measured the impact of headache on disability,
productivity, and quality of life among the workforce. METHODS: A total of 465
employees from four companies were interviewed for screening with the ID-Ms.
Subjects were included in the study if they reported two or more headaches in the
past 3 months and gave a positive answer to one of the two ID-Ms prescreening
questions. Eligible subjects completed the ID-Ms, the Migraine Disability
Assessment Questionnaire, and the Medical Outcomes Study 36-Item Short Form
Health Survey. Subjects were then evaluated for confirmation of their diagnosis
according to the International Classification of Headache Disorders, 2nd edition 
(ICHD-2) criteria. RESULTS: A total of 227 subjects (mean age 31.9 +/- 5.9 years;
65.6% women) completed the study. Migraine was diagnosed in 106 of the 227
subjects (46.7%) according to the ID-Ms and in 117 of the 227 subjects (51.5%)
according to ICHD-2 criteria. The sensitivity of the ID-Ms was 70.9%, specificity
was 79.1% and Cohen kappa value was 0.50. Workdays lost over the previous 3
months due to headache amounted to 8.7 +/- 9.5 days for migraine-positive and 4.9
+/- 6.6 days for migraine-negative subjects. CONCLUSION: The Turkish version of
the ID-Migraine screener is a valid tool for identifying subjects with migraine
in the workplace.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't
    Validation Studies

PMID: 18413587 [PubMed - indexed for MEDLINE]

286: Eur J Neurosci. 2008 Apr;27(8):2057-65.

Cortical spreading depression modulates synaptic transmission of the rat lateral 
amygdala.

Dehbandi S, Speckmann EJ, Pape HC, Gorji A.

Institut für Physiologie I, Westfalische Wilhelms-Universitat Munster,
Robert-Koch-Strasse 27a, D-48149 Münster, Germany.

Clinical and pathophysiological evidence connects migraine and the amygdala.
Cortical spreading depression (CSD) plays a causative role in the generation of
aura symptoms. However, the role of CSD in the pathophysiology of other symptoms 
of migraine needs to be investigated. An in vitro brain slice technique was used 
to investigate CSD effects on tetanus-induced long-term potentiation (LTP) in the
lateral amygdala (LA) of the combined rat amygdala-hippocampus-cortex slices.
More than 75% of CSD induced in temporal cortex propagated to LA. Induction of
CSD in combined amygdala-hippocampus-cortex slices in which CSD propagated from
neocortex to LA significantly augmented LTP in LA. LTP was inhibited when CSD
travelled only in the neocortical tissues. Separation of the amygdala from the
remaining neocortical part of the slice, in which CSD propagation was limited to 
the neocortex, increased LTP close to the control levels. Pharmacological
manipulations of the slices, in which CSD reached LA, revealed the involvement of
NMDA and AMPA glutamate subreceptors as well as dopamine D2 receptors in the
enhancement of LTP in LA. However, neither blocking of GABA receptors nor
activation of dopamine D1 receptors affected LTP in these slices. The results
indicate the disturbances of LA synaptic transmission triggered by propagation of
CSD. This perturbation of LA synaptic transmission induced by CSD may relate to
some symptoms occurring during migraine attacks.

PMID: 18412626 [PubMed - indexed for MEDLINE]

287: Catheter Cardiovasc Interv. 2008 Jun 1;71(7):921-6.

Comment in:
    Catheter Cardiovasc Interv. 2008 Jun 1;71(7):927.

Feasibility of patent foramen ovale closure with no-device left behind:
first-in-man percutaneous suture closure.

Ruiz CE, Kipshidze N, Chiam PT, Gogorishvili I.

Department of Cardiac and Vascular Interventional Services, Lenox Hill Heart and 
Vascular Institute of New York, New York, USA. cruiz@lenoxhill.net

OBJECTIVES: This study evaluated the feasibility of percutaneous patent foramen
ovale (PFO) closure using a transcatheter suture (Superstitch), leaving no device
behind. BACKGROUND: PFO has been implicated in cryptogenic strokes and migraine
with auras. Percutaneous PFO closure, being less invasive than surgical closure, 
is increasingly performed. There are, however, early and long-term risks
including device embolization, fracture, thrombosis, or infection, erosions into 
the free atrial wall and aorta, arrhythmias, and death. Furthermore, device
implantation may complicate future percutaneous access to the left atrium.
Partially reabsorbable devices and tissue welding to close PFO have recently been
introduced. The first-in-man transcatheter suture closure of a PFO in an
18-year-old female with chronic migraine with aura and a well documented stroke
is described. METHODS: The right femoral vein was cannulated under mild sedation 
and local anesthesia. Using intracardiac echocardiography imaging, bubble study
demonstrated a right-to-left shunt through the PFO at rest. A Superstitch device 
was advanced across the PFO and sutures were delivered through the septum primum 
and secundum. The sutures were exteriorized and a knot was advanced to the right 
atrial septum and cut. RESULTS: Bubble study confirmed successful PFO suture
closure. Transesophageal and transthoracic echocardiograms with bubble studies at
1 and 2 months, respectively showed complete closure with no right-to-left shunt 
even during Valsalva maneuver. At 6 months, the patient remained free of symptoms
or migraine episodes. CONCLUSION: Percutaneous transcatheter suture closure of a 
PFO can be successfully achieved with no residual shunt and leaving no device
behind. Technological refinements are required for wider scale use. 2008
Wiley-Liss, Inc.

Publication Types: 
    Case Reports

PMID: 18412251 [PubMed - indexed for MEDLINE]

288: BMC Complement Altern Med. 2008 Apr 14;8:12.

Study protocol for a pragmatic randomised controlled trial in general practice
investigating the effectiveness of acupuncture against migraine.

Vas J, Rebollo A, Perea-Milla E, Méndez C, Font CR, Gómez-Río M, Martín-Avila M, 
Carbrera-Iboleón J, Caballero MD, Olmos MA, Aguilar I, Faus V, Martos F.

Pain Treatment Unit, Primary Care Center, Dos Hermanas, Spain.
jorgef.vas.sspa@juntadeandalucia.es.

BACKGROUND: Migraine is a chronic neurologic disease that can severely affect the
patient's quality of life. Although in recent years many randomised studies have 
been carried out to investigate the effectiveness of acupuncture as a treatment
for migraine, it remains a controversial issue. Our aim is to determine whether
acupuncture, applied under real conditions of clinical practice in the area of
primary healthcare, is more effective than conventional treatment.
METHODS/DESIGN: The design consists of a pragmatic multi-centre, three-armed
randomised controlled trial, complemented with an economic evaluation of the
results achieved, comparing the effectiveness of verum acupuncture with sham
acupuncture, and with a control group receiving normal care only.Patients
eligible for inclusion will be those presenting in general practice with migraine
and for whom their General Practitioner (GP) is considering referral for
acupuncture. Sampling will be by consecutive selection, and by randomised
allocation to the three branches of the study, in a centralised way following a
1:1:1 distribution (verum acupuncture; sham acupuncture; conventional treatment).
Secondly, one patient in three will be randomly selected from each of the
acupuncture (verum or sham) groups for a brain perfusion study (by single photon 
emission tomography). The treatment with verum acupuncture will consist of 8
treatment sessions, once a week, at points selected individually by the
acupuncturist. The sham acupuncture group will receive 8 sessions, one per week, 
with treatment being applied at non-acupuncture points in the dorsal and lumbar
regions, using the minimal puncture technique. The control group will be given
conventional treatment, as will the other two groups. DISCUSSION: This trial will
contribute to available evidence on acupuncture for the treatment of migraine.
The primary endpoint is the difference in the number of days with migraine among 
the three groups, between the baseline period (the 4 weeks prior to the start of 
treatment) and the period from weeks 9 to 12. As a secondary aspect, we shall
record the index of laterality and the percentage of change in the mean count per
pixel in each region of interest measured by the brain perfusion tomography,
performed on a subsample of the patients within the real and sham acupuncture
groups. TRIAL REGISTRATION: Current Controlled Trials ISRCTN98703707.

Publication Types: 
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 18410686 [PubMed - indexed for MEDLINE]

289: Coll Antropol. 2008 Jan;32 Suppl 1:99-103.

Increased permeability of the blood-brain barrier following administration of
glyceryl trinitrate in common carp (Cyprinus carpio L.).

Kovacić S, Petrinec Z, Matasin Z, Gjurcević E, Ivkić G, Lovreneić-Huzjan A,
Segvić-Klarić M, Rumora L, Pepeljnjak S.

Department of Neurology, General Hospital Zabok, Zabok, Croatia.
sanja.drca@kr.htnet.hr

Nitric oxide (NO) has been implicated in the pathogenesis of migraine and
treatment with its exogenous donor glyceryl trinitrate (GTN) represents widely
accepted experimental "migraine model". In this study, glyceryl trinitrate was
administered intraperitoneally to carps, serum nitrite and nitrate levels were
determined, permeability of blood-brain barrier was investigated, and
histological changes of brain tissue were analyzed. Serum nitrite and nitrate
levels displayed characteristic biphasic pattern with moderate initial increase
and maximal terminal increase, suggesting the GTN-induced endogenous NO
synthesis. Increased permeability of the blood-brain barrier in GTN-treated
animals was determined based on Evans blue capillary leakage into the brain
tissue. Histological analysis revealed changes consistent with vasodilatation and
oedema. Our study strongly supports the importance of the NO role in the
pathogenesis of migraine attacks and increase in blood-brain barrier permeability
during the attack. The study has also provided evidence that this mechanism of
action is conserved to the lower vertebrate.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 18405066 [PubMed - indexed for MEDLINE]

290: Acta Otolaryngol Suppl. 2007 Dec;(559):45-9.

Migraine-associated vertigo: clinical characteristics of Japanese patients and
effect of lomerizine, a calcium channel antagonist.

Iwasaki S, Ushio M, Chihara Y, Ito K, Sugasawa K, Murofushi T.

Department of Otolaryngology, Faculty of Medicine, University of Tokyo, 7-3-1
Hongo, Bunkyo-ku, Tokyo, Japan. iwashin-tky@umin.ac.jp

CONCLUSION: Lomerizine, a calcium channel blocker, may be effective as a
treatment for migraine-associated vertigo (MAV). Objective. To determine the
clinical characteristics of patients with MAV in Japan and the effectiveness of
lomerizine. PATIENTS AND METHODS: This was a retrospective chart review carried
out in a university hospital of 33 patients who fulfilled the diagnostic criteria
for MAV. All patients were initially treated with dietary manipulation. If this
therapy was unsuccessful, oral medications, mainly lomerizine, were administered.
Medical records were reviewed to find clinical characteristics of patients with
MAV and to evaluate the effects of the therapy on vertigo/dizziness symptoms.
RESULTS: A marked female predominance was found (23 women, 10 men). The frequency
and the duration of vertigo varied across patients. About 60% of the patients had
cochlear symptoms during an attack, among which bilateral aural fullness was most
frequent. Oto-neurological examination showed abnormalities in 33% of the
patients. Overall, 27 of the 33 patients (82%) responded to our therapy. Among
the 22 patients who were prescribed lomerizine, 19 patients (87%) showed
resolution or significant improvement of the symptoms.

Publication Types: 
    Clinical Trial
    Research Support, Non-U.S. Gov't

PMID: 18340570 [PubMed - indexed for MEDLINE]

291: BMC Fam Pract. 2008 Apr 9;9:19.

Gender differences in sex life issues - a population-based study of migraine
sufferers.

Sumanen MP, Ojanlatva A, Rantala A, Sillanmäki LH, Mattila KJ.

University of Tampere, Medical School, Finland. markku.sumanen@uta.fi

BACKGROUND: Migraine is considered to have a negative influence on sex life. The 
present study was to analyse the perceptions of importance of and satisfaction
with sex life as well as the expression of interest in sex among people having
migraines in a prospective follow-up mail survey in 1998 and 2003. METHODS: The
random sample was stratified according to gender and age in four age groups
(20-24, 30-34, 40-44, and 50-54 years). Altogether 25 898 individuals responded
to the baseline and 19 626 to the follow-up questionnaire (75.8% response rate). 
We examined as to how the perceptions of sex life of those suffering from
migraine changed during a 5-year follow-up. Conditional logistic regression was
used to analyse the data of the responses on self-reported migraine in the
baseline and follow-up surveys (N = 2 977, 79.2% women). Each person with
migraine was assigned a gender- and age-matched control in the analysis. RESULTS:
All three outcome variables tended to decrease in value. Importance of sex life
was higher among men with migraine than among their controls. Among women
migraine lessened interest in sex life. CONCLUSION: Our findings suggested that
migraine has a different impact on sex life among women from that among men.

PMID: 18400102 [PubMed - indexed for MEDLINE]

292: Clin Genet. 2008 Nov;74(5):481-5. Epub 2008 Apr 8.

CACNA1A R1347Q: a frequent recurrent mutation in hemiplegic migraine.

Stam AH, Vanmolkot KR, Kremer HP, Gärtner J, Brown J, Leshinsky-Silver E, Gilad
R, Kors EE, Frankhuizen WS, Ginjaar HB, Haan J, Frants RR, Ferrari MD, van den
Maagdenberg AM, Terwindt GM.

Department of Neurology and Clinical Genetic, Erasmus Medical Centre, Leiden, The
Netherlands.

Of the 18 missense mutations in the CACNA1A gene, which are associated with
familial hemiplegic migraine type 1 (FHM1), only mutations S218L, R583Q and T666M
were identified in more than two independent families. Including the four novel
families presented here, of which two represent de novo cases, the R1347Q
mutation has now been identified in six families. A genotype-phenotype comparison
of R1347Q mutation carriers revealed a wide clinical spectrum ranging from
(trauma triggered) hemiplegic migraine with and without ataxia, loss of
consciousness and epilepsy. R1347Q is the third most frequent mutation in
hemiplegic migraine patients and should therefore be screened with priority for
confirmation of clinical diagnosis. This study clearly demonstrates that the
availability of multiple families better reflects the full clinical spectrum
associated with FHM1 mutations.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 18400034 [PubMed - indexed for MEDLINE]

293: J Natl Med Assoc. 2008 Mar;100(3):334-8.

Migraine and Meniere's disease: two different phenomena with frequently observed 
concomitant occurrences.

Ibekwe TS, Fasunla JA, Ibekwe PU, Obasikene GC, Onakoya PA, Nwaorgu OG.

ORL Division, Department of Surgery, Irrua Specialist Teaching Hospital and
College of Medicine, Ambrose Alli University, Ekpoma, Edo State, Nigeria.
ibekwets@yahoo.com

BACKGROUND: Some variants of migraine could be indistinguishable from Meniere's
disease, and this has prompted suggestions of possible association between the
two disease entities. AIM AND OBJECTIVES: This study aims at determining the
prevalence of migraine among Meniere's patients and a possible linkage between
the two diseases in our environment. METHODOLOGY: A 10-year retrospective study
of patients diagnosed with Meniere's disease using American Academy of
Otorhinolaryngology criteria, including those that had associated migranous
symptoms in accordance with the International Headache Society (IHS) diagnostic
criteria for migraine, between 1996 and 2005. The prevalence of migraine in the
Meniere's patients was also compared with lifetime prevalence recorded from a
previous population-based study within the same setting. The statistical
difference was tested with a Z nonparametric test (significance at P < 0.05).
Epicalc2000 and SPSS 11 were used for the statistical analysis. RESULT: A total
of 25 patients representing 0.22% of the 11,463 ear, nose and throat outpatients 
seen within the study period met the diagnostic criteria for Meniere's disease.
There were nine (36%) males and 16 (94%) females. Their ages ranged 27-65 years, 
mean 45.25 years +/- 11.05. Eight (32%) met IHS criteria for migraine. There is a
statistically significant difference between the prevalence of migraine in
Meniere's patients and migraine in the overall population (32% vs. 5.3%, P =
0.000). CONCLUSION: The significant preponderance in the prevalence of migraine
in Meniere's disease suggests a link between the two diseases. However, more
molecular or genetic studies are needed to unveil this phenomenon.

Publication Types: 
    Comparative Study

PMID: 18390027 [PubMed - indexed for MEDLINE]

294: J Headache Pain. 2008 Jun;9(3):147-50. Epub 2008 Apr 2.

Topiramate in the prevention of pediatric migraine: literature review.

Ferraro D, Di Trapani G.

Headache Center, Neurology Institute, Policlinico A. Gemelli, Università
Cattolica del Sacro Cuore, Largo A. Gemelli, Rome, Italy. perdiana@tin.it

Pediatric migraine is a disabling condition, which can cause a significant impact
on quality of life. Currently, no drugs have been approved by the FDA for its
preventive treatment. Our aim was to review the medical literature concerning the
efficacy and tolerability of topiramate in the prophylactic treatment of migraine
in children and adolescents. A total of five papers were reviewed: two randomized
controlled trials (RCTs), a post-hoc subset analysis of adolescents who had been 
included in three RCTs carried out on adults and two open studies. Topiramate has
been proven to reduce headache frequency and the accompanying disability. The
frequency of side effects varied considerably among studies, the most frequent
being weight loss, anorexia, abdominal pain, difficulties in concentrating,
sedation and paresthesia. Since these adverse events, although often transitory, 
may be distressing for the child, we strongly recommend to assess the disability 
caused by the migraine episodes before deciding to initiate a prophylactic
treatment. Nevertheless, dropout rates due to side effects in the studies were
very low.

Publication Types: 
    Review

PMID: 18385933 [PubMed - indexed for MEDLINE]

295: Cephalalgia. 2008 May;28(5):510-23. Epub 2008 Mar 31.

Validation of the revised Patient Perception of Migraine Questionnaire (PPMQ-R): 
measuring satisfaction with acute migraine treatment in clinical trials.

Kimel M, Hsieh R, McCormack J, Burch SP, Revicki DA.

Center for Health Outcomes Research, United BioSource Corporation, Bethesda, MD
20814, USA. miriam.kimel@unitedbiosource.com

This study was aimed to evaluate in clinical trial settings the psychometric
properties of the revised Patient Perception of Migraine Questionnaire (PPMQ-R), 
a satisfaction measure for acute migraine treatment. The PPMQ-R was administered 
24 h post dosing in 1304 migraineurs randomized to two identical Phase 3,
single-attack trials. Reliability, concurrent and construct validity and
known-groups validity were evaluated using Cronbach's alpha, Pearson correlations
and analysis of variance, respectively. PPMQ-R scale and Total scores (Efficacy, 
Functionality and Ease of use) showed very good internal consistency reliability 
(alpha 0.84-0.99). Efficacy, Functionality and Total PPMQ-R scores showed large, 
inverse relationships with migraine pain severity, number of migraine symptoms
and work ability (r = -0.62 to -0.75; all P < 0.0001). All scales discriminated
among migraine pain severity levels (all P < 0.001). The PPMQ-R has sufficient
evidence of validity and reliability for measuring patient satisfaction, an
important benchmark of quality and effective care.

Publication Types: 
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't
    Validation Studies

PMID: 18384420 [PubMed - indexed for MEDLINE]

296: Cephalalgia. 2008 May;28(5):563-6. Epub 2008 Mar 31.

Comparison of CGRP and NO responses in the human peripheral microcirculation of
migraine and control subjects.

Edvinsson ML, Edvinsson L.

Department of Emergency Medicine, Institute of Clinical Sciences, University
Hospital, Lund, Sweden. lars.edvinsson@med.lu.se

Calcitonin gene-related peptide (CGRP) and nitric oxide (NO) are two molecules
shown to have a role in migraine pathophysiology. Our objective was to test the
hypothesis that migraine subjects are particularly sensitive to these signal
molecules. The cutaneous microvascular responses to endothelial and
non-endothelial dependent dilators were tested using laser Doppler flowmetry in
combination with iontophoresis. The blood flow responses to iontophoretic
administration of the endothelium-dependent vasodilator acetylcholine (ACh), or
to the endothelium-independent dilators sodium nitroprusside (SNP) and CGRP, and 
to local warming (44 degrees C) were compared in this controlled trial. The
design was that of two arms: patients diagnosed with migraine without aura (n =
9) for >10 years were compared with nine healthy subjects matched for age and
gender (seven female and two male, age range 30-60 years). Iontophoretic
administration resulted in local vasodilation. ACh induced a relaxation of 1225
+/- 245% (relative to baseline) in controls and 1468 +/- 368% (P > 0.05) in
migraine. The responses to SNP were 873 +/- 193% in controls and 1080 +/- 102% (P
> 0.05) in migraine subjects. The responses to CGRP were 565 +/- 89% in controls 
and 746 +/- 675% (P > 0.05) in migraine patients. The responses to local heating 
which induced maximum dilation did not differ between the groups (1976 +/- 314%
for controls and 1432 +/- 226% in migraine; P > 0.05. We conclude that there is
no change in the microvascular responsiveness of the subcutaneous
microvasculature in migraine.

Publication Types: 
    Comparative Study
    Controlled Clinical Trial
    Research Support, Non-U.S. Gov't

PMID: 18384419 [PubMed - indexed for MEDLINE]

297: Cephalalgia. 2008 May;28(5):496-505. Epub 2008 Mar 31.

Familial hemiplegic migraine type 1 shows no hypersensitivity to nitric oxide.

Hansen JM, Thomsen LL, Olesen J, Ashina M.

Danish Headache Centre and Department of Neurology, Glostrup Hospital, University
of Copenhagen, Glostrup, Copenhagen, Denmark. jamoha01@glo.regionh.dk

Familial hemiplegic migraine type 1 (FHM-1) is a dominantly inherited subtype of 
migraine with aura and transient hemiplegia associated with mutations in the
CACNA1A gene. FHM-1 shares many phenotypical similarities with common types of
migraine, indicating common neurobiological pathways. Experimental studies have
established that activation of the nitric oxide-cyclic guanosine monophosphate
(NO-cGMP) pathway plays a crucial role in migraine pathophysiology. Therefore, we
tested the hypothesis that CACNA1A mutations in patients with FHM-1 are
associated with hypersensitivity to NO-cGMP pathway. We included eight FHM-1
patients with R583Q and C1369Y mutations and nine healthy controls, who received 
intravenous infusions of 0.5 microg kg(-1) min(-1) glyceryl trinitrate (GTN) over
20 min. We recorded: headache intensity on a verbal rating scale; mean flow
velocity in the middle cerebral artery (V(meanMCA)) by transcranial Doppler;
diameter of the superficial temporal artery (STA) by Dermascan. One patient
reported migraine without aura 5 h after start of the GTN infusion. No aura was
reported. The AUC(headache) in the immediate phase was more pronounced in
patients than in controls (P = 0.01). In the 14 h following GTN infusion, there
was no difference in the AUC(headache) between patients and controls (P = 0.17). 
We found no difference in the AUC(VmeanMCA) (P = 0.12) or AUC(STA) (P = 0.71)
between FHM-1 patients and controls. None of the control persons reported
migraine-like headache. FHM-1 patients do not show hypersensitivity of the
NO-cGMP pathway, as characteristically seen in migraine patients with and without
aura. This indicates that the pathophysiological pathways underlying migraine
headache in FHM-1 may be different from the common types of migraine.

Publication Types: 
    Controlled Clinical Trial
    Research Support, Non-U.S. Gov't

PMID: 18384418 [PubMed - indexed for MEDLINE]

298: Cephalalgia. 2008 Jun;28(6):609-13. Epub 2008 Mar 31.

Comment in:
    Nat Clin Pract Neurol. 2008 Aug;4(8):422-3.

Idiopathic intracranial hypertension with and without papilloedema in a
consecutive series of patients with chronic migraine.

Vieira DS, Masruha MR, Gonçalves AL, Zukerman E, Senne Soares CA,
Naffah-Mazzacoratti Mda G, Peres MF.

Instituto Israelita de Ensino e Pesquisa Albert Einstein, Instituto do Cérebro,
Hospital Israelita Albert Einstein, São Paulo, Brazil.

Chronic migraine (CM) has been associated with idiopathic intracranial
hypertension without papilloedema (IIHWOP), a significant percentage of these
cases occurring in obese patients with intractable headache. A prospective study 
from February 2005 to June 2006 was made of 62 CM patients who fulfilled
International Headache Society diagnostic criteria and had cerebral magnetic
resonance venography (MRV) and lumbar puncture (LP) done. Two patients were
excluded, six (10%) with elevated cerebrospinal fluid (CSF) open pressure (OP),
five with body mass index (BMI) > 25. None of the patients had papilloedema or
abnormal MRV. BMI and CSF OP were significantly correlated (r = 0.476, P < 0.001,
Pearson's correlation test). Obesity (defined as BMI > 30) was a predictor of
increase in intracranial pressure (defined as OP > 200 mmH(2)O) (f = 17.26, 95%
confidence interval 6.0, 8.6; P < 0.001). From our study we strongly recommend
that not only intractable CM patients with high BMI, but also first diagnosed
patients with BMI > 30 should be systematically evaluated by a LP to rule out
IIHWOP.

PMID: 18384415 [PubMed - indexed for MEDLINE]

299: Catheter Cardiovasc Interv. 2008 Jul 1;72(1):60-4.

Management of patients with refractory migraine and PFO: Is MIST I relevant?

Tobis J.

UCLA-David Geffen School of Medicine, BL-394 CHS, 10833 LeConte Ave., Los
Angeles, CA 90095-1717, USA.

The results of the randomized clinical trial entitled: Migraine Intervention with
Starflex Technology (MIST), produced surprising and disappointing results on the 
effect of PFO closure to decrease migraine headaches. There have been allegations
of misrepresentation of the effectiveness of this device. These issues have
significant implications in how randomized clinical trials are performed that
will impact current and future planned trials of PFO closure to treat migraine
headaches. (c) 2008 Wiley-Liss, Inc.

Publication Types: 
    Review

PMID: 18383146 [PubMed - indexed for MEDLINE]

300: Congenit Heart Dis. 2008 Mar;3(2):124-7.

Prevalence of migraine in adults with cyanotic congenital heart disease.

Hirth A, Nightingale S, Wilmshurst P, Disney P, Thorne S.

Institute of Clinical Medicine, University of Bergen, Bergen, Norway.
ahir@mac.com

OBJECTIVE: There is an increased prevalence of patent foramen ovale in patients
with migraine, leading to the suggestion that migraine is more common in patients
with potential right-to-left shunts. The aim of this study was to investigate the
prevalence of migraine in adults with large right-to-left shunts because of
cyanotic congenital heart disease. DESIGN AND PATIENTS: In total, 29 cyanotic
adult patients with congenital heart disease answered a questionnaire to
determine the prevalence of migraine with or without aura. A total of 38 matched 
acyanotic patients with congenital heart disease served as controls. A subgroup
of 18 acyanotic patients also underwent bubble contrast echocardiography to look 
for patent foramen ovale. RESULTS: Twenty (69%) of the cyanotic patients had
migraine, the majority 17 (59%) having migraine with aura. Twenty-two (58%) of
the 38 acyanotic patients had migraine, of whom 16 (42%) had migraine with aura. 
Nine (50%) of the 18 acyanotic patients who consented to an echocardiogram had
patent foramen ovale. Of those with patent foramen ovale, 8 (89%) had migraine
and 6 (67%) had migraine with aura. CONCLUSION: There is an increased prevalence 
of migraine with aura in both cyanotic and acyanotic patients with congenital
heart disease. The high prevalence of migraine in acyanotic patients with
congenital heart disease may be due to an increased prevalence of patent foramen 
ovale.

Publication Types: 
    Comparative Study

PMID: 18380761 [PubMed - indexed for MEDLINE]

301: Value Health. 2008 Mar-Apr;11(2):315-21.

Migraine frequency and health utilities: findings from a multisite survey.

Brown JS, Neumann PJ, Papadopoulos G, Ruoff G, Diamond M, Menzin J.

Department of Ambulatory Care and Prevention, Harvard Medical School/Harvard
Pilgrim Health Care, Boston, MA, USA.

OBJECTIVES: Assess the relationship between migraine frequency and health
utility. METHODS: Patients aged >/=18 years diagnosed with episodic migraine were
enrolled at three US sites representing varied models of health-care delivery.
All subjects completed a questionnaire that included demographic and clinical
information, a migraine-specific disability questionnaire, and the Health
Utilities Index Mark 3 (HUI3). The HUI3 is a generic health status and
health-related quality-of-life measure. HUI3 health status data are translated
into utility scores anchored by 0 (dead) and 1 (perfect health). RESULTS: The
study enrolled 150 patients. The mean age was 44 years and 87% were female. Mean 
(+/-SD) monthly migraine frequency was 4.4 +/- 3.6, with 34% reporting </=2
migraines per month and 20% reporting >6 migraines per month. The mean (+/-SD)
HUI3 score was 0.62 +/- 0.26. After controlling for study center, demographics,
comorbidities, migraine characteristics, and level of migraine disruptiveness,
migraine frequency was found to be significantly (P < 0.05) and negatively
associated with HUI3 scores. Subjects with >6 migraines per month had an adjusted
mean HUI3 score of 0.41; the corresponding mean for those reporting </=2
migraines per month was 0.67. Migraine frequency was positively associated with
higher levels of disability for the emotion, cognition, and pain components of
the HUI3. CONCLUSIONS: Among this group of care-seeking patients, migraineurs'
health utilities were inversely related to headache frequency. Although these
data may not be generalizable to the entire migraine population, they may be
useful in assessing the comparative cost-effectiveness of preventive migraine
therapies.

Publication Types: 
    Multicenter Study
    Research Support, Non-U.S. Gov't

PMID: 18380644 [PubMed - indexed for MEDLINE]

302: Headache. 2008 Apr;48(4):661-7.

Examining the essence of migraine--is it the blood vessel or the brain? A debate.

Dodick DW.

Department of Neurology, Mayo Clinic, Scottsdale, AZ, USA.

A debate is presented that examines whether it is the blood vessel or the brain
that determines the essence of migraine.

Publication Types: 
    Review

PMID: 18377395 [PubMed - indexed for MEDLINE]

303: Headache. 2008 Apr;48(4):621-4.

Vertebral artery dissection onset mimics migraine with aura in a graphic
designer.

Morelli N, Mancuso M, Gori S, Maluccio MR, Cafforio G, Chiti A, Orlandi G,
Ceretti E, Tartaglione A, Murri L.

University Centre for Adaptive Disorders and Headache (UCADH), Institute of
Neurology, Department of Neurosciences, University of Pisa, Pisa, Italy.

Headache is the most common symptom in patients with cervical artery dissection. 
This symptom, however, rarely occurs in isolation, and more commonly is
associated with other neurological symptoms and signs. Visual symptoms associated
with vertebral artery dissection (VD) have also been observed, but do not
typically mimic the migraine aura. Here, we report a young patient who presented 
VD, embolic ischemic lesions, and visual symptoms with the features of aura,
followed by migraine headache. The suggestion of VD dissection should be kept in 
mind in those cases complaining of the first attack of headache that mimics
migraine with aura. In these cases, an extensive neuroimaging study is advisable.

Publication Types: 
    Case Reports

PMID: 18377386 [PubMed - indexed for MEDLINE]

304: Headache. 2008 Apr;48(4):611-3.

Triptans: actions and reactions.

Nahas SJ, Silberstein SD.

Thomas Jefferson University Hospital-Neurology, Philadelphia, PA 19107-5092, USA.

Subcutaneous sumatriptan is superior to placebo in achieving headache relief.
Some commonly reported adverse events are paresthesias, tingling, and transient
worsening of headache. Why do patients develop these symptoms? Our unique case
may shed light on its actions.

Publication Types: 
    Case Reports

PMID: 18377383 [PubMed - indexed for MEDLINE]

305: Headache. 2008 Apr;48(4):601-5.

Comment in:
    Headache. 2008 Oct;48(9):1378-9.

Triptans vs other drugs for acute migraine. Are there differences in efficacy? A 
comment.

Tfelt-Hansen P.

Danish Headache Centre, Department of Neurology, University of Copenhagen,
Glostrup Hospital, Glostrup, Denmark.

The introduction of triptans in migraine treatment was apparently a revolution.
Comparative randomized clinical trials (RCTs) with triptan and other drugs do not
give a clear-cut picture. Oral triptans are superior to oral ergotamine most
likely because the bioavailability oral of ergotamine is extremely low (<1%).
Compared with NSAIDs, in most cases aspirin, triptans were not superior and in
several RCTs triptans caused more adverse events than aspirin plus
metoclopramide. Guidelines for treatment of migraine should be evidence-based. It
is suggested that based on current evidence, effervescent aspirin should be the
first-line drug for the treatment of migraine. Aspirin is also much cheaper than 
the triptans.

Publication Types: 
    Review

PMID: 18377382 [PubMed - indexed for MEDLINE]

306: Headache. 2008 Apr;48(4):578-85.

Trigemino-cervical reflex abnormalities in patients with migraine and cluster
headache.

Nardone R, Ausserer H, Bratti A, Covi M, Lochner P, Marth R, Florio I, Tezzon F.

Department of Neurology, F. Tappeiner Hospital, Merano, Italy.

BACKGROUND: Head pain arises within the trigeminal nociceptive system. Current
theories propose that the trigeminal system is intimately involved in the
pathogenesis of migraine. Short-latency responses can be recorded in
sternocleidomastoid muscles after stimulation of the trigeminal nerve
(trigemino-cervical reflex). This brainstem reflex could be a suitable method to 
evaluate the trigeminal system in migraine and CH. OBJECTIVE: The aim of the
present study was to further elucidate the pathophysiology of migraine and
cluster headache (CH) with special reference to the involvement of the central
trigeminal system in the different forms of primary headache. METHODS: The
trigemino-cervical reflex was investigated in 15 healthy subjects, in 15 patients
having migraine with aura, in 15 patients with migraine without aura, and in 10
patients with CH. RESULTS: Significant abnormalities were observed in a great
number of patients with both types of migraine and CH during the headache
attacks, but only in migraine patients during the interictal period. The
alterations are bilateral in migraine, unilateral in CH. CONCLUSIONS: Our results
further support the relevance of brainstem mechanisms in the pathogenesis of
migraine rather than of CH. These data, taken together with that from
experimental head pain and functional imaging studies, demonstrate that primary
headache syndromes may be distinguished on a functional basis by areas of
activation specific to the clinical syndrome.

PMID: 18377381 [PubMed - indexed for MEDLINE]

307: Headache. 2008 Apr;48(4):564-9.

Nurse-based education: an office-based comparative model for education of
migraine patients.

Cady R, Farmer K, Beach ME, Tarrasch J.

Headache Care Center-Health Psychology, Primary Care Network, Springfield, MO
65807, USA.

BACKGROUND: A person with migraine needs to be prepared to make therapeutic
decisions on her own. For this reason, patients often need education to
understand the nuisances of managing theirmigraines. In this study an
educationalCD-ROM/DVD that described the pathophysiology was utilized by nurses
in an office-based primary care setting for patient education. Outcomes from this
encounter were measured. OBJECTIVES: (1) Identify educational information that
assisted migraine patients feel empowered to more effectively manage migraine;
(2) encourage patients to intervene during the mild headache phase of the
migraine; (3) measure education related changes in patient satisfaction and
confidence regarding management of migraine; (4) measure changes in nurse
satisfaction and confidence in educating migraine patients; (5) compare the
effectiveness of 3 methods of delivery of nurse-based migraine education.
METHODS: One hundred and eighty migraineurs at 21 primary care practices were
divided into 4 groups: group A watched the CD-ROM/DVD in the office with a nurse 
available to answer questions; group B was given the CD-ROM/DVD by a nurse
knowledgeable of the content; group C received the educational CD-ROM/DVD from a 
nurse without comment; group D received no educational material. The 10 nurses in
groups A and B participated in a 45-minute teleconference that reviewed the
information on the CD-ROM/DVD. Patients and nurses answered a pre- and post-study
migraine questionnaire. Patients filled in a treatment diary online within 24
hours of treating a migraine. Nurses completed a satisfaction questionnaire.
RESULTS: Of the 17 educational points tested on the pre-test, 75% of patients and
nurses already knew about 1/3 of the information. There was significant
improvement noted for both patients and nurses on the post-test in groups A, B,
and C but not in group D. The percentage of correct responses by patients and
nurses was directly and statistically significantly correlated with the
involvement of the nurse in the educational effort. As a result of the education,
patients felt more confident in their ability to manage and treat migraine.
Likewise, nurses gained increased confidence in teaching patients about migraine.
Patients did not intervene with acute therapy during the mild headache phase.
Overall, 94% of the nurses were very satisfied or satisfied with the format and
information provided. CONCLUSIONS: All but objective 2 were met for groups A, B, 
and C compared to control group D. Patients readily accepted nurse-directed
education and assimilated information that increased their confidence to manage
migraine. This emphasizes the importance of training nurses about materials used 
to educate patients.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 18377379 [PubMed - indexed for MEDLINE]

308: Headache. 2008 Apr;48(4):523-8.

Predictors of disability in migraineurs referred to a tertiary clinic: neck pain,
headache characteristics, and coping behaviors.

Ford S, Calhoun A, Kahn K, Mann J, Finkel A.

Department of Neurology, University of North Carolina, Chapel Hill, NC 27599,
USA.

OBJECTIVE: The aim of this retrospective study was to determine if neck pain,
select headache characteristics, and migraine-related coping response predicted
disability in migraineurs referred to a tertiary headache clinic. METHODS:
Patients seeking treatment at a neurology-based headache clinic were included if 
they met diagnostic criteria for migraine with or without aura according to the
International Headache Society (1.1, 1.2). Subjects completed a self-report
headache history form and a detailed headache and neurologic examination. The
headache history form assessed: 1)weekly headache frequency; 2) number of weekly 
severe headaches; 3) presence of migraine-related neck pain; 4) photophobia; 5)
phonophobia; 6) headache duration; 7) vomiting; 8) monthly headache-free days;
and 9) behavioral coping style. Disability was assessed using a self-report
inventory (HIT-6). RESULTS: Self-reported headache severity, frequency, and
headache-free days were strongly associated with disability. The presence of neck
pain during migraine and one's coping response to migraine significantly
predicted disability independent of headache characteristics. CONCLUSIONS: These 
data suggest the need for prospective research exploring the causal mechanisms by
which neck pain and coping response influence disability and underscores the
importance of multidisciplinary approaches to headache management.

PMID: 18377378 [PubMed - indexed for MEDLINE]

309: Headache. 2008 Apr;48(4):517-22.

Post-traumatic stress disorder in episodic and chronic migraine.

Peterlin BL, Tietjen G, Meng S, Lidicker J, Bigal M.

Drexel University College of Medicine-Neurology, Philadelphia, PA 19102, USA.

OBJECTIVE: To assess and contrast the relative frequency of self-reported
post-traumatic stress disorder (PTSD) in patients with episodic migraine and
chronic/ transformed migraine. BACKGROUND: Several risk factors have been
identified as risk factors for chronification of headache disorders. Childhood
abuse has been suggested as a risk factor for chronic pain in adulthood. In
addition depression, as well as several other psychiatric disorders, are
co-morbid with migraine. Recent data suggest that PTSD may be more common in
headache sufferers than in the general population. METHODS: This was a
prospective, pilot study conducted at a headache center. Adult subjects with
episodic, chronic, or transformed migraine were included. Demographic
information, depression history, body mass index (BMI), and headache
characteristics were obtained. PTSD was assessed using the life events checklist 
(LEC) and the PTSD checklist, civilian version (PCL-C). We contrasted the data
from episodicmigraineurs and chronic/transformed migraine participants (CM) and
conducted multivariate analyses, adjusting for covariates. RESULTS: Of the 60
participants included, 91.7% were female with a mean age of 41.4+/-12.5 years
old. EM was diagnosed in 53.3% and CM in 46.7%. The mean BMI was not
significantly different between groups. In contrast, the relative frequency of
depression was significantly greater in subjects with CM (55.2%) than EM (21.9%, 
P=.016). There was no significant difference in the percentage of participants
reporting at least 1 significant traumatic life event (LE) or in the mean number 
of traumatic LEs between EM and CM participants. However, the relative frequency 
of PTSD reported on the PCL in CM (42.9%) was significantly greater as compared
to EM (9.4%, P=.0059. After adjusting for depression and other potential
confounders, the difference remained significant P=.023). CONCLUSION: PTSD is
more common in CM than in episodic migraineurs. This suggests that PTSD may be a 
risk factor for headache chronification, pending longitudinal studies to test
this hypothesis.

PMID: 18377377 [PubMed - indexed for MEDLINE]

310: Expert Opin Pharmacother. 2008 Apr;9(6):1001-11.

A review of the 5-HT1B/1D agonist rizatriptan: update on recent research and
implications for the future.

Mannix LK.

Headache Associates and ClinExcel Research 7908 Cincinnati-Dayton Road Suite J,
West Chester, OH 45069, USA. LKMannixMD@aol.com

BACKGROUND: Among the 5-HT(1B/1D) agonists or 'triptans,' which are considered
first-line therapy for acute migraine, rizatriptan has emerged as one of the most
efficacious. OBJECTIVE: Several comprehensive reviews of rizatriptan are
available in the literature; the aim of this paper is to review the most current 
research with rizatriptan. METHODS: The scope of the review addresses current
topics of clinical interest, including studies of time to pain relief, effect of 
early administration, use in combination with other drugs, and tolerability
updates, as well as trials of rizatriptan in certain subpopulations such as
patients with menstrual migraine, patients with motion sickness and pediatric
patients. CONCLUSION: In the context of these newly available data, the potential
for expansion of the role of rizatriptan in the clinic is evaluated.

Publication Types: 
    Review

PMID: 18377342 [PubMed - indexed for MEDLINE]

311: Eur J Pain. 2008 Nov;12(8):1090-101. Epub 2008 Mar 28.

Altered pain processing in children with migraine: an evoked potential study.

Zohsel K, Hohmeister J, Flor H, Hermann C.

Department of Clinical and Cognitive Neuroscience, Ruprecht-Karls-University of
Heidelberg, Central Institute of Mental Health, Square J5 D-68159 Mannheim,
Germany.

In adults, evidence is accumulating that migraine is associated with altered
central processing of pain stimuli and, possibly, changes in the allocation of
attentional resources to such stimuli. In pediatric migraine, however, little is 
known about altered pain processing. We examined 15 children with migraine and 15
controls (age 10-15) in an oddball standards task. Children had to respond to
rare targets (tones) and ignore frequent painful (pain threshold) or non-painful 
mechanical standard stimuli while evoked potentials were obtained. Painful as
compared to non-painful stimuli elicited significantly larger N150, P260 and P300
components of the somatosensory evoked potential in all children. The pain-evoked
N150 and P260 components did not differ significantly between groups. However, in
children with migraine, both painful and non-painful standard stimuli were
associated with significantly larger P300 amplitudes at significantly shorter
latencies. Perceived intensity of the painful and non-painful stimuli was
comparable in both groups. The evoked potentials and reaction times to the target
tones did not differ significantly between groups. Habituation across trials was 
similar in both groups. Hence, children with migraine may display an automatic
attentional bias towards painful and potentially painful somatosensory stimuli.
Consistent with the psychobiological perspective of chronic pain, such an
attentional bias could constitute an important mechanism for migraine becoming a 
chronic problem.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 18375159 [PubMed - indexed for MEDLINE]

312: Cereb Cortex. 2008 Nov;18(11):2701-5. Epub 2008 Mar 27.

Homeostatic metaplasticity of the motor cortex is altered during headache-free
intervals in migraine with aura.

Antal A, Lang N, Boros K, Nitsche M, Siebner HR, Paulus W.

Department of Clinical Neurophysiology, Georg-August University, 37073 Göttingen,
Germany. aantal@gwdg.de

Preconditioning of the human primary motor cortex (M1) with transcranial direct
current stimulation (tDCS) can shape the magnitude and direction of excitability 
changes induced by a subsequent session of repetitive transcranial magnetic
stimulation (rTMS). Here, we examined this form of metaplasticity in migraine
patients with visual aura and healthy controls. In both groups, facilitatory
preconditioning of left M1 with anodal tDCS increased the mean amplitudes of
motor-evoked potentials (MEPs) elicited in the contralateral hand, whereas
inhibitory preconditioning with cathodal tDCS produced a decrease in amplitude.
Following cathodal tDCS, a short train of low-intensity 5-Hz rTMS antagonized the
suppression of the mean MEP amplitude in both groups. In contrast, the
homeostatic effects of 5-Hz rTMS differed between groups when rTMS was given
after anodal tDCS. In controls 5-Hz rTMS induced a marked decrease in MEP
amplitudes, whereas in migraineurs rTMS induced only a modest decrease in MEP
amplitudes, which were still facilitated after rTMS when compared with baseline
amplitudes. These findings indicate that short-term homeostatic plasticity is
altered in patients with visual aura between the attacks.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 18372292 [PubMed - indexed for MEDLINE]

313: Neurosci Bull. 2008 Apr;24(2):110-6.

Migraine as a sex-conditioned inherited disorder: evidences from China and the
world.

Wang XP, Ding HL, Geng CM, Jiang YM.

Department of Neurology, Shanghai First People's Hospital, Shanghai Jiao-Tong
University, Shanghai 200080, China. x_p_wang@hotmail.com

Migraine is a complex and heterogeneous disorder. Although several genetic models
has been proposed including autosomal-dominant/autosomal recessive, sex-linked,
sex-limited, mitochondrial, and multi-gene, none of these models can well-explain
the transmission of the disease. We hypothesied that migraine is a
sex-conditioned inherited disorder (autosomal dominant in females and autosomal
recessive in males). This hypothesis is supported by the evidence such as the
locations of genes associated with familial hemiplegic migraine, possibly
"typical" migraine as well (dominantly on chromosome 19p, 1q, and 2q),
male:female ratio of prevalence (1:2-1:4), the mostly youth-onset, the
provocation by the contraceptives, the induction by menstruation, and the
self-limitation after menopause. Female sex-hormones appear to be the key
contributor to a higher prevalence of migraine in female. Socio-environmental
factors may also play an important role.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 18369391 [PubMed - indexed for MEDLINE]

314: BMC Neurol. 2008 Mar 26;8:4.

Angiotensin-converting enzyme gene insertion/deletion polymorphism in migraine
patients.

Tronvik E, Stovner LJ, Bovim G, White LR, Gladwin AJ, Owen K, Schrader H.

Department of Neurosciences, Norwegian University of Science and Technology,
Trondheim, Norway. Erling.Tronvik@ntnu.no

BACKGROUND: The main objective of this study was to investigate the angiotensin
converting enzyme (ACE) genotype as a possible risk factor for migraine (both
with and without aura) compared to controls. We also wanted to examine whether a 
clinical response to an ACE inhibitor, lisinopril, or an angiotensin II receptor 
blocker, candesartan, in migraine prophylaxis was related to ACE genotype.
METHODS: 347 migraine patients aged 18-68 (155 migraine without aura (MoA), 187
migraine with aura (MwA) and 5 missing aura subgroup data) and 403 healthy
non-migrainous controls > 40 years of age were included in the study. A
polymerase chain reaction (PCR) was performed on the genomic DNA samples to
obtain the ACE insertion (I)/deletion(D) polymorphisms. RESULTS: No significant
differences between migraine patients and controls were found with regard to ACE 
genotype and allele distributions. Furthermore, there was no significant
difference between the controls and the MwA or MoA subgroups. CONCLUSION: In our 
sample there is no association between ACE genotype or allele frequency and
migraine. In addition, ACE genotype in our experience did not predict the
clinical response to lisinopril or candesartan used as migraine prophylactics.

PMID: 18366776 [PubMed - indexed for MEDLINE]

315: South Med J. 2008 Mar;101(3):324-6.

Asymptomatic massive subdural hematoma in a patient with bitemporal agenesis and 
bilateral temporal arachnoid cysts.

Ziaka DS, Kouyialis AT, Boviatsis EJ, Sakas DE.

Department of Neurosurgery and Radiology, University of Athens Medical School,
Evangelismos General Hospital, Athens, Greece.

The case of a 38-year-old man with a history of chronic migraine is reported.
Despite a 3 week history of changes in his migraine pattern, a normal neurologic 
examination led to conservative treatment. He later presented with worsening
headaches and imbalance; tendon reflexes were increased on the right side, and
brain computed tomography and magnetic resonance imaging revealed a massive
subacute subdural hematoma over the left hemisphere, developing on the grounds of
bilateral temporal agenesis. The presence of bilateral temporal arachnoid cysts
along with bitemporal agenesis altered clinical findings, causing only mild
symptoms where an otherwise acute and devastating neurologic deterioration would 
be expected.

Publication Types: 
    Case Reports

PMID: 18364667 [PubMed - indexed for MEDLINE]

316: Epilepsia. 2008 Jun;49(6):1099-102. Epub 2008 Mar 21.

Headache in patients with epilepsy: a prospective incidence study.

Kwan P, Man CB, Leung H, Yu E, Wong KS.

Division of Neurology, Department of Medicine & Therapeutics, The Chinese
University of Hong Kong, Prince of Wales Hospital, Hong Kong, China.
patrickkwan@cuhk.edu.hk

High prevalence of headache has been reported in patients with refractory
epilepsy in cross-sectional surveys based on retrospective recall. We conducted a
prospective study to document the incidence of headache over a 3-month
observation period in a cohort of 227 adult patients with less refractory
epilepsy. The mean seizure frequency was 2.46 per month. Fifty (22%) patients
reported to have had at least one headache episode, 45 (19.8%) had interictal
headache, 11 (4.8%) had periictal headache, and 5 (2.2%) had both interictal and 
periictal headache. Forty-nine percent of the patients with headache took
over-the-counter analgesics as acute treatment. The headache was rated to have
made very severe or substantial impact on their lives by 34% of patients. A
formal headache diagnosis was not made in any of the patients prior to the
survey. Although the incidence of headache in epilepsy patients appeared to be
low, it was underdiagnosed and associated with substantial negative impact.

PMID: 18363711 [PubMed - indexed for MEDLINE]

317: Am J Med Genet B Neuropsychiatr Genet. 2008 Oct 5;147B(7):1186-95.

A genome-wide linkage scan provides evidence for both new and previously reported
loci influencing common migraine.

Ligthart L, Nyholt DR, Hottenga JJ, Distel MA, Willemsen G, Boomsma DI.

Department of Biological Psychology, Vrije Universiteit, Amsterdam, The
Netherlands. rsl.ligthart@psy.vu.nl

Latent class analysis was performed on migraine symptom data collected in a Dutch
population sample (N = 12,210, 59% female) in order to obtain empirical groupings
of individuals suffering from symptoms of migraine headache. Based on these
heritable groupings (h(2) = 0.49, 95% CI: 0.41-0.57) individuals were classified 
as affected (migrainous headache) or unaffected. Genome-wide linkage analysis was
performed using genotype data from 105 families with at least 2 affected
siblings. In addition to this primary phenotype, linkage analyses were performed 
for the individual migraine symptoms. Significance levels, corrected for the
analysis of multiple traits, were determined empirically via a novel simulation
approach. Suggestive linkage for migrainous headache was found on chromosomes 1
(LOD = 1.63; pointwise P = 0.0031), 13 (LOD = 1.63; P = 0.0031), and 20 (LOD =
1.85; P = 0.0018). Interestingly, the chromosome 1 peak was located close to the 
ATP1A2 gene, associated with familial hemiplegic migraine type 2 (FHM2).
Individual symptom analysis produced a LOD score of 1.97 (P = 0.0013) on
chromosome 5 (photo/phonophobia), a LOD score of 2.13 (P = 0.0009) on chromosome 
10 (moderate/severe pain intensity) and a near significant LOD score of 3.31 (P =
0.00005) on chromosome 13 (pulsating headache). These peaks were all located near
regions previously reported in migraine linkage studies. Our results provide
important replication and support for the presence of migraine susceptibility
genes within these regions, and further support the utility of an LCA-based
phenotyping approach and analysis of individual symptoms in migraine genetic
research. Additionally, our novel "2-step" analysis and simulation approach
provides a powerful means to investigate linkage to individual trait components.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 18361423 [PubMed - indexed for MEDLINE]

318: Neurobiol Dis. 2008 May;30(2):186-9. Epub 2008 Feb 1.

Degradation of endocannabinoids in chronic migraine and medication overuse
headache.

Cupini LM, Costa C, Sarchielli P, Bari M, Battista N, Eusebi P, Calabresi P,
Maccarrone M.

U.O.C. Neurologia, Dipartimento Cranio Spinale, Ospedale S. Eugenio, Roma, Italy.

Chronic migraine (CM) is frequently associated with medication overuse headache
(MOH). The endocannabinoid system plays a role in modulating pain including
headache and is involved in the common neurobiological mechanism underlying drug 
addiction and reward system. Anandamide (AEA) and 2-arachidonoylglycerol are the 
most biologically active endocannabinoids, which bind to both central and
peripheral cannabinoid receptors. The level of AEA in the extracellular space is 
controlled by cellular uptake via a specific AEA membrane transporter (AMT),
followed by intracellular degradation by the enzyme AEA hydrolase (fatty acid
amide hydrolase, FAAH). AMT and FAAH have also been characterized in human
platelets. We assayed the activity of AMT and of FAAH in platelets isolated from 
four groups of subjects: MOH, CM without MOH, episodic migraine and controls. AMT
and FAAH were significantly reduced in CM and MOH, compared to either controls or
episodic migraine group. This latter finding was observed in both males and
females with CM and MOH. Changes observed in the biochemical mechanisms degrading
endogenous cannabinoids may reflect an adaptative behaviour induced by chronic
headache and/or drug overuse.

Publication Types: 
    Comparative Study

PMID: 18358734 [PubMed - indexed for MEDLINE]

319: Cephalalgia. 2008 May;28(5):553-7. Epub 2008 Mar 17.

Migraine and left-handedness are not associated. A new case-control study and
meta-analysis.

Biehl K, Frese A, Marziniak M, Husstedt IW, Evers S.

Department of Neurology, University of Münster, Münster, Germany.
kbiehl@uni-muenster.de

To investigate the possible association between migraine and left-handedness, we 
enrolled 100 patients with a diagnosis of migraine according to the International
Headache Society diagnostic criteria and 100 age- and sex-matched control
subjects into a case-control study. Handedness was determined by the Edinburgh
Handedness Inventory. There was no significant difference in the frequency or
grade of left-handedness between the two groups. Additionally, we pooled our data
with those from five similar studies, which did not alter the result. Thus,
neither our study nor the meta-analysis support Geschwind and Behan's hypothesis 
of an association between migraine and left-handedness.

Publication Types: 
    Meta-Analysis

PMID: 18355349 [PubMed - indexed for MEDLINE]

320: Cephalalgia. 2008 May;28(5):531-40. Epub 2008 Mar 17.

Patent foramen ovale and migraine: a quantitative systematic review.

Schwedt TJ, Demaerschalk BM, Dodick DW.

Washington University School of Medicine, Washington University Headache Center, 
St Louis, MO, USA.

Initial studies indicate an increased prevalence of patent foramen ovale (PFO) in
migraineurs with aura, and an increased prevalence of migraine and migraine with 
aura in persons with PFO. Retrospective analyses of PFO closure suggest
clinically significant improvements in migraine patterns. The aim of this study
was to examine the prevalence of migraine in patients with PFO, the prevalence of
PFO in migraineurs, and the effect of PFO closure on migraine. We conducted a
quantitative systematic review of articles on migraine and PFO that met inclusion
criteria, then reviewed, appraised, and subjected them to data extraction. Of 134
articles identified, 18 met a priori selection criteria. The estimated strength
of association between PFO and migraine, reflected by summary odds ratios (ORs), 
was 5.13 [95% confidence interval (CI) 4.67, 5.59], and between PFO and migraine 
with aura the OR was 3.21 (95% CI 2.38, 4.17). The grade of evidence was low. The
association between migraine and PFO was OR 2.54 (95% CI 2.01, 3.08). The grade
of evidence was low to moderate. Six studies of PFO closure suggested improvement
in migraine, but had a very low grade of evidence. The low-to-moderate grade of
evidence from observational studies supports an apparent association between PFO 
and migraine. Although PFO closure seemed to affect migraine patterns favourably,
the very low grade of available evidence to support this association precludes
definitive conclusions.

Publication Types: 
    Meta-Analysis
    Review

PMID: 18355348 [PubMed - indexed for MEDLINE]

321: Neurology. 2008 Apr 22;70(17):1510-7. Epub 2008 Mar 19.

Comment in:
    Neurology. 2008 Apr 22;70(17):1506-7.

Decreased number and function of endothelial progenitor cells in patients with
migraine.

Lee ST, Chu K, Jung KH, Kim DH, Kim EH, Choe VN, Kim JH, Im WS, Kang L, Park JE, 
Park HJ, Park HK, Song EC, Lee SK, Kim M, Roh JK.

Stroke and Stem Cell Laboratory, Department of Neurology, Seoul National
University Hospital, 28, Yongon-Dong, Chongro-Gu, Seoul, 110-744, South Korea.

OBJECTIVE: Migraine carries an increased risk for cardiovascular and
cerebrovascular diseases that cannot be explained by traditional cardiovascular
risk factors. The circulating endothelial progenitor cell (EPC) number is a
surrogate biologic marker of vascular function, and diminished EPC counts are
associated with higher cardiovascular risk. We investigated whether abnormalities
in EPC levels and functions are present in migraine patients. METHODS:
Consecutive headache patients (n =166) were enrolled, including those with
tension type headache (TTH; n = 74), migraine without aura (MO; n = 67), and
migraine with aura (MA; n = 25). EPC colony-forming units in peripheral blood
samples and migratory capacity to chemoattractants (stromal cell-derived factor 1
and vascular endothelial growth factor) and cellular senescence levels were
assayed in risk factor-matched subjects (n = 6 per group). RESULTS: The TTH group
had more cardiovascular risk factors, more headache days, and higher Framingham
risk scores than the other two groups. Mean numbers of EPC colony-forming units
were 47.8 +/- 24.3 in TTH, 20.4 +/-22.2 in MO, and 8.6 +/- 10.1 in MA patients (p
< 0.001 in TTH vs MO; p = 0.001 in MO vs MA). EPC colony counts of normal
subjects (n = 37) were not significantly different from those with TTH. Multiple 
linear regression models identified only MO, MA, and the presence of migraine (MO
+ MA) as significant predictors of EPC levels. In addition, EPCs from migraine
patients (MO and MA) showed reduced migratory capacity and increased cellular
senescence compared with EPCs from TTH or normal subjects. CONCLUSION:
Circulating endothelial progenitor cell (EPC) numbers and functions are reduced
in migraine patients, suggesting that EPCs can be an underlying link between
migraine and cardiovascular risk.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 18354079 [PubMed - indexed for MEDLINE]

322: Ann Pharmacother. 2008 Apr;42(4):543-9. Epub 2008 Mar 18.

Use of 5-HT1 agonists in pregnancy.

Evans EW, Lorber KC.

Department of Clinical and Administrative Sciences, College of Pharmacy,
University of Louisiana at Monroe, Monroe, LA, USA. eevans@ulm.edu

OBJECTIVE: To report and evaluate available data on the use of serotonin 5-HT(1) 
agonists (triptans) during pregnancy. DATA SOURCES: A PubMed search, limited to
English-language articles on human subjects, was conducted (1990-December 2007)
using the search terms pregnancy, migraine, and the individual triptan drug
names. In addition, the manufacturers of all 7 available triptans were contacted 
regarding the existence of a pregnancy registry for their drug(s) and the
availability of registry reports. STUDY SELECTION AND DATA EXTRACTION: All
retrospective and prospective studies reporting on pregnancy outcomes after the
use of a triptan were included and critically evaluated. Data from all available 
manufacturer-sponsored pregnancy registries were also included. DATA SYNTHESIS:
Safe and effective treatment of migraine during pregnancy is imperative. Data
involving sumatriptan and, to a lesser extent, naratriptan and rizatriptan, exist
primarily regarding exposure in the first trimester. These data show no
significant differences in congenital malformations or poor pregnancy outcomes
when compared with expected rates in the general population or with the observed 
rates in control subjects. There is very little information regarding exposure in
middle and late pregnancy. CONCLUSIONS: Sumatriptan appears to be a safe
treatment alternative for pregnant women who experience new-onset or worsened
migraines in the first trimester. Further observation is needed prior to
recommending its use in later trimesters. Based upon available data, the other
agents in this class cannot be recommended for use during pregnancy at this time.

PMID: 18349309 [PubMed - indexed for MEDLINE]

323: J Clin Psychiatry. 2008 Feb;69(2):266-73.

Co-occurrence of binge eating disorder with psychiatric and medical disorders.

Javaras KN, Pope HG, Lalonde JK, Roberts JL, Nillni YI, Laird NM, Bulik CM, Crow 
SJ, McElroy SL, Walsh BT, Tsuang MT, Rosenthal NR, Hudson JI.

Department of Biostatistics, Harvard School of Public Health, Boston, Mass., USA.
javaras@wisc.edu

BACKGROUND: Prior studies suggest that certain psychiatric and medical disorders 
co-occur with binge eating disorder (BED). However, there has been no large,
community-based study with diagnoses made by clinician interviewers. We used data
from that type of study to assess the co-occurrence of various psychiatric and
medical disorders with DSM-IV BED and with subthreshold BED. METHOD: From October
2002 to July 2004, we interviewed 150 probands with BED, 150 probands without
BED, and 888 of their first-degree relatives (135 of whom had BED, and 54 of whom
met specific partial criteria for BED that we defined as subthreshold BED). Study
participants were interviewed using the Structured Clinical Interview for DSM-IV 
to assess BED and other psychiatric disorders and a supplemental structured
interview to assess certain medical disorders; participants also completed a
self-report questionnaire, the Bad Things Scale. For each psychiatric and medical
disorder, we calculated the age- and sex-adjusted co-occurrence odds ratio: the
odds of having that disorder in one's lifetime among individuals with (full or
subthreshold) lifetime BED compared to individuals without lifetime BED. We also 
used subjects' responses to the Bad Things Scale to adjust for adversity
over-reporting, a type of response bias that could result in spurious findings of
co-occurrence. RESULTS: Full BED co-occurred significantly with bipolar disorder,
major depressive disorder, bulimia nervosa but not anorexia nervosa, most anxiety
disorders, substance use disorders, body dysmorphic disorder, kleptomania,
irritable bowel syndrome, and fibromyalgia. These results changed little after
correcting for adversity over-reporting. Subthreshold BED co-occurred
significantly with many, but not all, of the significantly co-occurring disorders
for full BED. CONCLUSION: BED and, to a lesser degree, subthreshold BED exhibit
substantial lifetime co-occurrence with psychiatric and medical disorders.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 18348600 [PubMed - indexed for MEDLINE]

324: J Pediatr. 2008 Apr;152(4):527-33, 533.e1. Epub 2007 Dec 3.

The placebo response in studies of acute migraine.

Fernandes R, Ferreira JJ, Sampaio C.

Pediatrics Department, Santa Maria Hospital, Lisbon, Portugal.
ricardocunhafernandes@clix.pt

OBJECTIVES: To characterize the magnitude of the placebo response in trials of
migraine therapy in children and adolescents, and to identify its determinants.
STUDY DESIGN: MEDLINE and CENTRAL were searched through November 2006 for
randomized controlled trials or controlled clinical trials of pediatric acute
migraine pharmacologic treatment that included a placebo comparator group. The
main outcomes were headache relief and pain-free response, and effect estimates
for risk differences were calculated whenever possible. The influence of placebo 
response determinants was studied using subgroup analysis. A total of 13 trials
(1324 participants in the placebo groups) were included in the analysis. RESULTS:
The pooled placebo responses for pain relief and pain-free at 2 hours were 46%
(range, 38% to 53%) and 21% (range, 17% to 26%). Parallel studies conducted in
North American centers demonstrated a significantly higher placebo response, as
did trials that used 4-point pain scales. Other placebo determinants did not
influence the effect estimate, although insufficient data were available to study
some of them. CONCLUSIONS: There is a widely variable placebo response in
pediatric migraine trials, supporting the continued use of placebo groups and
suggesting the need for more research into the placebo effect in the pediatric
population.

Publication Types: 
    Meta-Analysis
    Review

PMID: 18346509 [PubMed - indexed for MEDLINE]

325: Expert Rev Neurother. 2008 Mar;8(3):385-95.

Managing headache during pregnancy and lactation.

Marcus DA.

Pain Evaluation & Treatment Institute, 5750 Centre Avenue, Pittsburgh, PA 15206, 
USA. marcusd@upmc.edu

Headache patterns for both primary and secondary headaches are often modified in 
women during pregnancy. Although approximately two thirds of women with migraines
experience headache improvement during pregnancy; women who continue to suffer
from migraine or other headaches during pregnancy need effective clinical care to
include appropriate diagnostic studies, counseling about expectations during
pregnancy and lactation, and modifications in therapeutic regimens to minimize
risk to the fetus and nursing baby. This review describes the epidemiology of
headache during pregnancy and lactation, to include both effects of these
conditions on headache activity and possible concerns about how a maternal
headache diagnosis may influence the course and outcome of pregnancy. Although
restrictions in diagnostic testing and medication interventions are often
necessary during pregnancy and breastfeeding, this review describes evaluation
and management strategies that provide effective clinical care while minimizing
risk to the developing baby.

Publication Types: 
    Review

PMID: 18345969 [PubMed - indexed for MEDLINE]

326: Arq Neuropsiquiatr. 2007 Dec;65(4B):1123-5.

Prevalence of HLA DQB1*0602 allele in patients with migraine.

Coelho FM, Pradella-Hallinan M, Abud PC, Predazzoli Neto M, Moreira F,
Bittencourt LR, Peres MF, Tufik S.

Psychobiology Department, Universidade Federal de São Paulo, São Paulo, SP,
Brazil. fernandomorgadinho@hotmail.com

BACKGROUND: Studies have shown a high prevalence of migraine among narcoleptic
patients. HLA-DQB1*0602 and HLA DRB1 alleles are closely associated with
narcolepsy. An increase in the HLA-DRB1 allele frequency in patients with visual 
aura has raised greater awareness of the genetic background in migraine. PURPOSE:
Since the regions DR and DQ of the HLA are in tightly linkage desiquilibrium we
hypothesize that HLA-DQB1*0602 might be associated to the pathophysiology of
migraine. METHOD: We analyzed the presence of HLA DQB1*0602 allele in 50 healthy 
subjects with no history of migraine, 53 patients with migraine without aura and 
52 patients with migraine with aura. RESULTS: There was no difference in the
frequency of HLA DQB1*0602 allele when control subjects and all patients were
compared. We failed to note any difference in frequencies when comparing migraine
patients with and without aura. CONCLUSION: Further studies with different
patient populations, with other hypothalamic markers (melatonin, hypocretin) in
migraine patients may shed light on to its pathophysiology.

PMID: 18345414 [PubMed - indexed for MEDLINE]

327: Oral Maxillofac Surg Clin North Am. 2008 May;20(2):221-35, vi-vii.

Neurovascular pains: implications of migraine for the oral and maxillofacial
surgeon.

Nixdorf DR, Velly AM, Alonso AA.

Division of TMD and Orofacial Pain, University of Minnesota, School of Dentistry,
515 Delaware Street SE, Minneapolis, MN 55455, USA. nixdorf@umn.edu

Epidemiologic studies have shown that migraine headaches are a common finding in 
the general population, often associated with a high degree of disability.
Additionally, migraine has a reported comorbidity with other medical conditions, 
most notably with chronic pains, such as temporomandibular disorders. The
pathophysiologic mechanisms involved with migraine are suggestive of an increased
and prolonged hyperexcitability to stimuli, especially within the trigeminal
distribution. Because migraine is mediated by branches of the trigeminal nerve it
has the potential to mimic other types of pains, such as toothache or sinusitis. 
It is therefore recommended that oral and maxillofacial surgeons be familiar with
the diagnostic criteria for migraine headaches to identify and appropriately
treat such individuals who present to their clinics.

Publication Types: 
    Review

PMID: 18343327 [PubMed - indexed for MEDLINE]

328: Cephalalgia. 2008 May;28(5):474-83. Epub 2008 Mar 3.

The role of cervical dysfunction in migraine: a systematic review.

Robertson BA, Morris ME.

School of Physiotherapy, The University of Melbourne, Melbourne, Victoria,
Australia. b.robertson3@pgrad.unimelb.edu.au

This systematic review evaluates the strength of the evidence for the role of
cervical musculoskeletal dysfunction in migraine. In this review, cervical
musculoskeletal dysfunction will refer to the abnormal sensory afferentation from
cervical region structures contained within the receptive field of the
trigeminocervical nucleus. Electronic database searches using MEDLINE, PubMed and
CINAHL were performed, and 17 studies investigating cervical musculoskeletal
dysfunction in people with migraine were selected for review. The methodological 
quality of the included studies was assessed by two independent reviewers using a
customized checklist. The review found that intersubject differences were
inadequately reported and controlled, which resulted in grouping of participants 
with varying pathologies and symptoms. A diverse range of assessment procedures
was used by the reviewed studies, which made comparison of their findings
difficult. The assessment procedures were mainly used to quantify the degree of
cervical musculoskeletal dysfunction, rather than to identify a cause and effect 
relationship between cervical structure and migrainous pain. Although animal
study evidence proposes a role for cervical musculoskeletal dysfunction in
migraine, this systematic review of the literature found that there is currently 
no convincing evidence to confirm this phenomenon in humans.

Publication Types: 
    Meta-Analysis
    Review

PMID: 18318747 [PubMed - indexed for MEDLINE]

329: J Headache Pain. 2008 Apr;9(2):71-6. Epub 2008 Mar 4.

Triptans in the Italian population: a drug utilization study and a literature
review.

Panconesi A, Pavone E, Vacca F, Vaiani M, Banfi R.

Previous studies performed in selected populations show a poor utilization of
triptans for migraine. The objectives of our study were to establish patterns of 
triptans utilization in a large sample, covering 1/10 of Italian population (5.57
millions), and to perform a review of published studies on this topic. We
investigated drug prescription database collected during 2006 from 33 health
authorities distributed in 8 different regions. About 0.6% of the subjects
received at least one prescription of triptans in 1 year: 77.7% were females and 
22.3% males. Age distribution shows that 9.5% of patients were aged above 65, and
received prescriptions for 8.2% of packages. The review of the literature
suggests that these percentages of utilization are common to several countries,
and shows that occasional triptan users who received only one prescription in 1
year are a large percentage (40-60%); moreover, a minor population of triptan
users utilize a large amount of total triptans. Finally triptans are frequently
prescribed in people aged above 65 years, a population in which triptans are
contraindicated or not recommended. Our study and the analyzed ones indicate
suboptimal treatment of migraine patients with triptans and also an incorrect use
in some patients (triptan abusers, elderly).

PMID: 18317865 [PubMed - indexed for MEDLINE]

330: J Headache Pain. 2008 Apr;9(2):113-7. Epub 2008 Mar 4.

Not only headache: higher degree of sexual pain symptoms among migraine
sufferers.

Ifergane G, Ben-Zion IZ, Plakht Y, Regev K, Wirguin I.

Headache Clinic, Department of Neurology, Soroka Medical Center, Ben-Gurion
University of the Negev, PO Box 151, Beer-Sheva, Israel. galif@clalit.org.il

Chronic illness and chronic pain can have profound negative effects on
relationship and sexual satisfaction, yet the influence of migraine on sexuality 
has not been previously evaluated. To assess sexual functions in subjects with
migraine compared to those with no migraine. We evaluated female university
students using the Israeli sexual behavior inventory (ISBI). Migraine was
diagnosed according to self-reported symptoms according to the IHS criteria.
Several dimensions of female sexuality--desire, orgasm, sexual avoidance,
interpersonal sexual relationship, health influence, satisfaction and pain were
evaluated using a structured questionnaire. Thirty-three (23.9%) of the
participants met the IHS criteria for episodic migraine with and without aura.
Sexual activity, desire, orgasm and satisfaction from sexual life did not differ 
significantly between migraine sufferers and non-sufferers. Migraine patients
reported lower ISBI scores, higher health influence on sexual life, higher levels
of sexual pain and lower sexual satisfaction. Migraine negatively affected the
sexual life of sufferers. Sexual pain disorder is more common among migraine
sufferers compared to non-migraineurs.

PMID: 18317864 [PubMed - indexed for MEDLINE]

331: Circulation. 2008 Mar 18;117(11):1397-404. Epub 2008 Mar 3.

Comment in:
    Circulation. 2008 Mar 18;117(11):1358-60.

Migraine Intervention With STARFlex Technology (MIST) trial: a prospective,
multicenter, double-blind, sham-controlled trial to evaluate the effectiveness of
patent foramen ovale closure with STARFlex septal repair implant to resolve
refractory migraine headache.

Dowson A, Mullen MJ, Peatfield R, Muir K, Khan AA, Wells C, Lipscombe SL, Rees T,
De Giovanni JV, Morrison WL, Hildick-Smith D, Elrington G, Hillis WS, Malik IS,
Rickards A.

The King's Headache Service, King's College Hospital, Denmark Hill, London SE5
9RS, UK. dr.dowson@btopenworld.com

BACKGROUND: Patent foramen ovale (PFO) is prevalent in patients with migraine
with aura. Observational studies show that PFO closure resulted in migraine
cessation or improvement in approximately 80% of such patients. We investigated
the effects of PFO closure for migraine in a randomized, double-blind,
sham-controlled trial. METHODS AND RESULTS: Patients who suffered from migraine
with aura, experienced frequent migraine attacks, had previously failed > or = 2 
classes of prophylactic treatments, and had moderate or large right-to-left
shunts consistent with the presence of a PFO were randomized to transcatheter PFO
closure with the STARFlex implant or to a sham procedure. Patients were followed 
up for 6 months. The primary efficacy end point was cessation of migraine
headache 91 to 180 days after the procedure. In total, 163 of 432 patients (38%) 
had right-to-left shunts consistent with a moderate or large PFO. One hundred
forty-seven patients were randomized. No significant difference was observed in
the primary end point of migraine headache cessation between implant and sham
groups (3 of 74 versus 3 of 73, respectively; P=0.51). Secondary end points also 
were not achieved. On exploratory analysis, excluding 2 outliers, the implant
group demonstrated a greater reduction in total migraine headache days (P=0.027).
As expected, the implant arm experienced more procedural serious adverse events. 
All events were transient. CONCLUSIONS: This trial confirmed the high prevalence 
of right-to-left shunts in patients with migraine with aura. Although no
significant effect was found for primary or secondary end points, the exploratory
analysis supports further investigation. The robust design of this study has
served as the model for larger trials that are currently underway in the United
States and Europe.

Publication Types: 
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 18316488 [PubMed - indexed for MEDLINE]

332: Clin Neurophysiol. 2008 May;119(5):1190-200. Epub 2008 Mar 7.

Brainstem auditory-evoked potential habituation and intensity-dependence related 
to serotonin metabolism in migraine: a longitudinal study.

Sand T, Zhitniy N, White LR, Stovner LJ.

Department of Neuroscience, Norwegian University of Science and Technology,
Norway. trond.sand@ntnu.no

OBJECTIVE: Reduced habituation and increased intensity-dependence of cortical
auditory-evoked potentials have been reported in migraine, but it is not known if
brainstem mechanisms are chiefly or partly responsible for this hypersensitivity,
if brainstem excitability or habituation changes across the migraine cycle, or
how excitability relates to symptoms and serotonin metabolism. METHODS: Brainstem
auditory-evoked potentials (BAEPs) to 40, 55, and 70dB binaural rarefaction
clicks were recorded in four blocks of 750 stimuli in a blinded longitudinal
study in 41 migraine patients. Serotonin was measured in a blood sample from the 
cubital vein. The test day was classified as baseline, attack, pre-attack or
post-attack. RESULTS: Pre-attack BAEP changes were not found. Wave I, V and
interpeak III-V latency increased after the attack. III-V latency correlated with
headache history duration and usual headache attack duration. Habituation in wave
IV-V dispersion to 40dB was found in controls but not in migraine (p=0.04).
Serotonin correlated with BAEP amplitude in controls. Low serotonin correlated
with more autonomic symptoms. BAEP intensity-dependence was normal in migraine.
CONCLUSIONS: BAEP latencies, but not amplitude, increase temporarily after a
migraine attack. Abnormal habituation of brainstem wave IV-V dispersion in
migraine may suggest increased excitation in colliculus inferior at low sound
intensities, but no relation to the migraine cycle was found for wave IV-V
amplitude, dispersion or habituation. The correlation between BAEP amplitude and 
serotonin was deranged in migraine patients, but reappeared temporarily within
72h after an attack. SIGNIFICANCE: No evidence for pre-attack brainstem auditory 
sensitization was found in migraine. Intensity-dependence of AEP in migraine is
probably not a passive reflection of brainstem dysfunction. BAEP changes seem to 
reflect a slight impact of migraine on serotonergic brainstem pathways.

PMID: 18316245 [PubMed - indexed for MEDLINE]

333: Cephalalgia. 2008 Apr;28(4):334-45.

Cost-effectiveness of acupuncture treatment in patients with headache.

Witt CM, Reinhold T, Jena S, Brinkhaus B, Willich SN.

Institute for Social Medicine, Epidemiology, and Health Economics, Charité,
University Medical Centre, Berlin, Germany. claudia.witt@charite.de

The aim was to assess costs and cost-effectiveness of additional acupuncture
treatment in patients with headache compared with patients receiving routine care
alone. A randomized, controlled trial was conducted, including patients (> or =18
years old) with primary headache (more than 12 months, at least two
headaches/month). Outcome parameters were quality of life (Short Form 36), direct
and indirect costs differences during the 3-month study period and the
incremental cost-effectiveness ratio (ICER) of acupuncture treatment. A total of 
3182 patients (1613 acupuncture; 1569 controls) with headache were included
(77.4% women, mean age and standard deviation 42.6 +/- 12.3; 22.6% men, 47.2 +/- 
13.4). Over 3 months costs were higher in the acupuncture group compared with the
control [euro857.47; 95% confidence interval 790.86, 924.07, vs. euro527.34
(459.81, 594.88), P < 0.001, mean difference: euro330.12 (235.27, 424.98)]. This 
cost increase was primarily due to costs of acupuncture [euro365.64 (362.19,
369.10)]. The ICER was euro11 657 per QALY gained. According to international
cost-effectiveness threshold values, acupuncture is a cost-effective treatment in
patients with primary headache.

Publication Types: 
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 18315686 [PubMed - indexed for MEDLINE]

334: J Altern Complement Med. 2008 Mar;14(2):199-208.

"Playing their parts": the experiences of participants in a randomized
sham-controlled acupuncture trial.

Paterson C, Zheng Z, Xue C, Wang Y.

Institute of Health Service Research, Peninsula Medical School, Universities of
Exeter & Plymouth, St. Luke's Campus, Exeter, United Kingdom.
charlotte.paterson@pms.ac.uk

OBJECTIVES: Qualitative research has an important part to play in investigating
how complex interventions are implemented within randomized controlled trials
(RCTs) and what impact the RCT context has on participants, their behavior, and
their outcomes. We explored these issues within a randomized sham-acupuncture
controlled trial of traditional Chinese acupuncture for people with migraine.
METHOD: All trial participants who consented to take part in this qualitative
study were interviewed twice by a researcher who was blind to all trial data. The
acupuncture practitioner was interviewed once. Nineteen (19) semistructured
interviews, 30-60 minutes long, were transcribed, coded, and analyzed both across
and within cases. RESULTS: The 10 participants, 6 female, age 23-70 years had
severe migraine and conventional treatment had been of limited benefit. They were
satisfied with the organization of the trial and no acupuncture was perceived as 
obviously "sham." Most participants, and the practitioner, actively "played their
part" in the trial, taking on research roles that differed from their usual roles
of "patient" and "doctor." The resulting changes to their normal expectations and
behavior influenced how the intervention was delivered and experienced. There was
a reduction in talking, explanations, and participation, and treatment was
focused on the migraine and usually excluded other conditions, even if the
participants considered them to be a cause or a trigger of the migraine.
CONCLUSIONS: We conclude that treatment in the trial differed from that described
in studies of "real life" traditional acupuncture. These differences affected the
needling-the characteristic or specific intervention-as well as contextual
factors. This trial design limitation appears to be inevitable when a
sham-controlled design is used to research an intervention that is based on a
holistic and participative treatment strategy. These findings should be taken
into account in the design and interpretation of RCTs of complex interventions
such as acupuncture.

Publication Types: 
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 18315508 [PubMed - indexed for MEDLINE]

335: J Clin Neurosci. 2008 Aug;15(8):891-4. Epub 2008 Mar 7.

Electroencephalographic changes and seizures in familial hemiplegic migraine
patients with the CACNA1A gene S218L mutation.

Chan YC, Burgunder JM, Wilder-Smith E, Chew SE, Lam-Mok-Sing KM, Sharma V, Ong
BK.

Division of Neurology, National University Hospital, 5 Lower Kent Ridge Road,
Singapore 119074, Singapore. yeecheun@yahoo.com.sg

The S218L CACNA1A mutation has been previously described in two families with
familial hemiplegic migraine. We present three siblings with the mutation with
the novel association of childhood seizures, and highlight the dynamic changes
seen on electroencephalography during hemiplegic migraine attacks. Depressed
activity contralateral to the hemiparesis was seen on electroencephalography
during acute hemiplegic migraine attacks, which may be due to changes to calcium 
channels caused by the S218L mutation. Both parents were asymptomatic and did not
carry the S218L mutation in their blood. This suggests the presence of mosaicism 
in the transmitting parent.

PMID: 18313928 [PubMed - indexed for MEDLINE]

336: Dev Med Child Neurol. 2008 Apr;50(4):305-10. Epub 2008 Feb 27.

Comment in:
    Dev Med Child Neurol. 2008 Apr;50(4):246.

Analysis of the International Classification of Headache Disorders for diagnosis 
of migraine and tension-type headache in children.

Rossi LN, Vajani S, Cortinovis I, Spreafico F, Menegazzo L.

1st Pediatric Department, University of Milan and IRCCS Ospedale Maggiore
Policlinico, Mangiagalli e Regina Elena, Milan, Italy. livia.rossi@unimi.it

In 2004, the revised International Classification of Headache Disorders (ICHD-II)
was published. This study evaluates: (1) the results obtained from applying
ICHD-II to children with primary headaches to distinguish between migraine
without aura (MO) and tension-type headache (TTH); and (2) the results obtained
from introducing modifications of the classification criteria for MO as suggested
by various authors. There were 200 participants (93 males, 107 females; age range
3-17 y, mean 9 y 8 mo [SD 2 y 7 mo]). According to the ICHD-II, MO compared with 
TTH was characterized by: higher intensity of pain; higher frequency of
associated symptoms; and higher number of precipitating factors. The significant 
difference found between patients with MO/probable MO and those with TTH/probable
TTH for the variables used in the ICHD-II shows that these variables describe the
two forms well. However, 15.5% of children proved to be unclassifiable, mainly
because they could not give information for some criteria; other reasons for this
were too short a duration of episodes and the possible overlap of criteria
describing probable MO and probable TTH. The frequency of one variable, pulsating
pain, significantly increased with age. Reduction of duration to 1 hour for MO
produced a statistically non-significant increase in the number of children with 
MO. Behaviour during attacks was found to be simple to apply in evaluating
intensity and therefore was introduced as a new criterion. Severe intensity was
related to MO, whereas moderate or low-intensity was related to TTH.

PMID: 18312425 [PubMed - indexed for MEDLINE]

337: Eur J Neurol. 2008 Apr;15(4):420-7. Epub 2008 Feb 26.

A double-blind, randomized, placebo-controlled, single-dose study of the
cyclooxygenase-2 inhibitor, GW406381, as a treatment for acute migraine.

Wentz AL, Jimenez TB, Dixon RM, Aurora SK, Gold M; CXA20008 Study Investigators.

Collaborators: Becker W, Christie SN, Chouinard G, Giammarco R, Giguere N, King
DB, Mackie GF, Shapero G, Shtybel WW, Sitwell LD, Farkkila M, Liukkonen J, Sako
E, Beckmann-Reinholdt A, Goebel H, Moeckesch B, Pfaffenrath V, Schellenberg R,
Ueberall M, Lisotto C, Mazzotta G, Montagna P, Panascia B, Pop PH, Tacke TJ,
Aguilar M, Belen Caminero A, Pareja J, Aldelman J, Anspach R, Bilchik T, Elliott 
SK, Foster C, Ishkanian G, Meyers SL, Schreiber C, Spierings E, Tomasovic JJ,
Tuchman M, Wheeler S.

Migraine Clinical Development, Neurosciences Medicines Development Center,
GlaxoSmithKline, NC, USA. alison.l.wentz@gsk.com

The objective of the present study was to explore the clinical efficacy and
tolerability of GW406381, a cyclooxygenase-2 (COX-2) inhibitor with relatively
high CNS penetration, in acute migraine. This was a double-blind, single-dose
study of GW406381 compared with placebo and naproxen sodium compared with placebo
(protocol number CXA20008). Three hundred and thirty-seven subjects were
randomized 1:1:1 to GW406381 (70 mg), naproxen sodium (825 mg), or placebo for
the treatment of one migraine headache of moderate or severe intensity in a
potential 8-week period. The primary end-point was the proportion of subjects
with headache relief [reduction in headache severity score from pre-dose 2
(moderate) or 3 (severe) to 0 (no pain) or 1 (mild)] at 2 h post-dose for
GW406381 compared with placebo. Significantly higher proportions of subjects
treated with GW406381 (50%, P = 0.032) or naproxen sodium (56%, P = 0.005) than
with placebo (35%) reported headache relief at 2 h post-dose. Additional
significant benefits were observed on many secondary outcomes, including
proportions of subjects pain-free, for both GW406381 and naproxen sodium
treatment compared with placebo. Both active treatments were well tolerated.
Single-dose GW406381 (70 mg) and naproxen sodium (825 mg) were effective and well
tolerated in the treatment of acute migraine.

Publication Types: 
    Clinical Trial, Phase II
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 18312401 [PubMed - indexed for MEDLINE]

338: Clin Neurophysiol. 2008 May;119(5):1020-7. Epub 2008 Mar 4.

Visual evoked potential latency, amplitude and habituation in migraine: a
longitudinal study.

Sand T, Zhitniy N, White LR, Stovner LJ.

Department of Neuroscience, Norwegian University of Science and Technology, St.
Olavs University Hospital, N-7006 Trondheim, Norway. trond.sand@ntnu.no

OBJECTIVE: It has not been previously studied with a paired longitudinal design
if visual excitability changes occur in the preattack period across the migraine 
cycle, or how excitability and habituation relate to migraine-attack severity,
clinical photophobia and serotonin metabolism. METHODS: Monocular 62' check
reversals were applied in 33 adult migraine patients without aura (MwoA), 8 with 
aura (MA) and 31 controls. VEP was recorded in four blocks of 50 stimuli. P1
(P100) and N2 (N145) latency and N1P1 and P1N2 amplitude were measured. Serotonin
was measured in plasma and platelets sampled before each session. Sessions were
classified as preattack, attack, postattack or interictal. RESULTS: Migraine
patients had significantly higher P1N2 amplitude before the attack compared to a 
paired interictal recording (n=13, p=0.03), but habituation difference was not
found. MA patients had significantly higher P1N2 and N1P1 amplitude than controls
and MwoA. P1 latency correlated positively with headache history duration. During
attack, a positive correlation between P1N2 amplitude habituation and serotonin
emerged in MA patients. CONCLUSIONS: Increased VEP P1N2 amplitude was observed
within a few days before the attack. Visual cortex excitability seems to be
generally increased in MA as compared to MwoA patients and controls.
SIGNIFICANCE: Increased excitability of the visual cortex seems to be detectable 
in the preattack state, supporting the concept of a cyclic CNS dysfunction in
migraine.

PMID: 18308628 [PubMed - indexed for MEDLINE]

339: Am J Cardiol. 2008 Mar 1;101(5):688-92. Epub 2007 Dec 21.

Incidence, timing, and predictive factors of new-onset migraine headache attack
after transcatheter closure of atrial septal defect or patent foramen ovale.

Rodés-Cabau J, Mineau S, Marrero A, Houde C, Mackey A, Côté JM, Chetaille P,
Delisle G, Bertrand OF, Rivest D.

Quebec Heart Institute, Laval Hospital, Quebec, Canada.
josep.rodes@crhl.ulaval.ca

The objectives of this study were to evaluate the incidence, predictive factors, 
and duration of migraine headache attack (MHA) after transcatheter atrial septal 
defect (ASD) or patent foramen ovale (PFO) closure. A total of 260 consecutive
patients who underwent ASD or PFO closure in our center answered a structured
headache questionnaire focused in 3 period times, including (1) at baseline (just
before closure), (2) within the 3 months after ASD-PFO closure, and (3) at the
last (median 27 months, range 6 to 80 months) follow-up. All questionnaires were 
evaluated by a neurologist who established the diagnosis of MHA with or without
aura, according to International Headache Society criteria. The Amplatzer ASD or 
PFO device was used in 95% of the patients, and aspirin, for at least 6 months,
was the antithrombotic treatment in 91% of the cases. A total of 185 patients
(71%) had no history of MHA before ASD-PFO closure, and these constituted the
study population (mean age 39 +/- 21 years). MHA occurred in 13 patients (7%)
after ASD-PFO closure, with aura in 9 of them. MHA appeared after a median of 10 
days (range 0.3 to 30 days) after the procedure and were still present at the
last follow-up (23 +/- 17 months) in 9 patients (69%). The median number of MHA
within the 3 months after the procedure was 4 per month (interquartile range 1 to
23), and decreased to 1 per month (interquartile range 0.3 to 1) at the latest
follow-up (p = 0.03). Compared with the patients who did not develop MHA,
patients with MHA after ASD-PFO closure were younger (26 +/- 16 vs 39 +/- 21
years; p = 0.02) and were more likely to have undergone ASD closure (100% vs 58%;
p = 0.001). In the multivariate analysis, ASD closure was the only predictor of
MHA occurrence after the procedure (odds ratio 7.7; 95% confidence interval 1.5
to 22; p = 0.01). In conclusion, MHA, mostly with aura, occurred in 7% of
patients after transcatheter ASD-PFO closure and persisted in most of them after 
a mean follow-up of 2 years. ASD closure was the only independent predictor of
MHA occurrence after the procedure. These results suggest that mechanisms other
than device composition are involved in the occurrence of MHA in these cases.

PMID: 18308022 [PubMed - indexed for MEDLINE]

340: Br J Gen Pract. 2008 Feb;58(547):98-101.

Acceptance or rejection of prophylactic medicine in patients with migraine: a
cross-sectional study.

Kol CM, Dekker F, Neven AK, Assendelft WJ, Blom JW.

Department of Public Health and Primary Care, Leiden University Medical Centre,
Leiden, The Netherlands.

Most patients with two or more migraine attacks per month do not use prophylactic
medication. The aim of this study is to investigate how many patients use
prophylaxis or would like to use them, and which aspects of migraine contribute
to the choice to use prophylactic treatment. In a cross-sectional survey in three
general practices, patients were selected who were diagnosed with migraine or had
prescriptions for migraine medication. A questionnaire was sent to 283 patients
and completed by 166 patients, of whom 15 were excluded. A total of 129 females
and 22 males were included (median age 41 years). Most patients had two or more
attacks per month (66.2%). Fifty-five per cent of patients with two or more
attacks per month wanted to use prophylaxis; only 8% actually used this
treatment. To get more insight into the ideas for or against prophylactic use,
qualitative research is indicated.

Publication Types: 
    Multicenter Study

PMID: 18307853 [PubMed - indexed for MEDLINE]

341: Am J Chin Med. 2008;36(1):37-44.

The efficacy of wet-cupping in the treatment of tension and migraine headache.

Ahmadi A, Schwebel DC, Rezaei M.

Kermanshah University of Medical Sciences, Iran. ahmadiar1012@yahoo.com

Wet-cupping is an ancient medical technique still used in several contemporary
societies, but little empirical study has been devoted to test its efficacy to
treat tension and migraine headache. Using a pre-post research design, 70
patients with chronic tension or migraine headache were treated with wet-cupping.
Three primary outcome measures were considered at the baseline and 3 months
following treatment: headache severity, days of headache per month, and use of
medication. Results suggest that, compared to the baseline, mean headache
severity decreased by 66% following wet-cupping treatment. Treated patients also 
experienced the equivalent of 12.6 fewer days of headache per month. We conclude 
that wet-cupping leads to clinical relevant benefits for primary care patients
with headache. Possible mechanisms of wet-cupping's efficacy, as well as
directions for future research are discussed.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 18306448 [PubMed - indexed for MEDLINE]

342: Ann Pharmacother. 2008 Mar;42(3):403-7. Epub 2008 Feb 26.

Use of intravenous valproic acid for acute migraine.

Frazee LA, Foraker KC.

Internal Medicine, Akron General Medical Center, Akron, OH 44307, USA.
lfrazee@agmc.org

OBJECTIVE: To review the literature regarding the use of intravenous valproic
acid in aborting an acute migraine attack. DATA SOURCES: A MEDLINE (1967-June
2007) and bibliographic search of the English-language literature was conducted
using the search terms valproic acid and migraine disorders. STUDY SELECTION AND 
DATA EXTRACTION: All articles identified through the search were included. DATA
SYNTHESIS: Divalproex sodium is approved by the Food and Drug Administration for 
the prevention of migraine headaches. The use of intravenous valproic acid has
been studied as a possible treatment for acute migraine. Available studies are
small, mostly open-label and non-placebo-controlled, and used variable doses.
Valproic acid has not been shown to be superior to comparator drugs and was
inferior to prochlorperazine in one trial. CONCLUSIONS: Intravenous valproic acid
has not been proven effective for acute migraine treatment. Future trials should 
be larger, placebo-controlled, and use a standardized dose and outcome measures.

Publication Types: 
    Review

PMID: 18303140 [PubMed - indexed for MEDLINE]

343: Headache. 2008 Mar;48(3):408-16.

Effects of distraction versus spatial discrimination on laser-evoked potentials
in migraine.

de Tommaso M, Baumgartner U, Sardaro M, Difruscolo O, Serpino C, Treede RD.

University of Bari - Neurologic and Psychiatric Sciences, Bari, Italy.

OBJECTIVES: To evaluate whether migraine patients exhibit less inhibition to
painful stimuli when distracted from pain as compared to healthy subjects,
testing the spatial discrimination of painful stimuli, the performance during the
mental arithmetic task used to contrast the discrimination performance and the
behavior of N1 and N2-P2 laser-evoked potentials (LEPs) amplitudes during spatial
discrimination and during distraction. METHODS: Eight migraine patients and 8
healthy controls were examined. During repetitive series of painful laser
stimulation of the hand, they had to (1) perform a spatial discrimination task,
contrasted by (2) a mental arithmetic task that served as distraction. RESULTS:
Patients made 50% to 100% more mistakes than controls in the spatial
discrimination task (P < .001) as well as during mental arithmetic (P < .05).
Whereas healthy subjects showed a marked decrease of the LEP vertex potential
amplitudes during distraction compared to the discrimination task, no such
attenuation of LEPs was seen in migraine patients (group x task interaction, P < 
.05). N1 amplitude exhibited a left-hemisphere dominance in both groups,
significantly smaller amplitude in migraine patients, but no significant task
modulation. CONCLUSION: Migraine patients exhibited reduced inhibition by
attentional modulation of pain processing, accompanied by impaired spatial
discrimination of painful stimuli.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 18302701 [PubMed - indexed for MEDLINE]

344: Headache. 2008 Mar;48(3):341-54.

Effect of early intervention with almotriptan vs placebo on migraine-associated
functional disability: results from the AEGIS Trial.

Freitag F, Smith T, Mathew N, Rupnow M, Greenberg S, Mao L, Finlayson G, Wright
P, Biondi D; AEGIS Investigator Study Group.

Collaborators: Adelman J, Alway D, Aurora S, Boop B, Brandes JL, Cady RK, Corser 
B, Ellenbogen A, Heiring J, Huddlestone J, Hull R, Ishkanian G, Kirchner J,
Kudrow DB, LaRoche H, Lindholm K, Mechtler L, Noram W, Nunez M, Packman B,
Pellegrino R, Philbrook B, Ramadan N, Rapoport A, Rozen T, Shockey G, Silberstein
S, Simmons LK, Spierings E, Todorov A, Tomasovic J, Wendt J, Yeoman G.

Diamond Headache Clinic, LTD., Chicago, IL, USA.

OBJECTIVE: To investigate the effect of early acute migraine intervention with
almotriptan vs placebo on functional disability and health-related quality of
life (HRQoL) indicators. DESIGN/METHODS: In this multicenter, double-blind,
parallel-group trial, adults with international classification of headache
disorders-defined migraine, with or without aura, were randomized 1:1 to treat 3 
consecutive headaches with either almotriptan 12.5 mg or placebo. Patients were
instructed to take their study medication at the first sign of migraine headache 
pain of any intensity, within 1 hour of onset. Patients recorded level of
functional disability (normal, disturbed, bed rest required, emergency room
[ER]/hospitalization required) at baseline (pretreatment), 0.5, 1, 2, 4, and 24
hours posttreatment and at time of pain-free. Patients completed the Migraine
Disability Assessment Scale (MIDAS) at randomization and completed the Migraine
Quality-of-Life Questionnaire (MQoL) at 24 hours after each attack. RESULTS:
Results are presented for 315 patients (160 almotriptan, 155 placebo) in the
evaluable for efficacy population. At 2 hours posttreatment of Attack 1, 54.4%,
32.5%, 13.1%, and 0%, respectively, of almotriptan-treated patients reported
normal function, disturbed function, bed rest required, and ER/hospitalization
required compared with 38.1%, 45.2%, 16.1%, and 0.6%, respectively, of
placebo-treated patients. The differences in level of functional disability
between the 2 treatment groups were statistically significant at 2 hours (P =
.007; Cochran-Mantel-Haenszel, stratified by center) and at 4 hours (P < .001).
Resolution of pain was associated with a normal level of function; at 2 hours
posttreatment, 91.7% of patients in the total population who achieved pain-free
reported normal function compared with 44.8%, 8.0%, and 0% of patients with mild,
moderate, and severe pain, respectively. The absence compared with the presence
of photophobia, phonophobia, and nausea at 2 hours also was associated with less 
disability (P < .0001 for each symptom). Treatment with almotriptan compared with
placebo resulted in consistently better 24-hour MQoL scores with significant
results for all 3 migraine headache attacks in the social function and
feelings/concern domains. A logistic regression model determined that
pretreatment functional level (P = .0117), pretreatment pain intensity (P =
.0089), and pretreatment MIDAS score (P = .0152) were significant covariates of
the proportion of patients who achieved normal function at 2 hours posttreatment.
CONCLUSIONS: Early treatment with almotriptan within 1 hour of migraine pain
onset significantly reduced levels of functional disability at 2 and 4 hours
posttreatment compared with placebo. Consistency in improvement of HRQoL
indicators was observed across 3 headaches treated.

Publication Types: 
    Multicenter Study
    Randomized Controlled Trial

PMID: 18302700 [PubMed - indexed for MEDLINE]

345: J Cardiovasc Med (Hagerstown). 2008 Mar;9(3):233-8.

Migraine, stroke and patent foramen ovale: a dangerous trio?

Butera G, Agostoni E, Biondi-Zoccai G, Bresolin N, Fumagalli L, Chessa M,
Gallanti A, Scacciatela P, Carminati M.

Department of Paediatric Cardiology, Policlinico San Donato IRCCS, San Donato
Milanese (MI), Italy. gianfrancobutera@libero.it

The relationship between migraine, stroke and patent foramen ovale (PFO) has been
the subject of considerable research efforts. Indeed, a lot of interest has
focused on the potential benefits of percutaneous PFO closure. The aim of this
article is to review data from the currently available literature. A total of 10 
relevant studies were found in the literature, for a total of 1038 patients
undergoing percutaneous PFO closure after events of cryptogenic stroke.
Thirty-eight percent of these patients suffered from migraine. Combining the
results of the available studies, 72% of patients were cured or improved
significantly. Analysing the results according to migraine type, 81% of patients 
with migraine with aura had complete resolution or significantly improved as
compared to 72% of patients with migraine without aura. Several limitations and
drawbacks exist, however, and they are extensively discussed in this paper.

Publication Types: 
    Review

PMID: 18301138 [PubMed - indexed for MEDLINE]

346: Pain Med. 2008 Mar;9(2):175-85.

Analysis of safety and tolerability data obtained from over 1,500 patients
receiving topiramate for migraine prevention in controlled trials.

Adelman J, Freitag FG, Lainez M, Shi Y, Ascher S, Mao L, Greenberg S, Hulihan J.

Headache Wellness Center, Greensboro, North Carolina 27405, USA.
jadelman@triad.rr.com

OBJECTIVE: Topiramate is an effective and generally well-tolerated migraine
preventive therapy, as shown in three large, randomized, double-blind,
placebo-controlled registration trials. Based upon efficacy/tolerability,
topiramate 100 mg/day (50 mg BID) is the recommended target dose for most
patients with migraine. To further assess the safety and tolerability of
topiramate for migraine prevention, we analyzed safety data from 1,580 patients
who participated in the three pivotal registration trials or an earlier pilot,
randomized, double-blind, placebo-controlled trial. METHODS: The safety
population consisted of all patients who took >or=1 dose of study medication
during the double-blind phase (topiramate 50 mg/day [N = 235], 100 mg/day [N =
386], 200 mg/day [N = 514], or placebo [N = 445]). Safety assessments included
adverse event (AE) reports, physical examination, and clinical laboratory tests. 
RESULTS: Paresthesia was the most common topiramate-associated AE (35%, 51%, and 
49% of patients receiving topiramate 50 mg/day, 100 mg/day, or 200 mg/day,
respectively [6% on placebo]). The most common topiramate-associated AE were
generally mild or moderate in severity and occurred at consistently higher rates 
during the titration period, compared with the maintenance period of the
double-blind phase. AEs leading to withdrawal from the recommended dose of
topiramate 100 mg/day included paresthesia (8%), fatigue (5%), nausea (2%), and
difficulty with concentration (2%). Serious AEs were infrequent, occurring in 2% 
of 1,135 topiramate-treated patients and 3% of 445 placebo-treated patients.
Patients on topiramate experienced significant decreases in mean body weight
compared with placebo. CONCLUSIONS: Topiramate is generally safe and reasonably
well tolerated for the prevention of migraine in adults. The most common
topiramate-associated AEs were mild or moderate in severity and occurred more
frequently during titration to target doses.

Publication Types: 
    Meta-Analysis

PMID: 18298700 [PubMed - indexed for MEDLINE]

347: Cephalalgia. 2008 Apr;28(4):329-33. Epub 2008 Feb 20.

The prevalence of headache among elderly in a low-income area of São Paulo,
Brazil.

Benseñor IM, Lotufo PA, Goulart AC, Menezes PR, Scazufca M.

Hospital Universitário, University of São Paulo, São Paulo, Brazil.
isabensenor@hu.usp.br

There are scarce data about headache prevalence and its characteristics among
elderly people. The aim was to carry out a cross-sectional study to determine the
1-year prevalence of tension-type and migraine headaches in people >65 years old 
in the city of São Paulo, Brazil. All 1615 people living in the study catchment
area who agreed to participate in the study answered a questionnaire based in the
International Headache Society criteria. Prevalence (mean and 95% confidence
interval) of any type of headache in the last year was 45.6% (43.2, 48.0).
Prevalence of tension-type headache in the last year was 33.1% (30.8, 35.4):
28.1% (24.6, 31.6) for men and 36.4% (33.4, 39.4) for women; for migraine
headaches, prevalence in the last year was 10.6% (9.1, 12.1): 5.1% (3.4, 6.8) for
men and 14.1% (11.9, 16.3) for women. One-year prevalence rates of headaches, and
especially of migraine headaches, are very high among the elderly in Brazil.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 18294252 [PubMed - indexed for MEDLINE]

348: Cephalalgia. 2008 Apr;28(4):383-91. Epub 2008 Feb 20.

Erratum in:
    Cephalalgia. 2008 Jun;28(6):679.

Early vs. non-early intervention in acute migraine-'Act when Mild (AwM)'. A
double-blind, placebo-controlled trial of almotriptan.

Goadsby PJ, Zanchin G, Geraud G, de Klippel N, Diaz-Insa S, Gobel H, Cunha L,
Ivanoff N, Falques M, Fortea J.

Headache Group, Institute of Neurology, London, UK. peterg@ion.ucl.ac.uk

The study was designed to compare the response to almotriptan in migraine
patients who take medication early in the course of the attack with that when
medication is taken after pain has become moderate or severe. A randomized,
four-arm, multicentre, multinational, double-blind, placebo-controlled trial of
almotriptan (12.5 mg) comparing treatment administration when pain intensity was 
mild and within 1 h of headache onset vs. pain that had become moderate or severe
was conducted. Of 491 migraineurs enrolled, 403 were evaluable
[intention-to-treat population (ITT)]. Their mean age was 38 years, 84% were
female and they had a mean of 3.7 attacks/month. Of these patients, 10% did not
take medication according to their randomly allocated basal pain intensity (mild 
or moderate/severe) and were subsequently reassigned to that group for this
analysis-'Act when Mild (AwM)' group. In the almotriptan arms, 53% of mild basal 
pain and 38% of moderate/severe basal pain patients were pain free at 2 h (P =
0.03; primary end-point). Corresponding proportions in the placebo groups were
25% and 17% (statistically significant vs. respective almotriptan arms).
Secondary end-points (ITT) were also significantly in favour of early
intervention with almotriptan, both between and across treatment groups, such as 
sustained pain free: 45.6% vs. 30.5% (P = 0.02). Adverse events were reported in 
< 5% of treated patients in all groups (NS), with no serious events. Treatment
with almotriptan while migraine pain is still mild provides statistically
significant and clinically relevant enhancements in efficacy compared with
treatment when pain has reached higher severity levels.

Publication Types: 
    Comparative Study
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 18294251 [PubMed - indexed for MEDLINE]

349: Cephalalgia. 2008 May;28(5):484-95. Epub 2008 Feb 20.

Erratum in:
    Cephalalgia. 2008 Jun;28(6):679.

Guidelines for controlled trials of prophylactic treatment of chronic migraine in
adults.

Silberstein S, Tfelt-Hansen P, Dodick DW, Limmroth V, Lipton RB, Pascual J, Wang 
SJ; Task Force of the International Headache Society Clinical Trials
Subcommittee.

Collaborators: Silberstein S, Tfelt-Hansen P, Dodick DW, Limmroth V, Lipton RB,
Pascual J, Wang SJ.

Jefferson Headache Center, Thomas Jefferson University Hospital, Philadelphia, PA
19107, USA. stephen.silberstein@jefferson.edu [corrected]

In 1991 the Clinical Trials Subcommittee of the International Headache Society
(IHS) developed and published its first edition of the Guidelines on controlled
trials of drugs in episodic migraine because only quality trials can form the
basis for international collaboration on drug therapy, and these Guidelines would
'improve the quality of controlled clinical trials in migraine'. With the current
trend for large multinational trials, there is a need for increased awareness of 
methodological issues in clinical trials of drugs and other treatments for
chronic migraine. These Guidelines are intended to assist in the design of
well-controlled clinical trials of chronic migraine in adults, and do not apply
to studies in children or adolescents.

Publication Types: 
    Practice Guideline

PMID: 18294250 [PubMed - indexed for MEDLINE]

350: Cephalalgia. 2008 Apr;28(4):367-75. Epub 2008 Feb 22.

Familial hemiplegic migraine type 2 does not share hypersensitivity to nitric
oxide with common types of migraine.

Hansen JM, Thomsen LL, Marconi R, Casari G, Olesen J, Ashina M.

Danish Headache Centre and Department of Neurology, Glostrup Hospital, Faculty of
Health Sciences, University of Copenhagen, Copenhagen, Denmark.
jamoha01@glo.regionh.dk

Familial hemiplegic migraine type 2 (FHM-2) and common types of migraine show
phenotypic similarities which may indicate a common neurobiological background.
The nitric oxide-cyclic guanosine monophosphate (NO-cGMP) pathway plays a crucial
role in migraine pathophysiology. Therefore, we tested the hypothesis that ATP1A2
mutations in patients with FHM-2 are associated with hypersensitivity to NO-cGMP 
pathway. Eight FHM-2 patients with R202Q, R763C, V138A and L764P mutations and
nine healthy controls received intravenous infusions of 0.5 mug kg(-1) min(-1)
glyceryl trinitrate (GTN) over 20 min. We recorded the following variables:
headache intensity on a verbal rating scale; mean flow velocity in the middle
cerebral artery (V(meanMCA)) by transcranial Doppler; diameter of the superficial
temporal artery (STA) by ultrasound. The primary end-points were differences in
incidence of migraine headache and area under the curve (AUC) for headache score 
during an immediate phase (0-120 min) and a delayed phase (2-14 h) after start of
infusion. We found no difference in the incidence of reported migraine between
FHM-2 patients, 25% (two out of eight), and controls, 0% (0 out of nine) (95%
confidence interval -0.06, 0.56) (P = 0.21). The AUC(headache) in the immediate
(P = 0.37) and delayed (P = 0.09) phase was not different between patients and
controls. The GTN infusion resulted in a biphasic response in patients. During
the immediate phase, the median peak headache occurred at 30 min and tended to be
higher in patients, 1 (0, 3.8), than in controls, 0 (0, 1) (P = 0.056). During
the delayed phase, the median peak headache occurred 4 h after the start of the
infusion and was significantly higher in patients, 2.5 (0, 3), than in controls, 
0 (0, 0) (P = 0.046). We found no difference in the AUC(VmeanMCA) (P = 0.77) or
AUC(STA) (P = 0.53) between FHM-2 patients and controls. GTN infusion failed to
induce more migraine in FHM-2 patients than in controls. The pathophysiological
pathways underlying migraine headache in FHM-2 may be different from the common
types of migraine.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 18294248 [PubMed - indexed for MEDLINE]

351: Cephalalgia. 2008 Apr;28(4):376-82. Epub 2008 Feb 22.

White matter lesions in migraine and right-to-left shunt: a conventional and
diffusion MRI study.

Del Sette M, Dinia L, Bonzano L, Roccatagliata L, Finocchi C, Parodi RC, Sivori
G, Gandolfo C.

Department of Neurosciences, Ophthalmology and Genetics, University of Genova,
Genova, Italy. mdelsette@neurologia.unige.it

Subjects with migraine with aura (MA) have a high prevalence of white matter
lesions (WMLs) on magnetic resonance imaging (MRI). Moreover, right-to-left shunt
(RILES), mainly due to patent foramen ovale, is frequently associated with MA.
The aim of this study was to clarify the relationship between RILES and WML in
MA. We enrolled 87 consecutive subjects affected by MA. Patients were screened
for migraine characteristics and cerebrovascular risk factors. Transcranial
Doppler was used to diagnose RILES and MRI with T2-weighted and
diffusion-weighted imaging (DWI) to evaluate presence, number and volume of WMLs.
RILES was present in 45% of patients. We did not detect any DWI hyperintense
lesion; WMLs were present in 61% of patients on T2-weighted images. Presence of
WMLs did not correlate with any migraine clinical feature, whereas the presence, 
number and volume of WMLs increased with subjects' age. There was no significant 
difference in the total volume and number of WMLs in the group with and without
RILES. In conclusion, RILES does not increase the likelihood of finding WMLs in
migraineurs.

PMID: 18294247 [PubMed - indexed for MEDLINE]

352: J Chin Med Assoc. 2008 Feb;71(2):74-8.

Impact of migraine on the employed labor force in Taiwan.

Fuh JL, Wang SJ, Lu SR.

The Neurological Institute, Taipei Veterans General Hospital, and National
Yang-Ming University School of Medicine, Taipei, Taiwan, ROC. jlfuh@vghtpe.gov.tw

BACKGROUND: To estimate the economic impact of migraine on the employed labor
force in Taiwan. METHODS: The age- and sex-specific migraine prevalence rates,
self-reported missed workdays due to migraine, and monthly income were obtained
from 3,377 subjects of a community-based headache questionnaire survey in the
greater Taipei area. The migraine-related loss was projected to the whole
Taiwanese population based on statistics from the Directorate General of Budget, 
Accounting and Statistics of the Executive Yuan, Taiwan. RESULTS: People
suffering from migraines had a median of 2 missed workdays due to migraine in the
year prior to the survey. It is estimated that there are about 1.7 million people
who have migraines over the course of 1 year in Taiwan. Migraine resulted in 3.7 
million estimated missed workdays and an estimated cost of NT$4.6 billion due to 
loss of workdays in 2005. Employed migrainous women aged 35-54 years accounted
for 56% of the cost. CONCLUSION: Migraine is related to high work absence rates
and causes significant economic loss to the society in Taiwan.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 18290251 [PubMed - indexed for MEDLINE]

353: Med Hypotheses. 2008;71(1):14-21. Epub 2008 Mar 4.

Migraine: sex-influenced trait model?

Wang XP, Liu JM, Zhao YB.

Department of Neurology, Shanghai first People's Hospital, Shanghai Jiao-Tong
University, Shanghai, PR China. wangxp@ustc.edu

Migraine is a periodic disorder with a worldwide prevalence of 5-19%. This study 
raises the hypothesis of a sex-influenced genetic model of migraine transmission.
That migraine may be sex-influenced (autosomal dominant in females and autosomal 
recessive in males) is supported by such evidences as: (1) familial hemiplegic
migraine, subtype from migraine with aura, being dominantly assigned to autosomal
chromosome 19p, 1q, and 2q; (2) a male to female prevalence of 1:2-4; (3)
primarily young age of onset; (4) provocation by pharmaceutical contraception;
(5) induction by menstruation; (6) self-limitation after menopause; and (7) only 
female migraineurs in some migraine families. Female sex hormone in the
migraineur may be the key factor, comparable to the male sex hormone: androgen,
in the genetic baldness. Migraine appears caused by a multi-factor inheritance
with higher rates among females than males, and influenced by environmental and
cultural factors.

PMID: 18289799 [PubMed - indexed for MEDLINE]

354: J Headache Pain. 2008 Apr;9(2):77-82. Epub 2008 Feb 20.

Erratum in:
    J Headache Pain. 2008 Aug;9(4):257. Mansoureh, Togha [corrected to Togha,
Mansoureh].

Cinnarizine in refractory migraine prophylaxis: efficacy and tolerability. A
comparison with sodium valproate.

Togha M, Rahmat Jirde M, Nilavari K, Ashrafian H, Razeghi S, Kohan L.

Department of Neurology, Medical Sciences/University of Tehran, Sina Hospital,
Imam Khomeini St, 11367-46911, Tehran Islamic Republic of Iran.
toghae@sina.tums.ac.ir

This was a double-blind clinical trial designed to assess the efficacy and safety
of the cinnarizine (CIN) in patients with migraine who were refractory to
propranolol and tricyclic antidepressants in comparison with sodium valproate
(SV) to investigate whether CIN could be at least as effective as SV. A total of 
125 patients were treated in a treatment period of 12 weeks. All patients had at 
least one intake of trial medication and 2-week post baseline efficacy
observation which all were included in the ITT analysis. Of the 125 subjects
treated, 46 discontinued prematurely: 25 from the CIN and 21 from the SV group.
The main reasons for premature discontinuation were: lost to follow up (25/46,
63.2%), insufficient response (16/46, 20%), and adverse events (5/46, 12.8%). No 
statistically significant inter-group differences in the number of
discontinuation was observed (p > 0.05). In both groups, number of attacks,
intensity, and duration of attacks significantly decreased (p < 0.05). No
statistically significant inter-group differences were observed regarding the
mean number of attacks, duration, and intensity of migraine attacks for any of
the time intervals analysed, except for the mean reduction of third and fourth
visits intensity from baseline which were significantly different in two groups
(p < 0.05), with the CIN group showing more reduction. Analysis of the number of 
responders showed that in the CIN group 61.2% subjects were responders, and 63.8%
in the SV group. No statistically significant differences between the treatment
groups were found for any of the secondary parameters. Overall 26 subjects
reported one or more adverse events during the study period: 13 subjects in each 
group. Five subjects discontinued prematurely due to adverse events; two in the
CIN group with significant weight gain, and 3 in the SV group with significant
weight gain and severe tremor. These results suggest that CIN is an effective and
safe prophylactic agent even in severe migraine headache.

Publication Types: 
    Randomized Controlled Trial

PMID: 18286231 [PubMed - indexed for MEDLINE]

355: Ann Pharmacother. 2008 Mar;42(3):397-402. Epub 2008 Feb 19.

Oral metoclopramide as an adjunct to analgesics for the outpatient treatment of
acute migraine.

Azzopardi TD, Brooks NA.

St. Louis College of Pharmacy, St. Louis, MO 63110, USA. tazzopardi@stlcop.edu

OBJECTIVE: To compare the combination of oral metoclopramide plus an analgesic
with oral triptan monotherapy in the treatment of migraine attacks in
outpatients. DATA SOURCES: A search of PubMed (1966-October 2007), EMBASE
(1974-October 2007), and International Pharmaceutical Abstracts (1970-October
2007) was conducted using the search terms metoclopramide, migraine, and oral.
References of articles identified initially were also reviewed. STUDY SELECTION
AND DATA EXTRACTION: Studies evaluating the efficacy and safety of oral
metoclopramide compared with oral triptans for migraine treatment were included. 
Studies of non-oral forms of metoclopramide or studies that compared oral
metoclopramide with placebo, analgesics, ergotamine, or other migraine therapies 
were excluded. Studies in which oral metoclopramide was combined with a triptan
were also excluded. DATA SYNTHESIS: In the studies identified, oral
metoclopramide was combined with aspirin or a similar analgesic. All of the
studies assessed headache severity using a 4-point scale (0 = no pain, 1 = mild
pain, 2 = moderate pain, 3 = severe pain). Headache relief was defined as a
decrease in headache pain from grade 3 or 2 to grade 1 or 0 and was commonly
assessed at 2 hours. For all primary and secondary efficacy outcomes-including
migraine-associated nausea and vomiting-oral triptans were similar or superior to
oral metoclopramide plus an analgesic. The combination was better tolerated, with
no reports of serious metoclopramide adverse events such as extrapyramidal
symptoms or tardive dyskinesia. CONCLUSIONS: Combinations containing oral
metoclopramide plus an analgesic may be an option for patients in whom triptans
are contraindicated or who experience intolerable adverse effects, or when cost
is an issue. However, patients and physicians should be aware that the
combination will likely be less effective than oral triptans in treatment of
migraine and its associated symptoms. To determine the role of combination
therapy that includes oral metoclopramide in mild-to-moderate migraines, further 
studies are warranted.

Publication Types: 
    Review

PMID: 18285561 [PubMed - indexed for MEDLINE]

356: Cephalalgia. 2008 Apr;28(4):309-17. Epub 2008 Feb 13.

Subclinical dysfunction of cochlea and cochlear efferents in migraine: an
otoacoustic emission study.

Bolay H, Bayazit YA, Gündüz B, Ugur AK, Akçali D, Altunyay S, Ilica S, Babacan A.

Department of Neurology, Faculty of Medicine, Gazi University, Besevler, Ankara, 
Turkey. hbolay@gazi.edu.tr

Otoacoustic emission (OAE) testing enables us to identify the cochlear component 
of a hearing disorder and to monitor objectively minute changes in cochlear
status undetectable by other audiological methods. Contralateral sound-induced
suppression is mediated by medial superior olivary complex efferents which induce
hyperpolarization counteracting the amplifying effects of outer hair cell (OHC)
activity. The aim of this study was to assess functions of cochlea and its
efferents in migraine using OAE testing and contralateral suppression of
transiently evoked OAEs (TEOAE). Fifty-three migraineurs (106 ears) and 41
healthy subjects (82 ears) were included and pure tone audiometry (PTA), speech
discrimination scores (SDS), distortion product OAE (DPOAE), TEOAE and
contralateral suppression of TEOAEs were tested. PTA and SDS of migraineurs and
controls were not different (P > 0.05). DPOAEs were tested between 1 and 6 kHz
and a significant difference was detected only at 5 kHz frequency, where DPOAE
amplitudes in migraine with aura (MA) were lower than in controls (P < 0.03). The
mean amplitudes of TEOAEs were statistically insignificant between controls and
migraine groups. Contralateral sound stimulus induced significant decrease in
amplitudes of TEOAE (P = 0.005) in controls. In patients with migraine without
aura and MA, mean amplitudes of TEOAEs were not suppressed by contralateral sound
stimulus (P > 0.05). As PTA, SDS and DPOAE tests demonstrate normal functioning
of inner ear between 1 and 4 kHz, absence of suppression of the TEOAEs by
contralateral sound stimulation indicates the presence of dysfunction either in
the medial olivocochlear complex in the brainstem or at the synaptic transmission
between olivocochlear efferents and OHCs in the cochlea. Disruption in the
contralateral suppression may be one of the mechanisms predisposing to the
phonophobia symptom associated with migraine headache.

PMID: 18279433 [PubMed - indexed for MEDLINE]

357: Cephalalgia. 2008 Apr;28(4):360-6. Epub 2008 Feb 14.

Is migraine associated with right-to-left shunt a separate disease? Results of
the SAM study.

Anzola GP, Meneghetti G, Zanferrari C, Adami A, Dinia L, Del Sette M; SAM Study
Group.

Service of Neurology, S. Orsola Hospital FBF, Brescia, Italy.
gpanzola@numerica.it

Migraine with aura (MA) is associated with the persistence of patent foramen
ovale (PFO) in about 50% of cases, and migraineurs tend to have larger shunts
than controls, suggesting that right-to-left shunt (RILES) determined by PFO
could play a role in triggering migraine attacks. Moreover, some preliminary
reports have suggested that PFO closure may give relief to both migraine and aura
attacks. The aim of this study was to clarify if shunt-associated migraine (SAM) 
has clinical features that allow a distinction from shunt-unrelated migraine
(SUM), in a prospective, multicentre, observational study (SAM study). We
enrolled consecutive MA patients, who underwent a structured, standardized
questionnaire for family and personal history and for detailed migraine features.
All were systematically screened for RILES with transcranial Doppler, and for
coagulation disorders. Overall, 460 patients were included; the SUM and SAM
classes comprised 58% and 42% of patients, respectively. SAM patients were
significantly younger (34.1 +/- 10 vs. 37.1 +/- 11 years), had a more frequent
family history of migraine (76% vs. 66%) and a higher frequency of sensory
symptoms of aura (51% vs. 41%); by contrast, there was a lesser association of
SAM with other cardiac abnormalities and with coagulation disorders. The SAM
study suggests that the effect of RILES on migraine features is not relevant. The
higher family history of migraine in SAM suggests a possible genetic linkage
between migraine and RILES.

Publication Types: 
    Multicenter Study
    Research Support, Non-U.S. Gov't

PMID: 18279428 [PubMed - indexed for MEDLINE]

358: Am J Emerg Med. 2008 Feb;26(2):124-30.

Intravenous dexamethasone vs placebo as adjunctive therapy to reduce the
recurrence rate of acute migraine headaches: a multicenter, double-blinded,
placebo-controlled randomized clinical trial.

Donaldson D, Sundermann R, Jackson R, Bastani A.

William Beaumont Hospital. ddonaldson87@hotmail.com

OBJECTIVES: Some physicians prescribe corticosteroids as adjunctive therapy for
patients with migraine headaches to decrease the rate of rebound headache. The
efficacy of this practice has not been tested. Our objective is to determine the 
efficacy of single-dose dexamethasone as adjunctive therapy for emergency
medicine patients with migraine headache in preventing headache recurrence at 3
and 30 days posttreatment. METHODS: From November 2004 to November 2005, we
conducted a multicenter, double-blinded, placebo-controlled randomized clinical
trial of adult patients who met the International Headache Society definition of 
migraine headache. After informed consent, patients were randomly assigned to one
of two groups: receiving either placebo or 24 mg dexamethasone intravenously. To 
ensure generalizability, all other aspects of patient care were left to the
discretion of the emergency physician. Clinical and demographic information was
obtained; and patients were subsequently contacted at both 3 and 30 days to
determine headache recurrence, current functional disability, and need for return
to the ED. Our primary outcome measures were the recurrence of migraine headache 
at 3 and 30 days. We used Fisher exact to test for statistical significance.
RESULTS: A total of 115 patients were enrolled, with 16 patients lost to
follow-up at 3 days and 3 additional patients lost at 30 days. Baseline
characteristics as well as adverse event profiles were equivalent in both study
groups. At 3-day follow-up, 45% (95% confidence interval [CI] 31%-60%) of the
placebo group had recurrence of their migraine compared with 35% (95% CI 24%-48%)
in the dexamethasone group (P = .68). At 30-day follow-up, this relative
reduction in migraine recurrence decreased to a 4% difference between the 2
groups (P = .68). Limitations include small sample size and significant
proportion lost to follow-up. CONCLUSION: A single dose of dexamethasone as
adjunctive therapy for migraine headache does not decrease the recurrence of
migraines at 3 or 30 days.

Publication Types: 
    Multicenter Study
    Randomized Controlled Trial

PMID: 18272089 [PubMed - indexed for MEDLINE]

359: Neurology. 2008 Feb 12;70(7):548-55.

Oxcarbazepine in migraine headache: a double-blind, randomized,
placebo-controlled study.

Silberstein S, Saper J, Berenson F, Somogyi M, McCague K, D'Souza J.

Jefferson Headache Center, Thomas Jefferson University Hospital, Philadelphia, PA
19107, USA. Stephen.Silberstein@Jefferson.edu

OBJECTIVE: To evaluate the efficacy, safety, and tolerability of oxcarbazepine
(1,200 mg/day) vs placebo as prophylactic therapy for patients with migraine
headaches. METHODS: This multicenter, double-blind, randomized,
placebo-controlled, parallel-group trial consisted of a 4-week single-blind
baseline phase and a 15-week double-blind phase consisting of a 6-week titration 
period, an 8-week maintenance period, and a 1-week down-titration period, after
which patients could enter a 13-week open-label extension phase. During the
6-week titration period, oxcarbazepine was initiated at 150 mg/day and increased 
by 150 mg/day every 5 days to a maximum tolerated dose of 1,200 mg/day. The
primary outcome measure was change from baseline in the number of migraine
attacks during the last 28-day period of the double-blind phase. RESULTS:
Eighty-five patients were randomized to receive oxcarbazepine and 85 to receive
placebo. There was no difference between the oxcarbazepine (-1.30) and placebo
groups in mean change in number of migraine attacks from baseline during the last
28 days of double-blind phase (-1.74; p = 0.2274). Adverse events were reported
for 68 oxcarbazepine-treated patients (80%) and 55 placebo-treated patients
(65%). The majority of adverse events were mild or moderate in severity. The most
common adverse events (>or=15% of patients) in the oxcarbazepine-treated group
were fatigue (20.0%), dizziness (17.6%), and nausea (16.5%); no adverse event
occurred in more than 15% of the placebo-treated patients. CONCLUSIONS: Overall, 
oxcarbazepine was safe and well tolerated; however, oxcarbazepine did not show
efficacy in the prophylactic treatment of migraine headaches.

Publication Types: 
    Multicenter Study
    Randomized Controlled Trial

PMID: 18268247 [PubMed - indexed for MEDLINE]

360: Arch Neurol. 2008 Feb;65(2):218-20.

Natural course and pathogenesis of transient focal neurologic symptoms during
pregnancy.

Liberman A, Karussis D, Ben-Hur T, Abramsky O, Leker RR.

Department of Neurology, Hebrew University Hadassah Medical Center, Hadassah Ein 
Kerem, Jerusalem, Israel.

OBJECTIVES: To determine the pathogenesis and course of transient focal
neurologic symptoms in pregnant women and to identify prognostic variables that
will enable targeted workup. DESIGN: Case-control series. SETTING: Tertiary care 
university hospital. PATIENTS: Pregnant patients with acute transient focal
neurologic symptoms. Women with histories of migraine, recurrent thromboembolism,
or cerebrovascular disease were excluded. INTERVENTIONS: Diffusion-weighted
imaging (DWI), perfusion-weighted imaging, fluid-attenuated inversion recovery
(FLAIR) imaging, gradient-recalled echo imaging, and magnetic resonance
venography (MRV) and angiography to determine the presence of brain ischemia and 
venous thrombosis. Patients underwent echocardiography, duplex ultrasonography,
and a battery of hypercoagulability tests and were followed up a mean of 12
months after the event. RESULTS: Twenty-eight controls and 14 patients were
enrolled from 23 773 pregnancies. Mean age was 31.2 (range, 24-41) years and mean
gestational age at symptom onset was 28 (range, 17-44) weeks. No controls
reported transient focal neurologic symptoms, migraine aura, or headache.
Presenting symptoms included dysphasia (6 patients) and hemisensory (5) and
hemimotor (7) syndrome. In 4 patients, these symptoms were preceded by
scintillating scotoma; in 9 patients, focal symptoms were followed by a
first-ever, throbbing, migraine-like headache. Only 1 patient had evidence of
frank infarction on magnetic resonance imaging (MRI); 2 patients had single,
small, hyperintense bright foci on FLAIR imaging without accompanying lesions on 
DWI, and 11 patients had normal MRI and MRV results. Echocardiography, carotid
duplex ultrasonography, and hypercoagulability results were negative in all
patients. None of the patients had ischemic events and 4 (29%) developed
migraines with aura headaches during follow-up. CONCLUSIONS: Focal neurologic
symptoms in healthy pregnant women are frequently preceded by aural visual
phenomena and can usually be attributed to a first-ever migraine attack. Cerebral
ischemia is less common than migraine and can be reliably diagnosed with MRI.
Extensive evaluations to assess a putative hypercoagulable state and
cardiocerebrovascular pathology may not be warranted in all such patients.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 18268190 [PubMed - indexed for MEDLINE]

361: Headache. 2008 Oct;48(9):1343-8. Epub 2008 Feb 4.

Histamine-N-methyl transferase polymorphism and risk for migraine.

García-Martín E, Martínez C, Serrador M, Alonso-Navarro H, Navacerrada F, Agúndez
JA, Jiménez-Jiménez FJ.

Department of Biochemistry and Molecular Biology, School of Biological Sciences, 
University of Extremadura, Madrid, Spain.

BACKGROUND/OBJECTIVES: Histamine has been implicated in the pathogenesis of
migraine. In the CNS, histamine is almost exclusively metabolized by the
polymorphic enzyme histamine N-methyltransferase (HNMT). The HNMT gene
(chromosome 2q22.1), shows diverse single nucleotide polymorphisms. One of these,
located in exon 4 C314T, causes the amino acid substitution Thr105Ile, related to
decreased enzyme activity. The aim of this study was to investigate the possible 
association between HNMT polymorphism and the risk for migraine. METHODS: We
studied the frequency of the HNMT genotypes and allelic variantes in 197 patients
with migraine and 245 healthy controls using a PCR-RLFP method. RESULTS: The
frequencies of the HNMT genotypes and allelic variants did not differ
significantly between migraine patients and controls, and were unrelated with the
age of onset of migraine attacks, gender, personal history of allergic diseases, 
family history of migraine, or presence of aura. CONCLUSION: The results of the
present study suggest that HNMT polymorphism in not related with the risk for
migraine.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 18266724 [PubMed - indexed for MEDLINE]

362: J Headache Pain. 2008 Apr;9(2):129-31. Epub 2008 Feb 12.

Influence of physiologic hormonal modification and of hormonal treatment in a
patient with a history of migraine with aura.

Maggioni F, Palmieri A, Tropea M, Zanchin G.

Headache Centre, Department of Neurosciences, University of Padua, Padua, Italy. 
ferdinando.maggioni@unipd.it

We present the case of 48-year-old woman suffering from migraine with aura (MA)
since menarche. During her life the patient frequently presented catamenial MA
attacks with an increasing frequency during pregnancy in particular in the second
and third trimesters, and then during breast-feeding. Treatment with oral
contraceptive (OC) for endometriosis and later with cyclophosphamide,
methotrexate, fluorouracil (CMF) for breast cancer produced a higher number of
attacks. Instead, she referred an improvement with gonadotropin releasing hormone
agonist (GnRH-a) for the treatment of endometriosis and then with tamoxifen as
hormonal therapy after mastectomy and chemotherapy for breast cancer. We
highlight the importance of physiological hormonal modification and hormonal
therapies on the course of MA.

Publication Types: 
    Case Reports

PMID: 18265933 [PubMed - indexed for MEDLINE]

363: Eur Neurol. 2008;59(5):237-42. Epub 2008 Feb 8.

Subcutaneous histamine versus topiramate in migraine prophylaxis: a double-blind 
study.

Millán-Guerrero RO, Isais-Millán R, Barreto-Vizcaíno S, Gutiérrez I,
Rivera-Castaño L, Trujillo-Hernández B, Baltazar LM.

Department of Neurology, Unidad de Investigación Médica en Epidemiología Clínica,
Hospital General de Zona UMF No 1 IMSS Colima, Colima, México.
millanrebeca@hotmail.com

BACKGROUND: Histamine has a selective affinity for H3 receptors and it may
specifically inhibit the neurogenic edema response involved in migraine
pathophysiology. OBJECTIVE: To evaluate the therapeutic potential of subcutaneous
administration of histamine in migraine prophylaxis, compared with oral
administration of topiramate. METHODS: Ninety patients with migraine were
selected in a 12-week double-blind controlled clinical trial to evaluate the
efficacy of subcutaneous administration of histamine (1-10 ng twice a week)
compared with oral administration of topiramate (100 mg daily dose). The
variables studied were: headache intensity, frequency, duration, analgesic intake
and Migraine Disability Assessment. RESULTS: The data collected during the 12
weeks of treatment revealed that headache symptoms improved in both the histamine
and topiramate groups, which was evident within the first month after the
initiation of treatment, with statistically significant (p < 0.001) reductions in
headache frequency (50%), Migraine Disability Assessment score (75%), intensity
of pain (51%), duration of migraine attacks (45%), as well as in the use of
rescue medication (52%). CONCLUSION: The present study provides evidence of the
efficacy of subcutaneously applied histamine and orally administered topiramate
in migraine prophylaxis. Subcutaneously applied histamine may represent a novel
and effective therapeutic alternative in resistant migraine patients. (c) 2008 S.
Karger AG, Basel.

Publication Types: 
    Randomized Controlled Trial

PMID: 18264012 [PubMed - indexed for MEDLINE]

364: J Child Neurol. 2008 Feb;23(2):184-91.

Headache in children's drawings.

Wojaczyńska-Stanek K, Koprowski R, Wróbel Z, Gola M.

Neuropaediatric Clinic, Mikolów, Poland. wojaczynska-stanek@wp.pl

Headache is a common health problem in childhood. Children's drawings are helpful
in the diagnosis of headache type. Children, especially younger ones, communicate
better through pictures than verbally. The aim of the present study is to
evaluate the usefulness of drawings of the child's headache in the diagnostic
process carried out by a pediatrician and a pediatric neurologist. At the
beginning of a visit in a neurological clinic, or on the first day of
hospitalization, the child was asked, "Please draw your headache," or "How do you
feel your headache?" without any additional explanations or suggestions. Clinical
diagnosis of headache type was made on the basis of the standard diagnostic
evaluation. For the purpose of this study, children's headaches were categorized 
as migraine, tension-type headache, or "the others." One hundred twenty-four
drawings of children with headaches were analyzed by 8 pediatricians and 8
pediatric neurologists. The analysts were unaware of the clinical history, age,
sex, and diagnosis of the patients. The clinical diagnosis was considered the
"gold standard" to which the headache drawing diagnosis was compared. There were 
68 girls 5-18 years of age and 56 boys 7-18 years of age. Of the 124 children, 40
were clinically diagnosed with migraine (32.2%), 47 with tension-type headache
(37.9%), and 37 (29.8%) as the others. Children with migraine most frequently
draw sharp elements. Children with tension-type headache mainly drew compression 
elements and pressing elements. In the group of "the other" headaches, 21
children were diagnosed with somatoform disorders. The most frequent element in
this group's drawings was a whirl in the head. Colors used most frequently were
black and red, which signify severe pain. There was no difference in sensitivity 
of diagnoses between neurologists and pediatricians. Because the evaluation of
drawings by children with headaches done both by pediatricians and pediatric
neurologists was correct for approximately half of the children, the authors
decided to prepare a set of test pictures, including characteristic presentations
of pain. Preparing a ready set of test drawings may facilitate differentiation
for the inexperienced doctors and encourage those children who refuse to draw.

Publication Types: 
    Comparative Study
    Validation Studies

PMID: 18263755 [PubMed - indexed for MEDLINE]

365: J Headache Pain. 2008 Apr;9(2):103-7. Epub 2008 Feb 7.

Relationship between high prolactine levels and migraine attacks in patients with
microprolactinoma.

Bosco D, Belfiore A, Fava A, De Rose M, Plastino M, Ceccotti C, Mungari P,
Iannacchero R, Lavano A.

Operative Unit of Neurology, S Giovanni di Dio Hospital, Via Largo Bologna, 88900
Crotone, Italy. nico_bosco@libero.it

The pathophysiology of pituitary-associated headache is unknown, although
structural and functional features of the tumour are proposed mechanisms. The
objective of this study was to evaluate whether headache in a population with
pituitary micro-adenomas was related to hyperprolactinemia. We recruited 29
patients with microprolactinoma and headache: 16 with migraine (group A) and 13
with tension-type-headache (group B). The prolactin (PRL) levels measured during 
attacks of headache were significantly higher in nine patients (56%) of group A
and in one patient (8%) of group B. In four of the nine patients of group A, PRL 
increased after thyrotropin-releasing-hormone (TRH) test and induced severe
attacks. After dopamine-agonist (DA) treatment, the headache improved in seven
(44%) patients of the group A and in two (15%) patients of the group B. Three of 
the four patients in whom the TRH-test induced headache attacks, improved after
DA treatment. We suggest that hyperprolactinemia may contribute to development of
pain in migraine subgroups and further TRH-test could be used to predict which
patients could benefit by DA therapy.

PMID: 18256782 [PubMed - indexed for MEDLINE]

366: Cephalalgia. 2008 Mar;28(3):237-49.

Longitudinal assessment of response preparation and evaluation in migraine gives 
evidence for deviant maturation.

Oelkers-Ax R, Schmidt K, Bender S, Reimer I, Möhler E, Knauss E, Resch F,
Weisbrod M.

Department of Child and Adolescent Psychiatriy, University of Heidelberg,
Germany. rieke_oelkers@med.uni-heidelberg.de

Evidence for deviant maturation of sensory processing in migraine has come
recently from cross-sectional studies during childhood. Age-dependent development
of response preparation and evaluation is characterized using a longitudinal
design in school-aged migraine patients and controls in order to challenge the
hypothesis of migraine as a maturation disorder. Forty-six children with migraine
and 57 healthy controls aged 6-18 years were investigated and followed up 4 years
later using a simple acoustic contingent negative variation (CNV) paradigm.
Maturation in controls was characterized by increasing negativity of late and
total CNV and stability of initial CNV (iCNV) and the motor postimperative
negative variation (mPINV). Migraine patients showed a lack of development for
late and total CNV and decreasing iCNV and mPINV negativity. This first
longitudinal study confirms cross-sectional results of deviant CNV maturation in 
migraine. Altered maturation was not correlated with clinical improvement and may
represent a vulnerability marker for migraine.

Publication Types: 
    Comparative Study
    Evaluation Studies
    Research Support, Non-U.S. Gov't

PMID: 18254894 [PubMed - indexed for MEDLINE]

367: Cephalalgia. 2008 Mar;28(3):226-36.

Vasoactive intestinal peptide causes marked cephalic vasodilation, but does not
induce migraine.

Rahmann A, Wienecke T, Hansen JM, Fahrenkrug J, Olesen J, Ashina M.

Danish Headache Centre, Department of Neurology, Glostrup Hospital, Copenhagen,
Denmark. rahmana@uni-muenster.de

We hypothesized that intravenous infusion of the parasympathetic transmitter,
vasoactive intestinal peptide (VIP), might induce migraine attacks in
migraineurs. Twelve patients with migraine without aura were allocated to receive
8 pmol kg(-1) min(-1) VIP or placebo in a randomized, double-blind crossover
study. Headache was scored on a verbal rating scale (VRS), mean blood flow
velocity in the middle cerebral artery (V(mean MCA)) was measured by transcranial
Doppler ultrasonography, and diameter of the superficial temporal artery (STA) by
high-frequency ultrasound. None of the subjects reported a migraine attack after 
VIP infusion. VIP induced a mild immediate headache (maximum 2 on VRS) compared
with placebo (P = 0.005). Three patients reported delayed headache (3-11 h after 
infusion) after VIP and two after placebo (P = 0.89). V(mean MCA) decreased (16.3
+/- 5.9%) and diameter of STA increased significantly after VIP (45.9 +/- 13.9%).
VIP mediates a marked dilation of cranial arteries, but does not trigger migraine
attacks in migraineurs. These data provide further evidence against a purely
vascular origin of migraine.

Publication Types: 
    Comparative Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 18254893 [PubMed - indexed for MEDLINE]

368: Cephalalgia. 2008 Mar;28(3):203-8.

Effects of topiramate on migraine frequency and cortical excitability in patients
with frequent migraine.

Artemenko AR, Kurenkov AL, Filatova EG, Nikitin SS, Kaube H, Katsarava Z.

Division of Autonomic Nervous System Pathology, Institute of General Pathology
and Pathophysiology, and Alexander Vein Headache Clinic, Moscow, Russia.
aartemenko@gmail.com

We studied the excitability of the visual and motor cortex in 36 patients with
frequent migraine without aura (30 women, mean age 38.6 +/- 10.0 years) before
and after treatment with topiramate (100 mg/day) using transcranial magnetic
stimulation. Treatment with topiramate resulted in reduction of both headache
frequency (12.0 +/- 1.3 to 5.8 +/- 3.2 migraine days per month; P = 0.004) and
cortical excitability: motor cortex thresholds increased on the right side from
43.8 +/- 7.5% to 47.7 +/- 9.2% (P = 0.049) and on the left side from 43.4 +/-
7.0% to 47.2 +/- 9.6% (P = 0.047), and phosphene thresholds increased from 58.9
+/- 11.1% to 71.2 +/- 11.2% (P = 0.0001). Reduction of headache frequency
correlated inversely with an increase of visual thresholds and did not correlate 
with motor thresholds. The effect of topiramate in migraine prevention is complex
and can not be explained simply by inhibition of cortical excitability.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 18254890 [PubMed - indexed for MEDLINE]

369: Med Lav. 2008 Jan-Feb;99(1):8-15.

The prevalence of headache in a population of health care workers and the effects
on productivity costs.

Cristofolini A, Dalla Serra P, Scherillo G, Orrico D, Micciolo R.

Occupational Health Unit, Trento, Italy. Antonio.Cristofolini@apss.tn.it

BACKGROUND: Headache is reported as one of the most frequent causes of lost work 
time and reduced work efficiency. AIMS: The aim of this study was to determine
the impact of headache and its consequences as regards absence from work among
health care workers and reduced work efficiency. METHODS: The prevalence of
headache and its effects on ability in daily activities and work productivity
were studied and assessed on occasion of the periodic health examination of 3,620
health care workers of the Provincial Health Care Trust, Trento, by means of the 
MIDAS disability scale and parameters derived from criteria established by the
International Headache Society. RESULTS: In the previous three months 27.1% had
suffered from at least one episode of headache. The prevalence of migraine was
9.9%, with a significantly higher percentage among women (12.9%). The total
administrative costs estimated per working year were about Euro 136,836 for
migraine and about Euro 44,614 for tension-type headache (TTH). The prevalence
and features of migraine and TTH were studied. CONCLUSIONS: Data regarding the
prevalence of migraine were similar to the results reported in other studies. The
vast majority of the individuals reported no absenteeism over the previous three 
months. The study confirmed that we should continue to manage the presumed
job-related trigger factors in the best possible manner, counselling should be
made available to health care workers during the periodic health examinations or 
upon request, and if needed, the patient should be sent to a neurology specialist
for a free examination and appropriate pharmacological treatment.

PMID: 18254535 [PubMed - indexed for MEDLINE]

370: J Headache Pain. 2008 Feb;9(1):29-32. Epub 2008 Feb 5.

Performances in cerebellar and neuromuscular transmission tests are correlated in
migraine with aura.

Ambrosini A, Sándor PS, De Pasqua V, Pierelli F, Schoenen J.

Headache Clinic, IRCCS INM Neuromed, via Atinense 18, 86077 Pozzilli, Isernia,
Italy. anna.ambrosini@neuromed.it

In previous studies, we described subclinical abnormalities of neuromuscular
transmission and cerebellar functions in migraineurs. The aim of this study was
to search if these two functions are correlated in the same patient. Thirteen
migraineurs [five without aura (MO) and eight with aura (MA)] underwent both
stimulation-SFEMG and 3D-movement analysis. Single fiber EMG (SFEMG) results were
expressed as the "mean value of consecutive differences" (mean MCD). Precision of
arm-reaching movements (measured with an infrared optoelectronic tracking system)
was expressed as the average deviation in the horizontal plane. Median values of 
mean MCD and mean horizontal deviation were not different between MO and MA.
However, in MA, but not in MO, both variables were positively correlated. Thus,
we conclude that neuromuscular transmission and cerebellar functions are
correlated in the same patient when affected by migraine with aura. We suggest
that this correlation might be due to a common molecular abnormality.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 18250962 [PubMed - indexed for MEDLINE]

371: Neurology. 2008 Feb 5;70(6):431-9.

Sumatriptan normalizes the migraine attack-related increase in brain serotonin
synthesis.

Sakai Y, Dobson C, Diksic M, Aubé M, Hamel E.

Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill
University, Montréal, Québec, Canada.

BACKGROUND: Altered serotonin (5-HT) neurotransmission has been implicated in the
pathophysiology of migraine headache. OBJECTIVES: To test this hypothesis in
migraine patients in vivo using PET and alpha-[(11)C]methyl-l-tryptophan as a
surrogate marker of brain 5-HT synthetic rate during different phases of their
migraine attack and after acute antimigraine therapy with sumatriptan, and to
compare them with normal controls. METHODS: Six patients were scanned 1) within 6
hours after the onset of a spontaneous migraine attack, 2) 2 hours after
subcutaneous sumatriptan, and 3) interictally when migraine free for at least 3
days. Head pain was rated before each scan, and before and every 15 minutes after
sumatriptan. RESULTS: Brain 5-HT synthesis was highest during attacks, lowest
after sumatriptan, and intermediate when patients were migraine free. All states 
were statistically different from the others in virtually all brain regions
examined. 5-HT synthetic rates in patients during migraine attacks did not differ
from those of age- and sex-matched controls, whereas they were significantly
lower after sumatriptan in a majority of regions. Interictally, global brain 5-HT
synthetic rate was slightly, albeit not significantly, lower (-14%) in migraine
patients than in controls, with specific cortical areas exhibiting proportionally
more severe reductions (-28% to 31%). CONCLUSIONS: These findings point to a low 
cortical serotonergic tone in migraine patients interictally. Further, they
demonstrate widespread increases in brain serotonin (5-HT) synthetic rate in
migraine patients during attacks, and that triptans exert a negative feedback
regulation of brain 5-HT synthesis concurrently with modulation of pain pathways.

Publication Types: 
    Clinical Trial
    Research Support, Non-U.S. Gov't

PMID: 18250288 [PubMed - indexed for MEDLINE]

372: Behav Brain Res. 2008 May 16;189(1):220-5. Epub 2007 Dec 23.

Emotional memory and migraine: effects of amitriptyline and sex related
difference.

Gasbarri A, Arnone B, Pompili A, Cifariello A, Marini C, Tavares MC, Tomaz C.

Department of Sciences and Biomedical Technologies, University of L'Aquila,
Italy. antonella.gasbarri@cc.univaq.it

Many studies suggest that emotional arousal improves memory storage. The aim of
this study was to evaluate the effects of emotional content on explicit memory in
untreated cephalalgic patients and in migraineurs treated with the antidepressant
amitriptyline. We utilized an adaptation of two versions of the same story, with 
different arousing properties (neutral or emotional), which have been already
employed in experiments involving the enhancing effects of emotions on memory
retention. Subjects of the present study were healthy subjects and cephalalgic
patients, suffering from migraine headache, which included untreated migraineurs 
and migraineurs treated with the antidepressant amitriptyline. The findings of
our experiments suggest that chronic migraine is related to memory impairment.
Taking into account that migraine is associated with major depression, in the
present research the effect of the antidepressant amitriptyline was also
evaluated. Our results showed that amitriptyline has an impairment effect on
memory. In fact, the untreated migraineurs, compared to treated, recalled the
most emotional phase of the arousal story significantly better. Then, our data
suggest that amitriptyline prevents the enhancing effects of emotional content on
memory processes. Moreover, in agreement with our previous data, this study
suggests the existence of gender differences in the processing of emotional
stimuli and underscores the importance of sex on emotional memory mechanisms.

Publication Types: 
    Controlled Clinical Trial

PMID: 18242724 [PubMed - indexed for MEDLINE]

373: Cephalalgia. 2008 Apr;28(4):346-54. Epub 2008 Feb 1.

Headache in acute stroke. A prospective study in the first 8 days.

Verdelho A, Ferro JM, Melo T, Canhão P, Falcão F.

Department of Neurosciences, Santa Maria Hospital, University of Lisbon, Lisbon, 
Portugal. averdelho@netcabo.pt

We aimed to describe and classify headaches associated with acute stroke, by
interviewing patients consecutively admitted to a stroke unit using a validated
headache questionnaire and the International Classification of Headache Disorders
of the International Headache Society (IHS). One hundred and twenty-four patients
(61% ischaemic and 39% haemorrhagic stroke) reported headache. Headaches started 
mostly on the day of stroke, were more often continuous, pressure-type, bilateral
and located in the anterior region, were increased by movement and by cough and
lasted for a mean of 3.8 days. Tension-type was the most frequent type of
headache. Eleven per cent of headaches could not be classified using the criteria
of the IHS. Previous primary headache was documented in 71 patients. The presence
of nausea/vomiting due to acute stroke can confound headache classification using
the IHS criteria. In up to half of the patients, headache seems to be a
reactivation of previous primary headache.

PMID: 18241222 [PubMed - indexed for MEDLINE]

374: Am J Cardiol. 2008 Feb 1;101(3):396-400.

Prevalence of migraine headaches in patients with congenital heart disease.

Truong T, Slavin L, Kashani R, Higgins J, Puri A, Chowdhry M, Cheung P, Tanious
A, Child JS, Perloff JK, Tobis JM.

Department of Medicine, Division of Cardiology, David Geffen School of Medicine
at UCLA, Los Angeles, California, USA.

The prevalence of migraine headaches (MH) is 12% in the general population and
increases to 40% in patients with patent foramen ovale. This study evaluated the 
prevalence of MH in patients with congenital heart disease (CHD). Of 466 patients
contacted from the UCLA Adult Congenital Heart Disease Center, 395 (85%)
completed a questionnaire to determine the prevalence of MH. Patients were
stratified by diagnosis of right-to-left, left-to-right, or no shunt. A group of 
252 sex-matched patients with acquired cardiovascular disease served as controls.
The prevalence of MH was 45% in adults with CHD compared to 11% in the controls
(p<0.001). Of the 179 patients with MH, 143 (80%) had migraines with aura and 36 
(20%) had migraines without aura versus 36% and 64% observed in the controls
(p<0.001). The frequency of MH was 52% in the right-to-left shunt group, 44% in
the left-to-right, and 38% in the no shunt group (p=NS). In patients with a
right-to-left shunt who underwent surgical repair, 47% had complete resolution of
MH, whereas 76% experienced >50% reduction in headache days per month. In
conclusion, the prevalence of MH in all groups of adults with CHD is 3 to 4 times
more than a sex-matched control population, with increasing prevalence of MH in
patients with no shunt, left-to-right, and right-to-left shunt. The higher than
expected frequency of MH in patients with CHD without an intracardiac shunt,
suggests additional mechanisms to explain the significant association with MH.

PMID: 18237608 [PubMed - indexed for MEDLINE]

375: Headache. 2008 Feb;48(2):248-58.

Characteristics of migraine attacks and responses to almotriptan treatment: a
comparison of menstrually related and nonmenstrually related migraines.

Diamond ML, Cady RK, Mao L, Biondi DM, Finlayson G, Greenberg SJ, Wright P.

Diamond Headache Clinic, Chicago, IL 60614, USA.

OBJECTIVES: To compare the clinical characteristics of menstrually related
migraines (MRMs) and nonmenstrually related migraines (nonMRMs) and to
investigate the efficacy of almotriptan in the treatment of these migraine
subtypes. DESIGN/METHODS: These are post hoc analyses of data from the AXERT
Early miGraine Intervention Study (AEGIS), a multicenter, double-blind,
parallel-group trial that evaluated adults with IHS-defined migraine with and
without aura. Patients were randomized 1:1 to treat 3 consecutive headaches with 
almotriptan 12.5 mg or matching placebo at the first sign of headache typical of 
their usual migraine, at any level of pain intensity but within 1 hour of onset. 
MRMs were defined as those occurring +/-2 days of the first day of menstrual
flow. Post hoc analyses to describe headache characteristics pooled all migraine 
attacks experienced by patients who reported > or = 1 menses during the study
regardless of assigned treatment group. The post hoc efficacy analyses included
outcomes of almotriptan treatment compared with placebo treatment for all
migraines in patients with a menstrual record. RESULTS: Of the 275 women in the
AEGIS intent-to-treat population, 190 (69.1%; 97 almotriptan, 93 placebo; aged
18-54 years) reported > or = 1 menses during the trial. Of the 506 migraines
reported by these patients, 95 (18.8%) occurred +/-2 days of the first day of
menstrual flow and were defined as MRM. Aura was associated with 11.7% of MRM and
15.0% of nonMRM. Allodynia-associated symptoms were present with 62.8% of MRM and
57.0% of nonMRM. Prior to treatment, 19.1% of MRM were associated with normal
functional ability, 68.1% with disturbed functional ability, and 12.8% required
bed rest compared with 18.9%, 68.8%, and 12.3%, respectively, of nonMRM.
Pretreatment pain intensity was mild in 40.0%, moderate in 47.4%, and severe in
12.6% of MRM compared with 43.6%, 47.2%, and 9.2%, respectively, of nonMRM.
Almotriptan treatment efficacy outcomes for MRM vs nonMRM, respectively, were:
2-hour pain relief, 77.4% vs 68.3%; 2-hour pain free, 35.4% vs 35.9%; and
sustained pain free, 22.9% vs 23.8%. Almotriptan was similarly effective in
relieving migraine-associated symptoms and improving functional disability
associated with both MRM and nonMRM. CONCLUSIONS: Prior to treatment, the
presence of migraine-associated characteristics including aura,
allodynia-associated symptoms, photophobia, phonophobia, and nausea were similar 
for both MRM and nonMRM attacks. The pretreatment levels of pain intensity and
functional disability were likewise similar across the migraine subtypes.
Almotriptan was equally effective in the treatment of both MRM and nonMRM attacks
and was associated with an adverse event profile that was similar to placebo
treatment.

Publication Types: 
    Clinical Trial
    Comparative Study
    Multicenter Study
    Randomized Controlled Trial

PMID: 18234046 [PubMed - indexed for MEDLINE]

376: Headache. 2008 Feb;48(2):184-93.

Predictors of migraine headache recurrence: a pooled analysis from the eletriptan
database.

Dodick DW, Lipton RB, Goadsby PJ, Tfelt-Hansen P, Ferrari MD, Diener HC, Almas M,
Albert KS, Parsons B.

Department of Neurology, Mayo Clinic, Scottsdale, AZ 85259, USA.

OBJECTIVE: To identify clinical variables associated with risk of headache
recurrence within 22 hours of initial successful treatment of a migraine attack
(2-hour headache response), and to analyze the effect of eletriptan in reducing
the incidence of recurrence. METHODS: Data were pooled from 10 randomized,
double-blind, placebo-controlled trials evaluating eletriptan 40 mg (E40),
eletriptan 80 mg (E80), and sumatriptan 100 mg (S100) for acute migraine
treatment. Patients who achieved a headache response (improvement from
moderate/severe pain at baseline to mild/no pain at 2 hours postdose) were
evaluable. A multivariable logistic regression analysis identified significant
predictors of headache recurrence (return to moderate/severe pain intensity
within 22 hours of initial headache response). Treatment response was assessed in
two high-risk subgroups, defined by the presence of significant recurrence
predictors. RESULTS: Of 4312 patients responding to acute treatment within 2
hours postdose, 1232 (29%) experienced recurrence. Initial headache response
within 2 hours was significantly higher for E40 (62.0%), E80 (67.4%), and S100
(57.9%) compared to placebo (25.1%; all P < .0001). Three clinical variables were
significant predictors of recurrence: female gender, age > or = 35 years, and
severe baseline headache pain. Among patients with all 3 risk factors (n = 742;
17% of total population), recurrence rates were lower with E40 (35.6%) and E80
(32.9%) than placebo (47.8% P < .01). The same result was observed in the
subgroup of patients with 2 risk factors (female gender and age > or = 35 years; 
P < .0001 vs placebo). Sustained headache and pain-free response rates (a
headache/pain-free response at 2 hours postdose with no headache recurrence and
no rescue medication use in the subsequent 22 hours) were significantly higher
with E40 and E80 than placebo in both high-risk subgroups (P < .05). CONCLUSION: 
Female gender, age > or = 35 years, and severe baseline headache pain are
significant predictors of headache recurrence during a migraine attack.
Eletriptan is effective at reducing the incidence of headache recurrence in
high-risk subgroups.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 18234045 [PubMed - indexed for MEDLINE]

377: J Headache Pain. 2008 Feb;9(1):19-27. Epub 2008 Jan 30.

Alcohol and migraine: trigger factor, consumption, mechanisms. A review.

Panconesi A.

ASL 11, Empoli, Florence, Italy. a.panconesi@virgilio.it

This study investigates the importance of alcohol as a migraine trigger factor,
the prevalence of alcohol consumers and the mechanism of headache provocation. A 
MEDLINE search from 1988 to October 2007 was performed for "headache and
alcohol", "headache and wine", "migraine and alcohol" and "migraine and wine". In
retrospective studies, about one-third of the migraine patients reported alcohol 
as a migraine trigger, at least occasionally, but only 10% of the migraine
patients reported alcohol as a migraine trigger frequently. Regional differences 
were reported, perhaps depending in part on alcohol habits. No differences were
found between migraine and tension headache and different genders. However,
prospective studies limit considerably the importance of alcohol as a trigger.
Recent studies show that migraine patients consume less alcohol than controls.
Red wine was reported to be the principal trigger of migraine, but other studies 
show that white wine or other drinks are more involved. Then, the discussion
based on the different composition of the various alcoholic beverages, in order
to discover the content of alcoholic drinks responsible for migraine attack,
reflects this uncertainty. Biogenic amines, sulphites, flavonoid phenols,
5-hydroxytryptamine mechanisms and vasodilating effects are discussed. The fact
that few headache patients cannot tolerate some alcoholic drinks does not justify
the consideration that alcohol is a major trigger and the suggestion of
abstinence. In fact, low doses of alcohol can have a beneficial effect on
patients such as migraineurs, who were reported to have an increased risk of
cardiovascular disease.

Publication Types: 
    Review

PMID: 18231712 [PubMed - indexed for MEDLINE]

378: Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2008 Feb;105(2):e35-7.

Hemicrania continua presenting as temporomandibular joint pain.

Taub D, Stiles A, Tucke AG.

Department of Oral and Maxillofacial Surgery, Thomas Jefferson University
Hospital, Philadelphia, PA, USA.

Patients presenting with unilateral facial pain present a unique diagnostic
challenge for dental practitioners. As dentists, we routinely look for
maxillofacial pathology, temporomandibular disorders, or odontogenic abscesses as
the etiology of pain in these patients. However, several types of the chronic
daily headaches may also produce signs and symptoms similar to dental or
maxillofacial pathology. One such headache, hemicrania continua, is typically
characterized by a continuous, throbbing, unilateral headache and is completely
responsive to treatment with indomethacin. In this article we present 2 cases in 
which initial symptoms suggested temporomandibular disorders but the patients
were ultimately diagnosed with hemicrania continua. A brief review of hemicrania 
continua and its treatment is included. Thoroughly understanding this entity and 
realizing that it may present as temporomandibular pain will allow us to more
readily diagnose the condition and implement effective treatment.

Publication Types: 
    Case Reports

PMID: 18230375 [PubMed - indexed for MEDLINE]

379: Br J Health Psychol. 2008 Feb;13(Pt 1):67-71.

Emotional approach coping and self-efficacy moderate the effects of written
emotional disclosure and relaxation training for people with migraine headaches.

Kraft CA, Lumley MA, D'Souza PJ, Dooley JA.

Wayne State University, Detroit, Michigan 48202, USA.

OBJECTIVES: We tested whether emotional skills and headache management
self-efficacy (HMSE) moderated effects of written emotional disclosure (WED)
compared with control writing and a different intervention, relaxation training
(RT). DESIGN/METHODS: Undergraduates with migraine headaches reported emotional
approach coping (EAC) and HMSE; were randomized to WED, RT, or control; and
assessed on health measures at baseline and 3-month follow-up. RESULTS: Greater
EAC predicted improvement following WED compared with RT and control, whereas low
HMSE predicted improvement following both WED and RT, compared with control.
CONCLUSIONS: Emotional skill may specifically - and low health management
self-efficacy may generally - predict positive responses to WED.

Publication Types: 
    Comparative Study
    Randomized Controlled Trial
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 18230235 [PubMed - indexed for MEDLINE]

380: Med Hypotheses. 2008;70(4):860-5. Epub 2008 Jan 15.

Migraine and circle of Willis anomalies.

Cucchiara B, Detre J.

Department of Neurology, University of Pennsylvania Medical Center, 3400 Spruce
Street, Philadelphia, PA 19104, United States. cucchiar@mail.med.upenn.edu

Several mechanisms are currently thought to contribute to migraine pathogenesis, 
including interictal neuronal hyperexcitability, cortical spreading depression
underlying the symptom of aura, and trigeminal nerve activation at a peripheral
and central level. However, these mechanistic concepts incompletely explain
migraine susceptibility in individual patients and do not fully account for the
well documented association between migraine and ischemic cerebrovascular
disease, including increased risk of both clinical stroke and subclinical brain
lesions in migraine patients. The circle of Willis is a major source of
collateral blood flow supply in the human brain, and developmental morphologic
variants of the circle of Willis are extremely frequent. Altered cerebral blood
flow (CBF) has been demonstrated in regions supplied by variant circle of Willis 
vessels. Our central hypothesis is that circle of Willis anomalies correlate with
alterations in cerebral hemodynamics and contribute to migraine susceptibility
and ischemic complications of migraine. Dysregulation of CBF may allow relative
ischemia to develop in the setting of increased metabolic demand related to
neuronal hyperexcitability, may trigger cortical spreading depression, and may
predispose individuals with migraine to ischemic lesions and stroke.
Identification of structural alterations in the cerebral vasculature in migraine 
patients would have several important pathophysiological and clinical
implications. First, it would provide a developmental mechanism for migraine
susceptibility that may lead to further insights into genetic predisposition to
migraine. Second, it would expand understanding of potential mechanisms
underlying migraine aura and linking migraine with both clinical and subclinical 
cerebral infarction. Third, it could help to identify the subpopulation of
patients at risk of progressive cerebral ischemia so as to target preventative
therapies appropriately. Fourth, it would suggest a role for further diagnostic
evaluation to determine migraine mechanism in individual patients, analogous to
the current paradigm in ischemic stroke in which determination of stroke
mechanism is critical to therapeutic decision-making.

PMID: 18226467 [PubMed - indexed for MEDLINE]

381: Ther Drug Monit. 2008 Feb;30(1):5-9.

Triptans in pregnancy.

Soldin OP, Dahlin J, O'Mara DM.

Department of Medicine, Georgetown University Medical Center, Washington, DC
20057, USA. os35@georgetown.edu

The triptans are a class of tryptamine-based drugs indicated for in the treatment
of migraine headaches. The triptans act as serotonin (5-hydroxytriptamine) (5-HT)
agonists by binding to various serotonin receptors, causing vasoconstriction and 
neuronal inhibition to alleviate migraines. There are 7 types of triptans
currently available on the U.S. market: almotriptan, eletriptan, frovatriptan,
naratriptan, rizatriptan, sumatriptan and zolmitriptan. The objective of this
study was to examine the use and effects of triptans in pregnancy. Although three
of the triptans have pregnancy registries maintained by the manufacturer, triptan
use in pregnancy has not been extensively studied. Information on the use of
sumatriptan during pregnancy is relatively more abundant, because it has been on 
the market longer than the other triptans and may also have a higher percentage
of the market share. There are no data to suggest teratogenicity for any of the
triptans, although preterm birth rates appear to be elevated.

Publication Types: 
    Review

PMID: 18223456 [PubMed - indexed for MEDLINE]

382: Recent Pat CNS Drug Discov. 2007 Jun;2(2):141-4.

The experience of combining agents, specially triptans and non steroidal
anti-inflammatory drugs, for the acute treatment of migraine - a review.

Krymchantowski AV, Jevoux Cda C.

Headache Center of Rio. Rio de Janeiro, Brazil. abouchkrym@globo.com

BACKGROUND AND OBJECTIVES: Migraine is a highly prevalent neurological disorder
with multiple mechanisms. Targeting a single mechanism has been found only
partially effective for treating individual attacks. Recently, the role of
combining agents for the acute migraine treatment has gained attention and the
combination of a triptan plus a nonsteroidal anti-inflammatory drug (NSAID) has
demonstrated better efficacy. This article focuses on the review of available
literature for treating migraine attacks with two or more agents, related patents
as well as analyzes the characteristics of the recently approved fixed
combination sumatriptan-naproxen. METHODS: The following terms migraine, acute
treatment, sumatriptan, naproxen and combination were searched on MEDLINE. In
addition, abstracts presented in the major meetings carried out by the American
Headache and the International Headache Societies along with the American Academy
of Neurology were also evaluated. RESULTS: Although most of the few studies
encountered were not controlled, there is a clear trend for the better efficacy
in combining triptans with NSAID. Additionally, the results of two recent large
and controlled studies using fixed combinations of sumatriptan (50mg and 85mg)
with 500mg naproxen sodium confirm the initial observations of the clear
superiority of this combination over the isolated use of each agent. The
differences in the endpoints of 24-hour pain relief response as well as pain-free
and pain-relief parameters at 2-hour time-points are the clearest efficacy
measures. Tolerability was not different between the two studied drugs.
CONCLUSIONS: Combining triptans with NSAID and other agents for the acute
treatment of migraine suggests better outcome efficacy measures than the use of
single agents. The fixed combination of sumatriptan and naproxen sodium offers
improved 2-hour and 24-hour benefits over the monotherapy. Recently, issued FDA
approval for marketing the combination (sumatriptan 50mg-naproxen 500mg)
emphasizes the usefulness and safety of this new treatment for migraine attacks.

Publication Types: 
    Review

PMID: 18221225 [PubMed - indexed for MEDLINE]

383: Eur J Neurol. 2008 Feb;15(2):190-5.

Cognitive and psychiatric effects of topiramate monotherapy in migraine
treatment: an open study.

Romigi A, Cervellino A, Marciani MG, Izzi F, Massoud R, Corona M, Torelli F,
Zannino S, Uasone E, Placidi F.

Servizio di Neurofisiopatologia, Centro di Medicina del Sonno, Policlinico Tor
Vergata, University of Rome 'Tor Vergata', Rome, Italy, and Fondazione Santa
Lucia, Rome, Italy. a_romigi@inwind.it

Few data are available on cognitive and psychiatric effects of topiramate (TPM)
monotherapy in migraine. Twenty patients affected by migraine were treated with
TPM monotherapy. At the same time, twenty control subjects were selected. A
comprehensive neuropsychological and behavioural battery of tests were performed 
at baseline (T0), at titration (T1) and in maintenance period (T2). Topiramate
serum levels were also investigated at T1 and T2. On comparison with the control 
group, no cognitive and psychiatric differences were detected at baseline. A
significant reduction of word fluency score (P < 0.05) was evident after TPM
treatment, both at T1 and T2. No patient developed psychiatric adverse events.
TPM induced an impairment of verbal fluency and no psychiatric adverse events,
demonstrating selective negative cognitive profile in migraine therapy. Slow
titration, low doses, lack of previous psychiatric disorders and/or familial
history may explain our data.

PMID: 18217888 [PubMed - indexed for MEDLINE]

384: Clin Ther. 2007;29 Suppl:2511-9.

Diagnosis of menstrual headache and an open-label study among those with
previously undiagnosed menstrually related migraine to evaluate the efficacy of
sumatriptan 100 mg.

Schreiber CP, Cady RK.

Clinvest/Headache Care Center, Springfield, Missouri 65807, USA.

BACKGROUND: Headache associated with menses is often not formally diagnosed.
OBJECTIVES: The goal of this study was to evaluate patients with menstrual
headache who had never previously been diagnosed with migraine and assign 1988
International Headache Society (IHS) diagnoses to their menstrual headaches.
Secondary objectives included evaluation of the treatment efficacy of newly
diagnosed menstrually related migraine (MRM) with sumatriptan 100 mg and patient 
satisfaction with sumatriptan versus satisfaction with previous therapy. METHODS:
Patients were recruited via advertisement in a local daily newspaper, and
headache diagnosis and eligibility criteria of respondents were assessed by
telephone. During telephone screening, IHS criteria for headache were applied to 
symptoms described by patients as menstrual headache. Those with previously
undiagnosed headaches who fulfilled criteria for migraine without or with aura
(IHS 1.1 or 1.2) and all inclusion/exclusion criteria at visit 1 were provided
with sumatriptan 100 mg to treat 1 MRM. Patients were instructed to treat their
next MRM as early as possible after the onset of headache. A treatment diary was 
provided with study medication for documentation of headache pain severity and
associated symptoms; time of treatment and response at 30, 60, and 90 minutes and
at 2, 4, 24, and 48 hours posttreatment; medication for persistence or
recurrence; adverse effects; and onset of menstrual cycle. In analysis, headache 
response was defined as a reduction in pretreatment head pain from moderate or
severe to mild or no pain. RESULTS: A total of 153 patients responded to an
advertisement seeking menstrual headache sufferers. After the preliminary
screening by telephone, 105 patients were assigned IHS diagnoses based on
reported symptoms associated with their menstrual headache. Overall, 63% (66/105)
fulfilled criteria for IHS 1.1 (migraine without aura), 12% (13/105) met criteria
for IHS 1.2 (migraine with aura), and 5% (5/105) met criteria for IHS 1.7
(migrainous disorder). Of the 79 patients meeting the criteria for IHS 1.1 or
1.2, 45 patients were enrolled. Thirty-nine (mean age, 34.8 years; mean duration 
of experiencing menstrual headaches, 11.1 years) of the 45 patients treated 1 MRM
with sumatriptan 100 mg per protocol (6 patients were lost to follow-up or
withdrew consent). Headache response was reported by 70% of patients at 2 hours
and 86% at 4 hours. The pain-flee response after treatment at the moderate or
severe phase occurred in 41% of patients at 2 hours and in 61% at 4 hours. All 39
patients reported previous use of nonsteroidal anti-inflammatory medications for 
acute treatment of headache; in addition, 1 of the 39 also took acetylsalicylic
acid/caffeine/butalbital, 1 took acetaminophen/caffeine/butalbital, 1 took
ketorolac, and 1 took acetaminophen plus codeine. In terms of patient
satisfaction, 69% of patients were satisfied with sumatriptan versus 15% of
patients who were satisfied with their previous therapy. CONCLUSIONS:
Seventy-five percent of women with previously undiagnosed menstrual headaches met
diagnostic criteria for migraine in this small sample. Two hours after treatment 
with sumatriptan 100 rag, 70% of patients with headaches treated at moderate to
severe pain had a pain relief response (reduction to mild or no pain).

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 18164918 [PubMed - indexed for MEDLINE]

385: J Headache Pain. 2008 Feb;9(1):5-12. Epub 2008 Jan 23.

Treatment of migraine attacks based on the interaction with the
trigemino-cerebrovascular system.

Link AS, Kuris A, Edvinsson L.

Biomedical Center Lund, Lund, Sweden.

Primary headaches such as migraine are among the most prevalent neurological
disorders, affecting up to one-fifth of the adult population. The scientific work
in the last decade has unraveled much of the pathophysiological background of
migraine, which is now considered to be a neurovascular disorder. It has been
discovered that the trigemino-cerebrovascular system plays a key role in migraine
headache pathophysiology by releasing the potent vasodilator calcitonin
gene-related peptide (CGRP). This neuropeptide is released in parallel with the
pain and its concentration correlates well with the intensity of the headache.
The development of drugs of the triptan class has provided relief for the acute
attacks but at the cost of, mainly cardiovascular, side effects. Thus, the
intention to improve treatment led to the development of small CGRP receptor
antagonists such as olcegepant (BIBN4096BS) and MK-0974 that alleviate the acute 
migraine attack without acute side events. The purpose of this review is to give 
a short overview of the pathological background of migraine headache and to
illustrate the mechanisms behind the actions of triptans and the promising CGRP
receptor blockers.

Publication Types: 
    Review

PMID: 18217201 [PubMed - indexed for MEDLINE]

386: J Headache Pain. 2008 Feb;9(1):13-8. Epub 2008 Jan 24.

Pharmacogenomics and migraine: possible implications.

Tfelt-Hansen P, Brøsen K.

Danish Headache Centre, Department of Neurology, University of Copenhagen,
Glostrup Hospital, Glostrup 2600, Denmark, tfelt@inet.uni2.dk

Pharmacogenomics is the science about how inherited factors influence the effects
of drugs. Drug response is always a result of mutually interacting genes with
important modifications from environmental and constitutional factors. Based on
the genetic variability of pharmacokinetic and in some cases pharmacodynamic
variability we mention possible implications for the acute and preventive
treatment of migraine. Pharmacogenomics will most likely in the future be one
part of our therapeutic armamentarium and will provide a stronger scientific
basis for optimizing drug therapy on the basis of each patient's genetic
constitution.

Publication Types: 
    Review

PMID: 18217199 [PubMed - indexed for MEDLINE]

387: Clin J Pain. 2008 Feb;24(2):106-15.

Acupuncture in migraine: investigation of autonomic effects.

Bäcker M, Grossman P, Schneider J, Michalsen A, Knoblauch N, Tan L, Niggemeyer C,
Linde K, Melchart D, Dobos GJ.

Complementary and Integrative Medicine, Department of Internal Medicine V,
University of Duisburg-Essen, Kliniken Essen Mitte, Germany.
marcus.baecker@uni-essen.de

OBJECTIVE: A dysregulation of the autonomic nervous system is discussed as a
pathogenetic factor in migraine. As acupuncture has been shown to exhibit
considerable autonomic effects, we tested whether the clinical effects of
acupuncture in migraine prophylaxis are mediated by changes of the autonomic
regulation. METHODS: We simultaneously monitored changes of heart-rate
variability (HRV) as an index of cardiac autonomic control and clinical
improvement during an acupuncture treatment in 30 migraineurs. HRV was derived
from spectral analysis of the electrocardiogram, which was performed before,
during, and after the first and the last session of a series of 12 acupuncture
sessions. Migraineurs were randomly allocated to 2 groups receiving either verum 
acupuncture (VA) or sham acupuncture (SA) treatment. RESULTS: Across the combined
VA and SA groups, the clinical responders (with at least 50% reduction of
migraine attacks) exhibited a decrease of the low-frequency (LF) power of HRV in 
the course of the treatment, which was not be observed in patients without
clinical benefit. VA compared with SA induced a stronger decrease of
high-frequency power. The mode of acupuncture, however, did not have an impact on
the LF component of HRV or the clinical outcome. DISCUSSION: The data indicate,
that VA and SA acupuncture might have a beneficial influence on the autonomic
nervous system in migraineurs with a reduction of the LF power of HRV related to 
the clinical effect. This might be due to a reduction of sympathetic nerve
activity. VA and SA induce different effects on the high-frequency component of
HRV, which seem, however, not to be relevant for the clinical outcome in
migraine.

Publication Types: 
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 18209515 [PubMed - indexed for MEDLINE]

388: Clin J Pain. 2008 Feb;24(2):98-105.

Acupuncture in migraine prevention: a randomized sham controlled study with
6-months posttreatment follow-up.

Alecrim-Andrade J, Maciel-Júnior JA, Carnè X, Severino Vasconcelos GM,
Correa-Filho HR.

Department of Medicine, Autonomous University of Barcelona, Barcelona, Catalunya,
Spain. jalecrim@uol.com.br

OBJECTIVE: To assess the efficacy of acupuncture in migraine prophylaxis.
METHODS: Thirty-seven patients with migraine were enrolled in a randomized
control trial at the Headache clinic located in a University Hospital. Real and
sham acupuncture groups received 16 acupuncture sessions over 3 months. Treatment
was individualized in the real acupuncture group and minimal acupuncture was used
in the sham group. The primary end point was the percentage of patients with a
>or=50% reduction in their migraine attack frequency in the second, third,
fourth, fifth, and sixth (months) compared with the first one (baseline period). 
Primary and secondary end points were measured comparing headache diaries.
RESULTS: Real acupuncture group showed improvement with significant differences
compared with the sham acupuncture group in the primary efficacy end point
(P=0.021) at the second month of the treatment. Differences also appeared in 2
secondary end points: number of days with migraine per month (P=0.007) in the
second month and the percentage of patients with >or=40% reduction in migraine
attack frequency in the first (P=0.044) and second months (P=0.004) of the
treatment. These differences disappeared in the third (last) month of the
treatment as a consequence of the high improvement of the sham acupuncture group.
Comparisons within each group showed that several migraine parameters evaluated
improved significantly in both groups. CONCLUSIONS: Individualized treatment
based on traditional Chinese medicine plays a role in preventing migraine
attacks. Nevertheless, sham acupuncture had similar effects. Major conclusions
were limited by the small sample sizes however the observed trends may contribute
to design future trials.

Publication Types: 
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 18209514 [PubMed - indexed for MEDLINE]

389: Prog Biophys Mol Biol. 2008 May;97(1):54-9. Epub 2007 Oct 30.

A numerical study of the blocking of migraine by Rolando sulcus.

Grenier E, Dronne MA, Descombes S, Gilquin H, Jaillard A, Hommel M, Boissel JP.

Unité de Mathématiques Pures et Appliqués U.M.R. 5669, E.N.S. Lyon, 46 allée
d'Italie, 69364 Lyon, et IMTh, France. egrenier@umpa.ens-lyon.fr

Migraine with aura is a complex phenomena, which remains still not completely
understood. A striking fact is that its clinical manifestations may change from
one patient to another. Migraine with aura may only consist in visual
hallucinations, but may as well go on to temporary aphasy. However, for all the
patients it always stops before it goes from area 3 to area 4, thus just before
crossing Rolando sulcus. In this paper, we give arguments showing that the
detailed geometry of Rolando sulcus in human cortex may by itself explain that
migraine attack never crosses Rolando sulcus.

Publication Types: 
    Review

PMID: 18207221 [PubMed - indexed for MEDLINE]

390: Acta Neurol Scand. 2008 Jul;118(1):29-41. Epub 2008 Jan 20.

Assessing quality and normalization of microarrays: case studies using
neurological genomic data.

Hershey AD, Burdine D, Liu C, Nick TG, Gilbert DL, Glauser TA.

Department of Pediatrics, Divisions of Neurology, Cincinnati Children's Hospital 
Medical Center, Cincinnati, OH, USA. andrew.hershey@chmcc.org

BACKGROUND: Genomic analysis using microarray tools has the potential benefit of 
enhancing our understanding of neurological diseases. The analysis of these data 
is complex due to the large amount of data generated. Many tools have been
developed to assist with this, but standard methods of analysis of these tools
have not been established. OBJECTIVE: This study analyzed the sensitivity and
specificity of different analytical methods for gene identification and presents 
a standardized approach. METHODS: Affymetrix HG-U133 plus 2.0 microarray datasets
from two neurological diseases - chronic migraine and new-onset epilepsy - were
used as source data and methods of analysis for normalization of data and
identification of gene changes were compared. Housekeeping genes were used to
identify non-specific changes and gender related genes were used to identify
specific changes. RESULTS: Initial normalization of data revealed that 5-10% of
the microarray were potential outliers due to technical errors. Two separate
methods of analysis (dChip and Bioconductor) identified the same microarray chips
as outliers. For specificity and sensitivity testing, performing a per-gene
normalization was found to be inferior to standard preprocessing procedures using
robust multichip average analysis. CONCLUSIONS: Technical variation in microarray
preprocessing may account for chip-to-chip and batch-to-batch variations and
outliers need to be removed prior to analysis. Specificity and sensitivity of the
final results are best achieved following this identification and removal with
standard genomic analysis techniques. Future tools may benefit from the use of
standard tools of measurement.

Publication Types: 
    Research Support, N.I.H., Extramural

PMID: 18205880 [PubMed - indexed for MEDLINE]

391: Headache. 2008 Apr;48(4):586-600. Epub 2008 Jan 18.

Neuromodulators for migraine prevention.

Kaniecki R.

University of Pittsburgh Headache Center, Pittsburgh, PA 15213, USA.

Migraine is a debilitating condition characterized by a cycle of painful
headaches and headache-related symptoms interspersed with periods of worry,
distress, and apprehension. The negative impact of migraine on patient
functioning, workplace productivity, and other daily activities has been
demonstrated through the use of a variety of clinician- and patient-reported
assessment tools, including the Migraine-Specific Questionnaire and the Migraine 
Disability Assessment questionnaire. In addition to considering the frequency and
severity of migraine, clinicians need to encourage more open dialogue with their 
patients about the impact of this disorder on daily activities and productivity. 
Only then can the most appropriate course of treatment be determined.
Appropriately prescribed acute and preventive therapies should break the cycle of
migraine and improve the daily activities of patients with this chronic
condition. Divalproex sodium and topiramate are neuromodulators that are approved
by the US Food and Drug Administration (FDA) for the prophylaxis (prevention) of 
migraine headache in adults. Non-FDA-approved neuromodulators sometimes used in
the management of migraine headache include gabapentin, lamotrigine,
levetiracetam, and zonisamide. All medications need to be titrated, and
treatment-related adverse events need to be managed appropriately. Preventive
medications should be taken for at least 2-3 months to ascertain their
therapeutic effect.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 18205800 [PubMed - indexed for MEDLINE]

392: Am J Hypertens. 2008 Mar;21(3):360-4. Epub 2008 Jan 17.

Comment in:
    Am J Hypertens. 2008 Mar;21(3):245.

Headaches and migraines are associated with an increased risk of preeclampsia in 
Peruvian women.

Sanchez SE, Qiu C, Williams MA, Lam N, Sorensen TK.

Health Direction V Lima City: Jr. Antonio Raymondi 220, La Victoria, Lima, Peru.

BACKGROUND: Migraine, a common chronic-intermittent disorder of idiopathic origin
characterized by severe debilitating headaches and autonomic nervous system
dysfunction, and preeclampsia, a hypertensive disorder of pregnancy, share many
common epidemiological and pathophysiological characteristics. Both conditions
are associated with higher subsequent risk of ischemic stroke. Moreover,
endothelial dysfunction, platelet activation, hyper-coagulation, and inflammation
are common to both disorders. We assessed the risk for preeclampsia in relation
to the maternal history of migraine before and during pregnancy in Peruvian
women. METHODS: Cases consisted of 339 women with preeclampsia, and controls were
337 normotensive women. During in-person interviews conducted at delivery, women 
were asked whether they had physician-diagnosed migraines, and they were asked
questions that allowed for headaches and migraines to be classified according to 
criteria established by the International Headache Society (IHS). Logistic
regression procedures were used to calculate odds ratios (ORs) and 95% confidence
intervals (CIs). RESULTS: A history of any headache before or during pregnancy
was associated with a 2.4-fold increased risk for preeclampsia (OR = 2.4; 95% CI 
1.7-3.3). Women classified as having migraines that began prior to pregnancy had 
a 3.5-fold increased risk for preeclampsia (95% CI 1.9-6.4) as compared with
those who reported no migraines. Women with migraines during pregnancy had a
fourfold increased risk of preeclampsia (OR = 4.0, 95% CI 1.9-8.2) compared with 
non-migraineurs. CONCLUSIONS: Our findings are consistent with previous reports
and we have extended them to the Peruvian population. Prospective cohort studies,
however, are needed to more rigorously evaluate the extent to which migraines
and/or its treatments are associated with the occurrence of preeclampsia.

Publication Types: 
    Research Support, N.I.H., Extramural

PMID: 18202669 [PubMed - indexed for MEDLINE]

393: Cephalalgia. 2008 Mar;28(3):250-6. Epub 2008 Jan 15.

Intravenous valproate aborts glyceryl trinitrate-induced migraine attacks: a
clinical and quantitative EEG study.

Thomaides T, Karapanayiotides T, Kerezoudi E, Avramidis T, Haeropoulos C, Zoukos 
Y, Spantideas A.

Department of Neurology, Greek Red Cross Hospital, Athens, Greece.
thomaides@ath.forthnet.gr

We evaluated EEG changes and pain relief in migraineurs with glyceryl trinitrate 
(GTN)-induced attacks treated with intravenous sodium valproate (iSVP). EEG
frequency analysis was performed in 45 migraineurs without aura and in 19
controls at baseline, at the time of maximum GTN-induced headache, and 30 min
after 300 mg iSVP. Nineteen migraineurs presented early specific headache
(migraine identical to spontaneous attacks; MSp) and 26 presented early
non-specific headache (MnSp). During attacks in MSp there was an increase of
theta [16.6% (14.8-19.3) to 19.4% (17.4-22.1), P = 0.02] and delta activity [3.6%
(3.1-4.4) to 5.4% (3.9-6.5), P = 0.009], whereas there was no decrease in alpha
[41.4% (36.2-45.1) to 39.7% (34.7-44.8)] or beta activity [37.6% (34.7-40.3) to
35.1% (33.5-38.8)]. iSVP reduced migraine from severe/moderate to mild/no pain in
17 (90%) MSp patients, and was associated with reversion of the slow rhythmic
activity to baseline levels [theta 16.9% (14.6-18.9); delta 3.2% (3-4.1)]. There 
was no change in EEG frequency activity after administration of GTN or iSVP in
controls and in MnSp. iSVP is well tolerated and effective in treating
GTN-induced migraine in migraineurs without aura, and appears to restore the
disturbances of cortical electrogenesis associated with these attacks.

Publication Types: 
    Comparative Study

PMID: 18201252 [PubMed - indexed for MEDLINE]

394: BMC Health Serv Res. 2008 Jan 16;8:13.

Profiling quality of care for patients with chronic headache in three different
German hospitals - a case study.

Melchart D, Wessel A, Brand R, Hager S, Weidenhammer W.

Centre for Complementary Medicine Research, Department of Internal Medicine II,
Technical University, Munich, Kaiserstr, 9, 80801 München, Germany.
dieter.melchart@lrz.tum.de

BACKGROUND: Legal requirements for quality assurance in German rehabilitation
hospitals include comparisons of providers. Objective is to describe and to
compare outcome quality of care offered by three hospitals providing in-patient
rehabilitative treatment exemplified for patients with chronic headache. METHODS:
We performed a prospective three center observational study on patients suffering
from chronic headache. Patients underwent interventions commonly used according
to internal guidelines of the hospitals. Measurements were taken at three points 
in time (at admission, at discharge and 6 months after discharge). Indicators of 
outcome quality included pain intensity and frequency of pain, functional
ability, depression, quality of life and health related behavior. Analyses of
differences amongst the hospitals were adjusted by covariates due to case-mix
situation. RESULTS: 306 patients from 3 hospitals were included in statistical
analysis. Amongst the hospitals, patients differed significantly in age,
education, diagnostic subgroups, beliefs, and with respect to some pain-related
baseline values (covariates). Patients in all three hospitals benefited from
intervention to a clinically relevant degree. At discharge from hospital, outcome
quality differed significantly after adjustment according to case-mix only in
terms of patients' global assessment of treatment results. Six months after
discharge, the only detectable significant differences were for secondary
outcomes like improved coping with stress or increased use of self-help. The
profiles for satisfaction with the hospital stay showed clear differences amongst
patients. CONCLUSION: The results of this case study do not suggest a definite
overall ranking of the three hospitals that were compared, but outcome profiles
offer a multilayer platform of reliable information which might facilitate
decision making.

Publication Types: 
    Multicenter Study
    Research Support, Non-U.S. Gov't

PMID: 18199321 [PubMed - indexed for MEDLINE]

395: Cephalalgia. 2008 Feb;28(2):127-38.

Migraine patients as trainers of their fellow patients in non-pharmacological
preventive attack management: short-term effects of a randomized controlled
trial.

Mérelle SY, Sorbi MJ, van Doornen LJ, Passchier J.

Department of Medical Psychology and Psychotherapy, Erasmus University Medical
Centre, Rotterdam, The Netherlands.

In conformity with current views on patient empowerment, we designed and
evaluated the effects of home-based behavioural training (BT) provided by lay
trainers with migraine to small groups of fellow patients. The primary aims of BT
were to reduce attack frequency and increase perceived control over and
self-confidence in attack prevention. In a randomized controlled trial the BT
group (n = 51) was compared with a waitlist-control group (WLC), receiving usual 
care (n = 57). BT produced a minor (-21%) short-term effect on attack frequency
and clinically significant improvement in 35% of the participants. Covariance
analysis showed a non-significant trend (P = 0.07) compared with WLC. However,
patients' perceived control over migraine attacks and self-confidence in attack
prevention increased significantly with large effect sizes. Patients with high
baseline attack frequency might benefit more from BT than those with low attack
frequency. In conclusion, lay trainers with migraine strengthened fellow
patients' perceived control, but did not induce a significant immediate
improvement in attack frequency.

Publication Types: 
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 18197883 [PubMed - indexed for MEDLINE]

396: Cephalalgia. 2008 Feb;28(2):105-13.

A review of the genetic relation between migraine and epilepsy.

Haan J, Terwindt GM, van den Maagdenberg AM, Stam AH, Ferrari MD.

Department of Neurology, Leiden University Medical Centre, Leiden, the
Netherlands. jhaan@rijnland.nl

A possible relation between migraine and epilepsy has been a matter of debate for
many decades. Clinical, epidemiological and therapeutic similarities may be
coincidental and are no proof of a common aetiological background. However, a
genetically determined dysfunction of ion channels seems to point to a common
underlying mechanism for both paroxysmal disorders. For example, mutations in the
three known genes for familial hemiplegic migraine can cause epilepsy. It is
likely that the development of specific drugs aimed at restoring ion-channel
function and/or related cellular signalling pathways might benefit patients with 
epilepsy as well as those with migraine. This review will briefly summarize the
clinical, epidemiological, pathophysiological and therapeutic similarities
between migraine and epilepsy. Most attention will be paid to the genetic
relationship between these two paroxysmal disorders.

Publication Types: 
    Review

PMID: 18197881 [PubMed - indexed for MEDLINE]

397: J Chin Med Assoc. 2007 Dec;70(12):535-40.

Erratum in:
    J Chin Med Assoc. 2008 Oct;71(10):549.

Comment in:
    J Chin Med Assoc. 2007 Dec;70(12):519-20.

Botulinum toxin type a in the prophylactic treatment of transformed migraine in
Taiwanese patients: a review of 30 consecutive cases.

Liu YC, Fuh JL, Chen RC, Lin KP, Wang SJ.

Department of Neurology, Ten Chan [corrected] Hospital, Chung-Li, Taiwan, R O C.

BACKGROUND: Botulinum toxin type A (BoNT-A) for the treatment of patients with
various forms of migraine has been studied, but there is a paucity of data
regarding the use of BoNT-A in Asian headache patients. Our study was designed to
evaluate the efficacy of BoNT-A in the treatment of transformed migraine (TM) in 
a population of Taiwanese patients. METHODS: We retrospectively analyzed 30
patients who underwent BoNT-A treatment for TM from July 2003 to May 2004. Of 30 
patients, 14 had palpable muscle tenderness (or tender points) in the pericranial
region and 16 did not. All patients received injections into the corrugator,
procerus, frontalis, and temporalis muscles (a total of 30 U), while a subset of 
TM patients with tender points (6 of 14 patients) also received injections to
additional muscles based on a follow-the-tenderness approach (mean dose, 45 U).
RESULTS: Twenty-seven of the 30 patients (90%) surveyed reported effective relief
of their symptoms with BoNT-A treatment (at least a 50% reduction in the number
of headache days or in headache intensity). The greatest reduction in headache
days per month and headache intensity was found in TM patients with tender points
who received a mean dose of 45 U compared to those who received fixed-site dosing
of 30 U. CONCLUSION: Our results suggest that BoNT-A may be an effective
prophylactic treatment for TM in Taiwanese patients. Interestingly, similar
efficacy was demonstrated in TM patients with tender points compared to those
without tender points when an additional dose of BoNT-A was injected into the
tender muscles in the former.

PMID: 18194894 [PubMed - indexed for MEDLINE]

398: Headache. 2008 Oct;48(9):1349-55. Epub 2008 Jan 11.

Responsiveness of migraine-ACT and MIDAS questionnaires for assessing migraine
therapy.

García ML, Baos V, Láinez M, Pascual J, López-Gil A.

CS Mendiguchía Carriche, Primary Care, Madrid, Spain.

BACKGROUND: Migraine is frequently undertreated. The 4-item Migraine Assessment
of Current Therapy (Migraine-ACT) questionnaire is a simple and reliable tool to 
identify patients requiring a change in current acute migraine treatment.
Objective: To investigate the responsiveness of the Migraine-ACT tool, and
compare it with that of the Migraine Disability Assessment (MIDAS) questionnaire,
for patients with migraine at 1100 primary care sites in Spain. METHODS: Patients
eligible for this open-label, 2-visit prospective study reported migraine for >1 
year and >or=1 migraine attack per month and were new to the clinic or on
follow-up care for <6 months. Validated Spanish versions of the Migraine-ACT and 
MIDAS questionnaires were administered, and patient satisfaction with treatment
was recorded, at baseline and at 3 months. RESULTS: A total of 3272 patients, 78%
female, were enrolled, and 2877 (88%) returned for the 3-month visit.
Investigators changed baseline migraine treatment for 72% of returning patients; 
85% and 80% of these patients had improved Migraine-ACT and MIDAS scores at 3
months, respectively. Patients who reported being completely or very satisfied
with migraine treatment numbered 492 (15%) at baseline and 1406 (49%) at 3
months. Migraine-ACT and MIDAS score agreement for improvement at 3 months was
poor (kappa = 0.339). Both the mean MIDAS score and the distribution of
Migraine-ACT scores improved over the course of 3 months; however, Migraine-ACT
scores were significantly (P < .001) more sensitive (83% vs 75%) and specific
(72% vs 58%) than MIDAS scores. The area under the curve in the
receiver-operating characteristic analysis was significantly (P < .0001) greater 
for Migraine-ACT (0.82) as compared with the MIDAS (0.70) questionnaire.
CONCLUSIONS: These results suggest that the Migraine-ACT questionnaire can be
used more reliably than the MIDAS questionnaire for detecting improvements in
treatment of new and follow-up patients with migraine.

Publication Types: 
    Clinical Trial
    Multicenter Study
    Research Support, Non-U.S. Gov't

PMID: 18194304 [PubMed - indexed for MEDLINE]

399: Headache. 2008 Apr;48(4):606-10. Epub 2008 Jan 11.

The risk of newly diagnosed asthma in migraineurs with or without previous
triptan prescriptions.

Becker C, Brobert GP, Almqvist PM, Johansson S, Jick SS, Meier CR.

Basel Pharmacoepidemiology Unit, Division of Clinical Pharmacology and
Toxicology, University Hospital Basel, Basel, Switzerland.

BACKGROUND: Previous observational studies reported an increased prevalence of
asthma in migraine patients. Whether triptans affect the asthma risk has not yet 
been explored in an epidemiological study. OBJECTIVE: To estimate the risk of
newly diagnosed asthma in patients with a general practitioner-diagnosed migraine
in the UK between 1994 and 2001. METHODS: A population-based follow-up study and 
a nested case-control analysis were conducted using the General Practice Research
Database. RESULTS: The study encompassed 51,688 migraineurs and the same number
of matched controls. In the follow-up analysis, the relative risk of developing
asthma in migraineurs compared with non-migraineurs was 1.3 (95% confidence
interval [CI] 1.1-1.4). In the nested case-control analysis, the adjusted odds
ratio for asthma in migraineurs overall was 1.17 (95% CI 1.01-1.35), and for
those with a recent triptan prescription 1.12 (95% CI 0.65-1.94). CONCLUSION: The
risk of developing asthma was not materially altered for patients with a general 
practitioner-recorded migraine diagnosis, regardless of triptan use.

PMID: 18194300 [PubMed - indexed for MEDLINE]

400: Headache. 2008 Feb;48(2):267-71. Epub 2008 Jan 8.

A migraine prophylaxis educational intervention in a Medicaid population.

Owens C, Pugmire B, Owens K.

College of Pharmacy, Idaho State University, Pocatello, ID 83209, USA.

OBJECTIVES: To assess migraine prophylactic drug utilization in the Idaho
Medicaid population and to evaluate responsiveness of practitioners to an
educational intervention from the Idaho Medicaid Drug Utilization Review (DUR)
Program. BACKGROUND: While established guidelines recommend migraine prophylactic
therapies for defined patient populations and several drugs have demonstrated
efficacy, their actual utilization is reportedly low. METHODS: Profiles for Idaho
Medicaid patients were reviewed retrospectively to identify candidates for
migraine prophylactic therapy based on excessive triptan utilization. Use of a
prophylactic agent was then characterized for these patients, and an educational 
mailing was sent to practitioners directly involved in the care of patients who
did not appear to be using prophylaxis. Patient profiles were again assessed 6
months following the mailing to determine if a trial of a prophylactic drug had
been attempted. RESULTS: A total of 1909 patients were identified as having at
least one claim for a triptan drug in the year studied. Of these patients, 360
appeared to be candidates for prophylaxis, but 154 had no record of prophylactic 
drug use. In the 6 months following the intervention mailing, 27 of the 91
non-prophylaxis patients (30%) who were still active clients of Idaho Medicaid
and who had seen their physician during that time, appeared to have been given a 
trial of a migraine prophylactic drug. CONCLUSIONS: Following an educational
intervention for Idaho Medicaid patients identified through retrospective DUR, a 
trial of a migraine prophylactic drug was initiated for approximately one-third
of potential candidates.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 18194289 [PubMed - indexed for MEDLINE]

401: Headache. 2008 Feb;48(2):284-6. Epub 2008 Jan 8.

Comment in:
    Headache. 2008 Oct;48(9):1380.

Memantine and NMDA antagonism for chronic migraine: a potentially novel
therapeutic approach?

Spengos K, Theleritis C, Paparrigopoulos T.

Department of Neurology, University of Athens School of Medicine, Eginition
Hospital, Athens, Greece.

We present the case of a woman with chronic migraine who unexpectedly reported
full remission of headache after memantine, an NMDA receptor antagonist, was
administered for treating concomitant mild cognitive impairment. An underlying
dose-dependent effect of memantine on headache symptoms in chronic daily headache
and chronic migraine could be assumed.

Publication Types: 
    Case Reports

PMID: 18194287 [PubMed - indexed for MEDLINE]

402: Clin Pharmacokinet. 2008;47(2):139-46.

Relevance of absorption rate and lag time to the onset of action in migraine.

Maas HJ, Spruit MA, Danhof M, Della Pasqua OE.

Leiden/Amsterdam Center for Drug Research, Leiden University, Leiden, The
Netherlands.

OBJECTIVE: The objective of this analysis was to simulate the performance of oral
triptan formulations with varying absorption characteristics and their impact on 
the onset and magnitude of the antimigraine effect using a Markov model for
migraine attacks. ANALYSIS: Sumatriptan pharmacokinetic data were obtained from
clinical pharmacology studies in which marketed solid formulations were
administered. Based on a population pharmacokinetic model, mean
concentration-time profiles were generated by varying the absorption rate
constant and lag time. Subsequently, the simulated profiles were evaluated in a
disease model of migraine to predict the onset and duration of the effect (the
pain-free, pain-relief response). RESULTS: Based on a therapeutic dose of 50 mg
of sumatriptan, a maximum gain in the pain-free response of 12% was achieved with
an increased absorption rate. This gain in the response was reached approximately
0.5 hours after administration. A decrease only in the lag time with respect to
the currently available formulations (i.e. 0.24 hours) resulted in a maximum gain
of 5% in the pain-free response, which in contrast may not be interpreted as
clinically relevant. CONCLUSION: Model-based predictions suggest that increases
in the absorption rate of the currently marketed oral formulation of sumatriptan 
result in a gain in the pain-free response that is both clinically and
statistically relevant.

PMID: 18193920 [PubMed - indexed for MEDLINE]

403: J Am Pharm Assoc (2003). 2008 Jan-Feb;48(1):32-7; quiz 1-4.

Impact of pharmacist interventions on seeking of medical care by migraineurs.

Skomo ML, Desselle SP, Berdine HJ, O'Neil CK.

Mylan School of Pharmacy, Duquesne University, Pittsburgh, PA, USA. skomo@duq.edu

OBJECTIVES: To determine the impact of a pharmacist-led educational intervention 
on the seeking of medical care from physicians by patients with migraine and
identify barriers to migraine care and lapsing from this care. DESIGN:
Prospective, multigroup, quasiexperimental. SETTING: Duquesne University in
Pittsburgh, November 2004 through June 2005. PARTICIPANTS: 100 university
employees and students. Information from the initial interview was used to divide
the patients into four groups: (1) not a migraineur, (2) migraineur who is
currently consulting a physician for care of headaches (current consulter), (3)
migraineur who has not consulted with a physician for more than 12 months
concerning headaches (lapsed consulter), and (4) migraineur who has never
consulted a physician regarding headache (never consulter). INTERVENTIONS: Verbal
counseling by a pharmacist and written education on migraine, as well as
self-administered questionnaires. MAIN OUTCOME MEASURES: Participants' physician 
consultation rates, perceived barriers to physician consultation, and perceived
reasons for lapsing from care. RESULTS: Of the 100 headache sufferers who
participated in the study, 82 met International Headache Society criteria for
migraine, of whom 22 were never consulters and 20 were lapsed consulters.
Cross-tabulation and chi-square statistics did not reveal any statistically
significant differences between the never-consulter control and intervention
groups for 3-month physician consultation rates or intention to seek consultation
during the next 6 months; however, 64% of never consulters contacted their
physician or expressed intentions to do so after the intervention. The top three 
barriers to physician consultation identified were misidentifying migraines as
headaches (50%), satisfaction with current treatment (45%), and inconvenience of 
physician consultation (41%). The top three reasons for lapsing from care were
reduced frequency of headache (40%), self-identification of effective therapy
(40%), and physician-directed effective therapy (30%). Cross-tabulation and
chi-square statistics revealed one significant difference among student/employee 
groups in their identification of barriers. CONCLUSION: This study identified
barriers associated with migraineur physician consultation behavior and reasons
for lapses in care. The role of pharmacists in encouraging migraineur physician
consultation should be further examined.

PMID: 18192128 [PubMed - indexed for MEDLINE]

404: Headache. 2008 Jan;48(1):118-25.

Nebivolol and metoprolol for treating migraine: an advance on beta-blocker
treatment?

Schellenberg R, Lichtenthal A, Wöhling H, Graf C, Brixius K.

Medical Institute for Health and Science, Hüttenberg, Germany.

OBJECTIVE: To evaluate the efficacy of oral treatment with nebivolol and
metoprolol in the prophylaxis of migraine attacks. BACKGROUND: Beta-blockers such
as propranolol and metoprolol are known to be effective in preventing migraine
attacks. Following earlier observations of successful use of nebivolol in a few
hypertensive patients with concomitant migraine, we conducted a prospective study
to ascertain whether nebivolol would be effective and better tolerated, in a
methodologically strict, randomized and double-blind setting. DESIGN AND METHODS:
Randomized, double-blind study in 30 patients with confirmed migraine diagnosis, 
a minimum 1-year history, onset prior to 50 years of age, written records of
attacks for the previous 3 months, and minimum 2 attacks per month. Primary
endpoint was frequency of attacks (prevention of migraine attacks) in the final 4
weeks of a 14-week treatment on full dose of metoprolol and nebivolol. Secondary 
endpoints were time to therapeutic effect, duration of attacks, intensity of
headache, consumption of analgesics, evaluation of accompanying symptoms,
migraine disability assessment, clinical global impression, quality of life, and 
responder rates. The statistical analysis was prospectively planned and conducted
for all randomized patients. RESULTS: Both metoprolol and nebivolol where
similarly effective regarding the main endpoint (prevention of migraine attacks) 
as well as the secondary ones, and both had a fast onset of action, typically
within 4 weeks from starting therapy, with responder rates increasing relatively 
little over time after the first 4 weeks. Use of acute pain medication decreased 
on both drugs, as well as accompanying symptoms. Both patients' and physicians'
evaluations of disability and disease status were similarly favorable to the 2
treatments. Regarding safety, nebivolol was considerably better tolerated than
metoprolol in terms of all reported events, treatment-related events, and event
severity. CONCLUSIONS: Our results suggest that nebivolol is as effective as
metoprolol in the prophylaxis of migraine attacks, with the advantages of being
better tolerated and not requiring up-titration to achieve therapeutic levels.
Further and larger trials should be conducted on nebivolol in the prevention of
migraine attacks as it may provide an improvement in current migraine prophylaxis
with beta-blockers.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 18184294 [PubMed - indexed for MEDLINE]

405: Headache. 2008 Jan;48(1):109-17.

Voxel-based morphometry reveals gray matter abnormalities in migraine.

Valfrè W, Rainero I, Bergui M, Pinessi L.

Neurology II, Headache Center, the Department of Neuroscience, University of
Torino, Italy.

BACKGROUND: Migraine is generally considered a functional brain disorder lacking 
structural abnormalities. Recent magnetic resonance imaging (MRI) studies,
however, suggested that migraine may be associated with subtle brain lesions.
OBJECTIVE: We evaluated the presence of global or focal gray or white matter
alterations in migraine patients using voxel-based morphometry (VBM), a fully
automated method of analyzing changes in brain structure. VBM data also were used
to evaluate possible differences between episodic and chronic migraine. METHODS: 
Twenty-seven migraine right-handed patients and 27 healthy controls were selected
for the study. Sixteen patients fulfilled the International Headache Society
criteria for episodic migraine and 11 for chronic migraine. MRI scans were
analyzed with MATLAB 6.5 and SPM2 software, using VBM method. RESULTS: In
comparison with controls, migraineurs presented a significant focal gray matter
reduction in the Right Superior Temporal Gyrus, Right Inferior Frontal Gyrus, and
Left Precentral Gyrus. Chronic migraine patients, compared to episodic, showed a 
focal gray matter decrease in the bilateral Anterior Cingulate Cortex, Left
Amygdala, Left Parietal Operculum, Left Middle and Inferior Frontal Gyrus, Right 
Inferior Frontal Gyrus, and bilateral Insula. Considering all the migraine
patients, a significant correlation between gray matter reduction in anterior
cingulate cortex and frequency of migraine attacks was found. CONCLUSIONS: Our
study shows that migraine is associated with a significant gray matter reduction 
in several of the cortical areas involved in pain circuitry. In addition, we
found a significant correlation between frequency of migraine attacks and signal 
alteration in the Anterior Cingulate Cortex. Our data provide new insight into
migraine pathophysiology and support the concept that migraine may be a
progressive disorder.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 18184293 [PubMed - indexed for MEDLINE]

406: Headache. 2008 Jan;48(1):101-8.

A novel ATP1A2 gene mutation in an Irish familial hemiplegic migraine kindred.

Fernandez DM, Hand CK, Sweeney BJ, Parfrey NA.

Department of Neurology, Cork University Hospital, Wilton, Cork, Ireland.

OBJECTIVE: We studied a large Irish Caucasian pedigree with familial hemiplegic
migraine (FHM) with the aim of finding the causative gene mutation. BACKGROUND:
FHM is a rare autosomal-dominant subtype of migraine with aura, which is linked
to 4 loci on chromosomes 19p13, 1q23, 2q24, and 1q31. The mutations responsible
for hemiplegic migraine have been described in the CACNA1A gene (chromosome
19p13), ATP1A2 gene (chromosome 1q23), and SCN1A gene (chromosome 2q24). METHODS:
We performed linkage analyses in this family for chromosome 1q23 and performed
mutation analysis of the ATP1A2 gene. RESULTS: Linkage to the FHM2 locus on
chromosome 1 was demonstrated. Mutation screening of the ATP1A2 gene revealed a G
to C substitution in exon 22 resulting in a novel protein variant, D999H, which
co-segregates with FHM within this pedigree and is absent in 50 unaffected
individuals. This residue is also highly conserved across species. CONCLUSIONS:
We propose that D999H is a novel FHM ATP1A2 mutation.

PMID: 18184292 [PubMed - indexed for MEDLINE]

407: Headache. 2008 Jan;48(1):95-100.

24-hour distribution of migraine attacks.

Alstadhaug K, Salvesen R, Bekkelund S.

Nordlandssykehuset--Neurology, Bodø, Norway.

BACKGROUND: It is a widespread opinion that migraine attacks arise more
frequently in the morning and that circadian rhythms may be responsible for the
temporal pattern in migraine. However, only one small prospective study has
previously been published on this topic. OBJECTIVE: To investigate circadian
variation in migraine. METHOD: Eighty-nine females in fertile age who had
participated in a previous questionnaire-based study volunteered to prospectively
record in detail every migraine attack for 12 consecutive months. We reviewed all
diary entries covering the period from March 2004 through April 2005, and did
time-series analysis. RESULTS: Fifty-eight patients had complete recordings over 
the 12 months and 26 completed the diaries for 1-11 months. Three patients were
excluded due to missing data and 2 patients were excluded due to chronic migraine
or medication-overuse headache. A total of 2314 attacks were experienced, in
average 27.5 per patient (range 1-75). By fitting a sine curve to the data there 
was a harmonic trend with a peak around 13.40 and the peak/low ratio was 25.6
(95% CI: 8.3-78.6). CONCLUSION: The main finding in our study is that migraine
attacks tend to recur in a harmonic 24-hour cyclic manner with a peak around the 
middle of the day and that there is no difference between migraine with aura and 
migraine without aura regarding this.

PMID: 18184291 [PubMed - indexed for MEDLINE]

408: Headache. 2008 Jan;48(1):86-94.

Language disturbances as a side effect of prophylactic treatment of migraine.

Coppola F, Rossi C, Mancini ML, Corbelli I, Nardi K, Sarchielli P, Calabresi P.

Neurologic Clinic, Department of Medical and Surgical Specialties and Public
Health, University of Perugia, Italy.

BACKGROUND: Language disturbances have been previously described as word-finding 
difficulties in epileptic patients. These disturbances have been recently
reported in migraineurs in treatment with topiramate but they have never been
defined and assessed in these patients with the aid of neuropsychological
testing. OBJECTIVE: To verify the occurrence of language disturbances as a side
effect of topiramate treatment in episodic and chronic migraine patients.
METHODS: Language disturbances were recorded on the basis of spontaneous reports 
of 30 migraine patients treated with topiramate and 2 control groups (20 patients
treated with other prophylactic drugs and 20 patients without prophylactic
treatment) and were explored with neuropsychological tests. Psychiatric
comorbidity was assessed using Zung Anxiety and Depression Scales. RESULTS:
Language disturbances were referred by 26.7% (n=8) of patients during topiramate 
treatment but by none of the patients in the 2 control groups. All patients in
the topiramate group had a worse performance on all tests compared to patients of
the 2 control groups. Moreover, in the topiramate group, patients with referred
language disturbances had higher scores for all neuropsychological test
variables, indicative of a worse performance. Some language functions (Trail
Making Tests A and B) seemed to be influenced by the concomitant presence of
psychiatric comorbidities, particularly anxiety and depression. CONCLUSION: It
can be hypothesized that a disorder such as migraine, which involves numerous
cortical and subcortical circuits implicated in the transmission and behavioral
and emotional processing of pain, represents a facilitated substrate for the
occurrence of language disturbances due to topiramate. This could be the
expression of a more generalized impairment of cognitive processing. These
aspects should be investigated in prospective studies involving larger migraine
patient samples.

PMID: 18184290 [PubMed - indexed for MEDLINE]

409: Headache. 2008 Jan;48(1):79-85.

Intrapatient variability of migraine attacks: stability analysis of the MIGSEV
scale.

Baha M, Nachit-Ouinekh F, El Hasnaoui A.

Epidemiology Department, GlaxoSmithKline Laboratory, Marly-le-Roi, France.

BACKGROUND: Various tools now exist to define migraine and its impact on everyday
life. Those are scales that help diagnosing the disease and managing treatment.
However, there is no such emphasis on defining individual migraine attacks and
their variability. Yet, as a chronic disease with variable frequency and
intensity among individuals, there should be a way of developing the management
of the disease based on knowledge of the attacks. OBJECTIVES: To determine the
variability of the severity of migraine attacks over time in individual patients 
using the MIGSEV scale. METHODS: A set of migraineurs recruited in general
practice filled a diary about their attacks during a 3-month period. The MIGSEV
scale was used to determine the severity of their attacks, which could be mild,
moderate, or severe. A Markov model was then adjusted with those 3 states and
explanatory variables were considered as possible covariates. RESULTS:
Probabilities were estimated that enabled to expect the severity of an attack to 
come, given the severity of the previous one. For instance, no matter the profile
of the patient, the severity of an attack had more chances of being similar to
the previous one: 74% of remaining mild, 60% of remaining moderate, and 55% of
remaining severe. When it was not similar, having an attack milder than the
previous one was more likely than having a more severe attack. For example, the
probability of going from moderate to severe was 0.105 whereas the probability of
going from moderate to mild was 0.219. Covariates had no significant effect on
estimated probabilities. CONCLUSIONS: An important aspect of the illness was
defined here: the severity profile of patients. The MIGSEV is stable over time
and severity of individual attacks represents a significant indicator in the
characterization of the disease.

PMID: 18184289 [PubMed - indexed for MEDLINE]

410: Headache. 2008 Jan;48(1):67-71.

Sinus CT scan findings in "sinus headache" migraineurs.

Mehle ME, Kremer PS.

Department of Anatomy, Northeastern Ohio Universities College of Medicine,
Cleveland, OH, USA.

OBJECTIVE: To evaluate the sinus CT scan findings in "sinus headache"
migraineurs, and to compare the findings to nonmigraine "sinus headache"
patients. BACKGROUND: The majority of patients presenting with "sinus headache"
satisfy the International Headache Society (IHS) criteria for migraine headache. 
Few studies have correlated the rhinologic complaints and computed tomography
(CT) findings in these patients. METHODS: Thirty-five patients with "sinus
headache" were evaluated prospectively and referred for CT of the paranasal
sinuses. The CT scans were assessed for sinus abnormality (recorded as a
Lund-Mackay [L-M] score) and were analyzed for concha bullosa and septal
deviation. The findings in the migraine cohort were compared with the nonmigraine
"sinus headache" patients. FINDINGS: Twenty-six patients (74.3%) satisfied the
IHS criteria for migraine. The mean CT scan L-M score did not differ
significantly between the migraine (2.07) and nonmigraine cohort (2.66). Five of 
the migraine group had substantial sinus disease radiographically (with L-M
scores of 5 or above). Concha bullosa of at least 1 middle turbinate was more
common in the nonmigraine cohort. An analysis of the sidedness of the headaches, 
sinus disease, concha bullosa, and/or septal deviation is presented. CONCLUSIONS:
The majority of "sinus headache" patients satisfy the IHS criteria for migraine. 
Surprisingly, these patients often have radiographic sinus disease. This raises
the possibility of selection bias in otolaryngology patients, inaccurate
diagnosis, or radiographic sinus disease and migraine as comorbid conditions.
Positive migraine histories apparently do not obviate the need for a thorough ENT
workup, possibly including CT scanning.

PMID: 18184288 [PubMed - indexed for MEDLINE]

411: Headache. 2008 Jan;48(1):7-15.

Concepts and mechanisms of migraine chronification.

Bigal ME, Lipton RB.

Department of Neurology, Albert Einstein College of Medicine, Bronx, NY, USA.

Migraine is a chronic recurrent disorder with episodic manifestations that is
progressive in some individuals. Migraine progresses clinically, physiologically,
and anatomically. Progression may be a consequence of the mechanisms that
generate the migraine attacks (eg, cortical spreading depression) or it may be a 
function of the activations generated by the attacks (eg, lesions in the
periaqueductal gray area), a hypothesis supported by the increase in lesions with
attack frequency. Progression may also be partially explained by common genetic
or environmental risk factors. Finally, migraine with aura is associated with an 
elevated Framingham score and with risk factors for cardiovascular disease.
Research on this issue is in its infancy and cautions are necessary before
extrapolating this information into clinical practice.

Publication Types: 
    Review

PMID: 18184280 [PubMed - indexed for MEDLINE]

412: Eur J Clin Pharmacol. 2008 May;64(5):489-95. Epub 2008 Jan 8.

Interindividual variability of oral sumatriptan pharmacokinetics and of clinical 
response in migraine patients.

Ferrari A, Pinetti D, Bertolini A, Coccia C, Sternieri E.

Division of Toxicology and Clinical Pharmacology, University Centre for Adaptive 
Disorders and Headache, Section Modena II, University of Modena and Reggio
Emilia, Modena, Italy. annaf@unimore.it

BACKGROUND: The marketing of sumatriptan, a selective serotonin (5-HT) 1B/1D
agonist, first of the class of triptans, has increased the therapeutic options
for the treatment of migraine attacks. However, almost one third of patients in
clinical trials fail to have headache relief after oral administration of
sumatriptan. OBJECTIVE: To evaluate whether the interindividual differences in
the clinical response following oral administration of sumatriptan are due to
differences in its pharmacokinetics. METHODS: We compared the pharmacokinetics of
sumatriptan after oral (100 mg) and subcutaneous (6 mg) administration in two
age- and gender-matched groups: ten subjects (group A) with satisfactory response
and ten (group B) with unsatisfactory response to oral sumatriptan. Patients were
studied during headache-free intervals. Blood samples were taken serially from
baseline to 360 min after oral administration and from baseline to 180 min after 
subcutaneous injection. Sumatriptan plasma concentrations were determined by
high-performance liquid chromatography (HPLC) with an electrochemical detector.
RESULTS: Following oral dosing, patients of group A absorbed sumatriptan
significantly faster and achieved early plasma levels significantly higher than
patients of group B. The systemic exposure to sumatriptan during the first 2 h,
which are the most important for rapid onset of action and for antimigraine
efficacy, was significantly greater in group A than in group B (P < 0.001,
Student's t test for independent data). On the other hand, after subcutaneous
injection of sumatriptan, the profile of the curves was similar in all patients, 
and there were no differences in pharmacokinetics between group A and group B.
CONCLUSION: The slow rate and low extent of absorption of the drug during the
first 2 h after dosing observed in patients of group B could explain their
unsatisfactory response to oral sumatriptan.

Publication Types: 
    Clinical Trial

PMID: 18180912 [PubMed - indexed for MEDLINE]

413: Headache. 2008 Feb;48(2):236-47. Epub 2007 Dec 27.

Meta-analysis of the efficacy and safety of zolmitriptan in the acute treatment
of migraine.

Chen LC, Ashcroft DM.

School of Pharmacy and Pharmaceutical Sciences, University of Manchester,
Manchester, UK.

OBJECTIVE: To assess the relative efficacy and safety of zolmitriptan in the
treatment of acute migraine attacks. BACKGROUND: Zolmitriptan is a
second-generation triptan developed for the treatment of migraine. Numerous
randomized controlled trials (RCTs) have been carried out to compare different
dosages and formulations of zolmitriptan against other treatments for acute
migraine. METHODS: Random effects meta-analysis of 24 RCTs, including 15,408
patients suffering from acute migraine attacks. Subgroup analyses compared
differences in response between different dosages and formulations of
zolmitriptan, and other triptan comparators. RESULTS: Zolmitriptan 2.5 mg tablet 
was found to be as effective as almotriptan 12.5 mg, eletriptan 40 mg,
sumatriptan 50 mg and 100 mg and more effective than naratriptan 2.5 mg in terms 
of 2-hour pain-free rates. Likewise, zolmitriptan 5 mg tablet was as effective as
sumatriptan 50 mg and 100 mg in 2-hour pain-free rates. Compared against
zolmitriptan 2.5 mg tablet, eletriptan 80 mg was more effective in achieving
headache relief, pain-free and sustained pain-free responses, and rizatriptan 10 
mg was more effective in terms of sustained pain-free rates. Zolmitriptan 2.5 mg 
tablet was associated with a lower risk of adverse events than eletriptan 80 mg
but higher risk than naratriptan 2.5 mg and rizatriptan 10 mg. Zolmitriptan 5 mg 
tablet was superior to zolmitriptan 2.5 mg tablet in achieving 1- and 2-hour
pain-free response. There were no significant differences in 1- and 2-hour
headache relief and adverse event rates between the different formulations of
zolmitriptan 2.5 mg. CONCLUSIONS: Zolmitriptan 2.5 mg tablet is an effective
treatment for acute attacks of migraine showing similar efficacy to almotriptan
12.5 mg, eletriptan 40 mg, and sumatriptan 50 mg, and being more effective than
naratriptan 2.5 mg in terms of pain-free response at 2 hours post dose.
Zolmitriptan 2.5 mg tablet was also as effective as rizatriptan 10 mg in terms of
headache relief and pain-free response but less effective in terms of sustained
pain-free response.

Publication Types: 
    Meta-Analysis
    Research Support, Non-U.S. Gov't

PMID: 18179569 [PubMed - indexed for MEDLINE]

414: Headache. 2008 Mar;48(3):430-41. Epub 2007 Dec 28.

The migraine cycle: patient burden of migraine during and between migraine
attacks.

Brandes JL.

Nashville Neuroscience Group, Nashville, TN, USA.

Migraine is a neurologic disorder characterized by a cycle of attacks, including 
headache, separated by attack-free periods. Increasingly, episodic migraine is
recognized as a disorder that may escalate to chronic migraine, with a frequency 
of 15 or more attacks per month. Migraine exacts a toll on the quality of life
(QoL) of affected individuals, their families, and their workplace. Migraine
adversely affects a patient's QoL during an attack, but also has an impact
between attacks. This interictal burden on the patient manifests itself as worry 
in anticipation of the next painful attack and concern over its possible adverse 
impact on future plans or activities. The high prevalence of migraine, 12% in
industrialized countries and approximately 28 million people in the United
States, is considered a low estimate. Patients with disruptive migraines
frequently overuse self-prescribed medications or may postpone a visit to a
physician, which delays accurate diagnosis and appropriate treatment for
migraine. Consequently, migraine remains underdiagnosed and undertreated. An
extensive literature search of migraine reviewed its associated disability and
reduced QoL during, and especially between, attacks. Assessment tools to evaluate
the interictal burden on QoL, and to help in migraine diagnosis and
patient-physician communication, are readily available. Nevertheless, patients
with frequent and recurring migraines, who suffer a reduced QoL, continue to be
underrecognized and undertreated. This segment of the migraine population could
benefit from preventive therapy.

Publication Types: 
    Review

PMID: 18179565 [PubMed - indexed for MEDLINE]

415: Curr Pain Headache Rep. 2007 Dec;11(6):449-53.

Migraine, tension-type headache, and transformed migraine.

Peres MF, Gonçalves AL, Krymchantowski A.

Al Joaquim Eugenio de Lima, 881 cj 708, 01403-001, São Paulo, SP, Brazil.
marioperes@yahoo.com

Migraine and tension-type headache (TTH) are highly prevalent primary headaches
that remain underdiagnosed and undertreated in clinical practice. The
similarities and differences between migraine and TTH may impose diagnostic
challenges as well as management difficulties. In addition, the possibility of
migraine chronification or transformation in daily or near-daily headache raises 
the potential level of interaction between pathophysiologic mechanisms of TTH and
migraine. The continuum concept is a possible key to the understanding of this
association. Future studies are necessary to clarify epidemiology,
pathophysiology, and management of these two most prevalent headaches.

Publication Types: 
    Review

PMID: 18173980 [PubMed - indexed for MEDLINE]

416: J Med Internet Res. 2007 Dec 31;9(5):e38.

Mobile Web-based monitoring and coaching: feasibility in chronic migraine.

Sorbi MJ, Mak SB, Houtveen JH, Kleiboer AM, van Doornen LJ.

Department of Clinical and Health Psychology, Utrecht University, PO Box 80.140, 
3508 TC Utrecht, The Netherlands. m.j.sorbi@uu.nl

BACKGROUND: The Internet can facilitate diary monitoring (experience sampling,
ecological momentary assessment) and behavioral coaching. Online digital
assistance (ODA) is a generic tool for mobile Web-based use, intended as an
adjuvant to face-to-face or Internet-based cognitive behavioral treatment based. 
A current ODA application was designed to support home-based training of
behavioral attack prevention in chronic migraine, focusing on the identification 
of attack precursors and the support of preventive health behaviour. OBJECTIVE:
The aim was to establish feasibility of the ODA approach in terms of technical
problems and participant compliance, and ODA acceptability on the basis of
ratings of user-friendliness, potential burden, and perceived support of the
training for behavioral attack prevention in migraine. METHODS: ODA combines
mobile electronic diary monitoring with direct human online coaching of health
behavior according to the information from the diary. The diary contains three
parts covering the following: (1) migraine headache and medication use, (2)
attack precursors, and (3) self-relaxation and other preventive behavior; in
addition, menstruation (assessed in the evening diary) and disturbed sleep
(assessed in the morning diary) is monitored. The pilot study consisted of two
runs conducted with a total of five women with chronic migraine without aura. ODA
was tested for 8.5 days (range 4-12 days) per participant. The first test run
with three participants tested 4-5 diary prompts per day. The second run with
another three participants (including one subject who participated in both runs) 
tested a reduced prompting scheme (2-3 prompts per day) and minor adaptations to 
the diary. Online coaching was executed twice daily on workdays. RESULTS: ODA
feasibility was established on the basis of acceptable data loss (1.2% due to the
personal digital assistant; 5.6% due to failing Internet transmission) and good
participant compliance (86.8% in the second run). Run 1 revealed some annoyance
with the number of prompts per day. Overall ODA acceptability was evident by the 
positive participant responses concerning user-friendliness, absence of burden,
and perceived support of migraine attack prevention. The software was adapted to 
further increase the flexibility of the application. CONCLUSIONS: ODA is feasible
and well accepted. Tolerability is a sensitive issue, and the balance between
benefit and burden must be considered with care. ODA offers a generic tool to
combine mobile coaching with diary monitoring,independently of time and space.
ODA effects on improvement of migraine remain to be established.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 18166526 [PubMed - indexed for MEDLINE]

417: J Behav Med. 2008 Apr;31(2):169-77.

Internet-administered cognitive behavior therapy for health problems: a
systematic review.

Cuijpers P, van Straten A, Andersson G.

Department of Clinical Psychology, VU University Amsterdam, Van der
Boechorststraat 1, 1081 BT Amsterdam, The Netherlands. P.Cuijpers@psy.vu.nl

Cognitive-behavioral interventions are the most extensively researched form of
psychological treatment and are increasingly offered through the Internet.
Internet-based interventions may save therapist time, reduce waiting-lists, cut
traveling time, and reach populations with health problems who can not easily
access other more traditional forms of treatments. We conducted a systematic
review of twelve randomized controlled or comparative trials. Studies were
identified through systematic searches in major bibliographical databases. Three 
studies focused on patients suffering from pain, three on headache, and six on
other health problems. The effects found for Internet interventions targeting
pain were comparable to the effects found for face-to-face treatments, and the
same was true for interventions aimed at headache. The other interventions also
showed some effects, although effects differed across target conditions.
Internet-delivered cognitive-behavioral interventions are a promising addition
and complement to existing treatments. The Internet will most likely assume a
major role in the future delivery of cognitive-behavioral interventions to
patients with health problems.

Publication Types: 
    Review

PMID: 18165893 [PubMed - indexed for MEDLINE]

418: CNS Spectr. 2007 Dec;12(12):921-5.

Comment in:
    CNS Spectr. 2008 Mar;13(3):185-6; author reply 186-7.

Unexpected reduction in migraine and psychogenic headaches following rTMS
treatment for major depression: a report of two cases.

O'Reardon JP, Fontecha JF, Cristancho MA, Newman S.

University of Pennsylvania, Transcranial Magnetic Stimulation Laboratory,
Philadelphia, PA, USA. oreardon@mail.med.upenn.edu

Our objective is to report a coincident reduction in headache pain in patients
treated with repetitive transcranial magnetic stimulation (rTMS) for major
depressive disorder (MDD). Two patients with a Diagnostic and Statistical Manual 
of Mental Disorders, Fourth Edition diagnosis of MDD, non-responsive to prior
antidepressant treatment who were enrolled in a sham-controlled, double-blind
study of rTMS for MDD. After the study, it was revealed that both were in the
active-treatment arm. Both patients suffered from near daily headaches and kept
logs of headache frequency and severity before, during, and after the study.
Headache pain was significantly reduced under double-blind conditions with rTMS
treatment, but returned to baseline following cessation of rTMS treatment.
Ultimately, when receiving rTMS post-study as a maintenance intervention for MDD 
(approximately 2 rTMS sessions/week), the positive effects on headache
amelioration were sustained. Headache pain is frequently comorbid with mood
disorders and has been reported as the most common side effect with rTMS. In
these subjects, rTMS was, in fact, associated with relief of depressive symptoms 
and preexisting headache pain. This indicates that rTMS may be beneficial for
both disorders in some patients.

Publication Types: 
    Case Reports
    Research Support, Non-U.S. Gov't

PMID: 18163038 [PubMed - indexed for MEDLINE]

419: J Affect Disord. 2008 Jun;108(3):217-24. Epub 2007 Dec 21.

Non-right-handedness is associated with migraine and soft bipolarity in patients 
with mood disorders.

Fasmer OB, Akiskal HS, Hugdahl K, Oedegaard KJ.

Department of Clinical Medicine, Section for Psychiatry, Faculty of Medicine,
University of Bergen, Norway.

BACKGROUND: There is a substantial body of data showing differences in the
functioning of the two hemispheres in unipolar depressive and bipolar disorders. 
Migraine is a frequent co-morbid disorder in these patients, and it has been
proposed that migraine may be associated with left-handedness. It would therefore
be interesting to study migraine and handedness in a population of patients with 
mood disorders. METHODS: A total of 201 patients with an index episode of either 
major depression or mania were interviewed with a semi-structured interview based
partly on DSM-IV criteria and partly on TEMPS-I for affective temperaments. The
criteria of the Headache Classification Committee of the International Headache
Society were used to establish the diagnosis of migraine. Hand preference was
assessed using the Edinburgh inventory, and the patients were classified as
having right-, left-, or mixed-handedness. RESULTS: In the whole group 117
patients had migraine (58%) and 59 (29%) were classified as having non-right hand
preference. There was a significant increased prevalence of non-right-handedness 
in the migraine group (37% vs. 19%, p=0.021, Chi-square test; OR 2.5; 95% CI 1.3 
-4.8, p=0.007). In patients with cyclothymic, hyperthymic or irritable
temperaments the prevalence of non-right-handedness (42%) was significantly
higher (p=0.013, Chi-square test; OR 2.2, 95% CI 1.2-4.3) compared to patients
with a depressive or no affective temperament (24%). The prevalence of
non-right-handedness was also significantly higher both in patients with
co-morbid eating disorders (48% vs. 26%, p=0.008 Chi-square test; OR 2.7, 95% CI 
1.3-5.9, p=0.01) and asthma (45% vs. 26%, p=0.026 Chi-square test; OR 2.3, 95% CI
1.1-5.1, p=0.029). LIMITATIONS: Non-blind evaluation of affective diagnosis,
migraine and handedness. CONCLUSIONS: Our main finding supports the hypothesis
that non-right-handedness is associated with migraine and bipolar affective
temperaments ("soft bipolarity") in a sample of patients with major affective
disorders.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 18160136 [PubMed - indexed for MEDLINE]

420: Agri. 2007 Oct;19(4):39-42.

Prevalence of patent foramen ovale in patients with migraine.

Tatlidede AD, Oflazoğlu B, Celik SE, Anadol U, Forta H.

Sişli Etfal Training and Research Hospital, Neurology Clinic, Istanbul, Turkey.

Recent evidence supports that the prevalence of patent foramen ovale is higher in
patients with migraine with aura. We conducted a case-control study and searched 
for intra-atrial right to left shunt in 53 patients with migraine. PFO was
detected by means of transthoracic echocardiography with administration of
contrast medium during valsalva maneuver and the results were compared with age
and sex matched 27 healthy controls. Patent foramen ovale was more frequent in
the migraine group (p<.01). The percentages of PFO in migraine patients with
aura, without aura and the control group were 66.7%, 47.4% and 22.2%,
respectively. Our results are supportive of an association between PFO and
migraine, especially with aura.

PMID: 18159578 [PubMed - indexed for MEDLINE]

421: Emerg Med J. 2008 Jan;25(1):26-9.

Impact of oral dexamethasone versus placebo after ED treatment of migraine with
phenothiazines on the rate of recurrent headache: a randomised controlled trial.

Kelly AM, Kerr D, Clooney M.

Joseph Epstein Centre for Emergency Medicine Research at Western Health and The
University of Melbourne, Melbourne, Australia. anne-maree.kelly@wh.org.au

OBJECTIVE: Evidence suggests that the rate of recurrent headache after treatment 
of migraine in the emergency department (ED) is high. The mechanisms for this are
unclear, but neurogenic inflammation may play a role. There is conflicting
evidence about whether adjuvant dexamethasone reduces the rate of recurrent
headache. The aim of this study was to compare the rate of recurrent headache in 
patients with migraine randomised to receive a single dose of oral dexamethasone 
or placebo at discharge after treatment in the ED with intravenous phenothiazine.
METHODS: A double-blind, randomised, placebo-controlled trial was conducted in
the ED of three community teaching hospitals. Adult patients with
physician-diagnosed migraine were treated with intravenous phenothiazine and at
discharge were randomised to receive either 8 mg oral dexamethasone or placebo as
a single dose. Follow-up was by telephone at 48-72 h and the proportion of
patients with recurrent headache overall and in the subgroup with headache
duration <24 h was recorded. RESULTS: 63 patients (76% women) of median age 39
years were enrolled, 61 of whom (97%) completed follow-up. The pooled rate of
recurrent headache was 33%. 32 were randomised to placebo and 31 to
dexamethasone. The rate of recurrent headache in the dexamethasone and control
groups was 27% (8/30) vs 39% (12/31) (relative risk (RR) 0.69, 95% CI 0.33 to
1.45, p = 0.47). For 40 patients with headache lasting <24 h the rate of
recurrent headache in the dexamethasone and control groups was 15% (3/20) vs 45% 
(9/20), a reduction in absolute risk of 30% (RR 0.33, 95% CI 0.11 to 1.05, p =
0.08). CONCLUSION: A single oral dose of dexamethasone following phenothiazine
treatment for migraine in the ED did not reduce the rate of recurrent headache.
There is weak evidence for a possible benefit in the subgroup who present within 
<24 h of symptom onset. A multicentre trial to confirm this finding is warranted.

Publication Types: 
    Comparative Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 18156535 [PubMed - indexed for MEDLINE]

422: Eur J Neurol. 2008 Feb;15(2):162-8. Epub 2007 Dec 18.

Side-to-side differences in pressure pain thresholds and pericranial muscle
tenderness in strictly unilateral migraine.

Fernández-de-Las-Peñas C, Cuadrado ML, Arendt-Nielsen L, Pareja JA.

Department of Physical Therapy, Occupational Therapy, Physical Medicine and
Rehabilitation of Universidad Rey Juan Carlos, Alcorcón, Madrid, Spain.
cesar.fernandez@urjc.es

Previous studies dealing with pressure pain sensitivity or muscle tenderness in
migraine have shown conflicting results. Our aim was to explore the differences
in mechanical pain sensitivity and pericranial muscle tenderness between patients
with unilateral migraine and healthy controls, and to analyse side-to-side
differences in both study groups. Pressure pain thresholds (PPT) at cephalic and 
neck points, plus local and total tenderness scores were blindly assessed in 25
patients with strictly unilateral migraine and 25 healthy subjects. For PPT in
the neck there were significant differences between groups (F = 47.029; P <
0.001) and sides (F = 6.363; P < 0.01), and a significant interaction between
group and side (F = 5.201; P = 0.02), while PPT in the cephalic point showed
differences between groups (F = 11.774; P < 0.001), but not sides (F = 2.838; P =
0.1). The total tenderness score showed significant differences between groups (F
= 6.800; P < 0.01) and sides (F = 17.699; P < 0.001), along with a significant
interaction between group and side (F = 14.420; P < 0.001). Patients had lower
PPT and increased pericranial tenderness on the symptomatic side as compared with
the non-symptomatic side and to either side in controls (P < 0.001), whereas no
significant differences were identified between the non-symptomatic side and
controls (P > 0.9). In migraine patients, PPT levels and muscle tenderness scores
were negatively correlated (P < 0.001). The enhancement of local tenderness
scores was related to hyperesthesia of specific muscles (sternocleidomastoid,
suboccipital, and temporalis) rather than a generalized pericranial tenderness.
Future studies should investigate the neuro-physiological basis for the
laterality of allodynic and hyperalgesic responses in unilateral migraine.

PMID: 18093151 [PubMed - indexed for MEDLINE]

423: Epilepsia. 2008 Apr;49(4):650-6. Epub 2007 Dec 18.

Clinical and psychopathological definition of the interictal dysphoric disorder
of epilepsy.

Mula M, Jauch R, Cavanna A, Collimedaglia L, Barbagli D, Gaus V, Kretz R, Viana
M, Tota G, Israel H, Reuter U, Martus P, Cantello R, Monaco F, Schmitz B.

Department of Neurology, Amedeo Avogadro University, Novara, Italy.
marcomula@yahoo.it

PURPOSE: Different authors suggested the occurrence of a pleomorphic affective
syndrome in patients with epilepsy named interictal dysphoric disorder (IDD). We 
sought to investigate whether IDD occurs only in patients with epilepsy and to
validate IDD features against DSM-IV criteria. METHODS: Consecutive patients with
a diagnosis of epilepsy (E) or migraine (M) have been assessed using the BDI,
MDQ, and the Interictal Dysphoric Disorder Inventory (IDDI), a questionnaire
specifically created to evaluate IDD symptoms. Diagnosis of current and lifetime 
DSM-IV Axis I disorders was established using the MINI Plus version 5.0.0.
RESULTS: A total of 229 patients (E = 117; M = 112) were evaluated. Females were 
significantly more represented in the migraine group (E = 46.5% vs. M = 73.3% p =
0.009), but there was no difference in age, duration of the disease, or education
level. Patients with epilepsy were more likely to screen positively at MDQ (E =
17% vs. M = 5.3% p = 0.006) and to have a diagnosis of bipolar disorder (E =
14.5% vs. M = 4.5% p = 0.013) as compared to migraine patients. There was no
between-groups difference in IDD prevalence (E = 17%; M = 18.7%) and IDDI total
scores (E = 4.1 +/- 2.0 vs. M = 3.8 +/- 2.0). Validation of IDD against DSM-IV
categories showed current major depression being the foremost diagnostic category
correlated with IDD in both epilepsy (OR = 0.32-0.12-0.88, p = 0.028) and
migraine (OR = 0.10, 95% CI = 0.02-0.49, p = 0.004) samples. Current anxiety
disorder correlated with IDD only in migraine patients (OR = 0.19, 95% CI =
0.05-0.77, p = 0.02). CONCLUSION: IDD represents a homogenous construct that can 
be diagnosed in a relevant proportion of patients but it is not typical only of
epilepsy, occurring in other central nervous system disorders such as migraine.

Publication Types: 
    Comparative Study

PMID: 18093149 [PubMed - indexed for MEDLINE]

424: J Interv Cardiol. 2008 Feb;21(1):32-7. Epub 2007 Dec 18.

Migraine headache relief after percutaneous transcatheter closure of interatrial 
communications.

Dubiel M, Bruch L, Schmehl I, Liebner M, Winkelmann A, Stretz A, Grad MO, Kleber 
FX.

Department of Internal Medicine, UKB, Academic Teaching Hospital, Charité Medical
School, Humboldt University, Berlin, Germany.

BACKGROUND: Migraine headache (MHA) is present in 12% of adults, but has been
reported to have a higher prevalence in patients with presumed paradoxical
embolism and patent foramen ovale. PFO closure in these patients has been
reported to improve migraine, but follow-up periods in previous studies have been
relatively short and concomitant medical therapy as well as placebo effects might
have influenced the results. This study investigated the long term course of MHA 
in a large cohort of patients after closure of PFO well beyond the initial phase 
of concomitant antiplatelet medication. METHODS: 191 consecutive patients with
presumed paradoxical embolism underwent percutaneous transcatheter closure of
patent interatrial communications for prevention of recurrent thromboembolism. We
report the course of MHA before and after closure. RESULTS: Before the procedure,
MHA was present in 24% of patients. At a mean follow-up of 38 months (range 6 to 
82) after the procedure MHA had disappeared completely in 24% of patients, and in
another 63% symptoms had improved. At a mean duration of follow-up of 38 months a
significant reduction (p < 0.000) of number, intensity, duration of episodes, and
in the number of accompanying symptoms during an MHA episode was found.
CONCLUSIONS: Percutaneous transcatheter closure of patent interatrial
communications results in significant amelioration of MHA in 87% of patients
(complete resolution in 24% and significant improvement in symptoms in 63%).
Ongoing randomized trials and larger epidemiologic surveys need to further
elucidate the role of device therapy for MHA.

PMID: 18093099 [PubMed - indexed for MEDLINE]

425: Prescrire Int. 2007 Dec;16(92):244.

Ibuprofen: new indication. Migraine attacks: don't begin with 400 mg!

[No authors listed]

Ibuprofen, initially at a dose of 200 mg, is a second-line option for treating
migraine attacks after paracetamol fails.

PMID: 18092409 [PubMed - indexed for MEDLINE]

426: J Neuroophthalmol. 2007 Dec;27(4):300-3.

Migraine-like visual hallucinations as the presenting manifestations of focal
seizures in neurocysticercosis.

Jha S, Kumar R.

Department of Neurology, Sanjay Gandhi Sanjay Gandhi Post Graduate Institute of
Medical Sciences, Lucknow, Uttar Pradesh, India. sjha@sgpgi.ac.in

We report three patients with visual hallucinations as the initial manifestations
of neurocysticercosis (NCC) in whom migraine was the first diagnosis. The correct
diagnosis was suspected when electroencephalograms were abnormal and was
confirmed by characteristic brain imaging. The visual hallucinations ceased
promptly after treatment with antiepileptic and anti-NCC medications. We caution 
that NCC may present with focal seizures manifesting as visual hallucinations
with features of migraine.

Publication Types: 
    Case Reports

PMID: 18090566 [PubMed - indexed for MEDLINE]

427: Headache. 2008 Mar;48(3):476-8. Epub 2007 Dec 11.

Lifetime basilar migraine: a pontine syndrome?

Mishra NK, Cereda C, Carota A.

Department of Neurology, University Hospital of Lausanne (CHUV), Lausanne,
Switzerland.

We describe the clinical and radiological findings of an 82-year-old woman
patient with basilar type migraine attacks occurring over 70 years with a similar
pattern of intensity and symptoms. We provide some evidence to suggest that
gradual development of calcifications in the pontine tegmental nuclei can trigger
attacks of basilar type migraine.

Publication Types: 
    Case Reports

PMID: 18081824 [PubMed - indexed for MEDLINE]

428: Pain Res Manag. 2007 Winter;12(4):291-5.

Health care utilization and changes in health status over time for migraineurs.

Chuck A, Jacobs P, Ohinmaa A, Schopflocher D, Rashiq S, Feroe R.

Department of Public Health Sciences, University of Alberta, Edmonton, Canada.

BACKGROUND: Determining how migraineurs manage their condition from the viewpoint
of health resource utilization (including both medical and personal resources)
may provide insights that could lead to more effective care strategies.
OBJECTIVES: To determine the relative importance of modifiable health-influencing
activities for migraineurs, and to compare the effects of these activities
between migraineurs and nonmigraineurs in the general population. METHODS: Linear
regression analysis was applied to all persons older than 19 years of age with
migraine in the Canadian Community Health Survey Cycle 1.1. The dependent
variable was reported health status change over time. Explanatory variables were 
a series of health care utilization, health behaviour and background control
variables. RESULTS: Results showed that health status was positively associated
with higher levels of physical activity and negatively associated with smoking
for both migraineurs and nonmigraineurs, even when controlling for all other
variables. CONCLUSION: By modifying controllable resources and behaviours, the
reported health status of migraineurs can be improved as effectively as
nonmigraineurs.

PMID: 18080049 [PubMed - indexed for MEDLINE]

429: J Child Neurol. 2008 Jan;23(1):39-43. Epub 2007 Dec 13.

Canadian adolescents with migraine: impaired health-related quality of life.

Brna P, Gordon K, Dooley J.

Department of Pediatrics, Division of Neurology, IWK Health Centre, Halifax, Nova
Scotia. pbrna@hotmail.com

The objective of this study was to determine the impact of migraine headaches on 
health-related quality of life among Canadian adolescents. The Canadian Community
Health Survey (CCHS) collects information related to health status, health care
utilization, and health determinants for the Canadian population. Analysis was
limited to those adolescents 12-19 years of age residing in Manitoba. Respondents
reported whether they had migraine and mood/anxiety disorders. Health-related
quality of life was measured using the Short Form-36 survey, which covers 8
health concepts related to functional status, well-being, and overall health.
Multivariate linear regression analysis was used to model each Short Form-36
scale against age (12-14 years vs 15-19 years), gender, migraine, and the
presence of a mood or anxiety disorder. The CCHS was completed by 994
respondents; 9.3% (95% confidence interval, 7.3%-11.5%) reported a diagnosis of
migraine. Reported migraine predicted both statistically (P < .0001) and
clinically significantly lower health-related quality of life in all Short
Form-36 domains except vitality and general health perceptions. Adolescents
reporting a mood disorder (2.1%) scored significantly lower in 6 of 8
health-related quality of life domains, most pronounced for emotional role,
general mental health, and social functioning. Canadian adolescents with migraine
report clinically and statistically significant impairment in health-related
quality of life compared to their peers, independent of psychiatric
comorbidities.

PMID: 18079320 [PubMed - indexed for MEDLINE]

430: J Neurol Neurosurg Psychiatry. 2008 Jan;79(1):89-90.

Clearance of a status aurae migraenalis in response to thrombendarterectomy in a 
patient with high grade internal carotid artery stenosis.

Klingebiel R, Friedman A, Shelef I, Dreier JP.

Department of Neurology, Charité, University Medicine Berlin, Schumannstr. 20/21,
10098 Berlin, Germany.

We report a patient with high grade internal carotid artery (ICA) stenosis who
had frequent migrainous aura-like symptoms for a period of 3 weeks (Latin: status
aurae migraenalis). This syndrome has been described previously but it was
unclear whether ischaemic damage was associated with it. Using MRI, we
demonstrated widely scattered focal laminar cortical infarcts. Importantly, after
ICA thrombendarterectomy, the status aurae migraenalis abruptly ceased which
supports the concept that high grade ICA stenosis can be the cause of status
aurae migraenalis.

Publication Types: 
    Case Reports
    Research Support, Non-U.S. Gov't

PMID: 18079300 [PubMed - indexed for MEDLINE]

431: Ann Pharmacother. 2008 Jan;42(1):39-45. Epub 2007 Dec 11.

Beliefs about medicines and adherence among Swedish migraineurs.

Hedenrud T, Jonsson P, Linde M.

Department of Social Medicine, The Sahlgrenska Academy at Göteborg University,
Göteborg, Sweden. tove.hedenrud@socmed.gu.se

BACKGROUND: The problem of low adherence to drug therapy is as prevalent in
migraine as in any other disorder, with important consequences for the patient,
such as impaired quality of life and absence from work. Beliefs about medicines
have been identified as one of the most significant factors for adherence.
OBJECTIVE: To analyze whether beliefs about medicines and medication-related
factors are associated with adherence to prophylactic drug therapy among
migraineurs at a Swedish tertiary care clinic. METHODS: A questionnaire was
distributed to migraineurs visiting a tertiary care clinic in Sweden. All
participants had recently been prescribed prophylactic medicine. The
questionnaire was comprised of background questions, questions about disease
characteristics, perceived effects, and adverse effects of migraine medications
used, the Beliefs about Medicines questionnaire, and the Medication Adherence
Report Scale. Medication-related variables, collected from patients' records with
consent, were also included. Logistic regression analysis was performed to
analyze the association between beliefs about medicines, medication-related
variables, and adherence to prophylactic drugs. RESULTS: Of the 174 participants 
in the study, 64% were considered to be adherent to their prescribed prophylactic
medicine. Users of beta-blockers were significantly more adherent compared with
patients using other drugs (eg, tricyclic antidepressants [TCAs] or
antiepileptics); the reverse was true for patients taking TCAs. Respondents with 
the lowest level of education (<or=9 y) expressed less concern about drugs and
had a higher necessity-concerns differential compared with respondents with a
higher educational level. In the final regression model, no variable was
significantly associated with adherence. CONCLUSIONS: About one-third of the
migraineurs did not adhere to their prophylactic drugs. Beliefs about medicines
and medication-related factors could not predict nonadherence. We recommend
further research on medication-related variables in relation to adherence among
migraineurs.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 18073328 [PubMed - indexed for MEDLINE]

432: Acta Neurol Belg. 2007 Sep;107(3):84-90.

The prevalence and characteristics of migraine among the Belgian working
population.

Moens G, Johannik K, Verbeek C, Bulterys S.

IDEWE, External Service for Prevention and Protection at Work, Dept of Research
and Development, Leuven, Belgium. guido.moens@idewe.be

INTRODUCTION: Migraine is a very common disease. For the first time in Belgium, a
study has been set up to assess some characteristics of the migraine problem like
occurrence, frequency, duration, in a convenience sample of employees. METHODS
AND STUDY POPULATION: A total of 1660 persons participated in the study.
Employees completed a short international validated self-administered
questionnaire (ID-Migraine Screener) in which migraine-related characteristics
have been assessed. RESULTS AND DISCUSSION: Lifetime prevalence of migraine in
this study was 20.2% (95% CI: 18.3-22.2%), was significantly higher for women
than for men and was the highest in the age group 35-44 years. On average 10.6
lost working days due to migraine were reported per absentee and per year, or per
migraineur on average 2.3 days, and per employee 0.4 days. Migraine is estimated 
to account for about 1,154,336 lost working days each year in Flanders and
Brussels. However underreporting of symptoms, attacks and sick leave days was
estimated at about 50%, depending on the time frame. Sixty-nine percent of the
migraine sufferers use medication regularly. Only minor differences have been
detected in migraine prevalence according to the recorded occupational risks.
Finally, the limitations of the study are discussed.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 18072336 [PubMed - indexed for MEDLINE]

433: J Headache Pain. 2007 Dec;8(6):329-33. Epub 2007 Dec 10.

Helicobacter pylori infection as an environmental risk factor for migraine
without aura.

Yiannopoulou KG, Efthymiou A, Karydakis K, Arhimandritis A, Bovaretos N, Tzivras 
M.

Department of Neurology, Laiko General Hospital of Athens, Athens, Greece.
ekati2@otenet.gr

Helicobacter pylori (H. pylori) infection has recently been associated with
various extraintestinal pathologies and migraine. The aim of this study was to
investigate the correlation of the H. pylori infection with the pathogenesis of
migraine without aura, especially in cases not affected by endogenous risk
factors, like hereditary pattern or hormonal fluctuations.A total of 49
outpatients (37 females and 12 males; age range: 19-47 years; mean age: 31,+/-14 
years) affected by migraine without aura was evaluated. We divided them in 2
subgroups: a) with positive familial history, and/or with menstrual type of
migraine b) with negative familial history and with menstrual unrelated type of
migraine. H. pylori infection was diagnosed by the 13 C- urea breath test (INFAI 
- test).Control subjects consisted of 51 patients without any primary headache
history (38 females; mean age of 32,+/-14,4 years; range 21-49 years), who
underwent upper gastrointestinal (GI) endoscopy for investigation of anaemia or
non ulcer dyspepsia. H. pylori detection was based on the histologic analysis of 
gastric mucosa biopsy.The prevalence of H. pylori infection was significantly
higher in the migraineurs without aura compared to controls (p=0.016).The
prevalence of H. pylori infection was significantly high in the mixed and in the 
female group of our patients without other predisposing factors for migraine
without aura (81 and 87% respectively), while in the same groups with
predisposing factors (menstruation and/or family history) the prevalence was only
36 and 37% respectively (p=0,001 for the first group and p=0,002 for the second
group). Our results seem to highlight the role of H. pylori infection as a
probable independent environmental risk factor for migraine without aura,
especially in patients that are not genetically or hormonally susceptible to
migraine.

PMID: 18071631 [PubMed - indexed for MEDLINE]

434: J Headache Pain. 2007 Dec;8(6):340-1. Epub 2007 Dec 10.

Temporary confusion depending on the usage of naratriptan.

Kutluhan S, Incekara F, Sozen A, Koyuncuoglu HR, Tak R, Gokalp O, Gultekin F.

Department of Neurology, Medical Faculty, Süleyman Demirel University, A.D. 32260
Isparta, Turkey. skutluhan@hotmail.com

In this report, a case with vitamin B12 deficiency showing a temporary confusion 
depending on the usage of naratriptan during the migraine attack was presented.

Publication Types: 
    Case Reports

PMID: 18071630 [PubMed - indexed for MEDLINE]

435: J Headache Pain. 2007 Dec;8(6):342-4. Epub 2007 Dec 10.

Headache in a patient with Klinefelter's syndrome and hyperostosis frontalis
interna.

Ramchandren S, Liebeskind DS.

Department of Neurology, University of Michigan at Ann Arbor, 300 North Ingalls
St., #3D06, Ann Arbor, MI 48109, USA. sindhur@med.umich.edu

Hyperostosis frontalis interna (HFI) has been reported in older women, but
reports in men are rare. We present a novel case of migraine headache in a
gentleman with Klinefelter's syndrome and HFI, along with a discussion of
possible pathophysiologic mechanisms underlying both the headache and the HFI.

Publication Types: 
    Case Reports
    Research Support, N.I.H., Extramural

PMID: 18071629 [PubMed - indexed for MEDLINE]

436: Headache. 2008 Apr;48(4):501-16. Epub 2007 Dec 7.

Comorbidity of migraine and psychiatric disorders--a national population-based
study.

Jette N, Patten S, Williams J, Becker W, Wiebe S.

Department of Clinical Neurosciences, University of Calgary, Calgary, Alberta,
Canada.

BACKGROUND: Migraine is common, with an estimated lifetime prevalence of 7-17%.
Population-based studies have reported an association between various psychiatric
conditions and migraine. This is a population-based study exploring the
association between migraine and psychiatric disorders in a large cohort and
assessing various health-related outcomes. OBJECTIVE: (1) Determine the
prevalence of various psychiatric conditions in association with migraine; (2)
describe the patterns of association of these comorbidities with a variety of
health-related outcomes. METHODS: Data from the 2002 Canadian Community Health
Survey were used. This is a national health survey which included administration 
of the World Mental Health Composite International Diagnostic Interview to a
sample of 36,984 subjects. Health-related outcomes included 2-week disability,
restriction of activities, quality-of-life, and mental health care utilization.
RESULTS: The prevalence of physician-diagnosed migraine (n=36,984) was 15.2% for 
females and 6.1% for males. Migraine was most common in those between ages 25 and
44 years and in those of lower income. Migraine was associated with major
depressive disorder, bipolar disorder, panic disorder, and social phobia, all
occurring more than twice as often in those with migraines compared with those
without. Migraine was not associated with drug, alcohol, or substance dependence.
The higher prevalence of psychiatric disorders in migraineurs was not related to 
sociodemographic variables. Psychiatric disorders were less common in those over 
65 years, in those who were in a relationship, and in those of higher income
whether migraine was present or not. Health-related outcomes were worst in those 
with both migraines and a psychiatric disorder and intermediate in those with
either condition alone. CONCLUSION: Migraine is associated with major depressive 
disorder, bipolar disorder, panic disorder, and social phobia. Migraine in
association with various mental health disorders results in poorer health-related
outcomes compared with migraine or a psychiatric condition alone. Understanding
the psychiatric correlates of migraine is important in order to adequately manage
this patient population and to guide public health policies regarding health
services utilization and health-care costs.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 18070059 [PubMed - indexed for MEDLINE]

437: Headache. 2008 Feb;48(2):221-5. Epub 2007 Dec 7.

Comment in:
    Headache. 2008 Jun;48(6):973.

Heart rate recovery in migraine and tension-type headache.

Yerdelen D, Acil T, Goksel B, Karatas M.

Department of Neurology, Baskent University Faculty of Medicine, Adana, Turkey.

OBJECTIVE: There are reports proposing that migraine and tension-type headache
(TTH) may affect the autonomic nervous system (ANS). Abnormalities in both
sympathetic and parasympathetic nervous system have been suggested in
migraineurs. However, in TTH, reports on the ANS function are limited and only
associated with sympathetic system. Techniques for evaluating parasympathetic
activity are more limited when compared with sympathetic function. Hence, the aim
of the study was to measure heart rate recovery (HRR), an index of vagal
activity, in migraine, TTH, and control subjects. METHODS: Forty-seven episodic
migraine, 10 episodic TTH, 11 chronic TTH, and 25 control subjects underwent
exercise tolerance test according to modified Bruce protocol, and HRR at 1 minute
and 3 minutes (HRR1 and HRR3) were calculated. RESULTS: The HRR 1 and 3 were
found to be similar in 3 groups of subjects. However, resting heart rate of
migraine and chronic TTH were found to be higher than episodic TTH, but not
different from the control group. CONCLUSION: These results suggest that
parasympathetic function has not been affected in migraine and TTH patients.
However, sympathetic tonus, which is evaluated by resting heart rate, is higher
in migraine and chronic TTH than in episodic TTH.

PMID: 18070058 [PubMed - indexed for MEDLINE]

438: Headache. 2008 Apr;48(4):553-63. Epub 2007 Dec 7.

Direct cost burden among insured US employees with migraine.

Hawkins K, Wang S, Rupnow M.

IMS Health, Brooklyn, MI, USA.

OBJECTIVE: To provide a current estimate of the national direct health-care cost 
burden of illness associated with migraine among a US insured population.
BACKGROUND: Individuals with migraine use health-care resources more than those
without migraine, incurring substantial costs to US employers. METHODS: The
Thomson Medstat's Commercial Claims and Encounters 2004 database was utilized for
this study. Only paid claims were analyzed. The migraine cohort had a primary
migraine diagnosis and/or a migraine-specific abortive drug prescription during
2004. A matched control cohort with no evidence of migraine was generated using
propensity score techniques. Demographic characteristics and overall
comorbidities were similar between cohorts. A second-stage regression controlled 
for any remaining significant intergroup differences. The burden of illness of
migraine was defined as the difference in average total health-care expenditures 
per person between cohorts. The national burden of illness was defined as the
average expenditure for migraine of national population estimates of privately
insured individuals, and was estimated by projecting the migraine prevalence rate
and average expenditure using Medical Expenditure Panel Survey population
estimates. RESULTS: Patients with migraine (n=215,209) had significantly higher
average health-care expenditures compared with matched controls ($7007 vs $4436
per person per year; difference of $2571; P<.001). Migraine-associated national
expenditure estimates: outpatient care, $5.21 billion; prescriptions, $4.61
billion; inpatient care, $0.73 billion; and emergency department care, $0.52
billion. CONCLUSIONS: The direct costs associated with patients with migraine
were found to be $2571 per person per year higher than in matched nonmigraine
controls. The projected national burden of migraine of $11.07 billion is
substantially higher than previous estimates.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 18070057 [PubMed - indexed for MEDLINE]

439: Mov Disord. 2008 Feb 15;23(3):425-9.

Concurrent hemichorea and migrainous aura--a perfusion study on the basal ganglia
using xenon-computed tomography.

Yamada K, Harada M, Inoue N, Yoshida S, Morioka M, Kuratsu J.

Department of Neurosurgery, Graduate School of Medical Sciences, Kumamoto
University, Kumamoto, Japan. yamadakazu@fc.kuh.kumamoto-u.ac.jp

A variety of etiologies underlie the neurophysiological imbalance resulting in
chorea. We report a 57-year-old woman with a long-history of migraine who
suddenly experienced concurrent scintillating scotoma and rapid involuntary
movement of her neck and right extremities. Diffusion-weighted magnetic resonance
imaging (MRI) failed to detect any fresh ischemic and/or hemorrhagic lesions.
Xenon-computed tomography (CT) disclosed gross reduction in the cerebral blood
flow (CBF) of the left occipital area. With precise mapping to the brain atlas,
extreme hyperperfusion in the motor thalamus was found on the left side.
Asymmetrical CBF reduction of the left subthalamic nucleus was also noted. Her
symptoms gradually improved and completely disappeared within 15 days. Repeated
xenon-CT 1 month post-onset demonstrated normalized CBF in the affected areas.
Our study suggests that vascular event underlies the migrainous aura in this case
and secondarily provokes a loss of inhibitory control of the motor thalamus
resulting in the manifestation of hemichorea. 2007 Movement Disorder Society

Publication Types: 
    Case Reports

PMID: 18067174 [PubMed - indexed for MEDLINE]

440: Can J Physiol Pharmacol. 2007 Nov;85(11):1108-15.

Gene response of human monocytic cells for the detection of antimigraine activity
of feverfew extracts.

Chen CF, Leung AY.

Department of Genetics and Biochemistry, Jordan Hall 100, Clemson University,
Clemson, SC 29634, USA. cchen@clemson.edu

The herb feverfew is a folk remedy for various conditions, including
inflammation, fever, psoriasis, rheumatism, and asthma. Like many herbal
medicines, feverfew's mechanisms of action in the human body are largely unknown 
and its active ingredients remain elusive. Very often, different extraction
methods of herb material produce different physical and biochemical properties
and variation in clinical efficacy. We identified 3 major methods of extraction
for feverfew aerial parts and used microarray technology to test the hypothesis
that extracts produced by different methods elicit different gene expression
profiles. We have identified approximately 200 genes that are consistently
regulated by the 2 presumptive active antimigraine feverfew extracts but not
associated with the inactive extract. Our results suggest that the presumptive
active feverfew extracts potently stimulate more genes in human cells than the
inactive extracts. We also identified several genes as unique signatures for
these active extracts. All 3 feverfew extracts exhibited similar blockades on
lipopolysaccharide-mediated TNF-alpha (tumor necrosis factor alpha) release,
implicating that TNF-alpha is not responsible for the differences in the effects 
of the 3 feverfew extracts in human cells. In contrast, the active extracts more 
effectively suppressed CCL2 (also known as monocyte chemoattractant protein 1,
MCP-1) than the inactive extracts, suggesting that CCL2 is a potential cellular
target for feverfew's antimigraine effects.

Publication Types: 
    Research Support, N.I.H., Extramural

PMID: 18066113 [PubMed - indexed for MEDLINE]

441: Oftalmologia. 2007;51(3):8-15.

Ocular migraine and antiphospholipid antibodies--where we stand?

Coroi M, Bontas E, Visan R, Defranceschi M, Cioranu CD.

Department of Ohthalmology, Oradea University, Oradea, Romania.
opticlar@gmail.com

There is no doubt that ocular migraine also known as retinal migraine or
ophthalmic migraine should not to be confused with ophthalmoplegic migraine. The 
hallmark of ocular migraine is the unilateral visual loss or "monocular transient
loss of vision" associated or followed by the headache. Better safe than sorry,
therefore an ophthalmologic examination during the migraine attack is the most
diagnostic method. age with typical history for ocular migraine. Importantly
supportive data sustain that different neuro-ophthalmologic manifestations as
amaurosis fugax, retinal vascular thrombosis and optic neuropathy, may be
considered as the ocular hallmarks of the Hughes's syndrome. Clues for the
evaluating of antiphospholipid antibodies include recurrent thrombosis especially
in young people, recurrent fetal loss, and thrombocytopenia. There are no studies
that focus exclusively on the prophylaxis of ocular migraine. Ocular features due
to antiphospholipid antibodies - induced thrombosis or Hughes's syndrome should
be treated with anticoagulant therapy.

Publication Types: 
    Review

PMID: 18064948 [PubMed - indexed for MEDLINE]

442: Can J Neurol Sci. 2007 Nov;34(4):S3-9.

Migraine prevalence, diagnosis, and disability.

Becker WJ, Gladstone JP, Aubé M.

Division of Neurology, University of Calgary, Calgary, AB, Canada.

The goal of the Canadian Migraine Forum was to work towards improving the lives
of Canadians with migraine by reducing their migraine-related disability. This
paper reviews the epidemiology and diagnosis of migraine, and the effects of
migraine on health related quality of life. Many patients with migraine do not
consult a physician for their headaches, and when they do they often do not
receive a correct diagnosis. The discussion at the Forum concluded that better
education, both for physicians and the public, on issues relating to migraine was
a necessary step in improving migraine diagnosis. The degree of disability caused
by migraine is often not recognized by society, and can be substantial for
individuals with migraine. Once again, education of the public and of the health 
professionals who see these patients is key, so that the best migraine management
can be instituted to minimize the impact of migraine on the individual, the
family, and society at large.

Publication Types: 
    Congresses
    Research Support, Non-U.S. Gov't

PMID: 18064751 [PubMed - indexed for MEDLINE]

443: Can J Neurol Sci. 2007 Nov;34(4):S20-6.

Moving forward to improve migraine management in Canada.

Becker WJ, Giammarco R, Wiebe V.

Division of Neurology, University of Calgary, Calgary, AB, Canada.

The goal of the Canadian Migraine Forum was to work towards improving the lives
of Canadians with migraine by reducing their migraine-related disability.
Migraine has been ranked 19th by the World Health Organization among causes of
years of life lived with disability. To improve management of migraine in Canada,
the participants in the forum identified several important needs and strategies. 
There is a need for more leaders in the field of migraine to work with other
stakeholders to obtain funding and develop treatment programs across Canada.
Leadership is also required to address the under use of both migraine specific
symptomatic medications and prophylactic medications in Canada. More
non-physician health professionals are required to work with physicians in
migraine treatment teams. This could assist with a shortage of physician
resources, and could also help to better meet the needs of the migraine patient. 
Individuals with migraine need to be identified who could work with health care
professionals to help meet the needs of the migraine patients in our communities.
Application of the chronic disease management model for migraine treatment was
also seen as an important factor for the management of migraine. Programs are
needed to promote earlier diagnosis, long-term follow-up, comprehensive patient
education, and the use of multidisciplinary treatment teams where appropriate.
Also considered important was the need to increase knowledge about migraine
through public awareness campaigns, websites, medical education, and appropriate 
reading material for patients. The public needs to be aware that migraine is a
biological disorder that can cause significant disability and suffering. Lastly, 
there is a pressing need to promote more migraine research, including careful
outcome assessments for treatment programs that involve non-pharmacological
treatments and a team based approach to migraine management. There are many
challenges that must be overcome if we are to be successful in reducing migraine 
related disability in Canada. Success will depend upon the joint efforts of
physicians, other healthcare professionals, individuals with migraine, and the
public at large.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 18062467 [PubMed - indexed for MEDLINE]

444: Can J Neurol Sci. 2007 Nov;34(4):S10-9.

Migraine treatment.

Becker WJ, Gawel M, Mackie G, South V, Christie SN.

Division of Neurology, University of Calgary, Calgary, AB, Canada.

The goal of the Canadian Migraine Forum was to work towards improving the lives
of Canadians with migraine by reducing their migraine-related disability. This
paper focuses on migraine treatment in its many aspects, including symptomatic
therapy of individual migraine headache attacks, prophylactic drug therapy,
non-pharmacological interventions, and diagnosis and management of symptomatic
medication overuse. Many patients with difficult migraine experience significant 
frustration in trying to obtain the help they need from our current medical
system. Although many symptomatic medications are available for use in migraine, 
migraine specific medications are still underutilized. An ideal migraine
preventative medication does not yet exist, but currently available preventatives
do have utility, and are also thought to be underutilized. Behavioral approaches 
to migraine management as an adjunct to medication therapy show promise, but the 
availability of programs to bring these to patients is limited, and more research
is needed on their efficacy. Symptomatic medication overuse in migraine sufferers
remains a large problem in Canada, and better defined treatment paradigms and
programs are needed both to prevent and to treat this problem. Such programs
should include strong elements of public, patient, and health professional
education. A potential solution to some of these problems may be to develop
treatment approaches to migraine similar to those that are being developed for
other chronic medical disorders. For patients with severe migraine, these would
optimally include multidisciplinary teams so that the multiple facets of migraine
management can be adequately addressed.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 18062466 [PubMed - indexed for MEDLINE]

445: Ann Neurol. 2008 Feb;63(2):148-58.

Comment in:
    Ann Neurol. 2008 Feb;63(2):130-2.

Cutaneous allodynia in the migraine population.

Lipton RB, Bigal ME, Ashina S, Burstein R, Silberstein S, Reed ML, Serrano D,
Stewart WF; American Migraine Prevalence Prevention Advisory Group.

Department of Neurology, Albert Einstein College of Medicine, Bronx, NY 10461,
USA. rlipton@aecom.yu.edu

OBJECTIVE: To develop and validate a questionnaire for assessing cutaneous
allodynia (CA), and to estimate the prevalence and severity of CA in the migraine
population. METHODS: Migraineurs (n = 11,388) completed the Allodynia Symptom
Checklist, assessing the frequency of allodynia symptoms during headache.
Response options were never (0), rarely (0), less than 50% of the time (1), > or 
= 50% of the time (2), and none (0). We used item response theory to explore how 
well each item discriminated CA. The relations of CA to headache features were
examined. RESULTS: All 12 questions had excellent item properties. The greatest
discrimination occurred with CA during "taking a shower" (discrimination = 2.54),
wearing a necklace (2.39) or ring (2.31), and exposure to heat (2.1) or cold
(2.0). The factor analysis demonstrated three factors: thermal, mechanical
static, and mechanical dynamic. Based on the psychometrics, we developed a scale 
distinguishing no CA (scores 0-2), mild (3-5), moderate (6-8), and severe (> or =
9). The prevalence of allodynia among migraineurs was 63.2%. Severe CA occurred
in 20.4% of migraineurs. CA was associated with migraine defining features (eg,
unilateral pain: odds ratio, 2.3; 95% confidence interval, 2.0-2.4; throbbing
pain: odds ratio, 2.3; 95% confidence interval, 2.1-2.6; nausea: odds ratio, 2.3;
95% confidence interval, 2.1-2.6), as well as illness duration, attack frequency,
and disability. INTERPRETATION: The Allodynia Symptom Checklist measures overall 
allodynia and subtypes. CA affects 63% of migraineurs in the population and is
associated with frequency, severity, disability, and associated symptoms of
migraine. CA maps onto migraine biology.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Validation Studies

PMID: 18059010 [PubMed - indexed for MEDLINE]

446: J Headache Pain. 2007 Dec;8(6):334-9. Epub 2007 Dec 5.

Genetics of migraine and pharmacogenomics: some considerations.

Piane M, Lulli P, Farinelli I, Simeoni S, De Filippis S, Patacchioli FR,
Martelletti P.

Department of Diagnostic Sciences, Medical Genetics Section, 2nd School of
Medicine, University of Rome La Sapienza, I-00185, Rome, Italy.
maria.piane@uniroma1.it

Migraine is a complex disorder caused by a combination of genetic and
environmental factors.Although family and twin studies show that there is a
genetic component in migraine, no genes predisposing to common forms of the
disorder, migraine with and without aura, have been identified. Patients with
migraine respond differently to a given drug administered. The efficacy of
therapy and the occurrence of adverse drug response are a consequence of
individual variability. Genetic profiling of predisposition to migraine should
facilitate the development of more effective diagnostic and therapeutic
applications. The development of International Hap Map project could provide a
powerful tool for identification of the candidate genes in this complex disease
and pharmacogenomics research could be the promise for individualized treatments 
and prevention of adverse drug response.

Publication Types: 
    Review

PMID: 18058067 [PubMed - indexed for MEDLINE]

447: Eur Neurol. 2008;59(3-4):148-51. Epub 2007 Nov 30.

Toward a further elucidation: role of vertebral artery hypoplasia in migraine
with aura.

Chuang YM, Hwang YC, Lin CP, Liu CY.

Department of Neurology, Tao-Yuan General Hospital, Taipei, Taiwan, ROC.

A higher frequency of hypoplastic vertebral artery (VA) in patients with migraine
with aura than in normal controls has been documented. However, the role of a
hypoplastic VA in a migraine attack remains unclear. The aim of our work was to
measure the net VA flow volume and related spectral parameters in patients with
migraine with aura and a hypoplastic VA. From January 2005 to October 2005 we
reviewed the records of 250 migraine outpatients (108 men and 142 women; mean age
= 30.8 +/- 14.0 years, range = 25-55). Ninety-two patients with migraine with
aura were selected. Among these patients, 26 had a hypoplastic VA that was
delineated by cervical magnetic resonance angiography. We performed a
case-control study that included these 26 migrainous patients. Duplex color-coded
ultrasonography was utilized to calculate the spectral parameters during attacks 
and headache-free periods. The net VA flow volume did not decrease during
attacks. A reduction in the resistance index of the hypoplastic VA was noted
during attacks in subjects who had migraine with aura. Our observation of VA
vasomotor alteration during migraine attacks extends the understanding of the
role of a hypoplastic VA. Vasomotor regulation of the VA could be neurogenic in
origin. We hypothesize that VA hypoplasia contributes to migraine through complex
neurovascular pathways rather than through its low flow volume. Copyright 2007 S.
Karger AG, Basel.

PMID: 18057902 [PubMed - indexed for MEDLINE]

448: Audiol Neurootol. 2008;13(2):113-22. Epub 2007 Nov 29.

Neuro-otological findings in patients with migraine- and nonmigraine-related
dizziness.

Vitkovic J, Paine M, Rance G.

Department of Otolaryngology, The University of Melbourne, East Melbourne,
Australia. jessicav@unimelb.edu.au

This study presents the neuro-otological findings of 523 patients attending a
tertiary vestibular clinic with migraine- and nonmigraine-related dizziness.
Subjects were categorized into one of 4 groups, definite migrainous vertigo,
probable migrainous vertigo, vestibular disorder coexisting with migraine and
nonmigraine-related dizziness. No notable relationship was found between the
numbers of abnormal findings between the groups for the majority of the
neuro-otological tests. However, there was a significant trend in emetic response
to caloric testing. The definite migrainous vertigo group were at least 4 times
more likely to be nauseous to caloric testing than any other migraine category.
This difference was independent of the magnitude of caloric responses between the
emetic migraine groups. While further investigation is required, this study has
potentially identified that nauseous/emetic response to caloric stimulation may
be a distinguishing factor between migrainous vertigo and other vestibular
disorders including those with a coexisting history of migraine. (c) 2007 S.
Karger AG, Basel

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 18057875 [PubMed - indexed for MEDLINE]

449: Neurology. 2007 Dec 4;69(23):2170-6.

Systematic analysis of three FHM genes in 39 sporadic patients with hemiplegic
migraine.

de Vries B, Freilinger T, Vanmolkot KR, Koenderink JB, Stam AH, Terwindt GM,
Babini E, van den Boogerd EH, van den Heuvel JJ, Frants RR, Haan J, Pusch M, van 
den Maagdenberg AM, Ferrari MD, Dichgans M.

Departments of Human Genetics, Leiden University Medical Centre, PO Box 9600,
2300 RC Leiden, The Netherlands.

BACKGROUND: Familial (FHM) and sporadic (SHM) hemiplegic migraine are severe
subtypes of migraine associated with transient hemiparesis. For FHM, three genes 
have been identified encoding subunits of a calcium channel (CACNA1A), a
sodium-potassium pump (ATP1A2), and a sodium channel (SCN1A). Their role in SHM
is unknown. Establishing a genetic basis for SHM may further the understanding of
its pathophysiology and relationship with common types of migraine. It will also 
facilitate the often difficult differential diagnosis from other causes of
transient hemiparesis. METHODS: We systematically scanned 39 well-characterized
patients with SHM without associated neurologic features for mutations in the
three FHM genes. Functional assays were performed for all new sequence variants. 
RESULTS: Sequence variants were identified in seven SHM patients: one CACNA1A
mutation, five ATP1A2 mutations, and one SCN1A polymorphism. All six mutations
caused functional changes in cellular assays. One SHM patient later changed to
FHM because another family member developed FHM attacks. CONCLUSION: We show that
FHM genes are involved in at least a proportion of SHM patients without
associated neurologic symptoms. Screening of ATP1A2 offers the highest likelihood
of success. Because FHM gene mutations were also found in family members with
"nonhemiplegic" typical migraine with and without aura, our findings reinforce
the hypothesis that FHM, SHM, and "normal" migraine are part of a disease
spectrum with shared pathogenetic mechanisms.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 18056581 [PubMed - indexed for MEDLINE]

450: Headache. 2007 Nov-Dec;47(10):1455-6.

Diffusion MRI during migraine with aura attack associated with diagnostic
microbubbles injection in subjects with large PFO.

Dinia L, Roccatagliata L, Bonzano L, Finocchi C, Del Sette M.

Department of Neurosciences, Ophthalmology and Genetics, University of Genova,
Italy.

The relationship between migraine with aura and patent foramen ovale (PFO) is
still debatable. We report 2 cases of migraine with aura attacks after diagnostic
microbubble injection for contrast transcranial Doppler (cTCD), in subjects with 
large PFO. In one case MR images, including diffusion weighted imaging and
apparent diffusion coefficient, performed during aura did not show any signal
abnormality. Patients with migraine with aura may have an attack during cTCD,
probably by a "non-ischemic" mechanism.

Publication Types: 
    Case Reports

PMID: 18052957 [PubMed - indexed for MEDLINE]

451: Headache. 2007 Nov-Dec;47(10):1436-42.

Comment in:
    Headache. 2008 Apr;48(4):644-5.    Headache. 2008 Oct;48(9):1381-2.

Insulin metabolism is altered in migraineurs: a new pathogenic mechanism for
migraine?

Cavestro C, Rosatello A, Micca G, Ravotto M, Marino MP, Asteggiano G, Beghi E.

Headache Center, Department of Neurology, San Lazzaro Hospital, Alba, Italy.

BACKGROUND: Migraine is a complex biochemical dysfunction attributed to a
disorder of the trigeminal and hypothalamic pathways. Impairment of glucose
metabolism has been reported in migraine, but data are scanty and inconsistent.
OBJECTIVE: The main aim was to verify whether migraineurs have abnormalities of
the glucose and insulin metabolism.We also studied correlations between blood
glucose and insulin and between insulin levels and migraine severity. PATIENTS
AND METHODS: Patients with migraine or headache other than migraine, and healthy 
volunteers were included. All had general blood tests and a standard oral glucose
tolerance test after a 12-hour fast, and glucose and insulin were measured.
RESULTS: Over a 6-month period, we recruited 84 migraineurs (73 women, 11 men),
25 patients with nonmigraine headache (20 women, 5 men), and 26 healthy controls 
(24 women, 2 men). Multivariate analysis confirmed a significant difference
between groups for glucose levels (P < .0001), but no significant time
interaction. The differences were mostly between migraine and healthy controls (P
< .0001) and to a lesser extent between other headaches and healthy controls (P <
.05). A significant difference between groups was also found for insulin (P <
.0001), with a significant time interaction. The difference was confirmed for
migraine compared to other headaches (P < .0001) and healthy controls (P <
.0001). CONCLUSIONS: Blood glucose levels may be high in headache patients, but
do not seem to be specific to migraineurs. Insulin levels were higher in
migraineurs, and seemed specific to this group. These findings are in keeping
with recent reports on the effects of insulin on brain functions and lend support
to the possibility that insulin is involved in the pathogenesis of migraine.

PMID: 18052953 [PubMed - indexed for MEDLINE]

452: Headache. 2007 Nov-Dec;47(10):1427-35.

Comment in:
    Headache. 2008 Jun;48(6):973-4.

Prevalence of vertigo, dizziness, and migrainous vertigo in patients with
migraine.

Vuković V, Plavec D, Galinović I, Lovrencić-Huzjan A, Budisić M, Demarin V.

University Hospital Sestre milosrdnice-Department of Neurology, Zagreb, Croatia.

OBJECTIVE: The aim of this study was to determine the lifetime prevalence of
vertigo and dizziness in patients with migraine as compared with controls and to 
establish the lifetime prevalence of migrainous vertigo. BACKGROUND: Dizziness
and vertigo are relatively frequent complaints in general population; however,
the prevalence of migrainous vertigo has not been extensively studied so far.
METHODS: The study included 327 migraine patients and 324 controls who do not
suffer from frequent headaches. The study and control group were assessed
clinically and through diagnostic workup for having vertigo, dizziness,
hypotension, and sideropenic anemia. RESULTS: Vertigo or dizziness was
experienced by 51.7% of migraine patients (MVL group) and 31.5% in the control
group (CVL group), P < .0001. Among the MVL group, 23.2% of patients met the
criteria for migrainous vertigo. There was no difference between the MVL group
and CVL group in frequency of attacks or the pattern of symptom appearance in
relation to head movement. Patients in the MVL group more frequently had
hypotension, P = .011. Patients with migraine with aura significantly more often 
had migraine attacks in association with vertigo or dizziness, P < .0001.
CONCLUSION: The lifetime prevalence of migrainous vertigo is relatively frequent 
in migraine patients, especially in migraine with aura.

PMID: 18052952 [PubMed - indexed for MEDLINE]

453: Headache. 2007 Nov-Dec;47(10):1418-26.

Hypothalamic activation in spontaneous migraine attacks.

Denuelle M, Fabre N, Payoux P, Chollet F, Geraud G.

Neurology Service, Rangueil Hospital, Toulouse Cedex 9, France.

BACKGROUND: Migraine sufferers experience premonitory symptoms which suggest that
primary hypothalamic dysfunction is a likely trigger of the attacks.
Neuroendocrine and laboratory data also support this hypothesis. To date,
positron emission tomography (PET) scans of migraine sufferers have demonstrated 
activation of brainstem nuclei, but not of the hypothalamus. OBJECTIVE: To record
cerebral activations withH2 15OPET during spontaneous migraine without aura
attacks. METHODS: We scanned 7 patients with migraine without aura (6 females and
1 male) in each of 3 situations: within 4 hours of headache onset, after headache
relief by sumatriptan injection (between the fourth and the sixth hour after
headache onset), and during an attack-free period. RESULTS: During the headache
we found not only significant activations in the midbrain and pons, but also in
the hypothalamus, all persisting after headache relief by sumatriptan.
CONCLUSION: Hypothalamic activity, long suspected by clinical and experimental
arguments as a possible trigger for migraine, is demonstrated for the first time 
during spontaneous attacks.

Publication Types: 
    Clinical Trial
    Research Support, Non-U.S. Gov't

PMID: 18052951 [PubMed - indexed for MEDLINE]

454: Headache. 2007 Nov-Dec;47(10):1409-17.

A double-blind, dose comparison study of topiramate for prophylaxis of
basilar-type migraine in children: a pilot study.

Lewis D, Paradiso E.

Division of Pediatric Neurology, Department of Pediatrics, Children's Hospital of
the King's Daughters, Eastern Virginia Medical School, Norfolk, VA 23507-1972,
USA.

BACKGROUND: Basilar-type migraine (BM) is the most common migraine "variant,"
representing 3-19% of migraine in children.BMis characterized by attacks of
dizziness, vertigo, visual disturbances, ataxia, and/or diplopia, followed by
migraine headache. OBJECTIVE: The objective of this study is to assess the
efficacy and safety of topiramate for prophylaxis of BM in children and
adolescents (6-18 years). DESIGN: Outpatient, double-blind, parallel-group, dose 
comparison study with 2 phases: prerandomization (screening/washout and 4-week
prospective baseline) and 12-week double blind (titration and maintenance).
METHODS: Following consent and assent, subjects with BMs, as defined by the
International Classification of Headache Disorders (second edition), and > or =4 
migraines/month were randomized to receive either 25 mg per day or 100 mg per day
of topiramate in a 1 : 1 ratio. RESULTS: Fourteen children (4 boys, 10 girls)
completed the double-blind phase (7 in the 25-mg group and 7 in the 100-mg
group). During the prospective baseline, the mean headache frequency of the
combined group "all migraines" per month was 4.5/month (25 mg) and 4.8/month (100
mg). Average duration of migraine was 5.5 hours (25 mg) and 5.0 hours (100 mg)
and average mean pain (5-point faces scale) was 3.3 for both (25 mg 100 mg). The 
reduction in median monthly migraine rate during the double-blind treatment phase
relative to baseline was 2.9 (64.4%) and 3.6 (75.0%) for the 25-mg and 100-mg
topiramate-treated groups, respectively (P < .001). The reduction in median
monthly BM rate during the double-blind treatment phase relative to baseline was 
2.5 (74.24%) and 2.3 (82.8%) for the 25-mg and 100-mg topiramate-treated groups, 
respectively. The overall reduction in BM attacks reduced from 2.84/month to
0.59/month (79.2%; P < .0042). Overall, 86% of patients responded with a greater 
than 50% reduction in migraine frequency (100%, 25 mg and 71%, 100 mg). Mean
reduction in migraine duration was 18 minutes (25 mg) and 89 minutes (100 mg).
There was no significant difference in migraine severity between the 2 groups.
Parent Global Assessment was "very much" or "much improved" in 6 of 7 (25 mg) and
3 of 7 (100 mg) patients. Migraine disability as measured by PedMidas reduced
from moderate to no disability (P < .001). There were no serious adverse events. 
CONCLUSIONS: Preventive therapy with topiramate resulted in reducing the overall 
migraine frequency and the frequency of attacks of BM at both 25 mg and 100 mg
doses relative to the historical baseline and prospective baseline periods. The 2
treatment groups resulted in comparable outcomes.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 18052950 [PubMed - indexed for MEDLINE]

455: Headache. 2007 Nov-Dec;47(10):1398-408.

The impact of topiramate on health-related quality of life indicators in chronic 
migraine.

Dodick DW, Silberstein S, Saper J, Freitag FG, Cady RK, Rapoport AM, Mathew NT,
Hulihan J, Crivera C, Rupnow MF, Mao L, Finlayson G, Greenberg SJ.

Mayo Clinic College of Medicine, Department of Neurology, Scottsdale, AZ, USA.

BACKGROUND: Chronic migraine is a disabling primary chronic daily headache
disorder that significantly impacts the daily activities of patients with this
disorder. To our knowledge, this is the first report of a large, randomized,
double-blind, placebo-controlled trial that assessed the impact of topiramate on 
the daily activities, emotional distress, headache-related disability, and global
impression of change in patients with chronic migraine. OBJECTIVE: To assess
whether topiramate 100 mg/day reduces migraine-related disability and limitations
of daily activities in patients with chronic migraine. STUDY DESIGN/METHODS:
Patients aged > or =18 years with chronic migraine were randomized 1 : 1 ratio to
topiramate 100 mg/day or placebo. The double-blind period lasted 16 weeks. Three 
patient-reported outcome measures were administered: Migraine Disability
Assessment, Migraine-Specific Quality of Life Questionnaire (Domains: Role
Function Restrictive and Preventive and Emotional Function), and Subject's Global
Impression of Change. Investigators completed a Physician's Global Impression of 
Change for each patient. Subject's Global Impression of Change and Physician's
Global Impression of Change were completed one time, at the end of study, and
measured on a 7-point scale (1 = very much improved to 7 = very much worse). The 
Migraine-Specific Quality of Life Questionnaire was analyzed using analysis of
covariance (last observation carried forward) approach. Results were not adjusted
for multiplicity. RESULTS: A total of 328 patients were randomized (topiramate, n
= 165; placebo, n = 163), and 306 patients were included in the intent-to-treat
population. Mean age was 38.2 years, and a majority of the patients were female
(85.3%). Fifty-six percent of topiramate-treated patients vs 45% of
placebo-treated patients reported >50% improvement from baseline in Migraine
Disability Assessment scores (P = .074). The Migraine-Specific Quality of Life
Questionnaire analysis demonstrated significant improvements at week 4 in all 3
domains, and at weeks 8 and 16 in both Role Function-Restrictive and Emotional
Function domains (P < .05). Role Function-Preventive approached, but did not
reach significance, at week 8 (P = .053). Seventy-five percent and 72% of
topiramate-treated patients vs 61% and 59% of placebo-treated patients reported
improvements on the Subject and Physician's Global Impression of Change scales (P
= .025 and P = .037, respectively). CONCLUSION: Compared with placebo-treated
patients, topiramate 100 mg/day appears to contribute to reductions in
migraine-related limitations on daily activities and emotional distress beginning
as early as week 4 and continuing up to week 16 after treatment. Physician's
Global Impression of Change results are very similar with Subject's Global
Impression of Change, indicating concordance between the physician's and the
subject's assessment of improvement.

Publication Types: 
    Clinical Trial
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 18052949 [PubMed - indexed for MEDLINE]

456: Headache. 2007 Nov-Dec;47(10):1374-84.

Migraine and the risk of stroke, TIA, or death in the UK (CME).

Becker C, Brobert GP, Almqvist PM, Johansson S, Jick SS, Meier CR.

Basel Pharmacoepidemiology Unit, Division of Clinical Pharmacology and
Toxicology, University Hospital Basel, Switzerland.

BACKGROUND: Previous observational studies have reported a higher risk of stroke 
in migraine patients. Objective.- We aimed to estimate the risk of stroke,
transient ischemic attack (TIA), or death in migraineurs in the UK. METHOD: We
conducted a population-based follow-up study within the General Practice Research
Database from 1994 to 2001. RESULTS: The relative risk (RR) of stroke in
migraineurs compared with non-migraineurs was 2.2 (95% confidence interval [CI]
1.7-2.9). It was highest for patients with a migraine diagnosis recorded within
30 days prior to a stroke (odds ratio 11.1, 95% CI 5.69-21.5). The RR of TIA in
migraineurs compared with non-migraineurs was 2.4 (95% CI 1.8-3.3), the mortality
of migraineurs was slightly decreased. CONCLUSION: In our study, the RR of
developing a stroke or a TIA was doubled in migraineurs as compared with
non-migraineurs, while that for death was close to unity.

PMID: 18052947 [PubMed - indexed for MEDLINE]

457: Expert Rev Neurother. 2007 Dec;7(12):1659-73.

Almotriptan: meeting today's needs in acute migraine treatment.

Láinez MJ.

Department of Neurology, University Clinic Hospital, University of Valencia, Avda
Blasco Ibáñez, 17 46010 Valencia, Spain. jlaineza@meditex.es

Migraine is a common disorder associated with considerable individual and
economic burden. Triptans are recommended for the treatment of migraine of any
severity in patients who have failed to gain adequate relief with nonspecific
medication; early transition to triptans avoids prolonged morbidity in patients
failing to respond to nonspecific medications. There is evidence that early
intervention therapy with oral formulations in migraine, soon after the onset of 
an attack and when pain is still mild, improves efficacy. Seven different
triptans are currently marketed, with differing pharmacologic, efficacy and
tolerability profiles. Almotriptan has many positive features, which include
rigorously demonstrated efficacy in sumatriptan nonresponders, as early therapy
and in menstrual migraine. In addition, almotriptan has a favorable pharmacologic
profile with a lack of clinically relevant pharmacokinetic interventions with
other drugs, adverse reactions rate similar to placebo, superior
cost-effectiveness and excellent performance on composite clinical outcome
measures that incorporate features of greatest importance to patients. Although
effective in both triptan-naive and -experienced patients, and as both early and 
standard therapy, almotriptan shows greater efficacy in triptan-naive patients
and as early treatment, and is consistently one of the preferred triptans in
multiattribute decision-making analyses incorporating attributes of significance 
for patients and physicians. Therefore, almotriptan has many features that make
it an ideal choice for a triptan-naive patient moving from nonspecific
medication, a patient switching from another triptan owing to inefficacy or
tolerability issues and patients being advised to take a triptan early in the
course of a migraine attack.

Publication Types: 
    Review

PMID: 18052762 [PubMed - indexed for MEDLINE]

458: Headache. 2008 Feb;48(2):210-20. Epub 2007 Nov 28.

Botulinum toxin type A and divalproex sodium for prophylactic treatment of
episodic or chronic migraine.

Blumenfeld AM, Schim JD, Chippendale TJ.

The Neurology Center, Encinitas, CA 92024, USA.

OBJECTIVE: To compare the efficacy and safety of botulinum toxin type A (BoNTA;
BOTOX: Allergan, Inc.) and divalproex sodium (DVPX; DEPAKOTE: Abbott
Laboratories) as prophylaxis in reducing disability and impact associated with
migraine. BACKGROUND: There is a need for effective, well-tolerated prophylactic 
treatment of migraine. DESIGN/METHODS: This was a randomized, double-blind,
single-center prospective study. Fifty-nine patients received either BoNTA 100
U/placebo-DVPX bid or placebo-BoNTA/DVPX 250 mg bid. BoNTA/placebo injections
were given at Day 0 and at Month 3. Patients were evaluated at Months 1, 3, 6,
and 9. RESULTS: Both treatments showed significant improvements in migraine
disability scores and reductions in headache days and headache index. A trend to 
decreased headache severity was observed with BoNTA. A greater percentage of DVPX
patients reported adverse events possibly related to treatment (DVPX 75.8% vs
BoNTA 50%, P = .04) and discontinued because of adverse events (DVPX 27.6% vs
BoNTA 3.3%, P = .012). CONCLUSIONS: Both BoNTA and DVPX significantly reduced
disability associated with migraine; BoNTA had a favorable tolerability profile
compared with DVPX.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 18047502 [PubMed - indexed for MEDLINE]

459: Headache. 2008 Jun;48(6):900-13. Epub 2007 Nov 28.

Botulinum toxin type A as migraine preventive treatment in patients previously
failing oral prophylactic treatment due to compliance issues.

Cady R, Schreiber C.

Headache Care Center, Springfield, MO, USA.

OBJECTIVE: To examine the efficacy and safety of and satisfaction with botulinum 
toxin type A (BoNTA; BOTOX: Allergan, Inc., Irvine, CA) for prophylactic
treatment of migraine headache in patients previously failing prophylaxis because
of issues pertaining to compliance. Background.- Numerous factors (eg, adverse
effects, tolerability, cost, frequency of dosage, hesitancy to take daily
medication, failure to complete treatment) negatively influence compliance with
the preventive pharmacology for migraine prophylaxis. BoNTA may offer benefit in 
improving compliance because of its long duration of action, injectable route of 
administration, and its tolerability (adverse event [AE]) profile. METHODS: This 
was a randomized, double-blind, single-center, placebo-controlled study (months 1
to 3) of BoNTA with a cross-over to open-label BoNTA treatment (months 4 to 6).
Criteria for enrollment included patients with disabling headache (International 
Headache Society, International Classification of Headache Disorders [ICHD-I]
diagnosis 1.1, 1.2, 1.7, or 2.2, and Headache Impact Test [HIT]-6 scores >/=56)
previously failing prophylaxis because of compliance, tolerability, or adherence 
issues. After baseline evaluation, subjects were randomized 2 : 1 to a single set
of BoNTA (139 units [U] total; 17 sites/6 muscle groups) or placebo injections.
After month 3, only placebo-treated subjects were eligible to receive BoNTA in
the open-label continuation study. Treatment outcomes were evaluated by headache 
episodes and days and maximum headache severity. Headache impact was assessed by 
the HIT-6, Migraine Disability Assessment (MIDAS) score, and Quality of Life
(QoL) questionnaires. Treatment satisfaction was assessed with the Migraine
Impact Questionnaire (MIQ), which included MIDAS and QoL. RESULTS: Of the 73
subjects screened, 61 (40 BoNTA; 21 placebo) with migraine headache diagnosis 1.1
and 1.2 who met all study criteria were enrolled in the 3-month, blinded study,
with 54 completing the study; 19 of 21 placebo-treated subjects participated in
the open-label period (months 4 to 6), with 18 completing the study.
Between-group comparisons, demonstrated through analysis of the subjects'
headache diaries, did not reach statistical significance at months 1 to 3 for the
number of headache episodes or days (primary endpoint). At month 2, a decrease
from baseline in the number of headache episodes (-0.99 +/- 2.38; P = .0147 vs
0.42 +/- 3.23; P = not significant [NS]) and headache days (-1.52 +/- 3.84; P =
.0194 vs 0.23 +/- 4.67; P = NS) was noted in the BoNTA-treated subjects but not
in the placebo-treated subjects, respectively. During the open-label study,
BoNTA-treated subjects had a decrease in the number of headache episodes at
months 5 and 6 (-1.58 +/- 2.88 and -1.58 +/- 2.85, respectively; P < .05 vs
baseline for both) and headache days at months 5 and 6 (-2.84 +/- 4.47 and -2.73 
+/- 4.86, respectively; P < .05 vs baseline for both). BoNTA did not affect
maximum headache severity compared with baseline or placebo during the first 3
months of the study. A decrease in HIT-6 scores was significantly greater for
BoNTA-treated subjects than for placebo-treated subjects at month 3 (-7.77 vs
-3.58, P = .0466). Within-group decreases in HIT-6 scores were significant in
BoNTA-treated subjects during each month of the blinded trial (-5.10 +/- 8.85,
-6.63 +/- 7.49, -7.77 +/- 8.78 for months 1 to 3, respectively; P < .0001 for all
vs baseline) and throughout the open-label portion of the study (-7.89 +/- 6.48, 
-10.39 +/- 10.81, -9.00 +/- 11.12 for months 4 to 6, respectively; P < .01 for
all vs baseline). The within-group decrease in placebo-treated subjects was
significant at months 1 and 3 (-3.35 +/- 6.07 and -3.58 +/- 5.40, respectively; P
< .05 for both). At 3 months, BoNTA was significantly better than placebo (P =
.001) in the reduction of MIDAS total score. The change from baseline in the
MIDAS total scores was significant in BoNTA-treated subjects (-21.62 +/- 38.70; P
< .0001) but not in placebo recipients (4.76 +/- 18.85; P = NS). BoNTA-treated
subjects showed improvement in 11 of 13 and 7 of 13 assessments of treatment
satisfaction in MIQ at months 3 and 6, respectively, while the placebo group
showed no improvement at any measured time interval in the study. At month 3
(blinded period), there were no treatment-related AEs reported in both groups.
However, there were 18 possible/probable occurrences of treatment-related AEs in 
the BoNTA group. At month 6 (open-label period), 4 treatment-related AEs were
reported, along with 2 possible occurrences. The majority of treatment-related
AEs were transient and mild to moderate in severity, with no subjects
discontinuing the study because of AEs. CONCLUSIONS: BoNTA-treated subjects
showed improvements from baseline in measures of headache frequency, and
improvements from baseline and in comparison with placebo treatment in headache
impact and treatment satisfaction at multiple time points in this study. However,
BoNTA-treated subjects did not differ from placebo-treated subjects in measures
of headache frequency and severity. BoNTA may be a useful treatment option for
headache patients demonstrating poor compliance, adherence, or AE profile with
oral prophylactic regimens.

Publication Types: 
    Randomized Controlled Trial

PMID: 18047501 [PubMed - indexed for MEDLINE]

460: Headache. 2008 Mar;48(3):368-77. Epub 2007 Nov 28.

Elimination of migraine-associated nausea in patients treated with rizatriptan
orally disintegrating tablet (ODT): a randomized, double-blind,
placebo-controlled study.

Freitag F, Taylor FR, Hamid MA, Rodgers A, Hustad CM, Ramsey KE, Skobieranda F.

Diamond Headache Clinic, Chicago, IL 60614, USA.

OBJECTIVE: To confirm the efficacy of rizatriptan 10 mg orally disintegrating
tablet (ODT) for the elimination of migraine-associated nausea. BACKGROUND:
Pooled studies of rizatriptan analyzing elimination of nausea as a secondary
endpoint showed that 65% of rizatriptan patients reported elimination of nausea
at 2 hours compared with 41% of patients taking placebo. METHODS: This was a
multicenter, randomized, double-blind, placebo-controlled single-attack trial
enrolling adult patients with at least a 6-month history of migraine who
typically experience migraine-associated nausea. Patients treated a moderate or
severe migraine headache at the earliest sign of nausea with either rizatriptan
10 mg ODT or placebo (2 : 1). The primary endpoint was elimination of nausea at 2
hours postdose, and the secondary endpoint was pain relief at 2 hours postdose.
RESULTS: Although not statistically significant, a greater percentage of patients
had elimination of nausea at 2 hours with rizatriptan compared with placebo
(70.3% vs 62.0%, P = .165, odds ratio [95% CI] = 1.45 [0.86, 2.46]). When
patients were grouped by baseline headache severity, rizatriptan showed a greater
advantage than placebo for patients with moderate pain (rizatriptan 72.8% vs
placebo 57.4%), but no difference for patients with severe pain (rizatriptan
67.7% vs placebo 66.7%). There were significantly more patients who achieved
2-hour pain relief with rizatriptan (69.7% vs 54.3%, P = .012, odds ratio [95%
CI] = 1.94 [1.16, 3.25]). CONCLUSION: Although the efficacy of rizatriptan 10 mg 
ODT for the elimination of migraine-associated nausea was comparable to that seen
in previous rizatriptan trials, the higher-than-usual placebo response prevented 
a finding of a statistically significant difference. There was a sizable
difference in placebo response between patients who treated moderate vs severe
migraine. Rizatriptan was effective for 2-hour pain relief.

Publication Types: 
    Multicenter Study
    Randomized Controlled Trial

PMID: 18047500 [PubMed - indexed for MEDLINE]

461: Headache. 2008 Mar;48(3):333-40. Epub 2007 Nov 28.

Randomized controlled trial of intravenous dexamethasone to prevent relapse in
acute migraine headache.

Rowe BH, Colman I, Edmonds ML, Blitz S, Walker A, Wiens S.

School of Public Health, University of Alberta, Edmonton, Alberta, Canada.

OBJECTIVES: Migraine headache is a common presentation in the emergency
department (ED). Inflammation is thought to play a role in the pathophysiology of
migraine and there is conflicting evidence regarding the effect of
corticosteroids on reducing early recurrences. We conducted a randomized clinical
trial to test the hypothesis that dexamethasone (DEX) reduced headaches after
discharge and examine the factors associated with relapse. METHODS: Consenting
adults (18 and older) presenting with acute migraine at 4 EDs were enrolled. In
addition to standard intravenous (IV) abortive therapy, using concealed
allocation patients were randomized to receive IV DEX (15 mg) or placebo (PLA) in
a double-blind fashion. Relapse was defined as a return to the ED, an urgent
clinic visit, or a headache that precluded normal activity reported during
follow-up telephone interviews 48-72 hours and 7 days after ED discharge.
Intention to treat was used for all final analyses. RESULTS: A total of 130
patients were randomized; 126 patients are included in the analysis (one patient 
left prior to treatment and 3 enrolled twice); 64 received DEX and 62 received
PLA. Mean age was 35 years, 81% was female; most (77%) suffered from headaches at
least monthly. On a 10-point visual analog scale (VAS), the median pain scores
were 8 at presentation, and 2 at discharge. At 48-72 hours, relapses occurred in 
14/64 (22%) in the DEX group and 20/62 (32%) in the PLA groups (OR = 0.6; 95% CI:
0.3-1.3). By day 7, 18/64 (28%) in the DEX group had relapsed, compared with
25/62 (40%) in the PLA group (OR = 0.6; 95% CI: 0.3-1.3). Controlling for
treatment assignment, relapse was more common when headache pain was incompletely
relieved (VAS > 2) at ED discharge (OR = 2.2; 95% CI: 1.1-5.4). CONCLUSIONS: The 
overall relapse rate differed from those previously reported; however, DEX failed
to reduce headache relapses after ED discharge. Relapse was closely associated
with incomplete pain relief at discharge. Further research is needed to determine
the factors associated with migraine relapse.

Publication Types: 
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 18047499 [PubMed - indexed for MEDLINE]

462: Otol Neurotol. 2008 Jan;29(1):93-6.

Familial clustering of migraine, episodic vertigo, and Ménière's disease.

Cha YH, Kane MJ, Baloh RW.

Department of Neurology, University of California-Los Angeles, Los Angeles,
California 90095, USA. yhcha@mednet.ucla.edu

OBJECTIVE: To evaluate the association between migraine, episodic vertigo, and
Ménière's disease in families. STUDY DESIGN: Clinical report. SETTING: University
Neurotology Clinic. PATIENTS: Index patients identified with Ménière's disease
and migraine and their family members. INTERVENTION: Structured interview to
assess a diagnosis of migraine, episodic vertigo, and Ménière's disease in 6
families. Genotyping was performed on 3 sets of twins to analyze monozygosity or 
dizygosity. MAIN OUTCOME MEASURES: Clinical history of migraine, episodic
vertigo, and Ménière's disease. RESULTS: Six index patients and 57 family members
were interviewed either by a senior neurologist in person or over the phone by a 
trained study coordinator. An additional 6 family members completed
questionnaires by mail. All 6 index patients had Ménière's disease and migraine. 
Twenty-six (41%) of the 63 relatives met International Classification of Headache
Disorders II criteria for migraine headaches. Thirteen (50%) of these 26
experienced migraine with aura. Three others experienced typical aura without
headache. Seventeen (27%) of 63 family members experienced recurrent spells of
spontaneous episodic vertigo. There was one twin pair in each of 3 families; 2
pairs were monozygotic and one was dizygotic. In each twin pair, one twin had
migraine and Ménière's disease, whereas the other experienced migraine and
episodic vertigo without auditory symptoms. CONCLUSION: The frequent association 
of episodic vertigo, migraine, and Ménière's disease in closely related
individuals, including identical twins supports the heritability of a
migraine-Ménière's syndrome, with variable expression of the individual features 
of hearing loss, episodic vertigo, and migraine headaches.

Publication Types: 
    Case Reports
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 18046258 [PubMed - indexed for MEDLINE]

463: Pediatr Int. 2007 Dec;49(6):943-9.

Prevalence and clinical findings of migraine and tension-type headache in
adolescents.

Unalp A, Dirik E, Kurul S.

Department of Pediatric Neurology, Dokuz Eylül University Faculty of Medicine,
Izmir, Turkey. aycanunalp@mynet.com

BACKGROUND: The majority of previous studies on headache in children and
adolescents have focused mainly on migraine. There is a paucity of
population-based studies investigating the prevalence of tension-type headache
(TTH). The objectives of the present study were to estimate the prevalence of
migraine and TTH in adolescents using the 2004 International Headache Society
(IHS) criteria and to determine the sociodemographic and clinical differences
between the migraine and TTH. METHODS: Stratified group sampling was used in the 
present analytic, school-based, cross-sectional study. From the city of Izmir,
2384 students aged 14-18 years were invited to complete a questionnaire. RESULTS:
Migraine was found to be more common than TTH (21.3% vs 5.1%). The prevalence
increased considerably to 29.9 and 15%, respectively, when the criteria defining 
the number and duration of headaches were excluded. All types of headaches were
more frequent in female subjects but no significant difference was found in
gender between the headache groups (P= 0.073). Headache in temples, number of
siblings (more than one sibling), mother's and father's education (at least high 
school graduation) were more commonly seen in students with TTH. Absenteeism rate
due to the headache was found to be higher in the migraine group than in the TTH 
group (P= 0.000). CONCLUSIONS: Migraine and TTH were found to be common types of 
headaches in adolescents. It was thought that, with the use of modified IHS
criteria, the number of undiagnosed patients with headache will decrease.

PMID: 18045302 [PubMed - indexed for MEDLINE]

464: Headache. 2008 Feb;48(2):201-9. Epub 2007 Nov 28.

Botulinum Toxin Type A in the treatment of chronic migraine without medication
overuse.

Freitag FG, Diamond S, Diamond M, Urban G.

Diamond Headache Clinic, Chicago, IL 60614, USA.

INTRODUCTION: Chronic migraine is a recent diagnostic term that has undergone
evolution from its original description. Clinically it has been believed that
medication overuse contributed to its development and would block attempts at
prevention. Previous studies with Botulinum Toxin Type A have demonstrated that
it is effective even in patients with medication overuse. This study undertakes
to examine the effects of Botulinum Toxin Type A in the absence of medication
overuse in patients with chronic migraine. STUDY DESIGN: Double-blind
placebo-controlled randomized trial of Botulinum Toxin Type A 100 units
administered in a fixed dose and site paradigm. PATIENTS: In total, 86 patients
were enrolled. A total of 60 patients were randomized and 41 patients were
treated with the study medication or placebo. Five patients failed to complete
the study, which lasted 4 months after the study medication was injected.
RESULTS: Botulinum Toxin Type A was statistically superior to placebo for the
primary endpoint of reduction in migraine headache episodes. Six patients on
Botulinum Toxin Type A compared with 3 patients on Placebo had at least a 50%
reduction in their migraine episodes. Active treatment was superior to placebo
for the secondary endpoints of total headache days, headache index, and quality
of life measures. It showed numerical superiority to placebo for acute medication
use and Migraine Disability Assessment Scores. Adverse events were rare and
similar in both treatment groups. CONCLUSIONS: The use of Botulinum Toxin Type A 
may be an effective treatment for chronic migraine when the patient does not have
concomitant medication overuse. It was well tolerated in this trial.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 18042229 [PubMed - indexed for MEDLINE]

465: J Am Osteopath Assoc. 2007 Nov;107(10 Suppl 6):ES10-6.

Comment in:
    J Am Osteopath Assoc. 2008 Apr;108(4):191; author reply 191, 214.

Diagnosing and managing migraine headache.

Mueller LL.

University Headache Center, University of Medicine and Dentistry of New
Jersey-School of Osteopathic Medicine, 42 E Laurel Rd, University Doctors
Pavilion, Ste 1700, Stratford, NJ 08084-1354, USA. SOMPhysicians@umdnj.edu

Headache is one of the chief complaints among patients visiting primary care
physicians. Diagnosis begins with exclusion of secondary causes for headache.
More than 90% of patients will have a primary-type headache, so diagnosis can
often be completed without further testing. Although tension-type headaches are
the most common kind of headache, patients with this type of headache rarely seek
treatment unless occurrence is daily. Migraine, which affects more than 30
million people in the United States, is the most common headache diagnosis for
which patients seek treatment. Migraine is a chronic, often inherited condition
involving brain hypersensitivity and a lowered threshold for trigeminal-vascular 
activation. Intermittent debilitating attacks are characterized by autonomic,
gastrointestinal, and neurologic symptoms. Migraine results in a marked decrease 
in a patient's quality of life, as measured by physical, mental, and social
health-related instruments. Accurate assessment of a patient's disability will
guide physicians in prescribing appropriate modes of therapy. However, migraine
remains underdiagnosed, and patients with migraine remain undertreated. A
comprehensive treatment approach to migraine may include nonpharmacologic
measures, as well as abortive and prophylactic medications. Informing patients
about realistic treatment expectations, possible delayed efficacy of medications,
and avoidance of caffeine and overuse of medications is critical for successful
outcomes. Management of migraine is a dynamic process, because headaches evolve
over time and medication tachyphylaxis may occur, necessitating changes in
therapy. Pathologic findings in the neck constitute an accepted etiology or
precipitant for headache. Osteopathic manipulative treatment may reduce pain
input into the trigeminal nucleus caudalis, favorably altering
neuromuscular-autonomic regulatory mechanisms to reduce discomfort from headache.

Publication Types: 
    Review

PMID: 17986672 [PubMed - indexed for MEDLINE]

466: J Pharmacol Exp Ther. 2008 Feb;324(2):416-21. Epub 2007 Nov 26.

Pharmacological characterization of MK-0974
[N-[(3R,6S)-6-(2,3-difluorophenyl)-2-oxo-1-(2,2,2-trifluoroethyl)azepan-3-yl]-4-(
2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridin-1-yl)piperidine-1-carboxamide], a
potent and orally active calcitonin gene-related peptide receptor antagonist for 
the treatment of migraine.

Salvatore CA, Hershey JC, Corcoran HA, Fay JF, Johnston VK, Moore EL, Mosser SD, 
Burgey CS, Paone DV, Shaw AW, Graham SL, Vacca JP, Williams TM, Koblan KS, Kane
SA.

Merck Research Laboratories, WP26A-2000, West Point, PA 19486, USA.
christopher_salvatore@merck.com

Calcitonin gene-related peptide (CGRP) is a potent neuropeptide that plays a key 
role in the pathophysiology of migraine headache. CGRP levels in the cranial
circulation are increased during a migraine attack, and CGRP itself has been
shown to trigger migraine-like headache. The correlation between CGRP release and
migraine headache points to the potential utility of CGRP receptor antagonists as
novel therapeutics in the treatment of migraine. Indeed, clinical
proof-of-concept in the acute treatment of migraine was demonstrated with an
intravenous formulation of the CGRP receptor antagonist BIBN4096BS (olcegepant). 
Here we report on the pharmacological characterization of the first orally
bioavailable CGRP receptor antagonist in clinical development, MK-0974
[N-[(3R,6S)-6-(2,3-difluorophenyl)-2-oxo-1-(2,2,2-trifluoroethyl)azepan-3-yl]-4-(
2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridin-1-yl)piperidine-1-carboxamide]. In
vitro, MK-0974 is a potent antagonist of the human (K(i) = 0.77 nM) and rhesus
(K(i) = 1.2 nM) CGRP receptors but displays >1500-fold lower affinity for the
canine and rat receptors as determined via (125)I-human CGRP competition binding 
assays. A rhesus pharmacodynamic assay measuring capsaicin-induced changes in
forearm dermal blood flow via laser Doppler imaging was utilized to determine the
in vivo activity of CGRP receptor antagonism. MK-0974 produced a
concentration-dependent inhibition of dermal vasodilation, generated by
capsaicin-induced release of endogenous CGRP, with plasma concentrations of 127
and 994 nM required to block 50 and 90% of the blood flow increase, respectively.
In conclusion, MK-0974 is a highly potent, selective, and orally bioavailable
CGRP receptor antagonist, which may be valuable in the acute treatment of
migraine.

Publication Types: 
    Comparative Study

PMID: 18039958 [PubMed - indexed for MEDLINE]

467: Cephalalgia. 2008 Feb;28(2):164-73. Epub 2007 Nov 26.

SMILE: first observational prospective cohort study of migraine in primary care
in France. Description of methods and study population.

Géraud G, Valade D, Lantéri-Minet M, Radat F, Lucas C, Vives E, Joubert JM,
Mekies C.

Department of Neurology, Rangueil Hospital, Toulouse, France.
geraud.g@chu-toulouse.fr

The SMILE study was conducted among migraine patients consulting in primary care 
in France. The first phase aimed to describe the study sample of patients at
entry to the study, especially emotional dimension (Hospital Anxiety and
Depression scale), functional impact (abridged Migraine Specific Questionnaire), 
stress (Perceived Stress Scale) and coping behaviours (brief COPE inventory
avoidance subscale, Coping Strategies Questionnaire catastrophizing subscale), as
well as treatments used and their effectiveness and treatments prescribed at end 
of consultation. Results indicate that consulting migraine patients suffer
frequent migraine attacks, exhibit substantial levels of anxiety, functional
impact and stress, and often use maladaptive coping strategies. Abortive
treatments appear ineffective in most patients (74%). Patients with more affected
psychometric variables and treatment ineffectiveness are more likely to be deemed
eligible for prophylactic treatment. These data highlight the seriousness of
migraine and maladjustment of patients consulting in primary care.

PMID: 18039338 [PubMed - indexed for MEDLINE]

468: Eur J Pharmacol. 2008 Feb 2;580(1-2):43-7. Epub 2007 Oct 30.

5-hydroxytryptamine1B receptor and triptan response in migraine, lack of
association with common polymorphisms.

Velati D, Viana M, Cresta S, Mantegazza P, Testa L, Bettucci D, Rinaldi M, Sances
G, Tassorelli C, Nappi G, Canonico PL, Martignoni E, Genazzani AA.

DiSCAFF and DFB Center, Via Bovio, 6, 28100 Novara, Italy.

Triptans mediate vasoconstriction of meningeal vessels via stimulation of
vascular 5-hydroxytryptamine (5-HT)(1B) receptors. These drugs are recommended
for acute treatment in patients with moderate-to-severe migraine attacks and in
those patients with mild-to-moderate headache that are not controlled adequately 
by other agents. Yet, approximately 25% of all migraine users and 40% of all
attacks do not respond to triptan treatment. Among the hypothesis to explain this
is the possibility that genetic single nucleotide polymorphisms that alter the
receptor, for example changing the transcriptional rate and therefore the amount 
of target protein might change the clinical response to these drugs. In the
present contribution, we therefore decided to evaluate whether single nucleotide 
polymorphisms on the 5-HT(1B) gene might contribute to inter-individual
variability in clinical responses to triptans. Two polymorphisms in the promoter 
region of the 5-HT(1B) receptor (T-261G and A-161T) and the synonymous variation 
G861C in the coding region were genotyped by restriction fragment length
polymorphism in 105 migraine patients. In our sample population, 71% of patients 
responded to triptans. Allelic and diplotype frequencies were not significantly
different between responders and non-responders. On the other hand, extrapolation
of in vitro data on promoter activity would suggest that patients with higher
copy number of receptors respond slightly better. Our data therefore do not
support the involvement of 5-HT(1B) single nucleotide polymorphisms in mediating 
the inter-individual variability to triptans.

Publication Types: 
    Clinical Trial
    Research Support, Non-U.S. Gov't

PMID: 18035351 [PubMed - indexed for MEDLINE]

469: Cephalalgia. 2007 Dec;27(12):1442-53.

The brain is hyperexcitable in migraine.

Aurora SK, Wilkinson F.

Centre for Vision Research, York University, Toronto, Canada.
sheena.aurora@swedish.org

Migraine is a very common disorder occurring in 20% of women and 6% of men.
Central neuronal hyperexcitability is proposed to be the putative basis for the
physiological disturbances in migraine. Since there are no consistent structural 
disturbances in migraine, physiological and psychophysical studies have provided 
insight into the underlying mechanisms. This is a review of the
neurophysiological studies which have provided an insight to migraine
pathogenesis supporting the theory of hyperexcitability.

Publication Types: 
    Review

PMID: 18034688 [PubMed - indexed for MEDLINE]

470: Cephalalgia. 2007 Dec;27(12):1427-39.

Is the cerebral cortex hyperexcitable or hyperresponsive in migraine?

Coppola G, Pierelli F, Schoenen J.

G.B. Bietti Eye Foundation-IRCCS, Department of Neurophysiology of Vision and
Neurophthalmology, Rome, Italy.

Although migraineurs appear in general to be hypersensitive to external stimuli, 
they maybe also have increased daytime sleepiness and complain of fatigue.
Neurophysiological studies between attacks have shown that for a number of
different sensory modalities the migrainous brain is characterised by a lack of
habituation of evoked responses. Whether this is due to increased cortical
hyperexcitability, possibly due to decreased inhibition, or to an abnormal
responsivity of the cortex due a decreased preactivation level remains disputed. 
Studies using transcranial magnetic stimulation in particular have yielded
contradictory results. We will review here the available data on cortical
excitability obtained with different methodological approaches in patients over
the migraine cycle. We will show that these data congruently indicate that the
sensory cortices of migraineurs react excessively to repetitive, but not to
single, stimuli and that the controversy above hyper- versus hypo-excitability is
merely a semantic misunderstanding. Describing the migrainous brain as
'hyperresponsive' would fit most of the available data. Deciphering the precise
cellular and molecular underpinnings of this hyperresponsivity remains a
challenge for future research. We propose, as a working hypothesis, that a
thalamo-cortical dysrhythmia might be the culprit.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 18034686 [PubMed - indexed for MEDLINE]

471: Women Health. 2007;46(1):115-33.

The experience of chronic illness in women: a comparison between women with
endometriosis and women with chronic migraine headaches.

Barnack JL, Chrisler JC.

Department of Psychology, Connecticut College, USA. Jbarnack@uwm.edu

The diagnosis of a chronic illness is a life changing event that affects the
biological, psychological, and sociological aspects of a person's life. The
purpose of the present study was to compare the experiences of pain, physical and
psychological well-being, stress, patient satisfaction, social support, and
attitudes toward menstruation of women who suffer from endometriosis and women
who suffer from chronic migraine headaches. It was hypothesized that women with
endometriosis would have more negative scores than women who have migraines on
all measures because endometriosis is not understood by society to be a valid
source of pain. Participants were 41 women with endometriosis and 32 women with
migraines who were recruited from support groups and online listservs. Women with
endometriosis reported significantly more pain, stress, and negative attitudes
toward menstruation than did women with migraines. Implications for the
differential treatment of women with chronic illnesses related to the menstrual
cycle are discussed.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 18032178 [PubMed - indexed for MEDLINE]

472: Acta Neurol Scand. 2008 Jun;117(6):377-83. Epub 2007 Nov 20.

Migraine without aura: comparison with cervicogenic headache. Vågå study of
headache epidemiology.

Sjaastad O, Bakketeig LS.

Department of Neurology, St Olavs Hospital, Trondheim University Hospitals
(NTNU), Trondheim, Norway. eylert.brodtkorb@ntnu.no

OBJECTIVES: To study migraine without aura (MwoA) prevalence in the commune of
Vågå, Norway; 1838 (18- to 65-year-old) individuals were included. A special
search was made for cervicogenic characteristics in MwoA, as it has been claimed 
that such characteristics may frequently be present. A comparison with
cervicogenic headache (CEH) was made. METHODS: The MwoA and tension-type headache
(T-TH) diagnosis was based on IHS criteria. CEH diagnosis was based on the
principles of The Cervicogenic Headache International Study Group. RESULTS: There
were 562 cases of MwoA; prevalence: 31%. There were 425 cases of 'pure' MwoA,
i.e. without coexisting T-TH. These 'pure' cases were used for extracting MwoA
symptoms. The female/male ratio was 1.69, the corresponding ratio in CEH being
0.71. Typical MwoA symptoms such as nausea/photophobia were most frequently found
in migraine. This difference amounted to a factor of > or =2.6. On the other
hand, typical CEH traits, like mechanical pain provocation and 'posterior' onset 
of exacerbations, occurred more frequently in CEH than in MwoA. The difference
amounted to a factor of two or more. CONCLUSIONS: MwoA and CEH have clearly
different characteristics. The differences between MwoA and CEH are staggering.
It is unlikely that migraine and CEH are linked in a nosological sense.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 18031560 [PubMed - indexed for MEDLINE]

473: Clin Genet. 2008 Jan;73(1):37-43. Epub 2007 Nov 19.

Two novel functional mutations in the Na+,K+-ATPase alpha2-subunit ATP1A2 gene in
patients with familial hemiplegic migraine and associated neurological
phenotypes.

Castro MJ, Nunes B, de Vries B, Lemos C, Vanmolkot KR, van den Heuvel JJ, Temudo 
T, Barros J, Sequeiros J, Frants RR, Koenderink JB, Pereira-Monteiro JM, van den 
Maagdenberg AM.

Instituto de Ciências Biomédicas Abel Salazar, and UnIGENe, Instituto Biologia
Molecular Celular, Universidade do Porto, Porto, Portugal.

Mutations in the ATP1A2 gene, encoding the alpha2-subunit of the Na+,K+-ATPase,
are associated with familial hemiplegic migraine type 2. The majority of ATP1A2
mutations were reported in patients with hemiplegic migraine without any
additional neurological findings. Here, we report on two novel ATP1A2 mutations
that were identified in two Portuguese probands with hemiplegic migraine and
interesting additional clinical features. The proband's of family 1 (with a V362E
mutation) had mood alterations, classified as a borderline personality. The
proband in family 2 (with a P796S mutation) had mild mental impairment, in
addition to hemiplegic migraine; more severe mental retardation was observed in
his brother, who also had hemiplegic migraine and carried the same mutation.
Cell-survival assays clearly showed abnormal functioning of mutant Na+,K+-ATPase,
indicating that both ATP1A2 mutants are disease causing. Additionally, our
results suggest a possible causal relationship of the ATP1A2 mutations with the
complex clinical phenotypes observed in the probands.

Publication Types: 
    Case Reports
    Research Support, Non-U.S. Gov't

PMID: 18028456 [PubMed - indexed for MEDLINE]

474: Epilepsia. 2008 Mar;49(3):500-8. Epub 2007 Nov 19.

Epilepsy as part of the phenotype associated with ATP1A2 mutations.

Deprez L, Weckhuysen S, Peeters K, Deconinck T, Claeys KG, Claes LR, Suls A, Van 
Dyck T, Palmini A, Matthijs G, Van Paesschen W, De Jonghe P.

Neurogenetics Group, Department of Molecular Genetics, VIB; Antwerpen, Belgium.

PURPOSE: Mutations in the ATP1A2 gene have been described in families with
familial hemiplegic migraine (FHM). FHM is a variant of migraine with aura
characterized by the occurrence of hemiplegia during the aura. Within several FHM
families, some patients also had epileptic seizures. In this study we tested the 
hypothesis that mutations in ATP1A2 may be common in patients presenting with
epilepsy and migraine. METHODS: We selected 20 families with epilepsy and
migraine and performed mutation analysis of ATP1A2 in the probands by direct
sequencing of all exons and splice-site junctions. RESULTS: Novel ATP1A2
mutations were found in two of the 20 families (10%). The p.Gly900Arg mutation
was present in a family with epilepsy and FHM, and the p.Cys702Tyr mutation
occurred in a family with occipitotemporal epilepsy and migraine with and without
visual aura. In the two families together, six mutation carriers had the
combination of epilepsy and migraine, two had only epilepsy, and six had only
migraine. DISCUSSION: This study shows that a history of migraine and a family
history of both epilepsy and migraine should be obtained in all patients
presenting with epilepsy in the epilepsy clinic. It may be worthwhile to screen
patients with a combination of epilepsy and migraine and a positive family
history of either migraine or epilepsy for mutations in the ATP1A2 gene.

Publication Types: 
    Case Reports
    Research Support, Non-U.S. Gov't

PMID: 18028407 [PubMed - indexed for MEDLINE]

475: Headache. 2008 Mar;48(3):385-94. Epub 2007 Nov 20.

Results of screening with the brief headache screen compared with a modified
IDMigraine.

Maizels M, Houle T.

Kaiser Permanente-Department of Family Medicine, Woodland Hills, CA 91365-4084,
USA.

BACKGROUND: Patients with chronic migraine and chronic daily headache syndromes
have greater morbidity than patients with episodic migraine, and are less
frequently diagnosed. A screening tool which identifies daily headache syndromes 
as well as migraine would promote more patients receiving appropriate treatment, 
including prophylaxis. METHODS: A post-hoc analysis of data obtained to evaluate 
the prevalence of somatic symptoms in primary care patients was conducted on a
convenience sample of primary care patients who completed the Patient Health
Questionnaire portion of the PRIME-MD (Primary Care Evaluation of Mental
Disorders). Patients who endorsed the symptom of headache were asked to complete 
the Brief Headache Screen (BHS), a 4-item screening tool, supplemented by 3
clinical questions (nausea, light sensitivity, and noise sensitivity). The data
obtained allowed a post-hoc comparison of the BHS with a modified version of the 
screening tool, IDMigraine(TM) (IDM(TM)). Diagnostic interviews were performed on
patients whose diagnoses differed by the 2 screening methods, and on patients who
screened positive for daily headache on BHS. RESULTS: Of the 1000 patients who
completed the PRIME-MD, 302 (30.2%) indicated headache as a concern, and there
were sufficient data for both the BHS and IDM(TM) for 259. There was substantial 
concordance between the 2 instruments with 82.6% agreement in identified migraine
(95% confidence interval: 77.8%-87.4%). The BHS screened positive for migraine in
an additional 15.1% of patients who were not identified by IDM(TM), whereas the
IDM(TM) identified an additional 2.3% of patients. Of the 173 which both tools
recognized as migraine, the BHS identified 42.8% as having a daily headache
syndrome (chronic migraine: 23.1%; episodic migraine + chronic tension-type
headache [CTTH]: 19.7%). BHS also identified 7 non-migraine patients as having
CTTH alone. Diagnostic interviews confirmed that 6/18 (33%) of BHS+ but IDM-, and
one of 2 (50%) patients BHS-/IDM+ met full criteria for migraine. Additionally,
interviews confirmed the diagnoses of 85.4% of those patients who the BHS
identified with daily headache and 67% of those who were identified as medication
overuse headache. CONCLUSION: The BHS and a modified IDM(TM) are concordant in
screening for migraine in 82.6% of a primary care population who endorsed the
symptom of headache. However, the BHS screens effectively not only for migraine
but also for chronic daily headache and medication overuse. A screening paradigm 
based on headache frequency and the frequency of medication use can rapidly and
sensitively identify migraine, daily headache syndromes, and medication overuse. 
This paradigm may improve clinical care by identifying patients who merit
preventive as well as acute therapy for migraine.

Publication Types: 
    Comparative Study

PMID: 18028378 [PubMed - indexed for MEDLINE]

476: Curr Opin Pediatr. 2007 Dec;19(6):663-9.

Headaches.

Hershey AD, Winner P, Kabbouche MA, Powers SW.

Division of Neurology, Cincinnati Children's Hospital Medical Center and
Department of Pediatrics, College of Medicine, University of Cincinnati,
Cincinnati, Ohio 45229-3039, USA. Andrew.hershey@chmcc.org

PURPOSE OF REVIEW: Headaches and migraine occur frequently in children and
adolescents and may have a significant impact on the child's and parents' lives. 
Recent advances in diagnosis, epidemiology, and treatment have improved the
outcomes of children with headaches. This review summarizes some of these
findings. RECENT FINDINGS: Recent studies have revealed the increasing incidence 
of migraine and chronic migraine in the pediatric and adolescent age groups.
These studies have also begun to identify comorbidities that may affect the
impact over a lifetime. Limitations of the diagnosis of migraine have restricted 
some of these findings, but modifications to the criteria may assist with early
recognition. Proper evaluation and treatment, including acute, preventive, and
biobehavioral therapies, may need to be incorporated for optimal outcomes.
Long-term outcomes may be determined by the underlying pathophysiology as well as
early effective management. SUMMARY: Migraine in children is increasingly being
recognized as a problem. Early, effective treatment is available and may result
in long-term benefit and prevent disease progression. Further research into
childhood headaches should help reveal additional pathophysiological mechanisms
and treatment options.

Publication Types: 
    Review

PMID: 18025933 [PubMed - indexed for MEDLINE]

477: Neurology. 2007 Nov 20;69(21):1990-5.

Thickening in the somatosensory cortex of patients with migraine.

DaSilva AF, Granziera C, Snyder J, Hadjikhani N.

Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard
Medical School, Bldg. 36, First St., Room 417, Charlestown, MA 02129, USA.

OBJECTIVE: To examine morphologic changes in the somatosensory cortex (SSC) of
patients with migraine. METHODS: Cortical thickness of the SSC of patients with
migraine was measured in vivo and compared with age- and sex-matched healthy
subjects. The cohort was composed of 24 patients with migraine, subdivided into
12 patients who had migraine with aura, 12 patients who had migraine without
aura, and 12 controls. Group and individual analyses were performed in the SSC
and shown as average maps of significant changes in cortical thickness. RESULTS: 
Migraineurs had on average thicker SSCs than the control group. The most
significant thickness changes were noticed in the caudal SSC, where the
trigeminal area, including head and face, is somatotopically represented.
CONCLUSIONS: Our findings indicate the presence of interictal structural changes 
in the somatosensory cortex (SSC) of migraineurs. The SSC plays a crucial role in
the noxious and nonnoxious somatosensory processing. Thickening in the SSC is in 
line with diffusional abnormalities observed in the subcortical trigeminal
somatosensory pathway of the same migraine cohort in a previous study. Repetitive
migraine attacks may lead to, or be the result of, neuroplastic changes in
cortical and subcortical structures of the trigeminal somatosensory system.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 18025393 [PubMed - indexed for MEDLINE]

478: Pract Neurol. 2007 Nov;7(6):383-93.

Migraine prevention.

Dodick DW, Silberstein SD.

Department of Neurology, Mayo Clinic Arizona, Scottsdale, Arizona 85259, USA.
Dodick.David@mayo.edu

Preventive medications reduce migraine frequency and severity, and improve
migraine-specific quality of life. Recent evidence also suggests that these same 
medications enhance the patient's response to acute migraine therapies, and may
also reduce the likelihood of developing chronic daily headache. However, many
patients who should receive or be offered preventive treatment are not. Most
patients can be successfully managed when patient and physician expectations are 
realistic and aligned, the selection of preventive medications is individualised,
and the initiation and titration strategy is appropriate and carefully followed. 
Rational combinations of preventive medications may also be useful. This review
provides an evidence and experience-based approach to the preventive treatment of
migraine.

Publication Types: 
    Case Reports
    Review

PMID: 18024778 [PubMed - indexed for MEDLINE]

479: Pediatr Neurol. 2007 Dec;37(6):407-10.

Novel mutation confirms seizure locus SCN1A is also familial hemiplegic migraine 
locus FHM3.

Gargus JJ, Tournay A.

Department of Physiology and Biophysics, School of Medicine, University of
California Irvine, Irvine, CA 92697-4034, USA. jjgargus@uci.edu

Although SCN1A, the gene encoding the neuronal voltage-gated sodium channel, type
1A, is a well-recognized target of mutations underlying a spectrum of epilepsy
syndromes, and lies within an extended 12-Mb disease-associated haplotype at the 
familial hemiplegic migraine-3 locus, it remains to be confirmed that mutations
within this gene itself cause syndromes that include migraine phenotypes. The
novel T1174S missense mutation of this gene was detected segregating in a family 
with a heterozygous female child who presented with myoclonus and an abnormal
electroencephalogram, and in her heterozygous mother, who had an ataxic migraine 
syndrome similar to that of her own mother. This three-generation family exhibits
the broad phenotypic spectrum of the dominant neuronal hyperexcitability
syndromes produced by even a given allele of this sodium channel gene. It also
exhibits the second allele of this sodium channel gene associated with a migraine
syndrome similar to those caused at the two other familial hemiplegic migraine
loci, confirming that this gene itself, not some linked gene, is the familial
hemiplegic migraine-3 locus.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 18021921 [PubMed - indexed for MEDLINE]

480: Cephalalgia. 2008 Jan;28(1):87-91. Epub 2007 Nov 16.

Migrainous corpalgia: body pain and allodynia associated with migraine attacks.

Cuadrado ML, Young WB, Fernández-de-las-Peñas C, Arias JA, Pareja JA.

Department of Neurology, Fundación Hospital Alcorcón and Rey Juan Carlos
University, Alcorcón, Madrid, Spain. luz.cuadrado@urjc.es

Cephalic and extracephalic allodynia are recognized as a common sign of sensory
sensitization during migraine episodes. However, the occurrence of body pain in
migraine has not been thoroughly explored. Here we report three patients
presenting with spontaneous body pain in association with migraine attacks. A
41-year-old woman experienced face and limb pain along with migraine headaches;
it started before, during or after headache, was usually ipsilateral to head
pain, and could last from minutes to days. A 39-year-old woman had pain in her
right limbs, back and neck for 30-60 min prior to right-sided migraine headaches.
A 30-year-old woman perceived pain in her left upper limb for 24-48 h prior to
left-sided migraine headaches. All patients had allodynia to mechanical stimuli
over the painful areas. Spontaneous body pain may be associated with migraine
attacks. Together with allodynia, this might be a consequence of central
sensitization.

Publication Types: 
    Case Reports
    Comparative Study

PMID: 18021265 [PubMed - indexed for MEDLINE]

481: Mo Med. 2007 Sep-Oct;104(5):448-9.

Migraine induced strokes.

Khosla T, Ahmed I.

University of Missouri, Kansas City School of Medicine, USA.

Migraine can be a primary cause of stoke and has been the subject of recent
literature. This paper reviews the findings of these studies.

Publication Types: 
    Review

PMID: 18018535 [PubMed - indexed for MEDLINE]

482: J Child Neurol. 2007 Nov;22(11):1288-92.

Current therapies in childhood and adolescent migraine.

Pakalnis A.

Department of Pediatrics and Neurology, Ohio State University College of Medicine
and Columbus Children's Hospital, Columbus, Ohio, USA.
PakalnisA@pediatrics.ohio-state.edu

This review summarizes recent guidelines for diagnosis of migraine in children
and adolescents and inherent issues regarding their headaches that influence
evaluation of therapies. With the shorter duration of pediatric migraine attacks 
and the prominent placebo responder rate, design of randomized clinical trials
becomes more problematic than in the adult population. Regarding abortive
therapies, several agents have appreciable efficacy in randomized controlled
trials. Ibuprofen, acetaminophen, and sumatriptan nasal spray are probably
beneficial and safe to use in pediatric migraine. For the minority of children
who should be candidates for prophylactic therapy, there is a limited amount of
information available for clinicians to make judicious treatment decisions.

Publication Types: 
    Review

PMID: 18006958 [PubMed - indexed for MEDLINE]

483: Ann Emerg Med. 2008 Oct;52(4):399-406. Epub 2007 Nov 19.

A randomized controlled trial of prochlorperazine versus metoclopramide for
treatment of acute migraine.

Friedman BW, Esses D, Solorzano C, Dua N, Greenwald P, Radulescu R, Chang E,
Hochberg M, Campbell C, Aghera A, Valentin T, Paternoster J, Bijur P, Lipton RB, 
Gallagher EJ.

Department of Emergency Medicine, Albert Einstein College of Medicine, Bronx, NY 
10467, USA. befriedm@montefiore.org

STUDY OBJECTIVE: We compare prochlorperazine 10 mg intravenously versus
metoclopramide 20 mg intravenously for the emergency department (ED) treatment of
acute migraine. METHODS: This was a randomized, double-blind, clinical trial
comparing 2 parenteral dopamine antagonists. Both drugs were administered during 
15 minutes with 25 mg intravenous diphenhydramine. Pain scores on a numeric
rating scale were assessed at baseline, every 30 minutes for 2 hours, and by
telephone 24 hours after discharge. The primary endpoint was the between-group
difference in change in numeric rating scale from baseline to 1 hour
postbaseline. Secondary endpoints included mean differences in change in numeric 
rating scale at 2 and 24 hours, headache relief, adverse effects, and desire to
receive the same treatment for future migraines. RESULTS: Of 152 patients
screened, 97 were eligible and 77 were randomized. The mean change in numeric
rating scale scores at 1 hour was 5.5 and 5.2 in subjects receiving
prochlorperazine and metoclopramide, respectively (difference=0.3; 95% confidence
interval [CI] -1.0 to 1.6). Findings were similar at 2 hours and 24 hours.
Forty-six percent (18/39) of prochlorperazine and 32% (12/38) of metoclopramide
subjects reported adverse events (difference=15%; 95% CI -6% to 36%).
Seventy-seven percent (26/34) of prochlorperazine and 73% (27/37) of
metoclopramide subjects wanted to receive the same medication in future ED visits
(difference=4%; 95% CI -16% to 24%). CONCLUSION: Either prochlorperazine 10 mg
intravenously or metoclopramide 20 mg intravenously, combined with
diphenhydramine 25 mg intravenously, is an efficacious treatment for ED patients 
with acute migraine. Three quarters of subjects in both arms would want the same 
medication for their next migraine.

Publication Types: 
    Multicenter Study
    Randomized Controlled Trial
    Research Support, N.I.H., Extramural

PMID: 18006188 [PubMed - indexed for MEDLINE]

484: Headache. 2008 Feb;48(2):226-35. Epub 2007 Nov 13.

Efficacy of rizatriptan for menstrual migraine in an early intervention model: a 
prospective subgroup analysis of the rizatriptan TAME (Treat A Migraine Early)
studies.

Martin V, Cady R, Mauskop A, Seidman LS, Rodgers A, Hustad CM, Ramsey KE,
Skobieranda F.

University of Cincinnati, Cincinnati, OH 45267-0535, USA.

OBJECTIVE: A prospective subgroup analysis of the TAME (Treat A Migraine Early)
studies examined the efficacy of rizatriptan in patients treating a menstrual
migraine attack. METHODS: Both TAME studies were randomized, placebo-controlled, 
and double-blind. Adults with migraine were assigned (2:1) to either rizatriptan 
10-mg tablet or placebo. Patients were instructed to treat within 1 hour of
migraine onset and when the pain was mild. The primary endpoint was 2-hour pain
freedom. The diagnosis of menstrual migraine was established according to the
revised 2004 International Headache Society (IHS) diagnostic criteria. Data from 
both studies were pooled for logistic regression analyses. A test for interaction
was performed to compare rates of 2-hour pain freedom between patients treating a
menstrual and non-menstrual attack. RESULTS: A total of 94 patients (63 in the
rizatriptan group and 31 in the placebo group) met IHS criteria for menstrual
migraine and treated a menstrual attack. The percentage of patients reporting
2-hour pain freedom was significantly greater for rizatriptan than for placebo
(63.5% vs 29.0%; odds ratio = 4.5; 95% confidence interval: 1.7, 11.9; P = .002) 
in those treating a menstrual attack. In those treating with rizatriptan, the
percentage of patients with 2-hour pain freedom did not statistically differ
between those treating a menstrual or non-menstrual migraine attack (63.5% vs
57.5%; P = .454). CONCLUSION: Rizatriptan 10 mg was effective for the treatment
of menstrual migraine in an early intervention model, as measured by 2-hour pain 
freedom. Rates of 2-hour pain freedom were comparable for patients treating
menstrual and non-menstrual migraine attacks with rizatriptan.

Publication Types: 
    Clinical Trial
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 18005144 [PubMed - indexed for MEDLINE]

485: Headache. 2008 Jun;48(6):914-20. Epub 2007 Nov 13.

Does early migraine treatment shorten time to headache peak and reduce its
severity?

Hu XH, Ng-Mak D, Cady R.

Global Outcomes Research, Global Human Health, Merck & Co., Inc., Whitehouse
Station, NJ, USA.

OBJECTIVE: To explore whether early treatment would shorten the duration of
headache from headache onset to its peak and reduce headache severity at peak.
BACKGROUND: Prior clinical studies almost exclusively focused on headache relief 
after dosing. No data are available on whether early intervention affects the
duration from headache onset to peak and headache severity at peak. METHODS:
Adult migraineurs were enrolled in this observational study from multi-site
headache clinics. Patients recorded their migraine experiences via an electronic 
diary over 1 month. Patients reported the time and pain severity at onset,
dosing, and peak. We used a linear mixed model to evaluate the impact of the
timing of treatment and to adjust for covariates and correlation of observations 
within subjects. RESULTS: A total of 182 patients reported 970 migraine episodes,
620 of which were treated before headaches progressed to peak. Mean time from
headache onset to peak varied from 1.9 hours to 8.9 hours for patients treated
within 15 minutes of onset and those who waited for 4 or more hours,
respectively. However, early intervention was not associated with reduced
headache severity at peak. In multivariate analysis, early treatment, use of
triptans, and mild migraine headache in the past 3 months were significantly
associated with shorter time from onset to headache peak. A separate model
indicated that the timing of medication was not associated with the duration
between dosing and headache peak, but use of triptans shortened the time from
dosing to headache peak. CONCLUSIONS: Early treatment and use of triptans may
lead to shorter duration from migraine headache onset to its peak but did not
alleviate headache severity at peak. This could result in decreased migraine
burden by reducing total migraine headache duration.

Publication Types: 
    Clinical Trial
    Multicenter Study

PMID: 18005142 [PubMed - indexed for MEDLINE]

486: Headache. 2008 Jan;48(1):135-9. Epub 2007 Nov 13.

Increased plasma matrix metalloproteinase-9 levels in migraineurs.

Imamura K, Takeshima T, Fusayasu E, Nakashima K.

Department of Neurology, Institute of Neurological Sciences, Faculty of Medicine,
Tottori University, Yonago, Japan.

BACKGROUND AND OBJECTIVE: Cortical spreading depression and neurogenic
inflammation have been hypothesized to be key steps in the development of
migraine headache. Recent studies have highlighted matrix metalloproteinase-9
(MMP-9) in cortical spreading depression, neurogenic inflammation, and cerebral
ischemia. To seek their possible association, we investigated plasma MMP-9 levels
in migraineurs during headache-free periods. METHODS: Plasma MMP-9 levels in 84
migraine subjects and 61 controls were determined by enzyme-linked immunosorbent 
assay. In addition, 23 patients with tension type headache were included in the
study as comparative subjects. RESULTS: The MMP-9 levels in migraineurs
(42.5+/-4.6 ng/mL, mean+/-SE) were significantly higher than those in controls
(25.4+/-2.7 ng/mL, P< .005). Those levels in tension type headache subjects
(24.6+/-4.8 ng/mL) did not differ from those in controls. There was no
significant difference between subjects having migraine with aura and those
without aura. The MMP-9 levels did not correlate with age, duration of illness,
frequency of migraine attack, duration of headache attack, or medication for
headache. Mean plasma MMP-9 levels were the highest in subjects from whom blood
samples were taken 2-4 days after their latest attack. CONCLUSIONS: The
degradation of extracellular matrix showing the increase of MMP-9 in migraineurs 
may be associated with an abnormality in their blood vessel permeability. MPP-9
plays some role in migraine pathophysiology. Further studies of MMPs are
necessary to elucidate their role.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 18005141 [PubMed - indexed for MEDLINE]

487: Headache. 2008 Jun;48(6):883-9. Epub 2007 Nov 14.

The prevalence and impact of migraine on US Military officer trainees.

Helseth EK, Erickson JC.

Madigan Army Medical Center, Tacoma, WA, USA.

OBJECTIVE: To determine the prevalence and impact of migraine in US Army officer 
trainees. BACKGROUND: The prevalence of migraine in military officer trainees,
frequency of diagnosis, pharmacologic management, and the impact of migraine on
military training has not been previously determined. We sought to elucidate the 
above and also to identify trainee characteristics associated with impaired
training performance because of the disabling effects of migraine. METHODS: An
anonymous voluntary migraine questionnaire was administered to 1389 consecutive
US Army Reserve Officer Training Corps cadets upon completion of 5 weeks of
military training. Headaches were classified as definite migraine or possible
migraine. Migraine frequency, prior diagnosis, number of missed or suboptimal
training days attributable to migraine, patterns of analgesic use, and trainee
characteristics associated with impaired training performance were identified.
RESULTS: In total, 741 of 1389 (54%) officer trainees completed the migraine
questionnaire, including 582 males and 159 females. The prevalence of definite
migraine was 18% in all cadets including 14% in males and 31% in females.
Migraines had been previously diagnosed in only 10% of trainees meeting criteria 
for definite or possible migraine. During training, male trainees experienced a
mean of 0.70 migraines/month compared with female trainees at 1.4
migraines/month. Only 3% of trainees meeting criteria for definite or possible
migriane had ever been prescribed triptans. Eight percent of cadets experienced
impaired training performance because of migraine resulting in 63 days of
suboptimal or missed training. Characteristics associated with impaired training 
performance included a prior diagnosis of migraine, screening positive for
definite migraine vs possible migraine, and a higher baseline frequency of
migraine. CONCLUSIONS: Migraine is common yet underdiagnosed and undertreated in 
US Army officer trainees and adversely impacts military training. We identified
characteristics which place military trainees at risk for impaired training
performance. We predict that improved diagnosis and treatment of migraine would
result in improved training performance.

PMID: 18005047 [PubMed - indexed for MEDLINE]

488: Eur J Clin Pharmacol. 2008 Jan;64(1):1-8. Epub 2007 Nov 15.

Endocannabinoids in platelets of chronic migraine patients and medication-overuse
headache patients: relation with serotonin levels.

Rossi C, Pini LA, Cupini ML, Calabresi P, Sarchielli P.

Neurologic Clinic, Department of Medical and Surgical Specialties and Public
Health, University of Perugia, Perugia, Italy.

BACKGROUND: Chronic migraine (CM) and medication-overuse headaches (MOH) are
well-recognized disabling conditions affecting a significant portion of the
headache population attending centers specialized in treating headaches. A
dysfunctioning of the serotonergic system has been demonstrated in MOH and CM
patients. Here we report on our assessment of the dysfunctioning of the
endocannabinoid system as a potential underlying factor in pathogenic mechanisms 
involved in CM and MOH. METHOD: To test the hypothesis of an impairment in the
endocannabinoid system in patients with MOH and CM and to assess its relationship
with any disruption of the serotonergic system, we determined the levels of the
two main endogenous cannabinoids, anandamide (AEA) and 2-acylglycerol (2-AG), in 
platelets of 20 CM patients, 20 MOH patients and 20 control subjects and also
measured the platelet serotonin levels in the same patients. RESULTS: We found
that 2-AG and AEA levels were significantly lower in MOH patients and CM patients
than in the control subjects, without significant differences between the two
patient groups. Serotonin levels were also strongly reduced in the two patient
groups and were correlated with 2-AG levels, with higher values for MOH patients.
CONCLUSION: These data support the potential involvement of a dysfunctioning of
the endocannabinoid and serotonergic systems in the pathology of CM and MOH.
These systems appear to be mutually related and able to contribute to the
chronification of both CM and MOH.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 18004553 [PubMed - indexed for MEDLINE]

489: Conf Proc IEEE Eng Med Biol Soc. 2007;2007:1834-7.

Migraine detection through spontaneous EEG analysis.

Bellotti R, De Carlo F, de Tommaso M, Lucente M.

Dipartimento di Fisica, Università di Bari, Italy.

Spontaneous EEG patterns are studied to detect migraine patients both during the 
attack and in headache-free periods. The EEG signals are analyzed through the
wavelets and both scale-dependent and scale-independent features are computed to 
characterize the patterns. The classification is carried out by a supervised
neural network. The efficiency of the method is evaluated through the Receiver
Operating Characteristic (ROC) analysis and the Wilcoxon-Mann-Whitney (WMW) test.
Although a high discrimination is observed with one single neural output, a
complete separation among MwA patients and healthy subjects is obtained when a
scatter plot is drawn in the plane of two suitable neural outputs.

PMID: 18002337 [PubMed - indexed for MEDLINE]

490: Expert Opin Pharmacother. 2007 Dec;8(17):3029-33.

Frovatriptan review.

Markus F, Mikko K.

University Hospital Helsinki, Department of Neurology, Haartmaninkatu 4, 00290
Helsinki, Finland.

Frovatriptan belongs to the triptan compounds used for the acute treatment of
migraine. Its affinity for the migraine-specific serotonin 5HT1B-receptors is
highest in the class. Its long half-life in plasma (26 h) and metabolism by
multiple pathways are unique characteristics among the triptans. These features
can translate into long duration of action and low risk of interactions with
other drugs. Frovatriptan has been effective and well tolerated over a wide range
of doses in randomised, double-blind, placebo-controlled acute migraine trials
and long-term, open-label trials. The 2.5-mg dose is recommended for both
efficacy and a favourable side effect profile for acute migraine treatment.
Frovatriptan has the lowest headache recurrence rate of all the triptans.
Frovatriptan was better tolerated than sumatriptan in a head-to-head comparison
study. Frovatriptan could make its mark especially in slowly progressing migraine
attacks and in attacks that are highly predictable. For example, for the
short-term prophylaxis of menstrual migraine, frovatriptan is the triptan of
first choice.

Publication Types: 
    Review

PMID: 18001261 [PubMed - indexed for MEDLINE]

491: J Womens Health (Larchmt). 2007 Nov;16(9):1269-80.

The impact of migraine on the health and well-being of women.

Diamond M.

Diamond Headache Clinic, Chicago, Illinois 60614, USA. drmerle@aol.com

Migraine is a painful condition that predominantly affects women. Aside from the 
headache pain, migraine sufferers can experience symptoms of depression, anxiety,
fatigue, and increased levels of stress, anger, and apprehension both during and 
between attacks (the cycle of migraine). Moreover, migraine is associated with
the impairment of social, family, and work-related activities. Unfortunately,
clinicians tend to focus treatment on the frequency and severity of migraine and 
often fail to address the overall functional impairment associated with this
disorder. The goal of this review is to highlight the cycle of migraine and
discuss its impact on the health and well-being of women. The frequency and
severity of migraines, including interictal symptoms, should be considered when
deciding on the most appropriate migraine therapy. Attention should also be given
to the potential association between migraine and the physiological and hormonal 
changes that occur during menarche, pregnancy, or perimenopause. Healthcare
providers should ask specific questions and be encouraged to expand dialogue with
patients to reveal the full impact that migraine has on the daily activities of
women both during and between attacks. This can help improve treatment strategies
for the patient, with the goal of substantially improving symptoms, interictal
distress, and the performance of their daily activities.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 18001183 [PubMed - indexed for MEDLINE]

492: Cephalalgia. 2008 Jan;28(1):72-7. Epub 2007 Nov 12.

Migrainous vertigo: clinical, oculographic and posturographic findings.

Celebisoy N, Gökçay F, Sirin H, Biçak N.

Ege University Medical School, Department of Neurology, Bornova, Izmir, Turkey.
nese.celebisoy@ege.edu.tr

Migrainous vertigo (MV) is accepted as a common cause of episodic vertigo. The
peripheral or central vestibular localization of the deficit as well as the
pathophysiology is unclear. This prospective study was designed to assess the
clinical features of MV and to search for the localization of the vestibular
pathology. Thirty-five patients with MV, 20 patients with migraine and 20 healthy
volunteers were studied. Comprehensive neurotological tests were performed
between attacks. None of the normal controls or the patients with migraine had
ocular motor deficits or caloric test abnormalities. Three patients in the MV
group showed saccadic pursuit (8.6%), in one of whom saccadic hypometria was also
present. Caloric test results revealed unilateral caloric hypofunction in seven
patients (20%). Static posturography results revealed increased sway velocity
when the eyes were closed or the platform was distorted in patients with MV.
These findings during the symptom-free period revealed that peripheral vestibular
dysfunction was more common than a central deficit.

Publication Types: 
    Comparative Study

PMID: 17999681 [PubMed - indexed for MEDLINE]

493: Curr Med Res Opin. 2007 Dec;23(12):3177-87.

Aerosol delivery of ergotamine tartrate via a breath-synchronized plume-control
inhaler in humans.

Armer TA, Shrewsbury SB, Newman SP, Pitcairn G, Ramadan N.

MAP Pharmaceuticals, Mountain View, CA 94043, USA.

OBJECTIVE: To compare systemic delivery of ergotamine tartrate (ET) via a
breath-synchronized, plume-control inhaler (BSPCI) (Tempo ET) with a sublingual
ergot preparation and a commercial inhaler. METHODS: Study 1 determined plasma ET
concentrations in seven healthy subjects after administration of ET by a 2 mg
tablet (Lingraine) and a BSPCI delivering 258 microg of ET. Study 2 determined
plasma ET concentrations in 16 healthy subjects after administration via an ET
metered dose inhaler (ME) (Medihaler) delivering 2052 microg of ET and a BSPCI
delivering 129 microg of ET. Gamma scintigraphy with (99m)Tc validation was used 
to quantify lung deposition. RESULTS: For both studies, ET C(max) was higher with
the BSPCI (study 1: sublingual ET 134 pg/mL at 37 min; BSPCI 3743 pg/mL at 3 min;
study 2: metered-dose inhaler 1109 pg/mL at 4 min; BSPCI 1210 pg/mL at 2.5 min). 
Mean dose normalized AUC was several-fold higher with the BSPCI compared with
sublingual ET and ME dosing. Lung deposition of ET with the BSPCI was 33.5, 8.9, 
11.4, and 13.2% for whole, central, intermediate, and peripheral lung,
respectively, with a 1.5 peripheral : central ratio. CONCLUSION: Based on these
open-label studies, the BSPCI allows rapid delivery of potentially therapeutic
plasma concentrations of ET at approximately 1/15th the dose of comparators.

Publication Types: 
    Comparative Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 17991308 [PubMed - indexed for MEDLINE]

494: Lancet Neurol. 2007 Dec;6(12):1054-62. Epub 2007 Nov 7.

Erratum in:
    Lancet Neurol. 2008 Jan;7(1):25.

Comment in:
    Lancet Neurol. 2007 Dec;6(12):1035-6.    Nat Clin Pract Neurol. 2008 Jun;4(6):294-5.

Cessation versus continuation of 6-month migraine preventive therapy with
topiramate (PROMPT): a randomised, double-blind, placebo-controlled trial.

Diener HC, Agosti R, Allais G, Bergmans P, Bussone G, Davies B, Ertas M,
Lanteri-Minet M, Reuter U, Del Río MS, Schoenen J, Schwalen S, van Oene J;
TOPMAT-MIG-303 Investigators Group.

Department of Neurology, Universität Duisburg-Essen, Germany.
hans.diener@uni-duisburg-essen.de

BACKGROUND: Use of preventive therapy for migraine is often recommended for only 
6-9 months, but no randomised, placebo-controlled trials have investigated
migraine frequency after the end of prophylaxis. We assessed the effects of
discontinuation of topiramate after a treatment period of 6 months. METHODS: 818 
patients who have migraines were enrolled from 88 clinics in 21 countries. After 
a 4-8-week lead-in period, patients received topiramate in a 26-week open-label
phase. Daily dose was increased from 25 mg to 100 mg in steps of 25 mg every
week; the dose could be adjusted further in the range 50-200 mg/day, but was
stable for the final 4 weeks. Patients were randomly assigned to continue this
dose or switch to placebo for a 26-week double-blind phase. The primary endpoint 
was the difference in number of days with migraine during the last 4 weeks of the
double-blind phase compared with the last 4 weeks of the open-label phase.
Analysis was by intention to treat. This trial is registered with EudraCT, number
2005-000321-29. FINDINGS: 559 patients (68.3%) completed the open-label phase;
514 entered the double-blind phase and were assigned to topiramate (n=255) or
placebo (n=259). The mean increase in number of migraine days was greater in the 
placebo group (1.19 days in 4 weeks, 95% CI 0.71 to 1.66; p<0.0001) than in the
topiramate group (0.10, -0.36 to 0.56; p=0.5756; mean difference between groups
-1.09, -1.75 to -0.43; p=0.0011) [corrected] Patients in the placebo group had a 
greater number of days on acute medication than did those in the topiramate group
(mean difference between groups -0.95, -1.49 to -0.41; p=0.0007). Quality of
life, as assessed by the MIDAS questionnaire, fell in the placebo group but
remained stable in the topiramate group. Patients were more satisfied with the
efficacy of topiramate than with that of placebo, whereas satisfaction with
tolerability was similar in both treatment groups. INTERPRETATION: Sustained
benefit was reported after discontinuation of topiramate, although number of
migraine days did increase. These findings suggest that patients should be
treated for 6 months, with the option to continue to 12 months in some patients.

Publication Types: 
    Clinical Trial
    Comparative Study
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 17988947 [PubMed - indexed for MEDLINE]

495: J Neurol. 2007 Dec;254(12):1629-35. Epub 2007 Nov 7.

Molecular mechanisms of migraine?

Ramagopalan SV, Ramscar NE, Cader MZ.

Dept. of Clinical Neurology, University of Oxford, Oxford, UK.
sreeramr@well.ox.ac.uk

Migraine is a common debilitating neurological disease characterised by attacks
of severe headache with or without preceding aura. Its aetiology remains elusive;
however it is clear that an interplay of genetic and environmental components
play an important role. Familial hemiplegic migraine (FHM) is a rare and severe
variant of migraine with aura and follows an autosomal dominant pattern of
inheritance. This disease is genetically heterogeneous,with three causative genes
having been identified.This review uses insights garnered from FHM to try and
shed light on possible migraine disease pathogenesis.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 17987250 [PubMed - indexed for MEDLINE]

496: Cephalalgia. 2008 Jan;28(1):1-4. Epub 2007 Nov 6.

Subtle grey matter changes between migraine patients and healthy controls.

Schmidt-Wilcke T, Gänssbauer S, Neuner T, Bogdahn U, May A.

Department of Neurology, University of Regensburg, Regensburg, Germany.

Local morphological alterations of the brain have recently been detected in
cluster headache and chronic tension-type headache, but not in migraine. We
investigated 35 patients suffering from migraine and compared them with 31
healthy controls with no headache history. Using magnetic resonance imaging and
voxel based morphometry, we found a significant decrease of grey matter in areas 
ascribable to the transmission of pain (cingulate cortex), but not in areas
specific for migraine, such as the brainstem. Our data are in line with recent
findings in chronic pain states, such as chronic phantom pain and chronic back
pain. We suggest that the grey matter change in migraine patients is the
consequence of frequent nociceptive input and should thus be reversible when
migraine attacks cease.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 17986275 [PubMed - indexed for MEDLINE]

497: Cephalalgia. 2008 Jan;28(1):57-64. Epub 2007 Nov 6.

Migraine incidence, comorbidity and health resource utilization in the UK.

Becker C, Brobert GP, Almqvist PM, Johansson S, Jick SS, Meier CR.

Basel Pharmacoepidemiology Unit, Division of Clinical Pharmacology and
Toxicology, University Hospital Basel, Switzerland.

Population-based data on migraine incidence and comorbidity are scarce. We
therefore aimed to quantify incidence rates and comorbidity of diagnosed migraine
and health resource utilization (HRU) in migraineurs in the UK primary care
setting. We conducted a follow-up study with a nested case-control analysis on
the General Practice Research Database. The study encompassed 51,688 patients
with a first-time diagnosis of migraine between 1994 and 2001, and the same
number of matched controls. The migraine incidence rate was 3.69 (95% confidence 
interval 3.66, 3.73) cases per 1000 person-years. It was around 2.5 times higher 
in women. Most chronic diseases were slightly more prevalent in migraineurs than 
in controls. Triptan users had higher health resource utilization than other
migraineurs. This study shows that migraine is a common diagnosis in general
practice and associated with a high prevalence of comorbidity. The increased HRU 
in triptan users suggests greater migraine severity.

Publication Types: 
    Comparative Study

PMID: 17986274 [PubMed - indexed for MEDLINE]

498: Cephalalgia. 2008 Jan;28(1):65-71. Epub 2007 Nov 6.

Comment in:
    Nat Clin Pract Neurol. 2008 May;4(5):246-7.

Can ID Migraine be used as a screening test for adolescent migraine?

Zarifoğlu M, Karli N, Taşkapilioğlu O.

Uludag University, School of Medicine, Department of Neurology, Bursa, Turkey.
mzarif@uludag.edu.tr

Although the ID Migraine has been developed and used for adults, it can also be
used in adolescents. We aimed to investigate the validity of the ID Migraine in
the adolescent student population. The study was performed on 1064 adolescents
aged 12-17 years. A face-to-face semistructured interview was conducted with
students after they had answered a 17-item questionnaire on sociodemographics and
headache. Students who had had two or more headache attacks during the last 3
months then answered the ID Migraine. The sensitivity and specificity of the ID
Migraine were 62.1% and 71.1%, respectively. The sensitivity was higher for
patients with migraine with aura (71.1%), for girls (71.3%) and for younger
adolescents (69.1%). The specificity was higher for boys (77.9%) and for older
adolescents (73.3%). The kappa value was 0.316 (P < 0.001). Although the kappa
value of the ID Migraine is low, the test may be a useful tool in screening
adolescent migraine after some changes are made.

Publication Types: 
    Comparative Study
    Validation Studies

PMID: 17986273 [PubMed - indexed for MEDLINE]

499: Cephalalgia. 2007 Dec;27(12):1360-7. Epub 2007 Nov 6.

Interictal abnormalities of gamma band activity in visual evoked responses in
migraine: an indication of thalamocortical dysrhythmia?

Coppola G, Ambrosini A, Di Clemente L, Magis D, Fumal A, Gérard P, Pierelli F,
Schoenen J.

G.B. Bietti Eye Foundation-IRCCS, Department of Neurophysiology of Vision and
Neurophthalmology, Rome, Italy. gianluca.coppola@gmail.com

Between attacks, migraineurs lack habituation in standard visual evoked
potentials (VEPs). Visual stimuli also evoke high-frequency oscillations in the
gamma band range (GBOs, 20-35 Hz) assumed to be generated both at subcortical
(early GBOs) and cortical levels (late GBOs). The consecutive peaks of GBOs were 
analysed regarding amplitude and habituation in six successive blocks of 100
averaged pattern reversal (PR)-VEPs in healthy volunteers and interictally in
migraine with (MA) or without aura patients. Amplitude of the two early GBO
components in the first PR-VEP block was significantly increased in MA patients. 
There was a significant habituation deficit of the late GBO peaks in migraineurs.
The increased amplitude of early GBOs could be related to the increased
interictal visual discomfort reported by patients. We hypothesize that the
hypofunctioning serotonergic pathways may cause, in line with the thalamocortical
dysrhythmia theory, a functional disconnection of the thalamus leading to
decreased intracortical lateral inhibition, which can induce dishabituation.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17986271 [PubMed - indexed for MEDLINE]

500: Cephalalgia. 2008 Jan;28(1):49-56. Epub 2007 Nov 6.

Migraine and biomarkers of cardiovascular disease in women.

Kurth T, Ridker PM, Buring JE.

Division of Preventive Medicine, Department of Medicine, Brigham and Women's
Hospital, Harvard Medical School, Boston, MA 02215-1204, USA.
tkurth@rics.bwh.harvard.edu

Migraine has been associated with an unfavourable cardiovascular risk profile and
with increased risk of cardiovascular disease. In a cross-sectional analysis of
27,626 women aged >or=45 years, we evaluated the association of migraine and
migraine aura status with elevated levels of total cholesterol, low- and
high-density lipoprotein cholesterol (HDL-C), non-HDL-C, apolipoprotein (Apo) A-1
and B(100), lipoprotein (a), C-reactive protein (CRP), fibrinogen, intercellular 
adhesion molecule-1, homocysteine and creatinine. A total of 5087 (18.4%) women
reported any history of migraine. Compared with women with no migraine history,
women who reported any history of migraine had modestly increased adjusted odds
ratios (95% confidence interval) of 1.09 (1.01, 1.18) for elevated total
cholesterol, 1.14 (1.05, 1.23) for non-HDL-C, 1.09 (1.01, 1.18) for Apo B(100)
and 1.13 (1.05, 1.22) for CRP. The increase did not meaningfully differ according
to migraine aura status and migraine frequency. In this large cohort of women,
only a modest association was found between migraine and adverse levels of
certain cardiovascular biomarkers.

Publication Types: 
    Comparative Study

PMID: 17986270 [PubMed - indexed for MEDLINE]

501: Pain Pract. 2007 Dec;7(4):313-23. Epub 2007 Nov 6.

The burden of headache in neurology outpatient clinics in Turkey.

Baykan B, Ertas M, Karli N, Akat-Aktas S, Uzunkaya O, Zarifoglu M, Siva A, Saip
S; MIRA-Neurology Study Group.

Istanbul University, Istanbul Medical School, Department of Neurology, Istanbul, 
Turkey. baykanb@istanbul.edu.tr

BACKGROUND AND AIM: The aim of the study was to investigate the burden of
headache in neurology outpatient clinics (NOCs) regardless of their primary
complaint. METHODS: Patients presenting for their routine appointments in 41 NOCs
were screened during the course of 1 week. All eligible subjects (n = 3682; 61.9%
female, mean age 45.2 +/- 16.5 years) were evaluated by a neurologist for the
headache diagnosis and some demographic characteristics. RESULTS: Of all
patients, 66.4% reported headache, and in 35.1% headache was the primary cause
for admitting to the NOC. Of 3682 patients, 917 (24.9%) were diagnosed as
migraine according to International Headache Society (IHS) criteria. Thirty-three
and nine-tenths percent of all patients admitted and 56% of the migraineurs
according to IHS had severe headaches. As the headache severity increases, the
ratio of the patients admitted with headache as the primary complaint increases
significantly. The distribution of burden and other characteristics of headache
did not differ in seven geographic regions and 41 different centers. CONCLUSION: 
Headache complaint caused at least 1/3 of all neurological outpatient visits in
Turkey and 2/3 of all patients admitted to NOC had headache. Of these patients,
1/4 had migraine according to IHS with substantial disability and severity level.

Publication Types: 
    Multicenter Study
    Research Support, Non-U.S. Gov't

PMID: 17986162 [PubMed - indexed for MEDLINE]

502: Tohoku J Exp Med. 2007 Nov;213(3):277-82.

Headache characteristics in senior medical students in Turkey.

Bicakci S, Over F, Aslan K, Bozdemir N, Saatci E, Sarica Y.

Department of Neurology, School of Medicine, Cukurova University, Adana, Turkey. 
sebnemb@cu.edu.tr

Headache is one of the most common neurological complaints of the young
population and it affects the quality of life due to limitation of daily
activities. In this study, our main goal was to appraise the general headache
characteristics in senior medical students just before graduation and to
determine the impact of headache on the quality of life, as well as the general
attitude of students about their headaches. The study group consisted of 141
senior students. As the first step, the question about "having headache within
the past one year period" was asked. Of the 141 students, 127 students answering 
"yes" were invited to a face-to-face interview. Of these, 67 students (52.8%)
participated in the second evaluation. The second evaluation consisted of history
taking and neurological and physical examination. All subjects were classified
according to the International Classification of Headache Disorders (2nd edition)
criteria. Validated Turkish version of Migraine Disability Assessment
questionnaire was given to the subjects to evaluate the socio-economical impact
of headache. Tension-type headache, which is the most common form of primary
headaches, was identified in 34 students (50.7%) out of 67 students. Migraine was
detected in 31 students (46.3%). This is the first study performed on a
face-to-face interview basis with medical students using the new classification
criteria in Turkey. Astonishingly, most of the students (n:65) ignored their
headaches and did not seek medication, despite the negative impact of headache on
daily functioning and overall quality of life.

PMID: 17984625 [PubMed - indexed for MEDLINE]

503: Nat Clin Pract Neurol. 2007 Nov;3(11):610-9.

Emerging therapies for migraine.

Goadsby PJ.

Institute of Neurology, The National Hospital for Neurology and Neurosurgery,
Queen Square, London WC1N 3BG, UK. peterg@ion.ucl.ac.uk

Migraine is a common disabling brain disorder that--considering its clinical and 
economic impact--is understudied and in need of additional management options.
Currently, treatments are classified as preventive or acute-attack therapies,
although it is expected that this distinction will become blurred over time. The 
gap-junction blocker tonabersat, an inducible nitric oxide synthase (NOS)
inhibitor and botulinum toxin A are all being investigated in clinical trials as 
preventive therapies. Device-based approaches using neurostimulation of the
occipital nerve have provided promising results, whereas the first study of
patent foramen ovale closure for migraine prevention produced disappointing
results. Calcitonin gene-related peptide receptor antagonists, vanilloid TRPV1
receptor antagonists and NOS inhibitors are all being investigated in clinical
trials for acute migraine. There is much cause for optimism in this area of
neurology and considerable benefit awaits our patients.

Publication Types: 
    Review

PMID: 17982431 [PubMed - indexed for MEDLINE]

504: J Pain. 2008 Jan;9(1):88-94. Epub 2007 Nov 5.

Metoclopramide versus hydromorphone for the emergency department treatment of
migraine headache.

Griffith JD, Mycyk MB, Kyriacou DN.

Department of Emergency Medicine, Northwestern University Feinberg School of
Medicine, Chicago, Illinois 60611, USA.

We conducted a retrospective cohort study to compare the effects of
metoclopramide versus hydromorphone for the initial emergency department
treatment of migraine headache at an urban teaching hospital. The primary outcome
measure was the mean difference in the subjects' self-reported pain scores before
and after the administration of the initial medication treatment. We also
estimated crude and adjusted relative risks (using Poisson multivariate
regression modeling) to assess and control potential confounding by age, gender, 
race, and pain score before initial medication. Two hundred subjects were
included, with 51 (25.5%) receiving intravenous or intramuscular hydromorphone,
95 (47.5%) receiving intravenous metoclopramide, and 54 (27.0%) receiving 1 of
several other medications. Using a standardized pain scale of 0 to 10, mean pain 
score reductions were 2.3 points for hydromorphone, 3.7 points for
metoclopramide, and 2.8 points for all other medications combined (P < .001).
When comparing metoclopramide versus hydromorphone, the crude relative risk for
pain reduction of 3 or more points was 1.76 (95% CI, 1.12-2.75, P = .01), and the
adjusted relative risk was 1.60 (95% CI, 0.84-3.03, P = .15). Metoclopramide also
resulted in less use of rescue medications, faster times to discharge, and no
difference in the frequency of adverse reactions. PERSPECTIVE: Metoclopramide
appears to be an effective initial medical treatment for migraine headaches in
the emergency department setting, but its pharmacologic mechanism remains
incompletely understood. A double-blinded, randomized, controlled trial comparing
standard dosages of hydromorphone versus metoclopramide will be needed to
definitively determine which medication is more effective.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 17981511 [PubMed - indexed for MEDLINE]

505: J Reprod Med. 2007 Oct;52(10):888-95.

Menstrually related migraine: breaking the cycle in your clinical practice.

Silberstein SD, Goldberg J.

Department of Neurology, Jefferson Headache Center, Division of General
Obstetrics and Gynecology and Jefferson Fibroid Center, Jefferson Medical
College, Philadelphia, Pennsylvania, USA. stephen.silberstein@jefferson.edu

The purpose of this review is to provide a simple, evidence-based approach to the
diagnosis and treatment of migraine. The review is based on clinical experience
data, results from placebo-controlled trials and pharmacokinetic information of
clinical importance and is a distillation of material from a comprehensive
literature review of the epidemiology, pathophysiology, diagnostic features and
treatment of menstrual migraine. Migraine, particularly menstrual migraine, is
most prevalent in women of childbearing age. Menstrual migraine is generally
severe, lasts longer, recurs more frequently, results in greater disability and
is more resistant to therapy than nonmenstrual migraine. Despite the associated
disability for otherwise-healthy women, migraine is frequently not diagnosed. The
initial visit to an obstetrician/gynecologist is an ideal time to screen women
for menstrual migraine. Triptans are effective in the acute treatment of
menstrual migraine. Naratriptan and frovatriptan also have been evaluated for
prophylactic efficacy. Both agents were effective in reducing the incidence of
menstrual migraine. Frovatriptan also reduced the severity and duration of
breakthrough headaches. Acute treatment is typically the same for menstrual and
nonmenstrual migraine, involving the use of nonsteroidal antiinflammatory agents 
(NSAIDs), triptans or, rarely, ergot derivatives. In addition, NSAIDs, magnesium 
supplementation, estrogen therapy and triptans have been proven effective for
short-term prevention of menstrual migraine. In some patients, continuous
estrogen therapy may be necessary to control these headaches. Improved diagnosis 
and treatment of menstrual migraine is critical to decrease the associated
disability. Acute and shortterm preventive therapy with triptans is effective;
oral contraceptives may be used for long-term preventive therapy.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 17977161 [PubMed - indexed for MEDLINE]

506: Cephalalgia. 2007 Nov;27(11):1308-14.

Dopamine and migraine: biology and clinical implications.

Akerman S, Goadsby PJ.

Department of Neurology, University of California, San Francisco, San Francisco, 
CA 94143, USA. simon.akerman@ucsf.edu

In the last 30 years dopamine has been considered as playing a role in the
pathogenesis of migraine. The literature indicates that migraineurs are
hypersensitive to dopamine agonists with respect to some of the premonitory
symptoms of migraine such as nausea and yawning. There are various non-specific
dopamine D(2) receptor antagonists that show good clinical efficacy in migraine, 
and also a number of polymorphisms of dopaminergic genes related to migraine.
Animal studies have also shown that dopamine receptors are present in the
trigeminovascular system, the area believed to be involved in headache pain, and 
neuronal firing here is reduced by dopamine agonists. There appears to be little 
effect of dopamine on peripheral trigeminal afferents. We assess some of the
limitations of the clinical studies with regard to the therapeutics, and those
found in the studies that discovered differences in genetic polymorphisms in
migraine, and consider the implications of this on a dopaminergic hypothesis of
migraine.

Publication Types: 
    Review

PMID: 17970991 [PubMed - indexed for MEDLINE]

507: Cephalalgia. 2007 Nov;27(11):1293-300.

Serotonin and migraine: biology and clinical implications.

Hamel E.

Montreal Neurological Institute, Department of Neurology and Neurosurgery, McGill
University, 3801 University Street, Montréal, Québec, Canada, H3A 2B4.
edit.hamel@mcgill.ca

Migraine is the most frequent neurological disorder in the adult population
worldwide, affecting up to 12% of the general population and more frequent in
women ( approximately 25%). It has a high impact on our society due to its
disabling nature and, therein, reduced quality of life and increased absenteeism 
from work. Headache is the primary clinical manifestation and it has been
associated with 'a hereditary or predisposed sensitivity of neurovascular
reactions to certain stimuli or to cyclic changes in the central nervous system' 
(1). Amongst the many neurotransmitters in the brain, the serotonergic
(serotonin, 5-HT) system from the brainstem raphe nucleus has been most
convincingly implicated in migraine pathophysiology. The documented changes in
5-HT metabolism and in the processing of central 5-HT-mediated responses during
and in between migraine attacks have led to the suggestion that migraine is a
consequence of a central neurochemical imbalance that involves a low serotonergic
disposition. Although the exact cascade of events that link abnormal serotonergic
neurotransmission to the manifestation of head pain and the accompanying symptoms
has yet to be fully understood, recent evidence suggests that a low 5-HT state
facilitates activation of the trigeminovascular nociceptive pathway, as induced
by cortical spreading depression. In this short review, we present and discuss
the original and most recent findings that support a role for altered
serotonergic neurotransmission in the manifestation of migraine headache.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 17970989 [PubMed - indexed for MEDLINE]

508: Cephalalgia. 2007 Dec;27(12):1339-59. Epub 2007 Oct 29.

Evaluation and proposal for optimization of neurophysiological tests in migraine:
part 2--neuroimaging and the nitroglycerin test.

Magis D, Bendtsen L, Goadsby PJ, May A, Sánchez del Rio M, Sandór PS, Kaube H,
Sandrini G, Schoonman GG, Schoenen J; EUROHEAD Project.

Headache Research Unit, Department of Neurology, University of Liège, Liège,
Belgium.

Neuroimaging methods have been widely used in headache and migraine research.
They have provided invaluable information on brain perfusion, metabolism and
structure during and outside of migraine attacks, contributing to an improved
understanding of the pathophysiology of the disorder. Human models of migraine
attacks are indispensable tools in pathophysiological and therapeutic research.
This review of neuroimaging methods and the attack-provoking nitroglycerin test
is part an initiative by a task force within the EUROHEAD project (EU Strep
LSHM-CT-2004-5044837-Workpackage 9) with the objective of critically evaluating
neurophysiological tests used in migraine. The first part, presented in a
companion paper, is devoted to electrophysiological methods, this second part to 
neuroimaging methods such as functional magnetic resonance imaging, positron
emission tomography and voxel-based morphometry, as well as the nitroglycerin
test. For each of these methods, we summarize the results, analyse the
methodological limitations and propose recommendations for improved methodology
and standardization of research protocols.

Publication Types: 
    Evaluation Studies
    Research Support, Non-U.S. Gov't
    Review

PMID: 17970767 [PubMed - indexed for MEDLINE]

509: Cephalalgia. 2007 Dec;27(12):1323-38. Epub 2007 Oct 29.

Evaluation and proposal for optimalization of neurophysiological tests in
migraine: part 1--electrophysiological tests.

Magis D, Ambrosini A, Bendtsen L, Ertas M, Kaube H, Schoenen J; EUROHEAD Project.

Headache Research Unit, Department of Neurology, University of Liège, Liège,
Belgium.

Neurophysiological testing has become a valuable tool for investigating brain
excitability and nociceptive systems in headache disorders. Previous reviews have
suggested that most neurophysiological tests have limited value for headache
diagnosis, but a vast potential for exploring the pathophysiology of headaches,
the central effects of certain pharmacological treatments and phenotype-genotype 
correlations. Many protocols, however, lack standardization. This meta-analytical
review of neurophysiological methods in migraine was initiated by a task force
within the EUROHEAD project (EU Strep LSHM-CT-2004-5044837-Workpackage 9). Most
of the neurophysiological approaches that have been used in headache patients are
reviewed, i.e. evoked potentials, nociception-specific blink reflex, single-fibre
electromyography, neuroimaging methods (functional MRI, PET, and voxel-based
morphometry) and the nitroglycerin attack-provoking test. For each of them, we
summarize the results, analyse the methodological limitations and propose
recommendations for improved methodology and standardization of research
protocols. The first part is devoted to electrophysiological methods, the second 
to neuroimaging techniques and the NTG test.

Publication Types: 
    Comparative Study
    Evaluation Studies
    Research Support, Non-U.S. Gov't
    Review

PMID: 17970766 [PubMed - indexed for MEDLINE]

510: Cephalalgia. 2008 Jan;28(1):83-6. Epub 2007 Oct 29.

Crossed cerebellar diaschisis during migraine with prolonged aura: a possible
mechanism for cerebellar infarctions.

Dodick DW, Roarke MC.

Department of Neurology, Mayo Clinic, Scottsdale, AZ, USA. dodick.david@mayo.edu

Migraineurs with frequent aura (>or=1 per month) are at a 12-fold increased risk 
of posterior circulation infarctions. Although the mechanism is unclear, these
lesions are located in the arterial borderzone of the cerebellum. This case
illustrates, for the first time, crossed cerebellar diaschisis in a patient with 
migraine with prolonged aura, and raises the possibility that hypoperfusion may
be responsible in part for the development of these lesions.

Publication Types: 
    Case Reports

PMID: 17970765 [PubMed - indexed for MEDLINE]

511: Curr Med Res Opin. 2007 Dec;23(12):3033-9.

Predictive model for the Migraine-ACT questionnaire in primary care.

Pascual J, Láinez MJ, Baos V, García ML, López-Gil A.

Neurology Service, Hospital Universitario de Salamanca, Spain.

BACKGROUND: Migraine is frequently under-treated. The 4-item Migraine Assessment 
of Current Therapy (Migraine-ACT) questionnaire is a simple, patient-friendly
tool to identify patients requiring change in acute migraine treatment.
OBJECTIVE: To establish a predictive model for the Migraine-ACT questionnaire in 
primary care. RESEARCH DESIGN AND METHODS: This open-label, prospective,
two-visit study at 1100 primary care sites enrolled patients reporting migraine
for > 1 year and > or = 1 migraine attack/month. Predictive validity of the
Migraine-ACT questionnaire was evaluated using a logistic regression model
adjusted for baseline disability, diagnosis, sex, age, attack frequency, attack
duration, baseline treatment change, treatment(s) for the study period and
baseline Migraine-ACT score. RESULTS: A total of 3272 patients, 78% female,
entered the study and 2877 patients (88%) returned at 3 months. Investigators
changed baseline migraine treatment for 72% of returning patients. Percentages of
patients who were completely or very satisfied with migraine therapy increased
from 15% at baseline to 49% at 3 months. The adjusted logistics regression model 
yielded sensitivity of 86% and specificity of 85% to detect > or = 1-point change
in Migraine-ACT score at 3 months (p < 0.001). The model yielded 77% sensitivity 
and 95% specificity to detect > or = 1-point improvement in patient satisfaction 
at 3 months among patients who improved > or = 1 point in the Migraine-ACT score 
(adjusted odds ratio, 2.63; 95% confidence interval, 1.97-3.51; p < 0.001).
CONCLUSIONS: The Migraine-ACT questionnaire is a simple but sensitive and
specific tool to predict improvements at 3 months resulting from changes in
migraine treatment and can be used to detect patients with suboptimal migraine
management and to monitor treatment effectiveness.

Publication Types: 
    Evaluation Studies
    Research Support, Non-U.S. Gov't

PMID: 17967220 [PubMed - indexed for MEDLINE]

512: Trends Pharmacol Sci. 2007 Nov;28(11):580-7. Epub 2007 Oct 25.

CGRP antagonists: unravelling the role of CGRP in migraine.

Doods H, Arndt K, Rudolf K, Just S.

Boehringer Ingelheim Pharma GmbH & Co. KG, 88397 Biberach, Germany.
henri.doods@boehringer-ingelheim.com

Migraine is a complex, debilitating neurovascular disorder. Although knowledge on
the main molecular players is still incomplete, recent preclinical and clinical
findings indicate that there is a clear correlation between migraine-associated
headache and the release of the neuropeptide calcitonin gene-related peptide
(CGRP). BIBN4096 was the first CGRP antagonist to be tested in clinical trials
for the treatment of migraine. The proven efficacy of this agent, and also the
CGRP antagonist MK-0974, to alleviate acute migraine headache provided
significant support for the hypothesis that CGRP has an important role in
migraine pathophysiology. Moreover, the recently published results from Phase II 
trials are encouraging and suggest that this new type of drug might offer
advantages over existing therapies for patients suffering from migraine and
related headaches.

Publication Types: 
    Review

PMID: 17963849 [PubMed - indexed for MEDLINE]

513: Stroke. 2007 Dec;38(12):3145-51. Epub 2007 Oct 25.

Comment in:
    Stroke. 2007 Dec;38(12):3117-8.

Migraine mediates the influence of C677T MTHFR genotypes on ischemic stroke risk 
with a stroke-subtype effect.

Pezzini A, Grassi M, Del Zotto E, Giossi A, Monastero R, Dalla Volta G, Archetti 
S, Zavarise P, Camarda C, Gasparotti R, Magoni M, Camarda R, Padovani A.

Dipartimento di Scienze Mediche e Chirurgiche, Stroke Unit, Neurologia Vascolare,
Spedali Civili di Brescia, P. le Spedali Civili, 1, 25100 Brescia, Italia.
ale_pezzini@hotmail.com

BACKGROUND AND PURPOSE: The objective was to investigate the role of C677T MTHFR 
polymorphism in migraine pathogenesis and in the migraine-ischemic stroke
pathway. METHODS: A first genotype-migraine association study was conducted on
100 patients with migraine with aura (MA), 106 with migraine without aura (MO),
and 105 subjects without migraine, which provided evidence in favor of
association of the TT677 MTHFR genotype with increased risk of MA compared with
both control subjects (OR, 2.48; 95% CI, 1.11 to 5.58) and patients with MO (OR, 
2.21; 95% CI, 1.01 to 4.82). Based on these findings, mediational models of the
genotype-migraine-stroke pathway were fitted on a group of 106 patients with
spontaneous cervical artery dissection, 227 young patients whose ischemic stroke 
was unrelated to a spontaneous cervical artery dissection (noncervical artery
dissection), and 187 control subjects, and a genotype-migraine partial mediation 
model was selected. RESULTS: Both migraine and the TT genotype were more strongly
associated to the subgroup of patients with spontaneous cervical artery
dissection (OR, 4.06; 95% CI, 1.63 to 10.02 for MA; OR, 5.45; 95% CI, 3.03 to
9.79 for MO; OR, 2.87; 95% CI, 1.45 to 5.68 for TT genotype) than to the subgroup
of patients with noncervical artery dissection ischemic stroke (OR, 2.22; 95% CI,
1.00 to 4.96 for MA; OR, 1.81; 95% CI, 1.02 to 3.22 for TT genotype) as compared 
with controls. CONCLUSIONS: Migraine may act as mediator in the
methylenetetrahydrofolate reductase-ischemic stroke pathway with a more prominent
effect in the subgroup of patients with spontaneous artery dissection.

PMID: 17962595 [PubMed - indexed for MEDLINE]

514: Postgrad Med. 2006 Apr;Spec No:27-31.

Use of combination therapy in migraine: a review of the clinical evidence.

Taylor F, Smith T.

The previous article in this supplement sets forth a compelling argument for use 
of multimechanism combination pharmacotherapy as a strategy to improve outcomes
for patients with migraine. This article picks up where the previous one left off
by providing a concise review of data regarding use of combined agents to treat
migraine. Included in this review are clinical studies of both over-the-counter
(OTC) and prescription agents whose performance in combination has been assessed 
in comparison to placebo and/or monotherapy. Also, this review is not limited to 
fixed drug combinations; studies that used different single-agent tablets
administered together are also included.

Publication Types: 
    Review

PMID: 17960688 [PubMed - indexed for MEDLINE]

515: Postgrad Med. 2006 Apr;Spec No:20-6.

Combination therapy in acute migraine treatment: the rationale behind the current
treatment options.

Silberstein SD, Ruoff G.

Combination therapy is used to treat many disorders; for some conditions, it has 
become first-line treatment or the standard of care. The development and use of
novel drug combinations will grow as the understanding of disease pathophysiology
and drug pharmacokinetics and pharmacodynamics progresses. In the acute
management of migraine, existing drug combinations have proven to be effective,
safe, and tolerable. They may offer distinct advantages compared with
monotherapy, including both enhanced therapeutic benefits and fewer adverse
events (AEs). This article discusses the types of interactions that can occur
with combination therapy and their potential effects on efficacy and
tolerability. The rationale for using combination therapy will first be discussed
within the context of clinical conditions in which it is already the standard of 
care. This will be followed by a discussion of the rationale for use in migraine.

Publication Types: 
    Review

PMID: 17960687 [PubMed - indexed for MEDLINE]

516: Postgrad Med. 2006 Apr;Spec No:5-13.

An update on migraine pathophysiology and mechanism-based pharmacotherapeutics
for migraine.

Cady R, Biondi DM.

The pathophysiologic mechanisms of migraine are complex but appear to primarily
involve the trigeminovascular system. Within this system, a number of factors may
contribute to the generation and perpetuation of pathophysiologic changes leading
to migraine. Current migraine medications exert their therapeutic benefit via
actions at various points relating to these pathophysiologic changes. However, no
single agent currently exists that targets all the hypothesized anatomical and
cellular mechanisms of the migraine process. A future strategy for achieving
optimal therapeutic effect and improving clinical outcomes in migraine involves
rational targeting of the multiple mechanisms involved in its pathophysiology;
conceptually, this may require concomitant use of multiple pharmacotherapeutic
agents.

Publication Types: 
    Review

PMID: 17960686 [PubMed - indexed for MEDLINE]

517: Postgrad Med. 2006 Apr;Spec No:14-9.

Migraine headaches: treatment limitations and opportunities.

Kaniecki RG, Hutchinson S.

In recent years, migraine treatment options have expanded to the extent that the 
practicing clinician now has a myriad of pharmacologic agents in varied drug
classes and delivery systems from which to choose. Drug classes most commonly
employed for treatment of migraine attacks include non-migraine-specific agents, 
such as nonsteroidal anti-inflammatory drugs (NSAIDs), opioids, barbiturates,
combination analgesics, and antiemetics, and migraine-specific agents, such as
triptans and ergot alkaloids and derivatives. Delivery options range from
conventional, orally disintegrating, and rapid-release tablets to injection,
nasal spray, and suppository. The US Headache Consortium offers guidelines
classifying migraine treatments into different groups based on evidence of
clinical benefit (Table 1). Clinicians must be aware of the advantages and
limitations of each class and delivery system and possible opportunities to
improve their usefulness in different clinical contexts.

Publication Types: 
    Review

PMID: 17957856 [PubMed - indexed for MEDLINE]

518: Brain. 2007 Dec;130(Pt 12):3102-10. Epub 2007 Oct 22.

Association between cortical metabolite levels and clinical manifestations of
migrainous aura: an MR-spectroscopy study.

Schulz UG, Blamire AM, Corkill RG, Davies P, Styles P, Rothwell PM.

Stroke Prevention Research Unit, University Department of Clinical Neurology,
Radcliffe Infirmary, Woodstock Road, Oxford OX2 6HE, UK.
ursula.schulz@doctors.net.uk

Previous studies suggest an abnormal cerebral cortical energy metabolism in
migraineurs. If causally related to the pathophysiology of migraine, these
abnormalities might show a dose-response relationship with the duration and
severity of aura symptoms. While such a trend has been suggested in phosphorus
spectroscopy (31P-MRS) studies, it has not been considered in proton spectroscopy
(1H-MRS) studies and it has not been studied in cerebral white matter. We aimed
to determine whether for any of the metabolites measured by 31P-MRS or 1H-MRS
there was a dose-response relationship with aura duration and severity, and
whether such an association was also present in cerebral white matter. We studied
patients with migraine with aura and healthy controls with 31P-MRS and with
1H-MRS. We measured metabolite ratios in grey and in white matter and in the
patients, we related metabolite levels to the clinical characteristics and
duration of the aura. In patients, the phosphocreatine/phosphate (PCr/Pi) ratio
decreased significantly with increasing aura duration and was significantly lower
in patients with hemiplegic migraine than in patients with non-motor aura.
Overall the metabolite ratios did not differ significantly between patients and
controls, but compared with controls the PCr/Pi ratio in patients with hemiplegic
migraine and in patients with persistent aura >7 days was significantly lower.
These changes were only present in grey matter. Results for 1H-MRS did not differ
significantly between patients and controls, and they showed no association with 
duration or severity of symptoms. In this study, metabolite ratios differed
significantly between patients with different aura phenotypes and with increasing
aura duration. In addition, only in some patient subgroups were metabolite ratios
significantly different from controls. These findings support the concept that
migraine with aura is a heterogeneous disorder with distinct pathophysiological
subtypes. They further suggest that rather than determining the susceptibility to
developing a migraine attack, changes in cortical energy metabolism may determine
the clinical manifestations of the migrainous aura once an attack has started.

Publication Types: 
    Multicenter Study
    Research Support, Non-U.S. Gov't

PMID: 17956910 [PubMed - indexed for MEDLINE]

519: Cephalalgia. 2008 Jan;28(1):18-25. Epub 2007 Oct 23.

Work stress and new-onset migraine in a female employee population.

Mäki K, Vahtera J, Virtanen M, Elovainio M, Keltikangas-Järvinen L, Kivimäki M.

Department of Psychology, University of Helsinki, Helsinki, Finland.
m.kivimaki@ucl.ac.uk

This prospective cohort study examined whether work stress, as indicated by the
job strain model and the effort-reward imbalance model, predicts new-onset
migraine among 19,469 female employees with no history of migraine at study
entry. A baseline survey between 2000 and 2002 assessed work stress and
demographic factors. Self-reported newly diagnosed migraine was measured at
follow-up between 2004 and 2005 and 1281 new cases of migraine were detected. In 
logistic regression analysis adjusted for age, socioeconomic position and
depression at baseline, no association between job strain and migraine was found.
In contrast, high effort-reward imbalance was associated with slightly increased 
risk of migraine at follow-up, odds ratio 1.23 (95% confidence interval 1.04,
1.45). The proportion of new migraine cases attributable to high effort-reward
imbalance was 6.2%. If the observed association is causal, our findings suggest
that high effort-reward imbalance might function as a modifiable risk factor for 
new-onset migraine.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 17956575 [PubMed - indexed for MEDLINE]

520: Expert Opin Pharmacother. 2007 Nov;8(16):2811-23.

Topiramate for migraine prophylaxis.

Fontebasso M.

York Hospital, Headache Clinic, Department of Neuroscience, Wigginton Road, York,
UK. manuela.fontebasso@york.nhs.uk

Topiramate is one of several antiepileptic drugs that are used in the prevention 
of migraine, but the only one licensed for use in the UK. Topiramate has an
extensive evidence base provided by double-blind, placebo-controlled trials to
show that it is a safe, effective and well tolerated drug in the management of
migraine. It has also been shown to have a role in the management of chronic
migraine, which represents a challenge to primary care clinicians as well as
headache specialists. Studies have demonstrated that topiramate can also be
effective in preventing migraine in childhood and adolescence, although this is
unlicensed in the UK. It has been shown in models both in the US and the UK to
offer a cost benefit when direct and indirect costs are evaluated by reducing
work loss, improving quality of life and reducing the use of increasingly scarce 
health resources.

Publication Types: 
    Review

PMID: 17956201 [PubMed - indexed for MEDLINE]

521: Headache. 2007 Sep;47 Suppl 2:S86-94.

Understanding the causes and prevention of menstrual migraine: the role of
estrogen.

Newman LC.

Albert Einstein College of Medicine, The Headache Institute, St. Luke's -
Roosevelt Hospital Center, New York, NY 10019, USA.

Menstruation increases the risk of migraine in susceptible women. In a
subpopulation of women with menstrual migraine, headaches occurring in
association with onset of menses may be more severe and of longer duration than
headaches experienced by the same woman at other times of her menstrual cycle.
Although menstrual migraines share many clinical characteristics of other types
of migraines, their occurrence is predictable provided that the patient has
regular menstrual cycles. Therefore, short-term prevention regimens can be
considered for women whose headaches are not adequately managed with acute
therapies.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 17850539 [PubMed - indexed for MEDLINE]

522: Headache. 2007 Sep;47 Suppl 2:S79-85.

Cortical spreading depression and estrogen.

Eikermann-Haerter K, Kudo C, Moskowitz MA.

Department of Radiology, Stroke and Neurovascular Regulation Laboratory,
Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129,
USA.

Cortical spreading depression (CSD) is an electrophysiological phenomenon
characterized by a wave of excitation followed by inhibition. The aura phase that
precedes migraine headache in about 20-30% of migraineurs shares overlapping
characteristics with CSD. Studies of rare autosomal-dominant forms of migraine
with aura provide strong evidence that the threshold for evoking CSD and aura are
related to neuronal excitability. Although the relationship between CSD and
migraine without aura is not completely understood, the molecular abnormalities
that predispose to migraine with aura illustrate the importance of physiologic
events associated with neuronal hyperexcitability, and provide a basis for
understanding a more generalized view of migraine.

Publication Types: 
    Review

PMID: 17850538 [PubMed - indexed for MEDLINE]

523: J Headache Pain. 2007 Oct;8(5):273-6. Epub 2007 Oct 23.

Parenteral vs. oral sumatriptan and naratriptan: plasma levels and efficacy in
migraine. a comment.

Tfelt-Hansen P.

Danish Headache Centre, Department of Neurology, University of Copenhagen,
Glostrup Hospital, DK-2600, Glostrup, Denmark. tfelt@inet.uni2.dk

The clinical efficacy in migraine was compared for oral and subcutaneous
sumatriptan and naratriptan. Doses of the two administration forms were chosen as
resulting in comparable blood concentrations. Subcutaneous administrations of the
drugs were superior for efficacy than the oral forms. This most likely due to a
quicker rise in blood concentrations after subcutaneous injections.. In designing
new therapies for migraine one should aim at a quick absorption of the drug,
which will probably result in an increased efficacy.

Publication Types: 
    Comparative Study
    Review

PMID: 17955173 [PubMed - indexed for MEDLINE]

524: J Headache Pain. 2007 Oct;8(5):289-93. Epub 2007 Oct 23.

Transcranial Doppler measurements in migraine and nitroglycerin headache.

Kassab MY, Majid A, Bakhtar O, Farooq MU, Patel K, Bednarczyk EM.

Department of Neurology, Michigan State University, 138 Service Road, A-217, East
Lansing, MI 48824, USA. mounzer.kassab@ht.msu.edu

The objective of this study was to examine the cerebral circulation during
spontaneous migraine attacks and to compare changes to an experimental headache
model induced by nitroglycerin (NTG) infusion. This prospective study was carried
out in a tertiary care hospital on migraineurs with or without aura. Healthy
volunteers served as controls. There were no interventions. Flow velocity (FV)
and pulsatility index (PI) were measured in migraineurs between and during
headache attacks. In controls, FV and PI of the middle cerebral arteries were
performed at baseline and after each IV infusion of 0.125, 0.25 and 0.5
microg/kg/min of NTG. In migraineurs, a significant increase in the mean flow
velocity (MFV) in the left vertebral artery (VA) and the PI of the right VA
during spontaneous migraine headache was found. In controls, all FV significantly
decreased after infusion of NTG. The NTG model produces expected and
substantially different vascular effects than those seen with spontaneous
migraine headache.

PMID: 17955171 [PubMed - indexed for MEDLINE]

525: J Headache Pain. 2007 Oct;8(5):301-5. Epub 2007 Oct 23.

Uncontrolled headache induced by oxcarbazepine.

Piovesan EJ, Teive HG, de Paola L, Silvado CE, Crippa A, Amaral VC, Della Colleta
MV, Di Stani F, Werneck LC.

Headache Clinic, Neurology Service, Department of Internal Medicine, Hospital de 
Clínicas, Federal University of Paraná, Rua General Carneiro 181, 120 andar, sala
1236, CEP-80060-900, Curitiba-Paraná, Brazil. piovesan@avalon.sul.com.br

Headache induced by acute exposure to a specific drug constitutes an
idiosyncratic side effect. Metabolic imbalance appears as the leading aetiology, 
among several other hypotheses. Either primary headaches show a higher
susceptibility to this idiosyncratic reaction or a drug-induced primary headache 
evolves in intensity and duration, becoming uncontrolled until the complete
discontinuation of the drug in consideration. The goal of this study is to
describe three patients diagnosed with migraine and epilepsy (both under control)
who evolved into status migrainosus after the introduction of oxcarbazepine
(OXC), as part of a switch off from carbamazepine (CBZ). Twenty-four to
seventy-two hours following the switch, all patients developed intractable
headache, despite the use of different symptomatic drugs. Complete recovery of
the headache symptoms occurred only after OXC was discontinued. We discuss the
potential mechanisms associated to OXC and status migrainosus, drug-induced
headaches and uncontrolled headaches.

Publication Types: 
    Case Reports

PMID: 17955169 [PubMed - indexed for MEDLINE]

526: J Headache Pain. 2007 Oct;8(5):283-8. Epub 2007 Oct 23.

Frovatriptan vs. transdermal oestrogens or naproxen sodium for the prophylaxis of
menstrual migraine.

Guidotti M, Mauri M, Barrilà C, Guidotti F, Belloni C.

Neurologic Unit, Valduce General Hospital, Via Dante 11, I-22100 Como, Italy.
mguidotti@valduce.it

Acute treatment of menstrual migraine (MM) attacks is often incomplete and
unsatisfactory, and perimenstrual prophylaxis with triptans, oestrogen
supplementation or naproxen sodium may be needed for decreasing frequency and
severity of the attack. In this pilot, open-label, non-randomised, parallel group
study we evaluated, in 38 women with a history of MM, the efficacy of
frovatriptan (n=14) 2.5 mg per os or transdermal oestrogens (n=10) 25 microg or
naproxen sodium (n=14) 500 mg per os once-daily for the short-term prevention of 
MM. All treatments were administered in the morning for 6 days, beginning 2 days 
before the expected onset of menstrual headache. All women were asked to fill in 
a diary card, in the absence of (baseline) and under treatment, in order to score
headache severity. All women reported at least one episode of MM at baseline.
During treatment all patients taking transdermal oestrogens or naproxen sodium
and 13 out of the 14 patients (93%) taking frovatriptan had at least one migraine
attack (p=0.424). Daily incidence of migraine was significantly (p=0.045) lower
under frovatriptan than under transdermal oestrogens or NS. At baseline, the
overall median score of headache severity was 4.6, 4.2 and 4.3 in the group
subsequently treated with frovatriptan, transdermal oestrogens and naproxen
sodium, respectively (p=0.819). During treatment the median score was
significantly lower under frovatriptan (2.5) than under transdermal oestrogens
(3.0) and naproxen sodium (3.9, p=0.049). This was evident also for each single
day of observation (p=0.016). Among treatments differences were particularly
evident for the subgroup of patients with true MM (n=22) and for frovatriptan vs.
naproxen sodium. This study suggests that short-term prophylaxis of MM with
frovatriptan may be more effective than that based on transdermal oestrogens or
naproxen sodium.

Publication Types: 
    Clinical Trial
    Comparative Study

PMID: 17955167 [PubMed - indexed for MEDLINE]

527: MedGenMed. 2007 Jun 7;9(2):53.

Two double-blind, multicenter, randomized, placebo-controlled, single-dose
studies of sumatriptan/naproxen sodium in the acute treatment of migraine:
function, productivity, and satisfaction outcomes.

Landy S, DeRossett SE, Rapoport A, Rothrock J, Ames MH, McDonald SA, Burch SP.

Wesley Neurology Clinic, Memphis, Tennessee, USA. wesleyhead@aol.com

OBJECTIVE: To describe return to normal function, productivity, and satisfaction 
of patients with moderate or severe migraine attacks treated with combined
sumatriptan/naproxen sodium, sumatriptan alone, naproxen sodium alone, or
placebo. PATIENTS, DESIGN, AND SETTING: Patients in 2 identical, US, phase 3,
randomized, double-blind, parallel-group, placebo-controlled, single-dose,
multicenter studies treated a single moderate or severe migraine attack with
sumatriptan/naproxen sodium (85 mg sumatriptan formulated with RT Technology and 
500 mg naproxen sodium in a single-tablet formulation), sumatriptan, naproxen
sodium, or placebo. MAIN OUTCOME MEASURES: Ability to function (not impaired,
mildly impaired, severely impaired, or required bed rest) was collected in diary 
cards completed immediately prior to treatment, every 30 minutes for the first 2 
hours, and hourly from 2 to 24 hours while awake. Patients completed the
Productivity Assessment Questionnaire (PAQ) 24 hours after study drug
administration. The Patient Perception of Migraine Questionnaire (PPMQ) was
administered at screening and 24 hours post treatment to capture patient
satisfaction. RESULTS: Compared with the other groups, the sumatriptan/naproxen
sodium group reported significantly higher levels of normal or mildly impaired
functioning as early as 2 and 4 hours after dosing. They also demonstrated
greater reductions in workplace productivity loss compared with placebo in both
studies, and were consistently more satisfied with their treatment compared with 
patients in other treatment groups and compared with their usual medications.
CONCLUSIONS: Treatment with sumatriptan/naproxen sodium allowed significantly
more subjects to return to normal or mildly impaired functioning more quickly,
and sumatriptan/naproxen sodium patients were significantly more satisfied with
their treatment compared with other treatment groups. Overall productivity loss
was significantly reduced following use of sumatriptan/naproxen sodium.

Publication Types: 
    Multicenter Study
    Randomized Controlled Trial

PMID: 17955107 [PubMed - indexed for MEDLINE]

528: J Hum Genet. 2007;52(12):990-8. Epub 2007 Oct 19.

Recurrent ATP1A2 mutations in Portuguese families with familial hemiplegic
migraine.

Castro MJ, Stam AH, Lemos C, Barros J, Gouveia RG, Martins IP, Koenderink JB,
Vanmolkot KR, Mendes AP, Frants RR, Ferrari MD, Sequeiros J, Pereira-Monteiro JM,
van den Maagdenberg AM.

Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, Porto,
Portugal.

Familial hemiplegic migraine is a rare autosomal dominant subtype of migraine
with aura. Three genes have been identified, all involved in ion transport. There
is considerable clinical variation associated with FHM mutations.
Genotype-phenotype correlation studies are needed, but are challenging mainly
because the number of carriers of individual mutations is low. One exception is
the recurrent T666M mutation in the FHM1 CACNA1A gene that was identified in
almost one-third of FHM families and showed variable associated clinical features
and severity, both within and among FHM families. Similar studies in the FHM2
ATP1A2 gene have not been performed because of the low number of carriers with
individual mutations. Here we report on the recurrence of ATP1A2 mutations M731T 
and T376M that affect sodium-potassium pump functioning in two Portuguese FHM
families. Considerably increasing the number of mutation carriers with these
mutations indicated a clear genotype-phenotype correlation: both mutations are
associated with pure FHM. In addition, we show that recurrent mutations for
ATP1A2 are more frequent than previously thought, which has implications for
genotype-phenotype correlations and genetic testing.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17952365 [PubMed - indexed for MEDLINE]

529: Cephalalgia. 2007 Dec;27(12):1368-77. Epub 2007 Oct 18.

Migraine aura and related phenomena: beyond scotomata and scintillations.

Vincent MB, Hadjikhani N.

Hospital Universitário Clementino Fraga Filho, Faculdade de Medicina,
Universidade Federal do Rio de Janeiro, Brazil. vincent@ufrj.br

Migraine affects the cortical physiology and may induce dysfunction both ictally 
and interictally. Although visual symptoms predominate during aura, other
contiguous cortical areas related to less impressive symptoms are also impaired
in migraine. Answers from 72.2% migraine with aura and 48.6% of migraine without 
aura patients on human faces and objects recognition, colour perception, proper
names recalling and memory in general showed dysfunctions suggestive of
prosopagnosia, dyschromatopsia, ideational apraxia, alien hand syndrome, proper
name anomia or aphasia, varying in duration and severity. Symptoms frequently
occurred in a successively building-up pattern fitting with the geographical
distribution of the various cortical functions. When specifically inquired,
migraineurs reveal less evident symptoms that are not usually considered during
routine examination. Spreading depression most likely underlies the aura symptoms
progression. Interictal involvement indicates that MWA and MWoA are not
completely silent outside attacks, and that both subforms of migraine may share
common mechanisms.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 17944958 [PubMed - indexed for MEDLINE]

530: Cephalalgia. 2007 Dec;27(12):1378-85. Epub 2007 Oct 18.

The difference between epileptic auras and migrainous auras in the 19th century.

Lardreau E.

Institute for the History and Philosophy of Science and Technology, National
Center for Scientific Research, Paris, France. esthercotelle@wanadoo.fr

In the International Headache Society classification of headaches, the concept of
aura is given a key role. It serves as a boundary between 'migraine without aura'
and 'migraine with aura'. Historically, the concept of an aura was borrowed from 
the epilepsy vocabulary; a borrowing that took place in English medicine at the
beginning of the 19th century and in French medicine in the mid-19th century. It 
would therefore be interesting to see which features of the epileptic aura are
used to explain the migraine aura. Based on the French and English medical
literature of the 19th century, two processes have been reviewed: (i) the
emergence of the concept of aura, and (ii) the modifications of this concept
throughout the 19th century. It appears that the original medical use of the term
'aura' as a set of rising tactile sensations was in use from the 2nd century
until late in the 19th century, but then various other symptoms were recognized
and the aura gradually became accepted as an early part of the seizure. By the
end of the 19th century the aura that preceded a migraine was seen as a similar
process, and thought of as part of the migraine sequence.

Publication Types: 
    Historical Article

PMID: 17944957 [PubMed - indexed for MEDLINE]

531: Neurology. 2007 Nov 27;69(22):2038-44. Epub 2007 Oct 17.

Comment in:
    Neurology. 2007 Nov 27;69(22):2034-5.

Randomized trial of IV dexamethasone for acute migraine in the emergency
department.

Friedman BW, Greenwald P, Bania TC, Esses D, Hochberg M, Solorzano C, Corbo J,
Chu J, Chew E, Cheung P, Fearon S, Paternoster J, Baccellieri A, Clark S, Bijur
PE, Lipton RB, Gallagher EJ.

Department of Emergency Medicine, Albert Einstein College of Medicine, Montefiore
Medical Center, 111 East 210th Street, Bronx, NY 10467, USA.
befriedm@montefiore.org

BACKGROUND: It is not yet clear if corticosteroids are useful for the treatment
of migraine. We determined the efficacy of 10 mg of IV dexamethasone as adjuvant 
therapy for patients presenting to an emergency department (ED) with acute
migraine. METHODS: This was a randomized, double-blind, placebo-controlled
multicenter trial. Subjects were randomized to dexamethasone 10 mg IV or placebo.
As primary treatment for their migraine, all subjects received IV metoclopramide.
Our primary hypotheses were the following: a greater percentage of patients with 
migraine who received dexamethasone would 1) achieve a headache-free state in the
ED and maintain it for 24 hours and 2) have no headache-related functional
impairment after ED discharge when compared to placebo. RESULTS: A total of 656
patients were approached for participation and 205 were randomized. The
persistent pain-free outcome was achieved in 25% of those randomized to
dexamethasone and 19% of placebo (p = 0.34). No functional impairment after ED
discharge occurred in 67% of those randomized to dexamethasone and 59% of placebo
(p = 0.20). In the subgroup of subjects with migraine lasting longer than 72
hours, 38% of those randomized to dexamethasone were persistently pain-free vs
13% of placebo (p = 0.06). Side effect profiles were similar, with the exception 
of acute medication reactions, which occurred more commonly in the dexamethasone 
group. CONCLUSION: A moderate dose of IV dexamethasone should not be administered
routinely for the emergency department-based treatment of acute migraine,
although it might be useful for patients with migraine lasting longer than 72
hours.

Publication Types: 
    Comparative Study
    Multicenter Study
    Randomized Controlled Trial
    Research Support, N.I.H., Extramural

PMID: 17942818 [PubMed - indexed for MEDLINE]

532: Cephalalgia. 2007 Dec;27(12):1398-407. Epub 2007 Oct 16.

The GRIM2005 study of migraine consultation in France II. Psychological factors
associated with treatment response to acute headache therapy and satisfaction in 
migraine.

Lucas C, Lantéri-Minet M, Massiou H, Nachit-Ouinekh F, Pradalier A, Mercier F, El
Hasnaoui A, Radat F.

Hôpital Roger Salengro, Lille, France.

The objective of this analysis was to identify variables associated with
treatment response in subjects with migraine. Data were collected from a sample
of 10,000 subjects. A battery of questionnaires assessing clinical and
psychological variables was completed. Migraine diagnosis was attributed using an
algorithm based on the IHS criteria and treatment response using the ANAES
criteria. We identified 1534 subjects, of whom 1443 were treated. For 54.2%, at
least one ANAES criterion for treatment response was unfulfilled. Non-response
was associated with female gender, high HIT-6 impact scores and high HAD
psychological distress scores. The strongest associations with non-response were 
identified for four psychological variables: elevated scores on the CSQ
catastrophization subscale and the 'Consequences' and 'Acceptance' dimensions of 
the Brief COPE, and low scores on the 'Positive Reinterpretation' Brief COPE
dimension. In conclusion, many individuals with migraine respond inadequately to 
treatment. Behavioural interventions aimed at modifying coping strategies may
improve outcome.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17941879 [PubMed - indexed for MEDLINE]

533: Eur J Neurol. 2007 Dec;14(12):1363-8. Epub 2007 Oct 17.

Migraine and delayed ischaemic neurological deficit after subarachnoid
haemorrhage in women: a case-control study.

Dreier JP, Kremer C, Lammers G, Lohmann F, Hansen HC, Valdueza JM.

Department of Neurology, Charité University Medicine Berlin, Germany.
jens.dreier@charite.de

The aim of the present case-control study was to investigate the role of migraine
as a potential risk factor for a delayed ischaemic neurological deficit (DIND)
after subarachnoid haemorrhage (SAH). A telephone interview was performed in
patients or their relatives to determine the prevalence of migraine. Thirty-six
women aged <60 years had SAH with Hunt & Hess grade I-III and DIND (group A).
This group was compared with an age-matched group of 36 female SAH patients, Hunt
& Hess grade I-III without DIND (group B). The two populations were also
characterized regarding hypertension, smoking, diabetes mellitus and alcohol use.
A significant difference was only found for the prevalence of migraine with 47%
in group A and 25% in group B (P < 0.05; odds ratio: 2.68, confidence interval:
0.99-7.29). Migraineurs revealed similar prevalences of risk factors
independently of the presence of DINDs. This retrospective study suggests that
women with migraine have a higher risk to develop a DIND than women without
migraine.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17941853 [PubMed - indexed for MEDLINE]

534: Semin Neurol. 2007 Nov;27(5):425-33.

Migraine in pregnancy.

Loder E.

Division of Headache and Pain, Department of Neurology, Brigham and
Women's/Faulkner Hospital, Boston, Massachusetts 02130, USA. eloder@partners.org

Migraine is the headache disorder that most commonly complicates pregnancy.
Migraine often, but not always, improves during pregnancy. Postdelivery migraine 
flares are common, and it can be difficult to distinguish these from dangerous
causes of postpartum headache. Many pregnant or lactating migraineurs require
intermittent use of medication for treatment of individual headache attacks, and 
some also need preventive treatment aimed at decreasing the number or severity of
headache attacks. In general, medication use should be limited and
nonpharmacologic approaches are preferred. Appropriate treatment choices also
vary with the stage of pregnancy, and may differ for pregnancy and lactation.
Risk rating systems are available that help guide decisions. Women with migraine 
have an increased risk for several serious pregnancy complications, but there is 
little convincing evidence of an increase in neonatal complications. Migraine is 
not a contraindication to breast-feeding.

Publication Types: 
    Review

PMID: 17940921 [PubMed - indexed for MEDLINE]

535: Eur J Ophthalmol. 2007 Sep-Oct;17(5):828-35.

Asymmetric distribution of visual evoked potentials in patients with migraine
with aura during the interictal phase.

Coppola G, Parisi V, Fiermonte G, Restuccia R, Pierelli F.

G.B. Bietti Eye Foundation, IRCCS, Roma, Italy.

PURPOSE: One of the most commonly described electrocortical phenomena in patients
with migraine is an increased interhemispheric asymmetry, in response to
different sensory stimuli. This study aims to evaluate the bioelectrical activity
of both occipital cortices in patients with migraine with visual aura (MA) during
the interictal period, and its possible relationship with visual symptoms.
METHODS: The authors recorded visual evoked potentials (VEPs) simultaneously from
the left (O1) and right (O2) occipital cortices (80% contrast 60', 30', 15', and 
7.5' checkerboard stimuli reversed at 2 Hz) in 22 patients with MA and 20 control
subjects. The main outcome measure was interhemispheric asymmetry (IA) for both
implicit time and amplitude, defined as the difference between the left and right
scalp derivation (in absolute values). RESULTS: IA was significantly different in
patients with MA with respect to controls when employing 60' (p<0.001) and 15'
(p<0.05) checkerboard stimuli for implicit times, and 60' (p<0.05) checkerboard
stimuli for amplitudes. On the other hand, IA was not statistically different
(p>0.05) in patients with MA with respect to controls when employing 30' and 7.5'
checkerboards for both implicit times and amplitudes, and 15' checkerboards for
amplitudes. No correlations were found between IA and age, onset of disease,
attack frequency, or side of headache/aura. CONCLUSIONS: Patients with MA
presented asymmetries in VEP responses not related to visual aura or to headache 
side during the pain-free phase. These abnormalities may be ascribed to abnormal 
visual information processing, resulting in a different cortical activation when 
both foveal and parafoveal stimuli are used.

PMID: 17932863 [PubMed - indexed for MEDLINE]

536: J Med Chem. 2007 Nov 15;50(23):5564-7. Epub 2007 Oct 11.

Potent, orally bioavailable calcitonin gene-related peptide receptor antagonists 
for the treatment of migraine: discovery of
N-[(3R,6S)-6-(2,3-difluorophenyl)-2-oxo-1- (2,2,2-trifluoroethyl)azepan-3-yl]-4- 
(2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridin- 1-yl)piperidine-1-carboxamide
(MK-0974).

Paone DV, Shaw AW, Nguyen DN, Burgey CS, Deng JZ, Kane SA, Koblan KS, Salvatore
CA, Mosser SD, Johnston VK, Wong BK, Miller-Stein CM, Hershey JC, Graham SL,
Vacca JP, Williams TM.

Department of Medicinal Chemistry, Merck Research Laboratories, P.O. Box 4, West 
Point, Pennsylvania 19486, USA. daniel_paone@merck.com

Calcitonin gene-related peptide (CGRP) has been implicated in the pathogenesis of
migraine. Herein we describe optimization of CGRP receptor antagonists based on
an earlier lead structure containing a (3R)-amino-(6S)-phenylcaprolactam core.
Replacement of the phenylimidazolinone with an azabenzimidazolone gave stable
derivatives with lowered serum shifts. Extensive SAR studies of the C-6 aryl
moiety revealed the potency-enhancing effect of the 2,3-difluorophenyl group, and
trifluoroethylation of the N-1 amide position resulted in improved oral
bioavailabilities, ultimately leading to clinical candidate 38 (MK-0974).

PMID: 17929795 [PubMed - indexed for MEDLINE]

537: Headache. 2007 Oct;47(9):1349-51.

Hemicrania Continua-like headache due to nonmetastatic lung cancer--a vagal
cephalalgia.

Evans RW.

Park Plaza Hospital - Neurology, Houston, TX 77004, USA.

A 72-year-old man presented with a 7-week history of a new onset constant severe 
right-sided headache associated with redness and tearing of the right eye, which 
resolved on indomethacin due to nonmetastatic small cell carcinoma producing a
large suprahilar mass. This is the first case report of a hemicrania
continua-like headache with autonomic features due to lung cancer. I propose the 
term "vagal cephalalgia" to include headache and/or facial pain due to
nonmetastatic lung cancer and cardiac cephalalgia which result from vagal
afferent stimulation.

Publication Types: 
    Case Reports

PMID: 17927655 [PubMed - indexed for MEDLINE]

538: Headache. 2007 Oct;47(9):1342-4.

Efficacy of folic acid in children with migraine, hyperhomocysteinemia and MTHFR 
polymorphisms.

Di Rosa G, Attinà S, Spanò M, Ingegneri G, Sgrò DL, Pustorino G, Bonsignore M,
Trapani-Lombardo V, Tortorella G.

Department of Medical and Surgical Pediatrics, Unit of Infantile Neuropsychiatry,
University Hospital of Messina, Messina, Italy.

MTHFR gene variants C677T and A1298C seem to be related to an increased risk of
migraine. Folates' metabolism could play a role in the pathophysiology of
migraine. We supplemented 16 children with migraine, hyperhomocysteinemia, and
MTHFR polymorphisms with folic acid and obtained a resolution/reduction of
migraine attacks. Although the mechanism leading to these effects has been not
made clear, we believe that the use of folic acid needs further investigations in
migraineurs with hyperhomocysteinemia and MTHFR variants. A randomized,
double-blind, placebo controlled crossover trial is needed to support these
findings.

PMID: 17927652 [PubMed - indexed for MEDLINE]

539: Headache. 2007 Oct;47(9):1326-33.

Determinants of migraine emergency department utilization in the georgia medicaid
population.

Kwong WJ.

Department of Clinical and Administrative Pharmacy, University of Georgia,
Athens, GA 30602-2354, USA.

OBJECTIVE: This study examined factors that may predispose migraine patients to
emergency department (ED) visits. BACKGROUND: Headache is noted as the sixth most
common reason for ED visits. Previous studies found that migraine headache
patients may repeatedly use ED services for headache care. An understanding of
the profile of patients who are at high risk of using the ED is important so that
interventions to reduce ED use for nonurgent care can be targeted to those that
are affected the most. METHODS: Retrospective analysis of medical and
prescription claims data was performed. Patients who had at least 1 migraine
medical claim (ICD-9 of 346.xx) or 1 prescription claim of a triptan or ergot
medication between January 2002 and December 2005, and were continuously eligible
for at least 6 months before and 12 months after the date of the first migraine
medical or prescription claim (index date) were included in the analysis.
RESULTS: A total of 43,791 migraine patients met the inclusion criteria. Mean age
was 31 years (SD = 17). About 77% were females and 56% were whites. About 7%
patients used a butalbital medication and 28% used a narcotic medication 6 months
before index date. About 3% (n = 1211) patients had at least 1 migraine ED visit 
during the 12 months after index date. Female, non-white patients or patients
residing in counties that had fewer general practice physicians or more hospitals
were significantly more likely to use the ED for migraine. Prior butalbital use
had no effect on ED use, but prior narcotic medication use significantly
increased the risk of ED visit. CONCLUSIONS: Patient demographics and health care
resource availability significantly affected the likelihood of ED use of
diagnosed migraine patients. Additional research is needed for the undiagnosed
migraine population to inform the development of interventions to reduce ED
utilization for migraines.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17927649 [PubMed - indexed for MEDLINE]

540: Headache. 2007 Oct;47(9):1311-8.

Comment in:
    Headache. 2008 Apr;48(4):637-8.    Headache. 2008 Mar;48(3):479-81.

Relationship between migraine and patent foramen ovale: a study of 121 patients
with migraine.

Domitrz I, Mieszkowski J, Kamińska A.

Department of Neurology, Medical University, Warsaw, Poland.

BACKGROUND: Migraine is a common neurological disorder, the origins of which
remain unknown. Patent foramen ovale (PFO) is considered to have a role in
migraine. The relationship between migraine and patent foramen ovale may be
stronger in patients suffering from migraine with aura compared to patients with 
common migraine. OBJECTIVES: The aim of the study was to evaluate the frequency
of PFO in patients with migraine with aura (MA+) and compare it with the
prevalence of PFO in migraine patients without aura (MA-), and in a healthy
age-matched control group. We investigated PFO association with migraine,
considering such factors as: A type of migraine aura, frequency of attacks,
familial occurrence, sex and age of patients. Patients.-121 patients: 61 patients
suffering from migraine with aura, 60 without aura and 65 normal controls. The
group of patients with migraine with aura was divided into subgroups regarding to
the type of aura. METHODS: In order to detect PFO the contrast transcranial
Doppler was performed during Valsalva maneuver. RESULTS: The presence of PFO was 
found in 33/61 (54%) patients with MA(+) compared to 15/60 (25%) without aura and
16/65 (25%) control subjects. The difference between MA(+) patients and MA(-)
patients and the difference between MA(+) patients and control group was
statistically significant (P < .05). There was no association between type of
migraine aura and PFO, as well as we found no association between PFO and
frequency of attacks, familial occurrence, sex and age of patients and PFO.
CONCLUSIONS: Our findings suggest possible association of migraine with aura and 
PFO. It seems that PFO does not influence the type of aura and frequency of
attacks of migraine as well as it is not associated with familial occurrence of
migraine.

PMID: 17927647 [PubMed - indexed for MEDLINE]

541: Headache. 2007 Oct;47(9):1293-302.

Feasibility assessment of telephone-administered behavioral treatment for
adolescent migraine.

Cottrell C, Drew J, Gibson J, Holroyd K, O'Donnell F.

Headache Treatment and Research Project--Ohio University, Westerville, OH 43081, 
USA.

OBJECTIVES: To examine the feasibility of administering behavioral migraine
management training by telephone (TAT) and the acceptability of TAT to
adolescents with episodic migraine. METHODS: 34 adolescents (M = 14 years) with
migraine (M = 3.6 migraines/month; M = 29.2 hours duration) were randomly
assigned to a two-month telephone administered behavioral migraine management
program (TAT) or to a standard Triptan Treatment (TT). Outcome was assessed at
three- and eight-month evaluations. Participants completed a daily migraine diary
that yielded information about number, duration and severity of migraines and
migraine-related disability, as well as the Migraine Specific Quality of Life
Questionnaire - Adolescent. In addition, TAT participants evaluated key aspects
of the TAT program using 5-point Likert-like rating scales. Lastly, the ability
of adolescents to demonstrate specific headache management skills following TAT
was assessed. RESULTS: All fifteen adolescents who entered TAT successfully
demonstrated either full or partial mastery of two or more skills and nearly half
demonstrated at least partial mastery of all four skills evaluated. Ninety three 
percent of the TAT participants reported having a positive relationship with
their phone counselor. They also reported a preference for the telephone-based
treatment over in-clinic visits and rated the manual and tapes as helpful.
Treatment effects (in terms of percent improvement) ranged from consistently
large across both evaluations for improvement in number of migraines (54% and
71%), disability equivalent hours (80% and 63%) and quality of life (44% and
48%), to moderate or variable for migraine duration (35% and 23%) and severity
(30% and 34%). The TT group also showed clinically meaningful reductions in
headache parameters and improvements in quality of life. CONCLUSIONS: Completion 
rates for TAT were high; adolescents evaluated their experience with TAT
positively and were able to exhibit key behavioral headache management skills
following treatment. While clinically significant improvements in migraine and
migraine-related disability/quality of life were observed with both TAT and
treatment as usual (triptan therapy), the small study size and the absence of a
control group do not permit conclusions about the effectiveness of either
treatment. Nonetheless these results indicate TAT may be a promising treatment
format for improving access to behavioral treatments for underserved adolescents 
and justifies further evaluation of TAT both alone and in combination with drug
therapy.

Publication Types: 
    Evaluation Studies
    Research Support, N.I.H., Extramural

PMID: 17927645 [PubMed - indexed for MEDLINE]

542: Headache. 2007 Oct;47(9):1282-92.

French general practitioners' management of children's migraine headaches.

Cuvellier JC, Fily A, Joriot S, Cuisset JM, Vallée L.

Department of Child Neurology, Pediatric Clinic, University Hospital, Lille,
France.

OBJECTIVES: This study sought to examine the treatment of children with migraine 
headaches in a prospective sample of children referred to a tertiary center for
headaches. BACKGROUND: Despite the wide diffusion of guidelines for headache
management in children, their application in general practice is far from
optimal. METHODS: This prospective study analyzed previous headache treatment by 
general practitioners in 151 consecutive children (F/M: 0.82; mean age 10.4 +/-
3.2 years) referred for migraines to the Lille University Hospital Neuropediatric
department between October 1, 2003, and November 30, 2005. The physician
completed a questionnaire according to the parents' responses to questions about 
previous advice about life-style adjustments (diet, exercise, and sleep hygiene) 
and abortive and prophylactic treatment. Questions about abortive treatment
covered ergot derivatives, triptans, and 3 aspects of ibuprofen use-appropriate
dose (ie, more than 7.5 mg/kg), recommendation to administer the drug early in
attacks, and warnings about drug abuse. Under the topic of prophylactic
treatment, we asked about information from general practitioners about preventive
therapy and advice to keep a headache diary. RESULTS: Fewer than 15% of patients 
had received advice about life-style adjustments. Only 30.3% had received
ibuprofen at a correct dose (more than 7.5 mg/kg); only 26.5% were told to use it
early during the headache; and only 9.1% were warned about drug abuse. Ergot
derivatives were prescribed to 4.6% of children and triptans to 9.1%. Families of
17.9% reported that the general practitioners gave them information about
prophylactic treatment. Only 8.0% were advised to keep a headache diary.
CONCLUSION: This study shows the need to increase the role and the involvement of
family doctors in the management of primary headache in children in general, and 
of pediatric migraine in particular.

PMID: 17927644 [PubMed - indexed for MEDLINE]

543: Headache. 2007 Oct;47(9):1277-81.

Disability in chronic migraine with medication overuse: treatment effects at 3
years.

Andrasik F, Grazzi L, Usai S, D'Amico D, Kass S, Bussone G.

Department of Psychology, University of West Florida, Pensacola, FL 32514, USA.

OBJECTIVES: To determine the clinical status, with respect to pain indices and
disability level, of chronic migraine patients with medication overuse who were
treated 3 years previously. BACKGROUND: Patients who have chronic migraine
accompanied by medication overuse are particularly difficult to treat.
Investigations are limited in number, few have included follow-up beyond 6
months, and almost none have examined whether treatment leads to concurrent
improvements in disability and functional impairment. In a prior report, we
described the clinical course of 84 such patients followed for 1 full year after 
treatment. METHODS: These same 84 patients were followed for 2 additional years
to assess longer term maintenance of effects, using measurement procedures
identical to those in the original investigation. RESULTS: Both endpoint and
completer analyses revealed significant improvement on all measures
studied-headache days per month, analgesic consumption, and MIDAS scores (Total, 
Headache Frequency, and Headache Intensity)-with some loss of benefits over time 
for the pain indices. MIDAS total scores, however, were lower at 36 months than
at 6 months. Comparisons of those who completed the 3-year follow-up to those who
did not revealed few differences at baseline. All of this suggests attrition did 
not have a bearing on outcome. DISCUSSION: High levels of maintenance were
revealed at 3 years. Even though reports of pain revealed some lessening of
effects, this was not accompanied by reports of deterioration in functioning.
This suggests that patients have learned to adapt and adjust to headaches in
their daily lives.

PMID: 17927643 [PubMed - indexed for MEDLINE]

544: CNS Drugs. 2007;21(11):877-83.

Over-the-counter triptans for migraine : what are the implications?

Tfelt-Hansen P, Steiner TJ.

Department of Neurology, Danish Headache Centre, University of Copenhagen,
Glostrup Hospital, Glostrup, Denmark. tfelt@inet.uni2.dk

In 2006, the triptans sumatriptan 50mg and naratriptan 2.5mg were approved as
over-the-counter (OTC) drugs in pharmacies in the UK and Germany, respectively.
Both drugs have been used in a large number of patients with migraine and are
considered to have good safety profiles.The implications of OTC triptan
availability for clinical practice are that more migraine patients will use a
triptan and will tend to medicate early when their headache is still mild, which 
should be beneficial. The problem with OTC access to triptans is medication
overuse; therefore, patients should be warned of this and advised to use a
triptan on fewer than 10 days per month.Pharmacists should be educated regarding 
migraine types and symptoms and on contraindications to triptans, so they are
then able to discern the patients who should receive triptans and, as
importantly, those who should not.The annual cost of migraine is euro27 billion
in Europe, $US1.4 billion in the UK and $US16.6 billion in the US. By far the
greatest opportunity for cost-savings comes from the potential to reduce costs
associated with lost productivity from migraine. OTC availability of triptans
will inevitably result in easier access to these medications, which, in turn, may
result in improved treatment and lower migraine-related disability. There is
currently a lack of empirical evidence that treating migraine effectively does in
fact recover lost productivity; well designed studies are required to show
this.The availability of triptans OTC is a logical development for the better
management of a common, benign, self-limiting but nonetheless burdensome disorder
that is currently grossly undertreated. We welcome this development, but
recognise that advice at the point of sale is crucial for effective and safe use 
of these drugs.

Publication Types: 
    Review

PMID: 17927293 [PubMed - indexed for MEDLINE]

545: Funct Neurol. 2007 Jul-Sep;22(3):133-6.

Genes, proteases, cortical spreading depression and migraine: impact on
pathophysiology and treatment.

Moskowitz MA.

Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, USA.
moskowitz@helix.mgh.harvard.edu

Migraine headaches have a complex pathophysiology; both vascular and neuronal
mechanisms have been proposed. One possible scenario begins with a series of
destabilising events within the brain that trigger cortical spreading depression 
(CSD). CSD can cause both migraine aura and trigeminal activation which, in turn,
promotes neuropeptide release and triggers peripheral and central mechanisms that
promote headache and autonomic activation. Susceptibility to CSD and to migraine 
is, in part, genetically determined. The best evidence to date comes from certain
subtypes of migraine with aura in which point mutations in genes controlling
translocation of calcium, sodium and potassium have been implicated. This review 
briefly summarises recent migraine research that supports CSD as an upstream
driver of the migraine attack as well as an activator of the trigemino-vascular
system.

Publication Types: 
    Review

PMID: 17925161 [PubMed - indexed for MEDLINE]

546: Arch Intern Med. 2007 Oct 8;167(18):1964-70.

Body mass index and episodic headaches: a population-based study.

Bigal ME, Tsang A, Loder E, Serrano D, Reed ML, Lipton RB.

Department of Neurology, Albert Einstein College of Medicine, 1300 Morris Park
Avenue, Bronx, NY 10461, USA. mbigal@aecom.yu.edu

BACKGROUND: We investigated the influence of the body mass index (BMI [calculated
as weight in kilograms divided by height in meters squared]) on the frequency,
severity, and patterns of treatment of migraine, probable migraine (PM), and
severe episodic tension-type headache (S-ETTH). METHODS: A validated
questionnaire was mailed to 120 000 households selected to be representative of
the US population. The participants were divided into 5 categories based on BMI: 
underweight (<18.5), normal weight (18.5-24.9), overweight (25.0-29.9), obese
(30.0-34.9), and morbidly obese (>35.0). Analyses were adjusted by covariates
that included demographic variables (age, sex, race, and income), duration of
illness, comorbidities, use of preventive medication, and use of opioids.
RESULTS: The response rate was 65%. We identified 18 968 individuals with
migraine, 7564 with PM, and 2051 with S-ETTH. The distribution of very frequent
headaches (10-14 d/mo) was assessed by BMI. Among individuals with migraine, very
frequent headaches (10-14 d/mo) occurred in 7.4% of the overweight (P = .10),
8.2% of the obese (P < .001), and 10.4% of the morbidly obese (P < .0001)
subjects, compared with 6.5% of those with normal weight, in adjusted analyses.
Among individuals with PM and S-ETTH, the differences were not significant (P =
.20). The disability of migraineurs, but not of those with PM or S-ETTH, also
varied as a function of BMI. Among migraineurs, 32.0% of those with normal weight
had some disability compared with 37.2% of the overweight (P < .01), 38.4% of the
obese (P < .001), and 40.9% of the morbidly obese (P < .001) subjects.
CONCLUSION: These findings support the concept that obesity is an exacerbating
factor for migraine but not for other types of episodic headaches.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17923596 [PubMed - indexed for MEDLINE]

547: Sleep Med. 2008 Jul;9(5):542-8. Epub 2007 Oct 24.

Relationships between headache and sleep in a non-clinical population of children
and adolescents.

Bruni O, Russo PM, Ferri R, Novelli L, Galli F, Guidetti V.

Center for Pediatric Sleep Disorders, Department of Developmental Neurology and
Psychiatry, University of Rome La Sapienza, Via dei Sabelli 108-00185, Rome,
Italy. oliviero.bruni@uniroma1.it

BACKGROUND: Headache and sleep are related in different ways and alterations of
chronobiological mechanisms are involved in headache. We investigated the
relationships between headache and sleep quality in a large non-clinical
population of children and adolescents and evaluated the relationship between
headache and circadian typologies. METHODS: A total of 1073 children and
adolescents (50.9% males; mean age=10.56; range=8-15 years) were recruited from
four schools in Rome. They filled out the questionnaires individually in
classrooms, after brief group instruction about answer formats. The
questionnaires included (a) a self-report headache questionnaire to collect
information on different aspects of headache attacks based on the International
Classification of Headache Disorders-2nd edition (ICHD-2); (b) the School Sleep
Habits Survey that incorporated questions about sleep habits, the Sleep-Wake
Problems Behaviour Scale (SWPBS), the Sleepiness Scale (SLS) and the
Morningness/Eveningness Questionnaire (MEQ). RESULTS: According to ICHD-2
criteria, we classified 70 (6.5%) children as Migraine Group (MG), 135 (12.7%) as
Non-Migraine Headache Group (NMG), and the remaining 868 (80.8%) were classified 
as Headache-Free Group (HFG). No clear differences have been found between MG and
NMG regarding the frequency of the attacks, although MG showed a significantly
increased frequency of long-lasting attacks. The modality of onset of pain and
the location of pain was similar in both groups. The most frequent triggering
factor for headache in MG and NMG was "a bad sleep" (32.2%) followed by emotional
distress (27.8%). No differences have been found between MG, NMG and HFG in sleep
schedule or sleep duration. MG and NMG showed significantly higher scores on the 
SWPBS vs. HFG, while MG presented higher scores on the SLS compared to NMG and
HFG. MG presented lower MEQ scores, indicating a more pronounced eveningness.
CONCLUSIONS: The relationships between headache and sleep problems are evident
even in a non-clinical population of children and adolescents, with MG showing
poorer sleep quality, sleepiness and a tendency toward eveningness.

PMID: 17921055 [PubMed - indexed for MEDLINE]

548: Cephalalgia. 2007 Nov;27(11):1201-5. Epub 2007 Oct 5.

Investigation of neuromuscular transmission in some rare types of migraine.

Baslo MB, Coban A, Baykan B, Tutkavul K, Karli N, Saip S, Orhan EK, Ertas M.

Department of Neurology, Istanbul University, Istanbul Faculty of Medicine,
Istanbul, Turkey.

The aim of this study was to delineate any dysfunction of neuromuscular
transmission (NMT) by single-fibre electromyography (SFEMG) in some rare types of
migraine. Recent studies have shown subclinical dysfunction of NMT in migraine
with aura and cluster headache by using SFEMG, whereas another recent study has
shown NMT to be normal in familial hemiplegic migraine (FHM) with CACNA1A
mutations. Thirty patients with rare primary headache syndromes [18 with sporadic
hemiplegic migraine (SHM), six with FHM and six with basilar-type migraine (BM)] 
and 15 healthy control subjects without any headache complaints underwent nerve
conduction studies, EMG and SFEMG during voluntary contraction of the extensor
digitorum communis muscle. Ten to 20 different potential pairs were recorded and 
individual jitter values calculated. The results obtained from patient groups
were compared with those from the normal subjects. Of 600 individual jitter
values of the patients, 27 (4.5%) were abnormally high, whereas only 3/205 (1.5%)
jitter values from normal subjects were abnormal. Abnormal NMT was found in 4/30 
(13.3%) patients (three SHM and one BM), but in none of the control subjects.
Only in SHM patients was the number of individual abnormal jitter values slightly
but significantly different from normal controls. The present study demonstrates 
that subclinical NMT abnormality is slightly present in only SHM and BM patients,
but not in FHM patients.

PMID: 17919307 [PubMed - indexed for MEDLINE]

549: Health Qual Life Outcomes. 2007 Oct 4;5:56.

The impact of migraine prevention on daily activities: a longitudinal and
responder analysis from three topiramate placebo-controlled clinical trials.

Dahlöf C, Loder E, Diamond M, Rupnow M, Papadopoulos G, Mao L.

Gothenburg Migraine Clinic, c/o Läkarhuset, Södra vägen 27, S-41135 Gothenburg,
Sweden. carl.dahlof@migraineclinic.se

BACKGROUND: Topiramate is approved for the prophylaxis (prevention) of migraine
headache in adults. The most common adverse events in the three pivotal,
randomized, double-blind, placebo-controlled trials were paresthesia, fatigue,
cognitive impairment, anorexia, nausea, and taste alteration. In these trials,
topiramate 100 mg/d significantly improved Migraine-Specific Questionnaire (MSQ) 
scores versus placebo (p < 0.001). The MSQ measures how much migraine
limits/interrupts daily performance. Pooled analyses of pivotal trial data were
conducted to further assess how topiramate 100 mg/d affects daily activities and 
patient functioning. METHODS: Mean MSQ and Medical Outcome Study Short Form 36
(SF-36) change scores (baseline to each double-blind assessment point) were
calculated for pooled intent-to-treat (ITT) patients. Additionally, pooled ITT
patients receiving topiramate 100 mg/d or placebo were combined and divided into 
two responder groups according to percent reduction in monthly migraine
frequency: < 50% responders or >or= 50% responders. Between-group differences
were assessed using analysis of covariance. RESULTS: Of 756 patients (mean age
39.8 years, 86% female), 384 received topiramate 100 mg/d and 372 placebo.
Topiramate significantly improved all three MSQ domains throughout the
double-blind phase versus placebo (p = 0.024 [week 8], p < 0.001 [weeks 16 and
26] for role prevention; p < 0.001 for role restriction and emotional function
[all time points]). Topiramate 100 mg/d significantly improved SF-36 physical
component scores (PCS) throughout the double-blind phase versus placebo (p <
0.001, all time points) and significantly improved mental component scores (MCS) 
at week 26 (p = 0.043). The greatest topiramate-associated improvements on SF-36 
subscales were seen for bodily pain and general health perceptions (p < 0.05;
weeks 8, 16, and 26), and physical functioning, vitality, role-physical, and
social functioning (p < 0.05; weeks 16 and 26). Significantly greater
improvements in all three MSQ domains, as well as the PCS and MCS of SF-36, were 
observed for >or= 50% responders versus < 50% responders (p < 0.001).
Significantly greater percentages of topiramate-treated patients were >or= 50%
responders versus placebo (46% versus 23%; p < 0.001). CONCLUSION: Topiramate 100
mg/d significantly improved daily activities and patient functioning at all time 
points throughout the double-blind phase. Daily function and health status
significantly improved for those achieving a >or= 50% migraine frequency
reduction.

Publication Types: 
    Comparative Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 17916258 [PubMed - indexed for MEDLINE]

550: Neurology. 2008 Apr 15;70(16):1304-12. Epub 2007 Oct 3.

Comment in:
    Neurology. 2008 Apr 15;70(16):1300-1.

Randomized controlled trial of an oral CGRP receptor antagonist, MK-0974, in
acute treatment of migraine.

Ho TW, Mannix LK, Fan X, Assaid C, Furtek C, Jones CJ, Lines CR, Rapoport AM;
MK-0974 Protocol 004 study group.

Collaborators: Berman G, Block S, Coats T, De Sola Pool N, Eade J, Elinoff V,
Elkind A, Kayota S, Mannix L, Ramadan N, Rapoport A, Rederich GJ, Saper J, Seger 
W, Seidman L, Spierings E, Stringer JC, Strout C, Tuchman M, Von Seggern R.

Merck Research Laboratories, UG 4C-18, PO Box 1000, North Wales, PA 19454-1099,
USA. tony_ho@merck.com

OBJECTIVE: To determine an effective and tolerable dose of a novel oral
calcitonin gene-related peptide (CGRP) receptor antagonist, MK-0974, for the
acute treatment of migraine. METHODS: Randomized, double-blind, parallel-group,
clinical trial with a two-stage, adaptive, dose-ranging design. Patients were
allocated to treat a moderate or severe migraine attack with MK-0974 (25, 50,
100, 200, 300, 400, or 600 mg), rizatriptan 10 mg, or placebo taken orally. The
primary endpoint was pain relief (reduction to mild or none) 2 hours after
dosing. Secondary endpoints included pain freedom at 2 hours and sustained pain
relief at 24 hours. A prespecified, blinded, automated interim analysis was used 
to discontinue randomization to less effective doses. RESULTS: Per the adaptive
study design, the four lowest MK-0974 groups (25, 50, 100, 200 mg) were
discontinued due to insufficient efficacy. For the remaining treatment groups,
the estimated pain relief proportions at 2 hours were 300 mg (n = 38) 68.1%, 400 
mg (n = 45) 48.2%, 600 mg (n = 40) 67.5%, rizatriptan 10 mg (n = 34) 69.5%, and
placebo (n = 115) 46.3%. The prespecified primary efficacy hypothesis test, which
compared the average 2-hour pain relief response proportion of the combined 300, 
400, and 600 mg MK-0974 groups to placebo, was significant (P = 0.015). A
generally similar efficacy pattern was seen for other endpoints. MK-0974 was
generally well tolerated and there did not appear to be an increase in adverse
events with increasing dose. CONCLUSIONS: The novel, orally administered
calcitonin gene-related peptide (CGRP) receptor antagonist, MK-0974, was
effective and generally well tolerated for the acute treatment of migraine.

Publication Types: 
    Comparative Study
    Randomized Controlled Trial

PMID: 17914062 [PubMed - indexed for MEDLINE]

551: Niger J Clin Pract. 2007 Jun;10(2):147-51.

Pattern of neuro-ophthalmic disorders in a tertiary eye centre in Nigeria.

Omoti AE, Waziri-Erameh MJ.

Department of Ophthalmology, University of Benin Teaching Hospital, Benin-city,
Nigeria. afeomoti@yahoo.com

AIM: To determine the incidence and types of neuro-ophthalmic disorders at the
eye clinic of University of Benin Teaching Hospital, Benin City, Nigeria.
METHODS: All the new patients presenting to the eye clinic of the University of
Benin Teaching Hospital between May 2001 and April 2003 with neuro-ophthalmic
disorders were interviewed, examined and investigated when possible. They were
analysed in the context of age, gender, diagnosis, major clinical features and
visual acuity. RESULTS: A total of 76 patients with neuro-ophthalmic disorders
were seen among a total of 1,698 new patients giving an incidence of 4.47%. The
most common disorders were motor nerve palsies (27.6%), optic neuropathies
(22.4%) and migraine (14.5%). The most presenting features were poor vision
(39.5%), double vision (18.4%) and headache (17.1%). Twenty-nine patients (38.2%)
were blind in the affected eye. CONCLUSION: The incidence of neuro-ophthalmic
disorders is relatively low but constitute a significant cause of ocular
morbidity and blindness. Improvement in diagnostic facilities and awareness are
required.

PMID: 17902508 [PubMed - indexed for MEDLINE]

552: J Headache Pain. 2007 Sep;8(4):205-8. Epub 2007 Sep 24.

The effects of a sensitisation campaign on unrecognised migraine: the Casilino
study.

Di Piero V, Altieri M, Conserva G, Petolicchio B, Di Clemente L, Hettiarachchi J;
"General Practitioners' Co-operative" of the Casilino district of Rome.

Dipartimento di Scienze Neurologiche, Università degli Studi La Sapienza di Roma,
Via dell'Università 30, I-00185, Rome, Italy. vittorio.dipiero@uniroma1.it

A striking feature of migraine is the difference between the estimated migraine
prevalence and the actual number of migraineurs consulting their general
practitioners (GPs). We investigated the impact of a sensitisation campaign on
migraine in a large cohort of patients, living in a district of Rome. The study
involved 10 GPs and a population of about 12 000 people, contacted by mail and
posters located in GP clinics. Both the letter and poster stressed the impact of 
headache on quality of life and included the Italian version of the three-item
Identification of Migraine (ID Migraine) screening test, consisting of questions 
on disability, nausea and photophobia. If the subjects suffered from headaches,
they were invited to contact their GPs for a visit and a free consultation with a
headache expert. By means of this sensitisation campaign, 195 headache patients
consulted their GPs. Ninety-two percent of them (n=179) were migraineurs; 73% of 
them had never consulted a physician for headache. The ID Migraine test had a
sensitivity of 0.92 (95% CI 0.86-0.95), a specificity of 0.75 (95% CI 0.47-0.91) 
and a positive predictive value (PPV) of 0.97 (95% CI 0.93-0.99) for a clinical
diagnosis of migraine, according to the International Headache Society (IHS)
criteria. This study confirms that a large number of migraine patients never see 
a doctor for their headache. This awareness campaign is likely to identify the
severest cases of undiagnosed migraineurs. However, mailing campaigns do not seem
to be so effective in bringing undiagnosed migraine patients into the primary
care setting, and more efficient strategies have to be planned.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17901925 [PubMed - indexed for MEDLINE]

553: J Headache Pain. 2007 Sep;8(4):209-16. Epub 2007 Sep 24.

Migraineurs with patent foramen ovale have larger right-to-left shunt despite
similar atrial septal characteristics.

Jesurum JT, Fuller CJ, Velez CA, Spencer MP, Krabill KA, Likosky WH, Gray WA,
Olsen JV, Reisman M.

Department of Cardiovascular Research, Swedish Medical Center, Seattle, WA, USA. 
jill.jesurum@swedish.org

The objective of the study was to assess differences in proportion of large
right-to-left shunt (RLS) and atrial septal characteristics between migraineurs
and non-migraineurs referred for transcatheter closure of patent foramen ovale
(PF0). This retrospective study took place in a large metropolitan medical
centre. The patients were migraineurs with aura (n=52), migraineurs without aura 
(n=19) and non-migraineurs (n=149). RLS was evaluated before closure using
bilateral power m-mode transcranial Doppler at rest and after calibrated,
sustained Valsalva manoeuvre, and graded with a validated 0-5 scale. Intracardiac
echocardiography was used to assess atrial septal characteristics. Migraineurs
had a higher proportion of large RLS (Grade IV or V) than nonmigraineurs at rest 
and after calibrated Valsalva (rest, p=0.04; Valsalva, p=0.01). Atrial septal
characteristics were similar between groups. Migraine is associated with larger
RLS at rest and strain; however migraine status does not predict PFO
characteristics.

PMID: 17901924 [PubMed - indexed for MEDLINE]

554: J Headache Pain. 2007 Sep;8(4):217-23. Epub 2007 Sep 24.

The validation of ID Migraine screener in neurology outpatient clinics in Turkey.

Karli N, Ertas M, Baykan B, Uzunkaya O, Saip S, Zarifoglu M, Siva A; MIRA study
group.

Department of Neurology, School of Medicine, University of Uludag, 16059,
Gorukle, Bursa, Turkey. nkarli@uludag.edu.tr

The aim of this study was to investigate the validity of the ID Migraine test in 
neurology outpatient clinics (NOCs), regardless of their presenting complaints.
Patients admitted to 41 NOCs were screened. Eligible subjects (n=3682) were
evaluated by a neurologist for headache diagnosis according to the International 
Headache Society criteria and asked the 3-item screening questions of the ID
Migraine test. Of 3682 patients, 917 (24.9%) were diagnosed as migraine, whereas 
1171 (31.8%) were ID Migraine test positive. The sensitivity of the ID Migraine
test for neurologist's diagnosis of migraine was 91.8%, specificity was 63.4%,
positive predictive value was 71.9% and negative predictive value was 88.4%. The 
ID Migraine test is easy to use and a practical test that could alert the
neurologist to diagnose patients having other complaints. This test would help to
increase the diagnosis and treatment rate of undiagnosed migraine patients in
NOCs.

Publication Types: 
    Multicenter Study
    Research Support, Non-U.S. Gov't
    Validation Studies

PMID: 17901923 [PubMed - indexed for MEDLINE]

555: J Headache Pain. 2007 Sep;8(4):231-5. Epub 2007 Sep 24.

Genetic association study and meta-analysis of the HTR2C Cys23Ser polymorphism
and migraine.

Oterino A, Castillo J, Pascual J, Cayon A, Alonso A, Ruiz-Alegria C, Valle N,
Monton F, Ruiz-Lavilla N.

Service of Neurology, University Hospital Marques de Valdecilla, E-39008,
Santander, Spain. aoterino@humv.es

The objectives of this study were to determine if the HTR2C Cys23Ser polymorphism
is associated with migraine in a case-control study, and to perform a
meta-analysis with present and previous available studies. The HTR2C gene is
located at the Xq24-q28 chromosomal band. This band was linked to migraine with
aura (MA) in two Australian families. Using the HTR2C Cys23Ser allelic variant,
this gene has been ruled out as a migraine gene in 3 out of 4 studies. Only the
Japanese study reported a higher risk for MA (OR=6.11; 95% CI=1.70-21.97, p
trend<0.01). We performed a case-control study with 335 migraine subjects and 335
sex- and age-matched controls, and a meta-analysis pooling the results of the
available data from MA subsets of patients. In the association study we found no 
significant differences among migraine and MA patients for this polymorphism. In 
the meta-analysis, under the fixed-effect model, the Ser allele did not confer
higher risk for suffering MA (pooled OR=1.1; 99% CI=0.8-1.5, p=0.499). Our study 
did not confirm the HTR2C Cys23Ser polymorphism as a risk factor for migraine and
MA.

Publication Types: 
    Meta-Analysis
    Research Support, Non-U.S. Gov't

PMID: 17901921 [PubMed - indexed for MEDLINE]

556: J Headache Pain. 2007 Sep;8(4):248-50. Epub 2007 Sep 24.

Memantine for prevention of migraine: a retrospective study of 60 cases.

Charles A, Flippen C, Romero Reyes M, Brennan KC.

Headache Research and Treatment Program, Department of Neurology, David Geffen
School of Medicine at UCLA, 635 Charles Young Drive, Suite 575, Los Angeles, CA
90095, USA. acharles@ucla.edu

The objective was to retrospectively characterise the efficacy of memantine as
preventive therapy in a series of patients with frequent migraine. Patients in a 
university headache clinic completed a survey regarding their experience with
memantine, and medical records were reviewed. All patients who received memantine
as preventive therapy for migraine over a 15-month period were mailed surveys and
consent forms for record review. Patients were treated with memantine beginning
at a dose of 5 mg/day, increasing if needed by 5 mg/week up to 10 mg twice a day.
The majority of patients (36 out of 54) treated with memantine for at least 2
months reported a significant reduction in estimated headache frequency, and
improved function. Side effects were uncommon and generally mild. This limited
retrospective case review suggests that memantine may be an effective preventive 
therapy for patients with frequent migraine. A prospective trial is warranted.

PMID: 17901918 [PubMed - indexed for MEDLINE]

557: Curr Pain Headache Rep. 2007 Oct;11(5):390-5.

Genetics of migraine headache in children.

Hershey AD.

Division of Neurology, Cincinnati Children's Hospital Medical Center, 3333 Burnet
Avenue, Cincinnati, OH 45229, USA. andrew.hershey@cchmc.org

A family history of migraine is very frequently noted when evaluating a child for
recurrent headaches. This implies an inherited or genetic basis as a component to
the underlying pathophysiology. A variety of techniques have begun to elucidate
this contribution, including historical observation, population-based studies
including family and twin studies, gene polymorphism association studies, and
specific gene identification for isolated migraine subtypes. This line of
investigation should progress in the future to a better understanding of migraine
and clarification of the diagnostic subtypes for a genotype-phenotype
association.

Publication Types: 
    Review

PMID: 17894930 [PubMed - indexed for MEDLINE]

558: Curr Pain Headache Rep. 2007 Oct;11(5):375-82.

Epidemiology and diagnosis of migraine in children.

Winner P, Hershey AD.

Palm Beach Headache Center, 4631 North Congress Avenue, West Palm Beach, FL
33407, USA. eneuro@aol.com

Migraine headache occurs frequently in children and adolescents but is often not 
recognized. This underdiagnosis or misdiagnosis results in inappropriate and
potentially ineffective treatments. A variety of factors may contribute to this
deficiency, including limitations in the current standardized criteria, as well
as patient, parent, and care providers' misassumption as to the etiology. The
standardized criteria that have been developed to assist with the recognition and
accurate diagnoses have recently been revised (the International Classification
of Headache Disorders II). These criteria provide the scientific basis for the
study of headache, including the determination of the incidence and prevalence of
pediatric migraine.

Publication Types: 
    Review

PMID: 17894928 [PubMed - indexed for MEDLINE]

559: Curr Pain Headache Rep. 2007 Oct;11(5):343-51.

Sensitization, glutamate, and the link between migraine and fibromyalgia.

Sarchielli P, Di Filippo M, Nardi K, Calabresi P.

Neurologic Clinic, Department of Medical and Surgical Specialties and Public
Health, University of Perugia, Ospedale Santa Maria della Misericordia, Via Santa
Andrea delle Fratte, San Sisto, 06158 Perugia, Italy. neuro.pg@tiscalinet.it

Recent advances have shed insight on the pathophysiologic mechanisms of
fibromyalgia and migraine, especially in the chronic form. A growing body of
evidence supports the involvement of peripheral and central sensitization
disturbances of pain-related processes underlying both disorders. They involve
increased glutamate transmission through interaction with its ionotropic and
metabotropic receptors. Few studies supporting the implication of this excitatory
amino acid in chronic migraine and primary fibromyalgia demonstrated increased
levels of glutamate in the cerebrospinal fluid of affected patients. These
findings have implications for future therapies directed against glutamate
receptors (in particular, N-methyl-D-aspartate receptors). Limited clinical
experience in this regard, although promising, does not exclude additional
mechanisms contributing to the maintenance of pain, which can be the target of
therapeutic approaches in both disorders.

Publication Types: 
    Review

PMID: 17894924 [PubMed - indexed for MEDLINE]

560: J Child Neurol. 2007 Sep;22(9):1117-20.

Migraine in Thai children: prevalence in junior high school students.

Visudtibhan A, Siripornpanich V, Khongkhatithum C, Chiemchanya S, Sirijunpen S,
Ruangkanchanasetr S, Visudhiphan P.

Department of Pediatrics, Faculty of Medicine, Ramathibodi Hospital, Mahidol
University, Bangkok, Thailand. raavs@mahidol.ac.th

A cross-sectional study to determine the prevalence of migraine in seventh grade 
Thai students in 4 junior high schools in Bangkok, Thailand, according to the
diagnostic criteria of the second edition of the Classification of Headache of
the International Headache Society was conducted in July 2004. The study included
a screening self-administered questionnaire and face-to-face interview with
physical examination. The diagnosis of migraine was made and confirmed by 2
pediatric neurologists. All of 1789 students in participating schools completed
the questionnaire. After 2 interviews, 248 students (13.8%) were diagnosed with
migraine. The prevalence in girls was higher than that in boys (16.2% vs 11.7%). 
Migraine as having aura was diagnosed in 34 students (13.7%). One student had
sporadic hemiplegic migraine. Among 248 children, 176 (71%) reported the duration
of headache between 1 and 2 hours. The leading precipitating factor of migraine
was the stress related to daily school activities (17.7%). There were 32 students
(12.9%) with frequent and intense headache who were referred to their primary
physicians for further management. This study had disclosed a high prevalence of 
migraine in seventh grade Thai students in Bangkok City and reflected the
existing burden of this illness in Thai students.

PMID: 17890411 [PubMed - indexed for MEDLINE]

561: Cephalalgia. 2007 Nov;27(11):1219-25. Epub 2007 Sep 21.

Medication overuse headache: clinical features predicting treatment outcome at
1-year follow-up.

Zidverc-Trajkovic J, Pekmezovic T, Jovanovic Z, Pavlovic A, Mijajlovic M,
Radojicic A, Sternic N.

Headache Centre, Institute of Neurology, Clinical Centre of Serbia, Belgrade,
Serbia. jzidverc@gmail.com

We present a prospective study of 240 patients with medication overuse headache
(MOH) treated with drug withdrawal and prophylactic medications. At 1-year
follow-up, 137 (57.1%) patients were without chronic headache and without
medication overuse, eight (3.3%) patients did not improve after withdrawal and 95
(39.6%) relapsed developing recurrent overuse. Age at time of MOH diagnosis,
regular use of benzodiazepines, frequency and Migraine Disability Assessment
(MIDAS) score of chronic headache, age at onset of primary headache, frequency
and MIDAS score of primary headache, ergotamine compound overuse and daily drug
intake were significantly different between successfully and unsuccessfully
treated patients. Multivariate analysis determined the frequency of primary
headache disorder, ergotamine overuse and disability of chronic headache
estimated by MIDAS as independent predictors of treatment efficacy at 1-year
follow-up.

Publication Types: 
    Clinical Trial

PMID: 17888081 [PubMed - indexed for MEDLINE]

562: Cephalalgia. 2007 Nov;27(11):1255-60. Epub 2007 Sep 21.

Comorbidity of migraine and restless legs syndrome--a case-control study.

Rhode AM, Hösing VG, Happe S, Biehl K, Young P, Evers S.

Department of Neurology, Klinikum Bremen-Ost and University of Göttingen,
Göttingen, Germany.

In order to evaluate a possible association between migraine and restless legs
syndrome (RLS), we performed a case-control study on the comorbidity of RLS and
migraine. Patients with migraine (n = 411) and 411 sex- and age-matched control
subjects were included. Migraine was diagnosed according to International
Headache Society criteria, RLS according to the criteria of the International
Restless Legs Syndrome Study Group. Furthermore, all patients had to fill out a
self-assessment test performance on depression [Beck's Depression Inventory
(BDI)]. RLS frequency was significantly higher in migraine patients than in
control subjects (17.3% vs. 5.6%, P < 0.001; odds ratio 3.5, confidence interval 
2.2, 5.8). In our sample, there was no significant association between migraine
and depression as defined by the BDI score (9.6% in migraine vs. 4.0% in control 
subjects, P = 0.190). Depression was, however, not significantly more frequent in
migraine patients with RLS (13.6%) than in migraine patients without RLS (8.7%). 
In addition, migraine patients with RLS had a significantly higher BDI score. RLS
features did not differ significantly between migraine patients with RLS and
control subjects with RLS. There is an association between RLS and migraine and, 
in addition, a co-association with depression. The underlying mechanism, however,
remains undetermined and might be related to a dysfunction of dopaminergic
metabolism in migraine.

PMID: 17888079 [PubMed - indexed for MEDLINE]

563: Cephalalgia. 2007 Dec;27(12):1386-97. Epub 2007 Sep 19.

The GRIM2005 study of migraine consultation in France I. Determinants of
consultation for migraine headache in France.

Lantéri-Minet M, Massiou H, Nachit-Ouinekh F, Lucas C, Pradalier A, Radat F,
Mercier F, El Hasnaoui A.

Hôpital Pasteur, Nice, France.

The aim of this study was to evaluate determinants of consultation for migraine
in a representative sample of the French general adult population. We interviewed
10,032 subjects, of whom 1534 fulfilled the International Headache Society
diagnostic criteria for migraine. These were categorized into migraine, probable 
migraine and chronic migraine. Information was collected on consultation
experience; 436 subjects (28.4%) had never consulted for headache, 473 (30.8%)
were in active consultation and 625 (40.7%) had previously consulted but lapsed. 
Subjects with chronic migraine showed the highest active consultation rates
(51.8%). All subjects completed rating instruments for headache [Headache Impact 
Test (HIT)-6], psychiatric (Hospital Anxiety and Depression Scale scale) and
psychological [Brief Illness Perception Questionnaire (BIPQ), Brief COPE
Inventory and Coping Strategy Questionnaire] variables. The strongest
determinants of active consultation were BIPQ scores, HIT-6 scores and migraine
type. Consultation was associated with maladaptive coping strategies (social
support, emotional expression and acceptance). Determinants of remaining in
consultation were catastrophizing coping scores and previous consultation
experience.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17888013 [PubMed - indexed for MEDLINE]

564: Headache. 2007 Sep;47(8):1251-8.

From migraine to chronic daily headache: the biological basis of headache
transformation.

Meng ID, Cao L.

Department of Physiology, University of New England College of Osteopathic
Medicine, Biddeford, ME 04005, USA.

Migraine headache carries the potential of transforming into chronic daily
headache (CDH) over a period of time. Although several risk factors for migraine 
progression to CDH have been identified, the biological basis of this
transformation is unknown. In this review, the consequences of stressful life
events and medication overuse, 2 risk factors associated with the development of 
CDH, on brain processes involved in headache are examined. The extensive overlap 
in both neural circuitry and cellular events that occur with stress, medication
overuse, and migraine provide insight into potential mechanisms that may lead to 
CDH. Particular attention is devoted to the effect of stress and medication
overuse on peripheral and central neuroimmune interactions that can facilitate
pain signaling. These interactions include the degranulation of mast cells in the
dura, causing the sensitization of primary afferent neurons, as well as the
activation of glial cells in the brain that can lead to central sensitization. It
is hypothesized that the biological processes involved in migraine headache are
directly impacted by stress, medication overuse, and other risk factors,
resulting in a reduced threshold for induction of headache and transformation of 
episodic migraine to CDH.

Publication Types: 
    Research Support, N.I.H., Extramural
    Review

PMID: 17883547 [PubMed - indexed for MEDLINE]

565: Headache. 2007 Sep;47(8):1219-23.

Migraine and cephalic cutaneous allodynia in pediatric patients.

Eidlitz-Markus T, Shuper A, Gorali O, Zeharia A.

Day Hospitalization Unit, Schneider Children's Medical Center of Israel, Petah
Tiqwa, Israel.

Allodynia is a central sensitization state characterized by a perception of pain 
to normally nonpainful stimuli. The objective of this study was to determine the 
frequency of allodynia in children with migraine and to identify clinical
features specific to this patient group.

PMID: 17883532 [PubMed - indexed for MEDLINE]

566: Headache. 2007 Sep;47(8):1210-2.

Familial hemiplegic migraine: permanent attack-related neurologic deficits.

Dodick D, Roarke M.

Mayo Clinic, Scottsdale-Neurology, Scottsdale, AZ 85259, USA.

Hemiplegic migraine (HM) is characterized by motor weakness and at least one
other aura symptom or sign that is fully reversible within 24 hours. While
prolonged neurological impairment lasting weeks has been observed, persistent
attack-related neurological deficits have not been described. This case
illustrates the potential for permanent neurological deficits to occur as a
sequelae of HM in the absence of infarction, and highlights potentially important
pathophysiological and treatment implications.

Publication Types: 
    Case Reports

PMID: 17883529 [PubMed - indexed for MEDLINE]

567: Headache. 2007 Sep;47(8):1200-3.

Efficacy of duloxetine as a migraine preventive medication: possible predictors
of response in a retrospective chart review.

Taylor AP, Adelman JU, Freeman MC.

Headache Wellness Center, Greensboro, NC 27405, USA.

OBJECTIVE: This case series is a retrospective chart analysis conducted to
evaluate the efficacy of duloxetine as a migraine preventive medication and to
suggest possible predictors of response. BACKGROUND: Duloxetine, a relatively new
selective serotonin and norepinephrine reuptake inhibitor, is FDA-approved for
treatment of depression and diabetic peripheral neuropathic pain. The efficacy of
duloxetine as a headache preventive medication is currently unknown. METHOD: A
retrospective chart review was performed using the electronic medical records of 
Headache Wellness Center, a headache specialty practice in Greensboro, North
Carolina. From January 2004 to December 2006, 65 patients were identified who
were prescribed duloxetine for migraine prevention for at least 2 months. Doses
ranged from 30 mg qd to 90 mg qd. Frequency, severity, and impact of migraine
disability were measured at baseline and compared to values obtained after 2
months of treatment. RESULTS: The total patient sample demonstrated a reduction
in mean monthly headache frequency from 19.40 (SD=7.1) to 15.70 (SD=8.2) (P=
.01). The 50% responder rate was 22%. In subset analysis, individuals with
abnormal baseline Zung anxiety scores demonstrated a greater reduction in mean
monthly headache frequency (4.28, P= .03) and a greater responder rate (25%) than
those in the total patient sample. Non-statistically significant trends were
observed in those patients with abnormal baseline Zung Depression scores
exhibiting a less robust mean monthly migraine reduction (2.75, P= .18) than
those with normal baseline depression scores (3.42, P= .07). CONCLUSIONS:
Duloxetine demonstrates minimal effectiveness as a headache preventive
medication. An interesting trend suggests that the presence of anxiety may be a
positive predictor in treatment with duloxetine.

Publication Types: 
    Clinical Trial

PMID: 17883526 [PubMed - indexed for MEDLINE]

568: Headache. 2007 Sep;47(8):1195-9.

Association between migraine and the G1246A polymorphism in the hypocretin
receptor 2 gene.

Schürks M, Limmroth V, Geissler I, Tessmann G, Savidou I, Engelbergs J, Kurth T, 
Diener HC, Rosskopf D.

Department of Neurology, University of Duisberg-Essen, Essen, Germany.

BACKGROUND: The hypocretin receptor 2 (HCRTR2) G1246A polymorphism has been
associated with the risk for cluster headache. Since the hypothalamic
hypocretin/orexin system projects throughout the nervous system and affects
multiple vegetative functions including generation of rhythmicity, vasomotion,
autonomic symptoms as well as modulation of nociception, it may also be linked
with migraine. OBJECTIVE: We thus sought to evaluate whether the HCRTR2 G1246A
polymorphism is associated with the risk for migraine. METHODS: We prospectively 
established a cohort of 146 unrelated patients with migraine. The control group
consisted of 279 healthy volunteers. We genotyped patients and controls for the
HCRTR2 G1246A polymorphism and examined an association with presence or absence
of migraine. RESULTS: Genotype and allele frequencies were not significantly
different between migraine patients and controls (genotype distribution: chi(2)= 
4.13, 2 df, P= .13; allele distribution: chi(2)= 0.9, 1 df, P= .34). CONCLUSION: 
Our study does not support a major contribution of the HCRTR2 G1246A polymorphism
to the pathogenesis of migraine in contrast to its effects in cluster headache.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17883525 [PubMed - indexed for MEDLINE]

569: Headache. 2007 Sep;47(8):1184-8.

Insomnia and circadian variation of attacks in episodic migraine.

Alstadhaug K, Salvesen R, Bekkelund S.

Department of Neurology, Nordlandssykehuset, Bodø, Norway.

OBJECTIVES: To assess the influence of insomnia on the 24-hour temporal pattern
of migraine. BACKGROUND: Migraine attacks have been reported to occur in a
harmonic (monophasic) or a biphasic 24-hour cyclic manner, and in some studies to
have preponderance in the morning hours. The influence of insomnia on the
circadian pattern has not been evaluated. METHOD: Based on a previous study of
the circadian variation in migraine, an explorative data analysis was made to
compare the circadian pattern of insomnia-related migraine attacks to the
circadian pattern of migraine attacks not related to insomnia. If the patients
reported difficulties in falling asleep and/or maintaining sleep the night prior 
to the reported attack or the night the attack occurred, the attack was defined
as insomnia-related. Relapses were not counted as distinctive attacks. RESULTS:
Sixty-eight female migraineurs (mean +/- SD age: 35.5 +/- 7.0) prospectively
recorded 1869 migraine attacks. Five hundred-and-thirty-three attacks (29%) were 
insomnia-related. Insomnia-related attacks had a biphasic temporal pattern with
one peak in the morning hours and one peak after noon. They had a preponderance
in the morning hours compared to attacks not related to insomnia (t= 3.27, df =
62, P= .002). In 79% of attacks insomnia was experienced prior to the headache.
CONCLUSIONS: Episodic morning migraine is associated with insomnia. The cause and
consequences of insomnia in migraine is not clarified, but sleep obviously
protects against attacks rather than provokes them.

PMID: 17883523 [PubMed - indexed for MEDLINE]

570: Headache. 2007 Sep;47(8):1178-83.

Behavioral sleep modification may revert transformed migraine to episodic
migraine.

Calhoun AH, Ford S.

Department of Neurology, University of North Carolina, Chapel Hill, NC 27599,
USA.

BACKGROUND: Sleep problems have been linked with headaches for more than a
century, but whether the headaches are the cause or the result of the disrupted
sleep is unknown. OBJECTIVES: We previously reported that nonrestorative sleep
and poor sleep habits are almost universal in a referral population of women with
transformed migraine (TM). Since cognitive behavioral therapy is effective in
improving sleep quality in individuals with poor sleep hygiene, we designed a
randomized, placebo-controlled study to assess the impact of such treatment on
TM. We hypothesized that behavioral sleep modification (BSM) would be associated 
with improvement in headache frequency and intensity and with reversion to
episodic migraine. METHODS: Subjects were 43 women with TM referred to an
academic headache center. After obtaining informed consent, patients were
randomized to receive either behavioral sleep instructions or placebo behavioral 
instructions in addition to usual medical care. Subjects recorded headaches in
standardized diaries. The first postintervention visit was scheduled at 6 weeks. 
At that visit, the blind was broken and all subjects received BSM instructions. A
final visit was scheduled 6 weeks later. RESULTS: Compared to the placebo
behavioral group, the BSM group reported statistically significant reduction in
headache frequency [F (1, 33 = 12.42, P=.001)] and headache intensity [F(1, 33 = 
14.39, P= .01)]. They were more likely to revert to episodic migraine chi2 (2, n 
= 43) = 7.06, P= .029. No member of the control group reverted to episodic
migraine by the first postintervention visit. By the final visit, 48.5% of those 
who had received BSM instructions had reverted to episodic migraine. CONCLUSIONS:
In this pilot study of women with TM, we found that a targeted behavioral sleep
invention was associated with improvement in headache frequency, headache index, 
and with reversion to episodic migraine.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 17883522 [PubMed - indexed for MEDLINE]

571: Headache. 2007 Sep;47(8):1169-77.

Meta-analysis examining the efficacy and safety of almotriptan in the acute
treatment of migraine.

Chen LC, Ashcroft DM.

School of Pharmacy and Pharmaceutical Sciences, University of Manchester, Oxford 
Road, Manchester M13 9PT, UK.

OBJECTIVE: To evaluate the comparative efficacy and safety of oral almotriptan in
treating acute migraine attacks. BACKGROUND: Almotriptan is an oral selective
sertonin(1B/1D) receptor agonist (triptan) with a high bioavailability and short 
half-life, developed for the treatment of migraine. In recent years, a number of 
randomized controlled trials have been published examining the efficacy and
safety of almotriptan in the acute treatment of migraine. METHODS: Systematic
review and meta-analysis of randomized controlled trials (RCTs) using a
random-effects model to estimate the pooled rate ratios (RRs) and 95% confidence 
intervals (95%CI) for the proportions of patients achieving headache relief and
pain-free responses at 1 or 2 hours post-dose, sustained pain-free response at
2-24 hours post-dose, and safety outcomes (proportions of patients experiencing
any adverse events, dizziness, somnolence, asthenia, and chest tightness)
comparing almotriptan against placebo, other triptans, and different dosages of
almotriptan. Absolute rate differences (ARDs) for 2-hour headache relief, pain
free, and sustained pain free responses between almotriptan and placebo were also
calculated. RESULTS: Eight RCTs involving 4995 patients were included in the
analysis. Almotriptan 12.5 mg was significantly more effective than placebo for
all efficacy outcomes (RRs ranged from 1.47 to 2.15; ARDs ranged from 0.01 to
0.28) and there were no significant differences in any of the safety outcomes.
There were also no significant differences in efficacy outcomes comparing
almotriptan 12.5 mg against sumatriptan 100 mg and zolmitriptan 2.5 mg, but
almotriptan 12.5 mg was associated with significantly fewer adverse events than
sumatriptan 100 mg (RR: 0.39, 95%CI: 0.23, 0.67). However, there was no
significant difference between almotriptan and sumatriptan in terms of clinically
important adverse effects, such as dizziness, somnolence, asthenia, and chest
tightness. Almotriptan 12.5 mg was significantly less effective than almotriptan 
25 mg for 1-hour pain-free response (RR: 0.45, 95%CI: 0.21, 0.95), but associated
with significantly fewer patients experiencing adverse events (RR: 0.61, 95%CI:
0.41, 0.91) than almotriptan 25 mg. CONCLUSIONS: Almotriptan 12.5 mg is an
effective treatment for acute attacks of migraine, in particular, it has been
found to be as effective as sumatriptan 100 mg and zolmitriptan 2.5 mg. The risk 
of adverse events associated with almotriptan 12.5 mg was similar to placebo and 
significantly lower than sumatriptan 100 mg. Further research is required to
assess the comparative efficacy of almotriptan against other triptans.

Publication Types: 
    Meta-Analysis

PMID: 17883521 [PubMed - indexed for MEDLINE]

572: Headache. 2007 Sep;47(8):1152-68.

Comment in:
    Headache. 2008 Oct;48(9):1379-80.

Marketed oral triptans in the acute treatment of migraine: a systematic review on
efficacy and tolerability.

Pascual J, Mateos V, Roig C, Sanchez-Del-Rio M, Jiménez D.

University Hospital--Neurology, Salamanca, Spain.

BACKGROUND: In the current literature, there is neither a reported systematic
review comparing the efficacy of triptans at 30 minutes and 1 hour after the
migraine treatment, nor data related to efficacy of new marketed triptans.
OBJECTIVE: The main objective of this analysis was to compare the efficacy and
tolerability of currently marketed oral, non-reencapsulated triptan formulations 
vs placebo in the treatment of moderate-to-severe migraine attacks. METHODS: A
systematic review of double-blind, randomized clinical trials reporting data
after a single migraine attack was conducted. Efficacy results are shown using
relative risk ratios with 95% confidence intervals. A sensitivity analysis was
also conducted. RESULTS: After reviewing 221 publications, 38 studies were
included. All marketed triptans provided significant relief and/or absence of
pain at 2 hours, and relief at 1 hour when compared with placebo. After 30
minutes, fast-dissolving sumatriptan 50 and 100 mg, sumatriptan 50 mg, and
rizatriptan 10 mg showed significant relief when compared to placebo, whereas the
fast-dissolving formulation of sumatriptan 100 mg was the only oral triptan that 
was superior to placebo in meeting the pain-free endpoint. On the other hand,
fast-dissolving sumatriptan 50 and 100 mg and eletriptan 40 mg showed a lower
rate of recurrence than placebo, whereas rizatriptan 10 mg was the only triptan
with a recurrence rate greater than that of placebo. Adverse events associated
with treatment with tablet formulations of sumatriptan and zolmitriptan were
significantly more frequent than those of the placebo group. The inclusion of
trials with reencapsulated triptans in the analysis introduced minor specific
changes in these results. CONCLUSION: This analysis updates the comparative data 
available for the 7 currently marketed oral triptans and clearly demonstrates
their efficacy when compared to placebo, even with stricter endpoints, such as
efficacy at 30 minutes. No triptan exhibited better tolerability than placebo.
Results are diverse, depending on the triptan, which probably is a reflection of 
heterogeneous pharmacokinetics.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 17883520 [PubMed - indexed for MEDLINE]

573: Headache. 2007 Sep;47(8):1144-51.

Patient preference for triptan formulations: a prospective study with
zolmitriptan.

Dowson A, Bundy M, Salt R, Kilminster S.

King's Headache Service, King's College Hospital, London, UK.

OBJECTIVES: To investigate patterns of patient preference for 3 formulations of
zolmitriptan, in a primary care study utilizing a naturalistic longitudinal
design. BACKGROUND: Although differences in efficacy between individual triptans 
tend to be small, migraine patients show clear preferences for individual
triptans and formulations. The groups of patients suitable for the different
triptan formulations, and the reasons underlying individual preferences, are not 
clearly understood. METHODS: Migraine patients entered a prospective, randomized,
open, crossover, longitudinal design study, with patients receiving zolmitriptan 
formulations according to UK prescribing recommendations. Patients naïve to
zolmitriptan received zolmitriptan 2.5-mg film-coated tablets or 2.5-mg Orally
Disintegrating Tablets (ODT) for 1 month, before being crossed over to receive
the alternative formulation for Month 2. All patients then received zolmitriptan 
nasal spray 5 mg for Month 3. Patients could then choose the formulation(s) of
their choice for a further 7 months. Patients recorded their preferences for
individual formulations, the reasons for their preferences, and also the
headache-related disability (measured by the Migraine Disability Assessment
[MIDAS] score) at clinic visits. Primary endpoints were the individual
preferences and changes in MIDAS scores. Adverse events were also recorded.
RESULTS: Forty-eight patients took part in the study. At baseline, most patients 
expressed a preference for conventional tablets. After 4 months, 46.9% of
patients preferred zolmitriptan ODT, 43.8% zolmitriptan nasal spray, and 6.3% the
conventional tablet. The most common reasons given for preferring conventional
tablets were personal reasons: for zolmitriptan ODT, convenience and, to a lesser
extent, speed of onset: for zolmitriptan nasal spray, speed of onset, and overall
efficacy. MIDAS scores decreased significantly following treatment with
zolmitriptan. Zolmitriptan was well tolerated. CONCLUSIONS: Patient experience of
newer zolmitriptan formulations influenced a change in preference away from
conventional tablets. Speed and efficacy were the key drivers of preference for
zolmitriptan nasal spray, while convenience mostly drove preference for the ODT
formulation. Open, longitudinal, naturalistic studies may, allowing for biases,
sometimes be an appropriate way of conducting migraine studies in primary care.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 17883519 [PubMed - indexed for MEDLINE]

574: Headache. 2007 Sep;47(8):1134-43.

ED treatment of migraine headache: factors influencing pharmacotherapeutic
choices.

Hurtado TR, Vinson DR, Vandenberg JT.

121st General Hospital, US Army--Emergency Medicine, HHC 121st General Hospital, 
Box 662, APO AP 96205, USA.

STUDY OBJECTIVE: To evaluate the factors that influence clinicians' choices of
parenteral medications in the emergency department (ED) management of migraine
headache. BACKGROUND: Migraine headache is a common problem in the United States.
Many migraineurs require periodic ED management. Though a large variety of
parenteral medications are used by ED clinicians in the treatment of migraine,
little research has been directed to the reasons why providers use the
medications they do. METHODS: This study used a self-administered questionnaire
for providers from 3 geographically distinct EDs to evaluate their
pharmacotherapeutic preferences in the treatment of uncomplicated migraine based 
on a fictitious scenario. Factors influencing medication choices were rated on a 
5-point Likert scale and analyzed descriptively. Hypothetical practice patterns
from the questionnaires were compared with actual practice patterns from a prior 
study from the same institutions. RESULTS: Eighty-three percent of surveys were
returned, the majority from attending physicians (71%), as their initial
drugs-of-choice providers preferred dopaminergic antiemetics (93%) and parenteral
NSAIDs (22%). If initial therapy failed, opioids (40%) with nonspecific
antiemetics (24%) were preferred as second-line agents. Choice of therapy was
influenced (in descending order) by medication availability and its antimigraine 
properties, the providers' training, current departmental practice patterns, and 
national practice guideline recommendations. Opioid use was influenced by
patients' failure to respond to ED and outpatient alternatives and the presence
of contraindications/intolerances to non-opioids. When these results were
compared to a prior study of actual practice patterns, a range of discordance was
observed, which varied significantly by institution. CONCLUSION: Emergency
clinicians report that a variety of factors influence their parenteral
pharmacotherapy in the management of patients with migraine headache. The
comparison of hypothetical practice patterns with actual practice patterns
reveals a range of institution-specific discordance. There is discordance between
providers' responses to a fictitious scenario and their previously recorded
practice patterns with regional variation.

Publication Types: 
    Evaluation Studies

PMID: 17883518 [PubMed - indexed for MEDLINE]

575: Headache. 2007 Sep;47(8):1118-24.

Prognostic significance of personality profiles in patients with chronic
migraine.

Luconi R, Bartolini M, Taffi R, Vignini A, Mazzanti L, Provinciali L, Silvestrini
M.

Department of Neuroscience, Polytechnic University of Marche, Ancona, Italy.

BACKGROUND AND OBJECTIVE: The aim of this study was to assess whether the
psychological profile may have prognostic significance in chronic migraine
patients. METHODS: The Minnesota Multiphasic Personality Inventory-2 was used for
the psychological assessment of patients with chronic migraine to explore
personality traits. Patients with psychiatric disease and medication overuse were
excluded. One hundred and two patients completed the study. Migraine-related
disability was measured using the Migraine Disability Assessment questionnaire at
baseline (T(0)) and again after 2 years (T(1)), during which patients received
prophylactic treatment for migraine. At T(1) patients were classified into those 
exhibiting significant improvement (group 1: scores reduced by at least 50%) and 
those with unsatisfactory changes in headache-related disability (group 2: scores
reduced by less than 50%). RESULTS: At T(1) 49 patients were in group 1 and 53 in
group 2; at T(0), group 1 patients had significantly lower Minnesota Multiphasic 
Personality Inventory-2 scores in the neurotic (hypochondriasis: P < .01;
depression: P < .001; hysteria: P < .01) and schizophrenia (P < .05) scales. None
of the other variables studied, ie, age, sex, age at migraine onset, number of
years from chronic migraine onset, T(0) Migraine Disability Assessment score,
T(0) headache frequency, severity and temporal pattern (continuous vs
intermittent) differed significantly between the groups. CONCLUSIONS: Findings
suggest that psychological factors can influence the clinical course of chronic
migraine and that psychological evaluation with Minnesota Multiphasic Personality
Inventory-2 may be a reliable approach to obtain prognostic data and information 
for therapy planning in patients with chronic migraine.

PMID: 17883516 [PubMed - indexed for MEDLINE]

576: Eur J Neurol. 2007 Oct;14(10):1079-84.

Subcutaneous histamine versus sodium valproate in migraine prophylaxis: a
randomized, controlled, double-blind study.

Millán-Guerrero RO, Isais-Millán R, Barreto-Vizcaíno S, Rivera-Castaño L,
Garcia-Solorzano A, López-Blanca C, Membrila-Maldonado M, Muñoz-Solis R.

Department of Neurology, Unidad de Investigación Médica en Epidemiología Clínica,
Hospital General de Zona UMF No 1 IMSS, Colima, México.

Histamine has a selective affinity for H3-receptors and it may specifically
inhibit the neurogenic edema response involved in migraine pathophysiology. The
objective of this study was to evaluate the therapeutic potential of subcutaneous
administration of histamine in migraine prophylaxis, compared with oral
administration of sodium valproate, in an open clinical trial. Ninety-two
patients with migraine were selected under criteria established by the
International Headache Society and enrolled in a 12-week double-blind controlled 
clinical trial to evaluate the efficacy of subcutaneous administration of
histamine (1-10 ng twice a week; n = 46) compared with oral administration of
sodium valproate (500 mg daily dose; n = 46). The variables studied were headache
intensity, frequency, duration, analgesic intake and migraine disability
assessment (MIDAS). Two-tailed Student's t- test was used to compare means and
the Mann-Whitney U and anova tests were used. The data collected during the 4th, 
8th and 12th weeks of treatment revealed that histamine caused a significantly
greater reduction (P < 0.001) in intensity and duration of migraine attacks as
well as in analgesic intake. No difference was detected in the frequency of
attacks or in MIDAS. The present study provides evidence of the superior efficacy
of histamine applied subcutaneously in migraine prophylaxis when compared with
sodium valproate taken orally. Subcutaneously applied histamine may represent a
novel and effective therapeutic alternative in resistant migraine patients.

Publication Types: 
    Comparative Study
    Randomized Controlled Trial

PMID: 17880560 [PubMed - indexed for MEDLINE]

577: Ann Pharmacother. 2007 Nov;41(11):1782-91. Epub 2007 Sep 18.

Efficacy of low-dose ibuprofen in acute migraine treatment: systematic review and
meta-analysis.

Suthisisang C, Poolsup N, Kittikulsuth W, Pudchakan P, Wiwatpanich P.

Department of Pharmacology, Faculty of Pharmacy, Mahidol University, Bangkok,
Thailand. pycst@mahidol.ac.th

BACKGROUND: Nonsteroidal antiinflammatory drugs such as aspirin and ibuprofen
have been shown to be effective in treating migraine. OBJECTIVE: To evaluate the 
efficacy of low-dose ibuprofen for treatment of acute migraine attack. METHODS:
Clinical trials were identified through electronic searches (MEDLINE, EMBASE, EBM
review, and the Cochrane Library) up to November 2006 and historical searches of 
relevant articles. Studies were included if they (1) were double-blind,
randomized, placebo-controlled trials that evaluated ibuprofen tablets in
moderate or severe migraine attacks in patients greater than 16 years of age, (2)
evaluated at least one migraine attack, and (3) reported headache relief,
pain-free, sustained pain-free, or relief of other migraine-associated symptoms
at 2 hours. The MeSH search terms used were migraine disorders, headache,
vascular headache, ibuprofen, adult, and clinical trial. This was followed by a
key word search using migraine, cephalalgia, and cephalgia as key words. The
reference lists of relevant articles were also scanned to identify possible
published trials. There was no language restriction. Two authors extracted data
independently. Disagreements were resolved through discussion. RESULTS: Ibuprofen
200 and 400 mg were more effective than placebo in reducing pain intensity and
eliminating pain (pain-free) within 2 hours in adults with moderate or severe
migraine attacks. For the 200 mg dose, the number needed to treat was 8 (95% CI 5
to 20) for headache relief and 13 (95% CI 8 to 50) for pain-free. The risk ratios
for headache relief and pain-free were 1.89 (95% CI 1.45 to 2.46; p < 0.0001) and
2.15 (95% CI 1.24 to 3.73; p = 0.0063), respectively, for ibuprofen 400 mg. The
24-hour sustained pain-free outcome with ibuprofen was no better than with
placebo. Ibuprofen 400 mg increased the chance of relief in photophobia and
phonophobia by 30% (95% CI 8 to 57; p < 0.01) and 49% (95% CI 23 to 81; p <
0.0001), respectively. CONCLUSIONS: The available evidence suggests that
ibuprofen 200 and 400 mg are effective in reducing headache intensity and
rendering patients pain-free at 2 hours. Photophobia and phonophobia improved
with 400 mg dosing. Due to the limited data and the shortcomings of the available
evidence, further studies are needed.

Publication Types: 
    Comparative Study
    Meta-Analysis
    Review

PMID: 17878396 [PubMed - indexed for MEDLINE]

578: Clin Genet. 2007 Dec;72(6):517-23. Epub 2007 Sep 18.

Amino acid changes in the amino terminus of the Na,K-adenosine triphosphatase
alpha-2 subunit associated to familial and sporadic hemiplegic migraine.

Tonelli A, Gallanti A, Bersano A, Cardin V, Ballabio E, Airoldi G, Redaelli F,
Candelise L, Bresolin N, Bassi MT.

IRCCS E. Medea, Laboratory of Molecular Biology, Bosisio Parini Lecco, Italy.

Familial hemiplegic migraine (FHM) is a rare subtype of migraine with aura
inherited with an autosomal dominant pattern. Here, we report the genetic
analysis of four families and one sporadic case with hemiplegic migraine (HM) in 
whom we searched for mutations in the three genes associated with the disease
CACNA1A, ATP1A2 and SCN1A. Two novel amino acid changes p.Arg65Trp and p.Tyr9Asn,
in the Na,K-adenosine triphosphatase (ATPase) alpha-2 subunit encoded by the
ATP1A2 gene, were found in one FHM family and in the sporadic case, respectively.
These mutations are peculiar for their location in the extreme N-terminus, an
uncommon mutation target in this protein. Low frequency of migraine attacks in
all our mutant patients with low complexity of the associated aura symptoms in
the sporadic case is also observed. Besides the two novel mutations, the data
here reported confirm the involvement of ATP1A2 gene in the sporadic form of HM, 
while the negative results on the other families tested for all genes known in HM
strengthen the hypothesis of the existence of at least another locus involved in 
FHM.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17877748 [PubMed - indexed for MEDLINE]

579: Int J Clin Pract. 2007 Oct;61(10):1677-85.

Patient satisfaction with eletriptan in the acute treatment of migraine in
primary care.

Nett RB, Tiseo PJ, Almas M, Sikes CR.

Texas Headache Associates, San Antonio, TX, USA.

OBJECTIVE: The efficacy of triptans for acute migraine has been well established 
in clinical trials but not in primary care, where they are most commonly
prescribed. The aim of this open-label study was to evaluate the effectiveness of
eletriptan 40 mg in primary care, using a patient-weighted satisfaction scale.
METHODS: Eligible patients met International Headache Society criteria for
migraine, with 1-6 attacks per month. Patients completed questionnaires at
screening and following a single eletriptan-treated attack. Treatment
satisfaction was evaluated using a six-item Medication Satisfaction Questionnaire
(MSQ). MSQ item scores were weighted, based on the important score ratings, to
yield individualised satisfaction scores. The primary end-point was the
difference in weighted satisfaction scores between the patient's previous
treatment and eletriptan 40 mg. Secondary end-points assessed quality of life
(QOL), functioning and efficacy of treatment. RESULTS: Of 590 patients screened, 
437 completed the study. Degree (95.2%), time (88.8%) and duration (83.8%) of
headache pain relief were rated as most important by patients. The mean (+/-SD)
total satisfaction score on the MSQ was higher for eletriptan than previous
therapy (2.2 +/- 3.0 vs. 0.6 +/- 2.4; p < 0.001). The high level of satisfaction 
with eletriptan vs. previous treatment reflects the improvements in QOL and
functioning observed, and the high headache and pain-free response rates.
CONCLUSIONS: Patient-weighted satisfaction with eletriptan 40 mg was higher than 
with previous treatment for all items. The use of patient-weighted importance
ratings of satisfaction is a promising approach for establishing effectiveness of
treatment in primary care.

Publication Types: 
    Multicenter Study
    Research Support, Non-U.S. Gov't

PMID: 17877653 [PubMed - indexed for MEDLINE]

580: Eur Rev Med Pharmacol Sci. 2007 Jul-Aug;11(4):245-8.

An overview on immune system and migraine.

Bruno PP, Carpino F, Carpino G, Zicari A.

Department of Experimental Medicine and Pathology, University La Sapienza, Rome, 
Italy.

The pathogenesis of migraine is still unclear, but much evidence led us
hypothesize that it can be associated with immune system modification, so that a 
role for cytokines has been suggested. Cytokines are important mediators of the
immune and inflammatory pathways and their receptors are widely express in
central nervous system (CNS) by all cell types, including neurons, indicating
that they can act on neuronal receptors. Cytokines are now considered to be the
pain mediators in neurovascular inflammation. Furthermore cytokines may be a
cause of the migraine pain: in fact an high levels of chemokines could stimulate 
the activation of trigeminal nerves, the release of vasoactive peptides or other 
biochemical mediators, such as nitric oxide, and then to cause inflammation. In
this scenario, many studies on humans have focused the attention on peripheral
and central levels of cytokines, but data obtained are highly controversial.
Since at the moment there is not a conclusive evidence of the role played by
cytokines in migraine, the authors present and comment the latest reports
regarding cytokine modification and the role of the immune system in migraine.

Publication Types: 
    Review

PMID: 17876959 [PubMed - indexed for MEDLINE]

581: Arq Neuropsiquiatr. 2007 Sep;65(3A):599-604.

Massaging over the greater occipital nerve reduces the intensity of migraine
attacks: evidence for inhibitory trigemino-cervical convergence mechanisms.

Piovesan EJ, Di Stani F, Kowacs PA, Mulinari RA, Radunz VH, Utiumi M, Muranka EB,
Giublin ML, Werneck LC.

Neurology Division, Internal Medicine Department, Hospital de Clínicas, Federal
University of Paraná, Rua General Carneiro 181, 80060-900 Curitiba, PR, Brazil.
piovesan@avalon.sul.com.br

Activation of the trigemino-cervical system constitutes one of the first steps in
the genesis of migraine. The objective of this study was to confirm the presence 
of trigemino-cervical convergence mechanisms and to establish whether such
mechanisms may also be of inhibitory origin. We describe a case of a 39-years-old
woman suffering from episodic migraine who showed a significant improvement in
her frontal headache during migraine attacks if the greater occipital nerve
territory was massaged after the appearance of static mechanical allodynia
(cortical sensitization). We review trigemino-cervical convergence and diffuse
nociceptive inhibitory control (DNIC) mechanisms and suggest that the convergence
mechanisms are not only excitatory but also inhibitory.

Publication Types: 
    Case Reports

PMID: 17876398 [PubMed - indexed for MEDLINE]

582: Arq Neuropsiquiatr. 2007 Sep;65(3A):596-8.

Botulinum toxin type A in refractory chronic migraine: an open-label trial.

Menezes C, Rodrigues B, Magalhães E, Melo A.

Division of Neurology and Epidemiology, Federal University of Bahia, Salvador,
BA, Brazil.

Botulinum toxin type A (BT-A) has been described as an important strategy to
various types of pain such as cervical dystonia, myofascial pain syndrome and
headache. Although BT-A efficacy has not been proven in tension type headache,
its use in migraine continues controversial. In this open trial, we evaluated the
efficacy of BT-A in refractory migraine. BT-A was injected in patients diagnosed 
with migraine who had previously used three classes of prophylactic drugs by at
least one year with no response. The most important improvement was observed
within 30 days, but pain intensity and frequency of headache had been decreased
until the end of three months of follow up. Side effects of BT-A were mild and
self limited. We conclude that BT-A seems to be a safe and effective treatment to
refractory migraine patients.

Publication Types: 
    Clinical Trial

PMID: 17876397 [PubMed - indexed for MEDLINE]

583: Headache. 2008 Mar;48(3):398-407. Epub 2007 Sep 12.

Traditional acupuncture in migraine: a controlled, randomized study.

Facco E, Liguori A, Petti F, Zanette G, Coluzzi F, De Nardin M, Mattia C.

University of Padua - Department of Medico-Surgical Specialties - Sect.
Dentistry, Padua, Italy.

OBJECTIVE: To check the effectiveness of a true acupuncture treatment according
to traditional Chinese medicine (TCM) in migraine without aura, comparing it to a
standard mock acupuncture protocol, an accurate mock acupuncture healing ritual, 
and untreated controls. BACKGROUND: Migraine prevalence is high and affects a
relevant rate of adults in the productive phase of their life. Acupuncture has
been increasingly advocated and used in Western countries for migraine treatment,
but the evidence of its effectiveness still remains weak. A large variability of 
treatments is present in published studies and no acupoint selection according to
TCM has been investigated so far; therefore, the low level of evidence of
acupuncture effectiveness might partly depend on inappropriate treatment. DESIGN 
AND METHODS: A prospective, randomized, controlled study was performed in 160
patients suffering from migraine without aura, assessed according to the ICD-10
classification. The patients were divided into the following 4 groups: (1) group 
TA, treated with true acupuncture (according to TCM) plus Rizatriptan; (2) group 
RMA, treated with ritualized mock acupuncture plus Rizatriptan; (3) group SMA,
treated with standard mock acupuncture plus Rizatriptan; (4) group R, without
prophylactic treatment with relief therapy only (Rizatriptan). The MIDAS
Questionnaire was administered before treatment (T0), at 3 (T1) and 6 months (T2)
from the beginning of treatment, and the MIDAS Index (MI) was calculated.
Rizatriptan intake was also checked in all groups of patients at T0, T1, and T2. 
Group TA and RMA were evaluated according to TCM as well; then, the former was
submitted to true acupuncture and the latter to mock acupuncture treatment
resembling the same as TA. The statistical analysis was conducted with factorial 
ANOVA and multiple tests with a Bonferroni adjustment. RESULTS: A total of 127
patients completed the study (33 dropouts): 32 belonged to group TA, 30 to group 
RMA, 31 to group SMA, and 34 to group R. Before treatment the MI (T(0)) was
moderate to severe with no significant intergroup differences. All groups
underwent a decrease of MI at T(1) and T(2), with a significant group difference 
at both T(1) and T(2) compared to T(0) (P < .0001). Only TA provided a
significant improvement at both T(1) and T(2) compared to R (P < .0001). RMA
underwent a transient improvement of MI at T(1). The Rizatriptan intake
paralleled the MI in all groups. CONCLUSIONS: TA was the only treatment able to
provide a steady outcome improvement in comparison to the use of only
Rizatriptan, while RMA showed a transient placebo effect at T1.

Publication Types: 
    Randomized Controlled Trial

PMID: 17868354 [PubMed - indexed for MEDLINE]

584: Headache. 2008 Mar;48(3):395-7. Epub 2007 Sep 12.

The use of questions to determine the presence of photophobia and phonophobia
during migraine.

Evans RW, Seifert T, Kailasam J, Mathew NT.

Baylor College of Medicine - Neurology, Houston, TX, USA.

OBJECTIVE: To investigate whether the use of more detailed close-ended questions 
as part of the routine headache history is helpful when patients initially deny
that they are sensitive to light and noise during migraine headaches. BACKGROUND:
According to the International Headache Society 2004 criteria, the diagnosis of
migraine requires the presence of at least one of the following during a
headache: (1) nausea and/or vomiting, (2) photophobia and phonophobia. Evans
anecdotally noted that many patients answer the question, "does light or noise
bother you during a headache," with a "no" when the answer is really "yes" if
they are asked more detailed close-ended questions. METHODS: Consecutive patients
fulfilling International Headache Society 2004 criteria for migraine or probable 
migraine presenting to a headache clinic and a neurology clinic were asked the
following questions: "does light bother you during a headache?" If "no," they
were then asked, "during a headache, would you prefer to be in bright sunlight or
in a dark room?""does noise bother you during a headache?" If "no," they were
then asked, "during a headache, would you prefer to be in a room with loud music 
or in a quiet room?" RESULTS: Eighty-five consecutive patients with migraine or
probable migraine were questioned, 71 females (83.5%) and 14 males (16.5%). There
was denial of light and sound sensitivity in 24% of patients with routine
questioning and then awareness of sensitivity in 93% with the further
questioning. A total of 7.1% of the patients were diagnosed with probable
migraine. However, if the additional questions were not asked, 8% more of the
patients with definite migraine would have been incorrectly diagnosed as probable
migraine. CONCLUSION: When patients initially deny light and noise sensitivity
during migraine headaches, additional questions should be asked to ensure that
their answer is accurate. Not asking the additional questions may result in the
over-diagnosis of probable migraine.

PMID: 17868350 [PubMed - indexed for MEDLINE]

585: Headache. 2007 Nov-Dec;47(10):1453-5. Epub 2007 Sep 12.

Migraine and topiramate induced dyspnea.

Delpirou-Nouh C, Gelisse P, Chanez P, Carlander B.

Department of Neurology, Hôpital Gui-de-Chauliac, Montpellier Cedex 5, France.

Topiramate is effective in migraine headache prophylaxis. Pulmonary symptoms are 
rarely described as adverse effects. We report the case of a 42-year-old woman
with migraine headaches who developed chronic shortness of breath while taking
topiramate. Our patient experienced hand paresthesiae at a dose of 25 mg daily,
and exercise induced dyspnea at doses above 50 mg daily; these symptoms worsened 
with increasing topiramate doses. Physical exam and chest x-ray were normal.
Blood gas revealed a metabolic acidosis. Symptoms resolved after discontinuation 
of topiramate. Topiramate induces a lowering of blood carbon dioxide, which is
usually asymptomatic. This is due to inhibition of carbonic anhydrase at the
proximal renal tubule resulting in impaired proximal bicarbonate reabsorption.
The decrease in CO(2) blood level facilitates the occurrence of metabolic
acidosis. To our knowledge, this is the first case report of topiramate-induced
dyspnea in a patient with migraine headaches.

Publication Types: 
    Case Reports

PMID: 17868349 [PubMed - indexed for MEDLINE]

586: Headache. 2007 Nov-Dec;47(10):1443-6. Epub 2007 Sep 12.

Gastric stasis occurs in spontaneous, visually induced, and interictal migraine.

Aurora S, Kori S, Barrodale P, Nelsen A, McDonald S.

Swedish Neuroscience Institute - Swedish Headache Center, Seattle, WA 98104, USA.

OBJECTIVE: To evaluate and compare gastric motility and emptying during
spontaneous migraine to previous observations from induced migraine. BACKGROUND: 
We have previously demonstrated a delay in gastric emptying both during the
interictal period and during an induced migraine. A limitation noted in these
studies was whether there are differences gastrointestinally during a visually
induced migraine compared to spontaneous migraines. To address this, 9 additional
studies have been performed to ascertain if there is a similar delay during
spontaneous migraine METHODS: Gastric scintigraphy using a standard meal was
performed in 3 subjects during 3 periods: spontaneous migraine, induced migraine,
and interictal period. RESULTS: On average, the time to half emptying was delayed
during spontaneous migraine (124 minutes), during induced migraine (182 minutes),
and during the interictal period migraine (243 minutes) compared to normative
values established at our center (112 minutes). On average, similar gastric
slowing was seen in all 3 groups when the percentage of nuclear material
remaining in the stomach at 2 hours was measured. CONCLUSIONS: This study
provides additional evidence of gastric stasis in migraineurs interictally during
induced and spontaneous migraine.

PMID: 17868348 [PubMed - indexed for MEDLINE]

587: Expert Rev Neurother. 2007 Sep;7(9):1145-55.

Management of medication-overuse headache.

Obermann M, Katsarava Z.

University of Duisburg-Essen, Department of Neurology, Hufelandstr. 55, 45122
Essen, Germany. mark.obermann@uni-due.de

Medication-overuse headache (MOH) has developed into the third most common type
of headache after tension-type headache and migraine. The prevalence reaches
approximately 1% of the world's population and shows an increasing trend. Many
important studies on MOH have been published in the last year, some of which
investigated the pathophysiology of headache chronicity, with others focusing on 
the evaluation of risk factors. The International Headache Society revised its
classification criteria on MOH. Several large population-based longitudinal
studies clearly demonstrated that overuse of any kind of acute headache
medication is the main risk factor leading to the development of chronic
headache. Management of MOH remains difficult; the only effective treatment
concept is consequent withdrawal therapy.

Publication Types: 
    Meta-Analysis
    Review

PMID: 17868013 [PubMed - indexed for MEDLINE]

588: Expert Rev Neurother. 2007 Sep;7(9):1121-34.

Role of acupuncture in the treatment of migraine.

Endres HG, Diener HC, Molsberger A.

Ruhr University Bochum, Department of Medical Informatics, Statistics &
Epidemiology, D-44801 Bochum, Germany. heinz.endres@ruhr-uni-bochum.de

Since the last Cochrane review of acupuncture and headache in 2001, which found
methodological and/or reporting shortcomings in the majority of the studies,
several large, randomized trials on the effectiveness of acupuncture as a
treatment for headache have been published. Following a brief overview of the
pathophysiology of migraine and possible action mechanisms of acupuncture, we
look at current studies on acupuncture and migraine and discuss the results. From
these results and our own studies on acupuncture and migraine, we conclude that a
6-week course of acupuncture is not inferior to a 6-month prophylactic drug
treatment, but that specific Chinese point selection, point stimulation and
needling depth are not as important as had been thought. The review suggests that
acupuncture should be integrated into existing migraine therapy protocols.

Publication Types: 
    Meta-Analysis
    Review

PMID: 17868011 [PubMed - indexed for MEDLINE]

589: Expert Rev Neurother. 2007 Sep;7(9):1105-20.

Menstrual migraine: clinical and therapeutical aspects.

Allais G, Castagnoli Gabellari I, De Lorenzo C, Mana O, Benedetto C.

University of Turin, Women's Headache Center, Department of Gynecology &
Obstetrics, Via Ventimiglia 3, I-10126 Turin, Italy. gb.allais@tiscali.it

Estrogens fluctuations, particularly their premenstrual fall, are currently
regarded as the main triggers of menstrual migraine (MM). MM presents in two
clinical forms: pure MM, where attacks are confined to the perimenstrual period
(PMP), and menstrually related migraine, where attacks always occur during, but
are not confined to, the PMP. MM episodes are usually longer, more intense, more 
disabling and more refractory than nonmenstrual attacks. Acute management of MM
should initially be abortive and primarily sought with triptans. If this fails,
short-term perimenstrual prophylaxis with NSAIDs, coxibs, triptans or ergotamine 
derivatives can be considered. Hormone manipulations, mainly application of
percutaneous estradiol gel in PMP or administration of oral contraceptives in
extended cycles, constitute an alternative approach for nonresponders.

Publication Types: 
    Review

PMID: 17868010 [PubMed - indexed for MEDLINE]

590: Expert Rev Neurother. 2007 Sep;7(9):1097-104.

Associations between migraine and cardiovascular disease.

Kurth T.

Division of Aging, Brigham & Women's Hospital, 1620 Tremont Street, 3rd floor,
Boston, MA 02120-1613, USA. tkurth@rics.bwh.harvard.edu

Migraine is a common chronic, intermittent headache disorder that in some
patients is accompanied by neurological symptoms, particularly visual symptoms,
known as migraine aura. Several population-based studies have linked migraine,
and particularly migraine with aura, with increased risk of ischemic stroke.
Recent prospective data suggest an association between migraine with aura and any
ischemic vascular events, including coronary heart disease. The precise
biological mechanism by which migraine with aura may increase the risk of
vascular events is currently unknown and likely complex. Potential mechanisms
involve shared risk factors, inter-relationships between migraine and vascular
pathologies, migraine treatments, as well as genetic components. This review aims
to summarize the epidemiologic evidence linking migraine with ischemic vascular
events, discuss potential mechanisms and to outline potential consequences.

Publication Types: 
    Meta-Analysis
    Review

PMID: 17868009 [PubMed - indexed for MEDLINE]

591: J Paediatr Child Health. 2008 Jan;44(1-2):3-9. Epub 2007 Sep 14.

Acute treatment of paediatric migraine: a meta-analysis of efficacy.

Silver S, Gano D, Gerretsen P.

Michael G. DeGroote School of Medicine, McMaster University, Hamilton, Ontario,
Canada.

AIM: To undertake a meta-analysis of all randomised controlled trials (RCTs) on
the acute pharmacologic treatment of children and adolescents with migraine
headache. METHODS: In total, 139 abstracts of clinical trials specific to the
acute treatment of paediatric migraine were appraised. Inclusion criteria
required clinical trials to be randomised, blinded, placebo-controlled studies
with comparable endpoints. Non- English language publications were excluded. 11
clinical trials qualified for inclusion in the final meta-analysis. Two endpoints
were analysed: the proportion of patients with (1) headache relief, and (2)
complete pain relief, 2 h post-treatment. RESULTS: The following medications were
included in the analysis: acetaminophen (n = 1), ibuprofen (n = 2), sumatriptan
(n = 5), zolmitriptan (n = 1), rizatriptan (n = 2) and dihydroergotamine (n = 1).
Results are expressed as a relative benefit (RB) conferred over placebo and the
number needed to treat (NNT). Only ibuprofen and sumatriptan provided a
statistically significant relative efficacy in comparison with placebo. Two hours
post-treatment, ibuprofen was associated with an RB 1.50 (95% CI 1.15-1.95) in
the generation of headache relief (NNT 2.4) and RB 1.92 (95% CI 1.28-2.86) in the
production of complete pain relief (NNT 4.9). Sumatriptan rendered an RB 1.26
(95% CI 1.13-1.41) in headache relief (NNT 7.4) and an RB 1.56 (95% CI 1.26-1.93)
in the production of complete pain relief (NNT 6.9). CONCLUSION: Despite the
pharmacological options for the management of acute migraine, few RCTs in the
paediatric population exist. Composite data demonstrate that only ibuprofen and
sumatriptan are significantly more effective than placebo in the generation of
headache relief in children and adolescents.

Publication Types: 
    Meta-Analysis
    Review

PMID: 17854415 [PubMed - indexed for MEDLINE]

592: J Pharm Sci. 2008 Jun;97(6):2102-9.

Sumatriptan succinate transdermal delivery systems for the treatment of migraine.

Balaguer-Fernández C, Femenía-Font A, Del Rio-Sancho S, Merino V,
López-Castellano A.

Departamento de Fisiología, Farmacología y Toxicología, Facultad de Ciencias
Experimentales y de la Salud, Universidad CEU Cardenal Herrera, 46113 Moncada,
Spain.

We have successfully obtained sumatriptan transdermal systems with different
polymer compositions: methyl cellulose (MC), polyvinyl pyrrolidone (PVP) and a
polyvinyl pyrrolidone (PVP)-polyvinyl alcohol (PVA) mixture. The systems
contained 1,2-propylenglycol (MC) or sorbitol as a plasticizer (PVP and PVP-PVA),
methacrylate copolymer as an adhesive agent, and an occlusive liner. Azone (5%,
w/w) was incorporated into all the systems as a percutaneous enhancer.
Transdermal systems are thin, transparent and non-adhesive when in a dry state.
The permeation of sumatriptan succinate across pig ear skin was studied using the
systems prepared. The formulation with MC polymer produced a statistically
significant increment with respect to the PVP and PVP-PVA formulations (p <
0.05). Azone incorporation into the systems produced an increment in the
sumatriptan flux values of all three transdermal systems with respect to those of
the controls (p < 0.05). In addition, the application of iontophoresis to the wet
methyl cellulose-Azone formulation produced a much higher increase of sumatriptan
transdermal flux. 2007 Wiley-Liss, Inc

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17854062 [PubMed - indexed for MEDLINE]

593: Disabil Rehabil. 2008;30(3):231-9.

Force production and EMG activity of neck muscles in adolescent headache.

Oksanen A, Pöyhönen T, Ylinen JJ, Metsähonkala L, Anttila P, Laimi K, Hiekkanen
H, Aromaa M, Salminen JJ, Sillanpää M.

Department of Physical and Rehabilitation Medicine, Turku University Central
Hospital, Turku, Finland. airi.oksanen@tyks.fi

PURPOSE: This study compared the maximal force, EMG/force ratio and co-activation
characteristics of the neck-shoulder muscles between 30 adolescents with
migraine-type headache, 29 with tension-type headache, and 30 headache-free
controls. METHOD: Force was measured with surface electromyography (EMG) from the
cervical erector spinae (CES), the sternocleidomastoid (SCM) and trapezius
muscles during the maximal isometric neck flexion, neck extension and shoulder
flexion. RESULTS: Girls with migraine-type headache had higher EMG/force ratios
between the EMG of the left agonist SCM muscle and the corresponding maximal neck
flexion (p = 0.030) and neck rotation force to the right side (p = 0.024) than
the girls with tension-type headache. Migrainous girls had more co-activation of 
right antagonist CES muscle during maximal neck flexion force than the girls
without headache (p = 0.015). Neck force production showed no significant
differences between girls. Girls with tension-type headache displayed lower left 
shoulder flexion force than girls with migraine-type headache (p = 0.005) or with
no headache (p = 0.005). In boys, no significant differences were observed.
CONCLUSIONS: Girls with tension-type headache and migraine-type headache have
differences in neuromuscular function in the neck-shoulder muscles. The data
amplify our knowledge of the neck-shoulder muscle dysfunction in adolescent
headache, and may encourage the use of specific rehabilitation methods in the
management of different types of headache.

Publication Types: 
    Clinical Trial

PMID: 17852219 [PubMed - indexed for MEDLINE]

594: Acta Otolaryngol. 2007 Dec;127(12):1241-5.

The relevance of migraine in patients with Meńière's disease.

Cha YH, Brodsky J, Ishiyama G, Sabatti C, Baloh RW.

Department of Neurology, University of California, Los Angeles, CA, USA.
yhcha@mednet.ucla.edu

CONCLUSION: Coexistent migraine affects relevant clinical features of patients
with Ménière's disease (MD). OBJECTIVE: Epidemiological studies have shown an
association between migraine and MD. We sought to determine whether the
coexistence of migraine affects any clinical features in patients with MD.
PATIENTS AND METHODS: In this retrospective case-control study of University
Neurotology Clinic patients, 50 patients meeting 1995 AAO-HNS criteria for
definite MD were compared to 18 patients meeting the same criteria in addition to
the 2004 IHS criteria for migraine (MMD). All had typical low frequency
sensorineural hearing loss and episodes of rotational vertigo. Outcome measures
included: sex, age of onset of episodic vertigo or fluctuating hearing loss,
laterality of hearing loss, aural symptoms, caloric responses, severity of
hearing loss, and family history of migraine, episodic vertigo or hearing loss.
RESULTS: Age of onset of episodic vertigo or fluctuating hearing loss was
significantly lower in patients with MMD (mean +/- 1.96*SE = 37.2 +/- 6.3 years) 
than in those with MD (mean +/- 1.96*SE = 49.3 +/- 4.4 years). Concurrent
bilateral aural symptoms and hearing loss were seen in 56% of MMD and 4% of MD
patients. A family history of episodic vertigo was seen in 39% of MMD and 2% of
MD patients.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 17851970 [PubMed - indexed for MEDLINE]

595: Cephalalgia. 2007 Nov;27(11):1278-82. Epub 2007 Sep 10.

Comment in:
    Cephalalgia. 2008 Feb;28(2):199-200.

Migraine with isolated facial pain: a diagnostic challenge.

Obermann M, Mueller D, Yoon MS, Pageler L, Diener H, Katsarava Z.

Department of Neurology, University of Duisburg-Essen, Essen, Germany.
mark.obermann@uni-due.de

We present a series of seven migraine patients with typical features of a
migraine attack without aura, but atypical pain localization in the face in one
or both of the lower two distributions of the trigeminal nerve (V2 and V3). All
of them responded well to triptans. Three patients responded to preventive
treatment for migraine with beta-blockers (n = 2) or valproic acid (n = 1). These
cases underline the heterogenic clinical presentation of migraine, which is
sometimes difficult to diagnose even for headache specialists, and broaden the
pathophysiological understanding of trigeminal nociceptive processing in migraine
in the light of neuronal plasticity.

Publication Types: 
    Case Reports

PMID: 17850354 [PubMed - indexed for MEDLINE]

596: Cephalalgia. 2007 Oct;27(10):1109-14. Epub 2007 Sep 10.

Migraine pain location at onset and during established headaches in children and 
adolescents: a clinic-based study from eastern India.

Chakravarty A, Mukherjee A, Roy D.

Department of Neurology, Vivekananda Institute of Medical Sciences, 59 Beadon
Street, Calcutta 700 006, India. saschakra@yahoo.com

Literature documenting the location of pain at onset of migraine attacks and
during established headaches in children and adolescents is sparse. Through a
prospective study (2003-2005) of 200 children with migraine (ICHD-2: 1.1 and
1.2.1), we set out to document (i) the site of onset of pain and (ii) the
location of pain during established attacks (on >50% of occasions) through
semistructured interviews of patients and parents. Of the 200 children, the
male:female ratio was 118 : 82 (1 : 0.69), the age range was 7-15 years (mean
11.8 years) and the duration of migraine 6 months to 4 years (mean 1.6 years).
Ninety-three percent of subjects were ethnic Bengalis from the eastern Indian
state of West Bengal, capital city Calcutta. Migraine types were: 1.1, 197
(98.5%); 1.2.1, three (1.5%). Location of pain at onset: 20.5% of subjects had
unilateral onset; of these, 26.8% had eye pain, 65.9% frontal and 12.3% temporal 
pain. Thirty-three percent had bilateral location of pain, mostly bifrontal or
ocular. None had vertex onset pain. However, in 35% of subjects, pain was
holocranial at onset. Only 11.5% experienced pain in the occipito-cervical region
at onset. Location of established headaches: in 53.7% of subjects with unilateral
onset, headaches subsequently became holocranial. Hemicranial headaches occurred 
in only 19.5%. Of bilateral onset pains, 57.8% also became holocranial
subsequently. In all, 73.5% of children ultimately experienced holocranial
headaches. This study documents pain location at onset and during established
headaches in children with migraine largely from a specific ethnic group.

PMID: 17850349 [PubMed - indexed for MEDLINE]

597: Neurol Res. 2008 Apr;30(3):229-33. Epub 2007 Sep 10.

Metabolite concentration ratios in thalami of patients with migraine and
trigeminal neuralgia measured with 1H-MRS.

Gu T, Ma XX, Xu YH, Xiu JJ, Li CF.

Department of Radiology, Qilu Hospital of Shandong University, Jinan 250012,
China. gutao001@sina.com

OBJECTIVE: To investigate the metabolite concentration ratios including
N-acetylaspartate (NAA), choline-containing compounds (Cho) and creatine plus
phosphocreatine (Cr) in thalami of patients with migraine without aura, patients 
with trigeminal neuralgia and healthy comparison subjects using multi-voxel
proton magnetic resonance spectroscopy (1H-MRS). METHODS: 1H-MRS was performed
with a 3.0 T MR system on the thalamus bilaterally in 20 patients with migraine
without aura, 16 patients with trigeminal neuralgia and 14 healthy control
subjects. RESULTS: In the patients with trigeminal neuralgia, metabolite
concentration ratios except for Cho/Cr in thalami were different from those of
healthy subjects (p>0.05). In migraine group, only NAA/Cho is low in the left
thalamus (p>0.05). Comparing the metabolite concentration ratios of affected and 
contralateral sides in migraine and trigeminal neuralgia groups, only NAA/Cr
showed a significant difference (p>0.05). CONCLUSION: It was proved that migraine
and trigeminal neuralgia seemed to be associated with an abnormal balance of the 
neural activity in the thalamus using 1H-MRS. There was some significant
difference between metabolite concentration ratios in two diseases. 1H-MRS may
serve as a useful non-invasive tool for evaluating thalamic neural activity and
therapy effect in clinical performance of patients with migraine without aura.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 17848209 [PubMed - indexed for MEDLINE]

598: J Neurosci Nurs. 2007 Aug;39(4):213-6.

The impact of migraine: a case study.

Jung S.

Puget Sound Neurology, Tacoma, WA, USA. psnhogan@aol.com

Migraine headaches are common and among the most disabling nonfatal conditions of
humankind. They are frequently misdiagnosed, which may lead to undertreatment.
Patients often self-diagnose and self-medicate, resulting in inadequate
treatment. Consequently, patients may take additional doses, trying to gain
relief with inappropriate medications. Rebound can ensue. With adequate
treatment, a patient's condition and quality of life may improve considerably.
Patient education is extremely important to help patients identify appropriate
self-care measures, such as identification of triggering events and coping with
the chronic nature of their condition. This case study presents a patient who
began experiencing migraines following a neck injury. His headaches became more
frequent, and ergotamine and caffeine (Cafergot) suppositories were prescribed.
When he presented, he was experiencing daily headaches and using daily ergotamine
and caffeine suppositories. He was using the emergency department (ED) frequently
because of severe headaches. Cervical spasm was recognized as his trigger, and
the ergotamine and caffeine suppositories were discontinued. After 3 days of
severe headaches, his rebound ceased. He reverted back to episodic migraines,
which he treated with zolmitriptan (Zomig) nasal spray, which was effective. His 
cervical spasm was treated with botulinum toxin type A (Botox), with excellent
results. He has maintained reasonable headache control for 2 years.

Publication Types: 
    Case Reports

PMID: 17847668 [PubMed - indexed for MEDLINE]

599: Expert Opin Ther Targets. 2007 Sep;11(9):1179-88.

Novel migraine therapy with calcitonin gene-regulated peptide receptor
antagonists.

Edvinsson L.

Lund University Hospital, Department of Medicine, Institute of Clinical Sciences,
S-221 85 Lund, Sweden. lars.edvinsson@med.lu.se

Primary headaches, for example, migraine and cluster headaches represent the most
prevalent neurological disorders, affecting up to 15-20% of the adult population.
There is a clear association between head pain and the release of calcitonin
gene-related peptide (CGRP). In this review the role of CGRP in human cranial
circulation is described and the role for specific CGRP antagonism elucidated. It
is well known that triptans (5-HT(1B/1D) agonist) alleviate headache in part
through normalisation of CGRP levels. The central role of CGRP in migraine
pathophysiology has resulted in the development of small-molecule CGRP
antagonists with no cardiovascular side effects. Such compounds have high
selectivity for human CGRP receptors and are efficacious in the relief of acute
migraine attacks. Research indicates that they effect the abluminal side of the
blood-brain barrier and that they are not vasoconstrictive, providing a new
dimension in therapy.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 17845144 [PubMed - indexed for MEDLINE]

600: Eur Neurol. 2007;58(4):215-7. Epub 2007 Sep 7.

Cost-minimization analysis comparing topiramate with standard treatments in
migraine prophylaxis.

Ergun H, Gulmez SE, Tulunay FC.

Department of Pharmacology and Clinical Pharmacology, Ankara University Faculty
of Medicine, Ankara, Turkey. hergun@medicine.ankara.edu.tr

Migraine is a common disorder with a relatively high burden of disease from the
perspective of both society and the individual patient. Optimizing the use of
prophylactic treatment may decrease the frequency and severity of attacks thus
reducing the burden of disease. In this regard, topiramate has been found to be
as effective as propranolol in the prevention of migraine attacks. In the present
study, a cost-minimization analysis was performed. Monthly preventive medication 
cost and price per migraine attack reduced were used as measures. In comparison
with propranolol and flunarizine, topiramate was identified as being the most
costly option for migraine prophylaxis with a monthly drug cost of USD
24.97-45.04 as compared with propranolol (USD 1.72-6.87) and flunarizine (USD
6.09-12.18). Current treatment options would appear to offer better value for
money in achieving effective migraine prophylaxis unless additional benefits can 
be identified for topiramate in this patient group. (c) 2007 S. Karger AG, Basel.

PMID: 17827966 [PubMed - indexed for MEDLINE]

601: Clin Ther. 2007 Jul;29(7):1441-7.

Single-dose intravenous tramadol for acute migraine pain in adults: a
single-blind, prospective, randomized, placebo-controlled clinical trial.

Alemdar M, Pekdemir M, Selekler HM.

Department of Neurology, Medical Faculty, Kocaeli University Hospital, Kocaeli,
Turkey. drmuratalemdar@yahoo.com

BACKGROUND: Tramadol, an atypical opioid, is a narcotic analgesic used for pain
management. A search of the current literature found no studies examining the
efficacy of intravenous tramadol on migraine pain. OBJECTIVE: The aim of this
study was to investigate the efficacy and tolerability of a single dose of
intravenous tramadol hydrogen chloride 100 mg in comparison with placebo in
patients presenting with migraine. METHODS: Adult migraineurs admitted
consecutively to the emergency department of the Kocaeli University Hospital were
enrolled in this single-blind (patients), prospective, randomized,
placebo-controlled clinical trial. Patients were randomized to receive a
30-minute infusion of either intravenous tramadol (n = 17; 100 mg in 100-mL
saline) or placebo (n = 17; 100-mL saline). Pain response was defined as a
decrease of visual analogue scale (VAS) (0-100 mm) score to <50% of the
pretreatment (baseline) value and a decrease of 4-point verbal scale (FPVS) score
(0 = none, 1 = mild, 2 = moderate, 3 = severe) to mild or none. Pain-free
response was defined as a decrease of both VAS and FPVS scores to 0. Pain was
assessed at baseline and at 30 minutes and 1 hour after treatment completion.
Migraine symptoms (eg, photophobia, phonophobia, nausea, vomiting) and adverse
events (AEs) were assessed at the same time. A follow-up was also conducted by
phone 24 hours after treatment. RESULTS: Forty-four migraineurs were screened and
34 (28 women and 6 men; mean [SD] age, 39.5 [10.4] years; all were white) were
enrolled in the study. Each group contained 11 patients with severe pain and 6
patients with moderate pain at baseline FPVS. At the end of 1 hour, pain response
was reported by significantly more patients in the tramadol group than in the
placebo group (12 [70.6%] vs 6 [35.3%]; P = 0.040). Pain-free response was
reported by 5 (29.4%) patients in the tramadol group and 2 (11.8%) patients in
the placebo group, although the difference was not statistically significant.
Symptoms associated with migraine were also relieved in all patients reporting
pain response. No AEs were observed. However, at the 24-hour follow-up, 1 patient
in the tramadol group reported transient blurred vision and dizziness within the 
day of infusion. Headache recurrence was reported by 2 (16.7%) of the 12 patients
with pain response in the tramadol group and 1 (16.7%) of 6 patients with pain
response in the placebo group. CONCLUSIONS: Intravenous tramadol appeared to be
more effective than placebo in pain response rate at the end of the first hour.
The slow infusion of tramadol 100 mg in 100-mL saline solution was well tolerated
in this group of adult migraineurs.

Publication Types: 
    Randomized Controlled Trial

PMID: 17825695 [PubMed - indexed for MEDLINE]

602: Can J Neurol Sci. 2007 Aug;34(3):349-55.

Ophthalmoplegic migraine: inflammatory neuropathy with secondary migraine?

McMillan HJ, Keene DL, Jacob P, Humphreys P.

Department of Pediatrics, Division of Neurology, Children's Hospital of Eastern
Ontario, Ottawa, Ontario, Canada.

BACKGROUND: This critical review provides a summary of the clinical presentation,
neuroimaging, treatment and prognosis in pediatric ophthalmoplegic migraine (OM).
The features of OM are not in keeping with its classification as a
migraine-variant. METHOD: We review 3 new and 37 reported pediatric OM cases.
RESULTS: Headache was an inconsistent feature, with 25% patients showing no
evidence of pain at the initial OM episode. Patients demonstrated: 1) prolonged
time for symptom resolution to occur (median time 3 weeks); 2) tendency for
recurrent episodes to have more severe and persistent nerve involvement; 3)
evidence of permanent neurological sequelae with recurrent episodes (30% of
patients); 4) rapid improvement and shortened duration with corticosteroid
therapy and; 5) transient, reversible MRI contrast enhancement of the affected
cranial nerve (86% of patients). These features would not be expected in primary 
migraine headache. CONCLUSION: A detailed understanding of the natural history of
OM is essential for the clinical. This review provides support that OM may result
from cranial nerve inflammation with headache a secondary and later feature of
this condition.

Publication Types: 
    Case Reports
    Review

PMID: 17803036 [PubMed - indexed for MEDLINE]

603: Hypertens Res. 2007 Jul;30(7):577-83.

Migraine is associated with enhanced arterial stiffness.

Nagai T, Tabara Y, Igase M, Nakura J, Miki T, Kohara K.

Department of Geriatric Medicine, Ehime University Graduate School of Medicine,
Toon, Japan.

Migraine is a common subtype of headache. Epidemiological studies have revealed
that migraine could be an independent risk factor for ischemic stroke even in
elderly subjects. Arterial stiffness is one of the major pathophysiological bases
of stroke. In the present study, we cross-sectionally investigated the possible
relationship between migraine and arterial stiffness in community-dwelling
subjects. The study subjects were independently recruited from two sources (Group
A, n=134, 68+/-5 years; Group B, n=138, 68+/-7 years). Augmentation index (AI),
the ratio of augmented pressure by the reflection pressure wave to the pulse
pressure, was obtained from the radial arterial waveform as an index of arterial 
stiffness. Brachial blood pressure was also measured simultaneously. Migraine was
diagnosed using a previously validated questionnaire. The prevalence of migraine 
was 5.2% (Group A) and 16.7% (Group B). Subjects with migraine had higher radial 
AI in both Group A (migraine, 101+/-15%; other headache, 88+/-12%; no headache,
86+/-12%, p=0.003) and Group B (95+/-11%, 90+/-11%, 91+/-14%, p=0.058). Multiple 
linear regression analysis revealed that migraine was an independent determinant 
of AI (beta=0.154, p=0.002) after adjustment for other confounding factors: age
(beta=-0.024, p=0.654); sex (beta=0.141, p=0.069); body height (beta=-0.215,
p=0.005); systolic blood pressure (beta=0.174, p=0.001); medication for
hypertension, hyperlipidemia, and diabetes mellitus (beta=-0.014, p=0.787); and
heart rate (beta=-0.539, p<0.001). In a separate analysis by sex, migraine was
also a significant determinant for AI (male, beta=0.246, p=0.019; female,
beta=0.159, p=0.008). Migraine in the elderly could be a clinical manifestation
of enhanced arterial stiffness.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17785924 [PubMed - indexed for MEDLINE]

604: Neurology. 2007 Sep 4;69(10):959-68.

History of childhood maltreatment is associated with comorbid depression in women
with migraine.

Tietjen GE, Brandes JL, Digre KB, Baggaley S, Martin VT, Recober A, Geweke LO,
Hafeez F, Aurora SK, Herial NA, Utley C, Khuder SA.

Department of Neurology, College of Medicine, The University of Toledo-Health
Science Campus, Toledo, OH 43614, USA. gretchen.tietjen@utoledo.edu

BACKGROUND: A bidirectional relationship between migraine and depression suggests
a neurobiological link. Adverse experiences, particularly childhood maltreatment,
may alter neurobiological systems, and predispose to a multiplicity of adult
chronic disorders. Our objective is to determine, within a headache clinic
population of women, if depression moderates the abuse-migraine relationship.
METHODS: At six headache specialty clinics, women with migraine were diagnosed
using ICHD-II criteria, and frequency was recorded. A questionnaire regarding
maltreatment history, headache characteristics, current depression, and somatic
symptoms was completed. RESULTS: A total of 949 women with migraine completed the
survey: 40% had chronic headache (> or =15 headache days/month) and 72% had "very
severe" headache-related disability. Major depression was recorded in 18%.
Physical or sexual abuse was reported in 38%, and 12% reported both physical and 
sexual abuse in the past. Migraineurs with current major depression reported
physical (p < 0.001) and sexual (p < 0.001) abuse in higher frequencies compared 
to those without depression. Women with major depression were more likely to
report sexual abuse occurring before age 12 years (OR = 2.30, 95% CI: 1.14 to
4.77), and the relationship was stronger when abuse occurred both before and
after age 12 years (OR = 5.08, 95% CI: 2.15 to 11.99). Women with major
depression were also twice as likely to report multiple types of maltreatment (OR
= 2.07, 95% CI: 1.27 to 3.35) compared to those without depression. CONCLUSIONS: 
Childhood maltreatment was more common in women with migraine and concomitant
major depression than in those with migraine alone. The association of childhood 
sexual abuse with migraine and depression is amplified if abuse also occurs at a 
later age.

Publication Types: 
    Comparative Study
    Multicenter Study
    Research Support, Non-U.S. Gov't

PMID: 17785664 [PubMed - indexed for MEDLINE]

605: Cephalalgia. 2007 Oct;27(10):1150-5. Epub 2007 Sep 4.

Erratum in:
    Cephalalgia. 2007 Dec;27(12):1424. Bisdorff, A R [added].

The vestibulo-collic reflex is abnormal in migraine.

Allena M, Magis D, De Pasqua V, Schoenen J, Bisdorff AR.

Headache Research Unit, Department of Neurology, CHR Citadelle, University of
Liège, Boulevard du 12ème de Ligne 1, 4000 Liège, Belgium.

Interictal evoked central nervous system responses are characterized in
migraineurs by a deficit of habituation, at both cortical and subcortical levels.
The click-evoked vestibulo-collic reflex (VCR) allows the assessment of otolith
function and an oligosynaptic pathway linking receptors in the saccular macula to
motoneurons of neck muscles. Three blocks of 75 averaged responses to monaural
95-dB normal hearing level 3-Hz clicks were recorded over the contracted
ipsilateral sternocleidomastoid muscle in 25 migraineurs between attacks and 20
healthy subjects, without vestibular symptoms. Amplitudes, raw and corrected for 
baseline electromyography, were significantly smaller in migraine patients.
Whereas in healthy volunteers the VCR habituated during stimulus repetition
(-4.96% +/- 14.3), potentiation was found in migraineurs (4.34% +/- 15.3; P =
0.04). The combination with a reduced mean amplitude does not favour vestibular
hyperexcitability as an explanation for the habituation deficit in migraine, but 
rather an abnormal processing of repeated stimuli in the reflex circuit.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17784856 [PubMed - indexed for MEDLINE]

606: Cephalalgia. 2007 Oct;27(10):1156-65. Epub 2007 Sep 4.

Impaired functioning and quality of life in severe migraine: the role of
catastrophizing and associated symptoms.

Holroyd KA, Drew JB, Cottrell CK, Romanek KM, Heh V.

Department of Psychology, Ohio University, Athens, OH, USA. holroyd@ohio.edu

Migraine characteristics are associated with impaired functioning and quality of 
life (Fn/QoL), but the impact of other factors on Fn/QoL in headache patients is 
largely unexplored. We examined catastrophizing, comorbid anxiety/depression and 
migraine characteristics as related to Fn/QoL, and explored the consistency of
these relationships across five Fn/QoL measures. We evaluated 232 frequent
migraine sufferers for comorbid psychiatric diagnosis, and they completed
anxiety, depression and catastrophizing measures, recorded migraine
characteristics in a diary and completed five Fn/QoL measures (four self-report
questionnaires, one diary disability measure). Backward regression revealed
catastrophizing and severity of associated symptoms (photophobia, phonophobia,
nausea) independently predicted Fn/QoL across all five measures (beta weights
0.16-0.50, all P < 0.01). This is the first demonstration that a psychological
response to migraines (catastrophizing) is associated with impaired Fn/QoL
independent of migraine characteristics and other demographic and psychological
variables. Severity of associated symptoms also emerged as an important
contributor to Fn/QoL.

Publication Types: 
    Research Support, N.I.H., Extramural

PMID: 17784854 [PubMed - indexed for MEDLINE]

607: Clin Neuropharmacol. 2007 Jul-Aug;30(4):213-7.

Effects of valproate on vestibular symptoms and electronystagmographic findings
in migraine patients.

Celiker A, Bir LS, Ardiç N.

Department of Neurology, Pamukkale University Medical Faculty, Denizli, Turkey.

OBJECTIVES: To investigate the effects of valproic acid on vestibular symptoms
and electronystagmography (ENG) findings in patients with migraine-related
vestibulopathy. METHODS: Thirty-seven patients with migraine (13 with vertigo, 13
with dizziness, and 11 without vestibular symptoms) were included in the study.
Slow-released valproic acid (500 mg/d) was given for 3 months. Frequency of
headache and vestibular symptoms in the first, second, and third months of the
therapy were recorded and compared with the pretreatment values. The ENG findings
were also evaluated before and 2 months after the therapy. RESULTS: We determined
that prophylactic low-dose valproic acid decreased the frequency of headache and 
vestibular symptoms, although it does not cause any statistically meaningful
change in ENG findings. CONCLUSIONS: Valproate can be used satisfactorily for
patients with migraine who have vestibular complaints. Ineffectiveness of
valproic acid on ENG findings can be clarified by the permanent effect of
migraine on the vestibular system.

Publication Types: 
    Clinical Trial

PMID: 17762318 [PubMed - indexed for MEDLINE]

608: Agri. 2007 Apr;19(2):46-8.

Plasma cortisol levels in migraineurs between attacks.

Oncel C, Oflazoğlu B, Forta H, Yücel N, Eren N.

Department of Neurology, Pamukkale University, Denizli, Turkey.
cagatay_oncel@yahoo.com

We have studied the plasma cortisol levels between attacks in order to
investigate the role of hypothalamic-pituitary-adrenal axis in migraine patients.
We have not found any statistically significance between plasma cortisol levels
of patients and control group, after taking the blood of 25 patients and 24
healthy controls between 8.30-9.30 am.

PMID: 17760244 [PubMed - indexed for MEDLINE]

609: Singapore Med J. 2007 Sep;48(9):834-9.

Randomised, open label, controlled trial of celecoxib in the treatment of acute
migraine.

Loo CY, Tan HJ, Teh HS, Raymond AA.

Neurology Unit, Department of Medicine, Hospital Universiti Kebangsaan Malaysia, 
Jalan Yaacob Latif, Bandar Tun Razak, Cheras, Kuala Lumpur, Malaysia.
cyloo7@gmail.com

INTRODUCTION: Migraine is a common disabling condition that results in
considerable socioeconomic loss. The role of non-steroidal anti-inflammatory
drugs (NSAIDs) in acute migraine has been well-established. We compared the
efficacy of the cyclooxygenase-2 inhibitor celecoxib with the NSAID, naproxen
sodium, in the treatment of acute migraine. METHODS: This was a randomised, open 
label, controlled trial. We selected patients with a diagnosis of migraine, based
on the International Headache Society revised criteria. 60 patients were
randomised to either celecoxib 400 mg (30 patients) or naproxen sodium 550 mg (30
patients). Patients took the study medicine for the first acute migraine episode 
that occurred during the study period and reported the headache reduction based
on a visual analogue score (VAS). Patients were reviewed after a month to check
on VAS at one and two hours, compared to the baseline. Any side effects of the
medication were also recorded. RESULTS: Of the 52 patients who completed the
study, eight did not experience any headaches. The mean VAS in the celecoxib
group improved significantly from baseline (6.48 +/- 1.53) to one hour (4.28 +/- 
2.11) and two hours (2.24 +/- 2.57) (p-value is less than 0.0005). The mean VAS
in the naproxen sodium group also improved significantly from baseline (7.30 +/- 
1.66) to one hour (4.81 +/- 2.50) and two hours (2.63 +/- 2.65) (p-value is less 
than 0.0005). However, there was no significant difference between the magnitudes
of improvement between the treatment groups. The incidence of gastric pain was
significantly higher in the naproxen sodium group (p-value is equal to 0.029).
CONCLUSION: In comparison with naproxen sodium, celecoxib was equally effective
in relieving pain in acute migraine and caused significantly less gastric pain.

Publication Types: 
    Randomized Controlled Trial

PMID: 17728965 [PubMed - indexed for MEDLINE]

610: BMC Med Genet. 2007 Aug 29;8:57.

Association analysis of chromosome 1 migraine candidate genes.

Fernandez F, Curtain RP, Colson NJ, Ovcaric M, MacMillan J, Griffiths LR.

Genomics Research Centre, School of Health Science, Griffith University, Gold
Coast, Queensland, Australia. f.fernandez@griffith.edu.au

BACKGROUND: Migraine with aura (MA) is a subtype of typical migraine. Migraine
with aura (MA) also encompasses a rare severe subtype Familial Hemiplegic
Migraine (FHM) with several known genetic loci. The type 2 FHM (FHM-2)
susceptibility locus maps to chromosome 1q23 and mutations in the ATP1A2 gene at 
this site have recently been implicated. We have previously provided evidence of 
linkage of typical migraine (predominantly MA) to microsatellite markers on
chromosome 1, in the 1q31 and 1q23 regions. In this study, we have undertaken a
large genomic investigation involving candidate genes that lie within the
chromosome 1q23 and 1q31 regions using an association analysis approach. METHODS:
We have genotyped a large population of case-controls (243 unrelated Caucasian
migraineurs versus 243 controls) examining a set of 5 single nucleotide
polymorphisms (SNPs) and the Fas Ligand dinucleotide repeat marker, located
within the chromosome 1q23 and 1q31 regions. RESULTS: Several genes have been
studied including membrane protein (ATP 1 subtype A4 and FasL), cytoplasmic
glycoprotein (CASQ 1) genes and potassium (KCN J9 and KCN J10) and calcium
(CACNA1E) channel genes in 243 migraineurs (including 85% MA and 15% of migraine 
without aura (MO)) and 243 matched controls. After correction for multiple
testing, chi-square results showed non-significant P values (P > 0.008) across
all SNPs (and a CA repeat) tested in these different genes, however results with 
the KCN J10 marker gave interesting results (P = 0.02) that may be worth
exploring further in other populations. CONCLUSION: These results do not show a
significant role for the tested candidate gene variants and also do not support
the hypothesis that a common chromosome 1 defective gene influences both FHM and 
the more common forms of migraine.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17727731 [PubMed - indexed for MEDLINE]

611: Behav Neurol. 2007;18(3):187-92.

Persistent visual aura following catheter ablation in a patient with WPW
syndrome.

Koyama S, Kawamura M.

Department of Neurology, Showa University School of Medicine, Shinagawa-ku,
Tokyo, Japan. skoyama@med.showa-u.ac.jp

We report a patient who has had persistent visual disturbances since she
underwent catheter ablation to treat her Wolff-Parkinson-White (WPW) syndrome. We
examined her visual symptoms carefully and quantitatively by means of our newly
developed method combining image-processing and psychophysics. We first simulated
the patient's visual symptoms using image-processing techniques. Since the
simulation indicated that she would be very sensitive to the edges of the visual 
stimuli, we evaluated her sensitivity to the edges using psychophysics. The
results indicated that she was hypersensitive to the clear-cut edges of the
visual stimuli. Her visual symptoms were very similar to those of visual aura of 
migraine, rather than those of photosensitive epilepsy. Magnetic resonance
imaging (MRI) and single photon emission computed tomography (SPECT),
electroenchepalogram (EEG), and visual-evoked potentials (VEP) in the patient
were normal. No abnormalities in her fundus, visual field, or electroretinogram
were found, either. Transesophageal echocardiography with bubble study indicated 
that she had a preexisting right-to-left shunt. We hypothesize that visual aura
of migraine was triggered and made persistent by the catheter ablation in this
patient. Although the relationship between migraine, catheter ablation, and
right-to-left shunts is unknown, previous studies on the transcatheter closure of
patent foramen ovale suggest a possible link between them. Catheter ablation in
patients with migraine and preexisting shunts may lead to exacerbations in
migraine symptoms.

Publication Types: 
    Case Reports
    Research Support, Non-U.S. Gov't

PMID: 17726248 [PubMed - indexed for MEDLINE]

612: Cephalalgia. 2007 Oct;27(10):1136-41. Epub 2007 Aug 24.

Relationship between biofeedback and oxidative stress in patients with chronic
migraine.

Ciancarelli I, Tozzi-Ciancarelli MG, Spacca G, Di Massimo C, Carolei A.

Department of Neurology and Laboratory of Applied Physiology, University of
L'Aquila, Piazzale Salvatore Tommasi 1, 67010 L'Aquila, Italy.

Chronic migraine (1.5.1) is burdened with headache-related disability. During
noxious stimulation, changes of cerebral blood flow enhance the release of oxygen
free radicals that react with nitric oxide (NO). We investigated the role of
biofeedback in limiting migraine disability by influencing oxidative stress.
Peroxides, NO and superoxide dismutase (SOD) were analysed in 20 female subjects 
with chronic migraine and in 20 female healthy controls before and after
biofeedback sessions. NO(x) levels (23.7 +/- 4.2 vs. 34.9 +/- 4.6 microm; P <
0.05) and SOD activity (6.5 +/- 1.0 vs. 8.0 +/- 0.7 U/ml; P < 0.05) were lower in
migraine sufferers before treatment than in healthy controls, whereas peroxide
levels (145.8 +/- 40.3 vs. 78.0 +/- 20.0 microm; P < 0.05) were higher in
migraine sufferers before treatment than in healthy controls. In migraine
sufferers NO(x) levels (23.7 +/- 4.2 vs. 31.3 +/- 7.1 microm; P < 0.05) and SOD
activity (6.5 +/- 1.0 vs. 7.9 +/- 0.9 U/ml; P < 0.05) were lower before than
after treatment, whereas peroxide levels (145.8 +/- 40.3 vs. 82.4 +/- 21.1
microm; P < 0.05) were higher before than after treatment. SOD serum activity
correlated positively with NO(x) serum levels and negatively with peroxide serum 
levels in healthy controls and in chronic migraine sufferers before and after
biofeedback. The mean Migraine Disability Assessment Score before biofeedback
sessions was higher than after treatment (36.9 +/- 13.9 vs. 18.8 +/- 10.4; P <
0.001). The effectiveness of biofeedback in limiting chronic migraine may be
related to muscular relaxation associated with decreased oxidative stress
accompanied by psychological well-being.

Publication Types: 
    Clinical Trial

PMID: 17725652 [PubMed - indexed for MEDLINE]

613: Cephalalgia. 2007 Oct;27(10):1115-9. Epub 2007 Aug 24.

A case-control study on excessive daytime sleepiness in episodic migraine.

Barbanti P, Fabbrini G, Aurilia C, Vanacore N, Cruccu G.

Department of Neurological, Motor and Sensorial Sciences, IRCCS San Raffaele, Via
della Pisana 235, 00163 Rome, Italy. piero.barbanti@sanraffaele.it

Migraine patients often complain of sleepiness, a problem that manifests both
during and outside an attack, may impair the quality of life and can lead to
potentially harmful situations. Findings from an uncontrolled study suggest that 
a high percentage of migraineurs experience excessive daytime sleepiness (EDS).
We investigated EDS in a case-control study on 100 patients with episodic
migraine and 100 age- and sex-matched healthy controls and also assessed sleep
quality, anxiety and depression. Although it was found that EDS was more frequent
in migraineurs than in controls (14% vs. 5%; odds ratio 3.1; 95% confidence
interval 1.1-8.9), the frequency was lower than previously reported. EDS
correlated with migraine disability, sleep problems and anxiety. EDS in patients 
with migraine probably stems from the full constellation of
headache-sleep-affective symptoms resulting from the complex clinical burden of
the disease.

PMID: 17725651 [PubMed - indexed for MEDLINE]

614: Curr Med Res Opin. 2007 Oct;23(10):2433-40.

Use of almotriptan in triptan-experienced and triptan-naïve patients.

Pascual J, Diener HC.

Service of Neurology, University Hospital, Salamanca, Spain.
juliopascual@telefonica.net

OBJECTIVE: To evaluate the efficacy of oral almotriptan 12.5 mg as an acute
treatment for migraine with a focus on triptan-experienced versus triptan-naïve
patients. RESEARCH DESIGN AND METHODS: Four recent Almirall-sponsored clinical
trials of oral almotriptan 12.5 mg in acute migraine, in which data regarding
previous acute therapy were collected, are reviewed. The results and conclusions 
are limited by the open-label and post hoc design of some of these trials and
analyses. RESULTS: In two trials, almotriptan 12.5 mg was used to treat migraine 
sufferers who were dissatisfied with or were receiving inadequate results with
their previous therapy. One of these trials enrolled only patients whose
dissatisfaction with their current therapy was confirmed by a validated
questionnaire; the other looked at almotriptan 12.5 mg efficacy in patients with 
previous poor response to sumatriptan. In the other two trials, patients had been
achieving satisfactory results with their migraine therapy; one was a randomized,
double-blind clinical trial of almotriptan 12.5 mg and zolmitriptan 2.5 mg, the
other was an open-label almotriptan 12.5 mg satisfaction trial. Almotriptan 12.5 
mg is shown to be effective, well-tolerated, and preferred to previous agents in 
both patients who were satisfied with, and those who were dissatisfied with,
their previous therapy. CONCLUSIONS: Almotriptan should, therefore, not only be
considered as first-line therapy for acute migraine but should also be considered
for patients who are not satisfied with or not receiving optimal relief from
their current acute therapy.

Publication Types: 
    Clinical Trial
    Multicenter Study
    Research Support, Non-U.S. Gov't

PMID: 17723158 [PubMed - indexed for MEDLINE]

615: Catheter Cardiovasc Interv. 2007 Sep;70(3):429-33.

Comment in:
    Catheter Cardiovasc Interv. 2008 Apr 1;71(5):719; author reply 720.

Resolution of migraine by transcatheter patent foramen ovale closure with Premere
Occlusion System in a preliminary series of patients with previous cerebral
ischemia.

Rigatelli G, Cardaioli P, Braggion G, Giordan M, Fabio D, Aggio S, Roncon L,
Chinaglia M.

PFO-Related Syndromes Management Program, Cardiovascular Diagnosis and
Interventions Service, Rovigo General Hospital, Italy. jackyheart@hotmail.com

BACKGROUND: Transcatheter closure of PFO with nitinol devices may be problematic 
in young patients with migraine due the risk of late erosions. Alternative
devices with less amount of metal as the last generation devices may be
preferable in such cases. We present the results of transcatheter closure of PFO 
with the last generation Premere Occlusion System device in a preliminary series 
of young adults with migraine and previous cerebral ischemia. METHODS: During a
12-month period (January 31, 2006 to December 31, 2006) 26 patients (18 female
and 8 male, mean age 40 +/- 3.7 years) with previous stroke and severe disabling 
migraine were referred to our center for transcatheter closure of PFO. Migraine
disability assessment score (MIDAS) was used to assess MHA incidence and
severity. Patients were selected for Premere occlusion system (absence of atrial 
septal aneurysm and length >15 mm) on the basis of presence/absence of right and 
left bulging atrial septal aneurysm and length of PFO channel (<15 mm or >15 mm) 
on transesophageal echocardiography. Transesophageal echocardiography and
transcranial Doppler were performed at 1 month, transthoracic echocardiography
and cerebral magnetic resonance imaging at 6 and 12 months. Cardiologic and
neurological visit was scheduled at 1, 6, and 12 months with MIDAS questionnaire 
administration. RESULTS: Ten patients (2 males, mean age 32 +/- 7.6 years, mean
MIDAS score 38.9 +/- 5.8) underwent transcatheter PFO closure with the Premere
occlusion system. Mean fossa ovalis diameters by ICE measurement was 20.6 +/- 3.1
mm. Thus, two 20-mm and eight 25-mm Premere devices were implanted. The procedure
was successful in all of the patients with no perioperative and in-hospital
complications. After a mean follow-up of 10.9 +/- 5.8 months, all patients were
free from migraine symptoms (mean MIDAS score 2.9 +/- 1.9) with PFO complete
closure in all patients on transesophageal and transcranial Doppler ultrasound.
CONCLUSION: While waiting for larger studies evaluating the impact of new
generation devices in curing PFO-related migraine, this preliminary anecdotal
series suggests that the Premere occlusion system may be an effective and safe
device for young patients with previous cerebral ischemia and migraine at least
in the midterm period. (c) 2007 Wiley-Liss, Inc.

PMID: 17722021 [PubMed - indexed for MEDLINE]

616: J Neurol Sci. 2008 Jan 15;264(1-2):93-6. Epub 2007 Aug 27.

Clinical correlates of phosphene perception in migraine without aura: an Asian
study.

Lo YL, Lum SY, Fook-Chong S, Cui SL, Siow HC.

Department of Neurology, National Neuroscience Institute, Singapore General
Hospital, Outram Road, Singapore 169608, Singapore. lo.yew.long@sgh.com.sg

INTRODUCTION: Although controversy exists with regard to the presence of
hypoexcitability versus hyperexcitability of the visual cortex in migraine
patients, there remain a group who do not perceive phosphenes (P-). However, its 
clinical implications have not been systematically addressed. In this study, we
hypothesize that P- patients classified as migraine without aura (MO) have
distinct clinical features. METHODS: Twenty-nine Asian MO patients (7 men; mean
age: 44; median: 45; range: 25 to 65) were consecutively entered into the study. 
Visual cortex transcranial magnetic stimulation (TMS) was performed in the
migraine interictum. RESULTS: Of the 19 patients, 19 (66%) were able to perceive 
phosphenes (P+), while 10 (34%) were not able to after repeated TMS (P-). P-
patients had significantly higher headache frequency (p=0.008) and pain score
(p=0.002) compared with P+ patients. In addition, there was significant positive 
correlation of phosphene threshold with pain score (r=0.52, p=0.02) in P+
patients. There was no significant difference between P+ and P- patients in terms
of age (t-test, p=0.6). CONCLUSIONS: Our study is inkeeping with the hypothesis
that interictal visual cortex excitability is reduced in relation to the severity
of migraine in Asian MO patients, and lack of phosphene perception may be related
to significantly elevated thresholds beyond the output of TMS stimulators.

PMID: 17720202 [PubMed - indexed for MEDLINE]

617: Eur J Neurol. 2007 Sep;14(9):1053-6.

Treatment of hemiplegic migraine with triptans.

Artto V, Nissilä M, Wessman M, Palotie A, Färkkilä M, Kallela M.

Department of Neurology, Helsinki University Central Hospital, Finland.
ville.artto@hus.fi

The objective of this study was to investigate the efficacy, safety and
tolerability of triptans in patients who suffer from familial or sporadic
hemiplegic migraine. Seventy-six subjects had used triptans at least once as an
abortive treatment. Average triptan response was 6.9 (SD +/-3.1) and adverse
event severity 4.9 (SD +/-3.3) on a scale from 0 to 10 (no response or side
effect 0, excellent response or unbearable side effects 10). None of the patients
had an ischaemic stroke or a heart attack. One patient reported prolonged
neurological symptoms, related to a single dose of rizatriptan, but there were no
pathological findings in several MRI-scans. Triptans seem to be safe and
effective treatment for most hemiplegic migraine patients.

Publication Types: 
    Evaluation Studies
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 17718700 [PubMed - indexed for MEDLINE]

618: Eur J Neurol. 2007 Sep;14(9):983-8.

Circannual periodicity of migraine?

Alstadhaug KB, Bekkelund S, Salvesen R.

Department of Neurology, Nordlandssykehuset Bodø, Norway.
karl.bjornar.alstadhaug@nordlandssykehuset.no

Seasonal rhythm of migraine attacks may support a role of the suprachiasmatic
nucleus of the hypothalamus in the pathophysiology of migraine. The objective of 
this study was to provide evidence for seasonal variation in migraine.
Eighty-nine female migraineurs volunteered to record every migraine attack in
detail for 12 consecutive months. Attacks associated with sleep complaints were
defined as insomnia-related. By using Edwards' model for recognition and
estimation of cyclic trends, time-series analysis was made. Fifty-eight patients,
of which 26 had migraine without aura (MO) and 32 had migraine with aura (MA),
completed the study. A total of 1840 attacks were recorded. The mean age +/- SD
was 36.9 +/- 6.0. Patients with a lifetime history of MA showed marked seasonal
fluctuation with more attacks in the light season compared to the dark. Time of
peak was May 21. Peak/low ratio was 1.30 (95% CI: 1.08-1.55). When
insomnia-related attacks (n = 312) were removed the seasonal variation became
insignificant. There is a seasonal trend with more migraine attacks in the light 
season compared to the dark season in females with MA, but not MO, living in an
arctic area. This is caused by the seasonal variation of insomnia-related attacks
in patients with MA.

PMID: 17718689 [PubMed - indexed for MEDLINE]

619: Pain Med. 2007 Sep;8(6):478-85.

A double-blind, randomized, placebo-controlled comparison of botulinum toxin type
a injection sites and doses in the prevention of episodic migraine.

Saper JR, Mathew NT, Loder EW, DeGryse R, VanDenburgh AM; BoNTA-009 Study Group.

Michigan Head Pain & Neurological Institute, Ann Arbor, Michigan, USA.
jrsaper@aol.com

BACKGROUND: Several randomized, controlled studies have reported benefits of
botulinum toxin type A (BoNTA; Allergan Inc., Irvine, CA, USA) over placebo in
the treatment of migraine. Some studies reported significant benefits at dosages 
as low as 16 U, while other studies reported safety, tolerability, and efficacy
at dosages up to 260 U. However, the optimal treatment paradigm and patient
population have yet to be defined. OBJECTIVE: To compare different injection
sites and doses of BoNTA in the prevention of episodic migraine. DESIGN AND
METHODS: This was a randomized, double-blind, placebo-controlled study of 232
patients with a history of four to eight moderate to severe migraines per month, 
with or without aura. Patients were randomized to placebo or one of four BoNTA
groups that received injections into different muscle regions: frontal (10 U),
temporal (6 U), glabellar (9 U), or all three areas (total dose 25 U). For 3
months following a single treatment, patients recorded migraine-related variables
in a daily diary. RESULTS: BoNTA and placebo produced comparable decreases from
baseline in the frequency of migraines (P > or = 0.411). In general, no
statistically significant differences were observed for any efficacy variable.
The overall rates of adverse events (any type) or treatment-related adverse
events were similar among the groups. CONCLUSIONS: In this exploratory study of
episodic migraine patients, low-dose injections of BoNTA into the frontal,
temporal, and/or glabellar muscle regions were not more effective than placebo.
BoNTA was safe and well tolerated. Future studies may examine higher BoNTA doses,
flexible injection sites, multiple treatments, and disallow concomitant
prophylactic medications.

Publication Types: 
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 17716321 [PubMed - indexed for MEDLINE]

620: J Child Neurol. 2007 Jul;22(7):829-35.

Topiramate in the prophylaxis of pediatric migraine: a double-blind
placebo-controlled trial.

Lakshmi CV, Singhi P, Malhi P, Ray M.

Department of Pediatrics, Advanced Pediatric Center, Postgraduate Institute of
Medical Education and Research, Chandigarh, India.

Several large, randomized controlled trials have demonstrated the efficacy of
topiramate in migraine prophylaxis in adults. However, there are limited data
about the use of topiramate in migraine prophylaxis in children. We conducted
this single-center, double-blind, placebo-controlled trial to evaluate the
efficacy and safety of topiramate in the prophylaxis of migraine in children. A
total of 44 children with migraine were randomized using random number tables to 
receive topiramate (n = 22) or placebo (n = 22). The total duration of treatment 
was 4 months, including a baseline period of 1 month during which topiramate was 
titrated weekly in 25-mg increments to 100 mg/d in 2 divided doses or to the
maximum tolerated dose. The titration was followed by a 12-week maintenance phase
during which topiramate was given in 2 divided doses. The primary outcome
measures were the reduction in the mean migraine frequency and severity of
headache. Secondary outcome measures included the number of times analgesics were
required for a month for acute attacks and functional disability. Functional
disability was measured by comparing school absenteeism and Pediatric Migraine
Disability Assessment Scale (PedMIDAS). The decrease in mean (+/-SD) monthly
migraine frequency from 16.14 (+/-9.35) at baseline to 4.27 (+/-1.95) at the end 
of the study in the topiramate group was significantly greater as compared with a
decrease from 13.38 (+/-7.78) to 7.48 (+/-5.94) at the end of the study in the
placebo group (P = .025). The difference in number of rescue medications used for
topiramate and placebo was not statistically significant (P = .059). There was a 
statistically significant decrease in the PedMIDAS score from 50.66 (+/-32.1) to 
10.42 (+/-6.39) at the end of the study in the topiramate group compared with a
decrease from 42.66 (+/-27.5) to 23.7 (+/-19.1) at the end of 4 months in the
placebo group (P = .003). The decrease in school absenteeism was significant with
topiramate compared with placebo (P = .002). Weight loss, decreased concentration
in school, sedation, and parasthesias were important side effects with
topiramate. Most of these side effects were mild to moderate and were not
significant enough to cause dropout from the study.

Publication Types: 
    Randomized Controlled Trial

PMID: 17715274 [PubMed - indexed for MEDLINE]

621: Cephalalgia. 2007 Oct;27(10):1091-3. Epub 2007 Aug 21.

Pharmacokinetic and pharmacodynamic variability as possible causes for different 
drug responses in migraine. A comment.

Tfelt-Hansen P, Edvinsson L.

Danish Headache Centre, Depatment of Neurology, Glostrup Hospital, DK-2600
Glostrup, Denmark. tfelt@inet.uni2.dk

The pharmacokinetics of antimigraine drugs zolmitriptan and sumatriptan varied
considerably with a fourfold to 10-fold variation in plasma levels. In addition, 
the pharmacodynamics of triptans as investigated in vitro also varied
considerably. In theory, there should probably be a 10-fold variation in doses
available, but in clinical practice a fourfold difference in doses will probably 
cover the needs of most patients.

Publication Types: 
    Review

PMID: 17714521 [PubMed - indexed for MEDLINE]

622: Cephalalgia. 2007 Oct;27(10):1094-100. Epub 2007 Aug 17.

Interictal executive dysfunction in migraineurs without aura: relationship with
duration and intensity of attacks.

Camarda C, Monastero R, Pipia C, Recca D, Camarda R.

Adult Headache Centre-Section of Neurology and Psychiatry, Department of Clinical
Neuroscience, University of Palermo, Via La Loggia 1, 90129 Palermo, Italy.

Subjects with migraine are at increased risk of subcortical white matter lesions 
(WML). Reports of cognitive testing in adults with migraine have yielded
inconsistent results. We performed a cross-sectional study to assess whether
migraine without aura (MwA) is associated with impairment in executive
functioning, a typical cognitive correlate of subcortical WML. Forty-five
subjects with MwA and 90 controls, matched for age and education, underwent a
cognitive battery of tests evaluating executive functions. The following migraine
characteristics were collected: age at onset and length of migraine history, and 
frequency, duration and intensity of attacks. Subjects with MwA performed
significantly lower than controls in tests evaluating complex, multifactorial
executive functions. After multiple adjustments, the duration and intensity of
migraine attacks significantly predicted cognitive disturbances. In the
interictal phase of MwA there is evidence of mild executive dysfunction. The
cumulative effects of repeated migraine attacks on prefronto-cerebellar loop
probably account for our results.

PMID: 17711495 [PubMed - indexed for MEDLINE]

623: Cephalalgia. 2007 Oct;27(10):1142-9. Epub 2007 Aug 17.

Search for correlations between genotypes and electrophysiological patterns in
migraine: the MTHFR C677T polymorphism and visual evoked potentials.

Magis D, Allena M, Coppola G, Di Clemente L, Gérard P, Schoenen J.

Headache Research Unit, Department of Neurology, CHR Citadelle, University of
Liège, Boulevard du 12ème de Ligne 1, 4000 Liège, Belgium. dmagis@chu.ulg.ac.be

Interictally, migraineurs have on average a reduction in habituation of
pattern-reversal visual evoked potentials (PR-VEP) and in mitochondrial energy
reserve. 5,10-Methylenetetrahydrofolate reductase (MTHFR) is involved in folate
metabolism and its C677T polymorphism may be more prevalent in migraine. The aim 
of this study was to search in migraineurs for a correlation between the MTHFR
C677T polymorphism and the PR-VEP profile. PR-VEP were recorded in 52 genotyped
migraine patients: 40 female, 24 without (MoA), 28 with aura (MA). Among them 21 
had a normal genotype (CC), 18 were heterozygous (CT) and 13 homozygous (TT) for 
the MTHFR C677T polymorphism. Mean PR-VEP N1-P1 amplitude was significantly lower
in CT compared with CC, and tended to be lower in TT with increasing age. The
habituation deficit was significantly greater in CC compared with TT subjects.
The correlation between the cortical preactivation level, as reflected by the VEP
amplitude in the first block of averages, and habituation was stronger in CC than
in CT or TT. The MTHFR C677T polymorphism could thus have an ambiguous role in
migraine. On one hand, the better VEP habituation which is associated with its
homozygosity, and possibly mediated by homocysteine derivatives increasing
serotoninergic transmission, may protect the brain against overstimulation. On
the other hand, MTHFR C677T homozygosity is linked to a reduction of grand
average VEP amplitude with illness duration, which has been attributed to brain
damage.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17711493 [PubMed - indexed for MEDLINE]

624: Epilepsia. 2007 Nov;48(11):2181-6. Epub 2007 Aug 17.

A case with atypical childhood occipital epilepsy "Gastaut type": an ictal
migraine manifestation with a good response to intravenous diazepam.

Parisi P, Kasteleijn-Nolst Trenité DG, Piccioli M, Pelliccia A, Luchetti A,
Buttinelli C, Villa MP.

Child Neurology & Pediatric Sleep Centre, Chair of Pediatrics La Sapienza
University, II Faculty of Medicine Sant'Andrea Hospital, Via di Grottarossa
1035-1039, Rome, Italy. parpas@iol.it

We report the history of a 14-year-old girl with atypical childhood occipital
epilepsy "Gastaut type" whose first generalized tonic-clonic seizure was preceded
by migraine without aura and followed by a status migrainosus. This status lasted
for 3 days despite standard analgesic therapy. An EEG recording revealed an
occipital status epilepticus during her migraine complaints. Seven minutes after 
intravenous administration of 10 mg diazepam under continuous EEG recording, a
suppression of the epileptiform discharges over the right occipital was seen,
while the headache subsided 3 min later. After precise questioning about the
circumstances that possibly could have led to these events, it appeared that she 
had played for hours with a play station on the new color TV and she had visited 
an exhibition of Matisse and Bonnard with bright colors and contrast-rich text.
Standardized extensive intermittent photic stimulation (IPS), 2 days after the
status migrainosus, evoked besides asymmetrical right-sided driving, green spots 
in her left visual field, while in the EEG sharp waves were recorded over the
right parietotemporal region. After further IPS with 20 Hz (eye closure), she
started complaining of a light pulsating headache right occipitally and in the
EEG right parietotemporal sharp-waves were seen. This lasted for about 10 min.
Later, an interictal routine EEG was normal except for some theta over the right 
temporooccipital area. The most likely diagnosis is an atypical form of occipital
epilepsy "Gastaut type." We would therefore advocate recording EEGs with photic
stimulation in patients with atypical migraneous features.

Publication Types: 
    Case Reports

PMID: 17711460 [PubMed - indexed for MEDLINE]

625: J Med Assoc Thai. 2007 Jul;90(7):1309-16.

375 childhood primary headache: clinical features, the agreement between clinical
diagnosis and diagnoses using the international classification of headache
disorders in Thai children.

Ruangsuwan S, Sriudomkajorn S.

Division of Child Neurology, Queen Sirikit National Institute of Child Health,
Bangkok 10400, Thailand.

OBJECTIVE: To study the clinical features of patients with headache and agreement
between clinical diagnoses and ICHD II criteria diagnosis in primary headaches in
Thai children. MATERIAL AND METHOD: Patients with headache who, over a 4-year
period, consulted the neurological clinic, were interviewed by questionnaire,
examined, diagnosed, treated, and followed up by pediatric neurologists. The
result from the questionnaire was used to define the type of headache according
to the ICHD II criteria. The clinical features were analyzed and clinical
diagnosis was compared with diagnoses using the International Classification of
Headache disorders. RESULTS: Three hundred and seventy-five primary headache
patients were defined by ICHD II criteria. One hundred twenty eight (35.2%) were 
migraine, 47 (12.5%) were tension-type, 123 (33.3%) were probable migraine, 31
(8.3%) were probable tension-type, and 40 (10.7%) cannot be classified because
the symptoms were not compatible with diagnosed criteria. Using clinical
diagnosis as the standard, the sensitivity of the ICHD-based definition of
migraine without aura and probable migraine was 89.96% whereas the specific was
65.09%. On the other hand, the sensitivity of the International Classification of
Headache disorders-based definition of infrequent episodic tension-type and
probable infrequent episodic tension-type was 56.34% whereas the specific was
87.50%. CONCLUSION: The present study shows the increase of sensitivity but
decrease of the specificity of ICHD II criteria in diagnosed pediatric migraine
headache. However, the duration of attack and quality of headache are still the
limitation of diagnosis for pediatric headache. Therefore, the diagnosis criteria
in pediatric headache should be developed distinctly from adults.

PMID: 17710970 [PubMed - indexed for MEDLINE]

626: Acta Neurol Belg. 2007 Jun;107(2):40-6.

Is the Migraid device an asset in the non-pharmacologic treatment of migraine?

Pieterse H, Kuster JA, Van Bortel LM.

Heymans Institute of Pharmacology, Ghent University, Ghent, Belgium.
pieterse@profess.nl

Non-pharmacologic treatment of migraine attacks is advised by guidelines to be
considered. Some patients use digital massage of the temporal arteries. The
Migraid device exerts a constant pressure on the temporal arteries and may be an 
alternative for the tiring digital massage. The present study investigates
whether the new Migraid device may improve migraine symptoms. In a randomised
multi-centre cross-over study the efficacy, safety and tolerability of a 1-hour
use of the Migraid device at the start of the aura is compared with no-device in 
the treatment of migraine attacks with typical aura. Of the 134 patients who
entered the study, 98 were suitable for the intention-to-treat analysis and 83
patients completed the study. Data on 94 Migraid treated and 87 non-treated
attacks have been analysed. Twelve percent of patients (10/83) were pain-free at 
2 hours in the Migraid group versus 1.6% (1/64) in the non-treated group (p =
0.02). After 24-hours 9.6% of patients were pain-free with the Migraid versus 0% 
with no treatment. After 2 hours 31.3% of patients perceived the migraine
headache as severe using the Migraid versus 53.1% with no treatment. For nausea
this was 6.1% and 15.6%, respectively (p = 0.01). The device was well tolerated. 
In conclusion, 1-hour use of the Migraid device at the start of the aura improved
headache and other migraine symptoms compared to no treatment. Future research
with a more appropriate control should determine whether the Migraid effects are 
going beyond unspecific placebo effects.

Publication Types: 
    Clinical Trial
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 17710839 [PubMed - indexed for MEDLINE]

627: Clin Neurophysiol. 2007 Oct;118(10):2297-304. Epub 2007 Aug 20.

Effects of levetiracetam vs topiramate and placebo on visually evoked phase
synchronization changes of alpha rhythm in migraine.

de Tommaso M, Marinazzo D, Nitti L, Pellicoro M, Guido M, Serpino C, Stramaglia
S.

Center Tecnologie Innovative per la Rivelazione e l'Elaborazione del Segnale,
Università degli Studi di Bari, Italy. m.detommaso@neurol.uniba.it

OBJECTIVE: Recent theories about migraine pathogenesis have outlined an abnormal 
central processing of sensory signals, also suggested by an abnormal pattern of
EEG hyper-synchronization under visual stimulation. The aim of the present study 
was to test the efficacy of topiramate and levetiracetam vs placebo in a double
blind project observing the effects of the three treatments on the EEG
synchronization in the alpha band under sustained flash stimulation. METHODS:
Forty-five migraine without aura outpatients (MO) were selected and randomly
assigned to 100mg topiramate, 1000 mg levetiracetam or placebo treatment. In
addition, 24 non-migraine healthy controls were submitted to EEG analysis. The
EEG was recorded by 19 channels: flash stimuli with a luminosity of 0.2J were
delivered, in a frequency range from 3 to 30 Hz. We evaluated the phase
synchronization index, that we previously applied in migraine, after EEG signals 
filtering in the alpha band. Our approach was based on the Hilbert transform.
RESULTS: Both levetiracetam and topiramate significantly decreased migraine
frequency, compared with placebo. MO patients displayed increased alpha-band
phase synchronization as an effect of stimulus frequency; on the other hand the
stimuli had an overall desynchronizing effect on control subjects. The phase
synchronization index separates the two stages, before and after the treatment,
only for levetiracetam, at stimulus frequencies of 9, 18, 24 and 27 Hz.
CONCLUSIONS: An abnormal alpha band synchronization under visual stimuli was
confirmed in migraine; this phenomenon was reversed by levetiracetam preventive
treatment. SIGNIFICANCE: These results confirmed in humans the inhibiting action 
of levetiracetam on neuronal hyper-synchronization.

Publication Types: 
    Comparative Study
    Randomized Controlled Trial

PMID: 17709295 [PubMed - indexed for MEDLINE]

628: Clin Ther. 2007 May;29(5):939-49.

The cycle of migraine: patients' quality of life during and between migraine
attacks.

Freitag FG.

Diamond Headache Clinic Ltd, Chicago, IL 60614, USA. dhcdoc@aol.com

BACKGROUND: Despite advances in therapy, the prevalence of migraine has remained 
constant over the past 17 years. The current diagnostic procedure for migraine
does not take into account the entire cycle of migraine, which includes both the 
pain of the acute attack and the worry between attacks. OBJECTIVES: This review
discusses the effects of migraine on health-related quality of life. The focus is
on the impact of migraine between attacks and more successful clinical management
of the complete cycle of migraine in both the neurology and primary care
settings. METHODS: A search of MEDLINE (January 1997-January 2007) was conducted 
to determine the impact of migraine on quality of life and the need for and use
of migraine preventive treatment. The search terms were migraine prevention,
migraine prophylaxis, bead-ache and quality of life, migraine disability, and
head-ache disability. The inclusion of specific studies was based on subjective, 
comparative evaluation and standard levels of evidence. Older publications were
included to provide a historical perspective. RESULTS: Worry in expectation of
the next migraine attack can have negative effects on the family and social lives
and work productivity of patients with migraine. The benefits of preventive
pharmacotherapy for migraine may be measured over time in terms of changes in the
frequency of acute attacks, impact of acute treatment on headache recurrence
within the next 24 hours, and reduction in overall functional impairment.
Optimizing the acute treatment outcome and reducing the frequency of episodes may
help alleviate the cycle of migraine. The clinical assessment of migraine should 
include multiple dimensions. Several questionnaires, such as the Migraine
Disability Assessment and the 6-item Headache Impact Test, have been developed to
help clinicians assess the dimensions of migraine. These questionnaires should be
used in conjunction with open communication techniques that elicit any underlying
worry associated with migraines. Preventive therapies that have been approved by 
the US Food and Drug Administration include the neurostabilizers divalproex
sodium and topiramate, and the beta-blockers timolol and propranolol. Despite not
being approved for this indication, the antidepressant amitriptyline has shown
levels of evidence of efficacy in preventing migraine in controlled trials
similar to those for the approved medications. CONCLUSION: The assessment of
whether patients with migraine may benefit from preventive therapy should include
the use of open communication techniques to uncover possible impairment between
attacks.

Publication Types: 
    Meta-Analysis
    Research Support, Non-U.S. Gov't
    Review

PMID: 17697913 [PubMed - indexed for MEDLINE]

629: Anaesthesia. 2007 Sep;62(9):956-8.

Apnoeic spells following general anaesthesia in a patient with familial
hemiplegic migraine.

Willson J, Kapur S.

Department of Anaesthesia and Intensive Care, Russells Hall Hospital, Dudley,
West Midlands DY1 2HQ, UK. jeremy@willson.org.uk

Hemiplegic migraine is an unusual variant of migraine, characterised by a
temporary hemiparesis or hemiplegia associated with headache. We report a patient
with hemiplegic migraine who developed atypical migraine with apnoeic spells,
aphasia and hemiparesis following general anaesthesia. We review the clinical
features of hemiplegic migraine and the considerations for its anaesthetic
management.

Publication Types: 
    Case Reports

PMID: 17697227 [PubMed - indexed for MEDLINE]

630: Clin Exp Optom. 2007 Sep;90(5):371-5.

Branch retinal artery occlusion during a migraine attack.

Gutteridge IF, McDonald RA, Plenderleith JG.

Department of Optometry and Vision Sciences, The University of Melbourne,
Parkville VIC 3053, Australia. i.gutteridge@optometry.unimelb.edu.au

A 60-year-old male with a history of migraine presented with evidence of branch
retinal arterial occlusion that developed at the time of an attack of retinal
migraine. The diagnosis of branch arterial occlusion secondary to migraine was
made after exclusion of numerous possible medical conditions. The possible role
of vasospasm in this condition is discussed.

Publication Types: 
    Case Reports

PMID: 17697184 [PubMed - indexed for MEDLINE]

631: Expert Opin Pharmacother. 2007 Aug;8(12):1821-35.

A pharmacogenomic evaluation of migraine therapy.

Johnson MP, Fernandez F, Colson NJ, Griffiths LR.

Griffith University, Genomics Research Centre, School of Medical Science, PMB 50 
GCMC Gold Coast, Queensland, Australia.

Migraine is a common idiopathic primary headache disorder with significant
mental, physical and social health implications. Accompanying an intense
unilateral pulsating head pain other characteristic migraine symptoms include
nausea, emesis, phonophobia, photophobia and in approximately 20-30% of migraine 
cases, neurologic disturbances associated with the aura phase. Although selective
serotonin (5-HT) receptor agonists (i.e., 5-HT(1B/1D)) are successful in
alleviating migrainous symptoms in < or = 70% of known sufferers, for the
remaining 30%, additional migraine abortive medications remain unsuccessful, not 
tested or yet to be identified. Genetic characterization of the migrainous
disorder is making steady progress with an increasing number of genomic
susceptibility loci now identified on chromosomes 1q, 4q, 5q, 6p, 11q, 14q, 15q, 
17p, 18q, 19p and Xq. The 4q, 5q, 17p and 18q loci involve endophenotypic
susceptibility regions for various migrainous symptoms. In an effort to develop
individualized pharmacotherapeutics, the identification of these migraine
endophenotypic loci may well be the catalyst needed to aid in this goal. In this 
review the authors discuss the present treatment of migraine, known genomic
susceptibility regions and results from migraine (genetic) association studies.
The authors also discuss pharmacogenomic considerations for more individualized
migraine prophylactic treatments.

Publication Types: 
    Review

PMID: 17696786 [PubMed - indexed for MEDLINE]

632: CNS Neurol Disord Drug Targets. 2007 Aug;6(4):258-64.

Nitric oxide in migraine.

Neeb L, Reuter U.

Charité Campus Mitte, Universitätsmedizin Berlin, Department of Neurology,
Charitéplatz 1, 10117, Berlin, Germany.

The potent vasodilatator and messenger molecule nitric oxide (NO) is believed to 
play a key role in migraine pathogenesis. NO donors such as glyceryl trinitrate
(GTN) can cause headache. Infusion of GTN leads to a migraine attack in
migraineurs with a latency of 4 to 6 hours. In this review we focus in the role
of nitric oxide and the transcription factor nuclear factor-kappaB (NF-kappaB) in
migraine pathophysiology in humans and animal models. NO is involved in pain
transmission, hyperalgesia, chronic pain, inflammation and central sensitization 
mostly in a cyclic guanosinemono-phosphate (cGMP) dependent way. We aim to
illustrate how NO is implicated in the induction of a migraine attack in
migraineurs and how experimental animal models may help to elucidate the
mechanisms of the human GTN response. Because of the role of NO in migraine we
try to assess if and how the action of preventative migraine drugs involves the
NO pathways. More knowledge about the involvement of NO in the genesis of
migraine headache may also provide possible future therapeutic targets for acute 
migraine therapy.

Publication Types: 
    Review

PMID: 17691982 [PubMed - indexed for MEDLINE]

633: CNS Neurol Disord Drug Targets. 2007 Aug;6(4):251-7.

The role of glutamate and its receptors in migraine.

Vikelis M, Mitsikostas DD.

Athens Naval Hospital, Neurology Department, Athens, Greece.

Glutamate (Glu) is the principal excitatory neurotransmitter in the central
nervous system. Its receptors are classified into ionotropic receptors, which are
ion channels and include NMDA, AMPA and kainate receptors, named after the
agonists that selectively bind to them, and metabotropic receptors, which are
G-protein coupled receptors. The trigeminal system is considered to play a key
role in migraine pathophysiology, trafficking pain signals from the head and face
to the trigeminal nucleus caudalis. The role of glutamate in the pathophysiology 
of migraine is implicated by data from animal and human studies. Animal studies
include experiments of cortical spreading depression, studies of c-fos protein
expression in trigeminal nucleus caudalis, studies of plasma protein
extravasation and electrophysiological studies. Human studies investigating the
role of Glu in migraine pathogenesis measured the levels of Glu in plasma,
platelets and cerebrospinal fluid, studied its effect on migraine symptoms and
examined the effect of Glu in modulating sensitization. Findings from both the
animal and the human studies suggest a link between glutamate and migraine and
further suggest that glutamate plays a key role in migraine mechanisms. In the
future, efforts should be made to further investigate the role of glutamate in
migraine pathogenesis and, subsequently, in migraine treatment.

Publication Types: 
    Review

PMID: 17691981 [PubMed - indexed for MEDLINE]

634: CNS Neurol Disord Drug Targets. 2007 Aug;6(4):247-50.

GABAergic drugs for the treatment of migraine.

Puppe A, Limmroth V.

Department of Neurology, Cologne City Hospitals, University of Cologne, Germany.

Within the last decades significant progress has been made in the understanding
of the underlying pathophysiological mechanisms of migraine. There is a general
agreement now that migraine is not only a vascular phenomenon but also a
genetically determined heterogenic ion-channelopathy resulting in
cortical-spreading-depression-like events, the temporary impairment of
antinociceptive structures of the brainstem and the activation of the
trigeminal-vascular system. The development and use of drugs targeting
ion-channels and subsequently reducing cortical excitability appears as a
promising avenue for both the acute treatment of migraine and migraine
prevention. This review summarizes the current knowledge and evidence for
GABAergic drugs in the treatment of migraine.

Publication Types: 
    Review

PMID: 17691980 [PubMed - indexed for MEDLINE]

635: CNS Neurol Disord Drug Targets. 2007 Aug;6(4):240-6.

CGRP-receptor antagonism in migraine treatment.

Edvinsson L, Petersen KA.

Department of Medicine, Institute of Clinical Sciences, Lund University Hospital,
Lund, Sweden. lars.edvinsson@med.lu.se

Primary headaches are among the most prevalent neurological disorders, afflicting
up to 16% of the adult population. Associated pain originates from intracranial
blood vessels that are innervated by sensory nerves storing several
neurotransmitters. In primary headaches, there is a clear association between the
headache and the release of calcitonin gene-related peptide (CGRP) but not with
other neuronal messengers. The specific purpose of this review is to describe
CGRP in the human cranial circulation and to elucidate a possible role for a
specific antagonist in the treatment of primary headaches. Acute treatment by
administration of a triptan (5-HT(1B/1D) agonist) results in alleviation of the
headache and normalization of the elevated CGRP level. The mechanism of action of
triptans involves vasoconstriction of intracranial vessels and a presynaptic
inhibitory effect of the trigeminal sensory nerves. The central role of CGRP in
migraine and cluster headache pathophysiology has led to the search for small
molecule CGRP antagonists, which would predictably have less cardiovascular side 
effects as compared to the triptans. The initial pharmacological profile of such 
a group of compounds has recently been disclosed. These compounds have high
selectivity for human CGRP receptors and are reported to be efficacious in the
relief of acute attacks of migraine.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 17691979 [PubMed - indexed for MEDLINE]

636: CNS Neurol Disord Drug Targets. 2007 Aug;6(4):235-7.

5HT1F- and 5HT7-receptor agonists for the treatment of migraines.

Agosti RM.

Board Certified Neurologist, Headache Center Zurich Hirslanden, Zurich,
Switzerland. Reto.agosti@kopfwww.ch

Serotonin was the first neurotransmitter believed to be involved in cephalic pain
transfer forward to the cortex, but the precise mechanism was confirmed only
after sumatriptan, a 5-HT(1B/1D0) high affinity agonist, was introduced in the
acute treatment of migraine. Although very efficient for migraine relief,
activation of 5-HT(1B) receptor may also cause vasoconstriction outside brain,
within the heart arteries for example. Unlike 5-HT(1B), the 5-HT(1D) receptor is 
not located in vascular tissues but exclusively within neuronal, but high
affinity agonists for 5-HT(1D) failed to prove clinical significance in
randomized trials. The recent clone of 5-HT(1F) receptor together with data
showing that sumatriptan exerts high affinity for this receptor subtype generated
high expectations. Potent agonists for 5-HT(1F) receptors were effective in
animal models for migraine and later clinical trials showed efficacy even in
humans, introducing the first line future anti-migraine drugs. Apart from
5-HT(1F), another new cloned 5-HT subtype receptor, the 5-HT(7) also attracts
attention. Recently developed and clinically tested selective 5HT(7) antagonists 
SB-269970-A and SB-656104-A suggest that the receptor may play a role in other
CNS disorders including anxiety and cognitive disturbances, suggesting a
potential role for the migraine prophylaxis. These data and speculations are
discussed in details in this paper with special references.

Publication Types: 
    Review

PMID: 17691977 [PubMed - indexed for MEDLINE]

637: Acta Neurochir Suppl. 2007;97(Pt 1):121-8.

Stimulation of the occipital nerve for the treatment of migraine: current state
and future prospects.

Rogers LL, Swidan S.

Division Chronic Pain Management, Department of Anesthesiology, Duke University, 
USA. wcpc2001@earthlink.net

Migraine is a common disabling malady. Despite the development of therapeutic
agents such as the triptans, a significant number of patients continue to suffer.
The evolution of peripheral nerve stimulation for headache management, may
significantly improve the management of those who suffer from moderate to
refractory migraine symptoms.

Publication Types: 
    Review

PMID: 17691367 [PubMed - indexed for MEDLINE]

638: J Neural Transm. 2008;115(1):91-5. Epub 2007 Aug 10.

Family-based association analysis of functional VNTR polymorphisms in the
dopamine transporter gene in migraine with and without aura.

Karwautz A, Campos de Sousa S, Konrad A, Zesch HE, Wagner G, Zormann A, Wanner C,
Breen G, Ray M, Kienbacher C, Natriashvili S, Collier DA, Wöber C, Wöber-Bingöl
C.

Headache Outpatient Centre, Department of Child and Adolescent Psychiatry,
Medical University of Vienna, Vienna, Austria. andreas.karwautz@meduniwien.ac.at

Because of the role of dopamine in triggering migraine attacks, genes of the
dopamine system are candidates for involvement in migraine. We examined three
VNTR polymorphisms in the dopamine transporter, the 5'UTR VNTR, the intron 8 VNTR
and the intron 14 VNTR, in a sample of 205 family trios. We used the transmission
disequilibirium test (TDT) to examine the transmission of these three markers and
their haplotypes to offspring affected by migraine. We found no significant
transmission distortion of any marker. Likewise haplotypes of the three markers
did not show significant overall or individual association with migraine. Finally
we examined migraine with and without aura, and likewise found no association
between dopamine transporter VNTRs or their haplotypes and either classification 
of the disease. We conclude that functional genetic variation in the dopamine
transporter does not act as a significant risk factor for migraine.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17690944 [PubMed - indexed for MEDLINE]

639: Stroke. 2007 Sep;38(9):2438-45. Epub 2007 Aug 9.

Comment in:
    Stroke. 2007 Sep;38(9):2407-8.

Probable migraine with visual aura and risk of ischemic stroke: the stroke
prevention in young women study.

MacClellan LR, Giles W, Cole J, Wozniak M, Stern B, Mitchell BD, Kittner SJ.

Department of Epidemiology and Preventive Medicine, University of Maryland School
of Medicine, Baltimore, MD 21201, USA.

BACKGROUND AND PURPOSE: Migraine with aura is associated with ischemic stroke,
but few studies have investigated the clinical and anatomic features of this
association. We assessed the association of probable migraine with and without
visual aura with ischemic stroke within subgroups defined by stroke subtype,
vascular territory, probable migraine characteristics, and other clinical
features. METHODS: Using data from a population-based, case-control study, we
studied 386 women ages 15 to 49 years with first ischemic stroke and 614 age- and
ethnicity-matched controls. Based on their responses to a questionnaire on
headache symptoms, subjects were classified as having no migraine, probable
migraine without visual aura, or probable migraine with visual aura (PMVA).
RESULTS: Women with PMVA had 1.5 greater odds of ischemic stroke (95% CI, 1.1 to 
2.0); the risk was highest in those with no history of hypertension, diabetes, or
myocardial infarction compared to women with no migraine. Women with PMVA who
were current cigarette smokers and current users of oral contraceptives had
7.0-fold higher odds of stroke (95% CI, 1.3 to 22.8) than did women with PMVA who
were nonsmokers and non-oral contraceptive users. Women with onset of PMVA within
the previous year had 6.9-fold higher adjusted odds of stroke (95% CI, 2.3 to
21.2) compared to women with no history of migraine. CONCLUSIONS: PMVA was
associated with an increased risk of stroke, particularly among women without
other medical conditions associated with stroke. Behavioral risk factors,
specifically smoking and oral contraceptive use, markedly increased the risk of
PMVA, as did recent onset of PMVA.

Publication Types: 
    Research Support, N.I.H., Extramural

PMID: 17690308 [PubMed - indexed for MEDLINE]

640: J Pain. 2007 Nov;8(11):869-78. Epub 2007 Aug 9.

Contribution of myofascial trigger points to migraine symptoms.

Giamberardino MA, Tafuri E, Savini A, Fabrizio A, Affaitati G, Lerza R, Di Ianni 
L, Lapenna D, Mezzetti A.

Headache Center, Department of Medicine and Science of Aging, G. D'Annunzio
University; Ce.S.I., G. D'Annunzio Foundation, Chieti, Italy. mag@unich.it

This study evaluated the contribution of myofascial trigger points (TrPs) to
migraine pain. Seventy-eight migraine patients with cervical active TrPs whose
referred areas (RAs) coincided with migraine sites (frontal/temporal) underwent
electrical pain threshold measurement in skin, subcutis, and muscle in TrPs and
RAs at baseline and after 3, 10, 30, and 60 days; migraine pain assessment
(number and intensity of attacks) for 60 days before and 60 days after study
start. Fifty-four patients (group 1) underwent TrP anesthetic infiltration on the
3rd, 10th, 30th, and 60th day (after threshold measurement); 24 (group 2)
received no treatment. Twenty normal subjects underwent threshold measurements in
the same sites and time points as patients. At baseline, all patients showed
lower than normal thresholds in TrPs and RAs in all tissues (P < .001). During
treatment in group 1, all thresholds increased progressively in TrPs and RAs (P <
.0001), with sensory normalization of skin/subcutis in RAs at the end of
treatment; migraine pain decreased (P < .001). Threshold increase in RAs and
migraine reduction correlated linearly (.0001 < P < .006). In group 2 and normal 
subjects, no changes occurred. Cervical TrPs with referred areas in migraine
sites thus contribute substantially to migraine symptoms, the peripheral
nociceptive input from TrPs probably enhancing the sensitization level of central
sensory neurons. PERSPECTIVE: This article shows the beneficial effects of local 
therapy of active myofascial trigger points (TrPs) on migraine symptoms in
patients in whom migraine sites coincide with the referred areas of the TrPs.
These results suggest that migraine pain is often contributed to by myofascial
inputs that enhance the level of central neuronal excitability.

Publication Types: 
    Clinical Trial
    Controlled Clinical Trial
    Research Support, Non-U.S. Gov't

PMID: 17690015 [PubMed - indexed for MEDLINE]

641: Expert Opin Pharmacother. 2007 Aug;8(11):1605-13.

Menstrual migraine: a review of hormonal causes, prophylaxis and treatment.

Ashkenazi A, Silberstein S.

Thomas Jefferson University, Department of Neurology, Philadelphia, PA 19107,
USA. avi.ashkenazi@jefferson.edu

Migraine in some women is associated with changes in sex hormone levels. Many
women suffer from increased frequency of migraine around the time of menses.
Menstrual migraine (MM) may be more severe than migraine that occurs at other
times of the cycle. The pathogenesis of MM is probably related to declining
estrogen levels after exposure to high levels of the hormone for several days.
The acute treatment of MM is similar to that of non-menstrually-related attacks. 
5-HT(1B/1D) agonists (triptans), ergots, NSAIDs, or combination analgesics may be
used, although the response to some drugs may not be as robust as that of
non-menstrual attacks. Women who suffer from frequent or debilitating MM attacks 
may benefit from perimenstrual prophylaxis that can be either hormonal or
non-hormonal.

Publication Types: 
    Review

PMID: 17685879 [PubMed - indexed for MEDLINE]

642: BMC Neurol. 2007 Aug 7;7:23.

Cardiovascular responses to cognitive stress in patients with migraine and
tension-type headache.

Leistad RB, Sand T, Nilsen KB, Westgaard RH, Stovner LJ.

Department of Neurosciences, Norwegian University of Science and Technology,
Trondheim, Norway. rune.leistad@ntnu.no

BACKGROUND: The purpose of this study was to investigate the temporal
relationship between autonomic changes and pain activation in migraine and
tension-type headache induced by stress in a model relevant for everyday
office-work. METHODS: We measured pain, blood pressure (BP), heart rate (HR) and 
skin blood flow (BF) during and after controlled low-grade cognitive stress in 22
migraineurs during headache-free periods, 18 patients with tension-type headache 
(TTH) and 44 healthy controls. The stress lasted for one hour and was followed by
30 minutes of relaxation. RESULTS: Cardiovascular responses to cognitive stress
in migraine did not differ from those in control subjects. In TTH patients HR was
maintained during stress, whereas it decreased for migraineurs and controls. A
trend towards a delayed systolic BP response during stress was also observed in
TTH. Finger BF recovery was delayed after stress and stress-induced pain was
associated with less vasoconstriction in TTH during recovery. CONCLUSION: It is
hypothesized that TTH patients have different stress adaptive mechanisms than
controls and migraineurs, involving delayed cardiovascular adaptation and reduced
pain control system inhibition.

PMID: 17683636 [PubMed - indexed for MEDLINE]

643: Med J Malaysia. 2007 Mar;62(1):56-8.

The electroencephalogram changes in migraineurs.

Tan HJ, Suganthi C, Dhachayani S, Rizal AM, Raymond AA.

Department of Medicine, Faculty of Medicine, Universiti Kebangsaan Malaysia,
Kuala Lumpur.

Migraine is associated with a variety of electroencephalographic (EEG) changes.
Previous studies using analogue EEG and old diagnostic criteria may under or over
report the prevalence of EEG changes in migraine. The objective of this study was
to reevaluate the EEG changes in migraine patients diagnosed by applying the new 
International Classification of Headache Disorder -2 criteria. This was a case
control study involving 70 migraine patients and 70 age and gender matched
control who were subjected to scalp EEG. The EEG changes during hyperventilation 
(HV), which were significantly more common in the migraine group were theta
activity (34 vs 22, p = 0.038) and frontal intermittent rhythmic delta activity
(FIRDA) (10 vs 3, p = 0.042). Applying the new ICHD -2 diagnostic criteria and
digital EEG, this study yielded previously unrecognized features including FIRDA 
during HV on EEG.

PMID: 17682573 [PubMed - indexed for MEDLINE]

644: J Am Osteopath Assoc. 2007 Jul;107(7):251-8.

Analysis of pooled data from two pivotal controlled trials on the efficacy of
topiramate in the prevention of migraine.

Freitag FG, Forde G, Neto W, Wang DZ, Schmitt J, Wu SC, Hulihan J.

Diamond Headache Clinic, 467 W Deming Place, Chicago, IL 60614-1881, USA.
dhcdoc@aol.com.

CONTEXT: A substantial proportion of the patient population with migraine
headache should be considered for preventive treatment based on the frequency and
disability associated with this disorder. Use of the anticonvulsant topiramate
was previously examined in two large, double-blind, randomized,
placebo-controlled clinical trials of a subset of patients who have 3 to 12
migraine episodes per month. OBJECTIVE: To better characterize the efficacy of
topiramate for prevention of migraine, with or without aura, by pooling and
analyzing data from the two large clinical trials. METHODS: The pooled
intent-to-treat population included 937 patients receiving topiramate at one of
three dosages (50 mg/d, 100 mg/d, 200 mg/d) or placebo. Outcome measures included
change in mean monthly migraine frequency and categorical responder rate
throughout the 26-week doubleblind phase. Results: At daily doses of 100 and 200 
mg, topiramate was associated with significant reductions in mean monthly
migraine frequency throughout the double-blind phase compared with placebo
(P<.001). Significantly more patients treated with these topiramate doses
exhibited high-percentage reductions in monthly migraine frequency (>/=50%
[P<.001], >/=75% [P<.001], 100% [P=.049]) versus placebo. The most common adverse
events included anorexia, cognitive deficits, diarrhea, fatigue, nausea, and
paresthesia. Topiramate (100 mg/d, 200 mg/d) was associated with significant and 
sustained reductions in mean monthly migraine frequency beginning as early as 1
week into therapy. CONCLUSION: Pooled efficacy data from two large, similarly
designed, placebo-controlled migraine-prevention trials demonstrated that a
statistically significant proportion of patients using topiramate met or exceeded
two main outcome guidelines recommended by the International Headache Society
(>/=50% and >/=75% reduction in frequency of monthly attacks). Based on efficacy 
and tolerability, topiramate at a dosage of 100 mg per day (50 mg twice daily)
should be the target dosage for most patients with migraine.

Publication Types: 
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 17682112 [PubMed - indexed for MEDLINE]

645: J Neurol Neurosurg Psychiatry. 2008 Apr;79(4):415-7. Epub 2007 Aug 6.

Greater occipital nerve block using local anaesthetics alone or with
triamcinolone for transformed migraine: a randomised comparative study.

Ashkenazi A, Matro R, Shaw JW, Abbas MA, Silberstein SD.

Department of Neurology, Thomas Jefferson University, 111 South 11th Street,
Suite 8130, Philadelphia, PA 19107, USA. avi.ashkenazi@jefferson.edu

OBJECTIVE: To determine whether adding triamcinolone to local anaesthetics
increased the efficacy of greater occipital nerve block (GONB) and trigger-point 
injections (TPIs) for transformed migraine (TM). METHODS: Patients with TM were
randomised to receive GONB and TPIs using lidocaine 2% and bupivacaine 0.5% +
either saline or triamcinolone 40 mg. We assessed the severity of headache and
associated symptoms before and 20 minutes after injection. Patients documented
headache and severity of associated symptoms for 4 weeks after injections.
Changes in symptom severity were compared between the two groups. RESULTS:
Thirty-seven patients were included. Twenty minutes after injection, mean
headache severity decreased by 3.2 points in group A (p<0.01) and by 3.1 points
in group B (p<0.01). Mean neck pain severity decreased by 1.5 points in group A
(p<0.01) and by 1.7 points in group B (p<0.01). Mean duration of being
headache-free was 2.7+/-3.8 days in group A and 1.0+/-1.1 days in group B (p =
0.67). None of the outcome measures differed significantly between the two
groups. Both treatments were well tolerated. CONCLUSIONS: Adding triamcinolone to
local anaesthetics when performing GONB and TPIs was not associated with improved
outcome in this sample of patients with TM.

Publication Types: 
    Comparative Study
    Randomized Controlled Trial

PMID: 17682008 [PubMed - indexed for MEDLINE]

646: Cephalalgia. 2007 Sep;27(9):1055-60. Epub 2007 Aug 6.

Symptoms of cutaneous sensitivity pre-treatment and post-treatment: results from 
the rizatriptan TAME studies.

Cady R, Martin V, Mauskop A, Rodgers A, Hustad CM, Ramsey KE, Skobieranda F.

Banyan Group Inc, Springfield, MO 65807, USA. rcady@banyangroupinc.com

The presence of cutaneous allodynia may predict response to triptans. Identical
randomized double-blind studies were conducted comparing the efficacy of
rizatriptan 10 mg or placebo administered within 1 h of headache onset, while
pain was mild. The primary endpoint was freedom from pain at 2 h. Presence of
symptoms suggesting cutaneous sensitivity (SCS) at baseline and at 2 h
post-treatment was recorded. Before treatment, 29% of rizatriptan patients and
22% of placebo patients reported SCS. At 2 h, the percentage of patients with SCS
was significantly decreased with rizatriptan. The presence of SCS pre-treatment
was not predictive of response to rizatriptan. Most patients with SCS at 2 h were
non-responders. Early treatment with rizatriptan significantly reduced the
percentage of patients with SCS at 2 h. The presence of SCS at baseline did not
predict pain-free response, but presence of SCS at 2 h correlated with lack of a 
2-h pain-free response.

Publication Types: 
    Randomized Controlled Trial

PMID: 17681023 [PubMed - indexed for MEDLINE]

647: Cephalalgia. 2007 Sep;27(9):1000-4. Epub 2007 Aug 6.

Patterns of triptans use: a study based on the records of a community
pharmaceutical department.

Pavone E, Banfi R, Vaiani M, Panconesi A.

Pharmaceutical Department ASL 11, Empoli, Florence, Italy.
e.pavone@usl11.toscana.it

Studies performed in selected populations show that the use of triptans for
migraine is low. Our study was aimed at establishing patterns of triptan
utilization in a large community using the drug prescription database of a
regional Health Authority in Italy. In a population of 224,065 residents, 0.55%
received at least one prescription of triptans in 1 year: 77.9% were female and
22.1% male. Oral dosage forms accounted for 94% of prescriptions. About 60% of
patients received a single prescription (containing one or two packages) of one
triptan in 1 year. Age distribution showed that 7% of patients were aged > 65
years. They received 14% of packages, prevalently sumatriptan and zolmitriptan
(the two triptans with the longest commercialization in Italy); 5.7% of patients 
received 40% of packages. Moreover, 3.2% of triptans users received > 120 dosage 
units in the year in the form of tablets (>10 single doses/month), and were
potential triptan abusers. Our data indicate suboptimal treatment of migraine
patients and also incorrect treatment of some patients (potential triptans
abusers, the elderly).

PMID: 17681022 [PubMed - indexed for MEDLINE]

648: Cephalalgia. 2007 Sep;27(9):1061-8. Epub 2007 Aug 6.

Osmophobia in migraine and tension-type headache and its clinical features in
patients with migraine.

Zanchin G, Dainese F, Trucco M, Mainardi F, Mampreso E, Maggioni F.

Headache Centre, Department of Neurosciences, University of Padua, Padua, Italy. 
giorgio.zanchin@unipd.it

Intolerance to smell is often reported by migraine patients. This study evaluates
osmophobia in connection with the diagnosis of migraine and episodic tension-type
headache (ETTH). The characteristics of this symptom are also investigated. We
recruited from our Headache Centre 1005 patients (772 female, 233 male; age 37
+/- 11 years), of whom 677 were migraine without aura (MoA), 130 migraine with
aura (MA) and 198 TTH. Patients with two or more forms of primary headache were
excluded. Among migraine patients, 43.9% with MoA and 38.5% with MA reported
osmophobia during the attacks; none of the 198 TTH patients suffered this
symptom. Most frequently offending odours were scents (63.9%), food (55.2%) and
cigarette smoke (54.8%). Osmophobia appears structurally integrated into the
migraine history of the patient. It seems to be a peculiar symptom favouring the 
diagnosis of migraine (MoA and MA) in the differential diagnosis with ETTH.

PMID: 17681021 [PubMed - indexed for MEDLINE]

649: Cephalalgia. 2007 Sep;27(9):1024-32. Epub 2007 Aug 3.

Central mechanisms of controlled-release metoprolol in migraine: a double-blind, 
placebo-controlled study.

Siniatchkin M, Andrasik F, Kropp P, Niederberger U, Strenge H, Averkina N,
Lindner V, Stephani U, Gerber WD.

Neuropaediatric Department, Christian-Albrechts-University of Kiel, Kiel,
Germany. m.siniatchkin@pedneuro.uni-kiel.de

beta-Blockers are widely used in the prophylaxis of migraine and have been
described as very effective drugs in many studies. Some investigators have
demonstrated that the clinical improvement of migraine corresponds to the
normalization of the contingent negative variation (CNV), a slow cortical
potential measuring cortical information processing. However, most of these
studies have contained a variety of methodological pitfalls, which we attempted
to address in the current study. Twenty patients suffering from migraine without 
aura were randomly divided into two groups. The groups were treated either with
controlled-release metoprolol or placebo for 3 months, using a double-blind
design. Twice before and once after each month of the treatment the CNV was
recorded. After 3 months, a significant reduction of migraine frequency, duration
and intensity was demonstrated for the metoprolol compared with the placebo
group. The CNV was characterized by a marked reduction of the amplitude of the
total CNV and postimperative negative variation and normalization of the eartly
CNV habituation following treatment. Therefore, metoprolol may exert its
prophylactic effect in migraine through the influence on cortical information
processing and excitability represented by the CNV.

Publication Types: 
    Randomized Controlled Trial

PMID: 17680819 [PubMed - indexed for MEDLINE]

650: Med J Aust. 2007 Aug 6;187(3):142-6.

Management of migraine in Australian general practice.

Stark RJ, Valenti L, Miller GC.

Neurology Department, Alfred Hospital, Melbourne, VIC, Australia.
richard.stark@med.monash.edu.au

OBJECTIVES: To determine the proportion of patients who have a diagnosis of
migraine in a sample of Australian general practice patients, and to review the
prophylactic and acute drug treatments used by these patients. DESIGN, SETTING
AND PARTICIPANTS: A cohort of general practitioners collected data from about 30 
consecutive patients each as part of the BEACH (Bettering the Evaluation and Care
of Health) program; this is a continuous national study of general practice
activity in Australia. The migraine substudy was conducted in June-July 2005 and 
December 2005-January 2006. MAIN OUTCOME MEASURES: Proportion of patients with a 
current diagnosis of migraine; frequency of migraine attacks; current and
previous drug treatments; and appropriateness of treatment assessed using
published guidelines. RESULTS: 191 GPs reported that 649 of 5663 patients (11.5%)
had been diagnosed with migraine. Prevalence was 14.9% in females and 6.1% in
males. Migraine frequency in these patients was one or fewer attacks per month in
77.1% (476/617), two per month in 10.5% (65/617), and three or more per month in 
12.3% (76/617) (missing data excluded). Only 8.3% (54/648) of migraine patients
were currently taking prophylactic medication. Patients reporting three or more
migraines or two migraines per month were significantly more likely to be taking 
prophylactic medication (19.7% and 25.0%, respectively) than those with less
frequent migraine attacks (3.8%) (P < 0.0001). Prophylactic medication had been
used previously by 15.0% (96/640). The most common prophylactic agents used
currently or previously were pizotifen and propranolol; other appropriate agents 
were rarely used, and inappropriate use of acute medications accounted for 9% of 
"prophylactic treatments". Four in five migraine patients were currently using
acute medication as required for migraine, and 60.6% of these medications
conformed with recommendations of the National Prescribing Service. However,
non-recommended drugs were also used, including opioids (38% of acute
medications). CONCLUSIONS: Migraine is recognised frequently in Australian
general practice. Use of acute medication often follows published guidelines.
Prophylactic medication appears to be underutilised, especially in patients with 
frequent migraine. GPs appear to select from a limited range of therapeutic
options for migraine prophylaxis, despite the availability of several other well 
documented efficacious agents, and some use inappropriate drugs for migraine
prevention.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17680738 [PubMed - indexed for MEDLINE]

651: Am J Med Genet B Neuropsychiatr Genet. 2008 Jan 5;147B(1):37-41.

Genetic association studies of the chromosome 15 GABA-A receptor cluster in
migraine with aura.

Netzer C, Freudenberg J, Toliat MR, Heinze A, Heinze-Kuhn K, Thiele H, Goebel I, 
Nürnberg P, Ptácek LJ, Göbel H, Todt U, Kubisch C.

Institute of Human Genetics, University of Cologne, Cologne, Germany.

Recently, a novel susceptibility locus for migraine with aura (MA) on chromosome 
15q containing three GABA-A receptor subunits has been identified by linkage
analysis in several large pedigrees. To further study the role of this locus in
MA etiology we genotyped 56 SNPs capturing the known common haplotype variations 
of these three candidate genes in a sample comprising 270 MA patients and 273
matched controls. In a single marker analysis, four SNPs displayed nominally
significant (P < 0.05) association with MA. However, after permutation-based
correction for the number of tests performed, the P-values of these SNPs were
non-significant. Furthermore, a replication study of two of these SNPs in a
second independent sample of 379 MA patients and 379 controls did not result in a
significant finding. We also compared haplotype estimates based on case-control
genotypes. Again we could not demonstrate a significant association with the
phenotype after correction for multiple testing. In summary, we found no
convincing evidence for an involvement of common SNPs at the GABA-A receptor
cluster on 15q11-q12 in the pathophysiology of MA. (c) 2007 Wiley-Liss, Inc.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 17680603 [PubMed - indexed for MEDLINE]

652: Int Rev Neurobiol. 2007;82:373-82.

A role for brain cyclooxygenase-2 and prostaglandin-E2 in migraine: effects of
nitroglycerin.

Tassorelli C, Greco R, Armentero MT, Blandini F, Sandrini G, Nappi G.

IRCCS C. Mondino Institute of Neurology Foundation, Pavia, Italy.

Cyclooxygenase-2 (COX-2) may increase prostaglandin E(2) (PGE(2)) production in
central nervous system (CNS) and contribute to the severity of pain responses in 
inflammatory pain. In this chapter, we sought to evaluate the possible role of
COX-2 induction and prostaglandins (PGs) synthesis within neuronal areas proposed
to be involved in migraine genesis in the animal model of migraine based on the
administration of systemic nitroglycerin (NTG). Male Sprague-Dawley rats were
injected with NTG (10mg/kg, i.p.) or vehicle and sacrificed 2 and 4h later. The
hypothalamus and the lower brain stem were dissected out and utilized for the
evaluation of COX-2 expression by means of Western blotting and for the
determination of PGE(2) levels by means of ELISA immunoassay. COX-2 expression
increased in the hypothalamus at 2h and in the lower brain stem at 4h. PGE(2)
levels showed an opposite pattern of change with a decrease in PGE(2) levels at
2h in the hypothalamus and an increase at 4h in the lower brain stem. These data 
support the hypothesis that NTG administration is capable of activating the COX-2
pathway within cerebral areas. This activity may explain the pronociceptive
effect of NTG described in animal and human models of pain. Most importantly,
these findings point to mediators and areas that may be relevant for migraine
pathogenesis and treatment.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17678972 [PubMed - indexed for MEDLINE]

653: Expert Rev Neurother. 2007 Aug;7(8):927-34.

Sumatriptan fast-disintegrating/rapid-release tablets in the acute treatment of
migraine.

Barbanti P, Le Pera D, Cruccu G.

Headache & Pain Unit, Department of Neurological, Motor & Sensorial Sciences,
IRCCS San Raffaele, Rome, Italy. piero.barbanti@sanraffaele.it

Sumatriptan is the first serotonin (5-hydroxytryptamine [5-HT](1B/1D)) receptor
agonist specifically designed for the acute treatment of migraine. A new
sumatriptan fast disintegrating/rapid release tablet (FDT/RRT) using RT
technology has been developed to enhance tablet disintegration and dispersion in 
the stomach with the intention of speeding absorption and onset of effect, hence 
mitigating the effects on the gastrointestinal dysmotility that typically
accompanies the attack. Sumatriptan FDT/RRT is bioequivalent to conventional
tablets, although it provides slightly faster absorption during early post-dose
interval. Clinical trials indicate that sumatriptan FDT/RRT is rapidly effective 
in terms of freedom from pain and return to normal activities, both with early
and late treatment. The drug is well tolerated. In an oral formulation, which is 
the patients' preferred dosing route, sumatriptan FDT/RRT may therefore
constitute an advance in the management of acute migraine attacks.

Publication Types: 
    Review

PMID: 17678486 [PubMed - indexed for MEDLINE]

654: Pediatrics. 2007 Aug;120(2):390-6.

Efficacy of zolmitriptan nasal spray in adolescent migraine.

Lewis DW, Winner P, Hershey AD, Wasiewski WW; Adolescent Migraine Steering
Committee.

Division of Pediatric Neurology, Children's Hospital of the King's Daughters,
Eastern Virginia Medical School, Norfolk, VA 23510, USA. dlewis@chkd.org

OBJECTIVE: The goal was to evaluate the efficacy and tolerability of zolmitriptan
nasal spray in the treatment of adolescent migraine. METHODS: The
"Double-Diamond" study used a novel, single-blind, "placebo challenge" in a
multicenter, randomized, double-blind, placebo-controlled, 2-way, 2-attack,
crossover design. A total of 248 US adolescent patients (12-17 years of age) with
an established diagnosis of migraine, with or without aura, were enrolled. A
single-blind placebo challenge was used for each migraine attack. No additional
medications were taken if a headache response to the initial placebo treatment
was achieved at 15 minutes; if migraine intensity remained moderate or severe,
then patients treated the attack with zolmitriptan (5 mg) nasal spray or placebo 
according to a randomized, crossover schedule (double-blind). The primary
efficacy variable was headache response at 1 hour after treatment. A
comprehensive range of secondary end points included sustained headache response 
at 2 hours. RESULTS: A total of 171 patients (mean age: 14.2 years; 57.3% female)
treated > or = 1 attack with study medication (intention-to-treat population).
The onset of significant pain relief was apparent 15 minutes after treatment with
zolmitriptan nasal spray. At 1 hour after the dose, zolmitriptan nasal spray
produced a higher headache response rate than did placebo (58.1% vs 43.3%).
Zolmitriptan nasal spray was also significantly superior to placebo in
improvement in pain intensity, pain-free rates, sustained resolution of headache,
and resolution of associated migraine symptoms. Return to normal activities was
also consistently faster with zolmitriptan nasal spray than with placebo, with
less use of any escape medication. Treatment with zolmitriptan nasal spray was
well tolerated. CONCLUSIONS: This novel, placebo-challenge study demonstrated
that zolmitriptan nasal spray was well tolerated and provided fast and
significantly effective relief of migraine symptoms in the acute treatment of
adolescent migraine.

Publication Types: 
    Comparative Study
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 17671066 [PubMed - indexed for MEDLINE]

655: Cephalalgia. 2007 Jul;27(7):843-6.

Increased C-reactive protein in young adult patients with migraine.

Vanmolkot FH, de Hoon JN.

Centre for Clinical Pharmacology, University Hospital Gasthuisberg, Herestraat
49, 3000 Leuven, Belgium.

Interictal serum C-reactive protein (CRP) was measured in 50 young adult patients
with migraine and compared with 50 controls. The median CRP level was 1.42 mg/l
in patients with migraine and 0.90 mg/l in controls (P = 0.03). This finding
supports the role of inflammation in migraine, but needs confirmation in larger
controlled studies. Prospective studies may establish whether measurements of CRP
can identify patients with migraine at risk for cardiovascular events.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17668468 [PubMed - indexed for MEDLINE]

656: J Cardiovasc Med (Hagerstown). 2007 Aug;8(8):633-5.

ICE-guided patent foramen ovale (PFO) closure with lastest-generation devices:
the ideal strategy for PFO-related migraine?

Rigatelli G, Cardaioli P, Braggion G, Giordan M, Aggio S, Roncon L.

Interventional Cardiology Unit, Division of Cardiology, Rovigo General Hospital, 
Italy. jackyheart@hotmail.com

Previous studies have suggested that the closure of the patent foramen ovale
(PFO) may reduce or resolve migrainous symptoms, but ideal indications, devices
and techniques are far from being identified definitively. A 21-year-old woman
was referred to our center for evaluation of severe migraine (more than two
attacks per week, > 6 h in duration, inability to work, direct relationship with 
Valsalva manouvre and effort, presence of aura), migraine disability assessment
questionnaire (MIDAS) score of 42 and a large PFO with no atrial septal aneurysm:
on transesophageal echocardiography and instrumental data suggesting a close
relationship between migraine and PFO. Having explained the off-label indications
for transcatheter PFO closure in this particular case, the patient was recruited 
for our in-hospital study protocol for assessment for transcatheter closure of
PFO to relieve severe migraine and the patient gave consent. A 9-Fr, 9-MHz
UltraICE catheter (EP Technologies, Boston Scientific Corporation, San Jose,
California, USA) was then inserted through the left femoral vein and a complete
intracardiac study was carried out. A 25-mm Premere device was successfully
implanted. The patient was discharged the day after being on 75 mg aspirin once a
day for 6 months and, at 3-month follow-up, the patient was well with no further 
migraine attacks (MIDAS score 2). There was no evidence of thrombus formation on 
the surface of device and no shunt was detected on transesophageal
echocardiograhy and transcranial Doppler. Although more clear-cut indications are
required, this case study may be the stimulus and basis for further large
prospective randomized studies to assess the effectiveness of PFO closure in
treating migraine and the best implantation technique and device.

Publication Types: 
    Case Reports

PMID: 17667037 [PubMed - indexed for MEDLINE]

657: Cephalalgia. 2007 Sep;27(9):1043-9. Epub 2007 Jul 30.

Migraine aura lasting 1-24 h in children: a sequence of EEG slow-wave
abnormalities vs. vascular events.

Parain D, Hitzel A, Guegan-Massardier E, Lebas A, Blondeau C, Fédina I, Feray D, 
Véra P, Mihout B.

Department of Neurophysiology, Rouen University Hospital, Rouen Cedex, France.
dominique.parain@chu-rouen.fr

The aim of this study was to describe the abnormalities associated with migraine 
aura lasting 1-24 h in children as shown by EEG, trancranial Doppler (TCD) and
single photon emission computed tomography (SPECT). In this retrospective study, 
11 patients each underwent EEG, TCD and brain SPECT on the day of admission and
the day thereafter. On the day of admission, the migrainous hemisphere of all
patients showed that the mean velocities were decreased in the middle cerebral
artery by TCD, slow-wave abnormalities were recorded after several hours of aura 
by EEG and the SPECT showed hypoperfusion. On the day after, in the same
hemisphere, slow waves were recorded only in the occipital area by EEG, and SPECT
showed slight hyperperfusion. In these patients, there was a clear sequence of
EEG, TCD and SPECT abnormalities.

Publication Types: 
    Comparative Study

PMID: 17666084 [PubMed - indexed for MEDLINE]

658: IDrugs. 2007 Aug;10(8):566-74.

Olcegepant, a non-peptide CGRP1 antagonist for migraine treatment.

Recober A, Russo AF.

Department of Neurology, 2RCP, University of Iowa, Iowa City, IA 52242, USA.
ana-recober@uiowa.edu

Olcegepant is the first potent and selective non-peptide antagonist of the
calcitonin gene-related peptide 1 (CGRP1) receptor, a key modulator in neurogenic
inflammatory pain. Under development by Boehringer Ingelheim GmbH, olcegepant is 
an intravenously formulated treatment for acute attacks of migraine. In
preclinical studies, olcegepant attenuated arterial dilation induced by CGRP or
electrical stimulation. In a phase II clinical trial, olcegepant reduced the
severity of headache in 60% of migraine sufferers and met secondary endpoints
including headache-free rate and rate of sustained response. Only
mild-to-moderate transient adverse events were observed, with no adverse
cardiovascular symptoms reported. The compound appears to be an effective
anti-migraine medication that is well tolerated and does not display the
vasoconstrictive effect that precludes the use of triptans and dihydroergotamine 
in certain patients. For a successful marketing of olcegepant, larger clinical
trials and the development of an effective oral formulation will be necessary.

PMID: 17665333 [PubMed - indexed for MEDLINE]

659: Arq Neuropsiquiatr. 2007 Jun;65(2B):521-3.

Postmeningitis headache: case report.

Matta AP, Ribas MC, Moreira Filho PF.

Hospital Universitário Antônio Pedro, Universidade Federal Fluminense, Niterói
RJ, Brazil.

We report a case of a 18-year-old female patient that developed a migraine-like
headache following an acute meningococcal meningitis. She had no previous history
of recurrent headaches. The pain was intense, pulsatile and throbbing, typically 
unilateral, without aura. Its frequency increased during the following weeks and 
a prophylactic treatment with amitriptyline and atenolol was initiated. There was
remission of the attacks.

Publication Types: 
    Case Reports

PMID: 17665028 [PubMed - indexed for MEDLINE]

660: J Psychosom Res. 2007 Aug;63(2):123-9.

Migraine headaches are not associated with a unique depressive symptom profile:
results from the Baltimore Epidemiologic Catchment Area Study.

Kalaydjian A, Eaton W, Zandi P.

Department of Mental Health, Johns Hopkins Bloomberg School of Public Health,
Baltimore, MD, USA. kalaydjiana@mail.nih.gov

OBJECTIVE: There is a well-established link between migraine headaches and
depression. However, it is unclear whether individuals with migraine experience a
unique profile of depressive symptoms in comparison to individuals without
migraine. METHODS: This question was addressed using data from the Baltimore
cohort of the Epidemiologic Catchment Area Study. The cross-sectional association
between migraine headaches and each depressive symptom was calculated using
logistic regression, and symptom profiles among those with migraine headaches
(n=249) and those without (n=1480) were compared using generalized estimating
equations. RESULTS: Migraine headaches were associated with increased odds of
reporting seven of nine depressive symptom groups by a factor of roughly 2.
However, when the symptom profiles were compared, individuals with migraine
headaches did not differ in their profile of symptoms. CONCLUSION: These results 
suggest that individuals with migraine headaches are more likely to report
depressive symptoms but do not display a unique profile of symptoms.

Publication Types: 
    Research Support, N.I.H., Extramural

PMID: 17662747 [PubMed - indexed for MEDLINE]

661: Eur J Neurol. 2007 Aug;14(8):900-6.

Time course of adverse events most commonly associated with topiramate for
migraine prevention.

Láinez MJ, Freitag FG, Pfeil J, Ascher S, Olson WH, Schwalen S.

University Clinic Hospital, University of Valencia, Valencia, Spain.
jlaineza@meditex.es

The efficacy, safety and tolerability of topiramate has been demonstrated in
three large multicenter, randomized, double-blind, placebo-controlled trials. To 
characterize the time course of adverse events (AEs) that led to treatment
discontinuation in >/=2% of patients who received topiramate 100 mg/day during
three pivotal, multicenter, randomized, double-blind, placebo-controlled, and
26-week trials. The pooled population comprised all randomized patients who
reported safety data during the double-blind phase (topiramate 100 mg/day, n =
386; placebo n = 372), which consisted of a 4-week titration period and a 22-week
maintenance period. Incidence, time to onset, and cumulative mean rate of AEs
were assessed. Overall, AEs led to treatment discontinuation in 24.9% of patients
receiving topiramate 100 mg/day and 11.0% receiving placebo (P < 0.001). AEs
leading to discontinuation during the double-blind phase in > or =2% of patients 
included paresthesia (8.0% discontinued), any cognitive symptoms (7.3%
discontinued), fatigue (4.7% discontinued), insomnia (3.4% discontinued), nausea 
(2.3% discontinued), loss of appetite, anxiety, and dizziness (2.1% discontinued 
because each AE). Most AEs began during the titration period. Paresthesia, any
cognitive symptoms, nausea, and loss of appetite occurred at a higher rate in the
topiramate group than in the placebo group (P < 0.01). AEs leading to
discontinuation of topiramate are probably to occur during dose titration. If a
patient has not experienced one of these AEs within the first 6 weeks of
initiating topiramate 100 mg/day, these AEs are unlikely to occur.

Publication Types: 
    Multicenter Study
    Randomized Controlled Trial

PMID: 17662012 [PubMed - indexed for MEDLINE]

662: Cephalalgia. 2007 Aug;27(8):981-7.

Migraine and ischaemic heart disease and stroke: potential mechanisms and
treatment implications.

Tietjen EG.

Department of Neurology, The University of Toledo-Health Science Campus, Toledo, 
OH 43614, USA. gretchen.tietjen@utoledo.edu

The migraine-ischemia relationship is best understood in the context of the
pathophysiology of migraine. Potential mechanisms of migrainous infarction
(stroke occurring during migraine) include vasospasm, hypercoagulability, and
vascular changes related to cortical spreading depression. Stroke occurring
remote for the migraine attack may be related to arterial dissection,
cardioembolism, and endothelial dysfunction. Endothelial dysfunction, a process
mediated by oxidative stress, may be a cause or a consequence of migraine, and
explain the relationship of migraine to vascular factors and ischemic heart
disease. It remains uncertain whether stroke or myocardial infarction can be
prevented by migraine prophylaxis, endothelial repair, platelet inhibition, or a 
combination of these strategies. Although triptans are generally considered safe 
for use in migraine, caution is warranted in those with multiple vascular risk
factors. Known vascular disease is a contraindication to triptan use.

Publication Types: 
    Review

PMID: 17661875 [PubMed - indexed for MEDLINE]

663: Cephalalgia. 2007 Aug;27(8):965-75.

Erratum in:
    Cephalalgia. 2007 Nov;27(11):1290.

Migraine and ischaemic vascular events.

Kurth T.

Division of Aging, Bringham and Women's Hospital, Boston, MA 02120-1613, USA.
tkurth@rics.bwh.harvard.edu

An association between migraine and ischaemic vascular events, particularly
ischaemic stroke, has been debated for many years. The pathophysiology of
migraine has been explored in detail, and it is known that a dysfunction of brain
cells and arteries is a major component of this disorder. The involvement of
cerebral arteries during the migraine attack as well as the high prevalence of
migraine among young individuals with ischaemic stroke has led to the hypothesis 
that migraine may be a risk factor for ischaemic stroke. Furthermore, there is
evidence that the vascular nature of migraine is not limited to meningeal blood
vessels and that migraine and overall cardiovascular disease may share
aetiological pathways. The aim of this review is to summarize the epidemiological
evidence that links migraine with ischaemic stroke and ischaemic heart disease
and to discuss potential biological mechanisms.

Publication Types: 
    Review

PMID: 17661873 [PubMed - indexed for MEDLINE]

664: Cephalalgia. 2007 Aug;27(8):935-42.

Comment in:
    Cephalalgia. 2008 Sep;28(9):1001-2; author reply 1002.

Sex differences in the transmission of migraine.

Low NC, Cui L, Merikangas KR.

Department of Psychiatry, McGill University, Montreal, Quebec, Canada.

Consistent evidence demonstrates that migraine is far more common in women than
in men, but the explanations for this preponderance have not been systematically 
evaluated. We examined whether the female preponderance is attributable to
genetic factors using data from a controlled family study which included 260
probands and their 1232 first-degree adult relatives. We found that although the 
risk of migraine was three times greater among the relatives of probands with
migraine compared with controls, there was no differential risk of migraine among
the relatives of male vs. female probands with migraine. Taking these data
together with other family studies, we conclude that the increased risk of
migraine in females is likely to result from increased exposure to non-familial
endogenous or exogenous risk factors for migraine that lower the threshold for
expression of migraine in women.

PMID: 17661867 [PubMed - indexed for MEDLINE]

665: Eur J Pain. 2008 Apr;12(3):301-13. Epub 2007 Jul 30.

Butterbur root extract and music therapy in the prevention of childhood migraine:
an explorative study.

Oelkers-Ax R, Leins A, Parzer P, Hillecke T, Bolay HV, Fischer J, Bender S,
Hermanns U, Resch F.

Department of Child and Adolescent Psychiatry, University of Heidelberg,
Blumenstrasse 8, D-69115 Heidelberg, Germany. rieke_oelkers@med.uni-heidelberg.de

BACKGROUND: Migraine is very common in school-aged children, but despite a number
of pharmacological and non-pharmacological options for prophylaxis, randomized
controlled evidence in children is small. Evidence-based prophylactic drugs may
have considerable side effects. OBJECTIVE: This study was to assess efficacy of a
butterbur root extract (Petadolex) and music therapy in primary school children
with migraine. DESIGN: Prospective, randomized, partly double-blind,
placebo-controlled, parallel-group trial. METHODS: Following a 8-week baseline
patients were randomized and received either butterbur root extract (n=19), music
therapy (n=20) or placebo (n=19) over 12 weeks. All participants received
additionally headache education ("treatment as usual") from the baseline onwards.
Reduction of headache frequency after treatment (8-week post-treatment) as well
as 6 months later (8-week follow-up) was the efficacy variable. RESULTS: Data
analysis of subjects completing the respective study phase showed that during
post-treatment, only music therapy was superior to placebo (p=0.005), whereas in 
the follow-up period both music therapy and butterbur root extract were superior 
to placebo (p=0.018 and p=0.044, respectively). All groups showed a substantial
reduction of attack frequency already during baseline. CONCLUSION: Butterbur root
extract and music therapy might be superior to placebo and may represent
promising treatment approaches in the prophylaxis of paediatric migraine.

Publication Types: 
    Comparative Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 17659990 [PubMed - indexed for MEDLINE]

666: Cephalalgia. 2007 Nov;27(11):1271-3. Epub 2007 Jul 26.

Comorbidity of migraine and headache associated with sexual activity.

Biehl K, Evers S, Frese A.

Department of Neurology, University of Münster, Münster, Germany.
kbiehl@uni-muenster.de

In order to investigate the comorbidity of migraine and headache associated with 
sexual activity (HSA), we performed a case-control study based on migraine
patients. By means of a questionnaire and a personal interview, 100 migraine
patients and 100 control subjects were examined regarding a diagnosis of HSA. In 
five subjects from the migraine group vs. none from the control group, a
diagnosis of HSA could be established (P = 0.021). Previous studies that have
demonstrated comorbidity of migraine and HSA were all based on HSA patients.
Thus, it can now be concluded that the association between the two headache
disorders is bilateral. In addition, the prevalence of HSA in the general
population can be estimated to average around at least 0.9%, which concurs with
previously published data.

PMID: 17655717 [PubMed - indexed for MEDLINE]

667: Pharmacotherapy. 2007 Aug;27(8):1092-101.

Economic analysis of triptan therapy for acute migraine: a Medicaid perspective.

Mullins CD, Subedi PR, Healey PJ, Sanchez RJ.

Pharmaceutical Health Services Research Department, University of Maryland School
of Pharmacy, Baltimore, Maryland 21201, USA. dmullins@rx.umaryland.edu

STUDY OBJECTIVE: To compare triptan therapies for migraine in terms of the cost
to treat 100 migraine attacks and the cost per successfully treated patient
(cost/success), by analyzing utilization and reimbursement data from state
Medicaid programs. DESIGN: Pharmacoeconomic analysis. DATA SOURCE: Clinical
efficacy data were obtained from a previously published meta-analysis for 11
triptan-dose combinations: almotriptan 12.5 mg; eletriptan 20 and 40 mg;
naratriptan 2.5 mg; rizatriptan 5 and 10 mg; sumatriptan 25, 50, and 100 mg; and 
zolmitriptan 2.5 and 5 mg. Triptan reimbursement data were obtained from the
Medicaid Drug Rebate Program of seven geographically dispersed states (Florida,
Georgia, Illinois, North Carolina, Ohio, Wisconsin, and West Virginia).
MEASUREMENTS AND MAIN RESULTS: Efficacy measures were derived based on data from 
the published meta-analysis that evaluated headache pain status at 2 and 24 hours
after triptan dosing. Reimbursement data for the triptans were applied to a
previously developed model of migraine treatment outcomes to calculate the cost
to treat 100 migraine attacks and the cost/success. Sensitivity analysis around
dosing assumptions was conducted to assess robustness of estimates. Across the
seven states, the two treatments associated with the lowest cost to treat 100
migraine attacks were eletriptan 20 mg (range $1549-$1658) and eletriptan 40 mg
($1578-$1661). Naratriptan 2.5 mg (range $1734-$2018), sumatriptan 25 mg
($1853-1954), and zolmitriptan 5 mg ($1854-$1960) were associated with the
highest cost to treat 100 migraine attacks. Eletriptan 40 mg was associated with 
the lowest cost/success (range $57.03-$60.05); naratriptan 2.5 mg
($99.39-$115.65), sumatriptan 25 mg ($107.11-$112.93), and rizatriptan 5 mg
($99.41-$111.25) were associated with the highest cost/success values. Changes in
dosing assumptions did not significantly change the rank ordering of triptans
across either economic end point. CONCLUSIONS: Eletriptan 20- and 40-mg doses
were shown to be associated with the lowest cost to treat 100 migraine attacks
and the lowest cost/success in both the baseline and sensitivity analyses. These 
findings are consistent with results of similar economic analyses that compared
multiple triptan therapies.

Publication Types: 
    Comparative Study
    Meta-Analysis
    Research Support, Non-U.S. Gov't

PMID: 17655509 [PubMed - indexed for MEDLINE]

668: Cephalalgia. 2007 Oct;27(10):1166-70. Epub 2007 Jul 23.

Adult-onset hemiplegic migraine with cortical enhancement and oedema.

Cha YH, Millett D, Kane M, Jen J, Baloh R.

Department of Neurology, University of California-Los Angeles, 710 Westwood
Plaza, Los Angeles, CA 90095, USA. yhcha@mednet.ucla.edu

We present genetically identical twin patients who experienced late-onset
migraine with visual and somatosensory auras and later developed hemiplegic
migraines associated with severe cortical oedema and enhancement. Both positron
emission tomography and electroencephalography showed an increase in activity
contralateral to the hemiplegic side. Brain biopsy during the attack showed
reactive astrogliosis and microgliosis. Mutations in CACNA1A, ATP1A2, SLC1A3 and 
NOTCH3 were ruled out by sequencing. This report shows the clinical and genetic
evaluation of a severe form of familial hemiplegic migraine as well as the
evolution of the imaging changes.

Publication Types: 
    Case Reports
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 17645764 [PubMed - indexed for MEDLINE]

669: Cephalalgia. 2007 Aug;27(8):945-9. Epub 2007 Jul 23.

The 1246G-->A polymorphism of the HCRTR2 gene is not associated with migraine.

Pinessi L, Binello E, De Martino P, Gallone S, Gentile S, Rainero I, Rivoiro C,
Rubino E, Savi L, Valfrè W, Vaula G.

Neurology II, Headache Centre, Department of Neuroscience, University of Torino, 
Torino, Italy. lorenzo.pinessi@unito.it

Studies in experimental animals have suggested that the hypocretin/orexin system 
may be involved in migraine pathophysiology. Using a case-control design study,
we genotyped 246 migraine patients and 239 healthy controls for the 1246G-->A
polymorphism of the hypocretin receptor 2 (HCRTR2) gene. Genotypic and allelic
frequencies of the examined polymorphism were similarly distributed between cases
and controls (chi2 = 2.22, P = 0.14 and chi2 = 2.45, P = 0.29, respectively).
When different migraine subgroups were compared (migraine with aura vs. migraine 
without aura and episodic vs. chronic migraine) no significant difference was
found. Comparison of the clinical features of the disease with the 1246G-->A
genotypes showed no significant difference. Our data suggest that the HCRTR2 gene
is not a genetic risk factor in migraine.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17645762 [PubMed - indexed for MEDLINE]

670: Cephalalgia. 2007 Aug;27(8):920-8. Epub 2007 Jul 23.

Impact of preventive therapy with nadolol and topiramate on the quality of life
of migraine patients.

Garcia-Monco JC, Foncea N, Bilbao A, Ruiz de Velasco I, Gomez-Beldarrain M.

Service of Neurology, Hospital de Galdacano, Vizcaya, Spain. hospit05@sarenet.es

Preventive therapy is aimed at reducing migraine frequency, but should also
improve the much deteriorated quality of life of the migraneur. We aimed to
evaluate the impact of preventive therapy with two widely employed drugs
(topiramate and nadolol) on the quality of life of migraine patients. A
population of consecutive migraineurs aged > or = 16 years, with frequent
migraines, was selected prospectively for evaluation at baseline and after 16
weeks of therapy with nadolol or topiramate (40 mg and 100 mg daily,
respectively) by generic and specific quality of life questionnaires (SF-36 and
MSQOL) and by an anxiety and depression scale (HADS). Preventive therapy resulted
in a statistically significant improvement in physical domains of the SF-36,
whereas mental domains remained almost unchanged. Despite this improvement, all
domains remained below the population norms. The HADS revealed a moderate
depressive state at baseline that did not change with therapy. The MSQOL global
score also revealed statistically significant improvement. Both drugs were
similarly effective, although topiramate was superior on the role physical domain
compared with nadolol. Preventive therapy with nadolol and topiramate
significantly improves the quality of life of migraineurs, although additional
efforts are needed to place them in a nearer-to-normal situation compared with
the general population.

Publication Types: 
    Clinical Trial

PMID: 17645757 [PubMed - indexed for MEDLINE]

671: J Child Neurol. 2007 Jun;22(6):720-6.

Self-reported treatment patterns in patients with Sturge-Weber syndrome and
migraines.

Kossoff EH, Balasta M, Hatfield LM, Lehmann CU, Comi AM.

Department of Neurology, Johns Hopkins Medical Institutions, Baltimore, Maryland 
21287, USA. ekossoff@jhmi.edu

Migraine is common in patients with Sturge-Weber syndrome, yet treatment options 
are poorly described. An Internet-based questionnaire was completed anonymously
by 104 Sturge-Weber syndrome patients, 74 of whom reported experiencing migraines
(median age, 25 years; range, 3-64 years). Sixteen (22%) subjects self-reported
trying triptans. Five of 12 (42%) describing triptan response believed they were 
very efficacious (median time of onset of 26 minutes), compared to 13 of 65 (20%)
using over-the-counter analgesics (P = .08). Eighty-eight percent (14/16) of
triptan users self-reported that when they do not use medications, migraines had 
a moderate to severe impact on their quality of life; however, while taking
triptans, only 50% (7/14) of users reported such an impact (P = .03). Two
patients using triptans reported transient unilateral weakness. Of the 26
patients (35%) who received daily preventative medications, 80% experienced
improved quality of life. In addition, only 10 of 24 (42%) reported a significant
negative impact of migraines on quality of life with daily preventative use,
compared to 22 of 26 (85%) without their use (P = .002). Sturge-Weber syndrome
patients with migraines are using triptans and preventative agents and
self-reporting good efficacy. The small sample size precludes any safety
analysis, however, and future prospective trials of both treatment options are
needed.

PMID: 17641257 [PubMed - indexed for MEDLINE]

672: BMC Med. 2007 Jul 17;5:19.

Migraine aura or transient ischemic attacks? A five-year follow-up case-control
study of women with transient central nervous system disorders in pregnancy.

Ertresvg JM, Stovner LJ, Kvavik LE, Johnsen HJ, Zwart JA, Helde G, Bovim G.

Norwegian National Headache Centre, Department of Neurology and Clinical
Neurophysiology, St Olavs Hospital, Trondheim, Norway.
Janne.Ertresvag@helse-sunnmore.no

BACKGROUND: Migraine aura may be difficult to differentiate from transient
ischemic attacks and other transient neurological disorders in pregnant women.
The aims of the present study were to investigate and diagnose all pregnant women
with transient neurological disorders of suspected central nervous system origin,
and to compare this group with a control group of pregnant women with regard to
vascular risk factors and prognosis. METHODS: During a 28 month period, 41
patients were detected with transient neurological symptoms during pregnancy.
These were studied in detail with thorough clinical and laboratory investigations
in order to make a certain diagnosis and to evaluate whether the episodes might
be of a vascular nature. For comparison, the same investigations were performed
in 41 pregnant controls. To assess the prognosis, both patients and controls were
followed with questionnaires every year for five years. RESULTS: Migraine with
aura was the most common cause of symptoms during pregnancy, occurring in 34
patients, while 2 were diagnosed with stroke, 2 with carpal tunnel syndrome, 1
with partial epilepsy, 1 with multiple sclerosis and 1 with presyncope. Patients 
had more headache before pregnancy than controls, but the average levels of
vascular risk factors were similar. None of the patients or the controls reported
cerebrovascular episodes during the five-year follow-up. CONCLUSION: The
diagnosis of migraine aura was difficult because for many patients it was their
first ever attack and headache tended to be absent or of non-migraineous type.
The aura features were more complex, with several aura symptoms and a higher
prevalence of sensory and dysphasic aura than usual. Gradually developing aura
symptoms, or different aura symptoms occurring in succession as described in the 
International Classification of Headache Disorders, seem to be useful for
differentiating aura from other transient disorders. A meticulous history and
clinical neurological examination are more useful than routine supplementary
investigations for cerebrovascular disease. The five-year follow-up clearly
indicates that migraine with aura in pregnancy usually has a good prognosis with 
regard to cerebrovascular events.

PMID: 17640340 [PubMed - indexed for MEDLINE]

673: Cochrane Database Syst Rev. 2007 Jul 18;(1):CD003224.

Update of:
    Cochrane Database Syst Rev. 2001;(3):CD003224.

WITHDRAWN: Eletriptan for acute migraine.

Smith LA, Oldman AD, McQuay HJ, Moore RA.

Oxford Brookes University, School of Health and Social Care, Jack Straws Lane,
Marston, Oxford, UK, OX3 0FL. lesleysmith@brookes.ac.uk

BACKGROUND: Eletriptan (Relpax) is a new triptan soon to be made available by
prescription for the treatment of acute migraine. Currently five triptans are
available by prescription and more are under development. In light of the many
drugs for treating acute migraine, there is a need for evidence-based assessments
to help determine the relative efficacy and harm of these treatments. OBJECTIVES:
To determine the efficacy of eletriptan for treating a single migraine attack
using the outcomes of headache response and pain-free response at 0.5, 1, 2 and 4
hours, and sustained relief over 24 hours. To express efficacy in terms of
number-needed-to-treat (NNT). To determine the adverse effects of a single dose
of eletriptan and express this in terms of number-needed-to-harm (NNH). To allow 
for the comparison of the efficacy of eletriptan with other migraine treatments
evaluated systematically in the same way. SEARCH STRATEGY: Data from all Phase
III randomised placebo-controlled trials were made available by the manufacturer,
Pfizer Inc. To date, these trials comprise the only data on eletriptan relevant
to this review in a published or unpublished form; thus, searches of electronic
databases for further trials of eletriptan were not conducted. Date of last
search: January 2000. SELECTION CRITERIA: Trials of eletriptan for acute
migraine; randomised allocation to treatment groups, including a placebo group;
double-blind design; International Headache Society diagnostic criteria for
migraine with or without aura; single migraine attack; single-dose treatment at
standard doses; adult population; baseline pain of moderate or severe intensity
using a 4-point standardised rating scale (0 = no pain, 1 = mild pain, 2 =
moderate pain and 3 = severe pain); and dichotomous or percentage data for at
least one of the main efficacy outcomes. DATA COLLECTION AND ANALYSIS: Trials
were scored for quality and data extracted by two independent reviewers.
Dichotomous or percentage data were extracted and pooled to calculate the
relative benefit (RB) or relative risk (RR) and NNTs or NNHs for a number of
outcomes for eletriptan 20 mg, 40 mg and 80 mg. The main outcomes considered were
headache response at 1 and 2 hours, pain-free response at 2 hours, sustained
relief over 24 hours and adverse effects. Minor outcomes considered were headache
response at 0.5 and 4 hours, and pain-free response at 0.5, 1 and 4 hours. MAIN
RESULTS: Six trials met the inclusion criteria. Significant benefit of eletriptan
over placebo was shown for eletriptan 20 mg, 40 mg and 80 mg for the primary
efficacy outcomes of headache response and pain-free response at 2 hours. For
headache response at 2 hours, the NNTs (with 95% confidence intervals) were 4.4
(3.4 to 6.2), 2.9 (2.6 to 3.3) and 2.6 (2.4 to 3.0) for eletriptan 20 mg, 40 mg
and 80 mg, respectively. For pain-free response at 2 hours, the NNTs were 9.9
(6.9 to 18), 4.0 (3.6 to 4.5) and 3.7 (3.4 to 4.2), for eletriptan 20 mg, 40 and 
80 mg, respectively.There was no significant difference in the incidence of major
adverse effects between any dose of eletriptan and placebo. The incidence of
minor adverse effects was significantly higher for all eletriptan doses than for 
placebo, with NNHs of 11 (95% confidence interval, 6.2 to 39), 7.0 (5.2 to 11)
and 3.7 (3.1 to 4.5) for eletriptan 20 mg, 40 mg and 80 mg, respectively.
AUTHORS' CONCLUSIONS: Eletriptan 20 mg, 40 mg and 80 mg are effective for the
treatment of an acute migraine attack. Effectiveness is dose-related, with
statistically significant differences between doses for pain-free response and
24-hour outcomes. Eletriptan compares well with other triptans available for
outcomes measured up to 2 hours and provides meaningful relief for 24 hours.
Taken as a single dose, eletriptan was well tolerated and caused no major harm.
The incidence of minor harm was dose-dependent, with 80 mg giving significantly
more adverse effects than 40 mg.

Publication Types: 
    Review

PMID: 17636718 [PubMed - indexed for MEDLINE]

674: Cochrane Database Syst Rev. 2007 Jul 18;(1):CD003221.

Update of:
    Cochrane Database Syst Rev. 2001;(3):CD003221.

WITHDRAWN: Rizatriptan for acute migraine.

Oldman AD, Smith LA, McQuay HJ, Moore RA.

Churchill Hospital, c/o Pain Research Unit, Old Road, Headington, Oxford, UK, OX3
7LJ.

BACKGROUND: There are a number of different drug treatments for acute migraine,
including currently four triptans, with several more likely to become available
in the future. There is a need for evidence-based information to help determine
the balance of benefit and harm for acute migraine treatment. OBJECTIVES: To
quantitatively assess the efficacy of a single dose of rizatriptan (Maxalt) for
treating a single migraine attack using the outcomes of headache response and
pain-free response at half-an-hour, one hour, two hours, and sustained relief
over 24 hours. To express efficacy in terms of numbers-needed-to-treat (NNTs).
SEARCH STRATEGY: Trials were identified by searching MEDLINE (1966-July 2000),
EMBASE (1980-June 2000), the Cochrane Library (Issue 3, 2000) and the Oxford Pain
Relief Database (1950-1994). Date of last search: July 2000. SELECTION CRITERIA: 
The inclusion criteria were randomised, placebo-controlled trials of rizatriptan 
for acute migraine; double-blind design; International Headache Society
diagnostic criteria for migraine with or without aura; single migraine attack;
single-dose treatment at standard doses; adult population; baseline pain of
moderate or severe intensity using a four-point standardised rating scale;
dichotomous or percentage data for at least one of the main efficacy outcomes;
and full journal publication. DATA COLLECTION AND ANALYSIS: Main outcomes
considered were i) headache response at two hours, ii) headache response at one
hour, iii) pain-free response at two hours, iv) sustained relief over 24 hours,
v) pain-free response at 24 hours and vi) adverse effects. Minor outcomes were
headache response and pain-free response at half-an-hour and four hours, and
pain-free response at one hour.Dichotomous or percentage data were extracted and 
used to calculate the relative benefit (RB) and number-needed-to-treat (NNT) for 
each outcome. MAIN RESULTS: Seven trials met our inclusion criteria, with 2626
patients given rizatriptan and 902 given placebo. Significant benefit of
rizatriptan over placebo was shown for both doses of rizatriptan (5 mg and 10 mg)
for all five main efficacy outcomes (ranging from one to 24 hours). A dose
response was seen for the main outcomes. It was not possible to analyse adverse
effects information in a meaningful way. AUTHORS' CONCLUSIONS: Rizatriptan 5 mg
and 10 mg are effective in treating acute migraine, with a dose-related increase 
in efficacy.

Publication Types: 
    Review

PMID: 17636717 [PubMed - indexed for MEDLINE]

675: Headache. 2007 Jul-Aug;47(7):1069-78.

Endometriosis is associated with prevalence of comorbid conditions in migraine.

Tietjen GE, Bushnell CD, Herial NA, Utley C, White L, Hafeez F.

Department of Neurology, University of Toledo Medical Center, Health Science
Campus, 3120 Glendale Avenue, Toledo, OH 43614, USA.

OBJECTIVE: To examine the headache characteristics of women with migraine and
endometriosis (EM), and differences in the prevalence of comorbid conditions
between female migraineurs with EM, without EM and nonheadache controls.
BACKGROUND: Migraine and EM are common conditions in women of reproductive age,
and both are influenced by ovarian hormones. The comorbidity of migraine and EM
is newly recognized, but reasons for the association are uncertain. METHODS: This
is a cross-sectional study of female headache outpatients and healthy controls
conducted at University of Toledo and Duke University in 2005 and 2006. After a
headache specialist determined headache frequency and diagnosis (based on
criteria of the second International Classification of Headache Disorders),
patients completed a self-administered electronic survey with information on
demographics, headache-related disability, menstrual disorders, premenstrual
dysphoric disorder (PMDD), vascular event risk, and comorbid conditions,
including irritable bowel syndrome (IBS), fibromyalgia (FM), chronic fatigue
syndrome (CFS), interstitial cystitis (IC), depression, and anxiety. RESULTS:
Study enrolled 171 women with migraine and 104 controls. EM was reported more
commonly in migraineurs than in controls (22% vs 9.6%, P < .01). Frequency of
chronic headache was higher in migraineurs with EM compared to without EM (P=
.002) and median headache-related disability scores were also higher in the EM
group (P= .025). Symptoms of PMDD were more common in migraineurs, but frequency 
did not differ by EM status. Migraineurs with EM reported more menorrhagia,
dysmenorrhea, and infertility compared to the migraine cohort without EM and to
controls. Depression, anxiety, IBS, FM, CFS, and IC were more common in migraine 
with EM group than in controls. Anxiety (OR = 2.2, 95% CI 1.0-4.7), IC (OR =
10.6, 95% CI 1.9-56.5), and CFS (OR = 3.6, 95% CI 1.1-11.5) were more common in
migraine with EM group, than in the cohort with migraine without EM. CONCLUSION: 
Prevalence of EM is higher in women with migraine than in nonheadache controls.
Migraineurs with EM have more frequent and disabling headaches, and are more
likely to have other comorbid conditions affecting mood and pain, compared to
migraineurs without EM.

Publication Types: 
    Multicenter Study

PMID: 17635599 [PubMed - indexed for MEDLINE]

676: Headache. 2007 Jul-Aug;47(7):1056-62.

Association between a polymorphism in the lymphotoxin-a promoter region and
migraine.

Lee KA, Jang SY, Sohn KM, Won HH, Kim MJ, Kim JW, Chung CS.

Department of Laboratory Medicine, Yonsei University College of Medicine, Seoul, 
South Korea.

OBJECTIVE: The aim of this study was to determine whether polymorphisms in the
lymphotoxin (LTA)-tumor necrosis factor (TNF) region are associated with the risk
of migraine. BACKGROUND: Previous studies concerning the role of TNFalpha in
migraine have provided conflicting results. It has been reported that LTA could
be a susceptibility gene in migraine. It is possible that the TNFalpha
polymorphism associated with migraine is in linkage disequilibrium with other
functional polymorphisms that influence migraine risk. Moreover, there are
significant differences among the allele frequencies of TNF gene variants among
populations from different ethnic groups. METHODS: In a case-control study,
including 439 migraine patients and 382 controls, we examined the association
between 15 single nucleotide polymorphisms in the coding and promoter regions of 
LTA and TNFalpha genes, which are located within the 22 kb around TNF and the
risk of migraine. We performed a chromatin immunoprecipitation (ChIP) assay and
an electrophoretic mobility shift assay (EMSA) to identify differential
protein-DNA binding of LTA-294. RESULTS: Homozygosity for the LTA-294C allele was
significantly associated with an increased risk of migraine compared with CT/TT
carriers (corrected P= .005, odds ratio [OR]= 1.7, 95% confidence interval [CI]
1.3-2.3). Haplotype TGAAC was found to be significantly associated with a
protective effect against migraine (P= .0005, Bonferroni corrected P= .003, OR = 
0.7, 95% CI 0.5-0.8). There was no differential protein-DNA binding pattern in
both EMSA and ChIP assays. CONCLUSIONS: We found that the LTA haplotypes were
associated with migraine among Koreans and that the best marker for this is the
LTA-294 T/C polymorphism. Our results indicate that these associations should be 
defined in the context of the involvement of other genetically linked region,
such as human leukocyte antigen (HLA) loci.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17635597 [PubMed - indexed for MEDLINE]

677: Headache. 2007 Jul-Aug;47(7):1050-5.

Elevation of CSF tumor necrosis factor alpha levels in new daily persistent
headache and treatment refractory chronic migraine.

Rozen T, Swidan SZ.

Michigan Head Pain and Neurological Institute-Neurology, 3120 Professional Drive,
Ann Arbor, MI 48104, USA.

OBJECTIVE: To determine if patients with new daily persistent headache (NDPH)
have elevated levels of tumor necrosis factor alpha (TNF alpha) in the CSF.
BACKGROUND: NDPH is considered one of the most treatment resistant of all
headache syndromes. This reflects a lack of understanding of its pathogenesis. As
a certain percentage of NDPH patients have their headaches start after an
infection, the possibility of a persistent state of systemic or CNS inflammation 
comes into question. TNF alpha is a proinflammatory cytokine involved in brain
immune and inflammatory activities, as well as in pain initiation. The goal of
this study was to look at TNF alpha levels in the CSF of NDPH patients, to
determine if CNS inflammation may play some role in the pathogenesis of this
condition. METHODS: CSF TNF alpha levels were studied in 38 patients: 20 with
NDPH and a control population of 16 patients with chronic migraine (CM), and 2
with post-traumatic headache (PT). RESULTS: CSF TNF alpha levels were elevated in
19 of 20 NDPH patients, 16 of 16 CM patients, and both PT patients. Serum TNF
alpha levels were normal in most of the study subjects. CONCLUSION: An elevation 
of CSF TNF alpha levels was found in almost all NDPH patients and suggest a role 
for TNF alpha in the pathogenesis of this condition. Surprisingly, all CM and PT 
patients tested had elevated CSF TNF alpha levels. In most patients with elevated
CSF levels, serum TNF alpha levels were normal. All of these syndromes may be
manifestations of CNS inflammation. As most of the positive-tested patients
showed minimal to no improvement during aggressive inpatient treatment,
persistent elevation of CSF TNF alpha levels may be one of the causes of
treatment refractory CDH.

PMID: 17635596 [PubMed - indexed for MEDLINE]

678: Headache. 2007 Jul-Aug;47(7):1037-49.

Efficacy and tolerability of naratriptan for short-term prevention of menstrually
related migraine: data from two randomized, double-blind, placebo-controlled
studies.

Mannix LK, Savani N, Landy S, Valade D, Shackelford S, Ames MH, Jones MW.

Headache Associates, 7908 Cincinnati-Dayton Road, West Chester, OH 45069, USA.

BACKGROUND: In a pilot study, naratriptan was significantly more effective than
placebo in preventing menstrually related migraine (MRM) when given as 1 mg twice
daily for 5 days beginning 2 days before the predicted onset of MRM for up to 4
menstrual cycles. OBJECTIVE: To evaluate the efficacy and tolerability of
naratriptan for short-term prevention of MRM in 2 large, identically designed,
randomized, double-blind, placebo-controlled, parallel-group studies. METHODS:
MRM was defined as any migraine beginning during the perimenstrual period (PMP). 
By definition, the PMP consisted of Days -2, -1, 1, 2, 3, and 4, with Day 1 being
the first day of menstrual flow. Adult women were eligible if they reported a
history of MRM, had regular menstrual cycles, and could predict within 2 days
both the onset of menstrual flow and MRM. The studies comprised a baseline phase 
and a treatment phase. During the baseline phase, patients prophylactically
treated their first PMP after the screening visit with single-blind placebo.
Patients who documented an MRM while receiving placebo were eligible for the
treatment phase. During the treatment phase, patients were randomized to receive 
either naratriptan 1 mg twice daily or placebo beginning 3 days before the
predicted onset of MRM for a total of 6 days for 4 PMPs or 6 months, whichever
occurred sooner. The primary efficacy endpoint was the mean percentage of treated
PMPs without MRM per patient. Secondary efficacy endpoints included the
percentage of patients who were free of MRM during all treated PMPs, the median
number of days with MRM over 4 PMPs, and patient satisfaction. Safety and
tolerability measures included adverse events, standard clinical laboratory
tests, and vital signs. RESULTS: The intent-to-treat population was 287 in Study 
1 (149 in the naratriptan group and 138 in the placebo group) and 346 in Study 2 
(173 in each treatment group). Approximately 20% of randomized patients in each
treatment group in Study 1 and 10% in each treatment group in Study 2 withdrew
prematurely from the studies over the 4-month treatment period. The mean
percentage of PMPs without MRM per patient was 38% and 34% among
naratriptan-treated patients treating at least 1 PMP compared with 29% and 24%
among placebo-treated patients in each respective study (P < .05 naratriptan vs
placebo for both studies). Efficacy of naratriptan did not vary as a function of 
age, use of oral contraceptives, or use of migraine prophylaxis. More patients
who had received naratriptan reported attacks posttreatment compared to patients 
who had received placebo. Among patients treating at least 1 PMP, the percentage 
of patients with no MRM in any treated PMP was significantly (P < .05) higher in 
the naratriptan group (11%; 19/173) than the placebo group (3%; 6 of 173) in
Study 2. There were no differences in the percentages of patients with no MRM in 
any treated PMP in Study 1. The number of MRM days per patient across 4 PMPs was 
significantly lower in the naratriptan group than in the placebo group in both
studies (median 5.0 days vs 6.5 days in Study 1 [P= .005] and 5.3 days vs 6.0
days in Study 2 [P= .018]). Significantly more patients receiving naratriptan
were satisfied with the ability of naratriptan to control MRM either by
preventing their occurrence or reducing their severity or duration compared with 
patients receiving placebo. No single drug-related adverse event was reported by 
more than 2% of patients in a treatment group in either study, and no serious
drug-related adverse events were reported. CONCLUSIONS: Naratriptan 1 mg twice
daily for 6 days per month is effective and well tolerated when used for
short-term prevention of MRM. More patients receiving naratriptan than placebo
were satisfied with treatment. The observed increase in posttreatment attacks
needs further study.

Publication Types: 
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 17635595 [PubMed - indexed for MEDLINE]

679: Headache. 2007 Jul-Aug;47(7):1008-23; discussion 24-5.

Comment in:
    Headache. 2008 Feb;48(2):299-300.

Neuron-glia signaling in trigeminal ganglion: implications for migraine
pathology.

Thalakoti S, Patil VV, Damodaram S, Vause CV, Langford LE, Freeman SE, Durham PL.

Department of Biology, Missouri State University, Springfield, MO 65897, USA.

OBJECTIVE: The goal of this study was to investigate neuronal-glial cell
signaling in trigeminal ganglia under basal and inflammatory conditions using an 
in vivo model of trigeminal nerve activation. BACKGROUND: Activation of
trigeminal ganglion nerves and release of calcitonin gene-related peptide (CGRP) 
are implicated in the pathology of migraine. Cell bodies of trigeminal neurons
reside in the ganglion in close association with glial cells. Neuron-glia
interactions are involved in all stages of inflammation and pain associated with 
several central nervous system (CNS) diseases. However, the role of neuron-glia
interactions within the trigeminal ganglion under normal and inflammatory
conditions is not known. METHODS: Sprague-Dawley rats were utilized to study
neuron-glia signaling in the trigeminal ganglion. Initially, True Blue was used
as a retrograde tracer to localize neuronal cell bodies in the ganglion by
fluorescent microscopy and multiple image alignment. Dye-coupling studies were
conducted under basal conditions and in response to capsaicin injection into the 
TMJ capsule. S100B and p38 expression in neurons and glia were determined by
immunohistochemistry following chemical stimulation. CGRP levels in the ganglion 
were measured by radioimmunoassay in response to capsaicin. In addition, the
effect of CGRP on the release of 19 different cytokines from cultured glial cells
was investigated by protein microarray analysis. RESULTS: In unstimulated control
animals, True Blue was detected primarily in neuronal cell bodies localized in
clusters within the ganglion corresponding to the V3 region (TMJ capsule), V2
region (whisker pad), or V1 region (eyebrow and eye). However, True Blue was
detected in both neuronal cell bodies and adjacent glia in the V3 region of the
ganglion obtained from animals injected with capsaicin. Dye movement into the
surrounding glia correlated with the time after capsaicin injection. Chemical
stimulation of V3 trigeminal nerves was found to increase the expression of the
inflammatory proteins S100B and p38 in both neurons and glia within the V3
region. Unexpectedly, increased levels of these proteins were also observed in
the V2 and V1 regions of the ganglion. CGRP and the vesicle docking protein
SNAP-25 were colocalized in many neuronal cell bodies and processes. Decreased
CGRP levels in the ganglion were observed 2 hours following capsaicin
stimulation. Using protein microarray analysis, CGRP was shown to differentially 
regulate cytokine secretion from cultured trigeminal ganglion glia. CONCLUSIONS: 
We demonstrated that activation of trigeminal neurons leads to changes in
adjacent glia that involve communication through gap junctions and paracrine
signaling. This is the first evidence, to our knowledge, of neuron-glia signaling
via gap junctions within the trigeminal ganglion. Based on our findings, it is
likely that neuronal-glial communication via gap junctions and paracrine
signaling are involved in the development of peripheral sensitization within the 
trigeminal ganglion and, thus, are likely to play an important role in the
initiation of migraine. Furthermore, we propose that propagation of inflammatory 
signals within the ganglion may help to explain commonly reported symptoms of
comorbid conditions associated with migraine.

Publication Types: 
    Research Support, N.I.H., Extramural

PMID: 17635592 [PubMed - indexed for MEDLINE]

680: Headache. 2007 Jul-Aug;47(7):996-1003; discussion 1004-7.

Brainstem dysfunction in chronic migraine as evidenced by neurophysiological and 
positron emission tomography studies.

Aurora SK, Barrodale PM, Tipton RL, Khodavirdi A.

Swedish Headache Center, 1101 Madison #200, Seattle, WA 98104, USA.

BACKGROUND: The pathophysiology of chronic migraine (CM) is not fully understood.
We aimed to examine transcranial magnetic stimulation (TMS) indices of cortical
excitability in patients with CM and also performed PET studies to ascertain if
there were any areas of activation and inhibition for possible correlation.
METHODS: Excitability of the cortex was assessed by a reliable parameter of
magnetic suppression of perceptual accuracy (MSPA) profiles using transcranial
magnetic stimulation in 25 patients with CM. Of these 10 patients were also
studied with ((18)F-FDG PET) scans. RESULTS: MSPA demonstrated decreased
inhibition in CM compared to normal controls and episodic migraine. The
percentage of letters reported correct at 100 ms was 84.37 for CM compared to
19.14 for normal controls and 57.41 for episodic migraine. The PET evaluation in 
10 subjects demonstrated increased cerebral metabolism in areas of in the
brainstem compared to the global flow. There were also decreased areas of
cerebral metabolism in the medial frontal and parietal as well as the
somatosensory cortex. CONCLUSIONS: Patients with CM appear to be characterized by
reduced visual suppression correlating with high cortical excitability. In a
cohort of these subjects there was brainstem activation and inhibition in certain
areas of the cortex suggesting a potential dysfunction in the inhibitory
pathways.

PMID: 17635590 [PubMed - indexed for MEDLINE]

681: Cephalalgia. 2007 Aug;27(8):877-80. Epub 2007 Jul 17.

Migraine headache and obesity in women aged 40-74 years: a population-based
study.

Mattsson P.

Department of Neuroscience and Neurology, University Hospital, S-751 85 Uppsala, 
Sweden. Peter.Mattsson@neurologi.uu.se

This study investigates the associations between obesity and migraine. A
neurologist clinically assessed 684 women aged 40-74 years attending a
population-based mammography screening programme. Body height and weight were
measured and body mass index (BMI) calculated. Obesity was defined as a BMI > or 
= 30 kg/m2. The proportion of obesity did not differ between women with active
migraine, women with inactive migraine or women who had never experienced
migraine (P = 0.96). The distribution of frequency, intensity, duration or
severity of attacks did not differ between obese and non-obese women with
migraine. In this study there were no significant associations between migraine
or migraine characteristics on the one hand and obesity on the other.

PMID: 17635528 [PubMed - indexed for MEDLINE]

682: J Cardiol. 2007 Jun;49(6):357-60.

Efficacy of ticlopidine for preventing migraine after transcatheter closure of
atrial septal defect with Amplatzer septal occluder: a case report.

Tomita H, Hatakeyama K, Soda W, Kobayashi T.

Department of Cardiology, Hokkaido Children's Hospital and Medical Center,
Zenibako 1-10-1, Otaru, Hokkaido 047-0261. tomitah@sapmed.ac.jp

Transcatheter closure of an atrial septal defect using the Amplatzer septal
occluder is a current treatment option in Japan, but is occasionally associated
with transient exacerbation or new onset migraine. Clopidogrel is effective in
such a situation, but the efficacy of ticlopidine, an analog of clopidogrel, on
migraine remains unclear. A 15-year-old girl presented with typical migraine
attacks with aura 11 days after transcatheter closure of an atrial septal defect 
with an Amplatzer septal occluder. All examinations excluded thromboembolic
origin of the migrain. Her symptoms disappeared completely after medication with 
ticlopidine.

Publication Types: 
    Case Reports

PMID: 17633574 [PubMed - indexed for MEDLINE]

683: Pediatr Neurol. 2007 Jul;37(1):59-63.

MRI findings in pediatric ophthalmoplegic migraine: a case report and literature 
review.

Bharucha DX, Campbell TB, Valencia I, Hardison HH, Kothare SV.

Drexel University College of Medicine, Philadelphia, Pennsylvania, USA.

Ophthalmoplegic migraine (also recognized as a cranial neuralgia) is a form of
migraine characterized by recurrent episodes of headache with ophthalmoplegia
related to paresis of cranial nerves III, IV, or VI, with onset typically in
childhood. These symptomatic episodes may persist for several hours or for
several weeks, months, or permanently. To date, the exact etiology of
ophthalmoplegic migraine remains unknown. In previous case reports,
ophthalmoplegic migraine may or may not be associated with changes seen on
magnetic resonance imaging. Contrast-enhanced magnetic resonance imaging
performed during symptomatic and postsymptomatic periods in patients with
ophthalmoplegic migraine may hold great value in identifying the pathophysiologic
features of oculomotor nerve palsies. Of cases demonstrating abnormal magnetic
resonance imaging, a majority show improved but persistent changes on repeat
imaging. The present report describes a case of recurrent ophthalmoplegic
migraine in a 16-year-old girl. Although the patient presented with
ophthalmoplegic migraine during this episode in the same manner as her prior
episodes, enhancement of the cranial nerve III on magnetic resonance imaging was 
evident during the eighth episode whereas previous imaging had been normal.
Complete resolution of enhancement of the oculomotor nerve on repeat imaging adds
to the few cases that have shown such findings in patients with recurrent
ophthalmoplegic migraine. A review of previous reported cases of ophthalmoplegic 
migraine is offered.

Publication Types: 
    Case Reports
    Review

PMID: 17628225 [PubMed - indexed for MEDLINE]

684: Int J Clin Pract. 2007 Aug;61(8):1256-69.

Efficacy of dosing and re-dosing of two oral fixed combinations of indomethacin, 
prochlorperazine and caffeine compared with oral sumatriptan in the acute
treatment of multiple migraine attacks: a double-blind, double-dummy, randomised,
parallel group, multicentre study.

Sandrini G, Cerbo R, Del Bene E, Ferrari A, Genco S, Grazioli I, Martelletti P,
Nappi G, Pinessi L, Sarchielli P, Tamburro P, Uslenghi C, Zanchin G.

University Centre for Adaptive Disorders and Headache (UCADH), IRCCS C. Mondino
Institute of Neurology Foundation, Pavia, Italy.

AIMS AND METHODS: In this double-blind, double-dummy, randomised, parallel group,
multicentre study, the efficacy of dosing and re-dosing of a fixed combination of
indomethacin, prochlorperazine and caffeine (Indoprocaf) was compared with
encapsulated sumatriptan in the acute treatment of two migraine attacks.
Additionally, in the group taking Indoprocaf, two different oral formulations
were tested: effervescent tablets and encapsulated coated tablets. RESULTS: Of
297 patients randomised (150 assigned to Indoprocaf and 147 to sumatriptan), 281 
were included in the intention-to-treat efficacy analysis. The initial dosing of 
Indoprocaf and sumatriptan was similarly effective with pain-free rates higher
than 30% (95% CI of odds-ratio: 0.57-1.28) and headache relief rates of about 60%
(95% CI of odds-ratio: 0.82-1.84) with both the drugs. The efficacy of re-dosing 
of Indoprocaf as rescue medication was more effective than that of sumatriptan
with pain-free values of 47% vs. 27% in the total attacks with a statistically
significant difference in the first migraine attack in favour of Indoprocaf. The 
efficacy of re-dosing to treat a recurrence/relapse was very high without
differences between the drugs (pain-free: 60% with Indoprocaf and 50% with
sumatriptan in the total attacks). Indoprocaf and sumatriptan were
well-tolerated. CONCLUSION: The study demonstrated that the efficacy of the
initial dosing of Indoprocaf was not higher than that of sumatriptan, but that
the strategy to use the lowest effective dose as soon as the headache occurred,
followed by a second dose if the headache has not relieved or to treat a relapse,
was very effective, especially with Indoprocaf.

Publication Types: 
    Comparative Study
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 17627707 [PubMed - indexed for MEDLINE]

685: Neurologist. 2007 Jul;13(4):231-3.

Migraine with aura is a risk factor for cardiovascular and cerebrovascular
disease: a critically appraised topic.

Wingerchuk DM, Spencer B, Dodick DW, Demaerschalk BM.

Department of Neurology, Mayo Clinic College of Medicine, Scottsdale, Arizona
85259, USA. wingerchuk.dean@mayo.edu

OBJECTIVE: To determine whether migraine with aura and migraine without aura are 
independent risk factors for symptomatic cardiovascular and cerebrovascular
disease. METHODS: We addressed the objective through development of a structured 
critically appraised topic that included a clinical scenario, structured
question, search strategy, critical appraisal, results, summary of best evidence,
commentary, and bottom-line conclusions. Participants included consultant and
resident neurologists, clinical epidemiologists, medical librarians, and clinical
content experts. RESULTS: A prospective cohort study of 27,840 participants in
the Women's Health Study determined that, compared with women lacking a migraine 
history, women who reported active migraine with aura had adjusted hazard ratios 
of 2.15 (95% confidence interval [CI], 1.58-2.92) for major cardiovascular
disease, 1.91 (95% CI, 1.17-3.10) for ischemic stroke, 1.74 (95% CI, 1.23-2.46)
for coronary revascularization, 1.71 (95% CI, 1.16-2.53) for angina, and 2.33
(95% CI, 1.21-4.51) for ischemic cardiovascular disease death. Active migraine
without aura was not associated with increased risk of any of the vascular event 
categories. CONCLUSION: In women, active migraine with aura increases the risk of
major CVD and ischemic stroke by approximately 2-fold compared with women without
migraine. Active migraine without aura was not a risk factor for major CVD and
stroke outcomes in this study. Additional emphasis on identification and
treatment of modifiable vascular disease risk factors for women with active
migraine with aura is warranted.

Publication Types: 
    Case Reports

PMID: 17622918 [PubMed - indexed for MEDLINE]

686: Neurologist. 2007 Jul;13(4):197-204.

Recognition and treatment of menstrual migraine.

Lay CL, Payne R.

Albert Einstein College of Medicine, Bronx, New York, USA. clay@chpnet.org

BACKGROUND: Menstrual migraine is a chronic disorder affecting approximately 12.6
million women in the United States. In spite of its widespread prevalence,
menstrual migraine often goes undiagnosed. REVIEW SUMMARY: Characteristics of
menstrual migraine, which include functional disability, increased headache
severity, and lack of aura, are often overlooked, and therefore menstrual
migraine is often underdiagnosed. Use of a 3-month diary to record migraine
patterns can reveal the predictable patterns associated with menstrual migraine, 
and a diary is demonstrated to be a useful tool in diagnosis. Optimal treatment
of menstrual migraine takes advantage of the predictability of the disorder.
Treatment alternatives for menstrual migraine include acute therapy and short- or
long-term preventive therapies. Acute therapy is given shortly after the migraine
begins. Short-term preventive therapies are effective when administered during
the time that menstrual migraine is most likely to occur; the treatment window is
typically 2 days prior up to 3 days after the onset of menstruation. Providing
triptans, nonsteroidal anti-inflammatory drugs, or estrogen supplements (gel or
patches) during this window has been demonstrated to provide effective protection
during the days when patients are at greatest risk for menstrual migraine.
Alternatively, long-term preventive therapy may be required for recurrent
headaches in patients with concomitant medical conditions for whom migraine
therapy could serve a dual purpose. CONCLUSION: By recognizing the patterns
associated with menstrual migraine, prompt, acute, or preventive therapy can be
used to effectively manage the disorder and reduce its related disability.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 17622911 [PubMed - indexed for MEDLINE]

687: J Child Neurol. 2007 Mar;22(3):321-3.

Stenting for coarctation of the aorta precipitating migraine with aura.

Staals JE, Braun KP, van Loo-Maurus KE, Vles JS.

Department of Neurology, University Hospital Maastricht, Maastricht, The
Netherlands. j.staals@neurologie.azm.nl

The case of a 16-year-old girl with hypertension and coarctation of the aorta is 
presented. She underwent endovascular balloon dilation and stenting of the
coarctation. Two days after this uncomplicated procedure, she started suffering
from migraine with aura. Initially, the diagnosis of transient ischemic attacks
was briefly considered, but extensive further assessment revealed no
abnormalities. It is known that endovascular procedures, such as cerebral
angiography or embolization of an intracranial vascular malformation, can induce 
migraine. To our knowledge, this is the first report of migraine with aura
precipitated by an extracranial endovascular procedure: stenting for coarctation 
of the aorta. Series on both short-term results and long-term outcome of
endovascular management of aortic coarctation have never reported migraine as a
complication. Although the mechanism responsible for the onset of migraine in our
patient remains unclear, it is conceivable that there was a relative intracranial
hypertension before and a relative hypotension leading to hypoperfusion after
dilation of the aorta. This acute disturbance of the cerebral hemodynamic balance
may have set off the neurovascular mechanism leading to migraine attacks with
aura.

Publication Types: 
    Case Reports

PMID: 17621504 [PubMed - indexed for MEDLINE]

688: Am J Health Syst Pharm. 2007 Jul 15;64(14):1483-91.

Resource use associated with topiramate in migraine prophylaxis.

Feliu AL, Rupnow MF, Blount A, Boccuzzi SJ, Vermilyea J.

PharMetrics, Inc., Watertown, MA 02472, USA. afeliu@pharmetrics.com

PURPOSE: The effect of topiramate prophylaxis on medication use and medical
resource use for migraine patients was studied. METHODS: Medical and pharmacy
claims from a commercially insured population were analyzed from July 1, 1999, to
March 31, 2004. The study sample included patients with at least one physician
encounter or facility claim with a diagnosis of migraine at any point during the 
study's time frame. Patients either were naive to drugs labeled for migraine
prophylaxis or had switched to topiramate from another drug labeled for migraine 
prophylaxis. The date of topiramate initiation was between January 1, 2000, and
September 30, 2003; topiramate initiation was the index date. Demographic and
clinical characteristics were evaluated. Migraine-related medication use and
resource use were compared between the pre- and postindex periods. RESULTS: Of
the 1749 patients analyzed, 90.2% were female. Neurologists wrote 54% of the
index prescriptions. The mean +/- S.D. topiramate dosage was 98 +/- 65 mg/day.
Statistically significant decreases occurred in the proportion of patients using 
drugs not labeled for migraine prophylaxis, nonopioid analgesics, nonsteroidal
antiinflammatory drugs, and headache and migraine relief medications (p < 0.05). 
There was a 44.9% reduction in emergency room services, 53.2% reduction in
migraine- related diagnostic procedures, and 57.1% reduction in migraine-related 
hospitalization days. Encounter claims for physicians' office visits did not
change significantly. CONCLUSION: Migraine patients within commercially insured
health plans incurred substantial resource use. Within six months following
initiation of topiramate preventive therapy, reductions in acute migraine
medication and medical resource use were observed among this population of
migraine sufferers.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 17617498 [PubMed - indexed for MEDLINE]

689: Bioorg Med Chem Lett. 2007 Sep 1;17(17):4795-8. Epub 2007 Jun 26.

Caprolactams as potent CGRP receptor antagonists for the treatment of migraine.

Shaw AW, Paone DV, Nguyen DN, Stump CA, Burgey CS, Mosser SD, Salvatore CA,
Rutledge RZ, Kane SA, Koblan KS, Graham SL, Vacca JP, Williams TM.

Department of Medicinal Chemistry, Merck Research Laboratories, West Point, PA
19486, USA. anthony_shaw@merck.com

Calcitonin gene-related peptide (CGRP) has been implicated in the pathogenesis of
migraine. Replacements for the benzodiazepine core of an earlier lead structure 1
including 5-, 6-, and 7-membered lactams were explored. Within the 7-membered
ring scaffold, phenyl substitution at various positions afforded the potent
(3R)-amino-(6S)-phenyl caprolactam template. The phenylimidazolinone privileged
structure gave additional potency enhancements, as 24 showed good potency in both
CGRP binding (K(i)=2 nM) and cAMP (IC(50)=4 nM) assays and was orally
bioavailable in rats (27%).

PMID: 17616394 [PubMed - indexed for MEDLINE]

690: Brain Dev. 2008 Jan;30(1):86-90. Epub 2007 Jul 5.

Hemiplegic migraine: hyperperfusion and abortive therapy with intravenous
verapamil.

Hsu DA, Stafstrom CE, Rowley HA, Kiff JE, Dulli DA.

Department of Neurology H6/526, University of Wisconsin, 600 Highland Avenue,
Madison, WI 53792, USA. hsu@neurology.wisc.edu

A 20-year-old female with hemiplegic migraine was treated during an acute attack 
with intravenous verapamil, which reproducibly resolved the headache within 20
min but did not affect her hemiplegia. Magnetic resonance (MR) and computed
tomographic (CT) angiography and perfusion performed during the attack showed
vasodilation and hyperperfusion. Cerebral hyperperfusion concurrent with
hemiplegia suggests a dissociation between cerebral perfusion and neuronal
function in hemiplegic migraine. The beneficial effect of verapamil on headache
but not hemiplegia suggests a distinct mechanism for pain and neuronal
dysfunction in hemiplegic migraine, with the beneficial effect on pain not due to
vasodilation.

Publication Types: 
    Case Reports

PMID: 17614229 [PubMed - indexed for MEDLINE]

691: J Pain. 2007 Sep;8(9):737-45. Epub 2007 Jul 5.

Increased levels of neurotrophins are not specific for chronic migraine: evidence
from primary fibromyalgia syndrome.

Sarchielli P, Mancini ML, Floridi A, Coppola F, Rossi C, Nardi K, Acciarresi M,
Pini LA, Calabresi P.

Neurologic Clinic, Department of Medical and Surgical Specialties and Public
Health, University of Perugia, Perugia, Italy. neuro.pg@tiscalinet.it

All data obtained in experimental animal pain models support the role of nerve
growth factor (NGF) as a putative candidate intervening in the pathogenesis of
chronic pain, including chronic daily headache (CDH). Few studies have been
carried out to establish its role in maintaining pain states in humans. The
present study was aimed at investigating cerebrospinal fluid (CSF) levels of NGF 
and brain-derived neurotrophic factor (BDNF), both measured by sensitive
immunoassay, in 20 chronic migraine (CM) patients and 20 patients affected by
primary fibromyalgia syndrome (PFMS), compared with those of 20 age-matched
control subjects. Significantly higher levels of both neurotrophins and glutamate
were found. A significantly positive correlation emerged between CSF values of
BDNF and those of NGF (r = .61, P < .001; r = .53, P < .01) and glutamate (r =
.44, P < .02; r = .51, P < .01) in CM and PFMS patients, respectively. These
findings suggest the possibility of a NGF-mediated up-regulation of BDNF involved
in the pathophysiological events underlying long-term neuroplastic changes in
persistent chronic painful conditions, such as CM and fibromyalgia. NGF might
indirectly exert its effect through enhancing glutamatergic transmission via
BDNF. The above mechanisms could account for sustained central sensitization in
both chronic pain states. PERSPECTIVE: This article presents findings of higher
NGF and BDNF levels correlated to increased glutamate levels in the CSF of both
chronic migraine and fibromyalgia patients. This opens new insights into the
pathogenic mechanisms of chronic pain and offers clinicians new therapeutic
perspectives targeting the above mechanisms in both painful disorders.

PMID: 17611164 [PubMed - indexed for MEDLINE]

692: Pain Med. 2007 May-Jun;8(4):383-7.

Imaging intracranial plasma extravasation in a migraine patient: a case report.

Knotkova H, Pappagallo M.

Research Division, Department of Pain Medicine and Palliative Care, Beth Israel
Medical Center, Manhattan Campus for the Albert Einstein College of Medicine, New
York, NY 10003, USA. Hknotkov@chpnet.org

Despite recent research advances, the origin of nociception in migraine headaches
remains unclear and continues to be a topic of intense examination. Experiments
using animal models of dural neurogenic plasma extravasation (DNPE) as an index
of meningeal inflammation provided the basis for the meningeal inflammation
hypothesis of migraine pain. OBJECTIVE: We explore the possibility that DNPE can 
be detected in humans during a migraine attack. METHODS: DNPE single photon
emission computerized tomography (SPECT) with an intravenous injection of
technetium-99m (Tc-99m) human serum albumin (HSA) has been used in a 46-year-old 
migraine symptomatic patient who met the International Headache Society criteria 
for episodic migraine. The patient was injected with 10 mCi HSA and imaged by
SPECT. A second (delayed) SPECT was done 3 hours later. After 3 days, following
complete resolution of her migraine headache, the patient returned for the
control SPECT. RESULTS: All SPECT images were compared with the patient's
self-recorded pictorial description of her migraine head pain epicenter. Tc-99m
HSA extravasation appeared on the same side and approximately in the same region 
as the epicenter of the patient's head pain. CONCLUSION: This observation
suggests the occurrence of intracranial plasma extravasation during migraine
attacks. Activity on SPECT scans suggests that tracer extravasation and not
hyperemia is responsible for the positive finding.

Publication Types: 
    Case Reports
    Research Support, Non-U.S. Gov't

PMID: 17610461 [PubMed - indexed for MEDLINE]

693: Neurogenetics. 2007 Aug;8(3):195-200. Epub 2007 Jul 3.

Association of progesterone receptor with migraine-associated vertigo.

Lee H, Sininger L, Jen JC, Cha YH, Baloh RW, Nelson SF.

Department of Human Genetics, University of California, Los Angeles, Los Angeles,
CA 90095, USA. snelson@ucla.edu

While migraine has been demonstrated to be familial and have genetic
contributions, genome-wide linkage analyses and candidate gene studies have
highlighted that migraine is genetically complex. Despite substantial efforts, no
consistent replication of linkage or association has been reported for common
migraine syndromes. Among the candidate genes tested for association with
migraine by several groups were female sex hormone genes based on the observation
of a much higher incidence of migraine in females. Migraine-associated vertigo
(MAV) is a migraine syndrome also much more common in females than males. Because
MAV is less common in the general population than migraine or migraine with aura,
it may be a better migraine syndrome to detect susceptibility alleles. In this
study, we tested the association of two female hormonal genes, progesterone
receptor (PGR) and estrogen receptor (ESR1), which were previously reported to be
associated with migraine in women. We typed 150 MAV subjects and 145 genomic
matched control subjects. One SNP (rs1042838) within PGR, which is in high
linkage disequilibrium with the functional PROGINS variant, was significantly
associated with MAV (p = 0.0007). Two SNPs (rs2228480 and rs1801132) within ESR1 
demonstrated no significant association. No synergistic effect between ESR1
variants and PGR variants was identified.

Publication Types: 
    Research Support, N.I.H., Extramural

PMID: 17609999 [PubMed - indexed for MEDLINE]

694: Neurology. 2007 Jul 3;69(1):16-25.

Comment in:
    Neurology. 2007 Jul 3;69(1):12-3.    Neurology. 2008 Feb 19;70(8):657.

Migraine in adolescents: association with socioeconomic status and family
history.

Bigal ME, Lipton RB, Winner P, Reed ML, Diamond S, Stewart WF; AMPP advisory
group.

Department of Neurology, Albert Einstein College of Medicine, Bronx, NY 10461,
USA. mbigal@aecom.yu.edu

OBJECTIVE: The influence of socioeconomic status on the prevalence of migraine is
unknown in adolescents. Accordingly, we investigated the prevalence of migraine
in a large sample of adolescents by sociodemographic features. METHODS: A
validated headache questionnaire was mailed to 120,000 households representative 
of the US population. All individuals in the household were interviewed (probands
and their parents). We calculated sex-specific prevalence estimates of migraine
in adolescents derived by age, race, urban vs rural residence, household income, 
region of the country, and parental status of migraine, using log-linear models. 
RESULTS: A total of 32,015 adolescents were identified. Surveys were returned by 
18,714 of them (58.4% response rate).The 1-year prevalence of migraine was 6.3%
(5.0% in boys and 7.7% in girls). The prevalence was higher in girls than in boys
older than 12 and in whites than African Americans. In families with an annual
income lower than $22,500, the adjusted prevalence of migraine in adolescents
without a parental history of migraine was 4.4%; in families earning $90,000 or
more, it was 2.9% (OR = 0.49, 95% CI 0.38 to 0.63). In adolescents with a
parental history of migraine, the prevalence in the lower vs the higher income
group was 8.6% vs 8.4% (OR = 0.97, 0.81 to 1.15). CONCLUSIONS: In adolescents
with family history of migraine, household income does not have a significant
effect, probably because of the higher biologic predisposition. In those without 
a strong predisposition, household income is associated with prevalence. This
suggests social causation rather than social selection, highlighting the need for
exploration of environmental risk factors related to low income and migraine and 
the search for specific comorbidities and stressors in this group.

PMID: 17606878 [PubMed - indexed for MEDLINE]

695: Intern Med. 2007;46(13):959-63. Epub 2007 Jul 2.

Botulinum toxin type A for migraine prophylaxis in the Japanese population: an
open-label prospective trial.

Suzuki K, Iizuka T, Sakai F.

Department of Neurology, School of Medicine, Kitasato University, Sagamihara.
kosukes@med.kitasato-u.ac.jp

OBJECTIVE: To evaluate the efficacy and tolerability of Botulinum Toxin Type A
(BoNT-A) for migraine prophylaxis. METHODS: Nineteen Japanese adult patients (50 
+/- 10 years old), who met the International Classification of Headache Disorders
2nd Edition (ICHD II) criteria for migraine and had five or more migraine attacks
a month, were enrolled in this open-label prospective study. A total of 50 units 
of BoNT-A were injected in 19-fixed sites of the muscles including procerus,
corrugator, frontalis, temporalis and occipitalis. All participants were advised 
to stop taking preventive medicine from one month before and three months after
BoNT-A injection. Migraine disability assessment (MIDAS), migraine questionnaire 
and headache diary were used for the evaluation of efficacy. Seven patients
received repeated injection combined with prophylactic medication. RESULT: We
excluded five patients from the analysis because four patients had medication
overuse headache and one continued preventive medicine. Mean MIDAS score
decreased significantly two months after the injection. Thirteen of 14 patients
stated subjective improvement after the injection on the migraine questionnaire. 
The amount of analgesics consumption or headache frequency did not change after
injection, but the frequency of severe migraine attacks decreased significantly. 
No serious adverse event was reported. Repeated injections also showed
significant reduction in MIDAS score three months after the second and third
injections. CONCLUSION: BoNT-A injection was an effective and safe treatment for 
migraine prophylaxis among the Japanese population. A randomized placebo control 
trial is necessary to confirm its efficacy.

Publication Types: 
    Clinical Trial
    Research Support, Non-U.S. Gov't

PMID: 17603233 [PubMed - indexed for MEDLINE]

696: Cephalalgia. 2007 Jun;27(6):557-60.

Vanishing cerebellar infarcts in a migraine patient.

Rozen TD.

Michigan Head-Pain and Neurological Institute, Ann Arbor, MI 48104, USA.
tdrozmigraine@yahoo.com

Recent population-based studies have suggested that migraine is a risk factor for
the development of infarct-like lesions in the territory of the posterior
circulation. These lesions are thought to be true vascular infarcts based on
their size, location and magnetic resonance imaging (MRI) characteristics.
However, as there are no postmortem studies identifying the pathology of these
MRI findings, their true aetiology is unknown. A case patient with migraine is
presented, who developed what appeared to be cerebellar infarcts on MRI, but
these lesions vanished on repeat imaging 16 days later, questioning their
aetiology as vascular ischaemic based infarcts.

Publication Types: 
    Case Reports

PMID: 17598792 [PubMed - indexed for MEDLINE]

697: Cephalalgia. 2007 Jul;27(7):803-8.

Inhibition of the nociceptive R2 blink reflex after supraorbital or index finger 
stimulation is normal in migraine without aura between attacks.

Coppola G, Di Clemente L, Fumal A, Magis D, De Pasqua V, Pierelli F, Schoenen J.

G.B. Bietti Eye Foundation-IRCCS, Department of Neurophysiology of Vision and
Neurophthalmology, Rome, Italy.

In order to explore possible interictal brainstem dysfunctions in migraine, we
have studied the R2 component of the nociceptive specific blink reflex (nBR)
after conditioning by supraorbital or index finger stimuli in 14 untreated
migraine without aura patients (MO) between attacks and in 15 healthy volunteers.
We determined the R2 recovery curve at increasing inter-stimulus intervals
between 50 and 600 ms. The nBR was conditioned by a paired supraorbital stimulus 
and, in another session, by an ipsilateral electrical shock delivered to the
index finger. The R2 nBR recovery curves were normal in MO patients for both the 
supraorbital and peripheral conditioning. These results do not favour persistent 
interictal sensitization in the spinal trigeminal sensory system. They also
suggest that the control exerted by descending brainstem pathways on medullary R2
interneurones is normal in migraine between attacks.

PMID: 17598762 [PubMed - indexed for MEDLINE]

698: Cephalalgia. 2007 Jul;27(7):788-92.

Subclinical neuromuscular transmission abnormality detected by single-fibre EMG
is more pronounced in cluster headache than in migraine with aura.

Coban A, Baslo MB, Baykan B, Tutkavul K, Orhan EK, Ertas M.

Department of Neurology, Clinical Neurophysiology and Headache Subunits, Istanbul
University, Istanbul Faculty of Medicine, Istanbul, Turkey.

The aim was to investigate neuromuscular transmission (NMT) by single-fibre EMG
(SFEMG) in a large series of patients having migraine with aura (MA) or cluster
headache (CH). Recent studies using SFEMG have shown subclinical dysfunction of
NMT in MA and CH. Forty-three patients having MA, 51 with CH and 38 healthy
control subjects underwent nerve conduction studies, EMG and SFEMG during
voluntary contraction of the extensor digitorum communis muscle. Twenty different
potential pairs were recorded and individual, mean and total abnormal individual 
jitter values were calculated. The results obtained from MA patients were
compared with those from CH patients. In MA patients, 32 of 860 jitters were
abnormally high, whereas 73 of 1020 of the jitters showed this abnormality in CH 
patients. None of the control subjects, five MA patients (11.6%) and 11 CH
patients (21.6%) were designated as having subclinical NMT abnormality. Thus,
patients having junction dysfunction were significantly more common in the CH
group. The subclinical NMT abnormality shown by SFEMG is more common in CH than
in MA. These two primary headache syndromes may have some shared functional
abnormality of NMT constituents which is more evident in CH.

Publication Types: 
    Comparative Study

PMID: 17598760 [PubMed - indexed for MEDLINE]

699: Cephalalgia. 2007 Jul;27(7):781-7.

Epidemiology and clinical characteristics of migraine among school children in
the Menderes region.

Akyol A, Kiylioglu N, Aydin I, Erturk A, Kaya E, Telli E, Akyildiz U.

Adnan Menderes University, Faculty of Medicine, Deparment of Neurology, Aydin,
Turkey. aakyol59@hotmail.com

The goal of this study was to collect and analyse information on the prevalence
of childhood migraine and disability due to migraine in primary school children
of 4th to 8th grades (ages ranging from 9 to 17 years) in the Aydin urban area. A
cross-sectional school-based study was conducted between March and June 2004.
There were 76 333 children of 4th to 8th grades in primary schools in Aydin.
Nearly 10% of this population (7721 out of 76 333) was evaluated by a multistage 
clustered sampling procedure. Four questionnaire forms were applied to each child
by a study neurologist during class time. Questionnaire A consisted of a single
question, 'Have you ever had a headache?'. To those who responded 'yes',
questionnaire B was applied as a second step, which consisted of eight questions.
Diagnosis of migraine headache was made according to International Classification
of Headache Disorders 2004. Migraine disability was measured with questionnaire
C, which was originally the Pediatric Migraine Disability Assessment (PedMIDAS). 
Migraine history, previous migraine diagnosis and pain intensity were measured
with questionnaire D. According to questionnaire A, 79.6% of boys and 87.1% of
girls suffered from headaches. The prevalence of migraine was 9.7% (7.8% in boys,
11.7% in girls) according to questionnaire B. The male:female ratio was 1:1.5.
Total PedMIDAS score was 9.94 +/- 8.41 days in boys and 11.50 +/- 12.28 days in
girls. Only 1.9% of the children had previously been diagnosed with migraine. The
average migraine headache history was 2.48 +/- 1.18 years in girls and 2.57 +/-
1.18 years in boys. Although migraine is a common health problem among school
children in Aydin, it is mostly still under-recognized.

PMID: 17598759 [PubMed - indexed for MEDLINE]

700: Cephalalgia. 2007 Jul;27(7):773-80.

Family-based analysis of serotonin transporter gene polymorphisms in migraine
with and without aura.

Karwautz AF, Campos de Sousa S, Wöber C, Wagner G, Li T, Konrad A, Zesch HE,
Zormann A, Berger G, Wanner C, Wöber-Bingöl C, Collier DA.

Headache Outpatient Centre, Department of Neuropsychiatry of Childhood and
Adolescence, Medical University of Vienna, Vienna, Austria.
andreas.karwautz@meduniwien.ac.at

Genetic epidemiological twin studies have demonstrated a significant heritability
for migraine, with > 60% of liability to migraine either with or without aura
coming from additive genetic factors. Because of the essential role of serotonin 
in the pathophysiology and treatment of migraine, genes of the serotonin system
are candidates for involvement in migraine. Consequently, we examined two
functional VNTR polymorphisms in the serotonin transporter gene, the 5-HTTLPR and
the intron 2 VNTR, in a sample of 212 family trios each with a proband with
childhood migraine, 153 with migraine without aura (MoA) and 59 with migraine
with aura (MA). For the first time, we used transmission disequilibrium test
analysis with the program TDTPHASE to examine the transmission of these two
markers and their haplotypes to offspring affected by migraine. We found no
significant transmission distortion of any marker, with the common L allele of
the 5-HTTLPR transmitted 170 times and not transmitted 178 times, and the S
allele 130 vs. 122 times. Likewise, the common 12 allele of the intron 2 VNTR was
transmitted 201 times and not transmitted 188 times, and the 10 allele 107 vs.
120 times. The markers were not associated with MoA and MA and none of the
haplotypes was associated with overall migraine, MoA or MA. The 5-HTTLPR and the 
intron 2 VNTRs do not play a major role in susceptibility to migraine.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17598758 [PubMed - indexed for MEDLINE]

701: Cephalalgia. 2007 Aug;27(8):881-90. Epub 2007 Jun 15.

Comment in:
    Cephalalgia. 2008 Jun;28(6):676-7; author reply 677-8.

Effects of the remote C fibres stimulation induced by capsaicin on the blink
reflex in chronic migraine.

de Tommaso M, Sardaro M, Pecoraro C, Di Fruscolo O, Serpino C, Lamberti P, Livrea
P.

TIRES (Centre of Innnovative Technologies for Signal Detection and Processing),
Bari, Italy. m.detommaso@neurol.uniba.it

The aim of this study was to test the function of the diffuse noxious inhibitory 
control system (DNIC) in chronic and episodic migraine, exploring the blink
reflex (BR) modifications induced by topical application of capsaicin on the
hand. We evaluated 11 migraine without aura (MA) and nine chronic migraine (CM)
patients during the not symptomatic phase; they were compared with 14
non-headache subjects (N). The BR was elicited by weak electrical stimuli
delivered to the right supraorbital nerve; it was obtained 10 min and 20 min
after the application of 1 ml of 3% capsaicin in a cream base (Teofarma) on the
skin of the dorsum of the right hand, and 60 min after capsaicin removal. The
subjective pain sensation induced by capsaicin was significantly increased in CM 
with respect to both MA patients and normal subjects; the R2 area was increased
in CM patients during capsaicin application, with respect to controls and MA
patients, who did not exhibit any reflex alterations. These results may suggest a
failure of DNIC and a disturbed control of the trigeminal reflex at the central
level, linked with migraine frequency.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17593297 [PubMed - indexed for MEDLINE]

702: Anaesth Intensive Care. 2007 Jun;35(3):418-22.

Presentation of hemiplegic migraine--hemiplegia and hemi-sensory loss following
general anaesthesia.

Lin L, Adey C.

Department of Anaesthesia, Box Hill Hospital, Melbourne, Victoria, Australia.
linl@ausdoctors.net

We report a case of a 15-year-old male who developed severe left-sided hemiplegia
and hemi-sensory loss 20 minutes after arrival in post anaesthetic care unit
following an uneventful general anaesthesia for removal of a cannulated screw of 
left hip. Initial CT and MRI/MRA with diffusion-weighted imaging were
unremarkable. The patient was transferred to The Royal Children's Hospital
Melbourne and was commenced on heparin infusion pending investigation results.
Complete recovery occurred within 36 hours. Eventually, hemiplegic migraine was
diagnosed on the basis of negative investigations and a retrospective history of 
the patient's migraine. This case demonstrates that the management of
peri-operative neurological deficits must be approached in a systematic fashion. 
Hemiplegic migraine is a well-defined clinical syndrome. It is not merely a
diagnosis of exclusion.

Publication Types: 
    Case Reports

PMID: 17591140 [PubMed - indexed for MEDLINE]

703: Dis Manag. 2007 Jun;10(3):138-46.

Quality of care measures for migraine: a comprehensive review.

Gagne JJ, Leas B, Lofland JH, Goldfarb N, Freitag F, Silberstein S.

Department of Health Policy, Jefferson Medical College, Philadelphia,
Pennsylvania, USA. jgagne1@omjus.jnj.com

Migraine headache is a highly prevalent, chronic, episodic disorder that is
associated with high direct and indirect costs. Migraine headache impacts not
only patients, but also their employers due to substantial decreases in workplace
productivity. Despite the prevalence and clinical and economic burdens of
migraine, no national efforts to develop and implement standardized measures of
quality of care have been made. The objective of this study was to collect and
report on existing quality of care measures for migraine that could be suitable
for quality measurement at the health-plan level. Published literature, the
Agency for Healthcare Research and Quality's National Quality Measure
Clearinghouse, and resources available from quality organizations (eg, the
National Committee for Quality Assurance) were examined to identify existing
quality indicators that can be used to assess the quality of care delivered to
migraine sufferers at the health-plan level. Among the results of the study were 
the following: Quality of care measures for migraine include patient-reported
measures and non-patient reported, diagnosis-related, prevention-related, and
treatment-related indicators. Most existing measures have been developed by the
Institute for Clinical Systems Improvement or summarized and reported by the RAND
Corporation. Few of these measures can be used to assess migraine quality of care
at the health-plan level. In conclusion, many measures exist, but they are not
intended for use at the health-plan level. Incorporation of valid and reliable
quality of care measures may increase the ability of migraine disease management 
programs to conform to clinical care guidelines. Significant effort is needed to 
determine what and how to measure quality among health plans to improve the
quality of care delivered to individuals with migraine.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 17590144 [PubMed - indexed for MEDLINE]

704: J Clin Nurs. 2007 Jul;16(7B):159-67.

Migraine and chronic daily headache management: implications for primary care
practitioners.

Peters M, Vydelingum V, Abu-Saad HH, Dowson A.

European Institute of Health and Medical Sciences, Duke of Kent Building,
University of Surrey, Guildford, Surrey, UK.

AIMS AND OBJECTIVES: The aim of this paper is to outline the classifications of
migraine and chronic daily headaches (i.e. headaches occurring at more than 15
days per month) and briefly describe their epidemiology and management. After
outlining the patients' management behaviours, this review paper discuss the
implications for primary care practitioners, including general practitioners and 
nurses. Finally the paper sets out current resources for headache education for
healthcare practitioners. BACKGROUND: There is a scarcity of recent literature
about migraine and chronic daily headache in primary care and of the evidence
base for best practice. Patients with migraine and headache may see a variety of 
healthcare professionals and may not always be accessing the best sources of
help. METHODS: Various databases were searched, such as CINAHL, Cochrane,
Medline, MedlinePubmed and the BMJ. In addition, manual searches were conducted
by following on cited references from papers read. RESULTS: The results of the
literature reviews were critically read and evaluated by the team and the results
are discussed in the critical review presented in this paper. RELEVANCE TO
CLINICAL PRACTICE: The paper proposes multidisciplinary working in relation to
migraine and headache management in primary healthcare, using an evidence-based
approach that stresses the importance of making the correct diagnosis, patient
focused management and appropriate referrals to appropriate agencies to maximize 
benefits for patients.

Publication Types: 
    Review

PMID: 17584425 [PubMed - indexed for MEDLINE]

705: Am J Med Genet B Neuropsychiatr Genet. 2008 Jan 5;147B(1):33-6.

No association of migraine to the GABA-A receptor complex on chromosome 15.

Oswell G, Kaunisto MA, Kallela M, Hämäläinen E, Anttila V, Kaprio J, Färkkilä M, 
Wessman M, Palotie A.

The Finnish Genome Center, University of Helsinki, Helsinki, Finland.

To date, no gene variants predisposing to common forms of migraine have been
convincingly identified. Recently, significant linkage to a cluster of
gamma-amino butyric acid (GABA)-A receptors on Chr 15q11-q13 was reported. We
performed an extensive association study using 898 MA cases and 900 matched
controls by covering the same gene cluster with 34 single nucleotide
polymorphisms (SNPs). No association to MA was detected, suggesting that common
variants of the GABA cluster are unlikely to be major contributors of MA
susceptibility. (c) 2007 Wiley-Liss, Inc.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 17580321 [PubMed - indexed for MEDLINE]

706: Headache. 2007 Jun;47(6):922-6.

Relief from migraine headache with aripiprazole treatment.

LaPorta LD.

There have been many reports of the association between migraine headaches and
psychiatric disorders as well as of the utility of dopamine antagonists in the
treatment of migraine headache. There is increasing evidence to support the
activation of dopaminergic systems as a primary component of migraine
pathogenesis. This report documents 3 cases of female migraineurs who received
the dopamine modulator aripiprazole for treatment of co-occurring psychiatric
disorders and experienced a decrease in migraine frequency and severity. A
hypothesis as to the mechanism of action of dopamine regulation in migraine
treatment is discussed.

Publication Types: 
    Case Reports

PMID: 17578547 [PubMed - indexed for MEDLINE]

707: Headache. 2007 Jun;47(6):919-22.

Seizures with prolonged EEG abnormalities during an attack of migraine without
aura.

Merlino G, Valente M, D'Anna S, Gigli GL.

The term "migralepsy" indicates a particular condition in which seizures occur
during a migraine attack. Several cases of seizures associated with migraine with
aura and characterized by transient MRI abnormalities have been published. We
report the case of a patient who presented 2 generalized seizures during an
attack of migraine without aura and with a transient, diffuse, irregular, high
voltage slow activity without clear epileptiform abnormalities in subsequent EEG 
recordings.

Publication Types: 
    Case Reports

PMID: 17578546 [PubMed - indexed for MEDLINE]

708: Headache. 2007 Jun;47(6):917-9.

Comment in:
    Headache. 2008 Mar;48(3):481.

Cessation of hemiplegic migraine auras with greater occipital nerve blockade.

Rozen T.

Prolonged migraine auras can be disabling and potentially can cause permanent
neurologic deficits. Several medicinal agents have shown some efficacy in
aborting prolonged auras, but results are inconsistent. Greater occipital nerve
blockade can alleviate the pain of migraine and in 1 case report the migraine
aura. Hemiplegic migraine attacks are marked by motor weakness that can last for 
minutes to days. Two case patients with a history of hemiplegic migraine with
prolonged auras are presented, who both had complete alleviation of their aura
symptoms with GON blockade. A hypothesis on how GON blockade may inhibit cortical
spreading depression is also presented.

Publication Types: 
    Case Reports

PMID: 17578545 [PubMed - indexed for MEDLINE]

709: Headache. 2007 Jun;47(6):905-8.

A validation study of an Italian version of the "ID Migraine".

Brighina F, Salemi G, Fierro B, Gasparro A, Balletta A, Aloisio A, La Pegna G,
Randisi G, Saporito V, Calagna G, La Naia F, Morana R.

Department of Neurological Sciences, University of Palermo, Palermo, Italy.

BACKGROUND: Migraine is a highly prevalent and disabling disease which is
substantially underdiagnosed in primary care. Recently, the ID Migraine, a
self-administered questionnaire, consisting of only 3 items, was shown to be a
valid and reliable screening instrument for migraine in primary care in the
United States. OBJECTIVE: The aim of the present study was to validate an Italian
version of the "ID Migraine" questionnaire. METHODS: Two hundred and twenty-two
consecutive headache patients referring to 8 headache centers in Sicily (Italy)
completed an Italian version of the ID Migraine. The responses to the
questionnaire were compared with the diagnosis of headache made by a headache
specialist blind to the result of the questionnaire. Sensitivity, specificity,
positive and negative predictive values for migraine were calculated. RESULTS:
The statistical analysis of 222 patients examined showed a very good performance 
of the ID Migraine with high sensitivity: 0.95 (95% CI, 0.91 to 0.98),
specificity: 0.72 (95% CI, 0.62 to 0.82), and positive predictive value: 0.88
(95% CI, 0.82 to 0.93). ID Migraine showed also a very good accuracy level: 0.87 
(95% CI, 0.83 to 0.92). CONCLUSION: This validation study showed "ID Migraine" as
a valid tool for migraine screening also in Italian patients referring to
headache centers. If confirmed in a primary care setting, these results establish
the "ID Migraine" as a valid screening instrument for migraine in Italian
population.

Publication Types: 
    Multicenter Study
    Research Support, Non-U.S. Gov't
    Validation Studies

PMID: 17578542 [PubMed - indexed for MEDLINE]

710: Headache. 2007 Jun;47(6):895-904.

Impairment in color perception in migraine with and without aura.

De Marinis M, Rinalduzzi S, Accornero N.

Department of Neurological Sciences, La Sapienza University, Rome, Italy.

OBJECTIVE: To assess visual perception in 40 patients suffering from migraine
with aura (MA), 40 patients suffering from migraine without aura (MO), and 40
controls. BACKGROUND: Visual perception abnormalities are a common feature in
both MA and MO. METHODS: We performed luminance and color central perimetry.
Black and white pattern reversal visual-evoked potentials were also assessed.
RESULTS: Luminance perimetry was similar in patients and controls. Color
perimetry instead revealed an impairment in the perception of red ("quantitative 
perception index") in migraine patients; this impairment was more pronounced in
patients with MA (P < .001) than in those with MO (P < .05) and was related to
the degree of photophobia recorded before testing. A subgroup of MO patients who 
had a migraine attack shortly after being tested also displayed a marked
impairment in the perception of blue. This subgroup of patients had a
statistically significant (P < .001) lower perception of blue than the rest of
the MO patients, who had a migraine attack later; they also had a high degree of 
unpleasant perceptions after testing. Black and white visual evoked potentials
were similar in patients and controls. CONCLUSION: The impairment in visual
perception of red, which was more marked in MA than in MO patients, may be
related to the degree of photophobia recorded before testing. The reduced
perception of blue, which only occurred in a subgroup of MO patients in the
premonitory phase of the migraine attack, probably occurs through mechanisms that
involve dopaminergic function. We cannot exclude the possibility that the visual 
stimulations induced the migraine attack in this subgroup of MO patients shortly 
after they were tested.

PMID: 17578541 [PubMed - indexed for MEDLINE]

711: Headache. 2007 Jun;47(6):886-94.

Open-label, long-term tolerability of naratriptan for short-term prevention of
menstrually related migraine.

Brandes JL, Smith T, Diamond M, Ames MH.

Department of Neurology, Vanderbilt University School of Medicine, Nashville, TN,
USA.

BACKGROUND: Although naratriptan is not approved for prophylactic use in
migraine, naratriptan has been shown to be significantly more effective than
placebo for short-term prevention of menstrually related migraine (MRM). The
tolerability of naratriptan administered intermittently for prophylaxis for MRM
over the long term has not been assessed. OBJECTIVE: To assess the tolerability
of naratriptan 1 mg given twice daily for 6 days per month, administered for up
to 1 year for short-term prevention of MRM in an open-label study. METHODS:
Patients were eligible for the study if they were between 18 and 65 years of age 
and had at least a 1-year history of migraine, with or without aura, as defined
by 1988 International Headache Society criteria; reported a history of MRM; and
had at least 1 MRM attack during their last menstrual cycle. MRM was defined as
any migraine beginning during the perimenstrual period (PMP). By definition, the 
PMP consisted of Days -2, -1, 1, 2, 3, and 4, with Day 1 being the first day of
menstrual flow. During each menstrual cycle occurring over a 1-year period,
patients began short-term treatment with naratriptan 1 mg twice daily (BID) 3
days before the expected onset of MRM and treated for a total of 6 days.
Naratriptan 2.5 mg could be taken for breakthrough MRM attacks. Tolerability and 
safety measures included adverse events, standard clinical laboratory tests,
electrocardiograms (ECGs), and vital signs. The secondary endpoints were the
percentage of PMPs without MRM; headache disability as measured by the Headache
Impact Test (HIT), and psychological health as measured by the Beck Depression
Inventory version 2 (BDI-II). RESULTS: The number of patients who took at least 1
dose of study medication (safety population) was 457, and the numbers of patients
completing 6 months and 12 months of treatment were 318 and 131, respectively.
Note that 171 (37%) patients were asked to leave the study once target enrollment
numbers were met. The only adverse event occurring at an incidence of more than
2% during the 6-day treatment periods when naratriptan 1 mg BID was taken with or
without an additional 2.5-mg dose for breakthrough attacks was ear, nose, throat 
infection (3%). No specific adverse event considered at least possibly to be
related to study medication occurred in more than 2% of patients. No serious
drug-related adverse events were reported. Furthermore, no patient experienced
clinically relevant drug-related changes in 12-lead ECGs, vital signs, or
clinical laboratory tests. Patients in both the 6- and 12-month populations did
not experience an MRM in approximately 50% of treated PMPs. Health outcomes
results suggested that naratriptan reduced headache impact when used for up to 12
months for the short-term prevention of MRM. CONCLUSION: Naratriptan 1 mg BID,
with the optional use of an additional 2.5-mg dose for breakthrough attacks, was 
well tolerated when used for 6 continuous days per month for up to 1 year for
short-term prevention of MRM.

Publication Types: 
    Clinical Trial
    Research Support, Non-U.S. Gov't

PMID: 17578540 [PubMed - indexed for MEDLINE]

712: Headache. 2007 Jun;47(6):878-85.

Dihydroergotamine for early and late treatment of migraine with cutaneous
allodynia: an open-label pilot trial.

Silberstein SD, Young WB, Hopkins MM, Gebeline-Myers C, Bradley KC.

Jefferson Headache Center, Thomas Jefferson University, Philadelphia, PA 19107,
USA.

OBJECTIVE: To explore whether dihydroergotamine (D.H.E. 45) is equally effective 
and safe for migraine with allodynia, when administered either early or late in
an attack. BACKGROUND: Central sensitization may account for the extracranial
tenderness and cutaneous allodynia that can occur with migraine. Once allodynia
is established, triptans are less effective. Dihydroergotamine is often effective
for patients whose refractory headaches have failed prior triptan therapy.
METHODS: In this single-center, open-label pilot trial, patients with episodic
migraine associated with cutaneous allodynia were treated on 2 occasions with
dihydroergotamine 1.0 mg intramuscularly. One attack was treated within 2 hours
(early) and a second attack at 4 hours (late) after the onset of throbbing pain. 
Headache pain and any associated symptoms, subjective cutaneous allodynia, and
mechanical (brush) allodynia were assessed. All data were analyzed using the
Fisher's exact test. RESULTS: Thirteen patients met the entry criteria; however, 
data from only 9 patients, those who completed treatment for 2 migraine attacks, 
were used to evaluate the efficacy and safety of dihydroergotamine. Whether they 
took dihydroergotamine early or late in the attack, most patients (>55%) had
headache relief within 2 hours, and at least 44% of patients achieved
headache-free status by 8 hours postdose. Subjective cutaneous allodynia started 
to decline after 30 minutes postdose in the early treated group and after 120
minutes postdose in the late-treated group. Brush allodynia began to decline
after 15 minutes postdose in the early treated group and after 90 minutes
postdose in the late-treated group. Six of 9 patients (67%) reported at least 1
adverse event. CONCLUSIONS: The results of this pilot trial provide proof of
concept for the headache-relief benefit of dihydroergotamine in patients with
migraine headache and allodynia. A large, placebo-controlled trial of
dihydroergotamine in allodynic patients is warranted.

Publication Types: 
    Clinical Trial
    Research Support, Non-U.S. Gov't

PMID: 17578539 [PubMed - indexed for MEDLINE]

713: Headache. 2007 Jun;47(6):866-75.

Comment in:
    Headache. 2007 Jun;47(6):876-7.

Depression and anxiety: effect on the migraine-obesity relationship.

Tietjen GE, Peterlin BL, Brandes JL, Hafeez F, Hutchinson S, Martin VT, Dafer RM,
Aurora SK, Stein MR, Herial NA, Utley C, White L, Khuder SA.

Department of Neurology, The University of Toledo College of Medicine, Toledo, OH
43614, USA.

OBJECTIVE: To discern the effects of depression and anxiety on the
migraine-obesity relationship. BACKGROUND: Migraine and obesity are highly
prevalent conditions and are both independently linked to psychiatric conditions,
mainly depression and anxiety. METHODS: Data are from an ongoing cross-sectional 
multicenter study on comorbid conditions in clinic patients seeking treatment for
headache. The diagnosis of migraine was determined by the examining physician
based on the International Classification of Headache Disorders (ICHD)-II
criteria. Participants completed a self-administered questionnaire with
information on demographics, headache features, and physician-diagnosed comorbid 
medical and psychiatric disorders. The questionnaire included scales for
measuring current depression (PHQ-9), anxiety (BAI), and headache-related
disability (HIT-6). RESULTS: A total of 721 migraineurs (88% women) from 8
different headache treatment centers were included in this study (mean age = 42
years, SD = 12). Aura was reported in 45% and chronic headache (>or=15 headache
days/month) in 35% of the participants. Prevalence of obesity in our population
was 30% and only 38% had normal weight. Obesity was more common in men (P= .004),
African Americans (P= .026), and in lower education (P= .05) and household income
(P=.05) groups. Current depression (PHQ-9 score >or=10) was noted in 42% and
current anxiety (BAI score >or=8) in 70% of the obese migraineurs. In ordinal
logistic regression, obesity was associated with current depression (odds ratio
[OR]= 1.86, 95% confidence interval [CI]: 1.25 to 2.78) and anxiety (OR = 1.58,
95% CI: 1.12 to 2.22). A significant effect of depression on the body mass index 
(BMI) and headache frequency relationship was noted. Obese migraineurs with
depression were more likely to have higher headache frequency (OR = 4.16, 95% CI:
1.92 to 8.99) and headache-related disability (OR = 7.10, 95% CI: 2.69 to 18.77) 
compared to normal weight migraineurs without depression. Similarly, obese
migraineurs with anxiety were more likely to have higher headache frequency (OR =
1.96, 95% CI: 1.07 to 3.61) and headache-related disability (OR = 3.59, 95% CI:
1.64 to 7.86) compared to normal weight migraineurs without depression. Compared 
to migraineurs with either current depression or anxiety, those with both these
conditions were more likely to have higher headache frequency (OR = 3.18, 95% CI:
1.86 to 5.43) and headache disability (OR = 6.13, 95% CI: 2.58 to 14.59).
CONCLUSION: Depression and anxiety were common in obese migraineurs. The
relationship of obesity with migraine frequency and migraine-related disability
is modified by depression and by anxiety, with the strongest effect observed in
migraineurs with both depression and anxiety.

Publication Types: 
    Multicenter Study
    Research Support, Non-U.S. Gov't

PMID: 17578537 [PubMed - indexed for MEDLINE]

714: Headache. 2007 Jun;47(6):857-65.

Comment in:
    Headache. 2007 Jun;47(6):876-7.

Migraine comorbidity constellations.

Tietjen GE, Herial NA, Hardgrove J, Utley C, White L.

Department of Neurology, The University of Toledo College of Medicine, Toledo, OH
43614, USA.

OBJECTIVES: To identify distinct constellations of comorbid disorders occurring
in migraineurs, and to examine differences in demographics, headache profiles,
and psychosocial features between the comorbidity constellations. METHODS: This
is a retrospective electronic chart review of consecutive new female outpatients 
diagnosed with migraine (n = 223) using International Classification of Headache 
Disorders (ICHD)-II criteria. Questionnaire collected information on comorbid
diagnoses, current depression, somatic symptoms, psychosocial stressors, and
antidepressant use, social and abuse history. Cluster analysis, based on
nonheadache disorders, was performed and differences between the resulting groups
were examined. RESULTS: We identified 3 groups. Group 1 (n = 55) was defined by
hypertension, hyperlipidemia, diabetes mellitus, and hypothyroidism; Group 2 (n =
83) by depression, anxiety, and fibromyalgia; Group 3 (n = 85) by the absence of 
defining comorbidities. Group 1 had more males (22% vs 5% vs 12%, P < .05), was
older (median years: 52 vs 36 vs 32, P < .01), and had later age of headache
onset (median years: 22 vs 16 vs 18, P < .05). Group 2 had the greatest
disability (P < .05), and the lowest quality of life (P < .001). Persons in Group
2 more commonly reported sexual abuse (OR = 2.7, 95% CI: 1.1 to 6.5), physical
abuse (OR = 2.5, 95% CI: 1.2 to 5.1), and emotional abuse (OR = 4.3, 95% CI: 1.9 
to 8.9). CONCLUSION: Within a headache clinic population, we identified 3
different migraine comorbidity constellations, with differing headache and
psychosocial profiles, suggesting heterogeneity of genetic and environmental
factors. This may have implications for diagnosis and disease management.

PMID: 17578536 [PubMed - indexed for MEDLINE]

715: Headache. 2007 Jun;47(6):852-4.

Two cases of lesions in brainstem in multiple sclerosis and refractory migraine.

Fragoso YD, Brooks JB.

We report on 2 cases of multiple sclerosis in patients with refractory migraine
as one of the initial manifestations of the disease. In both cases, the magnetic 
resonance image showed lesions in the brainstem that could be implicated in the
genesis of such migraine attacks.

Publication Types: 
    Case Reports
    Letter

PMID: 17578534 [PubMed - indexed for MEDLINE]

716: Headache. 2007 Jun;47(6):842-7.

Glutamate levels in cerebrospinal fluid and triptans overuse in chronic migraine.

Vieira DS, Naffah-Mazzacoratti Mda G, Zukerman E, Senne Soares CA, Cavalheiro EA,
Peres MF.

Hospital Israelita Albert Einstein-Instituto Israelita de Ensino e
Pesquisa-Instituto do Cérebro, São Paulo, Brazil.

OBJECTIVE: Chronic migraine (CM) is a common disorder, affecting 2% to 3% of the 
general population. Glutamate is implicated in cortical spreading depression,
trigeminovascular activation, central sensitization, and may be linked to
migraine chronification. Triptans brought a novel option for the acute migraine
treatment. As the development of central sensitization impacts upon the
effectiveness of triptan therapy, we hypothesized that glutamate might be related
to triptan response mechanisms. METHODS: We studied 19 patients diagnosed with CM
according to the International Headache Society (2004) criteria. Patients were
divided in those overusing analgesics (NSAIDs); those without overuse, and those 
overusing triptans. RESULTS: Cerebrospinal fluid (CSF) glutamate levels were
similar in patients overusing acute medications (0.335 +/- 0.225 micromol)
compared to those without overuse (0.354 +/- 0.141 micromol), P= NS). In
contrast, patients overusing triptans had CSF glutamate levels significantly
lower than that observed in nonoverusers (0.175 +/- 0.057 vs 0.354 +/- 0.141
micromol, P= 0.015), and significantly higher than controls (0.175 +/- 0.057 vs
0.109 +/- 0.066 micromol, P= 0.039). In triptan overusers, CSF glutamate levels, 
although lower, were not significantly different from patients overusing other
types of analgesics. CONCLUSIONS: Our study showed lower glutamate levels in CSF 
of CM patients overusing triptans. Glutamate may be implicated in triptan
response mechanisms, triptans may work in part by reducing extracellular
glutamate levels in the brain.

PMID: 17578532 [PubMed - indexed for MEDLINE]

717: Headache. 2007 Jun;47(6):834-41.

An anthropological study about headache and migraine in native cultures from
Central and South America.

Carod-Artal FJ, Vázquez-Cabrera C.

Neurology Department, Sarah Hospital, Brasilia DF, Brazil.

OBJECTIVE: To describe the ritual and ethnobotanical treatments about migraine
performed by shamans from several native cultures. METHODS: Anthropological field
study conducted with Tzeltal Maya (Mexico), Kamayurá (Brazil), and Uru-Chipaya
(Bolivia) American Indians. RESULTS: Migraine is called yaxti-wanjol chawaj by
Tzeltal shamans. They wash the head of the patient with an herbal solution to
treat headache. The boiled leaves of a shrub called payté wamal (Tagetes
nelsonii) are used to relieve migraine. Migraine is called monkey's disease by
Kamayurá natives. The disease is originated by the revenge of the killed monkey's
spirit, striking to Kamayurá hunter on his head. It is treated with an herbal
infusion applied in the eyes of the patient. Migraine is called eskeclamix by
Chipaya people, and is treated by drinking the cañahua plant (Chenopodium
palludicale) boiled with water. The patient's head may also be washed with
shaman's fermented urine. CONCLUSIONS: Cultural equivalents of migraine exist in 
the healing system of isolated American cultures.

PMID: 17578531 [PubMed - indexed for MEDLINE]

718: Headache. 2007 Jun;47(6):820-33.

The cerebellum and migraine.

Vincent M, Hadjikhani N.

Hospital Universitário Clementino Fraga Filho, Faculdade de Medicina,
Universidade Federal do Rio de Janeiro, Brazil.

Clinical and pathophysiological evidences connect migraine and the cerebellum.
Literature on documented cerebellar abnormalities in migraine, however, is
relatively sparse. Cerebellar involvement may be observed in 4 types of
migraines: in the widespread migraine with aura (MWA) and migraine without aura
(MWoA) forms; in particular subtypes of migraine such as basilar-type migraine
(BTM); and in the genetically driven autosomal dominant familial hemiplegic
migraine (FHM) forms. Cerebellar dysfunction in migraineurs varies largely in
severity, and may be subclinical. Purkinje cells express calcium channels that
are related to the pathophysiology of both inherited forms of migraine and
primary ataxias, mostly spinal cerebellar ataxia type 6 (SCA-6) and episodic
ataxia type 2 (EA-2). Genetically driven ion channels dysfunction leads to
hyperexcitability in the brain and cerebellum, possibly facilitating spreading
depression waves in both locations. This review focuses on the cerebellar
involvement in migraine, the relevant ataxias and their association with this
primary headache, and discusses some of the pathophysiological processes
putatively underlying these diseases.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't
    Review

PMID: 17578530 [PubMed - indexed for MEDLINE]

719: Pharm Res. 2007 Oct;24(10):1919-26. Epub 2007 Jun 19.

A unique iontophoretic patch for optimal transdermal delivery of sumatriptan.

Siegel SJ, O'Neill C, Dubé LM, Kaldeway P, Morris R, Jackson D, Sebree T.

Division of Neuropsychiatry, University of Pennsylvania, Translational Research
Laboratories, 125 S. 31st St. Rm. 2223, Philadelphia, Pennsylvania 19104, USA.
siegels@mail.med.upenn.edu

PURPOSE: Migraines affect approximately 10% of the adult population worldwide.
The purpose of this study was to assess the pharmacokinetic and safety profile of
a novel iontophoretic sumatriptan delivery system, NP101, which uses an
electrical current to propel sumatriptan across intact skin and into underlying
tissue. Four unique prototype iontophoretic sumatriptan patch conditions were
compared to a 6 mg subcutaneous injection and an oral 50 mg tablet of sumatriptan
succinate. MATERIALS AND METHODS: This was a randomized, single-center,
single-dose, six-period Phase I study. RESULTS: Patches were well tolerated with 
fewer adverse events than the subcutaneous injection. Adverse events that were
more prevalent for NP101 than other formulations included localized sensations
and reactions at the patch site. A linear relationship was observed between total
applied current and sumatriptan delivery. Patches delivering 6 and 12 mA per h
yielded favorable sumatriptan systemic profiles, delivering drug at a rate that
maintained plasma levels above the target level (> or = 10 ng/ml) for greater
than 7 h. CONCLUSIONS: This study met the initial objective to define the
dose-current relationship in humans as well as delimiting specific current and
current density targets for a well tolerated patch design that can deliver
therapeutic drug levels for longer periods than currently possible.

Publication Types: 
    Clinical Trial, Phase I
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 17577644 [PubMed - indexed for MEDLINE]

720: Med Hypotheses. 2008;70(1):73-80. Epub 2007 Jun 14.

The minicolumnopathy of autism: A link between migraine and gastrointestinal
symptoms.

Casanova MF.

Department of Psychiatry and Behavioral Sciences, 500 South Preston Street,
Building 55A, Room #217, Louisville, KY 40292, United States.
M0CASA02@louisville.edu

Gastrointestinal symptoms are common medical problems among autistic patients. A 
leaky gut and viruses have been proposed as possible culprits but evidence for
these etiological agents remains elusive. In this article, we put forward an
alternate etiology: abdominal migraines. Recent postmortem studies in autism
indicate the presence of a minicolumnopathy and its relationship to both
serotonergic abnormalities and a hyperexcitable cortex. These features of
phenomenology are also observed in miganeurs. A putative relationship between
autism and migraine is further suggested by similarities in clinical histories
and laboratory evidence. Some commonalities include the presence of
neuroinflammation, sensory overstimulation (e.g., flickering of fluorescent
lights), "food allergies", benefits from similar diets, and the role of nitric
oxide. Abdominal migraine therefore stands as a falsifiable hypothesis with added
importance accrued to potential therapeutic interventions.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 17574771 [PubMed - indexed for MEDLINE]

721: Pain. 2007 Nov;132(1-2):124-31. Epub 2007 Jun 14.

Comment in:
    Pain. 2007 Nov;132(1-2):219-20; author reply 220-2.

Shortened cortical silent period in facial muscles of patients with migraine.

Curra A, Pierelli F, Coppola G, Barbanti P, Buzzi MG, Galeotti F, Serrao M,
Truini A, Casali C, Pauri F, Cruccu G.

Department of Neurological Sciences, La Sapienza University, Rome, Italy.
antonio.curra@uniroma1.it

Despite intensive neurophysiological research, evidence is lacking to show
whether abnormal cortical excitability in migraine reflects a primary cortical
disturbance or reduced control by thalamo-cortical loops. One way to contribute
to the scientific discussion on this topic is to deliver transcranial magnetic
stimulation (TMS) and test the cortical silent period (SP) recorded in facial
muscles. The facial-muscle SP is a purely cortical phenomenon that reflects the
excitability of inhibitory interneurons, and can disclose changes in cortical
inhibition even in patients without documented primary lesions of the motor
cortices. To test the interictal excitability of cortical motor inhibitory
interneurons in migraine, we investigated the facial-SP in patients with migraine
with and without aura between attacks. In 26 patients and 15 age-matched
controls, high-intensity magnetic stimuli were delivered with a round coil
centered at the vertex during a maximal muscle contraction. Electromyographic
responses were recorded from surface electrodes placed over the subjects'
perioral muscles. Facial SPs were significantly shorter in patients than in
controls. The SP shortening provides neurophysiological evidence showing
hypoexcitability of cortical inhibitory neurons in patients with migraine between
attacks. Despite a possible primary deficit of cortical inhibitory interneurons
in migraine, we favor the interpretation of a secondary disfacilitation by
hypoactive thalamo-cortical loops. Based on this interpretation, the interictal
reduced cortical inhibition documented by the shortened SP could be considered
the motor counterpart of the reduced preactivation excitability level in the
sensory cortices purported to explain why cortical evoked responses habituate
poorly in patients with migraine.

PMID: 17574759 [PubMed - indexed for MEDLINE]

722: Epilepsy Res. 2007 Jul;75(2-3):220-3. Epub 2007 Jun 15.

Co-occurrence of major depression or suicide attempt with migraine with aura and 
risk for unprovoked seizure.

Hesdorffer DC, Lúdvígsson P, Hauser WA, Olafsson E, Kjartansson O.

The Gertrude H. Sergievsky Center, Columbia University, 630 West 168th Street, P 
& S Unit 16, New York, NY 10032, USA. dch5@columbia.edu

We hypothesized and found that the co-occurrence of migraine with aura (MA) with 
major depression (MD) or with suicide attempt (SA) increases the risk for
developing unprovoked seizure more than these conditions alone. Number of
conditions showed a linear relationship to seizure risk. This may reflect a new
condition cluster defined by MA, MD, SA and unprovoked seizures. Identifying the 
biological underpinnings this cluster may affect clinical diagnosis and
treatment.

Publication Types: 
    Research Support, N.I.H., Extramural

PMID: 17572070 [PubMed - indexed for MEDLINE]

723: J Headache Pain. 2007 Jun;8(3):157-66. Epub 2007 Jun 11.

Noradrenaline and cortisol changes in response to low-grade cognitive stress
differ in migraine and tension-type headache.

Leistad RB, Stovner LJ, White LR, Nilsen KB, Westgaard RH, Sand T.

Department of Neuroscience, Norwegian University of Science and Technology,
N-7489 Trondheim, Norway. rune.leistad@ntnu.no

The goal of this study was to explore the relationship between indicators of
sympathoneural, sympathomedullar and hypothalamic-pituitary-adrenocortical (HPA) 
activity and stress-induced head and shoulder-neck pain in patients with migraine
or tension-type headache (TTH). We measured noradrenaline, adrenaline and
cortisol levels before and after low-grade cognitive stress in 21 migraineurs, 16
TTH patients and 34 controls. The stressor lasted for 60 min and was followed by 
30 min of relaxation. Migraine patients had lower noradrenaline levels in blood
platelets compared to controls. Pain responses correlated negatively with
noradrenaline levels, and pain recovery correlated negatively with the cortisol
change in migraineurs. TTH patients maintained cortisol secretion during the
cognitive stress as opposed to the normal circadian decrease seen in controls and
migraineurs. There may therefore be abnormal activation of the HPA axis in
patients with TTH when coping with mental stress, but no association was found
between pain and cortisol. A relationship between HPA activity and stress in TTH 
patients has to our knowledge not been reported before. In migraine, on the other
hand, both sympathoneural activation and HPA activation seem to be linked to
stress-induced muscle pain and recovery from pain respectively. The present study
suggests that migraineurs and TTH patients cope differently with low-grade
cognitive stress.

PMID: 17568991 [PubMed - indexed for MEDLINE]

724: J Headache Pain. 2007 Jun;8(3):167-74. Epub 2007 Jun 11.

Effects of remote cutaneous pain on trigeminal laser-evoked potentials in
migraine patients.

de Tommaso M, Difruscolo O, Sardaro M, Libro G, Pecoraro C, Serpino C, Lamberti
P, Livrea P.

Neurophysiopathology of Chronic Pain Unit, Neurological and Psychiatric Sciences 
Department, University of Bari, Clinica Neurologica, Policlinico, Piazza Giulio
Cesare 11, I-70124 Bari, Italy. m.detommaso@neurol.uniba.it

The present study aimed to evaluate heat pain thresholds and evoked potentials
following CO(2) laser thermal stimulation (laser-evoked potentials, LEPs), during
remote application of capsaicin, in migraine patients vs. non-migraine healthy
controls. Twelve outpatients suffering from migraine without aura were compared
with 10 healthy controls. The LEPs were recorded by 6 scalp electrodes,
stimulating the dorsum of the right hand and the right supraorbital zone in basal
condition, during the application of 3% capsaicin on the dorsum of the left hand 
and after capsaicin removal. In normal subjects, the laser pain and the N2-P2
vertex complex obtained by the hand and face stimulation were significantly
reduced during remote capsaicin application, with respect to pre-and
post-capsaicin conditions, while in migraine LEPs and laser pain were not
significantly modified during remote painful stimulation. In migraine a defective
brainstem inhibiting control may coexist with cognitive factors of focalised
attention to facial pain, less sensitive to distraction by a second pain.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17563842 [PubMed - indexed for MEDLINE]

725: J Headache Pain. 2007 Jun;8(3):175-9. Epub 2007 Jun 11.

Rizatriptan vs. ibuprofen in migraine: a randomised placebo-controlled trial.

Misra UK, Kalita J, Yadav RK.

Department of Neurology, Sanjay Gandhi Post Graduate Institute of Medical
Sciences, Raebareily Road, Lucknow 226014, India. ukmisra@sgpgi.ac.in

The objective of this study was to compare the efficacy of rizatriptan and
ibuprofen in migraine. The study was a randomised placebo-controlled trial in a
tertiary care teaching hospital. Migraine patients with <8 attacks/months were
included. One hundred and fifty-five migraine patients were randomised to
rizatriptan 10 mg (53), ibuprofen 400 mg (52) and placebo (50). Efficacy was
assessed by headache relief, and headache freedom at 2 h and 24 h. Two-hour
headache relief, was noted in 73% in rizatriptan, 53.8% in ibuprofen and 8% in
placebo groups. Headache freedom was achieved in 37.7% in rizatriptan, 30.8% in
ibuprofen and 2% in placebo groups. Rizatriptan was superior to ibuprofen and
placebo in relieving headache at 2 h but not at 24 h. Side effects were noted in 
9 patients in rizatriptan, 8 in ibuprofen and 3 in placebo, all of which were
nonsignificant. Rizatriptan and ibuprofen are superior to placebo. Rizatriptan is
superior to ibuprofen in relieving headache, associated symptoms and functional
disability.

Publication Types: 
    Comparative Study
    Randomized Controlled Trial

PMID: 17563841 [PubMed - indexed for MEDLINE]

726: J Headache Pain. 2007 Jun;8(3):185-9. Epub 2007 Jun 11.

Association study between clinical response to rizatriptan and some candidate
genes.

Asuni C, Cherchi A, Congiu D, Piccardi MP, Del Zompo M, Stochino ME.

Section of Clinical Pharmacology, Department of Neurosciences B.B. Brodie,
University of Galiari, P.O. San Giovanni di Dio, Via Ospedale 46, I-09124
Cagliari, Italy. carloasuni@tiscali.it

The aim of this study was to test genetic differences in the clinical response to
rizatriptan in patients affected by migraine without aura. These genetic
differences could be explained by various genes, the HTR1B, encoding the 5-HT(1) 
receptor subtype, MAOA gene that encodes the monoamino-oxidase, the main
metabolic enzyme of this triptan, SLC6A4 (gene encoding the serotonin
transporter) and DRD(2) (gene encoding the D(2) receptor), both involved in the
pathogenesis of migraine. Fifty unrelated patients affected by migraine without
aura (IHS) were included. Patients were divided into two groups (responders and
non-responders) according to clinical response. Thirty-one out of fifty patients 
responded to rizatriptan. A significant difference among the two groups was
observed in both allele (p=0.02) and genotype distribution (p=0.03) of DRD2/NcoI.
The significant association with the DRD2/NcoI polymorphism in responders
suggested that the DRD2/NcoI C allele may be considered a susceptibility factor
heralding a good response to rizatriptan.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17563839 [PubMed - indexed for MEDLINE]

727: Pharmacogenomics. 2007 Jun;8(6):609-22.

Pharmacogenetics of migraine: genetic variants and their potential role in
migraine therapy.

Fernandez F, Colson NJ, Griffiths LR.

Genomics Research Centre, School of Medical Science, Griffith University, Gold
Coast, Queensland, 9726 Australia.

Migraine is a paroxysmal neurological disorder affecting up to 6% of males and
18% of females in the general population, and has been demonstrated to have a
strong, but complex, genetic component. Genetic investigation of migraine
provides hope that new targets for medications and individual specific therapy
will be developed. The identification of polymorphisms or genetic biomarkers for 
disease susceptibility and treatment should aid in providing a better
understanding of migraine pathology and, consequently, more appropriate and
efficient treatment for migraineurs. In this review, we will discuss results
investigating genetic biomarkers for migraine and their potential role in future 
therapy planning.

Publication Types: 
    Review

PMID: 17559350 [PubMed - indexed for MEDLINE]

728: Ann Pharmacother. 2007 Jul;41(7):1181-90. Epub 2007 Jun 5.

Pediatric migraine: pharmacologic agents for prophylaxis.

Eiland LS, Jenkins LS, Durham SH.

Auburn University Harrison School of Pharmacy, Huntsville, AL, USA.
eilanls@auburn.edu

OBJECTIVE: To identify and evaluate the data regarding medication use for
migraine prophylaxis in the pediatric population. DATA SOURCES: Literature was
obtained through searches in PubMed (Mid 1950s-March 2007), Iowa Drug Information
Service/Web (1966-February 2007), International Pharmaceutical Abstracts
(1970-February 2007), and the Cochrane Library. The terms migraine, prophylaxis, 
child, and children were used and cross referenced with all drug names. Reference
citations from publications identified were also reviewed and included. STUDY
SELECTION AND DATA EXTRACTION: Only trials that evaluated migraine headaches in
the pediatric population were included. Trials including adolescent and adult
populations are briefly listed, but not reviewed. Trials involving
non-prescription medication were also included in the evaluation. Due to the
limited information, all clinical trials, retrospective reviews, and abstracts
evaluated were included in this review. DATA SYNTHESIS: Few controlled clinical
trials regarding prophylaxis therapy are available. Currently, no medications are
approved by the Food and Drug Administration for prophylaxis of migraines in
children. Seventeen drugs were identified and included in the review. Of the
drugs with available data, topiramate, valproic acid, flunarizine, amitriptyline,
and cyproheptadine have shown efficacy in decreasing migraine frequency and
duration in children. However, larger clinical trials are necessary to validate
the utility of these agents. Conflicting data exist for propranolol and
pizotifen, and additional data are needed for gabapentin, levetiracetam,
zonisamide, naproxen, and trazodone. In clinical trials, nimodipine, clonidine,
and natural supplements have shown a lack of efficacy versus placebo for
prophylaxis of migraines in children. CONCLUSIONS: Topiramate, valproic acid, and
amitriptyline have the most data on their use for prophylaxis of migraines in
children. Numerous agents have limited data in this population and several agents
lack efficacy. Prospective, well designed, controlled clinical trials that
include quality-of-life and functional outcomes are needed for guiding therapy of
migraine prophylaxis for children.

Publication Types: 
    Review

PMID: 17550953 [PubMed - indexed for MEDLINE]

729: Aviat Space Environ Med. 2007 May;78(5 Suppl):B113-8.

Botulinum toxin type-a in the prevention of migraine: a double-blind controlled
trial.

Vo AH, Satori R, Jabbari B, Green J, Killgore WD, Labutta R, Campbell WW.

AT&T Center for Telehealth Research & Policy, Electronic Health Network,
University of Texas Medical Branch, William C. Levin Hall, Room 5.518, 301
University Blvd., Galveston, TX 77555-1042, USA. ahvo@utmb.edu

INTRODUCTION: Migraine is a frequent medical complaint. In military populations, 
migraine can be detrimental to productivity and troop readiness, and can be
disqualifying for service in some military duty specialties. This study assessed 
the effectiveness of botulinum neurotoxin type-A (BTX-A) in reducing the
frequency of migraines in known migraineurs. METHODS: There were 32 subjects
(control = 17, test n = 15) who completed the assessment battery at baseline and 
monthly for 3 mo. Adult subjects with migraine headaches occurring more than 5
times/month were recruited and randomized to receive placebo saline injection vs.
BTX-A. The primary efficacy parameter was the average frequency of headache days 
for 3 mo. Secondary outcome measures were severity of attacks and quality of
life. RESULTS: Quadratic trends were noted for headache severity (F (2,29) =
14.1, p = 0.001) and headache indexes (F (2,29) = 4.5, p = 0.042) for both
groups, suggesting changes in severity of head pain and overall intensity of
headaches experienced over time; however, results were not significant for
headache frequency and severity between groups. Paired t-tests of the headache
index scores for the control group revealed a significant increase from the first
to the third follow-up periods (t = -2.58, p = 0.020). Such a trend was not
observed for the BTX-A group. Both groups, however, reported similarly low to
moderate quality of life as a result of their migraines. CONCLUSIONS: This
controlled trial failed to demonstrate efficacy of BTX-A in reducing the
frequency of migraine headaches. The pattern headache index in the botox group,
however, suggested a protective effect for botox against the headache severity.

Publication Types: 
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, Non-P.H.S.

PMID: 17547312 [PubMed - indexed for MEDLINE]

730: Dis Mon. 2007 Mar;53(3):156-61.

The neuropsychology of migraine.

Ravishankar N, Demakis GJ.

University of North Carolina, USA.

Migraine is a common and recurrent headache disorder that may present with a
variety of neurologic and non-neurologic manifestations. It has been classified
into migraine with aura and migraine without aura. Research has shown that
migraine affects verbal, visuo-spatial memory, and selective attention tasks.
Cognitive impairments observed in migraineurs have been found to occur during a
migraine attack, after the attack, and even when the individual does not exhibit 
any residual effects of the attack. Individuals with migraine are at a greater
risk of developing anxiety and depression. Migraine disability is most commonly
assessed using the Migraine Disability Assessment Scale (MIDAS), a simple
five-item scale that assesses the individual's level of performance and areas of 
impairment. This review assesses the neuropsychological aspects of the complex
malady that is migraine.

Publication Types: 
    Review

PMID: 17544646 [PubMed - indexed for MEDLINE]

731: J Invasive Cardiol. 2007 Jun;19(6):257-60.

Interatrial septal defect closure for prevention of cerebrovascular accidents:
impact on recurrence and frequency of migraine headaches.

Shammas NW, Dippel EJ, Harb G, Egts S, Jerin M, Stoakes P, Byrd J, Shammas GA,
Sharis P.

Midwest Cardiovascular Research Foundation, Cardiovascular Medicine, Davenport,
IA 52803, USA. shammas@mchsi.com

BACKGROUND: Recent data suggest that percutaneous closure of interatrial septal
defect (IASD) is associated with a reduction in the intensity, frequency and
duration of migraine headaches. In this study we review our own data to determine
if we can reproduce the relationship between IASD closure in patients with a
history of a central nervous system event (stroke or a transient ischemic attack 
[TIA]) and migraine headaches (HA). METHODS: Fifty-eight consecutive patients
with a history of unexplainable stroke or TIA with the exception of the presence 
of an IASD were included in this retrospective study. Multiple variables were
collected including age, gender, history of smoking, hypertension, diabetes,
hypercholesterolemia, ejection fraction, anticoagulant use pre- and
postprocedure, shunt grade across the IASD pre- and postprocedure, defect size
and right-sided filling pressures. All patients with a history of migraine HA
answered the Migraine Disability Assessment Test (MIDAS), a standardized migraine
questionnaire. Descriptive analysis was performed on all variables and compared
among migraine and nonmigraine HA patients. Pre and post closure intensity and
frequency of migraine HA were compared. RESULTS: Of 58 patients, 14 (24.14%) had 
migraine HAs prior to percutaneous closure. There were no significant differences
among the migraine and nonmigraine HA groups except that the migraine HA
sufferers were younger (p = 0.016). One patient with migraine HA died on follow
up from complications of cardiomyopathy. Only 5 (38.5%) of 13 patients reported
still having migraine HA post closure of IASD. The frequency (41.6 +/- 36.4 vs.
9.3 +/- 24.8; p = 0.005) and intensity (8.0 +/- 1.9 vs. 2.1 +/- 3.2; p = 0.001)
of the migraine HAs were markedly reduced post closure at 759 +/- 545.6 days
(range 89 to 1,433 days). There was no relationship between the shunt grade and
the frequency or intensity of migraine HA. CONCLUSION: We conclude that IASD
closure in patients with history of migraine HA and stroke or TIA have a marked
improvement in the frequency and intensity of their HA. Migraine HA resolved in
61.54% patients post closure. Larger randomized studies are needed to confirm
these findings, which could have significant implications for sufferers of
migraine HA.

PMID: 17541126 [PubMed - indexed for MEDLINE]

732: Eur J Neurol. 2007 Jun;14(6):706-7.

Association study of a functional variant in intron 8 of the dopamine transporter
gene and migraine susceptibility.

McCallum LK, Fernandez F, Quinlan S, Macartney DP, Lea RA, Griffiths LR.

Environmental Science and Research Ltd, Wellington, New Zealand.

Migraine is a common, genetically influenced neurovascular disorder. The dopamine
transporter gene is a candidate for migraine association studies. This study
tested a functionally linked variable number tandem repeat (VNTR) in intron 8 of 
the dopamine transporter gene (DAT(Int8)) in 550 migraine cases (401 with aura,
149 without aura) and 550 non-migraine controls. Chi-squared analysis of the
DAT(Int8) revealed that the allele and genotype frequency distributions for
migraine cases (including subtype analysis) and controls were not different (P > 
0.1). These findings offer no evidence for an association of the DAT(Int8) with
migraine with and without aura and therefore do not implicate the dopamine
transporter gene as a modifier of migraine risk.

PMID: 17539957 [PubMed - indexed for MEDLINE]

733: Eur J Neurol. 2007 Jun;14(6):701-3.

Comment in:
    Eur J Neurol. 2007 Jul;14(7):713-4.

Efficacy of lisinopril in migraine prophylaxis--an open label study.

Schuh-Hofer S, Flach U, Meisel A, Israel H, Reuter U, Arnold G.

Department of Neurology, Universitätsklinikum Tuebingen, Tuebingen,
Germany.sigrid.schuh-hofer@gmx.net

The ACE-inhibitor lisinopril has previously been shown to be effective in
migraine prophylaxis at a daily dose of 20 mg. To test the effect of a low dose
of lisinopril (5 mg daily) in migraine prevention, we performed an open label
study in 21 migraineurs. The primary outcome measure was frequency of migraine
attacks. Secondary efficacy measures were migraine hours, intake of acute
migraine drugs, pain intensity and responder rate. Compared with baseline
conditions, the attack frequency of migraine attacks was significantly reduced (P
< 0.0005). The number of acute migraine drugs dropped significantly (P = 0.002). 
Three patients dropped out because of intolerable cough. Our study suggests that 
even low doses of lisinopril may be effective in migraine treatment. However, its
use may be limited by intolerable side-effects.

Publication Types: 
    Clinical Trial

PMID: 17539955 [PubMed - indexed for MEDLINE]

734: Eur J Neurol. 2007 Jun;14(6):654-8.

Paresthesia as a favorable predictor of migraine prophylaxis using topiramate.

Lee ST, Chu K, Park JE, Park HJ, Park JH, Lee SH, Kim M.

Department of Neurology, Seoul National University Hospital, Seoul, South Korea.

Migraineurs treated with topiramate often experience adverse effects, such as
paresthesia, fatigue, memory difficulty, or taste perversion. To investigate
correlations between side effects and drug efficacy, we analyzed for these in 133
migraineurs treated with topiramate (100 mg/day). A 4-week baseline screening
phase preceded a 4-week titration period and a 20-week maintenance phase. A total
of 118 patients were evaluated at 3 months and 89 patients at 6 months. Patients 
who developed paresthesia (n = 73) showed lower headache days than those who did 
not (n = 60) (P = 0.026 at 3 months, P = 0.002 at 6 months), and had a higher
responder rate (3 months, 57.5% and 6 months, 65.8%) than those who did not
develop paresthesia (3 months, 38.3% and 6 months, 41.7%). Moreover,
retrospective analysis of patients that dropped out showed no survival bias
between paresthesia and headache improvement. Other adverse effects were not
found to correlate with drug efficacy. This study suggests that the development
of paresthesia predicts a favorable response to topiramate in migraine
prophylaxis.

Publication Types: 
    Clinical Trial
    Research Support, Non-U.S. Gov't

PMID: 17539944 [PubMed - indexed for MEDLINE]

735: Aviat Space Environ Med. 2007 May;78(5):530-1.

Migraine headaches and cerebrovascular accident secondary to patent foramen
ovale.

Bradley KR.

Civil Aerospace Medical Institute, USA.

Atrial septal defects are a frequent finding in young persons with strokes. New
research now suggests migraines with aura may also be associated with these types
of cardiac defects and that surgical treatment may result in a decrease or
resolution of migraines. This case emphasizes the importance of a thorough
evaluation of airmen with migraines, particularly migraines with aura.

Publication Types: 
    Case Reports

PMID: 17539450 [PubMed - indexed for MEDLINE]

736: Clin Neurol Neurosurg. 2007 Sep;109(7):592-6. Epub 2007 May 29.

Migrainous infarction with appearance of laminar necrosis on MRI.

Liang Y, Scott TF.

Department of Neurology, Allegheny General Hospital, Drexel University College of
Medicine, Pittsburgh, PA 15212, United States.

Although there is accepted criteria for migrainous infarction, the
pathophysiology of this disease process remains poorly defined. Delineation of
MRI characteristics of migrainous infarction may improve our understanding of the
pathophysiology, diagnosis, and prognosis of this disorder. We present a case of 
a migrainous infarction that involved apparent laminar necrosis of a "cortical
ribbon" of the right temporal, parietal, and occipital lobes.

Publication Types: 
    Case Reports

PMID: 17537570 [PubMed - indexed for MEDLINE]

737: Int J Clin Pract. 2007 Jul;61(7):1091-111. Epub 2007 May 30.

Times to pain relief and pain freedom with rizatriptan 10 mg and other oral
triptans.

Ng-Mak DS, Hu XH, Chen Y, Ma L, Solomon G.

Outcomes Research and Management, Merck & Co., Inc., West Point, PA 19486, USA.
daisy_ng_mak@merck.com

BACKGROUND: In the clinical trial setting, oral rizatriptan 10 mg has greater
efficacy than other oral triptans in freedom from migraine headache pain 2 h
after dosing. OBJECTIVE: The study objective is to compare the effectiveness of
rizatriptan 10 mg and other oral triptans for acute migraine attack in a
naturalistic setting. METHODS: A total of 673 patients took rizatriptan 10 mg or 
their usual-care oral triptans for two migraine attacks in a sequential,
cross-over manner and recorded outcomes using a diary and a stopwatch. Mean and
median times to pain relief (PR) and pain freedom (PF) for rizatriptan and other 
oral triptans were compared. The effect of rizatriptan on times to PR and PF,
adjusting for potential confounding factors (treatment sequence, treatment order 
and use of rescue medication), was computed via a Cox proportional hazard model. 
RESULTS: Significantly, more patients taking rizatriptan achieved both PR and PF 
within 2 h after dosing than other oral triptans. Times to PR and PF were shorter
with rizatriptan than with other oral triptans (median time to PR: 45 vs. 52 min,
p < 0.0001; median time to PF: 100 vs. 124 min, p < 0.0001). The adjusted
proportional hazard ratios (rizatriptan vs. other oral triptans) for times to PR 
and PF were 1.32 (95% CI: 1.22-1.44) and 1.27 (95% CI: 1.16-1.39) respectively.
CONCLUSION: The times to PR and PF in a 'naturalistic' setting were significantly
shorter for patients treating a migraine attack with rizatriptan 10 mg than with 
other oral triptans.

Publication Types: 
    Multicenter Study
    Research Support, Non-U.S. Gov't

PMID: 17537184 [PubMed - indexed for MEDLINE]

738: Magn Reson Med. 2007 Jun;57(6):1065-74.

Statistical group comparison of diffusion tensors via multivariate hypothesis
testing.

Whitcher B, Wisco JJ, Hadjikhani N, Tuch DS.

Clinical Imaging Centre, GlaxoSmithKline, Hammersmith Hospital, London, UK.
brandon.j.whitcher@gsk.com

Diffusion tensor imaging (DTI) provides a powerful tool for identifying white
matter (WM) alterations in clinical populations. The prevalent method for
group-level analysis of DTI is statistical comparison of the diffusion tensor
fractional anisotropy (FA) metric. The FA metric, however, does not capture the
full orientational information contained in the diffusion tensor. For example,
the FA test is incapable of detecting group-level differences in diffusion
orientation when the level of anisotropy is unaffected. Here, we apply
multivariate hypothesis testing procedures to the elements of the diffusion
tensor as an alternative to univariate testing using FA. Both parametric and
nonparametric tests are proposed with each choice carrying specific assumptions
about the diffusion tensor model. Of particular interest is the Cramér test,
which works on Euclidean interpoint distances and can be readily adapted to a
specific non-Euclidean framework by applying matrix logarithms to the diffusion
tensors. Using Monte Carlo simulations, we show that multivariate tests can
detect diffusion tensor principal eigenvector differences of 15 degrees with up
to 80-90% power under typical design conditions. We also show that some
multivariate tests are more sensitive to FA differences, when compared to a
univariate test on FA, even if there is no principal eigenvector difference. The 
Cramér test, using the Euclidean interpoint distances, performed best under both 
simulation scenarios. When applying the Cramér test of the diffusion tensor in a 
clinical population with a history of migraine, a 169% increase was observed in
the volume of a significant cluster compared to the univariate FA test.

Publication Types: 
    Comparative Study
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 17534902 [PubMed - indexed for MEDLINE]

739: Int Rev Neurobiol. 2007;79:281-302.

Migraine in multiple sclerosis.

Elliott DG.

Department of Neurology, Louisiana State University Health Sciences Center,
Shreveport, Louisiana 71103, USA.

Headache and migraine are common features in multiple sclerosis (MS) and can
influence the diagnosis, radiological evaluation, treatment, and quality of life 
of these patients. Similarities in symptoms between patients with migraine and MS
presenting with headache can lead to misdiagnosis. Likewise, MRI lesions which
may be found in migraine patients without other neurological symptoms or signs
may cause diagnostic confusion and patient anxiety. Studies addressing the
pathophysiology of these comorbid conditions have not found a clear link, but
brainstem lesions and inflammatory processes have been proposed. Management of de
novo or treatment-induced headache in the MS patient is fairly straightforward if
the physician is aware of the problem.

Publication Types: 
    Review

PMID: 17531846 [PubMed - indexed for MEDLINE]

740: Pain Physician. 2007 May;10(3):453-60.

Using peripheral stimulation to reduce the pain of C2-mediated occipital
headaches: a preliminary report.

Melvin EA Jr, Jordan FR, Weiner RL, Primm D.

Pain Center of Central Florida, Orlando, FL 32806, USA. paininthenet@hotmail.com

BACKGROUND: Peripheral nerve stimulation (PNS) is an accepted treatment for
neuropathic pain. Recent studies have focused on its potential for relieving
headache pain. OBJECTIVES: To investigate the effectiveness of PNS in reducing
occipital headache pain. DESIGN: A prospective, 12-week pilot study involving 11 
patients evaluated before and after implantation of PNS systems to treat
C2-mediated occipital headaches. METHODS: Prior to and at 4 and 12 weeks after
implantation, patients completed the Short-Form McGill Pain Questionnaire
(SF-MPQ), Visual Analog Scale (VAS), and Present Pain Index (PPI). Patients also 
answered questionnaires and kept diaries to record stimulator use, medication
consumption, and numbers of headaches. RESULTS: A comparison of pre- and
post-implantation evaluations showed statistically significant declines in scores
on the SF-MPQ (64%; p = 0.0013), VAS (67%; p < 0.0001), and PPI (68%; p =
0.0009). Most patients (91% and 64% respectively) reported reductions in
medication use and numbers of headaches. Patients also reported a reduction in
headache symptoms and the impact of headaches on activities. Two adverse events
were encountered, one due to a loose connection and, the other caused by lead
migration. CONCLUSIONS: PNS reduced headache pain, headache frequency and
medication use.

Publication Types: 
    Clinical Trial
    Research Support, Non-U.S. Gov't

PMID: 17525779 [PubMed - indexed for MEDLINE]

741: Neurology. 2007 May 22;68(21):1851-61.

Obesity, migraine, and chronic migraine: possible mechanisms of interaction.

Bigal ME, Lipton RB, Holland PR, Goadsby PJ.

Department of Neurology, Albert Einstein College of Medicine, Bronx, NY 10461,
USA. mbigal@aecom.yu.edu

Migraine and obesity are associated in several ways. First, both are prevalent
and disabling disorders influenced by genetic and environmental risk factors.
Second, migraine with aura, as obesity, seems to be a risk factor for
cardiovascular events. Finally, large population-based studies suggest that
obesity is a risk factor for chronic migraine after adjusting for comorbidities. 
In this article, we discuss plausible mechanisms that may account for this
association. Several of the inflammatory mediators that are increased in obese
individuals are important in migraine pathophysiology, including interleukins and
calcitonin gene-related peptide (CGRP). These mediators may increase the
frequency, severity, and duration of migraine attacks per se, which in turn would
cause central sensitization. Repeated central sensitization may be associated
with permanent neuronal damage close to the periaqueductal gray area, with poor
modulation to pain. Obesity is also a state of sympathetic activation, which may 
contribute to increase in headache frequency. Furthermore, the levels of
adiponectin are decreased in obesity. At low but not normal levels, adiponectin
is nociceptive. Shared biologic predisposition may also play a major role.
Orexins modulate both pain and metabolism. Dysfunction in the orexins pathways
seems to be a risk factor for both conditions. Finally, conditions that are
comorbid to both states (e.g., depression, sleep apnea) may also make the
relationship between both diseases more complex.

Publication Types: 
    Review

PMID: 17515549 [PubMed - indexed for MEDLINE]

742: Cell Mol Life Sci. 2007 Aug;64(16):2090-103.

The mechanisms of action of valproate in neuropsychiatric disorders: can we see
the forest for the trees?

Rosenberg G.

D-Pharm Ltd., Kiryat Weizman Science Park, Bldg. 7, P.O. Box 2313, Rehovot,
76123, Israel. grosenberg@dpharm.com

After more than 40 years of clinical use, the mechanisms of action of valproate
in epilepsy, bipolar disorder and migraine are still not fully understood.
However, recent findings reviewed here shed new light on the cellular effects of 
valproate. Beyond the enhancement of gamma-aminobutyric acid-mediated
neurotransmission, valproate has been found to affect signalling systems like the
Wnt/beta-catenin and ERK pathways and to interfere with inositol and arachidonate
metabolism. Nevertheless, the clinical relevance of these effects is not always
clear. Valproate treatment also produces marked alterations in the expression of 
multiple genes, many of which are involved in transcription regulation, cell
survival, ion homeostasis, cytoskeletal modifications and signal transduction.
These alterations may well be relevant to the therapeutic effects of valproate,
and result from its enhancement of activator protein-1 DNA binding and direct
inhibition of histone deacetylases, and possibly additional, yet unknown,
mechanism(s). Most likely, both immediate biochemical and longer-term genomic
influences underlie the effects of valproate in all three indications.

Publication Types: 
    Review

PMID: 17514356 [PubMed - indexed for MEDLINE]

743: Lancet Neurol. 2007 Jun;6(6):521-32.

Migraine: a complex genetic disorder.

Wessman M, Terwindt GM, Kaunisto MA, Palotie A, Ophoff RA.

Folkhälsan Research Center, Helsinki, Finland.

Although family and twin studies show that there is a genetic component to
migraine, no genes predisposing to common forms of the disorder have been
identified. The most encouraging findings have emerged from the identification of
genes causing rare mendelian traits that phenotypically resemble migraine. These 
studies have pointed migraine research towards ion-transport genes; however,
there is no direct evidence of the involvement of these genes in common forms of 
migraine. Family-based linkage studies have identified several chromosomal
regions linked to common forms of migraine, but there is little consistency
between studies. The modest success in the identification of contributing gene
variants has stimulated research into more effective strategies. These include
new phenotyping methods for genetic studies and new study designs-such as
case-control and whole-genome association studies-to identify common variants
contributing to the trait.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't
    Review

PMID: 17509487 [PubMed - indexed for MEDLINE]

744: Neurol Sci. 2007 May;28 Suppl 2:S97-S100.

Neurophysiology and neuromodulators.

Aguggia M, D'Andrea G, Bussone G.

Neurological Department, Via E. Raggio 12, I-15057 Novi Ligure (AL), Italy.
aguggiamarco@tiscali.it

Migraine is an episodic brain disorder that results in significant morbidity.
Antiepileptic drugs (neuromodulators) are increasingly recommended for migraine
prevention because of placebo-controlled double-blind trials that prove them
effective. Cortical spreading depression (CSD) is thought to be the
pathophysiological correlate of the neurological symptoms in migraine with aura
and neuromodulators may act on mechanisms involved in the initiation of CSD
itself. Inhibition of trigeminocervical complex directly, or neurons that
modulate sensory input, are also plausible mechanisms for the actions of
neuromodulators in preventive therapy in migraine. Although it is unlikely that a
single phenomenon serves as the only link between migraine and epilepsy, the
neuronal hyperexcitability that may contribute to each condition may explain the 
effect of these drugs for both conditions.

Publication Types: 
    Review

PMID: 17508189 [PubMed - indexed for MEDLINE]

745: Neurol Sci. 2007 May;28 Suppl 2:S89-93.

Pain pharmacology in migraine: focus on CGRP and CGRP receptors.

Benemei S, Nicoletti P, Capone JA, Geppetti P.

Clinical Pharmacology Unit, Department of Critical Care Medicine and Surgery,
University of Florence, Italy.

Over the last 100 years, the discovery of new analgesics has been a complex and
difficult task. However, remarkable progress in the identification of novel
molecular targets relevant for pain medicines has been reported. Here we will
focus on the neuropeptide calcitonin generelated peptide (CGRP) and its receptors
(CGRP-R) because of their role in migraine mechanism and migraine therapy. Recent
preclinical and clinical data on the localisation, regulation and plasma levels
of CGRP and on the function of CGRP-R will be summarised. The reviewed findings
highlight the major function of CGRP in migraine and the use of CGRP-R
antagonists as a novel approach for the treatment of migraine attack and,
perhaps, as migraine prophylactic medicines.

Publication Types: 
    Review

PMID: 17508187 [PubMed - indexed for MEDLINE]

746: Neurol Sci. 2007 May;28 Suppl 2:S239-41.

Basilar-type migraine responsive to lamotrigine: three case reports.

d'Onofrio F, Cologno D, Petretta V, Casucci G, Bussone G.

Institute of Neurology, San G. Moscati Hospital, Avellino, Italy.

Basilar-type migraine (BM) has been recognised in the revised International
Classification of Headache Disorders as a distinct clinical entity (subtype of
migraine with aura), characterised by disturbing migraine aura clearly
originating from the brainstem or from both hemispheres simultaneously affected. 
It differs from familial and sporadic hemiplegic migraines by the absence of
motor deficit. Lamotrigine has been shown to be effective in preventing migraine 
aura symptoms in typical aura and in some cases of BM. We tried lamotrigine in
three female cases of BM.

Publication Types: 
    Case Reports

PMID: 17508181 [PubMed - indexed for MEDLINE]

747: Neurol Sci. 2007 May;28 Suppl 2:S225-8.

Naproxen sodium in short-term prophylaxis of pure menstrual migraine:
pathophysiological and clinical considerations.

Allais G, Bussone G, De Lorenzo C, Castagnoli Gabellari I, Zonca M, Mana O,
Borgogno P, Acuto G, Benedetto C.

Women's Headache Center, Department of Gynecology and Obstetrics, University of
Turin, Via Ventimiglia 3, I-10126 Turin, Italy. gb.allais@tiscali.it

We investigated the biological and clinical effects of naproxen sodium (NxS) in
the short-term prophylaxis of pure menstrual migraine (PMM) in 25 women suffering
from migraine without aura, occurring exclusively from 2 days before to 5 days
after menstruation onset. Daily oral NxS (550 mg) from 7 days before menstruation
to 7 days after menstruation onset was given for 3 menstrual cycles, and 5 days
before menstruation to 5 days after menstruation onset over the next 3 menstrual 
cycles. In the month before initiation of treatment and in the third month of
treatment, 6-keto-PGF1(alpha), TXB(2) and PGE(2) were measured in plasma before
menstruation (day -2) and on the second day (day +2) after bleeding onset. In the
20 women analysed, 6-keto-PGF1(alpha) was 17% lower (p<0.0001) and TXB(2) was 30%
lower (p<0.0001) on day -2 during treatment than the same day pretreatment;
TXB(2) was also lower (p<0.02) on day +2 during treatment than day +2
pretreatment. The 6-keto-PGF1(alpha)/TXB(2) ratio was higher (p<0.01) on day -2
treatment than day -2 pretreatment. PGE(2) levels were significantly lower
(p<0.002) on day +2 than pre-treatment values on the same day. The number of
attacks reduced from 1.7+/-0.11 pretreatment to 1.2+/-0.10 at the 3rd month
(p<0.001), to 1.1+/-0.06 at the 6th month (p<0.0001). The duration reduced from
25.6+/-4.42 h pretreatment to 15.5+/-4.43 h in the 3rd month (p<0.02), to
13.35+/-4.26 h in the 6th month (p<0.001). The intensity reduced from 2.4+/-0.11 
pretreatment, to 1.2+/-0.10 in the 3rd month of treatment (p<0.0001), and
1.1+/-0.07 in the 6th month (p<0.0001).

PMID: 17508177 [PubMed - indexed for MEDLINE]

748: Neurol Sci. 2007 May;28 Suppl 2:S222-4.

Why do we need NIRS in migraine?

Liboni W, Molinari F, Allais G, Mana O, Negri E, Grippi G, Benedetto C, D'Andrea 
G, Bussone G.

Presidio Sanitario Gradenigo, Struttura Complessa di Neurologia, Corso Regina
Margherita 8, I-10153 Torino, Italy. william.liboni@h-gradenigo.it

Migraine patients may present altered values of the parameters related to their
cerebral circulation. The non-invasive assessment of the autoregulation of such
patients can be helpful in investigating the causes of migraine. We developed a
joint analysis protocol based on transcranial Doppler (TCD) and near-infrared
spectroscopy (NIRS) for assessing cerebral autoregulation. We tested 30 healthy
subjects and 30 patients suffering from migraine without aura. We measured the
baseline values of cerebral blood flow velocity (CBFV) in the middle cerebral
arteries and the concentration of oxygenated (oxy-Hb) and reduced (deoxy-Hb)
haemoglobin in brain tissue. Afterwards, the subjects performed a breath-holding 
(BH) task. In baseline conditions, we did not find significant difference between
the CBFVs of healthy subjects and of migraineurs, even though the latter group
showed a greater dispersion of the velocities (healthy: 70.6+/-6.8 cm/s;
migraine: 71.5+/-14.4 cm/s). Strong differences in the CBFV were observable
during the BH task: migraineurs showed a smaller BH index than controls
(0.83+/-0.55% vs. 1.29+/-0.71%; p<0.005) and a reduced increase of the oxy-Hb
(migraineurs: 0.033+/-0.019 micromol/l/s; healthy: 0.055+/-0.037 micromol/l/s;
p<0.01). Also, we found a different haemoglobin balancing during the BH phase
between migraineurs and controls, revealing that migraineurs do not show a marked
vasodilation as functional response to the CO(2) increase.We propose this joint
analysis protocol to assess cerebral autoregulation of migraine patients, and
suggest NIRS as a low-cost, easy, reliable and fast technique to deeply
investigate cerebral coupling deregulations.

PMID: 17508176 [PubMed - indexed for MEDLINE]

749: Neurol Sci. 2007 May;28 Suppl 2:S220-1.

Allodynia in different forms of migraine.

Lovati C, D'Amico D, Rosa S, Suardelli M, Mailland E, Bertora P, Pomati S,
Mariani C, Bussone G.

Department of Clinical Sciences, L. Sacco Hospital, University of Milan, Via G.B.
Grassi 74, I-20157 Milan, Italy. carlo.lovati@unimi.it

About 60% of patients complain of cutaneous allodynia during migraine episodes,
often in the periorbitary region of the pain side. Pre-clinical studies have
shown that the underlying mechanism is sensitisation of primary nociceptors and
central trigeminovascular neurons and that patients have a lower pain threshold
for mechanical stimulation compared to controls. The objective of this study was 
to determine the prevalence of allodynia during headache attacks in different
forms of migraine. The subjects were 221 outpatients consecutively evaluated in
the Headache Center of the L. Sacco Hospital in Milan: 114 had only attacks of
migraine without aura (MO), 63 had also attacks with aura (MA) and 44 patients
with chronic migraine with and without drug overuse (CM). Presence of head
allodynia was investigated by a semistructured interview. Statistical analysis
was performed by chi square test with Bonferroni correction for multiple
comparisons. Forty-seven out of 114 MO patients (41.2%) complained of allodynia
during headache episodes, 41 out of 63 MA patients (65.0%), and 29 out of 44 CM
patients (65.9%). A higher frequency of allodynia in MA and CM with respect to MO
patients was observed (p<0.01 at chi square test). Allodynia was a common
complaint in migraineurs, being present in more than 40% patients of each group. 
A higher frequency was observed in MA and in CM patients. This observation may
suggest that both frequency of attacks and presence of aura episodes may
contribute to induce changes in neuronal activation threshold thought to sustain 
allodynia.

PMID: 17508175 [PubMed - indexed for MEDLINE]

750: Neurol Sci. 2007 May;28 Suppl 2:S188-97.

Antiepileptic drugs in the prophylaxis of migraine, chronic headache forms and
cluster headache: a review of their efficacy and tolerability.

D'Amico D.

Fondazione IRCCS Istituto Neurologico C. Besta, Via Celoria 11, I-20123 Milan,
Italy. damicodo@tiscali.it

The studies of different antiepileptic drugs (AEDs) in the prophylaxis of
episodic migraine, cluster headache (CH) and chronic headache forms (chronic
daily headache, transformed or chronic migraine, chronic tension-type headache)
are reviewed. The main results from published trials are summarised - focusing on
responder rates as reported in placebo-controlled, double-blind studies. Most
common adverse events are also discussed. This review indicated that robust
evidence supports the use of sodium valproate-divalproex and of topiramate (TPM) 
in the prophylaxis of migraine, while definitive conclusions about the real
effects of other AEDs in migraine cannot be drawn. Overall, evidence of efficacy 
of different AEDs in chronic headache forms and in CH is still lacking, most
studies being open-label, small-sample trials. Nevertheless, encouraging data
from controlled trials are emerging for TPM in the treatment of chronic headache 
forms.

Publication Types: 
    Review

PMID: 17508169 [PubMed - indexed for MEDLINE]

751: Neurol Sci. 2007 May;28 Suppl 2:S184-7.

Is migraine a risk factor in pregnancy?

Allais G, Castagnoli Gabellari I, Airola G, Schiapparelli P, Terzi MG, Mana O,
Benedetto C.

Women's Headache Center, Department of Gynecology and Obstetrics, University of
Turin, Via Ventimiglia 3, I-10126 Turin, Italy,.gb.allais@tiscali.it

Most epidemiological studies demonstrate that women suffering from migraine note 
significant improvement of their headaches during pregnancy. It is generally
supposed, by both headache specialists and gynaecologists, that migraine does not
involve any risk to the mother or the foetus. Specific investigations of the
medical complications of pregnancy in migrainous women, however, have recently
cast doubt on this assumption. Most studies, indeed, have revealed a significant 
association between migraine and hypertension in pregnancy (i. e., preeclampsia
and gestational hypertension). Migraine has also been recently postulated as one 
of the major risk factors for stroke during pregnancy and the puerperium. There
is thus an urgent need for prospective studies of large numbers of pregnant women
to determine the real existence and extent of the risks posed by migraine during 
pregnancy.

Publication Types: 
    Review

PMID: 17508168 [PubMed - indexed for MEDLINE]

752: Neurol Sci. 2007 May;28 Suppl 2:S166-78.

The future of acute care and prevention in headache.

Krymchantowski AV, Rapoport AM, Jevoux CC.

Rua Siqueira Campos 43/1002 Copacabana, Rio de Janeiro, Brazil.
abouchkrym@globo.com

Migraine is a chronic neurological disease with heterogeneous characteristics
resulting in a range of symptom profiles, burden and disability. It affects
nearly 12% of the adult population in Western countries and up to 22% of the
Brazilian population, imposing considerable suffering as well as personal,
economic and social losses. The pharmacological treatment of migraine is divided 
into preventive and acute treatment. A better comprehension of migraine
pathophysiology, as well as the finding of novel molecular targets, has led to a 
growing number of upcoming therapeutic opportunities. The same is true of cluster
headache, which affects only about 0.07%-0.4% of most populations. This review
focuses on current and emerging agents and procedures for the treatment of
migraine and cluster headache.

Publication Types: 
    Review

PMID: 17508166 [PubMed - indexed for MEDLINE]

753: Neurol Sci. 2007 May;28 Suppl 2:S161-5.

Migraine and depression.

Frediani F, Villani V.

Neurological Department and Headache Center, Policlinico S. Pietro, Via Forlanini
15, I-24036 Ponte San Pietro (BG), Italy. fabio_frediani@yahoo.it

Investigations of migraine comorbidity have confirmed its association with
diverse psychiatric conditions. This association appears to be stronger for major
depression and anxiety disorders, but comorbidity has also been reported with
substance abuse and certain mood disorders. This literature also indicates that
greater psychiatric comorbidity exists for migraine sufferers with aura than
without. There is evidence that psychiatric comorbidity is higher in transformed 
migraine than in episodic migraine. However, research into the possible
mechanisms underlying these associations remains limited. Subjects with migraine 
should be carefully screened for depression, which should be managed to prevent
transformation of migraine, to increase quality of life and to gain more
successful migraine therapies.

Publication Types: 
    Review

PMID: 17508165 [PubMed - indexed for MEDLINE]

754: Neurol Sci. 2007 May;28 Suppl 2:S156-60.

Migraine and cerebrovascular disease.

Agostoni E, Rigamonti A.

Neurological Department, A. Manzoni Hospital, Via dell'Eremo 9/11, I-23900 Lecco 
(LC), Italy. e.agostoni@libero.it

The association between migraine and stroke is complex and bidirectional.
Epidemiological studies suggest that migraine may be a risk factor for stroke;
magnetic resonance studies suggest that white matter abnormalities may be more
frequent in migraine patients than in controls; and stroke may occur during the
course of a migraine with aura (MA) attack (migrainous stroke). However, the
relationship between migraine, aura and stroke is complex and mechanisms other
than a direct cause/effect relationship are possible. Migraine aura may be the
consequence, rather than the cause of cerebral ischaemia. Furthermore both MA and
stroke may be secondary to a third underlying condition. In this review we
analyse data regarding the relationship between migraine and stroke considering 3
aspects: (1) migraine as a risk factor for stroke, (2) migraine as a cause of
stroke and (3) migraine and cerebral ischaemia sharing a common cause.

Publication Types: 
    Review

PMID: 17508164 [PubMed - indexed for MEDLINE]

755: Neurol Sci. 2007 May;28 Suppl 2:S150-5.

Migraine and epilepsy: clinical and pathophysiological relations.

De Simone R, Ranieri A, Marano E, Beneduce L, Ripa P, Bilo L, Meo R, Bonavita V.

Headache Centre, Neurological Sciences Department, University Federico II of
Naples, Via Pansini 5, I-80131 Naples, Italy. rodesimo@unina.it

Migraine and epilepsy are both chronic disorders characterised by recurrent
neurological attacks, with a partial clinical and therapeutic overlap and
frequently occurring together. Although still incompletely clarified, the
possible existence of a link between migraine and epilepsy has long been debated.
In this paper the epidemiologic evidence of migraine and epilepsy comorbidity,
the possible occurrence of both disturbances in close temporal association,
possible shared physiopathologic mechanisms and the rationale for antiepileptic
drug use in migraine prophylaxis will be discussed.

Publication Types: 
    Review

PMID: 17508163 [PubMed - indexed for MEDLINE]

756: Neurol Sci. 2007 May;28 Suppl 2:S118-23.

The patent foramen ovale-migraine question.

Tepper SJ, Sheftell FD, Bigal ME.

The New England Center for Headache, 778 Long Ridge Road, Stamford, CT 06902,
USA. sjtepper@aol.com

A strong association between migraine with aura and patent foramen ovale (PFO)
with shunting has been suggested. Similarly, an association of migraine with aura
and Osler-Weber-Rendu disease, probably also due to shunting though pulmonary
arteriovenous malformations has been proposed. PFOs are also comorbid with
cryptogenic strokes, refractory hypoxaemia in right ventricular infarction or
severe lung disease, orthostatic oxygen desaturation and decompression illness in
scuba divers.Multiple open-label, retrospective and case-controlled studies of
PFO closure report improvement of migraine with aura. MIST, the only prospective 
sham-controlled study of PFO closure for migraine with aura, did not reach its
primary endpoint for migraine resolution, although it clearly demonstrated an
association between migraine with aura and the severity of the PFO shunt. One
reported secondary endpoint showed a significant 42% reduction of migraine days, 
suggesting the need for further randomised, sham-controlled PFO closure studies.

Publication Types: 
    Review

PMID: 17508157 [PubMed - indexed for MEDLINE]

757: Neurol Sci. 2007 May;28 Suppl 2:S114-7.

The role of the clinician in interpreting conventional neuroimaging findings in
migraine patients.

Moschiano F, D'Amico D, Di Stefano M, Rocca N, Bussone G.

L. Mandic Hospital, Via L. Mandic 1, I-23807 Merate (LC), Italy.
f.moschiano@ospedale.lecco.it

Changes in cerebral white matter at CT or MRI have been reported in patients with
migraine, especially in those with migraine with aura. Similar pictures may be
present in asymptomatic subjects, and their nature is not completely understood, 
but their infarct-like nature is strongly suggested. Clinicians play an important
role in the evaluation of those migraine patients in whom these nonspecific
abnormalities are present. We suggest ruling out specific syndromes in which
migraine attacks are associated with white matter changes (CADASIL, MELAS,
multiple sclerosis and central nervous system vasculitis), as well as evaluating 
the presence of different vascular risk factors (genetic prothrombotic factors,
patent foramen ovale, use of oral contraceptives, etc.). Their possible causative
role in MRI lesions and in enhancing the risk of a negative clinical evolution
must be considered in each individual case.

Publication Types: 
    Review

PMID: 17508156 [PubMed - indexed for MEDLINE]

758: Curr Pain Headache Rep. 2007 Jun;11(3):241-4.

Controlled trials in pediatric migraine: crossover versus parallel group.

Evers S.

Department of Neurology, University of Münster, Albert-Schweitzer-Str. 33,
Germany. everss@uni-muenster.de

Studies on the treatment of migraine in children and adolescents are rare and
difficult to design. In particular, the high placebo response makes it difficult 
to show efficacy of a verum drug. When analyzing all published trials in the
acute drug treatment of migraine in children, crossover trials show lower placebo
rates and higher therapeutic gain, compared with parallel group trials. This
should be considered in the future design of acute drug trials in childhood
migraine.

Publication Types: 
    Meta-Analysis
    Review

PMID: 17504653 [PubMed - indexed for MEDLINE]

759: Curr Pain Headache Rep. 2007 Jun;11(3):236-40.

Patent foramen ovale and migraine.

Diener HC, Kurth T, Dodick D.

Department of Neurology, University Duisburg-Essen, Hufelandstrasse 55, 45122
Essen, Germany. hans.diener@uni-duisburg-essen.de

Results from several observational studies indicate an association between
migraine and patent foramen ovale (PFO). Several biological mechanisms have been 
proposed to explain this link, including shared genetic inheritance. However,
there is currently insufficient evidence to support a causal link between PFO and
migraine. Although the results of uncontrolled observational studies suggest the 
PFO closure may have a beneficial effect on migraine frequency, a large
randomized trial failed to support such a conclusion. Until there is more
evidence from ongoing large controlled trials, PFO closure should not be
performed in clinical practice for the prophylaxis of migraine.

Publication Types: 
    Review

PMID: 17504652 [PubMed - indexed for MEDLINE]

760: Curr Pain Headache Rep. 2007 Jun;11(3):231-5.

Greater occipital nerve block for migraine and other headaches: is it useful?

Ashkenazi A, Levin M.

Department of Neurology, Jefferson Headache Center, Thomas Jefferson University
Hospital, 111 South 11th Street, Gibbon Building, Suite #8130, Philadelphia, PA
19107, USA. avi.ashkenazi@jefferson.edu

Peripheral nerve blocks have long been used in headache treatment. The most
widely used procedure for this purpose has been greater occipital nerve (GON)
block. The rationale for using GON block in headache treatment comes from
evidence for convergence of sensory input to trigeminal nucleus caudalis neurons 
from both cervical and trigeminal fibers. Although there is no standardized
procedure for GON blockade, the nerve is usually infiltrated with a local
anesthetic (lidocaine, bupivacaine, or both). A corticosteroid is sometimes
added. Several studies suggested efficacy of GON block in the treatment of
migraine, cluster headache, and chronic daily headache. However, few were
controlled and blinded. Despite a favorable clinical experience, little evidence 
exists for the efficacy of GON block in migraine treatment. Controlled studies
are needed to better assess the role of GON block in the treatment of migraine
and other headaches.

Publication Types: 
    Review

PMID: 17504651 [PubMed - indexed for MEDLINE]

761: Curr Pain Headache Rep. 2007 Jun;11(3):227-30.

Preventative treatment of menstrual migraine.

Lay CL, Broner SW.

The Headache Institute, St. Luke'Roosevelt Hospital Center, 1000 10th Avenue,
Suite 1C-10, New York, NY 10019, USA. clay@chpnet.org

More than 20 million US women suffer with migraine, two thirds of whom experience
menstrually related migraine. Estrogen plays an important role in triggering
migraine, and given the numerous hormonal fluctuations throughout a woman's
lifetime, there are many opportunities for a hormonal impact. Accurate diagnosis 
is key to initiating effective treatment, and when acute therapy fails, the
unique predictability of menstrual migraine lends itself to preventative
treatment.

Publication Types: 
    Review

PMID: 17504650 [PubMed - indexed for MEDLINE]

762: Curr Pain Headache Rep. 2007 Jun;11(3):217-26.

Migraine-related vertigo: diagnosis and treatment.

Eggers SD.

Department of Neurology, Mayo Clinic, 200 1st Street SW, Rochester, MN 55905,
USA. eggers.scott@mayo.edu

A comprehensive review of the neurotologic manifestations of migraine is
presented, focusing on the most recent publications regarding the epidemiology,
clinical presentation, pathophysiology, diagnosis, and management of
migraine-related vertigo (MV). A strong association exists between vertigo and
migraine, with MV being the most common cause of spontaneous (nonpositional)
episodic vertigo. Symptoms can be quite variable among patients and within
individual patients over time, creating a diagnostic challenge. MV generally
presents with attacks of spontaneous or positional vertigo lasting seconds to
days with associated migrainous symptoms. Operational diagnostic criteria have
been proposed but are not included in the most recent International Headache
Society classification of migraine. Better elucidation of the neurologic linkages
between the central vestibular pathways and migraine-related pathways and the
discovery of ion channel defects underlying some causes of familial migraine,
ataxia, and vertigo have furthered the understanding of MV pathophysiology.
Treatment of MV currently parallels that of migraine headache, as proper studies 
of optimal MV management are just beginning.

Publication Types: 
    Review

PMID: 17504649 [PubMed - indexed for MEDLINE]

763: Neurology. 2007 May 15;68(20):1694-700.

Comment in:
    Neurology. 2008 Feb 12;70(7):579; author reply 579-80.

Migraine and retinal microvascular abnormalities: the Atherosclerosis Risk in
Communities Study.

Rose KM, Wong TY, Carson AP, Couper DJ, Klein R, Sharrett AR.

Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel
Hill, NC 27514, USA. kathyrn_rose@unc.edu

OBJECTIVE: This study examined the association between vascular headaches and
retinal microvascular disease. METHODS: We investigated the cross-sectional
association between headaches (migraine/other headaches with aura, migraine
without aura, other headaches without aura, no headaches) and retinal
microvascular signs (retinopathy, focal arteriolar narrowing, arteriovenous
nicking; arteriolar and venular calibers) among middle-aged African American and 
white men and women from the third examination of the Atherosclerosis Risk in
Communities Study (1993 through 1995). RESULTS: After controlling for age,
gender, race, study center, and cardiovascular risk factors, we determined that
persons with headaches were more likely to have retinopathy than those without a 
history of headaches (odds ratio [OR] = 1.38, 95% CI = 0.96 to 1.99 for
migraine/other headaches with aura; OR = 1.49, 95% CI = 1.05 to 2.12 for migraine
without aura; and OR = 1.28, 95% CI = 0.99 to 1.65 for other headaches).
Associations with migraine were stronger among the subset of participants without
a history of diabetes or hypertension (OR = 1.79, 95% CI = 1.09 to 2.95 for
migraine/other headaches with aura; and OR = 1.74, 95% CI = 1.11 to 2.71 for
migraine without aura). Headaches were not associated with focal arteriolar
narrowing or arteriovenous nicking. Persons with headaches tended to have smaller
mean arteriolar and venular calibers; however, these associations did not tend to
persist among those without hypertension or diabetes. CONCLUSION: Middle-aged
persons with migraine and other headaches were more likely to have retinopathy
signs, supporting the hypothesis that neurovascular dysfunction may underlie
vascular headaches.

Publication Types: 
    Comparative Study
    Multicenter Study
    Research Support, N.I.H., Extramural

PMID: 17502551 [PubMed - indexed for MEDLINE]

764: Arch Neurol. 2007 May;64(5):643-6.

Genetic models of migraine.

van de Ven RC, Kaja S, Plomp JJ, Frants RR, van den Maagdenberg AM, Ferrari MD.

Department of Human Genetics, Leiden University Medical Centre, Leiden, the
Netherlands.

Migraine is a common, disabling, complex brain disorder, presenting in attacks
that may have up to 3 phases: a prodromal phase, the aura phase, and the headache
phase. The pathogenesis of the aura and headache phases is reasonably well
understood, but the mechanism by which migraine attacks are triggered is unknown.
Most likely, migraineurs have a genetically determined reduced threshold for
migraine triggers. Identifying "threshold genes" and deciphering their function
will help to unravel the triggering mechanisms for migraine attacks. Familial
hemiplegic migraine is a rare monogenic subtype of migraine with aura. Three
genes have been identified for familial hemiplegic migraine. Recently, knock-in
mice carrying human pathogenic FHM1 mutations were generated, which show
behavioral, electrophysiological, and neurobiological characteristics in line
with prevailing views of migraine physiological processes. Genetic migraine
models will be useful in unraveling the triggering mechanisms for migraine
attacks and in identifying novel migraine prophylactic targets and therapies.

Publication Types: 
    Review

PMID: 17502463 [PubMed - indexed for MEDLINE]

765: Headache. 2007 May;47(5):726-8.

Ophthalmoplegic migraine with alternating unilateral and bilateral internal
ophthalmoplegia.

Choi JY, Jang SH, Park MH, Kim BJ, Lee DH.

Department of Neurology, Korea University College of Medicine, Ansan,
Gyeonggi-do, Republic of Korea.

We describe a patient with ophthalmoplegic migraine and internal ophthalmoplegia 
with alternating unilateral involvement and bilateral involvement in whom brain
MRI scan showed alternating gadolinium enhancement on the cisternal portion of
the oculomotor nerve.

Publication Types: 
    Case Reports

PMID: 17501857 [PubMed - indexed for MEDLINE]

766: Headache. 2007 May;47(5):711-6.

The phe-124-Cys and A-161T variants of the human 5-HT1B receptor gene are not
major determinants of the clinical response to sumatriptan.

Mehrotra S, Vanmolkot KR, Frants RR, van den Maagdenberg AM, Ferrari MD,
MaassenVanDenBrink A.

Erasmus MC-Department of Pharmacology, Rotterdam, The Netherlands.

BACKGROUND: The 5-HT(1B/1D) receptor agonist sumatriptan is highly effective in
the treatment of migraine. However, some patients do not respond to sumatriptan
or experience recurrence of the headache after initial relief. In addition, some 
patients report chest symptoms after the use of sumatriptan. OBJECTIVE: To assess
whether 2 genetic variants (F124C changing a phenylalanine for a cysteine and
polymorphism A/T at nucleotide position -161 in the 5' regulatory region) of the 
5-HT(1B) receptor play a major role in the therapeutic response to sumatriptan.
The 5-HT(1B) receptor most likely mediates the therapeutic action and coronary
side effects of sumatriptan, and both F124C and A-161T have relevant functional
consequences on either the affinity of sumatriptan to bind to the 5-HT(1B)
receptor or on receptor expression level itself, respectively. METHOD: Genomic
DNA of a relatively small but very well-characterized set of migraine patients
with consistently good response to sumatriptan (n = 14), with no response (n =
12), with recurrence of the headache (n = 12), with chest symptoms (n = 13), and 
patients without chest symptoms (n = 27) was available for the genetic analyses
and screened for the F124C variant and the A-161T polymorphism in the human
5-HT(1B) receptor gene. RESULTS: F124C was not detected in any of the patients
studied. In addition, we did not observe drastic changes in allele frequencies of
the A-161T polymorphism that might hint to a causal relation with the therapeutic
effect of sumatriptan. CONCLUSION: We have not obtained any evidence that
variants F124C and A-161T of the 5-HT(1B) receptor are major determinants in the 
clinical response to sumatriptan.

Publication Types: 
    Clinical Trial

PMID: 17501853 [PubMed - indexed for MEDLINE]

767: Headache. 2007 May;47(5):703-10.

Emergency department management of acute migraine in children in Canada: a
practice variation study.

Richer L, Graham L, Klassen T, Rowe B.

University of Alberta-Pediatrics, Division of Neurology, Edmonton, Alberta,
Canada.

OBJECTIVES: Evidence-based guidelines for the treatment of children with migraine
are limited given the paucity of randomized controlled trials, especially in the 
emergency department (ED). Our objectives were to: (1) characterize the treatment
of children with migraine in the ED; (2) determine whether treatment varies in
pediatric versus mixed (pediatric and adult) EDs. METHODS: Children aged 5 to 17 
years presenting to 4 regional emergency departments in Edmonton, Alberta, Canada
during the 2003/2004 fiscal year with a diagnostic code of headache or migraine
were selected. A standardized retrospective chart abstraction was performed and
migraine or probable migraine cases were classified based on the International
Classification of Headache Disorders II. RESULTS: Three hundred and eighty-two
cases were identified of which 48.7% (n = 186/382) met sufficient criteria for
migraine. No treatment was given in 44.2% (n = 169/382). Simple oral analgesics
(23.3%; n = 89/182) and dopamine antagonists (metoclopramide and
prochlorperazine; 20.7%; n = 79/182) were prescribed first-line most commonly.
Opiate medications (5.5%), ketorolac (4.7%), dihydroergotamine (1%) were
prescribed first-line infrequently. There was a significant difference in the
management choices between pediatric and mixed adult/pediatric EDs (chi(2)=
19.695; df = 5; P= .001). The pediatric ED was more likely to prescribe a
dopamine antagonist (12.9 vs 6.8%; P= .044) while the mixed adult/pediatric EDs
were more likely to prescribe an opiate (28.1% vs 18.4%; P= .031). Children with 
migraine in all EDs were significantly more likely to receive drug therapy (68.3%
vs 42.9%; P < .001) or a dopamine antagonist (32.3% vs 9.7%; P < .001).
Polypharmacy (31.2%; n = 119/382) and neuroimaging (29.1%; n = 111/382) were
common. Outcome was poorly documented overall. No adverse events were recorded.
CONCLUSIONS: Significant variation in practice in the management of acute
headaches in children was observed between mixed population and pediatric-only
emergency physicians in the same city. Most children do not receive any drug
therapy. Children presenting to the pediatric ED were significantly more likely
to receive a dopamine antagonist while opiates were prescribed more commonly in
the mixed ED. More clinical trials are required in children to clarify areas of
clinical uncertainty on which evidence-based practice guidelines can be formed.

PMID: 17501852 [PubMed - indexed for MEDLINE]

768: Headache. 2007 May;47(5):698-702.

Mmp-9 immunoreactivity in acute migraine.

Leira R, Sobrino T, Rodríguez-Yáñez M, Blanco M, Arias S, Castillo J.

Headache and Stroke Unit and Neurovascular Research Laboratory, Department of
Neurology, Hospital Clínico Universitario, University of Santiago de Compostela, 
Spain.

OBJECTIVE: To examine the role of matrix metalloproteinase 9 (MMP-9) in migraine 
during headache and asymptomatic periods. METHODS: Thirty-four patients with
migraine with and without aura (according to International Headache Society
criteria) were studied. Clinical characteristic of headache were recorded. Blood 
samples for measurement of MMP-9 were drawn during headache attacks and during
asymptomatic periods in all patients and in 10 healthy controls. RESULTS: We
found higher plasma MMP-9 levels in migraine patients than in control group
(129.3 [78.0-258.9] vs. 49.6 [39.1-64.3] ng/mL; P < .001). Migrainous patients
showed higher MMP-9 plasma levels during headache attacks than in asymptomatic
periods, both in migraine without aura (338.4 [275.1-396.2] vs. 118.2
[75.3-137.5] ng/mL; P < .0001), and migraine with aura (389.3 [273.4-487.1] vs.
139.3 [107.3-191.4] ng/mL; P < .0001). CONCLUSIONS: Our study showed an increased
production of MMP-9 during migraine attacks. These data suggest a possible role
of inflammation or blood-brain barrier disruption during the migraine attack.

PMID: 17501851 [PubMed - indexed for MEDLINE]

769: Headache. 2007 May;47(5):683-92.

Sumatriptan/Naproxen sodium for migraine: efficacy, health related quality of
life, and satisfaction outcomes.

Smith T, Blumenthal H, Diamond M, Mauskop A, Ames M, McDonald S, Lener S, Burch
S.

Mercy Health Research and Ryan Headache Center, St. Louis, MO 63141, USA.

OBJECTIVE: To describe the pain relief, satisfaction, and health-related quality 
of life results of moderate or severe migraines treated with a
sumatriptan/naproxen sodium combination tablet. METHODS: Sumatriptan and naproxen
sodium as a single-dose formulation tablet was used to treat moderate to severe
migraines over a 12-month period in a phase 3, open-label, multicenter study (n =
565) in patients with at least 6 months' history of migraine headaches. RESULTS: 
Seventy percent of all attacks were treated with 1 dose of sumatriptan/naproxen
sodium. Overall subjects treated 24,485 attacks; of these, 81% attacks achieved
pain relief and 60% pain-free by 2 hours. At 3 months, the percentage of patients
satisfied or very satisfied increased from baseline on all 8 Patient Perception
of Migraine Questionnaire (PPMQ) items and remained high throughout the study.
Mean Migraine-Specific Quality of Life Questionnaire (MSQ) domain scores also
increased by 13-15 points from baseline during this time and remained high.
CONCLUSIONS: Sumatriptan/naproxen sodium provides consistent relief of migraine
attacks over 12 months, resulting in improved patient satisfaction and migraine
specific quality of life.

Publication Types: 
    Clinical Trial, Phase III
    Multicenter Study
    Research Support, Non-U.S. Gov't

PMID: 17501849 [PubMed - indexed for MEDLINE]

770: Headache. 2007 May;47(5):673-82.

Efficacy of eletriptan in migraine-related functional impairment: functional and 
work productivity outcomes.

Silberstein SD, Cady RK, Sheftell FD, Almas M, Parsons B, Albert KS.

Jefferson Headache Center, Philadelphia, PA 19107, USA.

OBJECTIVE: To provide a multidimensional assessment of the extent of functional
impairment during an acute migraine attack, and of the improvement in functioning
in response to treatment, using 4 concurrently administered scales: the 7-item
work productivity questionnaire (PQ-7), the functional assessment in migraine
(FAIM) activities and participation (FAIM-A&P) subscale, the FAIM-impact of
migraine on mental functioning (FAIM-IMMF) subscale, and the traditional 4-point 
global functional impairment scale (FIS). METHODS: Outpatients with an
International Classification of Headache Disorders diagnosis of migraine were
randomized to double-blind treatment of a single attack with either oral
eletriptan 20 mg (n = 192) once-daily, eletriptan 40 mg (N = 213) once-daily, or 
placebo (n = 208). Patients were encouraged to take study medication as soon as
they were sure they were experiencing a typical migraine headache, after the aura
phase (if present) had ended. Patients with moderate-to-severe functional
impairment were identified on each of the 4 disability scales, and 2-hour
functional response was compared between treatments. RESULTS: At baseline, the
PQ-7 and FAIM-IMMF items that assessed ability to perform tasks requiring
concentration, sustained work or attention, and ability to think quickly or
spontaneously, were especially sensitive to the effects of mild headache pain,
with 27% to 48% of patients (n = 92-112) reporting moderate-to-severe impairment.
Only 11.3% of patients (n = 112) reported this level of impairment due to mild
pain on the FIS. Functional response at 2 hours was significantly higher on
eletriptan 40 mg versus placebo on the FAIM-A&P (63% vs 36%; n = 218; P < .0001);
on the PQ-7 (56% vs 34%; n = 116; P= .0052); and on the FAIM-IMMF (50% vs 34%; n 
= 215; P= .017). These rates were all lower than the functional response rates on
the FIS for eletriptan 40 mg (75%) and eletriptan 20 mg (70%) versus placebo
(45%; P < .001). Conclusions.-In this exploratory analysis, use of
multidimensional scales was found to provide a sensitive measure of
headache-related functional impairment, especially for detecting clinically
meaningful cognitive effects, and for detecting drug versus placebo differences.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 17501848 [PubMed - indexed for MEDLINE]

771: Headache. 2007 May;47(5):654-61.

Effectiveness of yoga therapy in the treatment of migraine without aura: a
randomized controlled trial.

John PJ, Sharma N, Sharma CM, Kankane A.

Department of Zoology, University of Rajasthan, Jaipur, Rajasthan, India.

BACKGROUND: Numerous studies have explored the effectiveness of complementary and
alternative medicine in the treatment of migraine but there is no documented
investigation of the effectiveness of yoga therapy for migraine management.
OBJECTIVES: To investigate the effectiveness of holistic approach of yoga therapy
for migraine treatment compared to self-care. DESIGN: A randomized controlled
trial. METHODS: Seventy-two patients with migraine without aura were randomly
assigned to yoga therapy or self-care group for 3 months. Primary outcomes were
headache frequency (headache diary), severity of migraine (0-10 numerical scale) 
and pain component (McGill pain questionnaire). Secondary outcomes were anxiety
and depression (Hospital anxiety depression scale), medication score. RESULTS:
After adjustment for baseline values, the subjects' complaints related to
headache intensity (P < .001), frequency (P < .001), pain rating index (P <
.001), affective pain rating index (P < .001), total pain rating index (P <
.001), anxiety and depression scores (P < .001), symptomatic medication use (P < 
.001) were significantly lower in the yoga group compared to the self-care group.
CONCLUSION: The study demonstrated a significant reduction in migraine headache
frequency and associated clinical features, in patients treated with yoga over a 
period of 3 months. Further study of this therapeutic intervention appears to be 
warranted.

Publication Types: 
    Clinical Trial
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 17501846 [PubMed - indexed for MEDLINE]

772: Headache. 2007 May;47(5):645-53.

Can migraineurs accurately identify their headaches as "migraine" at attack
onset?

Ng-Mak DS, Cady R, Chen YT, Ma L, Bell CF, Hu XH.

Outcomes Research and Management, Merck & Co., Inc., West Point, PA, USA.

BACKGROUND: While treating migraine early when the headache is mild is believed
to link to improved treatment outcomes, it is not clear whether patients can
correctly self-identify a headache as a migraine at onset in real-world settings.
OBJECTIVE: This study aims to assess the likelihood that patients can correctly
self-identify a headache as a migraine at onset, and to evaluate cues that
patients use to correctly identify migraine attacks. METHODS: Adult migraineurs
were recruited from 14 headache clinics across the United States. Patients
recorded their headache experiences via an electronic diary daily over a period
of 30 days. On days when they experienced headaches, patients were asked to
recall the types of headache they experienced at both onset and peak. Patients
also identified cues for deciding whether the headache was a migraine or not.
Using identification of migraine at headache peak as the criterion, we examined
the sensitivity and specificity of migraine identification at onset. We employed 
generalized estimating equation (GEE) to evaluate factors identified at headache 
onset that predicted migraine identified at headache peak. RESULTS: Of the 192
enrolled patients, 182 patients recorded a total of 1197 headache episodes over
30 days. At headache onset, 888 episodes were deemed by patients as migraine and 
309 episodes not migraine; a majority (92%) of these early migraine
identifications were confirmed at headache peak. Sensitivity and specificity of
self-identification of migraine at onset were 91% and 97%, respectively. A number
of factors at headache onset were predictive of a migraine identified at peak:
sensitivity to light (OR = 3.1, 95% CI: 1.9-5.0), headache severity (OR = 2.0,
95% CI: 1.4-2.8), nausea symptoms (OR = 2.6, 95% CI: 1.5-4.5), and visual
disturbance (OR = 2.3, 95% CI: 1.1-4.9). Patients who ruled out tension-type
headache at onset were twice (OR = 2.0, 95% CI: 1.5-2.8) as likely to conclude a 
migraine at peak. CONCLUSIONS: Most migraineurs in tertiary care settings can
correctly self-identify a headache as a migraine at onset. Factors such as
headache severity, presence of nausea, visual disturbance, sensitivity to light, 
and no tension-type headache, appeared to augment the correct identification.

Publication Types: 
    Multicenter Study
    Research Support, Non-U.S. Gov't

PMID: 17501845 [PubMed - indexed for MEDLINE]

773: Cephalalgia. 2007 Jul;27(7):833-9. Epub 2007 May 10.

Transcranial direct current stimulation reveals inhibitory deficiency in
migraine.

Chadaide Z, Arlt S, Antal A, Nitsche MA, Lang N, Paulus W.

Department of Clinical Neurophysiology, Georg-August University, Göttingen,
Germany.

The issue of interictal excitability of cortical neurons in migraine patients is 
controversial: some studies have reported hypo-, others hyperexcitability. The
aim of the present study was to observe the dynamics of this basic interictal
state by further modulating the excitability level of the visual cortex using
transcranial direct current stimulation (tDCS) in migraineurs with and without
aura. In healthy subjects anodal tDCS decreases, cathodal stimulation increases
transcranial magnetic stimulation (TMS)-elicited phosphene thresholds (PT), which
is suggested as a representative value of visual cortex excitability. Compared
with healthy controls, migraine patients tended to show lower baseline PT values,
but this decrease failed to reach statistical significance. Anodal stimulation
decreased phosphene threshold in migraineurs similarly to controls, having a
larger effect in migraineurs with aura. Cathodal stimulation had no significant
effect in the patient groups. This result strengthens the notion of deficient
inhibitory processes in the cortex of migraineurs, which is selectively revealed 
by activity-modulating cortical input.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17498207 [PubMed - indexed for MEDLINE]

774: J Headache Pain. 2007 Apr;8(2):127-34. Epub 2007 May 11.

Acute pharmacotherapy of migraine, tension-type headache, and cluster headache.

Tfelt-Hansen P.

Dept. of Neurology, Glostrup Hospital, DK-2600, Glostrup, Denmark.
tfelt@inet.uni2.dk

In most migraine patients acute therapy is needed. Migraine can be treated either
with specific drugs, the triptans and ergot alkaloids, or with NSAIDs. Triptans
are a major step foreward in migraine therapy. The therapeutic gain for headache 
relief is 50% for subcutaneous sumatriptan whereas it is 30-40% for most oral
triptans. After oral triptans sustained pain free is only 30%. There is thus
still ample room for improvement of acute therapy in migraine. For tension-type
headache there is no specific therapy and it is treated with NSAIDs. Only 17-32% 
become pain free after these drugs. For attacks of cluster headache oxygen and
subcutaneous sumatriptan can be used. Intranasal triptans can be an alternative.

Publication Types: 
    Review

PMID: 17497267 [PubMed - indexed for MEDLINE]

775: J Headache Pain. 2007 Apr;8(2):119-22. Epub 2007 May 11.

Is migraine with cranial nerve palsy an ophthalmoplegic migraine?

Giraud P, Valade D, Lanteri-Minet M, Donnet A, Geraud G, Guégan-Massardier E;
Observatoire des Migraines et Céphalées of the French Headache Society.

Service de Neurologie A, Centre Hospitalier de la région Annecienne, 1 Avenue du 
Tresum, F-74000, Annecy, France. pgiraud@ch-annecy.fr

Ophthalmoplegic migraine (OM) is a rare form of primary headache. Because of its 
rarity, only a few cases, mostly symptomatic, are reported. We analyse nine cases
among 52 973 adults who suffer from headaches with an oculomotor palsy firstly
considered as OM. The study was retrospective and multicentric in a database set 
up in France. The aim of our investigation was to describe the clinical and
radiological aspects of these cases and to discuss the diagnosis of OM. We
demonstrate that the characteristics of the headaches were identical to usual
migraine without oculomotor nerve palsy for each case. The study emphasises the
difficulty of the OM diagnosis even with the new IHS criteria because of the
rarity of having all characteristics. A wide heterogeneity was noted in cranial
imagery and blood tests. We suggest adding the code of probable OM in the IHS
classification to increase the knowledge and detection of this type of headache. 
A biological blood test and an MRI are systematically required to help clinicians
in their diagnosis and to exclude alternative aetiology of headache with palsy.

Publication Types: 
    Multicenter Study
    Research Support, Non-U.S. Gov't

PMID: 17497265 [PubMed - indexed for MEDLINE]

776: J Headache Pain. 2007 Apr;8(2):105-13. Epub 2007 May 11.

Effect of daily migraine prevention on health care utilisation in an insured
patient population.

Devine J, Hadsall R, Cline R, Schommer J, Virnig B.

Fort Sam Houston, TX, 78234-6102, USA. josh.devine@amedd.army.mil

The economic benefits of daily migraine prevention have been subject to ongoing
debate. This study was undertaken to determine if the initiation of prevention
had an observable effect on ambulatory health care utilisation when compared to
acute migraine treatment alone. Administrative claims data from the Military
Health System were used to conduct a retrospective, longitudinal cohort study of 
3762 patients with migraine. New users of daily migraine prevention were matched 
to a reference group of non-users using propensity score methods. This matched
sample then was used to evaluate the effect of prevention on ambulatory health
care expenditures. The study results showed that exposure to daily migraine
prevention led to lower rates of utilisation relative to what new patients would 
have consumed in the absence of treatment. The results suggest that additional
economic benefits could be realised by increasing the appropriate use of daily
migraine prevention.

PMID: 17497263 [PubMed - indexed for MEDLINE]

777: J Headache Pain. 2007 Apr;8(2):77-82. Epub 2007 May 11.

A pilot methodological validation study for a population-based survey of the
prevalences of migraine, tension-type headache and chronic daily headache in the 
country of Georgia.

Katsarava Z, Kukava M, Mirvelashvili E, Tavadze A, Dzagnidze A, Djibuti M,
Steiner TJ.

Department of Neurology, University of Essen, Hufelandstrasse 55, DE-45122,
Essen, Germany. zaza.katsarava@uni-due.de

We report the methodology of an epidemiological survey of the prevalences of
migraine, tension-type headache and chronic daily headache in Georgia. Medical
residents visited adjacent households in Tbilisi to interview a pre-defined
target of 100 biologically unrelated subjects. All respondents reporting headache
in the previous year, as well as random 20 non-headache controls, were examined
by a neurologist. The response rate was 70%. Of 156 respondents, 93 were
biologically unrelated and 45 (48%) reported headache in the previous year. Eight
subjects fulfilled all IHS criteria for migraine (1-year prevalence 8.6% [95% CI:
2.9-14.3%]), and 13 had probable migraine, meeting all but the criterion for
duration. Nineteen had tension-type headache (20.4% [95% CI: 12.2-28.6%]) and
five had chronic daily headache (5.4% [95% CI: 1-10.0%]). In comparisons of
diagnoses by questionnaire and neurologist (considered the gold standard),
sensitivities for the questionnaire of 89% for migraine and 67% for tension-type 
headache were calculated (overall kappa=0.74).

PMID: 17497261 [PubMed - indexed for MEDLINE]

778: Neurologist. 2007 May;13(3):118-25.

Migraine aura.

Cutrer FM, Huerter K.

Department of Neurology, Mayo Clinic, Rochester, Minnesota 55905, USA.
cutrer.michael@mayo.edu

Recurrent episodes of transient focal neurologic symptoms, known as aura, occur
in association with migraine headache in about 11.9 million people in the United 
States. At present, the International Headache Society has recognized 3 "typical"
auras: visual, sensory, and language. Increasing evidence from investigations in 
human subjects suggests that typical auras may be the clinical manifestation of a
cortical spreading depression (CSD)-like phenomenon. Other studies have shown
altered reactivity and processing within the cortices of migraineurs who
experience an aura, which might render them more vulnerable to CSD-like events.
Recent investigations also support the hypothesis that events intrinsic to the
cerebral cortex are capable of activating trigeminal nociceptive neurons and of
affecting the caliber of vascular structures innervated by them. A better
understanding of the mechanisms underlying the aura may potentially lead to more 
effective therapies, which will aim at preventing migraine headaches before they 
start.

Publication Types: 
    Review

PMID: 17495755 [PubMed - indexed for MEDLINE]

779: Curr Opin Neurol. 2007 Jun;20(3):310-9.

Patent foramen ovale, stroke, and cardiovascular disease in migraine.

Diener HC, Kurth T, Dodick D.

Department of Neurology, University of Duisburg-Essen, Essen, Germany.
hans.diener@uni-duisburg-essen.de

PURPOSE OF REVIEW: We will review the literature on the association between
migraine with patent foramen ovale, stroke, and coronary heart disease. RECENT
FINDINGS: The prevalence of patent foramen ovale in patients with migraine with
aura is significantly higher than in nonmigraine controls and migraineurs without
aura. However, there is currently no evidence to support a causal relationship.
Migraine with aura has been consistently associated with increased risk of
ischemic stroke in several epidemiologic studies. Migraine with aura is
associated with a more unfavourable cardiovascular risk profile and recent data
suggest that the association between migraine with aura and stroke may extend to 
overall cardiovascular disease. Identification of migraine patients at particular
risk for stroke or other vascular events is impossible based on current
knowledge. SUMMARY: Migraine with aura and patent foramen ovale have higher
coincidences than expected by chance only. It is possible that both conditions
are inherited together. Until now there has been no evidence from
placebo-controlled randomized trials that closure of patent foramen ovale
improves migraine with aura. There is increasing evidence that migraine with aura
is not only a risk factor for ischemic stroke but also for myocardial infarction 
and other ischemic vascular events.

Publication Types: 
    Review

PMID: 17495626 [PubMed - indexed for MEDLINE]

780: Curr Opin Neurol. 2007 Jun;20(3):306-9.

New insights into migraine: application of functional and structural imaging.

May A, Matharu M.

Department of Systems Neuroscience, University of Hamburg, Germany.
a.may@uke.uni-hamburg.de

PURPOSE OF REVIEW: Functional neuroimaging in headache patients has
revolutionized our understanding of these syndromes. Further insights into the
pathophysiology of headache syndromes have been provided by innovative
neuroimaging analysis using structural data. This review highlights the recent
advances made in studying migraine using neuroimaging techniques. RECENT
FINDINGS: Several independent studies have reinforced the crucial role for the
brainstem in acute and probably also chronic migraine. Recently described
structural abnormalities in the visual network of motion-processing areas could
account for, or be caused by, the cortical hyperexcitability observed in
migraineurs. Although data from morphometric studies are heterogeneous, a recent 
study suggests an increased density of brainstem structures and decreased grey
matter in pain-transmitting areas in migraine patients. SUMMARY: Given the rapid 
advances in functional neuroimaging, in particular newer techniques such as
voxel-based morphometry and magnetic resonance spectrometry, functional imaging
continues to play a significant role and opens new avenues in targeting the
neural substrates in individual primary headache syndromes.

Publication Types: 
    Review

PMID: 17495625 [PubMed - indexed for MEDLINE]

781: Curr Opin Neurol. 2007 Jun;20(3):299-305.

Migraine: gene mutations and functional consequences.

van den Maagdenberg AM, Haan J, Terwindt GM, Ferrari MD.

Department of Human Genetics, Leiden, The Netherlands.

PURPOSE OF REVIEW: Genetic and functional studies of mutations in familial
hemiplegic migraine reveal a major role for disturbed ion transport. Gene
identification in common, multifactorial migraine remains challenging. RECENT
FINDINGS: Several new mutations have been identified in FHM1, FHM2 and FHM3
genes. Functional consequences of familial hemiplegic migraine mutations point to
an important role for cortical spreading depression in migraine pathophysiology. 
New genetic approaches have been tested in common migraine - novel chromosomal
loci - but no gene variants have been identified. SUMMARY: Identification and
analysis of gene mutations in familial hemiplegic migraine revealed a major role 
for disturbed ion transport in this disorder. Cellular and transgenic mouse
models of familial hemiplegic migraine genes suggest that increased potassium and
glutamate play a role in the pathophysiology of the disorder. Despite progress,
no genes have been discovered for common migraine.

Publication Types: 
    Review

PMID: 17495624 [PubMed - indexed for MEDLINE]

782: Expert Rev Neurother. 2007 May;7(5):463-70.

Botulinum toxin type A in chronic migraine.

Freitag FG.

The Chicago Medical School at Rosalind Franklin University of Medicine and
Science, Department of Family Medicine, North Chicago, IL, USA. dhcdoc@aol.com

The use of botulinum toxin type A continues to be investigated by the US FDA for 
potential use in the treatment of headache. As part of this process there has
been extensive research conducted by individual study sites as well as
multicenter trials. To date, the majority of the focus has been on migraine
headache as well as on tension-type headache. The results of these studies have
been mixed. A variety of issues may contribute to the mixed results, including
difference in the dose of toxin used, the number of injection sites utilized, the
treatment paradigm itself, confounding medications, high and prolonged placebo
response, as well as patient selection issues. Currently, the focus on botulinum 
toxin type A is on those patients who have chronic daily headache with a migraine
component to their clinical picture. The results of two large trials in this
population produced positive findings, especially when consideration is given to 
the a priori additional analyses of this complex patient population. The results 
of these studies have allowed a more focused program to be undertaken in the
Phase III evaluation. At the same time, additional work has been performed to
understand the mechanism by which botulinum toxin type A may work to alleviate
migraine. This work may contribute substantially to improving outcomes with
botulinum toxin type A. Characterization of the mechanism of action in pain may
be crucial to outcomes because many issues are related to central sensitization.

Publication Types: 
    Review

PMID: 17492897 [PubMed - indexed for MEDLINE]

783: Ann Neurol. 2007 Jun;61(6):603-6.

Comment in:
    Ann Neurol. 2007 Dec;62(6):678-9; author reply 679-80.

Reduced threshold for cortical spreading depression in female mice.

Brennan KC, Romero Reyes M, López Valdés HE, Arnold AP, Charles AC.

Department of Neurology, University of California, Los Angeles, CA 90095, USA.

The prevalence of migraine is much greater in female than male individuals.
Cortical spreading depression (CSD) is thought to be a fundamental mechanism of
migraine, and CSD in rodents is used as a model for migraine. We used optical
intrinsic signal imaging and electrophysiological techniques to investigate CSD
in C57Bl/6 mice. Using two different methods for induction of CSD, we found that 
female mice had a significantly reduced threshold for induction of CSD compared
with male mice. These results suggest an increased cortical excitability in
female mice that may be independent of the estrous cycle.

Publication Types: 
    Research Support, N.I.H., Extramural

PMID: 17474110 [PubMed - indexed for MEDLINE]

784: Ann Neurol. 2007 Jun;61(6):574-8.

A dopamine D4 receptor exon 3 VNTR allele protecting against migraine without
aura.

de Sousa SC, Karwautz A, Wöber C, Wagner G, Breen G, Zesch HE, Konrad A, Zormann 
A, Wanner C, Kienbacher C, Collier DA, Wöber-Bingöl C.

Social, Genetic and Developmental Centre, Institute of Psychiatry, University of 
London, London, United Kingdom.

OBJECTIVE: As dopamine plays an important role in the pathophysiology of migraine
and antimigraine drugs have an effect on the dopamine system, the objective of
this study was to examine the dopamine D4 receptor gene for involvement in the
cause of migraine. METHODS: We tested a VNTR-polymorphism in the dopamine D4
receptor gene, the exon 3 VNTR, in a sample of 190 family trios each with a
proband with childhood migraine by using transmission disequilibrium test tests. 
RESULTS: We found a trend for transmission distortion of this marker in migraine,
with the common seven-repeat allele of the VNTR transmitted 58 times and not
transmitted 82 times (global likelihood ratio score (LRS) = 12.27, degress of
freedom (DF) = 6, p = 0.06; for the 7-repeat allele: chi(2) = 5.1, p = 0.02).
This effect came only from migraine without aura (145 trios), with the common
7-repeat allele transmitted 45 times and not transmitted 69 times (global LRS =
15.18; DF = 6, p = 0.019; for the 7-repeat allele: chi(2) = 6.4, p = 0.01; odds
ratio, 0.47), whereas in migraine with aura (45 trios) there was no transmission 
distortion of the 7-repeat allele. INTERPRETATION: We conclude that seven-repeat 
allele of the dopamine D4 receptor VNTR is a protective factor for migraine
without aura. Because migraine is a common disorder, this protective effect may
have contributed to the positive selection acting on the dopamine D4 receptor
exon 3 VNTR seven-repeat allele in recent human history. We speculate that
dopamine function in the lateral parabrachial nucleus is involved in migraine
without aura.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17474108 [PubMed - indexed for MEDLINE]

785: Eur J Hum Genet. 2007 Aug;15(8):884-8. Epub 2007 May 2.

First case of compound heterozygosity in Na,K-ATPase gene ATP1A2 in familial
hemiplegic migraine.

Vanmolkot KR, Stam AH, Raman A, Koenderink JB, de Vries B, van den Boogerd EH,
van Vark J, van den Heuvel JJ, Bajaj N, Terwindt GM, Haan J, Frants RR, Ferrari
MD, van den Maagdenberg AM.

Department of Human Genetics, Leiden University Medical Centre, Leiden, The
Netherlands.

Familial hemiplegic migraine (FHM) is a rare autosomal-dominant subtype of
migraine with aura, associated with hemiparesis during the aura. Here we describe
a unique FHM family in which two novel allelic missense mutations in the
Na,K-ATPase gene ATP1A2 segregate in the proband with hemiplegic migraine. Both
mutations show reduced penetrance in family members of the proband. Cellular
survival assays revealed Na,K-ATPase dysfunction for both ATP1A2 mutants,
indicating that both mutations are disease causative. This is the first case of
compound heterozygosity for any of the known FHM genes.

Publication Types: 
    Case Reports
    Research Support, Non-U.S. Gov't

PMID: 17473835 [PubMed - indexed for MEDLINE]

786: Qual Life Res. 2007 Sep;16(7):1231-7. Epub 2007 Apr 28.

Validation of the Migraine-Specific Quality of Life Questionnaire version 2.1
(MSQ v. 2.1) for patients undergoing prophylactic migraine treatment.

Cole JC, Lin P, Rupnow MF.

QualityMetric, 640 George Washington Highway, Suite 201, Lincoln, RI 02865, USA. 
jcole@qualitymetric.com

OBJECTIVE: Health-related quality of life (HRQoL) is an important outcome measure
of migraine treatments. Although a number of migraine-specific HRQoL
questionnaires exist, their measurement characteristics have only been examined
for patients undergoing acute treatment of migraine. The goal of the current
study was to evaluate measurement properties of the widely used Migraine-Specific
Quality of Life Questionnaire version 2.1 (MSQ v. 2.1) within a group of patients
undergoing prophylactic migraine treatment. METHODS: Various measurement
properties of the MSQ were examined in a sample of 916 migraineurs undergoing
prophylactic treatment who had scores at baseline and follow-up, as well as
baseline SF-36. First, we used confirmatory factor analysis (CFA) and
differential item functioning (DIF) to assure the accuracy and stability across
groups of the MSQ scoring for all three subscales (Role Restrictive, Role
Preventive, and Emotional Functioning). Next, item- and scale-level properties
were examined, such as item-total correlations, internal consistency, and
convergent and discriminant validity. RESULTS: Initial findings revealed that
item 12 (measuring frustration on the Emotional Functioning subscale) performed
poorly. Subsequent to its removal, the 13-item MSQ displayed excellent
measurement properties, including stable latent structure at baseline and
endpoint, no gender or age biases on items, appropriate item-level and
scale-level reliabilities, and markedly higher convergent validity compared to
discriminant validity. CONCLUSION: The 13-item MSQ appears to be an appropriate
measure of migraine-specific HRQoL for patients undergoing migraine prophylaxis. 
Moreover, given the stability of the latent structure over time, the
interpretation of scores is likely to remain quite consistent throughout a
clinical trial.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Validation Studies

PMID: 17468941 [PubMed - indexed for MEDLINE]

787: Nat Rev Drug Discov. 2007 May;6(5):357-72.

Erratum in:
    Nat Rev Drug Discov. 2007 Jun;6(6):442.

The vanilloid receptor TRPV1: 10 years from channel cloning to antagonist
proof-of-concept.

Szallasi A, Cortright DN, Blum CA, Eid SR.

Department of Pathology, Monmouth Medical Center, Long Branch, New Jersey 07740, 
USA. aszallasi@sbhcs.com

The clinical use of TRPV1 (transient receptor potential vanilloid subfamily,
member 1; also known as VR1) antagonists is based on the concept that endogenous 
agonists acting on TRPV1 might provide a major contribution to certain pain
conditions. Indeed, a number of small-molecule TRPV1 antagonists are already
undergoing Phase I/II clinical trials for the indications of chronic inflammatory
pain and migraine. Moreover, animal models suggest a therapeutic value for TRPV1 
antagonists in the treatment of other types of pain, including pain from cancer. 
We argue that TRPV1 antagonists alone or in conjunction with other analgesics
will improve the quality of life of people with migraine, chronic intractable
pain secondary to cancer, AIDS or diabetes. Moreover, emerging data indicate that
TRPV1 antagonists could also be useful in treating disorders other than pain,
such as urinary urge incontinence, chronic cough and irritable bowel syndrome.
The lack of effective drugs for treating many of these conditions highlights the 
need for further investigation into the therapeutic potential of TRPV1
antagonists.

Publication Types: 
    Review

PMID: 17464295 [PubMed - indexed for MEDLINE]

788: Neurology. 2007 May 8;68(19):1563-70. Epub 2007 Apr 25.

Comment in:
    Neurology. 2007 May 8;68(19):1555-6.    Neurology. 2007 Nov 20;69(21):2028; author reply 2028-9.    Neurology. 2007 Nov 20;69(21):2028; author reply 2028-9.

Altered arterial function in migraine of recent onset.

Vanmolkot FH, Van Bortel LM, de Hoon JN.

Center for Clinical Pharmacology, University Hospital Gasthuisberg, Leuven,
Belgium.

OBJECTIVE: Migraine is associated with cardiovascular disorders but the
underlying mechanisms are unknown. Arterial structure and function are important 
determinants of cardiovascular morbidity and mortality. The aim of the present
study was to assess arterial properties in patients with migraine of recent
onset. METHODS: In a cross-sectional study, structural and functional arterial
properties were assessed using ultrasound and applanation tonometry in 50
patients with a history of migraine >1 and <6 years during a headache-free
interval and 50 age- and gender-matched subjects without a history of migraine.
RESULTS: Brachial artery diameter (4.82 +/- 0.93 mm vs 5.39 +/- 0.89 mm, p =
0.01) and compliance (0.30 +/- 0.17 mm(2)/kPa vs 0.37 +/- 0.19 mm(2)/kPa, p =
0.02) were decreased in migraine patients compared with controls. Femoral artery 
compliance was decreased in migraine patients (1.19 +/- 0.55 mm(2)/kPa vs 1.42
+/- 0.59 mm(2)/kPa, p = 0.04). Carotid arterial wall properties were similar
between groups. Aortic augmentation index was increased in migraine patients (4
+/- 10% vs -1 +/- 10%, adjusted p = 0.04). Flow-mediated vasodilation of the
brachial artery (normalized to peak shear rate) was decreased in patients with
migraine (29 +/- 15 vs 37 +/- 15 10(-3)%. sec, p = 0.006). CONCLUSION: Functional
arterial properties are altered in patients with migraine of recent onset.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17460157 [PubMed - indexed for MEDLINE]

789: Neurology. 2007 Jun 5;68(23):1995-2002. Epub 2007 Apr 25.

Comment in:
    Neurology. 2007 Jun 5;68(23):1969-70.    Neurology. 2008 Mar 11;70(11):896; author reply 896-7.

Familial occipitotemporal lobe epilepsy and migraine with visual aura: linkage to
chromosome 9q.

Deprez L, Peeters K, Van Paesschen W, Claeys KG, Claes LR, Suls A, Audenaert D,
Van Dyck T, Goossens D, Del-Favero J, De Jonghe P.

Neurogenetics Group, Department of Molecular Genetics, VIB, Antwerpen, Belgium.

OBJECTIVE: To map the disease-causing locus in a large Belgian family with
occipitotemporal lobe epilepsy associated with migraine with visual aura and to
describe the clinical, electrophysiologic, and imaging characteristics. METHODS: 
DNA samples from 21 family members were obtained and an 8 cM density genome-wide 
scan was performed. The authors interviewed 21 individuals and performed
interictal EEG in 14 and brain MRI in 13 individuals. RESULTS: Nine at risk
family members and one deceased individual had epilepsy with occipital and
temporal lobe symptomatology, variable age at onset, usually good prognosis, no
epileptic EEG features, and normal brain MRI. Five of the 10 patients had a
history of migraine with aura (p = 0.0026). Seizures and migraine attacks
occurred as separate episodes in all but one patient. Three patients described
light flashes both as epileptic and migraine aura. Epilepsy and migraine started 
at the same age in three patients and remitted simultaneously in two. The
epileptic phenotype had a dominant mode of inheritance with a reduced penetrance 
of 75%. A conclusive two-point lod score of 3.3 was obtained for marker D9S257 at
recombination fraction zero. Haplotype analysis defined a candidate region of
9.95 cM (5.96 Mb) between markers GATA152H04 and D9S253 located at chromosome
9q21-q22 based upon recombinations in affected individuals. CONCLUSIONS: The
clinical association in this family of occipitotemporal lobe epilepsy and
migraine with visual aura and the conclusive linkage of the occipitotemporal lobe
epilepsy/migraine with aura trait to a single locus suggests a common monogenic
gene defect.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17460155 [PubMed - indexed for MEDLINE]

790: Psychoneuroendocrinology. 2007 Jun;32(5):532-8. Epub 2007 Apr 24.

Is stress a trigger factor for migraine?

Schoonman GG, Evers DJ, Ballieux BE, de Geus EJ, de Kloet ER, Terwindt GM, van
Dijk JG, Ferrari MD.

Department of Neurology (K5-Q), Leiden University Medical Centre, P.O. Box 9600, 
2300 RC Leiden, The Netherlands. g.g.schoonman@lumc.nl

BACKGROUND: Although mental stress is commonly considered to be an important
trigger factor for migraine, experimental evidence for this belief is yet
lacking. OBJECTIVE: To study the temporal relationship between changes in
stress-related parameters (both subjective and objective) and the onset of a
migraine attack. METHODS: This was a prospective, ambulatory study in 17 migraine
patients. We assessed changes in perceived stress and objective biological
measures for stress (saliva cortisol, heart rate average [HRA], and heart rate
variability [low-frequency power and high-frequency power]) over 4 days prior to 
the onset of spontaneous migraine attacks. Analyses were repeated for subgroups
of patients according to whether or not they felt their migraine to be triggered 
by stress. RESULTS: There were no significant temporal changes over time for the 
whole group in perceived stress (p=0.50), morning cortisol (p=0.73), evening
cortisol (p=0.55), HRA (p=0.83), low-frequency power (p=0.99) and high-frequency 
power (p=0.97) prior to or during an attack. Post hoc analysis of the subgroup of
nine stress-sensitive patients who felt that >2/3 of their migraine attacks were 
triggered by psychosocial stress, revealed an increase for perceived stress
(p=0.04) but no changes in objective stress response measures. At baseline, this 
group also showed higher scores on the Penn State Worry Questionnaire (p=0.003)
and the Cohen Perceived Stress Scale (p=0.001) compared to non-stress-sensitive
patients. CONCLUSIONS: Although stress-sensitive patients, in contrast to
non-stress-sensitive patients, may perceive more stress in the days before an
impending migraine attack, we failed to detect any objective evidence for a
biological stress response before or during migraine attacks.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17459597 [PubMed - indexed for MEDLINE]

791: Pain. 2007 Jul;130(1-2):166-76. Epub 2007 Apr 24.

Mast cell degranulation activates a pain pathway underlying migraine headache.

Levy D, Burstein R, Kainz V, Jakubowski M, Strassman AM.

Department of Anesthesia, Critical Care and Pain Medicine, Beth Israel Deaconess 
Medical Center and Harvard Medical School, Harvard Institutes of Medicine, Room
856, 77 Avenue Louis Pasteur, Boston, MA 02115, USA. dlevy1@bidmc.harvard.edu

Intracranial headaches such as that of migraine are generally accepted to be
mediated by prolonged activation of meningeal nociceptors but the mechanisms
responsible for such nociceptor activation are poorly understood. In this study, 
we examined the hypothesis that meningeal nociceptors can be activated locally
through a neuroimmune interaction with resident mast cells, granulated immune
cells that densely populate the dura mater. Using in vivo electrophysiological
single unit recording of meningeal nociceptors in the rat we observed that
degranulation of dural mast cells using intraperitoneal administration of the
basic secretagogue agent compound 48/80 (2 mg/kg) induced a prolonged state of
excitation in meningeal nociceptors. Such activation was accompanied by increased
expression of the phosphorylated form of the extracellular signal-regulated
kinase (pERK), an anatomical marker for nociceptor activation. Mast cell-induced 
nociceptor interaction was also associated with downstream activation of the
spinal trigeminal nucleus as indicated by an increase in c-fos expression. Our
findings provide evidence linking dural mast cell degranulation to prolonged
activation of the trigeminal pain pathway believed to underlie intracranial
headaches such as that of migraine.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 17459586 [PubMed - indexed for MEDLINE]

792: Cephalalgia. 2007 Jun;27(6):550-6. Epub 2007 Apr 25.

Migraine symptoms related to the percutaneous closure of an ostium secundum
atrial septal defect: report of four paediatric cases and review of the
literature.

Fernández-Mayoralas DM, Fernández-Jaén A, Muñoz-Jareño N, Gutiérrez-Larraya F,
Calleja-Pérez B, San Antonio Arce V.

Neuropaediatrics Section, Hospital de la Zarzuela, Madrid, Spain.
dmfmayor@yahoo.es

Several publications have recently suggested that atrial septal defect may be
associated with the physiopathology of headache with migraine-type
characteristics. We describe four previously asymptomatic paediatric patients
with atrial septal defect who underwent percutaneous Amplatzer septal occluder
device implantation and who subsequently developed symptoms compatible with
migraine headache. The cases had normal echocardiograms after the intervention
and a benign course with headache improvement after several weeks or months.
There are paediatric patients with atrial septal defect who may dramatically
develop migraine symptoms with or without aura following percutaneous correction 
of their defect. Large paediatric studies are needed to offer accurate prognoses 
for children and their families. The possibility of using clopidogrel to treat
this type of headache is subject to debate.

Publication Types: 
    Case Reports

PMID: 17459082 [PubMed - indexed for MEDLINE]

793: Cephalalgia. 2007 Jun;27(6):528-34. Epub 2007 Apr 25.

Factors associated with the prophylactic effect of placebo injections in subjects
enrolled in a study of botulinum toxin for migraine.

Schwedt TJ, Hentz JG, Dodick DW.

Department of Neurology, Mayo Clinic College of Medicine, Scottsdale, AZ 85259,
USA.

We set out to identify predictors for the prophylactic effect of placebo
injections in subjects with migraine by post hoc analysis of 81 subjects with
episodic migraine receiving single-blind placebo injections in a prospective
trial of botulinum toxin. Possible predictors of placebo prophylaxis were
compared among placebo responders (PRs) and placebo non-responders (PNRs). There 
were 34 PRs (42%) and 47 PNRs (58%). Male gender [odds ratio (OR) 5.83, 95%
confidence interval (CI) 1.12, 30.14, P = 0.022], a history of opioid use (OR
4.44, 95% CI 1.47, 13.41, P = 0.005) and injections in the neck/shoulders (OR
2.44, 95% CI 0.93, 3.19, P = 0.033) were associated with placebo response. Of
subjects with two or more of these signs, 88% were PRs compared with 31% of
subjects with one or less. Male gender, opioid use and injections in the
neck/shoulders are associated with placebo prophylaxis. These findings may have
important implications for the design of future clinical trials and for the
clinical management of migraineurs.

Publication Types: 
    Clinical Trial
    Clinical Trial, Phase II
    Multicenter Study
    Randomized Controlled Trial

PMID: 17459081 [PubMed - indexed for MEDLINE]

794: Neurology. 2007 Apr 24;68(17):1417-24.

Comment in:
    Neurology. 2007 Aug 21;69(8):810.

Summary for patients in:
    Neurology. 2007 Apr 24;68(17):E23-4.

How migraines impact cognitive function: findings from the Baltimore ECA.

Kalaydjian A, Zandi PP, Swartz KL, Eaton WW, Lyketsos C.

Johns Hopkins Bloomberg School of Public Health, Department of Mental Health,
Baltimore, MD, USA. akalaydj@jhsph.edu

OBJECTIVE: To examine the cross-sectional and longitudinal relationship between
migraine headaches and cognitive functioning. METHODS: The data were from Waves
III (1993 through 1996) and IV (2004 through 2005) of the Baltimore Epidemiologic
Catchment Area Study. Migraine headaches were diagnosed according to modified
criteria of the International Headache Society. Scores on the immediate and
delayed recall tests and the Mini-Mental State Examination (MMSE) were compared
for migraineurs (n = 204) vs nonmigraineurs (n = 1,244). The longitudinal
association between migraine and cognitive changes was assessed by generalized
estimating equations. RESULTS: Migraineurs scored lower on tests of immediate and
delayed memory at baseline, but declined by less over time than nonmigraineurs.
These associations were specific to migraineurs with aura, who declined by 1.26
(p < 0.01) and 1.47 (p < 0.01) words less on the immediate and delayed recall
tests over the 12 years of follow-up. The effects of migraine, specifically with 
aura, on the MMSE were restricted to those older than 50 years. Among those
younger than 50 years, migraineurs with aura declined at the same rate on the
MMSE as nonmigraineurs. However, among those older than 50 years, migraineurs
with aura declined by 0.99 points (p < 0.01) less over the follow-up.
CONCLUSIONS: Migraineurs, specifically those with aura, exhibited less decline on
cognitive tests over time vs nonmigraineurs. For the Mini-Mental State
Examination, these effects were only apparent among those who were older than 50 
years.

Publication Types: 
    Comparative Study

PMID: 17452587 [PubMed - indexed for MEDLINE]

795: Arch Intern Med. 2007 Apr 23;167(8):795-801.

Comment in:
    Arch Intern Med. 2007 Nov 12;167(20):2264; author reply 2264-5.

Migraine and risk of cardiovascular disease in men.

Kurth T, Gaziano JM, Cook NR, Bubes V, Logroscino G, Diener HC, Buring JE.

Divisions of Preventive Medicine, Department of Medicine, Brigham and Women's
Hospital, Harvard Medical School, Boston, Mass 02215, USA.
tkurth@rics.bwh.harvard.edu

BACKGROUND: The vascular component of the migraine-specific physiologic profile
and the observed adverse cardiovascular risk profile in migraineurs suggest an
association between migraine and cardiovascular disease (CVD). In women, migraine
has been associated with increased risk of CVD, including coronary events.
Compatible data in men are lacking. METHODS: Prospective cohort study of 20 084
men aged 40 to 84 years participating in the Physicians' Health Study. In yearly 
questionnaires, men were asked for information on migraine, risk factors, and the
occurrence of study end points. We classified men as having migraine if they
indicated migraine during the first 5 years, after which time follow-up began.
Information on aura was not available. All the men were free of CVD at the start 
of follow-up. During a mean of 15.7 years, we followed up participants for the
occurrence of a first major CVD event (nonfatal ischemic stroke, nonfatal
myocardial infarction, or death from ischemic CVD). We also evaluated the
individual end points, coronary revascularization, and angina. RESULTS: A total
of 1449 men (7.2%) reported migraine, and during follow-up, 2236 major CVD events
occurred. Compared with nonmigraineurs, men who reported migraine had
multivariable-adjusted hazard ratios (95% confidence intervals) of 1.24
(1.06-1.46; P = .008) for major CVD, 1.12 (0.84-1.50; P = .43) for ischemic
stroke, 1.42 (1.15-1.77; P<.001) for myocardial infarction, 1.05 (0.89-1.24; P = 
.54) for coronary revascularization, 1.15 (0.99-1.33; P = .068) for angina, and
1.07 (0.80-1.43; P = .65) for ischemic cardiovascular death. CONCLUSION: In this 
large prospective cohort of apparently healthy men, migraine was associated with 
increased risk of major CVD, which was driven by increased risk of myocardial
infarction.

Publication Types: 
    Research Support, N.I.H., Extramural

PMID: 17452542 [PubMed - indexed for MEDLINE]

796: Eur J Pain. 2008 Jan;12(1):68-75. Epub 2007 Apr 23.

Placebo response in the prophylaxis of migraine: a meta-analysis.

Macedo A, Baños JE, Farré M.

Department of Pharmacology, Therapeutics and Toxicology, Universitat Autònoma de 
Barcelona, Bellaterra (Cerdanyola del Vallès), Spain.

BACKGROUND: Migraine constitutes a good model for the study of placebo response. 
It is a well-defined disease, affects a large population and a great number of
clinical trials have been performed, which have given homogeneous outcomes. AIM: 
The aim of this meta-analysis is to evaluate the placebo response rate in
migraine prophylaxis in all published clinical trials since 1988 and to estimate 
the influence of study design in response variability. METHODS: A computer-based 
information search was conducted on the Medline database. The outcomes studied
were patients who improved (reduction in migraine attacks of 50% or more);
attacks per month, and patients with adverse events. Study design and countries
in which the study was carried out were also analysed. The meta-analysis was
computed using the Mantel-Haenszel test. RESULTS: In the final analysis, 32
papers were considered. The pooled estimate of the placebo response (patients who
improved) was 21%. The placebo response rates were significantly higher in
studies with a parallel design than those in cross-over studies (p<0.01). This
response was also higher in European studies than in those performed in North
America (p<0.001). Adverse events occurred in 30% of the patients who took a
placebo, and the percentage of patients with adverse events was significantly
higher in the North American studies than in those conducted in Europe (p<0.01). 
CONCLUSION: These data reinforce the need to consider the placebo effect when
ascertaining the true therapeutic effect of any drug, as well as to design any
clinical trial in the prophylaxis of migraine.

Publication Types: 
    Meta-Analysis

PMID: 17451980 [PubMed - indexed for MEDLINE]

797: Cephalalgia. 2007 May;27(5):435-46.

Erratum in:
    Cephalalgia. 2007 Jun;27(6):570.

Migraine and adiponectin: is there a connection?

Peterlin BL, Bigal ME, Tepper SJ, Urakaze M, Sheftell FD, Rapoport AM.

Department of Neurology, Drexel University College of Medicine, Philadelphia, PA 
19102, USA. lee.peterlin@drexelmed.edu

Migraine is a common disorder, characterized by recurrent episodes of headache
and associated symptoms. The full pathophysiology of migraine is incompletely
delineated. Current theories suggest that it is a neurovascular disorder
involving cortical depression, neurogenic inflammation and vasodilation. Various 
neuropeptides and cytokines have been implicated in the pathophysiology of
migraine including calcitonin gene-related peptide, interleukin (IL)-1, IL-6 and 
tumour necrosis factor (TNF)-alpha. There is evidence demonstrating an
association between migraine and processes associated with inflammation,
atherosclerosis, immunity and insulin sensitivity. Similarly, adiponectin, an
adipocytokine secreted by adipose tissue, has protective roles against the
development of insulin resistance, dyslipidaemia and atherosclerosis and exhibits
anti-inflammatory properties. The anti-inflammatory activities of adiponectin
include inhibition of IL-6 and TNF-induced IL-8 formation, as well as induction
of the anti-inflammatory cytokines IL-10 and IL-1 receptor antagonist.
Adiponectin levels are also inversely correlated with C-reactive protein (CRP),
TNF-alpha and IL-6 levels. Likewise, recent studies have shown a possible
correlation between CRP, TNF-alpha and IL-6 and migraine attacks. In addition,
insulin sensitivity is impaired in migraine and obesity is a risk factor for the 
transformation from episodic to chronic migraine. In this review we discuss the
basic science of adiponectin and its potential connection to the pathophysiology 
of migraine. Future research may focus on how adiponectin levels are potentially 
altered during migraine attacks, and how that information can be potentially
translated into migraine therapy.

Publication Types: 
    Review

PMID: 17448181 [PubMed - indexed for MEDLINE]

798: Cephalalgia. 2007 May;27(5):414-21.

Rizatriptan for the acute treatment of ICHD-II proposed menstrual migraine: two
prospective, randomized, placebo-controlled, double-blind studies.

Mannix LK, Loder E, Nett R, Mueller L, Rodgers A, Hustad CM, Ramsey KE,
Skobieranda F.

Headache Associates and ClinExcel Research, West Chester, OH 45069, USA.
lkmannixmd@aol.com

These are the first prospective studies to use criteria for menstrual migraine
proposed in the 2004 revision of the International Classification of Headache
Disorders (ICHD-II) to examine the efficacy of rizatriptan for treatment of a
menstrual attack. Two identical protocols (MM1 and MM2) were randomized,
parallel, placebo-controlled, double-blind studies. Adult women with ICHD-II
menstrual migraine were assigned to either rizatriptan 10-mg tablet or placebo in
a 2 : 1 ratio. Patients treated a single menstrual migraine attack of moderate or
severe pain intensity. The primary end-point was 2-h pain relief and the
secondary end-point was 24-h sustained pain relief. A total of 707 patients (MM1 
357, MM2 350) treated a menstrual migraine attack. The percentage of patients
reporting 2-h pain relief was significantly greater for rizatriptan than for
placebo (MM1 70% vs. 53%, MM2 73% vs. 50%), as was the percentage of patients
reporting 24-h sustained pain relief (MM1 46% vs. 33%; MM2 46% vs. 33%).
Rizatriptan 10 mg was effective for the treatment of ICHD-II menstrual migraine, 
as measured by 2-h pain relief and 24-h sustained pain relief.

Publication Types: 
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 17448179 [PubMed - indexed for MEDLINE]

799: Headache. 2007 Apr;47(4):616-9.

Topiramate for migraine prophylaxis among Chinese population.

Li HL, Kwan P, Leung H, Yu E, Tsoi TH, Hui AC, Sheng B, Lau KK.

Department of Medicine and Geriatrics, Princess Margaret Hospital, Hong Kong,
China.

We evaluated the efficacy and safety of topiramate for migraine prophylaxis among
Chinese patients in a multicenter prospective observational study. We found that 
topiramate at low doses was effective in preventing migraine headache in Chinese 
patients and was generally well tolerated. There was no difference in baseline
headache frequency or intensity between responders and nonresponders.

Publication Types: 
    Clinical Trial
    Multicenter Study

PMID: 17445114 [PubMed - indexed for MEDLINE]

800: Headache. 2007 Apr;47(4):600-4.

Steroids and aseptic osteonecrosis (AON) in migraine patients.

Hussain A, Young WB.

Department of Neurology, Jefferson Headache Center, Thomas Jefferson University, 
Philadelphia, PA 19107, USA.

Osteonecrosis is a bony infarction caused by disruption of blood supply to the
bone. Aseptic osteonecrosis should be rare with intermittent use of steroids in
disabling and refractory migraine cases. We present 3 cases of patients who had
severe migraine and developed aseptic osteonecrosis with short-term, intermittent
pulse doses of corticosteroids. Migraine has been mentioned as a possible risk
factor for aseptic osteonecrosis, and we speculate that severe migraine may be a 
risk factor for developing aseptic osteonecrosis. Furthermore, migraineurs who
develop aseptic osteonecrosis may or may not have associated white matter changes
in the brain. We noted a triad of severe migraine, osteonecrosis, and
migraine-related white matter lesions in only 1 case. In severe cases of
migraine, steroids should be used cautiously.

Publication Types: 
    Case Reports

PMID: 17445109 [PubMed - indexed for MEDLINE]

801: Headache. 2007 Apr;47(4):585-99.

Pharmacological approaches to managing migraine and associated
comorbidities--clinical considerations for monotherapy versus polytherapy.

Silberstein SD, Dodick D, Freitag F, Pearlman SH, Hahn SR, Scher AI, Lipton RB.

Thomas Jefferson University, Philadelphia, PA 19107, USA.

Comorbidity is defined as an illness that occurs more frequently in association
with a specific disorder than would be found as a coincidental association in the
general population. Conditions that are frequently comorbid with migraine include
depression, anxiety, stroke, epilepsy, sleep disorders, and other pain disorders.
In addition, many common illnesses occur concomitantly (at the same time) with
migraine and influence the treatment choice. Migraine management, and especially 
migraine prevention, can be challenging when patients have comorbid or
concomitant illnesses. The objectives of this initiative are to review the
literature on managing patients who have migraine and common comorbidities,
present additional clinical approaches for care of these difficult patients, and 
evaluate the areas in which research is needed to establish evidence-based
guidelines for the management of migraine with associated comorbid conditions.

Publication Types: 
    Review

PMID: 17445108 [PubMed - indexed for MEDLINE]

802: Headache. 2007 Apr;47(4):546-51.

Validation of a german language questionnaire for screening for migraine,
tension-type headache, and trigeminal autonomic cephalgias.

Fritsche G, Hueppe M, Kukava M, Dzagnidze A, Schuerks M, Yoon MS, Diener HC,
Katsarava Z.

Department of Neurology, University Hospital Essen, Essen, Germany.

BACKGROUND: To develop a German language questionnaire for screening for
migraine, tension-type headache, and trigeminal autonomic cephalgias. OBJECTIVE: 
Aim of the study was to develop a German language self-administered headache
questionnaire for screening for migraine (MIG), tension-type headache (TTH), and 
trigeminal-autonomic cephalgias (TAC). METHODS: Questionnaire-based diagnoses
were blindly compared with those of headache experts. RESULTS: Overall 278
headache patients (MIG = 97, TTH = 60, TAC = 98, MIG plus TTH = 23) as well as 42
patients with low back pain without headache and 47 healthy subjects were
studied. The Cohen's kappa for 7 headache syndromes including all combination
diagnoses was 0.64 (95% CI 0.58-0.70). Sensitivity and specificity for migraine
were 0.73 and 0.96, for TTH 0.85 and 0.98, for TAC 0.63 and 0.99, and for MIG
plus TTH 0.62 and 0.97, respectively. Ignoring all combination diagnoses, the
kappa-coefficient for the monodiagnoses MIG, TTH, and TAC (193 out of 278
patients) was 0.93 (CI 0.83-1.0). The retest-reliability (4 weeks later) was
0.95. CONCLUSION: We present the first questionnaire in German language including
3 most common primary headaches for use in epidemiological research.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Validation Studies

PMID: 17445104 [PubMed - indexed for MEDLINE]

803: Headache. 2007 Apr;47(4):540-5.

Patients' preference for migraine preventive therapy.

Peres MF, Silberstein S, Moreira F, Corchs F, Vieira DS, Abraham N,
Gebeline-Myers C.

Instituto Israelita de Ensino e Pesquisa-Albert Einstein, São Paulo, and
UNIFESP--EPM, São Paulo, Brazil.

OBJECTIVE: Preventive treatment is an important part of migraine therapy. When
prescribing medication, physicians should understand patients' treatment
preferences and select drugs that most closely meet their patients' needs.
Understanding the factors that influence patients' preference increases
physicians' ability to select appropriate migraine therapy. However, unlike acute
migraine treatment, patients' preferences for migraine preventive treatment have 
never been studied. METHODS: We enrolled 250 patients who attended the Jefferson 
Headache Center and Sao Paulo Headache Center and had a primary headache
diagnosis. Patients' age, gender, body mass index (BMI), headache diagnosis,
headache frequency, duration, and intensity, headache disability (by MIDAS), and 
current preventive treatments were ascertained. Patients were asked to rate 7
aspects of headache prevention (efficacy, speed of onset, out-of-pocket expenses,
adverse events, formulation of therapy, type of treatment, and frequency of
dosing) in order of importance (1-7). Each patient also evaluated 12 different
clinical scenarios, each one containing a simulation of 2 hypothetical headache
preventive treatments, wherein patients could choose Product A, Product B, or
neither. Patients were informed of each product's efficacy data (50%, 75%, or
100% headache elimination), adverse event profile (weight gain, concentration
difficulty, and/or fatigue), and dosing frequency (once every 3 months, once per 
day, or twice per day). RESULTS: Most patients were Caucasian. Mean BMI was 26.55
+/- 5.34, range (17-45). Mean history of headache was 20.93 years. Fifty patients
(40%) had 45 or more headache days in the past 3 months. Mean headache intensity 
score (0-10 scale) was 5.7 +/- 1.8. Patients were on various preventive
treatments, including beta-blockers (48 [41%]), calcium-channel blockers (19
[16%]), antidepressants (52 [44%]), antiepileptics (46 [39%]), neurotoxins (16
[14%]), vitamins/herbal therapies (28 [24%]), and nonmedicinal therapy (38
[32%]). Of the 7 aspects of migraine prevention that patients were asked to rate,
72% rated effectiveness the most important aspect. Twelve percent rated speed of 
onset most important, 6% rated absence of adverse events most important, 3% rated
formulation of therapy most important, 3% rated out-of-pocket expenses most
important, and 2% rated type of treatment (prescription/vitamin) most important. 
None rated frequency of dosing as the most important factor. In the area of
preventive treatment scenarios, patients were more likely to choose treatments
with higher efficacy rates, fewer adverse events and less frequent dosing
schedule. Patients indicated that they preferred the treatment options with
higher efficacy rates even if side effects were present and a more frequent
dosing schedule was necessary. CONCLUSION: Patients' preference regarding
migraine prevention is very important in headache management. Patients rated
efficacy the most important aspect in preventive therapy and preferred treatment 
options with higher efficacy rates. Future studies are needed for a better
understanding of patients' preference for migraine prevention.

PMID: 17445103 [PubMed - indexed for MEDLINE]

804: Headache. 2007 Apr;47(4):531-9.

Cutaneous allodynia in transformed migraine patients.

Cooke L, Eliasziw M, Becker WJ.

Department of Clinical Neuroscience, University of Calgary, Calgary, Canada.

BACKGROUND: There is growing evidence that central sensitization plays a role in 
migraine pathogenesis, and that cutaneous allodynia is its clinical correlate. In
headache research, allodynia has largely been studied in episodic migraine. The
purpose of this investigation was to determine whether cutaneous allodynia occurs
in transformed migraine, using individuals without headaches as controls.
METHODS: Fifteen patients with a diagnosis of transformed migraine and 15 control
subjects with no history of headaches were included. All subjects were females
between 18 and 50. Similar to the methods of Burstein et al, Von Frey hairs (VFH)
were sequentially applied to territories supplied by divisions of the trigeminal 
nerve, cervical paraspinal muscles, trapezius muscles, ventral forearm, and lower
leg to determine a pain threshold. As a milder stimulus, a cotton swab was
stroked in the same locations. Each trial was repeated 3 times on 2 occasions.
Group comparisons were made using the Student's t-test. RESULTS: Mean pain
thresholds were lower among migraine patients than control subjects across all
test areas. The thresholds were statistically significantly lower in migraine
patients than in control subjects for the 1st division of the trigeminal nerve
(34.0 g versus 115.8 g, P= .035) and for the 2nd division (23.5 g versus 97.6 g, 
P= .039). Six patients found a cotton swab-stroke painful, compared to zero
control subjects. Using a quantitative definition of allodynia, 75% of patients
had allodynia to mechanical stimuli. CONCLUSIONS: This study is the first to
demonstrate allodynia in transformed migraine patients using a headache-free
control population and supports the hypothesis that central sensitization plays a
role in the evolution of transformed migraine.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17445102 [PubMed - indexed for MEDLINE]

805: Headache. 2007 Apr;47(4):519-30.

Effect of pain intensity and time to administration on responsiveness to
almotriptan: results from AXERT 12.5 mg Time Versus Intensity Migraine Study
(AIMS).

Freitag FG, Finlayson G, Rapoport AM, Elkind AH, Diamond ML, Unger JR, Fisher AC,
Armstrong RB, Hulihan JF, Greenberg SJ; AIMS Investigators.

Diamond Headache Clinic, Ltd, Chicago, IL 60614, USA.

OBJECTIVE: To determine whether time-based early treatment, independent of pain
intensity, is superior to a pain intensity-based treatment, where patients are
asked to treat at least moderate intensity headaches, resulting in a reduction of
overall migraine headache duration. BACKGROUND: Retrospective and prospective
trials have reported improved outcomes when triptans were used early or to treat 
mild migraine headache pain. However, tolerability as well as efficacy may be 2
of several key issues that have prevented this new treatment paradigm from
becoming universally accepted. METHODS: In this multicenter, open-label,
cluster-randomized study, patients with IHS-defined migraine were instructed to
treat 2 sequential migraine headaches with almotriptan 12.5 mg using either Early
Treatment (ET, ie, treat at earliest onset of headache pain, within 1 hour) or
Standard Treatment (ST, ie, treat when headache pain intensity is moderate or
severe). The novel trial design uses total migraine headache pain duration as the
primary endpoint. RESULTS: Results are presented for the first headache and
include an ITT population of 757 ET and 693 ST patients. Median headache duration
(time from onset of headache pain until no pain) was significantly shorter in ET 
patients compared to ST patients (3.18 vs 5.53 hours, P < .001). An analysis of
the ET subgroup treating headache pain within 1 hour of onset revealed pain
intensity, ie, treating mild or moderate versus severe pain, was significantly
correlated with treatment outcomes defined by total headache duration, 2-hour
pain free, sustained pain free, and use of rescue medication. Multivariate
analyses comparing ST subgroups that treated within 1 hour versus greater than 1 
hour after headache onset, demonstrate that both pain intensity, ie, treating
moderate versus severe headache pain, and treating early versus late, were
significantly correlated with total headache duration, 2-hour pain free,
sustained pain free, and use of rescue medication. The overall incidence of
adverse events was low; nausea and dizziness were the only adverse events with an
incidence > or =1% in either treatment group (nausea: 2.5% and 1.7% and dizziness
1.1% and 0.7%, in the ET and ST groups, respectively). CONCLUSION: Total headache
duration was significantly shorter in the early treatment group compared to the
standard treatment group. Considering time to treatment within a relatively early
range of 1 hour or less, efficacy results when treating mild versus moderate pain
were similar and both were associated with better outcomes than treatment of
severe pain. When considering the prognostic variables of time to treatment and
headache pain intensity (limited to moderate vs severe), both were independent
predictors, with time to treatment a better predictor of headache duration and
rescue medication use, and pain intensity a better predictor of 2-hour pain free 
and sustained pain free.

Publication Types: 
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 17445101 [PubMed - indexed for MEDLINE]

806: Headache. 2007 Apr;47(4):511-8.

Eletriptan for the acute treatment of migraine in adolescents: results of a
double-blind, placebo-controlled trial.

Winner P, Linder SL, Lipton RB, Almas M, Parsons B, Pitman V.

Nova Southeastern University, Fort Lauderdale, FL 33407, USA.

BACKGROUND: Eletriptan is a potent 5-HT(1B/1D) agonist with proven efficacy in
the acute treatment of migraine in adults. OBJECTIVE: To evaluate the efficacy
and tolerability of eletriptan 40 mg versus placebo in adolescent patients (aged 
12-17). METHODS: A multicenter, double-blind, parallel-group, placebo-controlled 
trial was conducted comparing 40 mg of oral eletriptan with placebo for the
treatment of migraine in adolescent patients. The primary efficacy endpoint was
2-hour headache response, and a number of secondary endpoints were also
evaluated. An exploratory analysis evaluated which clinical and demographic
characteristics might be correlated with high placebo response. RESULTS: Of 274
patients who treated a migraine attack, 267 were evaluated for efficacy (n = 138 
eletriptan; n = 129 placebo) at 2 hours post-dose. There was no significant
difference in 2-hour headache response for eletriptan 40 mg versus placebo (57%
vs 57%), and no significant improvements were observed for any of the outcomes at
1 or 2 hours post-dose. By contrast, there was a significant advantage for
eletriptan 40 mg in reducing headache recurrence within 24 hours post-dose (11%
vs 25%, P= .028), and post hoc analyses showed statistically significant
differences for sustained headache response rates (52% vs 39%; P= .04) and
sustained pain-free response rates (22% vs 10%; P= .013). The strongest clinical 
predictor of placebo response was triptan-naïve status (i.e., no previous use of 
any triptan). Eletriptan 40 mg was well tolerated in this population, and the
profile of adverse events was similar to that observed in Phase III trials in
adult patients. CONCLUSIONS: The high placebo response rates reported here for 1-
and 2-hour outcomes are in accordance with other studies of triptans in
adolescent patients. The evaluation of treatment effect in adolescent migraine
might benefit from use of more stringent outcome measures, such as headache
recurrence, sustained headache response, and sustained pain-free response at 24
hours post-dose.

Publication Types: 
    Clinical Trial, Phase IV
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 17445100 [PubMed - indexed for MEDLINE]

807: Headache. 2007 Apr;47(4):500-10.

Topiramate in migraine prophylaxis: long-term impact on resource utilization and 
cost.

Silberstein SD, Feliu AL, Rupnow MF, Blount AC, Boccuzzi SJ.

Department of Neurology, Thomas Jefferson University, Philadelphia, PA 19107,
USA.

OBJECTIVE: To evaluate the medical resource utilization and overall cost of care 
among patients treated with topiramate (TPM) for migraine prevention in a
commercially insured population. Background.-Preventive migraine therapy with TPM
significantly reduces the frequency of migraine attacks. Limited data exist on
the real-world health care consumption associated with TPM therapy for migraine
prevention. METHODS: Data were obtained from a large geographically diverse
integrated medical and pharmacy claims database representative of the
commercially insured population. The date of the first TPM claim between July
2000 and December 2003 was considered the index date. Patients needed at least 1 
triptan prescription (Rx) claim during the 6-month preindex period, and > or =2
TPM Rx claims in the 12 months following index TPM Rx to be included in the
analysis. Headache-related inpatient and outpatient resource use were compared:
preindex vs postindex period 1 (months 1-6) and preindex vs postindex period 2
(months 7-12). Subgroup analyses were conducted based on the triptan consumption 
during the 6-month preindex period: Cohort L (low triptan users) with < or =36
triptan doses, and Cohort H (high triptan users) with >36 triptan doses. RESULTS:
The sample included 2645 plan members (1778 patients in Cohort L, and 867
patients in Cohort H). TPM utilization was associated with significantly less
triptan utilization in the first (34.8 quantity dispensed; 7.5% decrease) and
second (30.2; 19.6% decrease) follow-up periods compared to the preindex period
(37.6; both P < .0001). In postindex period 1, there was a 46% decrease in
emergency department (ED) visits, 39% decrease in diagnostic procedures (eg, CT
scans and MRIs), and a 33% decrease in hospital admission; physician office
visits were unchanged. In postindex period 2, there was a 46% decrease in ED
visits, 72% decrease in diagnostic procedures, 61% decrease in hospital
admissions, and a 35% decrease in physician office visits. Decreases in resource 
use were observed in both cohorts L and H. Mean +/- SD total headache-related
cost was $2118 +/- $3406 per patient in the preperiod, versus $2450 +/- $3318 in 
follow-up period 1 and $2009 +/- $3136 in follow-up period 2. CONCLUSION: In this
sample of patients from a diverse set of health plans receiving TPM, significant 
decreases in resource use were observed within 6 months of TPM initiation, and
this trend continued in follow-up period 2. Although there was an initial
increase in total headache-related cost upon introduction of TPM (follow-up
period 1), the cost in follow-up period 2 was lower than in the preindex period, 
suggesting that benefits of long-term treatment with TPM can be achieved without 
increasing total cost.

Publication Types: 
    Evaluation Studies
    Research Support, Non-U.S. Gov't

PMID: 17445099 [PubMed - indexed for MEDLINE]

808: Headache. 2007 Apr;47(4):486-99.

Botulinum toxin type a prophylactic treatment of episodic migraine: a randomized,
double-blind, placebo-controlled exploratory study.

Aurora SK, Gawel M, Brandes JL, Pokta S, Vandenburgh AM; BOTOX North American
Episodic Migraine Study Group.

Swedish Pain Center, Seattle, WA 98104, USA.

OBJECTIVE: This exploratory trial evaluated the safety and efficacy of multiple
treatments of botulinum toxin type A (BoNTA; BOTOX, Allergan, Inc., Irvine, CA,
USA) as prophylactic treatment of episodic migraine headaches. DESIGN AND
METHODS: This was an 11-month randomized, double-blind, placebo-controlled,
exploratory study. Patients were screened during a 30-day baseline period, and
eligible patients with 4 or more migraine episodes and < or =15 headache days
entered a single-blind 30-day placebo run-in period. Patients were classified as 
placebo nonresponders (PNR) if they had at least 4 moderate-to-severe migraine
episodes and did not experience at least a 50% decrease from baseline in the
frequency of migraine episodes following their placebo treatment. All other
subjects were classified as placebo responders (PR). Patients were randomized
within each stratum (PNR, PR) to 3 treatments with BoNTA (110 to 260 U of BoNTA
per treatment cycle) or placebo at 90-day intervals using a modified
follow-the-pain treatment paradigm. The primary efficacy outcome measure was the 
mean change from baseline in the frequency of migraine episodes for the 30 days
prior to day 180 in the PNR group. Secondary efficacy measures included the
proportion of patients with a decrease from baseline of 50% or more migraine
episodes per 30-day period. Patients were allowed to take concomitant acute and
prophylactic headache medications. Adverse events were reported. RESULTS: A total
of 809 patients were screened and 369 patients (89.2% female; mean age, 45 years;
range, 20 to 65 years) entered the placebo run-in period and were subsequently
randomized to BoNTA or placebo. The mean total dose of BoNTA was 190.5 units (U) 
(range, 110 U to 260 U). The predetermined primary efficacy endpoint was not met.
Substantial mean improvements of 2.4 and 2.2 fewer migraine episodes per month at
day 180 in the PNR stratum treated with BoNTA and placebo, respectively, were
observed (P > .999). From day 180 through the end of the study (day 270) at least
50% of all patients in each treatment group had a decrease from baseline of 50%
or more migraine episodes per 30-day period. However, in the group of patients
with > or =12 headache days at baseline (and < or =15 headache days), BoNTA
patients experienced a mean change from baseline of -4.0 headache episodes at day
180 compared with -1.9 headache episodes in the placebo group (P= .048). The
majority of treatment-related adverse events were transient and mild to moderate 
in severity. Only 7 patients (1.9%) discontinued the study due to adverse events 
(6 BoNTA, 1 placebo). CONCLUSION: There were no statistically significant
between-group differences in the mean change from baseline in the frequency of
migraine episodes per 30-day period. There were substantial, sustained
improvements during the course of the study in all groups. Multiple treatments
with BoNTA were shown to be safe and well tolerated over an active treatment
period lasting 9 months.

Publication Types: 
    Clinical Trial, Phase II
    Evaluation Studies
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 17445098 [PubMed - indexed for MEDLINE]

809: Headache. 2007 Apr;47(4):475-9.

Satisfaction with current migraine therapy: experience from 3 centers in US and
Sweden.

Bigal M, Rapoport A, Aurora S, Sheftell F, Tepper S, Dahlof C.

Albert Einstein College of Medicine--Neurology, Bronx, NY 10461, USA.

OBJECTIVE: To assess the level of satisfaction and determinants of satisfaction
or dissatisfaction of patients presenting in tertiary care, in regard to their
usual care (UC) for the acute treatment of migraine. DESIGN/METHODS: Patients
seen in 3 headache centers were assessed by means of 21 attributes related to
their UC. Questions covered satisfaction with efficacy (including onset of
relief, degree of relief, consistency of action, ease of use), tolerability (lack
of side effects overall, CNS side effects, other side effects), and willingness
to continue using the same medication and to change to another medication. All
questions were answered on a 5-point scale (where 1 was strongly agree, 2 was
agree, 3 was neutral, 4 was disagree, and 5 was strongly disagree). RESULTS: We
assessed 183 subjects (74.8% women, mean age = 39.3 years). UC consisted, as a
single drug or combination, of: triptan conventional tablets--62%; triptan
disintegrating tablets--8%; sumatriptan nasal spray 9%; sumatriptan injection,
9%; nontriptans--19.6%. Most (54%) had no benefit within the first hour of
treatment. The maximum benefit took more than 1 hour to be reached in 69%, and
more than 2 hours in 36%. After the maximum benefit had been reached, pain
worsened in 61%. Although 58% were satisfied with the degree of relief, 37% were 
dissatisfied with the speed of effect, 50% with the recurrence of pain, and 42%
with the need for a second dose. Most were satisfied with the tolerability (56%).
Finally, most (79.7%) said they were willing to try another acute medication.
CONCLUSIONS: An important subset of patients, including a large subgroup of
patients using triptans, is dissatisfied with their UC. Clinical trials assessing
patients' preference should be conducted to complement the information from
clinical trials.

Publication Types: 
    Clinical Trial
    Multicenter Study
    Research Support, Non-U.S. Gov't

PMID: 17445096 [PubMed - indexed for MEDLINE]

810: Cephalalgia. 2007 Jul;27(7):814-23. Epub 2007 Apr 18.

Erratum in:
    Cephalalgia. 2007 Aug;27(8):962.

Topiramate reduces headache days in chronic migraine: a randomized, double-blind,
placebo-controlled study.

Diener HC, Bussone G, Van Oene JC, Lahaye M, Schwalen S, Goadsby PJ;
TOPMAT-MIG-201(TOP-CHROME) Study Group.

Department of Neurology, University of Duisburg-Essen, Germany.

The aim of this study was to evaluate the efficacy and tolerability of topiramate
for the prevention of chronic migraine in a randomized, double-blind,
placebo-controlled trial. Chronic migraine is a common form of disabling headache
presenting in headache subspecialty practice. Preventive treatments are essential
for chronic migraine management, although there are few or no controlled
empirical trial data on their use in this patient population. Topiramate is
approved for the prophylaxis of migraine headache in adults. Patients (18-65
years) who experienced chronic migraine (defined as > or =15 monthly migraine
days) for > or =3 months prior to trial entry and had > or =12 migraine days
during the 4-week (28-day) baseline phase were randomized to topiramate or
placebo for a 16-week, double-blind trial. Topiramate was titrated (25 mg weekly)
to a target dose of 100 mg/day, allowing dosing flexibility from 50 to 200
mg/day, according to patient need. Existing migraine preventive treatments,
except for antiepileptic drugs, were continued throughout the trial. The primary 
efficacy measure was the change in number of migraine days from the 28-day
baseline phase to the last 28 days of the double-blind phase in the
intent-to-treat population, which consisted of all patients who received at least
one dose of study medication and had one outcome assessment during the
double-blind phase. Health-related quality of life was evaluated with the
Migraine Specific Quality of Life Questionnaire (MSQ, Version 2.1), the Headache 
Impact Test (HIT-6) and the Migraine Disability Assessment (MIDAS)
questionnaires, and tolerability was assessed by adverse event (AE) reports and
early trial discontinuations. Eighty-two patients were screened. Thirty-two
patients in the intent-to-treat population (mean age 46 years; 75% female)
received topiramate (mean modal dose +/- SD = 100 +/- 17 mg/day) and 27 patients 
received placebo. Mean (+/-SD) baseline number of migraine days per 4 weeks was
15.5 +/- 4.6 in the topiramate group and 16.4 +/- 4.4 in the placebo group. Most 
patients (78%) met the definition for acute medication overuse at baseline. The
mean duration of treatment was 100 and 92 days for topiramate- and
placebo-treated patients, respectively. Study completion rates for topiramate-
and placebo-treated patients were 75% and 52%, respectively. Topiramate
significantly reduced the mean number of monthly migraine days (+/-SD) by 3.5 +/-
6.3, compared with placebo (-0.2 +/- 4.7, P < 0.05). No significant intergroup
differences were found for MSQ and HIT-6. MIDAS showed improvement with the
topiramate treatment group (P = 0.042 vs. placebo). Treatment emergent adverse
events were reported by 75% of topiramate-treated patients (37%, placebo). The
most common AEs, paraesthesia, nausea, dizziness, dyspepsia, fatigue, anorexia
and disturbance in attention, were reported by 53%, 9%, 6%, 6%, 6%, 6% and 6% of 
topiramate-treated patients, respectively, vs. 7%, 0%, 0%, 0%, 0%, 4% and 4% of
placebo-treated patients. This randomized, double-blind, placebo-controlled trial
demonstrates that topiramate is effective and reasonably well tolerated when used
for the preventive treatment of chronic migraine, even in the presence of
medication overuse.

Publication Types: 
    Multicenter Study
    Randomized Controlled Trial

PMID: 17441971 [PubMed - indexed for MEDLINE]

811: J Clin Ultrasound. 2007 Sep;35(7):372-5.

A transcranial doppler study in interictal migraine and tension-type headache.

Arjona A, de Torres LA, Serrano-Castro PJ, Guardado-Santervas PL, Olivares J,
Rubí-Callejon J.

Neurology Section, Torrecardenas Hospital, Paraje Torrecardernas s/n, Almeria
E-04009, Spain.

PURPOSE: To use transcranial Doppler (TCD) sonography to determine if patients
with migraine without aura have interictal hemodynamic abnormalities compared
with patients who have episodic tension-type headache (TH). METHODS: Thirty-six
migraine patients without aura and 51 TH patients (age range, 16-50 years) who
were diagnosed according to the criteria of the International Headache Society
1988 participated in the study. Forty-four healthy volunteers, matched for age
and sex, formed the control group. Time-averaged mean velocity (TAMV),
pulsatility index (PI), and breath-holding index (BHI) were measured via TCD
sonography in the middle cerebral artery. RESULTS: TAMV was higher in migraine
without aura than in episodic TH (p = 0.034). There were no differences between
groups regarding PI or BHI. CONCLUSION: Our findings support the arteriolar
vasodilatation theory in migraine without aura. (c) 2007 Wiley Periodicals, Inc.

Publication Types: 
    Evaluation Studies

PMID: 17436316 [PubMed - indexed for MEDLINE]

812: Neuroreport. 2007 Mar 5;18(4):301-5.

Interictal alterations of the trigeminal somatosensory pathway and periaqueductal
gray matter in migraine.

DaSilva AF, Granziera C, Tuch DS, Snyder J, Vincent M, Hadjikhani N.

Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard
Medical School, Charlestown, Massachusetts 02129, USA.

Migraine has been traditionally considered a nonprogressive, paroxysmal disorder 
with no brain abnormalities between attacks. We used diffusion tensor imaging to 
examine interictal diffusion properties of the brains of migraineurs with aura,
migraineurs without aura and matched healthy controls. Areas of lower fractional 
anisotropy were present in migraineurs along the thalamocortical tract. In
addition, migraineurs with aura had lower fractional anisotropy in the ventral
trigeminothalamic tract, and migraineurs without aura had lower fractional
anisotropy in the ventrolateral periaqueductal grey matter. Our results indicate 
the presence of permanent interictal changes in migraineurs, pointing to an
effect of migraine on the trigeminal somatosensory and modulatory pain systems.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 17435592 [PubMed - indexed for MEDLINE]

813: J Neurol Neurosurg Psychiatry. 2007 May;78(5):523-6.

Prolonged hemiplegic episodes in children due to mutations in ATP1A2.

Jen JC, Klein A, Boltshauser E, Cartwright MS, Roach ES, Mamsa H, Baloh RW.

Department of Neurology, UCLA School of Medicine, Los Angeles, California
90095-1769, USA. jjen@ucla.edu

BACKGROUND: Familial hemiplegic migraine (FHM) is an unusual migraine syndrome
characterised by recurrent transient attacks of unilateral weakness or paralysis 
as part of the migraine aura. Genetically and clinically heterogeneous, FHM1 is
caused by mutations in CACNA1A and FHM2 by mutations in ATP1A2. AIM: Three
children with prolonged hemiplegia were tested for mutations in CACNA1A or
ATP1A2. METHODS: Mutations in CACNA1A and ATP1A2 were screened for by denaturing 
high performance liquid chromatography and confirmed by sequencing. Expression
studies were performed to characterise the functional consequences of these
mutations. RESULTS: No mutation was found in the FHM1 gene while three mutations 
were identified in the FHM2 gene. All three mutations were missense: two were
novel and one was de novo; none was found in controls. Functional studies in HeLa
cells showed complete loss of mutant pump function without interfering with the
wild-type pump, consistent with haploinsufficiency. CONCLUSION: We identified
novel disease causing mutations in the FHM2 gene. Genetic screening for FHM
should be considered in a child with prolonged hemiplegia even if there is no
prior history or family history of migraine or hemiplegic episodes.

Publication Types: 
    Case Reports
    Research Support, N.I.H., Extramural

PMID: 17435187 [PubMed - indexed for MEDLINE]

814: Eur J Paediatr Neurol. 2007 Nov;11(6):325-30. Epub 2007 Apr 10.

Sumatriptan nasal spray in the acute treatment of migraine in adolescents and
children.

Callenbach PM, Pels LP, Mulder PG, Linssen WH, Gooskens RH, van der Zwan JL,
Brouwer OF; SUM30042 Trial Group.

Department of Neurology, University Medical Centre Groningen, University of
Groningen, P.O. Box 30 001 9700 RB Groningen, The Netherlands.
p.m.c.tijink@neuro.umcg.nl

About 4-10% of children and adolescents suffer from migraine. In the last few
years, several studies have been performed to assess the efficacy and safety of
triptans for the acute treatment of migraine in children and adolescents. Only
sumatriptan nasal spray has been approved for the treatment of acute migraine
with or without aura in adolescents aged 12-17 years in Europe. This review
describes the results of the studies with sumatriptan nasal spray that have been 
performed in children and adolescents, including a study performed in the
Netherlands.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 17428708 [PubMed - indexed for MEDLINE]

815: Cephalalgia. 2007 Jun;27(6):492-503. Epub 2007 Apr 11.

A multicentre, double-blind, randomized, placebo-controlled, parallel group study
of multiple treatments of botulinum toxin type A (BoNTA) for the prophylaxis of
episodic migraine headaches.

Relja M, Poole AC, Schoenen J, Pascual J, Lei X, Thompson C; European BoNTA
Headache Study Group.

Department of Neurology, Medical School University of Zagreb, Zagreb, Croatia.
mrelja@mef.hr

Our aim was to evaluate the safety and efficacy of botulinum toxin type A (BoNTA;
BOTOX) for prophylaxis of episodic migraine. In this double-blind,
placebo-controlled study, patients were randomized to 225, 150 or 75 U of BoNTA
or placebo after a 30-day placebo run-in for three 90-day treatment cycles. The
primary efficacy end-point was the mean reduction from baseline in the frequency 
of migraine episodes at day 180 in the placebo non-responder stratum. All groups 
(N = 495) improved, with no significant differences. At day 180, the frequency of
migraine episodes was reduced from baseline means of 4.3, 4.7, 4.7 and 4.4 by
1.6, 1.7, 1.5 and 1.4 for BoNTA 225 U, 150 U and 75 U and placebo, respectively. 
The primary end-point was not met. Treatment-related adverse events were
transient and mild to moderate. BoNTA treatment was safe and well tolerated but
did not result in significantly greater improvement than placebo in this study.
Several factors may have confounded the results.

Publication Types: 
    Clinical Trial
    Clinical Trial, Phase II
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 17428299 [PubMed - indexed for MEDLINE]

816: Cephalalgia. 2007 Jun;27(6):504-9. Epub 2007 Apr 11.

Prevalence of trigeminal autonomic symptoms in migraine: a population-based
study.

Obermann M, Yoon MS, Dommes P, Kuznetsova J, Maschke M, Weimar C, Limmroth V,
Diener HC, Katsarava Z.

Department of Neurology, University of Duisburg-Essen, Essen, Germany.
mark.obermann@uni-essen.de

Epidemiological data on trigeminal unilateral autonomic symptoms in patients with
migraine are scarce. The authors wanted to provide a population-based evaluation 
of the prevalence of unilateral autonomic features in migraine patients and an
assessment of the expression of unilaterality of autonomic symptoms and head pain
in patients with UAs compared to other migraine patients. A population based
sample of 6000 inhabitants of the city of Essen in Germany was screened using a
previously validated standard questionnaire. Three thousand three hundred and
sixty subjects (56% of a total 6000) responded. 841 subjects had migraine, out of
which 226 reported accompanying unilatral auetonomic symptoms (26.9%, CI 95%
[23.9-30%]). Unilateral autonomic symptoms in patients with migraine are common
and have been widely underestimated in the past. One out of four migraine
patients regularly experiences one or more unilateral autonomic symptoms during
their attack. Migraine patients with accompanying autonomic symptoms seem to
experience their pain more unilateral and more severe than non-UA patients.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17428298 [PubMed - indexed for MEDLINE]

817: J Occup Environ Med. 2007 Apr;49(4):368-74.

Indirect cost burden of migraine in the United States.

Hawkins K, Wang S, Rupnow MF.

Thomson Medstat, Cambridge, MA 02140, USA.

OBJECTIVE: The purpose of this study was to determine the indirect cost burden
associated with migraine. METHODS: Data were obtained from Thomson-Medstat's
Health and Productivity Management (HPM) database for the 2002 through 2003
calendar years. The migraine cohort was composed of patients who had a diagnosis 
of migraine or migraine-specific abortive prescription medication, or both. A
control cohort of patients without migraine was matched to patients in the
migraine cohort. The average annual indirect burden of illness (BOI) of migraine 
and a national indirect BOI were estimated. RESULTS: Annual indirect expenditures
were significantly higher in the migraine group compared with the control group
($4453 vs $1619; P<0.001). The national annual indirect BOI, excluding
presenteeism, was estimated to be $12 billion (mostly attributed to absenteeism).
CONCLUSIONS: Migraine imparts a substantial indirect cost burden. Projected to a 
national level, this amounts to an annual cost to US employers of approximately
$12 billion.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17426520 [PubMed - indexed for MEDLINE]

818: Headache. 2007 Apr;47 Suppl 1:S52-7.

Current trends in migraine prophylaxis.

Ramadan NM.

Department of Neurology, Chicago Medical School at Rosalind Franklin University
of Medicine and Science, North Chicago, IL 60064, USA.

A variety of drugs from diverse pharmacological classes are in use for migraine
prevention. Traditionally, they have been discovered by serendipity. Examples
include beta-adrenergic blockers, anticonvulsants, tricyclic antidepressants, and
serotonin receptor antagonists. The mechanisms of action of migraine preventive
drugs are multiple but it is postulated that they converge on two targets: (1)
inhibition of cortical excitation; (2) restoring nociceptive dysmodulation. The
antiepileptic drugs (e.g., topiramate, valproate, gabapentin), calcium channel
blockers such as verapamil, and inhibitors of cortical spreading depression are
some examples of drugs that reduce neuronal hyperexcitability. On the other hand,
modulators of the serotonergic and adrenergic systems and cholinergic enhancing
drugs may restore descending nociceptive inhibition and play a role in migraine
prevention. To date, Level 1 evidence and clinical experience favor the use of
the antidepressant amitriptyline, the anticonvulsants divalproex and topiramate, 
and the beta-adrenergic blockers propranolol, timolol and metoprolol as first
line migraine preventive drugs. The evidence for others (e.g., verapamil) is not 
as strong. Migraine preventive drugs have varying degrees of adverse effects,
some of which could be limiting, and their efficacy should balanced with their
risks of adverse effects, patients' expectations and desires, and compliance. It 
is hoped that future migraine preventive drugs target migraine mechanisms more
specifically, which could well enhance the therapeutic index.

Publication Types: 
    Review

PMID: 17425710 [PubMed - indexed for MEDLINE]

819: Headache. 2007 Apr;47 Suppl 1:S44-51.

The convergence hypothesis.

Cady RK.

Headache Care, Primary Care Network, Inc, Springfield, MO, USA.

The Convergence Hypothesis postulates a single pathophysiological mechanism to
explain the clinical spectrum of primary headaches seen in patients with
migraine. The history and the scientific underpinnings of the Convergence
Hypothesis are presented. Extrapolations from the Convergence Hypothesis are used
to explore the evolution of episodic to chronic migraine and the development of
common migraine co-morbidities as a consequence of frequent migraine. A patient
staging system is presented to illustrate this transformation process in migraine
patients.

Publication Types: 
    Review

PMID: 17425709 [PubMed - indexed for MEDLINE]

820: Headache. 2007 Apr;47 Suppl 1:S26-43.

New migraine and pain research.

Hargreaves R.

Merck and Co., Inc., West Point, PA, USA.

An understanding of the pathophysiology and pharmacology of migraine has been
driven by astute clinical observations, elegant experimental medicine studies and
importantly by the introduction of highly effective selective anti-migraine
agents such as the Triptan 5-HT(1B/1D) agonists. New investigational migraine
therapies such CGRP antagonists target key components of the trigeminal sensory
neuroinflammatory response and show promise for the future. Cutting edge
molecular profiling studies looking at gene expression during chronic pain are
now being used to reveal the cell biology of pain and new potential therapeutic
targets. Translational neuroimaging research can link the laboratory and the
clinic and is now being used to help understand the neural systems biology of
migraine. Research into migraine has generated sophisticated hypotheses that
encompass primary CNS dysfunction, trigeminovascular activation, pain perception 
and activation of associated neural circuits involved in affective functions
providing a rich framework within which to design and test future migraine
treatment strategies.

Publication Types: 
    Review

PMID: 17425708 [PubMed - indexed for MEDLINE]

821: Headache. 2007 Apr;47 Suppl 1:S2-9.

Ten lessons on the epidemiology of migraine.

Lipton RB, Bigal ME.

Montefiore Headache Unit, Department of Neurology, Albert Einstein College of
Medicine, Bronx, NY 10461, USA.

The epidemiologic studies of the last 15 years have taught many lessons that will
help define the clinical and research agenda in migraine for the next 15 years.
Because the condition is common, disabling, and costly (Lesson 1) and because it 
has major comorbidities (Lesson 2), migraine is an important target for
treatment. Because consultation, diagnosis, and effective treatment rates are low
(Lessons 3 and 4) it is important to develop strategies for closing the gap
between treatment available and treatment delivered in the primary care setting
where the majority of patients seek care (Lesson 5 and 6). Strategies include
public and provider education as well as the use of screening tools such as
ID-migraine to improve the recognition of migraine in primary care (Lesson 7). In
addition, strategies that measure disability, with tools such as MIgraine
Disability ASssessment, when coupled with treatment guidelines which consider
illness severity in the selection of treatment provide great hope for improving
patient outcomes (Lesson 8). Finally, the emerging evidence that migraine is
progressive in a subgroup (Lesson 9) mandates the development of strategies to
reduce the risk of progression by addressing modifiable risk factors and by
assessing the effects of treatment on headache progression (Lesson 10).

Publication Types: 
    Review

PMID: 17425705 [PubMed - indexed for MEDLINE]

822: Headache. 2007 Apr;47 Suppl 1:S10-9.

The discovery of a new drug class for the acute treatment of migraine.

Humphrey PP.

Theravance, Inc., 901 Gateway Boulevard, South San Francisco, CA 94080, USA.

The history of the scientific ideas and events that led to the discovery of
sumatriptan is outlined with personal reminiscences about individuals who
influenced the approach. The development of sumatriptan revolutionized the acute 
treatment of migraine and led to the availability of a number of other triptans. 
The anti-migraine effects of all the triptans are mediated via 5-HT(1B), and
possibly 5-HT(1D) receptors, which transduce their effects via G; proteins. This 
suggests that agonists at other G(i) protein-coupled receptor types appropriately
located (eg, somatostatin sst(2), adenosine A(1)) should be examined for their
effects on the trigeminovascular system, Studies on such receptor targets may
provide insight into a novel approach towards the design of new anti-migraine
drugs.

Publication Types: 
    Historical Article
    Review

PMID: 17425704 [PubMed - indexed for MEDLINE]

823: Expert Opin Pharmacother. 2007 Apr;8(6):731-44.

Recommendations for the management of migraine in paediatric patients.

Balottin U, Termine C.

Child Neuropsychiatry Unit, Department of Clinical and Biological Sciences,
University of Insubria and Macchi Foundation Hospital, Varese, p.zza Biroldi, 19,
21100 Varese, Italy. umberto.balottin@uninsubria.it

Migraine is a common and disabling condition in children and adolescents. The
complexity of migraine on a pathogenetic and clinical level results from the
interaction between biological, psychological and environmental factors.
Appropriate management requires an individually tailored strategy giving due
consideration to both pharmacological and non-pharmacological measures. Ibuprofen
(7.5-10.0 mg/kg) and acetaminophen (15 mg/kg) are safe and effective, and should 
be considered for symptomatic treatment. Sumatriptan nasal spray (5 and 20 mg) is
also likely to be effective, but at the moment, should be considered for the
treatment of adolescents only. With reference to prophylactic drug treatment, the
available data suggest that flunarizine (5 mg/day) is likely to be effective and 
pizotifen and clonidine are likely to be ineffective. The efficacy data regarding
propranolol, nimodipine and trazodone are conflicting. Insufficient evidence is
available on cyproheptadine, amitriptyline, divalproex sodium, topiramate,
levetiracetam, gabapentin or zonisamide. The management of migraine in children
needs an individualised therapeutic approach, directed to the whole person of the
child, taking into account the developmental perspective and the high rate of
psychiatric comorbidities. It is the authors' opinion that for the prophylaxis of
migraine, interventions such as identification and avoidance of trigger factors, 
regulation of lifestyle, relaxation, biofeedback, cognitive behavioural treatment
and psychological or psychotherapeutic interventions (e.g., psychodynamics) could
be much more effective than pharmacotherapy.

Publication Types: 
    Review

PMID: 17425470 [PubMed - indexed for MEDLINE]

824: J Neuroophthalmol. 2007 Mar;27(1):3-8.

Comment in:
    J Neuroophthalmol. 2007 Mar;27(1):1-2.    J Neuroophthalmol. 2007 Sep;27(3):242-3; author reply 244-5.    J Neuroophthalmol. 2007 Sep;27(3):243-4; author reply 244-5.

Most cases labeled as "retinal migraine" are not migraine.

Hill DL, Daroff RB, Ducros A, Newman NJ, Biousse V.

Departments of Ophthalmology, Emory University School of Medicine, Atlanta,
Georgia, USA.

BACKGROUND: Monocular visual loss has often been labeled "retinal migraine." Yet 
there is reason to believe that many such cases do not meet the criteria set out 
by the International Headache Society (IHS), which defines "retinal migraine" as 
attacks of fully reversible monocular visual disturbance associated with migraine
headache and a normal neuro-ophthalmic examination between attacks. METHODS: We
performed a literature search of articles mentioning "retinal migraine,"
"anterior visual pathway migraine," "monocular migraine," "ocular migraine,"
"retinal vasospasm," "transient monocular visual loss," and "retinal spreading
depression" using Medline and older textbooks. We applied the IHS criteria for
retinal migraine to all cases so labeled. To be included as definite retinal
migraine, patients were required to have had at least two episodes of transient
monocular visual loss associated with, or followed by, a headache with migrainous
features. RESULTS: Only 16 patients with transient monocular visual loss had
clinical manifestations consistent with retinal migraine. Only 5 of these
patients met the IHS criteria for definite retinal migraine. No patient with
permanent visual loss met the IHS criteria for retinal migraine. CONCLUSIONS:
Definite retinal migraine, as defined by the IHS criteria, is an exceedingly rare
cause of transient monocular visual loss. There are no convincing reports of
permanent monocular visual loss associated with migraine. Most cases of transient
monocular visual loss diagnosed as retinal migraine would more properly be
diagnosed as "presumed retinal vasospasm."

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't
    Review

PMID: 17414865 [PubMed - indexed for MEDLINE]

825: J Neurol. 2007 Jun;254(6):705-12. Epub 2007 Apr 10.

Efficacy and safety of 1,000 mg effervescent aspirin: individual patient data
meta-analysis of three trials in migraine headache and migraine accompanying
symptoms.

Lampl C, Voelker M, Diener HC.

Dept. of Neurology, Pain and Headache Center, Krankenhaus der Barmherzigen
Schwestern, Seilerstätte 4, A-4010 Linz, Austria.

Migraine is often associated with health consequences including impaired quality 
of life, and the cost of treating migraine headaches places a significant
financial burden on patients who suffer from migraines. Nonsteroidal
anti-inflammatory drugs (NSAIDs) and triptans are commonly used for the treatment
of acute migraine attacks. Aspirin is widely accepted as a treatment option for
migraine pain relief and could provide an alternative not only for treatment of
moderate migraine attacks, but also for severe migraine attacks. The efficacy and
safety of 1,000 mg effervescent aspirin (eASA) was evaluated in comparison to 50 
mg sumatriptan and placebo in an individual patient data meta-analysis of three
randomized, placebo-controlled, single- dose migraine trials. Pain-relief at 2 h,
pain-free at 2 h and sustained pain-free up to 24 h were calculated. For eASA,
the response rates were 51.5 % (95 % CI: 46.6-56.5 %), 27.1 % (95 % CI: 22.6-31.4
%), and 23.5 % (95 % CI: 19.3-27.7 %). For sumatriptan, the response rates were
46.6 % (95% CI: 40.0-53.2 %), 29% (95 % CI: 23.0-34.9 %), and 22.2 % (95 % CI:
16.7-27.6 %). The corresponding rates for placebo were 33.9 % (95% CI: 29.1-38.6 
%), 15.1 % (95 % CI: 11.5-18.7 %), and 14.6 % (95 % CI: 11.0-18.1 %). The
treatment effect of eASA and sumatriptan were significantly different from
placebo (p < 0.001), but differences between eASA and sumatriptan were not
significant. The remission of accompanying symptoms and the subgroup analyses of 
patients with moderate or severe migraine pain at baseline revealed no
significant differences between eASA and sumatriptan. Safety was evaluated based 
on the frequency of reported adverse events, and treatment with eASA was
associated with lower incidence of adverse events than was with sumatriptan. This
individual patient data meta-analysis provided evidence that eASA 1,000 mg is as 
effective as sumatriptan 50mg for the treatment of acute migraine attacks and has
a better side effect profile. This is also true for patients with moderate as
well as severe headache at baseline. Patients therefore should be advised to use 
eASA first for migraine attacks and use a triptan in case of no response.

Publication Types: 
    Comparative Study
    Meta-Analysis

PMID: 17406776 [PubMed - indexed for MEDLINE]

826: JAMA. 2007 Apr 4;297(13):1443-54.

Comment in:
    J Fam Pract. 2007 Jul;56(7):536.    JAMA. 2007 Sep 19;298(11):1276; author reply 1276-7.    Nat Clin Pract Neurol. 2007 Nov;3(11):604-5.

Sumatriptan-naproxen for acute treatment of migraine: a randomized trial.

Brandes JL, Kudrow D, Stark SR, O'Carroll CP, Adelman JU, O'Donnell FJ, Alexander
WJ, Spruill SE, Barrett PS, Lener SE.

Nashville Neuroscience Group, Nashville, Tenn 37203, USA.
jbrandes@nashvilleneuroscience.com

CONTEXT: Multiple pathogenic mechanisms may be involved in generating the
migraine symptom complex, and multimechanism-targeted therapy may confer
advantages over monotherapy. OBJECTIVE: To evaluate the efficacy and safety of a 
fixed-dose tablet containing sumatriptan succinate and naproxen sodium relative
to efficacy and safety of each monotherapy and placebo for the acute treatment of
migraine. DESIGN, SETTING, AND PARTICIPANTS: Two replicate, randomized,
double-blind, single-attack, parallel-group studies conducted among 1461 (study
1) and 1495 (study 2) patients at 118 US clinical centers who were diagnosed as
having migraine and received study treatment for a moderate or severe migraine
attack. INTERVENTIONS: Patients were randomized in a 1:1:1:1 ratio to receive a
single tablet containing sumatriptan, 85 mg, and naproxen sodium, 500 mg;
sumatriptan, 85 mg (monotherapy); naproxen sodium, 500 mg (monotherapy); or
placebo, to be used after onset of a migraine with moderate to severe pain. MAIN 
OUTCOME MEASURES: Primary outcome measures included the percentages of patients
with headache relief 2 hours after dosing, absence of photophobia, absence of
phonophobia, and absence of nausea for the comparison between
sumatriptan-naproxen sodium and placebo, and the percentages of patients with
sustained pain-free response for the comparison between sumatriptan-naproxen
sodium and each monotherapy. RESULTS: Sumatriptan-naproxen sodium was more
effective than placebo for headache relief at 2 hours after dosing (study 1, 65% 
vs 28%; P<.001 and study 2, 57% vs 29%; P<.001), absence of photophobia at 2
hours (58% vs 26%; P<.001 and 50% vs 32%; P<.001), and absence of phonophobia at 
2 hours (61% vs 38%; P<.001 and 56% vs 34%; P<.001). The absence of nausea 2
hours after dosing was higher with sumatriptan-naproxen sodium than placebo in
study 1 (71% vs 65%; P = .007), but in study 2 rates of absence of nausea did not
differ between sumatriptan-naproxen sodium and placebo (65% vs 64%; P = .71). For
2- to 24-hour sustained pain-free response, sumatriptan-naproxen sodium was
superior at P<.01 (25% and 23% in studies 1 and 2, respectively) to sumatriptan
monotherapy (16% and 14% in studies 1 and 2), naproxen sodium monotherapy (10%
and 10% in studies 1 and 2), and placebo (8% and 7% in studies 1 and 2). The
incidence of adverse events was similar between sumatriptan-naproxen sodium and
sumatriptan monotherapy. CONCLUSION: Sumatriptan, 85 mg, plus naproxen sodium,
500 mg, as a single tablet for acute treatment of migraine resulted in more
favorable clinical benefits compared with either monotherapy, with an acceptable 
and well-tolerated adverse effect profile. TRIAL REGISTRATION: clinicaltrials.gov
Identifiers: NCT00434083 (study 1); NCT00433732 (study 2).

Publication Types: 
    Comparative Study
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 17405970 [PubMed - indexed for MEDLINE]

827: Seizure. 2007 Jul;16(5):465-8. Epub 2007 Apr 2.

Epilepsy and migraine in a patient with Urbach-Wiethe disease.

Claeys KG, Claes LR, Van Goethem JW, Sercu S, Merregaert J, Lambert J, Van Marck 
EA, Parizel PM, De Jonghe P.

Neurogenetics Group, Department of Molecular Genetics, Flanders Interuniversity
Institute for Biotechnology (VIB), University of Antwerp, Universiteitsplein 1,
B-2610 Antwerpen, Belgium. kristl.claeys@ua.ac.be

We report the clinical, neuroradiological, and molecular genetic findings in a
patient with lipoid proteinosis or Urbach-Wiethe disease. Interestingly, in this 
patient epilepsy and migraine were the symptoms leading to the diagnosis of the
disease, contrary to most patients in whom skin abnormalities are the first
recognized symptoms.

Publication Types: 
    Case Reports
    Research Support, Non-U.S. Gov't

PMID: 17403608 [PubMed - indexed for MEDLINE]

828: Cephalalgia. 2007 May;27(5):394-402. Epub 2007 Mar 30.

The triggers or precipitants of the acute migraine attack.

Kelman L.

Headache Center of Atlanta, Atlanta, GA 30342, USA. lkelman@mindspring.com

The aim of this study was to evaluate and define the triggers of the acute
migraine attack. Patients rated triggers on a 0-3 scale for the average headache.
Demographics, prodrome, aura, headache characteristics, postdrome, medication
responsiveness, acute and chronic disability, sleep characteristics and social
and personal characteristics were also recorded. One thousand two hundred and
seven International Classification of Headache Disorders-2 (1.1-1.2, and 1.5.1)
patients were evaluated, of whom 75.9% reported triggers (40.4% infrequently,
26.7% frequently and 8.8% very frequently). The trigger frequencies were stress
(79.7%), hormones in women (65.1%), not eating (57.3%), weather (53.2%), sleep
disturbance (49.8%), perfume or odour (43.7%), neck pain (38.4%), light(s)
(38.1%), alcohol (37.8%), smoke (35.7%), sleeping late (32.0%), heat (30.3%),
food (26.9%), exercise (22.1%) and sexual activity (5.2%). Triggers were more
likely to be associated with a more florid acute migraine attack. Differences
were seen between women and men, aura and no aura, episodic and chronic migraine,
and between migraine and probable migraine.

PMID: 17403039 [PubMed - indexed for MEDLINE]

829: Hum Mutat. 2007 May;28(5):522.

The novel p.L1649Q mutation in the SCN1A epilepsy gene is associated with
familial hemiplegic migraine: genetic and functional studies. Mutation in brief
#957. Online.

Vanmolkot KR, Babini E, de Vries B, Stam AH, Freilinger T, Terwindt GM, Norris L,
Haan J, Frants RR, Ramadan NM, Ferrari MD, Pusch M, van den Maagdenberg AM,
Dichgans M.

Department of Human Genetics, Leiden University Medical Centre, Leiden, The
Netherlands.

Familial hemiplegic migraine (FHM) is a severe subtype of migraine with
hemiparesis during attacks. We scanned 10 families with FHM without mutations in 
the CACNA1A (FHM1) and ATP1A2 (FHM2) genes. We identified the novel p.L1649Q
mutation (c.4946T>A) in Na(v)1.1 sodium channel gene SCN1A (FHM3) in a North
American kindred with FHM without associated ataxia or epilepsy. Functional
analysis of the mutation, introduced in the highly homologous human SCN5A,
revealed markedly slowed inactivation and a two-fold faster recovery from fast
inactivation predicting enhanced neuronal excitation. Our findings establish the 
role of neuronal Na(v)1.1 sodium channels in FHM and reinforce the involvement of
ion channel dysfunction in the pathogenesis of this episodic brain disorder. 2007
Wiley-Liss, Inc.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17397047 [PubMed - indexed for MEDLINE]

830: Auton Neurosci. 2007 Jul 31;134(1-2):81-4. Epub 2007 Mar 28.

Habituation of sympathetic skin response in migraine and tension type headache.

Ozkul Y, Ay H.

Harran University, Faculty of Medicine, Department of Neurology, Turkey.
ozkul@harran.edu.tr

This study aimed to investigate the changes of habituations in the autonomic
function of patients suffering from migraine or tension type headache through
sympathetic skin responses. Patients with migraine without aura (n=26), with
episodic tension type headache without migraine (n=28) and 30 healthy controls
were studied. During continuous stimulation, four blocks of 20 responses were
sequentially recorded. Mean amplitude changes in the second, third and fourth
blocks are expressed as the percentages of the first block. In both headache
groups, there was a lack of habituation compared to the control group.

Publication Types: 
    Comparative Study

PMID: 17395550 [PubMed - indexed for MEDLINE]

831: Neurotherapeutics. 2007 Apr;4(2):274-84.

Familial hemiplegic migraine.

Pietrobon D.

Department of Biomedical Sciences, University of Padova, 35121 Padova, Italy.
daniela.pietrobon@unipd.it

Familial hemiplegic migraine (FHM) is a rare and genetically heterogeneous
autosomal dominant subtype of migraine with aura. Mutations in the genes CACNA1A 
and SCNA1A, encoding the pore-forming alpha(1) subunits of the neuronal
voltage-gated Ca2+ channels Ca(V)2.1 and Na+ channels Na(V)1.1, are responsible
for FHM1 and FHM3, respectively, whereas mutations in ATP1A2, encoding the alpha2
subunit of the Na+, K+ adenosinetriphosphatase (ATPase), are responsible for
FHM2. This review discusses the functional studies of two FHM1 knockin mice and
of several FHM mutants in heterologous expression systems (12 FHM1, 8 FHM2, and 1
FHM3). These studies show the following: (1) FHM1 mutations produce
gain-of-function of the Ca(V)2.1 channel and, as a consequence, increased
Ca(V)2.1-dependent neurotransmitter release from cortical neurons and
facilitation of in vivo induction and propagation of cortical spreading
depression (CSD: the phenomenon underlying migraine aura); (2) FHM2 mutations
produce loss-of-function of the alpha2 Na+,K+-ATPase; and (3) the FHM3 mutation
accelerates recovery from fast inactivation of Na(V)1.5 (and presumably Na(V)1.1)
channels. These findings are consistent with the hypothesis that FHM mutations
share the ability of rendering the brain more susceptible to CSD by causing
either excessive synaptic glutamate release (FHM1) or decreased removal of K+ and
glutamate from the synaptic cleft (FHM2) or excessive extracellular K+ (FHM3).
The FHM data support a key role of CSD in migraine pathogenesis and point to
cortical hyperexcitability as the basis for vulnerability to CSD and to migraine 
attacks. Hence, they support novel therapeutic strategies that consider CSD and
cortical hyperexcitability as key targets for preventive migraine treatment.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 17395138 [PubMed - indexed for MEDLINE]

832: Cephalalgia. 2007 May;27(5):429-34. Epub 2007 Mar 26.

GNAS1 T393C polymorphism is associated with migraine.

Oterino A, Ruiz-Alegría C, Castillo J, Valle N, Bravo Y, Cayón A, Alonso A,
Tejera P, Ruiz-Lavilla N, Muñoz P, Pascual J.

Service of Neurology, University Hospital Marqués de Valdecilla (UC), Santander, 
Spain. aoterino@humv.es

Migraineurs have an interictal sympathetic nervous system (SNS) hypofunctionality
and hypersensitivity to adrenergic amines. The GNAS1 T393C polymorphism has been 
associated with a distinct SNS sensitivity in healthy subjects. We tested GNAS1
T393C variant in two independent sets of subjects. In the case-control subset,
365 migraine patients [194 with aura (MA)] vs. 347 healthy controls were studied.
A significant excess of the CC genotype was found in migraneurs (31.2%) as
opposed to controls (20.2%; P=0.003). Using a logistic regression model corrected
for sex, the CC genotype conferred a general risk for migraine twice [odds ratio 
(OR) 1.79, 95% confidence interval (CI) 1.27-2.53; P=0.001] higher than CT/TT
genotypes. Using parents from 117 migraine families, a marginally significant
trend for association could be observed (P=0.025), but the transmission
disequilibrium test for alleles maternally transmitted failed to demonstrate
familial association. In this subgroup, CC genotype conferred a risk for migraine
over twice (OR 2.20; 95% CI 1.14-4.40; P=0.019) higher than TT/TC genotypes. In
conclusion, the GNAS1 T393C variant is associated with migraine, which suggests a
genetic basis for its higher SNS sensitivity.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17388805 [PubMed - indexed for MEDLINE]

833: Cephalalgia. 2007 May;27(5):456-60. Epub 2007 Mar 26.

Migraine with persistent aura in a Mexican patient: case report and review of the
literature.

San-Juan OD, Zermeño PF.

Department of Neurology, National Institute of Neurology and Neurosurgery of
Mexico, Mexico City, Mexico. pegaso31@yahoo.com

Persistent aura symptoms in patients with migraine are rare but well documented. 
The International Headache Society defines persistent aura without infarction as 
when the aura symptoms persist for > 1 week without radiographic evidence of
infarction. The visual aura of migraine attacks has been explained by cortical
spreading depression. We describe a case of a 28-year-old Mexican woman, who
presented with persistent aura symptoms, and a literature review. The patient had
a 24-year history of migraine headache. In November 2005 the patient had an
attack which started with scintillating scotomas bilaterally associated with
photopsias and amaurosis followed by migraine headache. All imaging studies were 
negative. The episode lasted 35 days and probably resolved with nimodipine
therapy. Persistent aura symptoms are rare entities. This is the first case
documented of a Mexican patient with persistent aura without infarction and
probably resolved with nimodipine therapy.

Publication Types: 
    Case Reports
    Review

PMID: 17388804 [PubMed - indexed for MEDLINE]

834: Stat Med. 2007 Sep 30;26(22):4163-78.

Analysis of responses in migraine modelling using hidden Markov models.

Anisimov VV, Maas HJ, Danhof M, Della Pasqua O.

Research Statistics Unit, Biomedical Data Sciences, GlaxoSmithKline, New
Frontiers Science Park (South), Third Avenue, Harlow, Essex CM19 5AW, UK.

Markov-type models have been used in the analysis of disease progression.
Although standard errors of model parameters are usually estimated, available
software often does not permit the construction of confidence intervals around
predictions of the dependent or response variable. A method is presented to
calculate means and confidence intervals of model-predicted responses in time
governed by a non-homogeneous hidden Markov model in continuous time. The
Kolmogorov equations serve as the basis for the calculations. The method is
realised in S-Plus and is applied to the prediction of headache responses in
clinical studies of anti-migraine treatment. Means and confidence intervals are
calculated by numerically solving differential equations that are non-linear in
the explanatory variable. Results indicate that uncertainty on predicted drug
responses is larger than that on predicted placebo responses and that pain-free
responses are less precisely predicted than pain-relief responses. This is due to
the uncertainty in the drug-specific parameters which is not present in predicted
placebo responses.

PMID: 17385187 [PubMed - indexed for MEDLINE]

835: Singapore Med J. 2007 Apr;48(4):307-10.

The coexistence of anxiety and depressive personality traits in migraine.

Tan HJ, Suganthi C, Dhachayani S, Rizal AM, Raymond AA.

Department of Medicine, Universiti Kebangsaan Malaysia, Jalan Yaacob Latif,
Cheras, Kuala Lumpur 56000, Malaysia. tanhuijan@hotmail.com

INTRODUCTION: Migraine is associated with a variety of personality traits. The
objective of this study was to reevaluate the personality traits using Minnesota 
Multiphasic Personality Inventory-2 (MMPI-2) in migraine patients diagnosed by
applying the new International Classification of Headache Disorders-2 criteria.
METHODS: This was a case control study involving 70 migraine patients and 70 age-
and gender-matched controls. The personality traits in the two groups were
analysed using the MMPI. Data was analysed using the chi-square test. RESULTS:
The migraine patients showed a higher MMPI score on the following personality
traits: depression (39 versus 15, p-value is less than 0.0005), and anxiety (24
versus 11, p-value equals 0.011). Both depressive and anxiety personality traits 
were significantly higher in migraine patients. CONCLUSION: All migraine patients
should probably be screened for their personality traits and psychopathology
using the MMPI.

PMID: 17384877 [PubMed - indexed for MEDLINE]

836: Neurosci Lett. 2007 May 17;418(2):122-6. Epub 2007 Mar 12.

Prevention of electrical stimulation-induced increase of c-fos immunoreaction in 
the caudal trigeminal nucleus by kynurenine combined with probenecid.

Knyihár-Csillik E, Toldi J, Krisztin-Péva B, Chadaide Z, Németh H, Fenyo R,
Vécsei L.

Department of Neurology, University of Szeged, Hungary.
knyihar@nepsy.szote.u-szeged.hu

The systemic administration of nitroglycerine, regarded as a migraine model, was 
previously observed to result in an increased number of c-fos immunoreactive
secondary sensory neurons in the caudal trigeminal nucleus, which forward
nociceptive impulses to the thalamus. The present investigation tested the
hypothesis of whether kynurenine in combination with systemically administered
probenecid protects second-order trigeminal neurons against stimulation arriving 
via central processes of trigeminal ganglion cells. Electrical stimulation of the
trigeminal ganglion, one of the experimental migraine models, is known to induce 
an increase in the number of c-fos immunoreactive second-order nerve cells
projecting to the thalamus. Since the synapses between first- and second-order
trigeminal neurons are presumed to be mediated by excitatory amino acids,
postsynaptic NMDA receptors should be inhibited by kynurenic acid, an endogenous 
NMDA receptor antagonist. Kynurenic acid, however, does not cross the blood-brain
barrier, and its use as a neuroprotective agent is therefore not feasible. In
contrast, kynurenine, from which kynurenic acid is formed on the action of
kynurenine aminotransferase, passes the blood-brain barrier without difficulty.
After the i.p. injection of kynurenine combined with probenecid it was found that
the stimulation-induced increase in the c-fos immunoreactivity of the secondary
sensory neurons does not occur.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17382471 [PubMed - indexed for MEDLINE]

837: Cephalalgia. 2007 Mar;27(3):275-8.

The aetiology and management of long-lasting sixth nerve palsy in ophthalmoplegic
migraine.

Manzouri B, Sainani A, Plant G, Lee J, Sloper J.

Department of Paediatrics and Strabismus, Moorfields Eye Hospital, London, UK.

The features and management of two adult patients with ophthalmoplegic migraine
and longlasting sixth nerve palsies are described. Both had had previous shorter 
episodes of diplopia following migraine-like headaches. One recovered following
an injection of botulinum toxin to the medial rectus of her affected eye 11
months after the onset of diplopia. The other patient had previously had surgery 
for a consecutive divergent squint and required further squint surgery to realign
his eyes 1 year after the onset of his sixth nerve palsy. Both botulinum toxin
and squint surgery may be useful in the management of longstanding sixth nerve
palsy in patients with ophthalmoplegic migraine. The aetiology of ophthalmoplegic
migraine is discussed.

Publication Types: 
    Case Reports

PMID: 17381560 [PubMed - indexed for MEDLINE]

838: Cephalalgia. 2007 Mar;27(3):235-43.

Combined effects of ACE and MMP-3 polymorphisms on migraine development.

Kara I, Ozkok E, Aydin M, Orhan N, Cetinkaya Y, Gencer M, Kilic G, Tireli H.

Department of Neuroscience, Institute of Experimental Medicine Research, Istanbul
University, Istanbul, Turkey.

Migraine is a primary headache disorder which involves both genetic and
environmental components. Since angiotensin-converting enzyme (ACE) and matrix
metalloproteinase (MMP) share the same homology, we investigated whether the
MMP-3 and ACE I/D gene variants are involved in migraine risk and whether the ACE
variant might act in combination with the MMP-3 genetic variant in patients with 
migraine. This is the first study to evaluate the association between MMP-3 and
ACE polymorphisms, and migraine. Genotypes were determined by polymerase chain
reaction. The frequencies of 5A5A genotypes of the MMP-3 and D allele of ACE were
significantly elevated, but II genotypes of the ACE and 6A allele of MMP-3
significantly decreased in all patients. The combined DD/5A5A and ID/5A5A
genotypes increased the risk of migraine. Individuals who were homozygous for the
deletion (D) allele showed increased ACE activity. Subjects with the 5A5A
genotype and/or D allele or with the combined DD/5A5A or ID/5A5A might be more
susceptible to migraine development. In contrast, subjects with the II and/or
6A6A genotypes may be protected from migraine development. The greater activity
of the 5A5A and DD genotypes might result in vascular reactivity that is more
pronounced in migraine. Taken together, our data suggest that numerous genes may 
influence ACE activity. Discovery of new genes might better clarify the
pathogenesis of migraine and open an avenue to therapeutic strategies against
migraine.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17381556 [PubMed - indexed for MEDLINE]

839: Clin Ther. 2007 Jan;29(1):99-109.

Efficacy of sumatriptan tablets in migraineurs self-described or
physician-diagnosed as having sinus headache: a randomized, double-blind,
placebo-controlled study.

Ishkanian G, Blumenthal H, Webster CJ, Richardson MS, Ames M.

Elkind Headache Center, Mount Vernon, New York 10550, USA.
gishkanian@optonline.net

BACKGROUND: Many patients and physicians interpret episodic headache in the
presence or absence of nasal symptoms as "sinus' headache, while ignoring the
possible diagnosis of migraine. OBJECTIVE: The purpose of this study was to
assess the efficacy and tolerability of sumatriptan succinate 50-mg tablets in
patients with migraine presenting with "sinus" headache. METHODS: A randomized,
double-blind, placebo-controlled, multicenter study was conducted in adult (aged 
18-65 years) migraine patients presenting with self-described or
physician-diagnosed "sinus" headache. From November 2001 to March 2002, patients 
meeting International Headache Society criteria for migraine (with > or =2 of the
following: unilateral location, pulsating quality, moderate or severe intensity, 
aggravation by moderate physical activity; and > or =1 of: phonophobia and
phonophobia, nausea and/or vomiting) and with no evidence of bacterial
rhinosinusitis were enrolled and randomized in a 1:1 ratio via computer-generated
randomization schedule to receive either 1 sumatriptan 50-mg tablet or matching
placebo tablet. The primary efficacy end point was headache response (moderate or
severe headache pain reduced to mild or no headache pain) at 2 hours after
administration. The presence or absence of migraine-associated symptoms and sinus
and nasal symptoms was also measured. Tolerability was assessed through
patient-reported adverse events (AEs). RESULTS: Two hundred sixteen patients with
self-described or physician-diagnosed "sinus" headache received a migraine
diagnosis and treated 1 migraine attack with sumatriptan 50 mg. The efficacy
(intent-to-treat) analysis included 215 patients treated with sumatriptan 50 mg
(n = 108; mean [SD] age, 39.6 [12.3] years; mean [SD] weight, 77.7 [17.7] kg;
sex, 71% female; race, 69% white) or placebo (n = 107; mean [SD] age, 41.0 [11.3]
years; mean [SD] weight 80.7 [20.9] kg; sex, 69% female; race, 64% white).
Significantly more patients treated with sumatriptan 50 mg achieved a positive
headache response at 2 and 4 hours after administration compared with those
treated with placebo (69% vs 43% at 2 hours and 76% vs 49% at 4 hours,
respectively; both, P < 0.001). Significantly more sumatriptan-treated patients
were free from sinus pain compared with placebo recipients at 2 hours (63% vs 49%
placebo, P = 0.049) and 4 hours (77% vs 55%, P = 0.001). All treatments were
generally well tolerated. The most common drug-related AEs reported in the
sumatriptan and placebo groups, respectively, were dizziness (5% vs < 1%), nausea
(3% vs 2%), other pressure/tightness (defined as sense of heaviness; heaviness of
upper body, upper extremities; jaw tension; neck tension) (4% vs 0%), and
temperature sensations (defined as warm feeling of back of neck, or flushing) (2%
vs 0%). No patients experienced any serious AEs. CONCLUSIONS: Sumatriptan 50-mg
tablets were effective and generally well tolerated in the treatment of these
patients presenting with migraine headaches that were self-described or
physician-diagnosed as sinus headaches.

Publication Types: 
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 17379050 [PubMed - indexed for MEDLINE]

840: Cephalalgia. 2007 Apr;27(4):347-54.

Headache prevalence among adolescents--the German DMKG headache study.

Fendrich K, Vennemann M, Pfaffenrath V, Evers S, May A, Berger K, Hoffmann W.

Institute for Community Medicine, Section Epidemiology of Health Care and
Community Health, University of Greifswald, Greifswald, Germany.

This population-based cross-sectional study examined the 3-month prevalence of
headache, migraine and tension-type headache (TTH) among adolescents aged 12-15
years in Germany. Students (n = 3324) from 20 schools completed a questionnaire
on general and headache-specific pain which included a sociodemographic module.
The headache-specific questionnaire complied with the respective revised criteria
of the International Headache Society (IHS). 'Modified criteria' changed the item
'duration' in migraine (>30 min instead of > 4 h). The overall 3-month prevalence
of headache was 69.4% (boys 59.5%, girls 78.9%), with 4.4% of the adolescents
suffering from frequent (>or=14 days/3 months) and severe (grade 8-10 on a
10-point visual analogue scale) headache and 1.4% (boys 0.9%, girls 1.9%) from
headache >or= 15 days/month. The 3-month prevalence of migraine was 2.6% (boys
1.6%, girls 3.5%) applying strict IHS criteria and 6.9% (boys 4.4%, girls 9.3%)
with modified criteria; 12.6% (boys 8.3%, girls 16.7%) suffered from probable
migraine, 0.07% fulfilled the criteria for chronic migraine, 4.5% (boys 4.6%,
girls 4.3%) suffered from TTH, 0.2% from chronic TTH and 15.7% (boys 14.5%, girls
16.9%) from probable TTH. Headache and migraine were more common in girls than in
boys and in teenagers, especially in girls, aiming at higher education. Recurrent
headache and primary headache disorders are common complaints among German
adolescents, especially among girls.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17376112 [PubMed - indexed for MEDLINE]

841: Cephalalgia. 2007 Apr;27(4):343-6.

Weekend migraine.

Alstadhaug KB, Salvesen R, Bekkelund S.

Department of Neurology, Nordlandssykehuset, Bodø, Norway.
alstadhaug@operamail.com

It is a general belief that migraine attacks are prone to occur on days off. Only
a few studies, however, have addressed this issue. The objective of this study
was to investigate the periodicity of migraine with respect to weekly
(circaseptan) variations. Eighty-nine females of fertile age who had participated
in a previous questionnaire-based study volunteered to record in detail every
migraine attack for 12 consecutive months. Eighty-four patients completed
recordings for a mean of 311 days (s.d. = 95.9, range 30-365). A total of 2314
attacks were recorded. Migraine occurrence was almost equally distributed during 
the week, except on Sundays, when there were significantly fewer attacks (t =
-4.42, d.f. = 83, P < 0.001). A Mantel-Haenszel estimate of the relative risk of 
having an attack on a holiday vs. another day, not Sundays included, was 0.64
(95% CI 0.49-0.85). Our study suggests that days off protect against migraine.

PMID: 17376111 [PubMed - indexed for MEDLINE]

842: Cephalalgia. 2007 Apr;27(4):336-42.

Validation of the eleven-point pain scale in the measurement of migraine headache
pain.

Kwong WJ, Pathak DS.

Department of Clinical and Administrative Pharmacy, College of Pharmacy,
University of Georgia, Athens, GA 30622-2354, USA. jkwong@mail.rx.uga.edu

The four-point pain scale (none, mild, moderate, severe) and the 11-point pain
scale (0 = no pain, 10 = pain as bad as it could be) have been used in migraine
studies to assess treatment efficacy. The primary objective of this study was to 
investigate the validity and responsiveness of the 11-point pain scale using the 
four-point pain scale as a benchmark. Using data from 95 migraine patients
recruited from headache clinics, this study found that 11-point pain scale scores
were highly correlated with four-point pain scores. The correlations between the 
pain scales were significantly higher than the correlations with quality of life 
measures such as functional ability and emotional feelings. The 11-point pain
scale was 55% more sensitive than the four-point pain scale in detecting
clinically important differences. The strong linear relationship between the two 
pain scales allowed researchers to transform four-point pain scores to 11-point
pain scores using regression weights.

Publication Types: 
    Evaluation Studies
    Multicenter Study
    Research Support, Non-U.S. Gov't
    Validation Studies

PMID: 17376110 [PubMed - indexed for MEDLINE]

843: Cephalalgia. 2007 Apr;27(4):330-5.

Prevalence of migraine in Noonan syndrome.

Piovesan EJ, Young Blood MR, Kowacs PA, Mulinari RA, Werneck LC, Sandrini R.

Headache Unit, Neurology Division, Internal Medicine Department, Hospital de
Clínicas, Universidade Federal do Paraná, Curitiba, Brazil.
piovesan@avalon.sul.com.br

A randomized double-controlled trial involving 22 patients with Noonan syndrome
(NS) and 22 normal individuals (control group) was carried out to determine the
prevalence of migraine in patients with NS. The NS group consisted of 11 males
aged 19.55 +/- 6.11 years and 11 females aged 18.81 +/- 5.47 years. The control
group consisted of 11 males aged 19.55 +/- 6.6 years and 11 females aged 18.81
+/- 5.47 years. Seven NS-group patients reported migraine without aura (MO), and 
three reported probable MO (PMO). Taken together, these represent a prevalence of
migraine in the NS group of 45.5%. Two control-group patients reported MO, a
prevalence of 9.09%. The prevalence of migraine was significantly higher in the
NS-group patients than in the controls (P < 0.005), suggesting a positive
association between NS and migraine. Nevertheless, further studies are needed to 
confirm our findings.

Publication Types: 
    Randomized Controlled Trial

PMID: 17376109 [PubMed - indexed for MEDLINE]

844: Cephalalgia. 2007 Apr;27(4):325-9.

Improved identification of allodynic migraine patients using a questionnaire.

Ashkenazi A, Silberstein S, Jakubowski M, Burstein R.

Department of Neurology, Thomas Jefferson University Hospital, Jefferson Headache
Center, Philadelphia, PA, USA.

Using quantitative sensory testing (QST), we found that many migraineurs seeking 
secondary and tertiary care exhibit cutaneous allodynia whenever they undergo a
migraine attack, but not interictally (i.e. between attacks). When such patients 
were questionned interictally in the clinic about symptoms of skin sensitivity in
past attacks, 76% of them were 'correctly' classified either as allodynic (>or=1 
symptom) or non-allodynic (zero symptoms) in line with the QST analysis. In this 
study, patients were classified as allodynic if they documented any one symptom
of allodynia during an actual migraine attack which they had already cited in an 
earlier interictal interview. Of a total of 151 patients, 77% were classified as 
allodynic, citing on average four symptoms of skin hypersensitivity, three of
which were consistently cited in the interictal interview and again during an
attack. Among the remaining 23% of patients who were classified as non-allodynic,
half cited zero symptoms as expected, while the other half cited between one and 
five symptoms, each of which was cited either interictally or during an attack,
but not in both. Further analysis showed that 97% of patients citing two or more 
symptoms during an attack consisted of the patients labelled as allodynic, and
that 75% of those citing just one symptom during an attack consisted of patients 
labelled as non-allodynic. Short of QST analysis, the results suggest that about 
90% of all patients can be identified as allodynic or non-allodynic depending on 
whether or not they (i) consistently cited the same item(s) both interictally and
during an attack or, alternatively, (ii) cited two or more symptoms during an
attack.

Publication Types: 
    Comparative Study
    Evaluation Studies
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 17376108 [PubMed - indexed for MEDLINE]

845: Cephalalgia. 2007 Apr;27(4):304-14.

Prospective analysis of factors related to migraine attacks: the PAMINA study.

Wöber C, Brannath W, Schmidt K, Kapitan M, Rudel E, Wessely P, Wöber-Bingöl C;
PAMINA Study Group.

Department of Neurology, Medical University of Vienna, Vienna, Austria.
christian.woeber@meduniwien.ac.at

Migraine is related to numerous factors such as hormones, stress or nutrition,
but information about their actual importance is limited. Therefore, we analysed 
prospectively a wide spectrum of factors related to headache in migraineurs. We
examined 327 migraineurs recruited via newspapers who kept a comprehensive diary 
for 3 months. Statistical analysis comprising 28 325 patient days and 116
dichotomous variables was based on the interval between two successive headache
attacks. We calculated univariate Cox regression analyses and included
covariables with a P-value of <0.05 in two stepwise multivariate Cox regression
analyses, the first accounting for a correlation of the event times within a
subject, the second stratified by the number of headache-free intervals. We
performed similar analyses for the occurrence of migraine attacks and for the
persistence of headache and migraine. Menstruation had the most prominent effect,
increasing the hazard of occurrence or persistence of headache and migraine by up
to 96%. All other factors changed the hazard by <35%. The two days before
menstruation and muscle tension in the neck, psychic tension, tiredness, noise
and odours on days before headache onset increased the hazard of headache or
migraine, whereas days off, a divorced marriage, relaxation after stress, and
consumption of beer decreased the hazard. In addition, three meteorological
factors increased and two others decreased the hazard. In conclusion,
menstruation is most important in increasing the risk of occurrence and
persistence of headache and migraine. Other factors increase the risk less
markedly or decrease the risk.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17376107 [PubMed - indexed for MEDLINE]

846: Cephalalgia. 2007 Apr;27(4):294-303.

Changing headache from preschool age to puberty. A controlled study.

Virtanen R, Aromaa M, Rautava P, Metsähonkala L, Anttila P, Helenius H, Sillanpää
M.

Department of Public Health, University of Turku, Turku, Finland.
ruut.virtanen@utu.fi

The characteristics of disturbing primary headache and the occurrence of headache
types were studied by sending a questionnaire to 1132 Finnish families of
6-year-old children. Children with headache in the preceding 6 months and their
controls were clinically examined at the ages of 6 and 13. During the follow-up, 
half of the headaches, classified as migraine at age 6 years, were unchanged and 
32% turned into tension-type headache. In children with tension-type headache,
the situation was unchanged in 35%, and in 38% of children the headache type had 
changed to migraine. At preschool age the most common location of headache was
bilateral and supraorbital, and at puberty bilateral and temporal. During the
follow-up, symptoms concurrent with headache, such as odour phobia, dizziness and
balance disturbances became more typical, whereas restlessness, flushing and
abdominal symptoms became less marked. The early manifestation of both migraine
and tension-type headache predict equally often migraine in puberty with marked
changes in concurrent symptoms and pain localization.

Publication Types: 
    Controlled Clinical Trial

PMID: 17376106 [PubMed - indexed for MEDLINE]

847: J AOAC Int. 2007 Jan-Feb;90(1):94-101.

Determination of the analgesic components of Spasmomigraine tablet by liquid
chromatography with ultraviolet detection.

Elbarbry FA, Mabrouk MM, El-Dawy MA.

University of Saskatchewan, College of Pharmacy and Nutrition, 110 Science Place,
Saskatoon SK S7N 5C9, Canada. fae008@mail.usask.ca

A procedure was developed for the determination of the analgesic components of
Spasmomigraine tablets, which are ergotamine (I), propyphenazone (II), caffeine
(III), camylofin (IV), and mecloxamine (V). They were subjected to
high-performance liquid chromatography on a column (300 x 3.9 mm, 10 rlm particle
size) packed with micro-Bondapak C18. Separations were achieved with the mobile
phase methanol-water-triethylamine (60 + 40 + 0.1, v/v/v) flowing at a rate of
1.5 mL/min, and quantitative determination was performed at 254 nm at ambient
temperature for I-III; acetonitrile-25 mM KH2PO4-acetic acid (45 + 55 + 0.2,
v/v/v), flowing at a rate of 1.5 mL/min and detection at 234 nm at ambient
temperature, was used for IV and V. Methyl paraben was used as an internal
standard. The detection limits were 0.35 (I), 5.0 (11), 1.5 (111), 3.0 (IV), and 
2.0 microg/mL (V). The method was accurate (mean recovery 98+/-2%, n = 4) and
precise (coefficient of variation <5%, n = 5). The proposed method is rapid and
sensitive and, therefore, suitable for the routine control of these ingredients
in multicomponent dosage forms.

PMID: 17373440 [PubMed - indexed for MEDLINE]

848: Minerva Med. 2007 Feb;98(1):43-52.

Acute treatment for migraine headache.

Rozen TD.

Michigan Head-Pain and Neurological Institute, Ann Arbor, MI 48104, USA.
tdrozmigraine@yahoo.com

Migraine headaches can be frequent and disabling. Effective acute treatment can
improve the quality of life for migraineurs. The migraine attack is made up of
phases, which include the prodrome, aura and the headache itself. Not every
migraineur experiences each phase. Each phase, however, has its own distinct
pathogenesis and its own unique acute therapy. This review article will help to
define the treatment strategies for the various phases of the migraine attack. It
will discuss some general principles of acute migraine treatment, specific acute 
medications and some unique clinical situations (treatment of the prolonged aura 
and treating when pain is mild versus moderate/severe). It should be very
apparent that a better understating of migraine pathogenesis has led to improved 
and more effective acute therapies for migraine.

Publication Types: 
    Review

PMID: 17372581 [PubMed - indexed for MEDLINE]

849: Minerva Med. 2007 Feb;98(1):25-36.

Patent foramen ovale in patients with migraine headache. Should it be closed?

Spies C, Kavinsky CJ, Schräder R.

Section of Cardiology, Rush University Medical Center, Chicago, IL 60612, USA.
christian_spies@rush.edu

Our objective is to review the epidemiology and proposed pathophysiology of
migraine headache and its association with patent foramen ovale (PFO). We further
elucidate the technical aspects of PFO closure and its possible impact on
migraine headache. Upon reviewing English-language publications listed in MEDLINE
relating to migraine headache, PFO; and transcatheter closure of PFO, we selected
case series, retrospective and prospective studies relevant to the topic. PFO
closure is being performed in annually increasing numbers worldwide for a variety
of indications. The percutaneous technique of PFO closure has been shown to be
safe and effective in multiple case series. Further, primarily retrospective
case-control studies demonstrate a link between PFO closure and improvement of
migraine headache. Few prospective data confirm the initial RESULTS: However, the
only randomized, controlled trial finished to date analyzing the effect of PFO
closure on migraine failed to reach its primary outcome of resolution of migraine
following the intervention. The evidence of a benefit on migraine headache
following PFO closure is not convincing, but certainly intriguing. With currently
ongoing trials, more information related to this topic can be expected. In the
meantime, the question whether we should close PFOs in patients with migraine
headaches cannot be answered.

Publication Types: 
    Review

PMID: 17372579 [PubMed - indexed for MEDLINE]

850: Headache. 2007 Mar;47(3):427-30.

Levetiracetam prophylaxis in pediatric migraine--an open-label study.

Pakalnis A, Kring D, Meier L.

Department of Neurology, Children's Hospital, Columbus, OH 43205, USA.

BACKGROUND: Migraine is common in the pediatric population. Levetiracetam, an
anti-epileptic drug, has shown some efficacy in small prospective adult headache 
studies. METHODS: We prospectively evaluated levetiracetam in an open-label study
in 20 pediatric migraine patients to assess tolerability and efficacy. RESULTS:
Eighteen of 20 patients had significant reduction in headache frequency. PedMIDAS
showed significant decrease in disability scores, side effects were minimal (mild
behavioral changes). CONCLUSION: Levetiracetam had some efficacy in reducing
migraine frequency and disability. Further larger studies are warranted, possibly
utilizing a placebo-controlled design.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17371359 [PubMed - indexed for MEDLINE]

851: Headache. 2007 Mar;47(3):402-12.

Low-dose topiramate versus lamotrigine in migraine prophylaxis (the Lotolamp
study).

Gupta P, Singh S, Goyal V, Shukla G, Behari M.

Department of Neurology, All India Institute of Medical Sciences, New Delhi,
India.

OBJECTIVE: To assess the efficacy and safety of topiramate and lamotrigine for
prophylaxis in patients with frequent migraine as compared to each other and to
placebo. METHODS: Sixty patients with frequent migraine (more than 4 attacks per 
month) from the headache clinic at a tertiary referral centre in India were
randomized to receive 50 mg topiramate/lamotrigine or matching placebo for 1
month each in 2 divided doses in 4 phases in a crossover manner with a washout
period of 7 days in between. Primary efficacy measure was responder rate (50%
decrease in mean migraine frequency/intensity). Secondary efficacy measures
included reduction in mean monthly frequency, intensity, duration, rescue
medication use, migraine associated symptoms, and adverse events. STATISTICAL
ANALYSIS: Analysis was on intention to treat basis. Data were analyzed as
correlated data. Generalized estimation equation was used to compute overall mean
standard deviation and 95% confidence intervals for each of the outcome
variables. Bonferroni's correction done for multiple comparisons. P value of <
.017 was taken as significant. RESULTS: Fifty-seven patients comprised the
intent-to-treat population. Four patients withdrew from the study at various
phases, none because of the side effects. Responder rate for frequency was
significantly higher for topiramate versus placebo (63% vs 30%, P < .001), and
versus lamotrigine (63% vs 46 %, P = .02). For intensity of headache also a
responder rate of topiramate versus placebo (50% vs 10%, P < .001), and versus
lamotrigine (50% vs 41%, P = .01) was observed. Topiramate showed statistically
significant benefits (P < .017) in most of the secondary efficacy measures while 
lamotrigine was beneficial for reduction in headache frequency, and migraine
associated symptoms. Adverse events were similar. CONCLUSION: Low-dose topiramate
is efficacious in migraine prophylaxis as compared to both placebo and
lamotrigine. Lamotrigine in low doses might be beneficial for headache frequency;
however, longer trials are required to establish its efficacy on the intensity
and frequency of migraine.

Publication Types: 
    Randomized Controlled Trial

PMID: 17371357 [PubMed - indexed for MEDLINE]

852: Headache. 2007 Mar;47(3):397-401.

A retrospective, comparative study on the frequency of abuse in migraine and
chronic daily headache.

Peterlin BL, Ward T, Lidicker J, Levin M.

Department of Neurology, Drexel University College of Medicine, Philadelphia, PA,
USA.

OBJECTIVE: To assess and contrast the relative frequency of a past history of
physical and/or sexual abuse in patients with chronic daily headache (CDH) versus
migraine. BACKGROUND: A number of risk factors have been identified as risk
factors for chronification of headache disorders. Limited data exist regarding
the influence of physical and/or sexual abuse on primary headache disorders.
METHODS: This was a retrospective chart review of 183 consecutive new headache
patients seen from December 2004 through August 2005 at an outpatient
tertiary-care center. Patients were included in the study if they had chronic
daily headache (with criteria for medication over-use headache or chronic
migraine), or migraine with or without aura. A history of physical and/or sexual 
abuse was systematically asked of all headache patients at their first visit in
the clinic. This information was then transferred to a semi-standardized form and
the relative frequency of abuse in both groups contrasted. RESULTS: Of the 161
patients included in the study, 90.1% were female with a mean age of 36.4 +/-
12.0. A total of 59.0% of the patients were diagnosed with CDH and 41.0% were
diagnosed with migraine. Overall, 34.8% of all patients, 40.0% of CDH patients,
and 27.3% of migraine patients had a history of physical and/or sexual abuse. The
relative frequency of a history of physical and/or sexual abuse was higher in the
CDH group as compared to the migraine group (P = .048). CONCLUSION: The relative 
frequency of abuse is higher in CDH sufferers than migraineurs, suggesting that
physical and sexual abuse may be risk factors for chronification.

Publication Types: 
    Comparative Study

PMID: 17371356 [PubMed - indexed for MEDLINE]

853: Headache. 2007 Mar;47(3):384-96.

Evaluation of an electronic diary as a diagnostic tool to study headache and
premenstrual symptoms in migraineurs.

Goldberg J, Wolf A, Silberstein S, Gebeline-Myers C, Hopkins M, Einhorn K, Tolosa
JE.

Department of Obstetrics and Gynecology, Jefferson Medical College, Philadelphia,
PA 19107, USA.

OBJECTIVE: To evaluate an electronic diary as a tool to evaluate the occurrence
and relationship of headaches and premenstrual syndrome (PMS) symptoms throughout
the menstrual cycle in women with migraine. BACKGROUND: Menstrually related
headache and PMS significantly impact the quality of life of many women. The time
relationship of these 2 menstrually related problems is not well understood and
not well described. METHODS: Twenty women with migraine experiencing regular
menstrual cycles were enrolled in a prospective study designed to date- and
time-stamp data, both self- and computer-prompted, headache and PMS symptoms, for
3 consecutive months. A previously validated PMS score was calculated by grading 
23 PMS criteria on a scale of 0 to 3 (0 = no symptoms, 3 = severe symptoms).
RESULTS: The total number of data entries recorded was 2009, composed of 56
menstrual cycles in 20 migraineurs. Five hundred forty-four entries reported a
current, prodromal, or previous headache. The mean daily occurrence of headache
increased beginning on cycle day -5, peaked on days +1 to +5, and returned to
baseline by day +7. Mean daily PMS scores ranged from 2.4 to 12. Mean daily PMS
scores peaked on days -6 to +2 and returned to baseline by day +8. CONCLUSIONS:
An electronic diary may have potential as a diagnostic tool in studying headaches
and PMS symptoms throughout the menstrual cycle. The occurrence of headache and
PMS symptoms in migraineurs follows similar time courses.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17371355 [PubMed - indexed for MEDLINE]

854: Headache. 2007 Mar;47(3):364-70.

Intracortical inhibition and facilitation in migraine--a transcranial magnetic
stimulation study.

Siniatchkin M, Kröner-Herwig B, Kocabiyik E, Rothenberger A.

Department of Child Neurology, University of Kiel, Kiel, Germany.

OBJECTIVE: Migraine is a disease of altered cortical excitability between
attacks. However, the mechanisms of abnormal excitability in migraine are
insufficiently investigated. Hence, the aim of the study was to investigate
intracortical inhibition/facilitation of the motor circuit in migraine. METHODS: 
Sixteen women suffering from migraine without aura and 15 healthy women were
investigated using a suprathreshold transcranial magnetic stimulation (TMS) in
the paired-pulse paradigm with long interstimulus intervals (ISI = 20, 60, 120
ms) and measurement of the cortical silent period. RESULTS: We found no
differences for the cortical silent period and for the long intracortical
inhibition between the groups. Concerning intracortical facilitation, this
ability was significantly more pronounced in patients suffering from migraine
compared with healthy controls. CONCLUSION: Migraineurs produce an increased
intracortical facilitation. The results may be discussed in line of glutamatergic
mechanisms in migraine, which could be related to altered facilitation.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17371353 [PubMed - indexed for MEDLINE]

855: Headache. 2007 Mar;47(3):355-63.

Erratum in:
    Headache. 2007 Oct;47(9):1365.

Patterns of diagnosis and acute and preventive treatment for migraine in the
United States: results from the American Migraine Prevalence and Prevention
study.

Diamond S, Bigal ME, Silberstein S, Loder E, Reed M, Lipton RB.

Diamond Headache Clinic, Chicago, IL [corrected] USA.

OBJECTIVE: To describe the patterns of medical treatment for migraineurs in the
United States. BACKGROUND: Over the past decade, many new treatments for migraine
have become available and awareness of migraine has improved. However, there is
little information about the patterns of medical treatment in the US society.
DESIGN/METHODS: A validated self-administered headache questionnaire was mailed
to a random sample of 120,000 US households. Each household member with severe
headaches was asked to complete the survey. The questionnaire assessed headache
features, disability, and patterns of medical treatment. Subjects were classified
according to their use of headache preventive medication, as current users,
coincident users (using effective medications for other medical reasons), lapsed 
users (had used in the past but not at the time of the survey), or never users.
RESULTS: In 162,576 participants, the prevalence of migraine was 17.1% in women
and 5.6% in men. Only 56.2% of those with migraine had ever received a medical
diagnosis. Ninety-eight percent of the migraineurs used acute treatment for their
migraine attacks. Forty-nine percent (49%) usually used over-the-counters, 20%
usually used prescription medications, and 29% used both. Only 12.4% of
migraineurs indicated that they were taking a migraine preventive medication, but
17.2% were using medications with potential antimigraine effects for other
medical reasons. Current or past use of preventive medication was more likely in 
women than men (odds ratio [OR] = 1.37, 95% confidence interval [CI] 1.27-1.48), 
increased with age and individuals with high MIDAS grade (Grade IV vs I, OR 2.35,
95% CI 2.09-2.64). Preventive medication use increased with awareness of migraine
and with illness severity. CONCLUSIONS: Migraine remains undertreated in the US
population. Barriers to preventive treatment are greater in younger age groups,
men, and people unaware that they have migraine.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17371352 [PubMed - indexed for MEDLINE]

856: Curr Pain Headache Rep. 2007 Apr;11(2):154-7.

Cluster-migraine: does it exist?

Applebee AM, Shapiro RE.

Given C219B, Department of Neurology, University of Vermont College of Medicine, 
89 Beaumont Avenue, Burlington, VT 05405, USA. robert.shapiro@uvm.edu

The nosological boundaries between cluster headache and migraine are sometimes
ill-defined. Although the two disorders are distinct clinical entities, patients 
sometimes present with clinical scenarios having characteristics of both headache
types, but either do not fully meet International Classification of Headache
Disorders, Second Edition diagnostic criteria for either disorder or have
sufficient symptoms and signs to allow both diagnoses to be present. These
occasions provide diagnostic challenges and include what is variously described
as migraine-cluster, cyclical migraine, clustering episodes of migraine, cluster 
with aura, or atypical cluster without autonomic symptoms or severe pain.
Patients with symptoms overlapping cluster headache and migraine likely reflect
the inherent clinical variability in each of these two disorders, rather than
distinct diagnostic entities in their own right.

Publication Types: 
    Case Reports
    Review

PMID: 17367596 [PubMed - indexed for MEDLINE]

857: Int J Clin Exp Hypn. 2007 Apr;55(2):207-19.

Review of the efficacy of clinical hypnosis with headaches and migraines.

Hammond DC.

University of Utah School of Medicine, Salt Lake City, Utah 84132-2119, USA.
D.C.Hammond@utah.edu

The 12-member National Institute of Health Technology Assessment Panel on
Integration of Behavioral and Relaxation Approaches into the Treatment of Chronic
Pain and Insomnia (1996) reviewed outcome studies on hypnosis with cancer pain
and concluded that research evidence was strong and that other evidence suggested
hypnosis may be effective with some chronic pain, including tension headaches.
This paper provides an updated review of the literature on the effectiveness of
hypnosis in the treatment of headaches and migraines, concluding that it meets
the clinical psychology research criteria for being a well-established and
efficacious treatment and is virtually free of the side effects, risks of adverse
reactions, and ongoing expense associated with medication treatments.

Publication Types: 
    Review

PMID: 17365074 [PubMed - indexed for MEDLINE]

858: Curr Cardiol Rep. 2007 Mar;9(1):13-9.

Stroke and migraine.

Weinberger J.

Department of Neurology, Box 1052, The Mount Sinai School of Medicine, 1 Gustave 
Levy Place, New York, NY 10029, USA. jesse.weinberger@mssm.edu

Young patients with migraine are at increased risk for stroke, particularly
patients with an aura of focal neurologic deficits. Other causes of ischemia are 
often identified in patients with migraine, including patent foramen ovale, lupus
anticoagulant, cervical carotid dissection, arteriovenous malformation, and
hyperactivity of the clotting system. Migrainous stroke is only diagnosed when
all other possible causes of stroke have been eliminated and the patient has
irreversibility of the usual aura, associated with an ischemic infarct in the
appropriate brain territory. Prophylactic therapy of migraine with aura may be
beneficial in preventing migrainous stroke.

Publication Types: 
    Review

PMID: 17362679 [PubMed - indexed for MEDLINE]

859: Curr Cardiol Rep. 2007 Mar;9(1):7-12.

Correlation or causation: untangling the relationship between patent foramen
ovale and migraine.

Adler E, Love B, Giovannone S, Volpicelli F, Goldman ME.

The Mount Sinai School of Medicine, 1 Gustave L. Levy Place, Box 1030, New York, 
NY 10029, USA.

Observational evidence from the literature has shown an association between
migraine headaches and patent foramen ovale (PFO). This observation has led to
hypotheses that could explain the etiology of migraines in those with a PFO,
including right-to-left shunting of venous agents such as serotonin that are
normally broken down in the pulmonary circulation. Further evidence suggests that
closure of a PFO may improve migraine symptoms and serve as an effective
treatment modality for migraines. Several randomized controlled double-blinded
studies are underway that will more definitively establish the role of specific
devices in PFO closure in those suffering from migraines.

Publication Types: 
    Review

PMID: 17362678 [PubMed - indexed for MEDLINE]

860: J Headache Pain. 2007 Feb;8(1):63-6. Epub 2007 Feb 19.

Lessons from placebo effects in migraine treatment.

Antonaci F, Chimento P, Diener HC, Sances G, Bono G.

University Centre for Adaptive Disorders and Headache, Section of Varese, Italy. 
neuronet@libero.it

In medical research, the placebo effect is an important methodological tool.
Placebo is given to participants in clinical trials, with the intention of
mimicking an experimental intervention. The "nocebo" effect, on the other hand,
is the phenomenon whereby a patient who believes that a treatment will cause harm
actually does experience adverse effects. The placebo effect strongly influences 
the way the results of clinical trials are interpreted. Placebo responses vary
with the choice of study design, the choice of primary outcome measure, the
characteristics of the patients and the cultural setting in which the trial is
conducted. In migraine trials, the placebo response is high, in terms of both
efficacy and side effects. Although medical ethics committees are becoming
increasingly resistant to the use of placebo in acute migraine trials, placebo
nevertheless remains the pivotal comparator in trials of migraine medications.

PMID: 17361384 [PubMed - indexed for MEDLINE]

861: J Headache Pain. 2007 Feb;8(1):56-9. Epub 2007 Feb 19.

Cephalalgiaphobia: a possible specific phobia of illness.

Peres MF, Mercante JP, Guendler VZ, Corchs F, Bernik MA, Zukerman E, Silberstein 
SD.

Instituto Israelita de Ensino e Pesquisa, Albert Einstein, São Paulo, Brazil.
marioperes@yahoo.com

Psychiatric comorbidity, mainly anxiety and depression, are common in chronic
migraine (CM). Phobias are reported by half of CM patients. Phobic avoidance
associated with fear of headache or migraine attack has never been adequately
described. We describe 12 migraine patients with particular phobic-avoidant
behaviours related to their headache attacks, which we classified as a specific
illness phobia, coined as cephalalgiaphobia. All patients were women, mean age
42, and all had a migraine diagnosis (11 CM, all overused acute medications).
Patients had either a phobia of a headache attack during a pain-free state or a
phobia of pain worsening during mild headache episodes. Patients overused acute
medication as phobic avoidance. It is a significant problem, associated with
distress and impairment, interfering with medical care. Cephalalgiaphobia is a
possible specific phobia of illness, possibly linked to progression of migraine
to CM and to acute medication overuse headache.

PMID: 17361383 [PubMed - indexed for MEDLINE]

862: J Headache Pain. 2007 Feb;8(1):43-8. Epub 2006 Dec 10.

Health-related quality of life among Canadians with migraine.

Brna P, Gordon K, Dooley J.

IWK Health Centre, Department of Pediatrics, Division of Neurology, 5850
University Ave, Halifax, NS B3K 6R8, Canada. pbrna@hotmail.com

The objective was to determine the impact of migraine on health-related quality
of life (HRQOL) among Canadians. Analysis was based on the public use microdata
set of the Canadian Community Health Survey (CCHS), limited to those aged > or = 
15 residing in Manitoba. HRQOL was measured using the SF-36 survey, which covers 
8 health concepts. Multivariate linear regression was used to model each SF-36
scale against age, gender, education, income, migraine status and presence of
mood or anxiety disorders. Of the 7236 CCHS respondents, 9.7% reported a
diagnosis of migraine. Reported migraine predicted statistically significant
(p<0.0001) lower HRQOL in all SF-36 domains with profound impairment of physical 
role, bodily pain and general health. Those reporting a mood disorder scored
significantly lower in all domains with pronounced effects on emotional role,
social functioning and general health. Reported anxiety disorder was associated
with lower HRQOL in 6/8 domains. Canadians with migraine report significant
impairment in HRQOL compared to the general population, independent of
psychiatric morbidity.

Publication Types: 
    Comparative Study

PMID: 17361382 [PubMed - indexed for MEDLINE]

863: J Headache Pain. 2007 Feb;8(1):7-12. Epub 2007 Feb 19.

Migraine, patent foramen ovale and migraine triggers.

Tembl J, Lago A, Sevilla T, Solis P, Vilchez J.

Neurology Service, Universitary Hospital, La Fe, Avda Campanar 21, E-46009,
Valencia, Spain. tembl-jos@gva.es

Little information exists about a causal association between PFO and migraine.
Some patients identify Valsalva-provoking activities (VPA) as migraine triggers. 
Therefore, we speculate about a pathogenic connection. The object of the study is
to investigate the prevalence of right-to-left shunt (RLS) in a cohort of
patients suffering migraine with aura (MA) and its possible association with
migraine attacks triggered by VPA. We investigated the circumstances triggering
the migraine attacks, in a consecutive series of 72 MA patients and in a series
of migraine without aura age and gender-matched. The presence and extent of RLS
was assessed by transcranial Doppler. Massive RLS appeared in 38.9% of MA and in 
6.5% of migraine without aura (p<0.001). MA patients identified at least one VPA 
as headache trigger in 45.8%. A trend was found between these triggering
activities and massive RLS, both in MA group OR 2.7 [1.02-7.17] and in all
migraine patients OR 2.5 [1.01-6.11]. According to our results, patients with
migraine who have larger RLS tend to recognize activities that increase the
extent of the shunt as a trigger of their migraine attacks.

Publication Types: 
    Comparative Study

PMID: 17361381 [PubMed - indexed for MEDLINE]

864: Surv Ophthalmol. 2007 Mar-Apr;52(2):209-12.

Migraine and anisocoria.

Gilbert ME, Friedman D.

Neuro-ophthalmology Service, Wills Eye Hospital, Thomas Jefferson University,
Philadelphia, Pennsylvania 19107, USA.

A 42-year-old woman presents with headache and anisocoria. Gonioscopy suggested
narrow angles. Ultrasound biomicroscopy confirmed the diagnosis. The patient
underwent bilateral peripheral iridotomies with resolution of her symptoms. The
differential diagnosis of headache and anisocoria are reviewed. Plateau iris
syndrome and subacute angle closure are discussed.

Publication Types: 
    Case Reports
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 17355858 [PubMed - indexed for MEDLINE]

865: Eur J Neurol. 2007 Mar;14(3):269-75.

Crossover, double-blind clinical trial comparing almotriptan and ergotamine plus 
caffeine for acute migraine therapy.

Láinez MJ, Galván J, Heras J, Vila C.

Neurology Department, Hospital Clínic Universitari, University of Valencia,
Valencia, Spain. jlaineza@meditex.es

In this randomized, double-blind, crossover clinical trial, adult patients
treated two migraine attacks: one with almotriptan 12.5 mg and the other with
ergotamine 2 mg plus caffeine 200 mg. Treatment with almotriptan was associated
with a significantly greater proportion of patients achieving 2-h pain free
(20.9% vs. 13.7%; P < 0.05) and 2-h pain relief (57.7% vs. 44.5%; P < 0.01)
compared with ergotamine plus caffeine therapy; significant differences were not 
seen at 1 h. Rates for sustained pain free and sustained pain free plus no
adverse events (AEs) also were significantly greater after almotriptan treatment 
than after the use of ergotamine plus caffeine (P < 0.05). Almotriptan was
associated with a significantly lower rate of photophobia at 90 min (P < 0.05),
phonophobia at 60, 90, and 120 min (P < 0.05 to <0.01), and nausea and vomiting
at 90 and 120 min (P < 0.01) compared with ergotamine plus caffeine. A
significantly greater proportion of patients were more satisfied with almotriptan
than with ergotamine plus caffeine (P < 0.05). Sixteen patients reported adverse 
events during almotriptan treatment and 27 patients reported AEs during the
ergotamine plus caffeine therapy. Most AEs were mild-to-moderate and did not
result in treatment-related discontinuations. In conclusion, almotriptan was
associated with significantly greater efficacy for treating migraine compared
with ergotamine plus caffeine, was generally well tolerated and was associated
with greater rate of treatment satisfaction.

Publication Types: 
    Comparative Study
    Multicenter Study
    Randomized Controlled Trial

PMID: 17355546 [PubMed - indexed for MEDLINE]

866: Headache. 2007 Jan;47(1):130-1.

Hashimoto's encephalopathy mimicking migraine with aura.

Huete AJ, Sanchez-Del-Rio M, Franch O.

Department of Neurology, Hospital Ruber Internacional, Madrid, Spain.

We describe a patient with Hashimoto's encephalopathy presenting as long-standing
episodes of aphasia associated with migraine-like headache. Repeated thyroid
hormone levels were within normal values, but high titers of antithyroid
antibodies in serum, and diffuse EEG slowing and CSF abnormalities during one
episode led to the diagnosis.

Publication Types: 
    Case Reports

PMID: 17355509 [PubMed - indexed for MEDLINE]

867: Headache. 2007 Jan;47(1):127-30.

Hemicrania continua-like headache associated with internal carotid artery
dissection may respond to indomethacin.

Ashkenazi A, Abbas MA, Sharma DK, Silberstein SD.

Department of Neurology, Thomas Jefferson University Hospital, Philadelphia, PA
19107, USA.

Hemicrania continua (HC) is an idiopathic, chronic disorder characterized by a
continuous, strictly unilateral headache associated with ipsilateral cranial
autonomic symptoms. The symptoms of HC typically respond dramatically to
indomethacin therapy. We describe a patient with traumatic internal carotid
artery dissection, who presented with a clinical picture mimicking HC that
initially responded to indomethacin. Patients with a clinical picture similar to 
HC should be managed with a high index of suspicion for a possible cervical
arterial dissection.

Publication Types: 
    Case Reports

PMID: 17355508 [PubMed - indexed for MEDLINE]

868: Headache. 2007 Jan;47(1):123-7.

Migrainous visual auras: a life history.

Reinecke RD, Silberstein SD.

Foerderer Eye Movement Center for Children, Wills Eye Hospital, Philadelphia,
PA19107, USA.

We document, as an autobiographical case report, a 72-year history of migraine
and its changing nature. Minor neurological events have waxed and waned, causing 
repeated searches for pathology, but instead reconfirming an intact central
nervous system. In this case it appears that visual migraine auras do not reflect
severity of pathology. Visual auras of migraine are cyclical in frequency and
intensity and may have remissions as long as 15 years.

Publication Types: 
    Case Reports

PMID: 17355507 [PubMed - indexed for MEDLINE]

869: Headache. 2007 Jan;47(1):104-10.

Increased dilator response to nitrate and decreased flow-mediated dilatation in
migraineurs.

Yetkin E, Ozisik H, Ozcan C, Aksoy Y, Turhan H.

Department of Cardiology, Inonu University School of Medicine, Malatya, Turkey.

BACKGROUND: It has been known that in a migraine attack intracranial and
extracranial arteries on the headache side dilate and when the migraine attack
has subsided, the intracranial arteries show segmental narrowing. We hypothesized
that patients with migraine had an underlying systemic vasomotion abnormality and
there might be an increased nitrate-mediated vasodilatory response in the
brachial artery of migraineurs. Accordingly we aimed to measure endothelium
dependent and independent functions of brachial artery in migraineurs and healthy
subjects. MATERIALS AND METHODS: Twenty-four patients who fulfilled the
diagnostic criteria of migraine were enrolled in the study. Twenty-six age- and
sex-matched healthy control subjects comprised the control group. Flow-mediated
dilatation and nitrate-mediated dilatation were measured in all patients and
control subjects by means of brachial artery ultrasonography. RESULTS:
Flow-mediated dilatation of patients with migraine was significantly lower than
that of control subjects (7.6 +/- 3.7% vs 10.4 +/- 3.5%, respectively, P= .008). 
However, nitrate-mediated dilatation in migraineurs was significantly higher than
that of nonmigraineurs (25% vs 14%, respectively, P< .001). CONCLUSION: We have
shown that migraineurs have decreased endothelium dependent function whereas
increased nitrate-mediated response in their brachial artery. It can be suggested
that the mechanism underlying migraine may be a diffuse vascular vasomotion
abnormalities and migraine may be a local manifestation of systemic vascular
abnormality rather than a primary cerebral phenomenon.

Publication Types: 
    Controlled Clinical Trial

PMID: 17355503 [PubMed - indexed for MEDLINE]

870: Headache. 2007 Jan;47(1):73-80.

Coenzyme Q10 deficiency and response to supplementation in pediatric and
adolescent migraine.

Hershey AD, Powers SW, Vockell AL, Lecates SL, Ellinor PL, Segers A, Burdine D,
Manning P, Kabbouche MA.

Division of Neurology, Cincinnati Children's Hospital Medical Center, 3333 Burnet
Avenue, Cincinnati, OH 45229, USA.

BACKGROUND: Coenzyme Q10 (CoQ10) has been suggested to be effective in the
prevention of migraine, and levels can be quantified with standardized reference 
ranges. OBJECTIVE: This study documents the prevalence of CoQ10 deficiency in
migraine headache and examines the potential effectiveness of supplementation.
METHODS: We assessed patients attending a tertiary care center with frequent
headaches for CoQ10 deficiency. We recommended patients with low CoQ10 levels
begin supplementation with CoQ10 as part of their multidisciplinary treatment
plan. We assessed response to treatment including correction of CoQ10 deficiency,
overall headache improvement, and headache disability. RESULTS: CoQ10 was
measured in 1550 patients (mean age 13.3 +/- 3.5, range 3 to 22 years). The mean 
total CoQ10 level was 0.60 +/- 0.20 microg/mL (range 0.21 to 1.77 microg/mL). Of 
these patients, 32.9% were below the reference range. Patients with low CoQ10
were recommended to start 1 to 3 mg/kg per day of CoQ10 in liquid gel capsule
formulation. In a subset of patients who returned for timely follow-up (mean, 97 
days), the total CoQ10 level improved to 1.20 +/- 0.59 microg/mL (P < .0001),
while the headache frequency improved from 19.2 +/- 10.0 to 12.5 +/- 10.8 (P <
.001) and headache disability assessed with PedMIDAS improved from 47.4 +/- 50.6 
to 22.8 +/- 30.6 (P < .001). CONCLUSIONS: Deficiency of CoQ10 may be common in
pediatric and adolescent migraine. Determination of deficiency and consequent
supplementation may result in clinical improvement. Further analysis involving
more scientifically rigorous methodology will be required to confirm this
observation.

Publication Types: 
    Clinical Trial
    Research Support, Non-U.S. Gov't

PMID: 17355497 [PubMed - indexed for MEDLINE]

871: Headache. 2007 Jan;47(1):65-72.

Similarities and differences between chronic migraine and episodic migraine.

Ferrari A, Leone S, Vergoni AV, Bertolini A, Sances G, Coccia CP, Ottani A,
Pinetti D, Sternieri E.

Division of Toxicology and Clinical Pharmacology, Headache Centre, University
Centre for Adaptive Disorders and Headache, Section Modena II, University of
Modena and Reggio Emilia, Modena, Italy.

OBJECTIVE: To quantify and characterize the similarities and the differences
between chronic migraine (CM) patients with medication overuse and episodic
migraine (EM) patients with only occasional analgesic use. BACKGROUND:
Population-level epidemiology, characteristics, mechanisms of chronic daily
headache, and medication-overuse headache have been widely studied but patient
characteristics have received less attention. Methods.-We compared
sociodemographic data, family history, physiological and medical history, health 
services utilized, drugs taken/prescribed, and outcome of 2 groups of subjects:
150 patients, suffering from CM, complicated by probable medication-overuse
headache (CM group), consecutively admitted during 2005 to the inpatients' ward
of the Headache Centre of the University Hospital of Modena and Reggio Emilia,
Italy, to undergo withdrawal from their overused medications; 100 patients
suffering from EM, uncomplicated by medication overuse (EM group), consecutively 
referred to the outpatients' ward of the Headache Centre during November and
December 2005. RESULTS: All sociodemographic characteristics were significantly
different between the 2 groups. As a whole, the CM group began to suffer from
migraine earlier than the EM group. Drug and/or alcohol abuse was significantly
higher among first-degree relatives of CM (19%) than of EM (6%) patients. The
most frequent comorbid disorders were psychiatric (67%) and gastrointestinal
diseases (43%) in the CM group, and allergies in the EM group (31%). Seventy
percent of CM patients and 42% of EM patients were taking daily at least another 
drug, besides those for headache treatment. Most overused medications in the CM
group were triptans (43%); the EM group used above all single NSAIDs (56%). At
3-month follow-up, prophylactic treatments reduced, by at least 50%, the
frequency of headache in about three-fourths of patients of both the groups;
however, headache remained significantly more frequent in the CM than in EM
group: only a minority (15%) of CM patients reverted to a headache frequency
comparable to that of the EM group. CONCLUSIONS: CM patients present more
multiple comorbid disorders, polypharmacy, and social impediments than EM
patients. These associated conditions complicate CM clinical management. Even
after withdrawal from medication overuse, CM could not be completely reverted by 
current prophylactic treatments.

Publication Types: 
    Comparative Study

PMID: 17355496 [PubMed - indexed for MEDLINE]

872: Headache. 2007 Jan;47(1):52-7.

A randomized double-blind placebo-controlled trial of thioctic acid in migraine
prophylaxis.

Magis D, Ambrosini A, Sándor P, Jacquy J, Laloux P, Schoenen J.

Headache Research Unit, Neurology Department, University of Liège, Liège,
Belgium.

BACKGROUND: Impaired mitochondrial phosphorylation potential may play a role in
migraine pathogenesis. Metabolic enhancers, such as riboflavin or coenzyme Q, are
effective in migraine prophylaxis and quasi-devoid of adverse effects. Thioctic
acid (-lipoic acid) is another substance known to enhance energy metabolism in
mitochondria and to be beneficial in diabetic neuropathy. OBJECTIVE: After an
open pilot study suggesting its therapeutic antimigraine potentials, we embarked 
therefore in a randomized controlled trial of thioctic acid (Thioctacid) in
migraine prophylaxis steered by the Belgian Headache Society. METHODS: Five
Belgian centers recruited 54 migraineurs (43 migraine without aura, 11 with aura;
mean age 38 +/- 8 years; 7 males). After a 1-month single-blinded run-in period, 
44 patients received either placebo (n = 18) or thioctic acid 600 mg p.o./day (n 
= 26) for 3 months. RESULTS: Statistical analysis was carried out on an
intention-to-treat basis. Monthly attack frequency tended to be reduced between
run-in and the 3rd month of treatment in the thioctic acid group compared to
placebo (P= .06). The proportion of 50% responders was not significantly
different between thioctic acid (30.8%) and placebo (27.8%). Within-group
analyses showed a significant reduction of attack frequency (P= .005), headache
days (P= .009), and headache severity (P= .03) in patients treated with thioctic 
acid for 3 months, while these outcome measures remained unchanged in the placebo
group. No adverse effects were reported. For logistical reasons this trial was
interrupted before the planned 80 patients were enrolled. CONCLUSION: Albeit
underpowered, this study tends to indicate that thioctic acid may be beneficial
in migraine prophylaxis. Before any firm conclusion can be drawn, however, a
large multicenter trial is necessary.

Publication Types: 
    Multicenter Study
    Randomized Controlled Trial

PMID: 17355494 [PubMed - indexed for MEDLINE]

873: Headache. 2007 Jan;47(1):45-51.

Endothelial function in patients with migraine during the interictal period.

Silva FA, Rueda-Clausen CF, Silva SY, Zarruk JG, Guzmán JC, Morillo CA, Vesga B, 
Pradilla G, Flórez M, López-Jaramillo P.

Instituto de Investigaciones, Grupo de Ciencias Neurovasculares, Grupo de
Investigación en Sistema Nervioso Autónomo, Fundación Cardiovascular de Colombia,
Floridablanca, Colombia.

OBJECTIVES: The aim of this study is to evaluate endothelial function in
migraineurs subjects during the asymptomatic period. BACKGROUND: Migraine has
been proposed as a risk factor for cerebrovascular events. The underlying
mechanisms that relate these 2 pathologies are unknown. Nitric oxide (NO) has
been proposed as the final causative molecule of migraine. Increased NO
metabolites concentrations have been reported in migraineurs subjects during
acute migraine attacks, but there is no evidence indicating alterations in
endothelial NO release during the symptom free period in theses subjects. DESIGN 
AND METHODS: Fifty migraineurs subjects and 25 healthy subjects matched by gender
and age were included. Every subject underwent a complete examination that
included medical history, physical examination, resting electrocardiogram,
forearm flow-mediated vasodilation (FMD), blood determinations of fasting
nitrates and nitrites (NO(2) (-)+ NO(3) (-)), glucose, lipid profile, creatinine,
C-reactive protein, and blood cell count. RESULTS: No differences in FMD or NO(2)
(-)+ NO(3) (-) were detected among groups. The only difference between
migraineurs and control subjects was a higher mean blood pressure 92.1 (8.8) mmHg
versus 86.7 (8.2) mmHg P= .01. CONCLUSION: The endothelial function is not
altered during the interictal period in migraineurs subjects.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17355493 [PubMed - indexed for MEDLINE]

874: Headache. 2007 Jan;47(1):22-6.

Borderline personality disorder and migraine.

Rothrock J, Lopez I, Zweilfer R, Andress-Rothrock D, Drinkard R, Walters N.

University of South Alabama Headache Center, University of South Alabama College 
of Medicine, Mobile, AL, USA.

BACKGROUND: Borderline personality disorder (BPD) may be disproportionately
common in the migraine patient population, but specific migraine features in the 
BPD subgroup remain incompletely characterized. PURPOSE: To define more clearly
the clinical characteristics of migraine patients with BPD, to evaluate their
clinical response to aggressive headache management, and to assess the
sensitivity of an instrument intended to screen for the presence of BPD. METHODS:
We evaluated 50 consecutive patients with migraine and previously documented BPD,
50 consecutive patients with migraine of all types and no history of BPD, and 50 
patients with migraine and no history of BPD matched to the first group for age, 
gender, and headache frequency. We assessed a variety of demographic and clinical
variables at baseline, and to all patients we administered the McLean Screening
Instrument for Borderline Personality Disorder (MSI-BPD). Patients in Groups 1
and 3 were treated for their headaches via a uniform pharmacologic management
program. Treatment outcome was assessed after 6 months. RESULTS: In this series
of migraine patients, coexisting BPD was associated with female gender, more
pervasive headache, more migraine-related disability, a higher prevalence of
medication overuse headache, more unscheduled visits for acute migraine
treatment, a higher prevalence of active, self-reported depression, and a lower
likelihood of responding to pharmacologic therapy intended for headache
management. The MSI-BPD was insensitive in detecting BPD. CONCLUSIONS: Migraine
patients with coexisting BPD are clinically distinct from the migraine patient
population as a whole; in particular, they are more severely affected by their
headache disorder and more treatment refractory. Simple screening instruments
used to detect BPD may be ineffective in the headache clinic setting.

Publication Types: 
    Evaluation Studies

PMID: 17355490 [PubMed - indexed for MEDLINE]

875: Headache. 2007 Jan;47(1):13-21.

Topiramate in patients with episodic migraine: reducing the risk for chronic
forms of headache.

Limmroth V, Biondi D, Pfeil J, Schwalen S.

Department of Neurology, Cologne City Hospitals, Cologne, Germany.

OBJECTIVE: The aim was to evaluate whether preventive treatment with topiramate
in patients with episodic migraine reduces the risk of developing chronic forms
of headache. BACKGROUND: Chronic forms of headache, including chronic migraine or
medication overuse headache (MOH), are characterized by 15 or more headache days 
per month. Acute medication overuse has been shown to be a risk factor for
developing chronic headache, but it is not known whether preventive treatment can
reduce the risk of developing chronic forms of headache or the development of
MOH. METHODS: Pooled data from 3 trials in patients with episodic migraine
randomized either to treatment with 100 mg topiramate per day (n = 384) or with
placebo (n = 372) were analyzed with regard to the number of headache days during
a prospective 4-week baseline period and the individual final 4 weeks of each
patient's treatment during the planned 26-week double-blind treatment period.
RESULTS: The number of headache days per month in the topiramate versus the
placebo-treated groups was 7.3 +/- 3.0 versus 7.3 +/- 3.1 during baseline and 4.1
+/- 4.2 versus 5.6 +/- 4.9 during the final 4 weeks, respectively (P < .001). At 
the end of the study, 8 versus 16 patients fulfilled International Headache
Society criteria of chronic headache (odds ratio: 2.11, P= .082). Moreover, a
significantly lower number of patients receiving topiramate treatment reported an
increase in headache days per month by the end of the study when compared to
placebo (66 vs 88 patients, respectively; odds ratio: 1.49, P < .05). Finally,
the number of days with usage of acute medication was significantly lower in the 
topiramate arm compared with placebo (3.3 +/- 3.7 vs 4.3 +/- 3.6, respectively; P
< .001). CONCLUSION: Preventive treatment with topiramate in patients with
episodic migraine may reduce the risk of developing chronic forms of headache.

Publication Types: 
    Multicenter Study
    Randomized Controlled Trial

PMID: 17355489 [PubMed - indexed for MEDLINE]

876: J Neurol. 2007 Jun;254(6):789-96. Epub 2007 Mar 12.

Increased serotonin transporter availability in the brainstem of migraineurs.

Schuh-Hofer S, Richter M, Geworski L, Villringer A, Israel H, Wenzel R, Munz DL, 
Arnold G.

Dept. of Neurology, Charité-Universitätsmedizin Berlin, Berlin, Germany.
sigrid.schuh-hofer@gmx.net

For decades, serotonin has been speculated to play a major role in migraine
pathophysiology. The central serotonergic system is located in the raphe nuclei
and the adjacent reticular formation in the brainstem. Recently, radioligands
targeting the brain serotonin transport protein (SERT) have been developed. We
used the highly specific SERT-radioligand (123)I-ADAM [2-((2-((dimethylamino)
methyl)phenyl)thio)-5-iodophenylamine] to test the hypothesis of the mesopontine 
serotonergic system being involved in the pathophysiology of migraine. Nineteen
migraine patients and 10 healthy, age- and sex-matched controls were enrolled.
The neuroimaging study was performed interictally during the pain-free interval. 
Single Photon Emission Computed Tomography (SPECT)-images were coregistered with 
MRI-scans. Region of interest (ROI)-analysis revealed a highly significant
increase of (123)I-ADAM uptake in the mesopontine brainstem of migraineurs (p <
0.001). In contrast, (123)IADAM uptake in the thalamus did not differ
significantly between migraineurs and controls. Our study demonstrates for the
first time a significant increase of brainstem SERT-availability in migraineurs, 
suggesting a dysregulation of the brainstem serotonergic system. It remains to be
elucidated whether the altered SERT-availability is causally related to migraine 
pathophysiology or whether it reflects secondary pathophysiological mechanisms.

PMID: 17351723 [PubMed - indexed for MEDLINE]

877: J Occup Environ Med. 2007 Mar;49(3):252-7.

Impact of topiramate migraine prophylaxis on workplace productivity: results from
two US randomized, double-blind, placebo-controlled, multicenter trials.

Lofland JH, Gagne JJ, Pizzi LT, Rupnow M, Silberstein SD.

Department of Health Policy (Drs Lofland, Gagne, and Pizzi), Jefferson Medical
College, Thomas Jefferson University, Philadelphia, PA 19107, USA.
jennifer.lofland@jefferson.edu

OBJECTIVE: We conducted this study to determine whether topiramate at 100 mg/d
for the treatment of migraine headache is associated with improved productivity
in the workplace. METHODS: Results were derived from two randomized,
double-blind, placebo-controlled trials among migraineurs. The number of hours of
absenteeism (A), presenteeism (P), and total lost productivity (TLP) (A + P) were
calculated. Results were not adjusted for multiplicity. RESULTS: A total of 325
(162 in the topiramate group and 163 in the placebo group) of 449 subjects were
included. Per person mean monthly A rate was only significantly less for
individuals within the topiramate group (1.0 hours per person) versus those in
the placebo group (1.5 hours per person) for month 3 (P < 0.05). Per person mean 
P and TLP rates were significantly lower for individuals in the topiramate group 
versus those in the placebo group for months 1 through 5 (P < 0.05). CONCLUSIONS:
Findings suggest that topiramate, compared with placebo, is associated with
decreased workplace presenteeism and TLP.

Publication Types: 
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 17351510 [PubMed - indexed for MEDLINE]

878: Cephalalgia. 2007 Apr;27(4):368-71. Epub 2007 Mar 7.

Migraine and coronary heart disease mortality: a prospective cohort study.

Liew G, Wang JJ, Mitchell P.

Centre for Vision Research, Department of Ophthalmology (Westmead Hospital), the 
Westmead Millennium Institute, University of Sydney, Sydney, Australia.

A recent population-based prospective study reported that in women, migraine with
aura (MA), but not migraine without aura (MoA), was associated with increased
risk of coronary heart disease events (CHD). We sought to confirm this
association in an Australian population-based cohort of older men and women (n = 
2331, aged 49-97 years). We defined MA and MoA from face-to-face interview using 
International Headache Society criteria. Over a mean 6-year follow-up, 30 women
(2.8%) and 30 men (4.4%) without any prior CHD history died from CHD-related
causes. In women, a history of MA was associated with a non-significant twofold
higher risk of CHD death (age-adjusted relative risk 2.2, 95% confidence interval
0.8, 5.8, P = 0.11), which remained similar after adjustment for cardiovascular
risk factors. There were no CHD deaths in men with a history of migraine. Our
findings support reports that in women, MA, but not MoA, may be associated with
increased risk of CHD.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17346306 [PubMed - indexed for MEDLINE]

879: J Chin Med Assoc. 2007 Feb;70(2):39-46.

Intranasal sumatriptan study with high placebo response in Taiwanese patients
with migraine.

Wang SJ, Fuh JL, Wu ZA.

Neurological Institute, Taipei Veterans General Hospital and National Yang-Ming
University School of Medicine, Taipei, Taiwan, ROC. sjwang@vghtpe.gov.tw

BACKGROUND: Triptan's efficacy in the treatment of migraine has never been
reported in Taiwanese. A high placebo effect was reported in Japanese. The
objective of this study was to evaluate the efficacy of intranasal sumatriptan in
the acute treatment of migraine in Taiwanese patients. METHODS: Fifty-eight
patients who had experienced migraine for at least 1 year were randomly assigned 
to 2 groups, self-administered intranasal sumatriptan 20 mg or placebo to treat a
single migraine attack of moderate or severe intensity. RESULTS: A significant
difference in headache relief rates between the 2 groups was observed at 30
minutes postdose (46% vs. 21%, p < 0.05). One hour postdose, 61% of sumatriptan
recipients experienced headache relief compared with 43% of placebo recipients (p
= 0.181). The difference in relief rates between groups diminished over time,
mainly due to a high placebo response (54% at 2 hours postdose). CONCLUSION: Our 
study suggests that ethnicity might have a role in placebo response, and
highlights the importance of a placebo group in acute migraine trials. However,
the small sample size in this study should also be taken into consideration.

Publication Types: 
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 17339143 [PubMed - indexed for MEDLINE]

880: Trends Pharmacol Sci. 2007 Apr;28(4):188-95. Epub 2007 Mar 6.

Antiepileptic drugs in migraine: from clinical aspects to cellular mechanisms.

Calabresi P, Galletti F, Rossi C, Sarchielli P, Cupini LM.

Clinica Neurologica, Università degli Studi di Perugia, Ospedale S. Maria della
Misericordia, Perugia 06156, Italy. calabre@unipg.it

Migraine and epilepsy share several clinical features, and epilepsy is a comorbid
condition of migraine. Clinical studies have shown that some antiepileptic drugs 
are effective at preventing migraine attacks. A rationale for their use in
migraine prophylaxis is the hypothesis that migraine and epilepsy share several
common pathogenetic mechanisms. An imbalance between excitatory
glutamate-mediated transmission and GABA-mediated inhibition in specific brain
areas has been postulated in these two pathological conditions. Moreover,
abnormal activation of voltage-operated ionic channels has been implicated in
both migraine and epilepsy. Cortical spreading depression has been found to be
involved in the pathophysiology of epilepsy, in addition to the generation of
migraine aura.

Publication Types: 
    Review

PMID: 17337068 [PubMed - indexed for MEDLINE]

881: J Neurol. 2007 Feb;254(2):242-9. Epub 2007 Mar 2.

Patient preference in migraine therapy. A randomized, open-label, crossover
clinical trial of acute treatment of migraine with oral almotriptan and
rizatriptan.

Díez FI, Straube A, Zanchin G.

Department of Neurology, Hospital General Yagüe, Avda. Del Cid 96, 09005 Burgos, 
Spain. iglesias@hgy.es

OBJECTIVE: To assess patient preference for almotriptan 12.5 mg vs rizatriptan 10
mg for the acute treatment of migraine. METHODS: Randomized, multicenter,
open-label, crossover trial in which triptan-naïve patients treated two
moderate/severe migraine attacks, the first with one triptan and the second with 
the other: 183 patients took rizatriptan followed by almotriptan and 189 treated 
in the reverse order. Patient preference was assessed with a self-administered
questionnaire. RESULTS: Of those recording a preference (209), 54.5% preferred
almotriptan, but statistical significance was not achieved. The main reason for
preference for one or the other triptan was efficacy: 43% of patients preferring 
almotriptan gave faster headache relief as the reason and 34% cited faster return
to normal activities. The corresponding values for rizatriptan were 47% and 38%. 
A significantly greater proportion of those preferring almotriptan cited fewer
adverse events (AEs) as the reason. Almotriptan and rizatriptan were of
comparable efficacy and both treatments were well tolerated; 9% of patients
experienced AEs probably or possibly related to study medication after
almotriptan vs 14% after rizatriptan. Almotriptan was associated with a
significantly lower incidence of triptan-associated AEs in triptan-naïve patients
(8.5% vs 18% with rizatriptan). CONCLUSION: Physicians should use information
from meta-analyses and preference studies like this one to aid in the selection
of a triptan with a high likelihood of providing rapid, sustained relief from
pain coupled with an absence of AEs. About 55% of patients recording a preference
in this trial preferred almotriptan, perhaps because of its combination of good
efficacy and lower incidence of triptan-associated AEs.

Publication Types: 
    Clinical Trial
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 17334957 [PubMed - indexed for MEDLINE]

882: East Mediterr Health J. 2006 Nov;12(6):809-17.

Prevalence of migraine and tension-type headache in primary-school children in
Shiraz.

Ayatollahi SM, Khosravi A.

Department of Biostatistics and Epidemiology, School of Public Health, Shiraz
University of Medical Science, Shiraz, Islamic Republic of Iran.
ayatolahim@sums.ac.ir

From January to June 2003 we determined the prevalence of the various types of
headache in 2226 schoolchildren in Shiraz (age 6-13 years) selected by multistage
random sampling. Data were collected by questionnaire and clinical examination.
International Headache Society criteria were used for diagnosis. The overall
prevalence of headache was 31%. Prevalence rates of migraine and tension-type
headache were 1.7% and 5.5% respectively. The prevalence of headache increased
with age and girls were significantly more likely to report tensions-type
headache. Positive family history of headache and abnormal sleep pattern were
significantly associated with migraine.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17333827 [PubMed - indexed for MEDLINE]

883: Med Sci Monit. 2007 Mar;13(3):RA47-9.

Autonomic dysfunction and cardiac repolarization abnormalities in patients with
migraine attacks.

Melek IM, Seyfeli E, Duru M, Duman T, Akgul F, Yalcin F.

Department of Neurology, Faculty of Medicine, Mustafa Kemal University, Hatay,
Turkey. ismetmelek@yahoo.com

The clinical symptoms of migraine are widely accepted to be related to the
involvement of the autonomic nervous system, and especially to dysfunction in the
regulation of the circulatory system and autonomic balance. Disturbance of the
autonomic nervous system is a primary characteristic of migraine Therefore,
patients with migraine have a variety of symptoms, such as vasodilatation
(flushing), pilo-erection, nausea, vomiting, diarrhea, cutaneous vasoconstriction
(pallor), and diaphoresis. The electrocardiographic changes seen during a
migraine attack compared with the pain-free period could be secondary to
reversible disturbances of the state of autonomic innervation of the heart and
coronary arteries. Dysfunction of ANS may affect atrial and ventricular
repolarization. For instance, increased sympathetic activity causes sinus
tachycardia, but increased parasympathetic activity causes sinus bradycardia,
atrioventricular block, and ST-segment and T-wave abnormalities. Comprehensive
electrocardiographic analyses have been providing more details in terms of the
detection of abnormalities in atrial and ventricular repolarization which
potentially may result in arrhythmias in patients with migraine. However, there
is no information in literature reporting the frequency of cardiac arrhythmias in
migraine patients who had cardiac repolarization abnormalities. In this review,
detailed electrocardiographic findings and their relation with the autonomic
nervous system, including recent observations, have been evaluated. However,
further studies are needed to investigate the association between autonomic
dysregulation and cardiac repolarization abnormalities in patients with migraine.

Publication Types: 
    Review

PMID: 17325646 [PubMed - indexed for MEDLINE]

884: AAOHN J. 2007 Feb;55(2):51-6.

Migraine disorder: workplace implications and solutions.

Berry PA.

Occupational Health and Safety Nursing, University of Cincinnati College of
Nursing, Cincinnati, OH, USA.

Migraine disorder is disabling, costly, underdiagnosed, and undertreated. It
affects employees' quality of life and ability to work or attend school,
potentially decreasing their earning ability. Migraine disorder impacts the
workplace substantially through absenteeism and presenteeism and increases health
care costs. Although research on migraine disorder is expansive, no systematic
research tool or design exists within population studies. This may account for
the different prevalence rates seen, especially in African studies, which rely on
verbal interviews instead of mail or telephone surveys. Women have a higher
prevalence rate throughout the research, but they seek help more often than men. 
This may contribute to their higher rates, although hormones also play a role.
Occupational health nurses can affect the outcome of migraine disorder for
employees and employers. They can assist in identifying those employees with
migraine disorder who are not diagnosed, those who have not investigated the
various available medications, or the lifestyle changes that would decrease the
intensity and frequency of migraine attacks. Research is needed to quantify the
cost savings of workplace intervention in identifying employees with migraine
disorder and its effect on absenteeism, presenteeism, and health care use.
Occupational health nurses can determine the effectiveness of education by
measuring motivation, lifestyle changes, and workplace modification against the
intensity and frequency of migraine attacks. This, in turn, will yield measurable
results in reducing absenteeism and presenteeism in the workplace. Occupational
health nurses can spread this information through employees to their families. As
more undiagnosed and undertreated individuals with migraine become educated and
pursue diagnosis, treatment, and lifestyle changes, a measurable decrease in
health care use and costs may occur. The economic impact of migraine disorder, in
terms of workplace absenteeism and presenteeism and increased health care use by 
employees, continues to be of great concern. This impact may motivate employers
to support workplace interventions that educate, screen, and refer migraineurs to
appropriate care. Employers may also be motivated to request that a managed care 
model for migraine be included in health and welfare programs, which would allow 
for assignment of a nurse case manager with automatic referral to a neurologist. 
The workplace is an ideal environment for identifying and referring migraine
sufferers who only self-treat for symptoms. Prompt and effective treatment, in
and out of the workplace, will decrease the frequency and intensity of migraine
attacks and increase the quality of life.

Publication Types: 
    Review

PMID: 17323870 [PubMed - indexed for MEDLINE]

885: Brain Dev. 2007 Sep;29(8):482-5. Epub 2007 Feb 23.

Prevalence and features of migraine in Japanese junior high school students aged 
12-15 yr.

Ando N, Fujimoto S, Ishikawa T, Teramoto J, Kobayashi S, Hattori A, Togari H.

Department of Pediatrics, Neonatology and Congenital Disorders, Nagoya City
University, Graduate School of Medical Sciences, Kawasumi, Mizuho-cho, Mizuho-ku,
Nagoya 467-8601, Japan. nando@med.nagoya-cu.ac.jp

Migraine is the most common cause of recurrent headache among children and
adolescents resulting in missing of school and disabling their daily life. The
purpose of this study is to determine the prevalence and clinical features of
headache in junior high school children in Japan. In December 2004,
questionnaires were sent to 14 junior high schools. There were multiple-choice
type questions on headache, mainly migraine. The questionnaires were given during
school hours, and 6472 answers were obtained. One thousand four hundred
seventy-eight (22.8%) students experienced severe headache and 476 (7.4%) had
consulted physicians. Three hundred thirteen (4.8%) were identified as having
migraine based on the ICHD-II criteria, consisting of 110/3346 boys (3.3%) and
203/3126 girls (6.5%): 91 (29.1%) with aura and 222 (70.9%) without aura. In
about half of the children the migraine attacks were of short duration, ranging
from 1 to 3 h. There were 36 boys (1.1%) and 45 girls (1.4%) who had shorter
attacks of less than 1 h, whom we did not diagnose as having migraine according
to the ICHD-II criteria. Although migraine is common among schoolchildren, it is 
often under- or miss-diagnosed since the clinical figure for childhood migraine
differs from that for adults.

PMID: 17321091 [PubMed - indexed for MEDLINE]

886: Arch Otolaryngol Head Neck Surg. 2007 Feb;133(2):170-6.

Expanding the differential diagnosis of chronic dizziness.

Staab JP, Ruckenstein MJ.

Department of Psychiatry, The Balance Center, University of Pennsylvania Health
System, Philadelphia, PA, USA.

OBJECTIVE: To improve treatment outcomes for patients with chronic dizziness by
identifying clinical conditions associated with persistent symptoms and
delineating key diagnostic features that differentiate its causes and direct
attention to specific treatments. DESIGN: Prospective cohort study from 1998 to
2004. SETTING: Tertiary care balance center. PATIENTS: A total of 345 men and
women, aged 15 to 89 years, referred for evaluation of chronic dizziness
(duration of > or =3 months) of uncertain cause. INTERVENTIONS: Patients were
systematically directed through multiple specialty examinations until definitive 
diagnoses were made. MAIN OUTCOME MEASURE: Final diagnoses associated with
dizziness. RESULTS: Nearly all patients with chronic subjective dizziness were
diagnosed with psychiatric or neurologic illnesses. These included primary and
secondary anxiety disorders (n = 206 [59.7%]) and central nervous system
conditions (n = 133 [38.6%]), specifically migraine headaches, mild traumatic
brain injuries, and neurally mediated dysautonomias. A small number of patients
(6 [1.7%]) had dysrhythmias. Four of 5 patients with migraine or dysrhythmias had
comorbid anxiety. CONCLUSIONS: Chronic dizziness has several common causes,
including anxiety disorders, migraine, traumatic brain injuries, and
dysautonomia, that require different treatments. Key features of the clinical
history distinguish these illnesses from one another and from active neurotologic
conditions. The high prevalence of secondary anxiety may give a false impression 
of psychogenicity.

PMID: 17309987 [PubMed - indexed for MEDLINE]

887: Headache. 2007 Feb;47(2):329-40.

Hormonal management of migraine associated with menses and the menopause: a
clinical review.

Loder E, Rizzoli P, Golub J.

Department of Neurology, Harvard Medical School, Boston, MA, USA.

OBJECTIVE: This article reviews hormonal strategies used to treat headaches
attributed to the menstrual cycle or to peri- or postmenopausal estrogen
fluctuations. These may occur as a result of natural ovarian cycles, or in
response to the withdrawal of exogenously administered estrogen. BACKGROUND: A
wide variety of evidence indicates that cyclic ovarian sex steroid production
affects the clinical expression of migraine. This has led to interest in the use 
of hormonal treatments for migraine. METHODS: A PubMed search of the literature
was conducted using the terms
"migraine,""treatment,""estrogen,""hormones,""menopause," and "menstrual
migraine." Articles were selected on the basis of relevance. RESULTS: The
overarching goal of hormonal treatment regimens for migraine is minimization of
estrogen fluctuations. For migraine associated with the menstrual cycle,
supplemental estrogen may be administered in the late luteal phase of the natural
menstrual cycle or during the pill-free week of traditional combination oral
contraceptives. Modified contraceptive regimens may be used that extend the
duration of active hormone use, minimize the duration or extent of hormone
withdrawal, or both. In menopause, hormonally associated migraine is most likely 
to be due to estrogen-replacement regimens, and treatment generally involves
manipulating these regimens. Evidence regarding the safety and efficacy of these 
regimens is limited. CONCLUSIONS: Hormonal treatment of migraine is not a
first-line treatment strategy for most women with migraine. Evidence is lacking
regarding its long term harms and migraine is a contraindication to the use of
exogenous estrogen in all women with aura and those aged 35 or older. The harm to
benefit balances of several traditional nonhormonal therapies are better
established.

Publication Types: 
    Review

PMID: 17300386 [PubMed - indexed for MEDLINE]

888: Headache. 2007 Feb;47(2):289-93.

A migraine-like headache induced by carotid-cavernous fistula.

Yamada SM, Masahira N, Shimizu K.

Carotid-cavernous fistula (CCF) generally causes periorbital aching with ocular
symptoms due to high venous pressure in the cavernous sinus, while migraine is
caused by arterial dilatation-stimulating trigeminal nerves around the vessels.
The authors present a case of 47-year-old woman with a 4-month history of a
temporal throbbing headache. As her symptoms were well controlled by triptans,
her headache was considered to be migraine in type. However, a Barrow's type-D
CCF was revealed by radiological examinations. Self-compression of common carotid
artery method was initially tried for therapy of the CCF, but endovascular
embolization was finally necessary due to intractable headache. Although the
headache was considered arterial in origin, transvenous embolization of the left 
cavernous sinus successfully ameliorated the patient's symptoms. CCF should be
considered as an unusual etiology of headaches that appear arterial in origin.

Publication Types: 
    Case Reports
    Letter

PMID: 17300373 [PubMed - indexed for MEDLINE]

889: Headache. 2007 Feb;47(2):287-9.

Symptomatic occipital epilepsy misdiagnosed as migraine.

Menon B.

Two young patients with symptomatic occipital lobe epilepsy due to discrete
lesions of cysticercosis were misdiagnosed and treated for 2 years as migraine
with visual aura. The patients suffered from frequent visual seizures often
followed by migraine-like headache. Seizures manifested with colored and mainly
circular elementary visual hallucinations of up to 1 minute duration. Headache,
often severe and of long duration, was frequently associated with nausea,
photophobia, and phonophobia. Both patients became seizure-free with appropriate 
treatment of the underlying disease and epileptic seizures.

Publication Types: 
    Case Reports
    Letter

PMID: 17300372 [PubMed - indexed for MEDLINE]

890: Headache. 2007 Feb;47(2):280-3.

Comment in:
    Headache. 2008 Mar;48(3):479.

MRA captures vasospasm in fatal migrainous infarction.

Marshall N, Maclaurin WA, Koulouris G.

A 57-year-old woman presented with an escalation of her headaches which
ultimately progressed to multiple strokes and death. MRI/MRA demonstrated diffuse
vasospasm and other causes of stroke were excluded on premortem investigation and
postmortem examination. Reversible MRI abnormalities, vasospasm on angiogram and 
fatal migrainous infarction have been previously reported; however, no previous
case with this combination of clinical, imaging, and postmortem findings has been
documented.

Publication Types: 
    Case Reports
    Letter

PMID: 17300370 [PubMed - indexed for MEDLINE]

891: Headache. 2007 Feb;47(2):253-65.

Influence of MTHFR genotype on contingent negative variation and MRI
abnormalities in migraine.

de Tommaso M, Difruscolo O, Sardaro M, Losito L, Serpino C, Pietrapertosa A,
Santeramo MT, Dicuonzo F, Carella A, Lamberti P, Livrea P.

Neurologic and Psychiatric Sciences, Neurological Clinical Section, University of
Bari, Italy.

BACKGROUND: The MTHFR C677T genotype has been associated with increased risk of
migraine, particularly of migraine with aura (MA) in selected clinical samples
and with elevated homocysteine. The hyper-homocysteinemia may favor the vascular 
and neuronal mechanism underlying migraine, and the risk of stroke. OBJECTIVE:
The first aim of the present study was to examine the Contingent Negative
Variation (CNV) amplitude and habituation pattern in a migraine sample versus
non-migraine subjects, at the light of the MTHFR genotype, according to an
unrelated and clinical based case-control panel. The second aim was to compare
the frequency of Magnetic Resonance Imaging (MRI) subclinical brain lesions
across the different C677 genotypes in the same migraine sample, selected for the
young age and the absence of any cardiovascular risk factor. METHODS: One hundred
and five 18-45 year old out-patients, 90 affected by migraine without aura (MO)
and 15 by MA, and 97 non-migraine healthy subjects, age and sex matched, were
selected for the genetic analysis. All subjects had a common ethnic origin from
Puglia. Sixty-four migraine subjects and 33 control subjects were submitted to
the recording of the CNV. All migraine subjects underwent the MRI evaluation.
RESULTS: The frequency of homozygosis was 14.33% in normal subjects, versus 25.7%
in MA + MO group (chi2-test: 10.80 P= .001). The frequency of homozygosis in MO
patients, was 25.5% (MA versus N: chi2-test: 9 P= .003), in MA group it was
26.6%. Considering the MTHFR genotype in migraine patients and controls, the
C677TT subjects exhibited a reduced habituation index of the early CNV (iCNV), in
respect with both C677TC and C677CC; in the migraine group, there was a
significant decrease of CNV habituation in patients with homozygosis and a
positive correlation between the habituation index values and the homocysteine
levels. Nineteen migraine patients exhibited subclinical brain lesions (18.05%): 
patients with C677T homozygosis did not exhibit a higher risk for MRI
abnormalities. CONCLUSIONS: This unrelated and clinical based case-control study 
showed that genetically induced hyper-homocysteinemia may favor the neuronal
factors predisposing to migraine, while it does not influence the presence of
subclinical vascular brain lesions probably linked with increased risk of stroke.

PMID: 17300365 [PubMed - indexed for MEDLINE]

892: Headache. 2007 Feb;47(2):247-52.

Clarification of developing and established clinical allodynia and pain-free
outcomes.

Landy SH, McGinnis JE, McDonald SA.

Wesley Headache Clinic, Memphis, TN 38018, USA.

OBJECTIVE: The aim of this study was to determine whether clinical indicators of 
cutaneous allodynia predict the success of migraine therapy with sumatriptan
using a brief questionnaire. BACKGROUND: Using quantitative sensory testing (QST)
recent studies demonstrate that the presence of cutaneous allodynia, a clinical
manifestation of central sensitization, can be detrimental to the success of
migraine therapy with sumatriptan. QST is costly and requires much time,
therefore it is not feasible to use in clinical practice. METHODS: In this
prospective study, migraineurs completed a questionnaire about their skin
sensitivity during migraine. Each migraineur treated 2 migraine headaches with
sumatriptan (100 mg): 1 headache at the earliest sign of migraine pain (mild,
within 1 hour of onset) and 1 headache at least 4 hours after the onset of pain
while moderate or severe. RESULTS: Thirty-six migraine headaches were evaluated
in 18 migraineurs. A total of 44% of the headaches were not associated with
allodynia at any time. Irrespective of allodynic status, headaches were more
likely to become pain-free with early versus late treatment (2 hours; 78% vs.
33%, respectively). Headaches were equally likely to become pain-free when
allodynia was reported before treatment but not 2 and 4 hours after treatment (2 
hours; 67 vs. 63%, respectively, 4 hours 80 vs. 81%, respectively). However, no
headaches were pain-free when allodynia was reported at 2 and 4 hours after
treatment. CONCLUSIONS: Headaches without allodynia were aborted when treated
early or late, and headaches with allodynia were aborted only when allodynia was 
not present after treatment. These findings suggest that different mechanisms
account for allodynia before and after treatment; a developing phase in which
central sensitization depends on incoming pain signals from the peripheral
nociceptors and an established phase in which the sensitization becomes
independent of the pain signals that come from the dura.

Publication Types: 
    Clinical Trial
    Research Support, Non-U.S. Gov't

PMID: 17300364 [PubMed - indexed for MEDLINE]

893: Headache. 2007 Feb;47(2):236-46.

Rat carotid artery responses to alpha-adrenergic receptor agonists and 5-HT after
ovariectomy and hormone replacement.

Mehrotra S, Gupta S, Villalón CM, Boomsma F, Saxena PR, MaassenVanDenbrink A.

Department of Pharmacology, Erasmus MC, University Medical Center Rotterdam,
Rotterdam, The Netherlands.

OBJECTIVE: To compare the contractile responses to alpha-adrenergic receptor
agonists and 5-HT in the rat carotid artery after ovariectomy and subsequent
hormone replacement with 17beta-estradiol, progesterone, or the combination of
17beta-estradiol and progesterone. BACKGROUND: The prevalence of migraine is
higher in women than in men, and changes in 17beta-estradiol levels seem to
affect the frequency of attacks in female migraineurs. However, the underlying
mechanisms are not yet completely understood. METHODS: After 1 week of
acclimatization (Day 0), female Sprague-Dawley rats were either sham-operated or 
bilateral ovariectomized. One week later (Day 7), the ovariectomized rats were
subcutaneously implanted with a pellet releasing over a 21-day period either
placebo, 0.25 mg 17beta-estradiol, 50 mg progesterone, or the combination of the 
2 hormones. Blood samples were collected on Days 0, 7, and 21 to measure plasma
norepinephrine and epinephrine. On days 25 to 28, the animals were killed to
isolate carotid artery and mount its segments in Mulvany myographs. Cumulative
concentration response curves to alpha-adrenergic receptor agonists and 5-HT were
constructed in the absence or presence of suitable antagonists. RESULTS: The
potency of norepinephrine in ovariectomized rats was significantly reduced in
animals treated with progesterone as compared to those with placebo. In
placebo-treated ovariectomized animals there was a noticeable response mediated
by alpha2-adrenoceptors, in contrast to that in sham-operated or ovariectomized
rats treated with 17beta-estradiol and progesterone, either alone or in
combination. The plasma levels of norepinephrine and epinephrine were not
significantly affected by either ovariectomy or the subsequent hormone
replacement. The potency of 5-HT was significantly reduced in animals having
circulating sex hormones as compared to that in placebo-treated ovariectomized
animals. CONCLUSION: Taken together, our results indicate that circulating
progesterone and/or 17beta-estradiol may reduce the contraction of the rat
carotid artery in response to norepinephrine and 5-HT. This effect of female sex 
hormones might be one of the factors through which these hormones aggravate
migraine in women.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17300363 [PubMed - indexed for MEDLINE]

894: Headache. 2007 Feb;47(2):225-35.

Female sex hormones and rat dural vasodilatation to CGRP, periarterial electrical
stimulation and capsaicin.

Gupta S, Villalón CM, Mehrotra S, de Vries R, Garrelds IM, Saxena PR,
MaassenVanDenbrink A.

Department of Pharmacology, Erasmus MC, University Medical Center Rotterdam,
Rotterdam, The Netherlands.

BACKGROUND: The prevalence of migraine is 2 to 3-fold higher in females than in
males, and it is intricately related to the levels of female sex hormones. These 
hormones may regulate the synthesis and receptor expression of calcitonin
gene-related peptide (CGRP), which mediates neurogenic dural vasodilatation and
is implicated in migraine pathogenesis. OBJECTIVE: To investigate the effects of 
the female sex steroids, 17beta-estradiol and progesterone, separately and in
combination, on dural vasodilatation induced by alphaCGRP, periarterial
electrical stimulation and capsaicin in ovariectomized rats, using intravital
microscopy. METHODS: Sprague-Dawley rats were ovariectomized and, 7 days later,
subcutaneously implanted with 21-day release pellets of 17beta-estradiol,
progesterone, their combination or placebo. On day 19 to 21, the animals were
anesthetized, overlying bone thinned to visualize the middle meningeal artery and
vasodilator responses to alphaCGRP (10 to 3000 ng kg(-1)), periarterial
electrical stimulation (25 to 125 microA) and capsaicin (0.3 to 18 microg kg(-1))
elicited. RESULTS: There were no significant differences in the vasodilator
potency or efficacy of alphaCGRP or capsaicin in the different groups studied. In
contrast, the vasodilator response to electrical stimulation was significantly
higher in rats treated with 17beta-estradiol (Emax:157 +/- 19%) as compared to
those observed after placebo treatment (Emax:93 +/- 11%). CONCLUSION: Our results
show that, in contrast to CGRP- or capsaicin-induced dural vasodilatation,
17beta-estradiol enhanced neurogenic vasodilatation, suggesting increased CGRP
release from perivascular nerves. This may be one of the mechanisms through which
17beta-estradiol exacerbates migraine in women.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17300362 [PubMed - indexed for MEDLINE]

895: Headache. 2007 Feb;47(2):213-24.

The Sinus, Allergy and Migraine Study (SAMS).

Eross E, Dodick D, Eross M.

Scottsdale Headache Center at Arizona Neurological Institute, Scottsdale, AZ
85255, USA. ericeross@yahoo.com

OBJECTIVE: The objective of this study is to classify (according to the current
International Headache Society's criteria [ICHD-II]) the headache types that
those with self-diagnosed sinus headache experience and to determine barriers to 
correct diagnosis. BACKGROUND: The American Migraine Study II estimates that 28
million Americans suffer from migraine headache. The majority of these patients
remain undiagnosed and many are erroneously diagnosed as having sinus headache.
Despite this common diagnosis, the concept of sinus headache remains an enigma
with a relative paucity of information in the literature. METHODS: Advertising in
the greater Phoenix, U.S. metropolitan area was used to recruit 100 willing and
consecutive subjects to participate in this descriptive clinical study (The
Sinus, Allergy and Migraine Study [SAMS]). All patients who believed they
suffered from sinus headache and were over 18 years of age were enrolled without 
exclusion. A detailed history and exam was performed in each patient, and
patients were given headache diagnoses based on the current International
Headache Society's (IHS) criteria. RESULTS: Of the 100 subjects with
self-diagnosed headache, IHS diagnoses mistaken as sinus headache included
migraine with or without aura (52%), chronic migraine associated with medication 
overuse versus probable medication overuse headache (11%), probable migraine
(23%), cluster headache (1%), hemicrania continua (1%), headache secondary to
rhinosinusitis (3%), and headaches nonclassifiable (9%). Weather changes (83%),
seasonal variation (73%), exposure to allergens (62%), and changes in altitude
(38%) were frequent migraine triggers. Seventy-six percent of migraine subjects
reported pain in the distribution of the second division of the trigeminal nerve 
(either unilateral or bilateral), and 62% experienced bilateral forehead and
maxillary pain with their headaches. The most common associated features included
nasal congestion (56%), eyelid edema (37%), rhinorrhea (25%), conjunctival
injection (22%), lacrimation (19%), and ptosis (3%). The headaches
nonclassifiable were characterized by a bilateral maxillary pressure of mild to
moderate intensity associated with at least one cranial autonomic symptom.
Features suggestive of migraine were absent in all 9 of these nonclassifiable
cases. CONCLUSIONS: The majority of those with self-diagnosed sinus headache have
migraine or probable migraine. In those patients with migraine, the most common
reasons for misdiagnosis include headache triggers, pain location, and associated
features ("guilt by provocation, location, and association") commonly attributed 
to sinus headache. The clinician must be aware of these unique presentations of
migraine so that a correct diagnosis can be made and effective treatment
instituted. A portion of patients with self-diagnosed sinus headache suffer from 
a headache type, which is unclassifiable by the current IHS criteria. These
headaches are characterized by bilateral maxillary pressure, mild to moderate
pain intensity, cranial autonomic symptoms, and the complete absence of migraine 
features.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17300361 [PubMed - indexed for MEDLINE]

896: Headache. 2007 Feb;47(2):204-12.

Is headache related to asthma, hay fever, and chronic bronchitis? The Head-HUNT
Study.

Aamodt AH, Stovner LJ, Langhammer A, Hagen K, Zwart JA.

Norwegian National Headache Centre, Trondheim University Hospital, Norway.

OBJECTIVES: To examine the relationship between migraine and nonmigrainous
headache and asthma, hay fever, and chronic bronchitis in a large cross-sectional
population-based study. BACKGROUND: Associations between prevalence of migraine
and asthma or allergy have been demonstrated in clinic-based and epidemiologic
studies whereas studies on chronic bronchitis are scarce. METHODS: A total of
51,383 subjects completed a headache questionnaire and constituted the
"Head-HUNT" Study. Of these 50,401 (98.1%) answered the questions about asthma
and chronic bronchitis, and 47,029 (91.5%) answered the question about hay fever.
Associations were assessed in multivariate analyses, estimating prevalence odds
ratios (ORs) with 95% confidence intervals (CI). RESULTS: Both migraine and
nonmigrainous headache were approximately 1.5 times more likely among those with 
current asthma, asthma related symptoms, hay fever, and chronic bronchitis than
those without. The association increased with increasing headache frequency.
CONCLUSIONS: This large questionnaire-based study confirms that migraine and
other headaches are associated with respiratory and allergic disorders. The
magnitude of the association between headache and asthma, hay fever, and chronic 
bronchitis tended to be in the same order. Headache frequency seems to have a
greater impact on the association with respiratory or allergic conditions than
headache diagnoses. Whether it is a causal relationship is uncertain, but the
results underline the importance of considering comorbid disorders among patients
with frequent headache.

PMID: 17300360 [PubMed - indexed for MEDLINE]

897: Headache. 2007 Feb;47(2):189-98.

Early intervention with almotriptan: results of the AEGIS trial (AXERT Early
Migraine Intervention Study).

Mathew NT, Finlayson G, Smith TR, Cady RK, Adelman J, Mao L, Wright P, Greenberg 
SJ; AEGIS Investigator Study Group.

Houston Headache Clinic, Houston, TX 77004, USA.

OBJECTIVE: To evaluate prospectively the efficacy and safety of almotriptan 12.5 
mg as compared to placebo when administered within 1 hour of headache pain onset 
for the acute treatment of 3 migraine headaches. BACKGROUND: Although clinical
trials have reported improved outcomes when triptans were used early or to treat 
mild pain, acceptance of this treatment strategy has been hampered by both
efficacy and tolerability issues. METHODS: In this multicenter, double-blind,
placebo-controlled, parallel-group trial, patients with IHS-migraine were
randomized in a 1:1 ratio to treat 3 consecutive migraine attacks with either
almotriptan 12.5 mg or placebo. Patients were instructed to take their study
medication at the first sign of headache pain of any intensity, within 1 hour of 
onset, and to record their symptoms at multiple time points during their
headaches using a personal digital assistant. Clinical trial efficacy results for
the first study headache and safety data for the entire study are presented.
RESULTS: A total of 378 patients were randomized, 189 to each group; 162
almotriptan-treated patients, and 155 placebo-treated patients were evaluable for
efficacy. Almotriptan treatment, compared to placebo, resulted in a significantly
greater proportion of patients achieving 2-hour pain free (37.0% vs 23.9%, P=
.010), 2-hour pain relief (72.3% vs 48.4%, P < .001) and sustained pain free
(24.7% vs 16.1%, P= .040). Significant differences in pain free (P= .026) and
pain relief (P= .019) between almotriptan and placebo also were observed at 1
hour. At 2 to 4 hours and 4 to 24 hours after treatment, the mean intensity of
phonophobia and photophobia were significantly lower in the patients treated with
almotriptan compared to the placebo-treated patients. A greater proportion of
patients treating with almotriptan versus placebo reported normal functionality
within 2 hours postdose (54.4% vs 38.1%, P= .007) and 4 hours postdose (74.5% vs 
54.3%, P < .001). The percentage of patients experiencing 1 or more
treatment-emergent adverse events (AE) was 9.8% for almotriptan and 6.4% for
placebo. The only treatment-emergent AEs that occurred with a frequency of at
least 1% (equivalent to 2 or more patients) in the almotriptan and placebo
groups, respectively, were somnolence (1.1% and 2.3%), nausea (1.1% and 1.7%),
vomiting (1.1% and 0.6%), and fatigue (1.1% and 0%). CONCLUSION: Treatment with
almotriptan within 1 hour of migraine onset resulted in significantly better
clinical outcomes than placebo and tolerability similar to placebo. Acute
medications, such as almotriptan, that are both effective and well tolerated may 
encourage patients to access acute treatment earlier.

Publication Types: 
    Multicenter Study
    Randomized Controlled Trial

PMID: 17300358 [PubMed - indexed for MEDLINE]

898: Headache. 2007 Feb;47(2):170-80.

Comment in:
    Nat Clin Pract Neurol. 2007 Aug;3(8):434-5.

Efficacy and safety of topiramate for the treatment of chronic migraine: a
randomized, double-blind, placebo-controlled trial.

Silberstein SD, Lipton RB, Dodick DW, Freitag FG, Ramadan N, Mathew N, Brandes
JL, Bigal M, Saper J, Ascher S, Jordan DM, Greenberg SJ, Hulihan J; Topiramate
Chronic Migraine Study Group.

Jefferson Headache Center, Philadelphia, PA 19107, USA.

OBJECTIVE: To evaluate the efficacy and safety of topiramate (100 mg/day)
compared with placebo for the treatment of chronic migraine. METHODS: This was a 
randomized, placebo-controlled, parallel-group, multicenter study consisting of
16 weeks of double-blind treatment. Subjects aged 18 to 65 years with 15 or more 
headache days per month, at least half of which were migraine/migrainous
headaches, were randomized 1:1 to either topiramate 100 mg/day or placebo. An
initial dose of topiramate 25 mg/day (or placebo) was titrated upward in weekly
increments of 25 mg/day to a maximum of 100 mg/day (or to the maximum tolerated
dose). Concomitant preventive migraine treatment was not allowed, and acute
headache medication use was not to exceed 4 days per week during the double-blind
maintenance period. The primary efficacy endpoint was the change from baseline in
the mean monthly number of migraine/migrainous days; the change in the mean
monthly number of migraine days also was analyzed. A fixed sequence approach (ie,
gatekeeper approach) using analysis of covariance was used to analyze the
efficacy endpoints. Assessments of safety and tolerability included physical and 
neurologic examinations, clinical laboratory parameters, and spontaneous reports 
of clinical adverse events. RESULTS: The intent-to-treat population included 306 
(topiramate, n = 153; placebo, n = 153) of 328 randomized subjects who provided
at least 1 efficacy assessment; 55.8% of the topiramate group and 55.2% on
placebo were trial completers. The mean final topiramate maintenance dose was
86.0 mg/day. The mean duration of therapy was 91.7 days for the topiramate group 
and 90.6 days for the placebo group. Topiramate treatment resulted in a
statistically significant mean reduction of migraine/migrainous headache days
(topiramate -6.4 vs placebo -4.7, P= .010) and migraine headache days relative to
baseline (topiramate -5.6 vs placebo -4.1, P= .032). Treatment-emergent adverse
events occurred in 132 (82.5%) and 113 (70.2%) of topiramate-treated and
placebo-treated subjects, respectively, and were generally of mild or moderate
severity. Most commonly reported adverse events in the topiramate group were
paresthesia (n = 46, 28.8%), upper respiratory tract infection (n = 22, 13.8%),
and fatigue (n = 19, 11.9%). The most common adverse events in the placebo group 
were upper respiratory tract infection (n = 20, 12.4%), fatigue (n = 16, 9.9%),
and nausea (n = 13, 8.1%). Discontinuations due to adverse events occurred in 18 
(10.9%) topiramate subjects and 10 (6.1%) placebo subjects. There were no serious
adverse events or deaths. CONCLUSIONS: Topiramate treatment at daily doses of
approximately 100 mg resulted in statistically significant improvements compared 
with placebo in mean monthly migraine/migrainous and migraine headache days.
Topiramate is safe and generally well tolerated in this group of subjects with
chronic migraine, a burdensome condition with important unmet treatment needs.
Safety and tolerability of topiramate were consistent with experience in previous
clinical trials involving the drug.

Publication Types: 
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 17300356 [PubMed - indexed for MEDLINE]

899: Catheter Cardiovasc Interv. 2007 Apr 1;69(5):740-6.

Is patent foramen ovale closure effective in reducing migraine symptoms? A
controlled study.

Kimmelstiel C, Gange C, Thaler D.

Cardiac Catheterization Laboratory, Division of Cardiology, Department of
Medicine, Tufts-New England Medical Center, Boston, Massachusetts 02111, USA.
ckimmelstiel@tufts-nemc.org

OBJECTIVES: We investigated the prevalence of migraine in patients with patent
foramen ovale (PFO), and the effect of PFO closure on migraine symptoms and
medications. BACKGROUND: Studies have shown an association between migraine and
PFO. Data have recently suggested a reduction in migraine symptoms following PFO 
closure. Most of these studies had no controls. METHODS: Subjects were divided
into three groups: No PFO (Controls, n = 65), PFO with no intervention ("Open
PFO", n = 63), and PFO treated with percutaneous closure ("Closed PFO", n = 41). 
We measured the frequency, severity, and impact of migraine on quality of life
employing MIDAS scores. Comparisons were made preceding and 90 days after either 
transesophageal echocardiography (Controls and "Open PFO") or PFO closure
("Closed PFO"). We compared the use of abortive medications between the two time 
points. RESULTS: Migraine, especially with aura, was more prevalent in both PFO
groups (P < 0.05). Migraine frequency was reduced by 83% in Closed PFO compared
with 0% of Open PFO and 10% of control patients (P < 0.0001). Migraine severity
and MIDAS scores were reduced by PFO closure when compared to the other two
groups (P < 0.0001, P = 0.035 respectively). Reduction in abortive medications
was noted in 71% after closure, 5% of Open PFO, and 10% of Controls (P < 0.001). 
CONCLUSIONS: In this controlled study, migraine, especially with aura, is more
frequent in subjects with PFO. PFO closure is associated with a reduction in
migraine frequency and severity, as well as an improvement in MIDAS scores. PFO
closure was associated with a significant reduction in the use of abortive
medications.

PMID: 17295330 [PubMed - indexed for MEDLINE]

900: J Clin Epidemiol. 2007 Mar;60(3):280-7. Epub 2006 Oct 2.

Randomized trial vs. observational study of acupuncture for migraine found that
patient characteristics differed but outcomes were similar.

Linde K, Streng A, Hoppe A, Weidenhammer W, Wagenpfeil S, Melchart D.

Centre for Complementary Medicine Research, Department of Internal Medicine II,
Technische Universität München, Munich, Germany. Klaus.Linde@lrz.tum.de

OBJECTIVE: To compare patient characteristics and outcomes between a randomized
controlled trial (RCT) and an observational study (OS) of acupuncture treatment
in patients with migraine. STUDY DESIGN AND SETTING: Within the framework of a
research program for acupuncture for chronic pain, both an RCT and an OS of
routine care were performed in patients with migraine. One hundred forty-five
patients received acupuncture in the RCT and 732 in the OS. All patients
completed a pain questionnaire, including instruments evaluating disability,
quality of life, and depression, at baseline and at 6-month follow-up. RESULTS:
At baseline, patients participating in the RCT had a significantly longer history
of complaints and more headache days but better quality of life and fewer
depressive symptoms than patients participating in the OS. In unadjusted
analyses, improvements after 6 months were more pronounced in the OS than in the 
RCT. After adjustment for potential confounders, the differences decreased but
were still significant for several outcomes. CONCLUSION: Participants of the RCT 
were probably not representative of migraine patients undergoing acupuncture
treatment in routine care under current regulations in Germany. However, changes 
after treatment were similar in the RCT and the OS of routine care.

Publication Types: 
    Comparative Study
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 17292022 [PubMed - indexed for MEDLINE]

901: Eur J Pain. 2007 Oct;11(7):764-72. Epub 2007 Feb 8.

Neck flexor muscle fatigue in adolescents with headache: an electromyographic
study.

Oksanen A, Pöyhönen T, Metsähonkala L, Anttila P, Hiekkanen H, Laimi K, Salminen 
JJ.

Department of Physical and Rehabilitation Medicine, Turku University Central
Hospital, FIN-20521, Turku, Finland. airi.oksanen@tyks.fi

BACKGROUND: Muscular disorders of the neck region may be of importance for the
etiology of tension-type headache. However, in adolescents, there are no data on 
the association between neck muscle fatigue and headache. AIM: To study
differences in fatigue characteristics of the neck flexor muscles in adolescents 
with and without headache. METHODS: A population-based sample of 17-year-old
adolescents with migraine-type headache (N=30), tension-type headache (N=29) and 
healthy controls without headache (N=30) was examined. Surface EMG data were
recorded from the sternocleidomastoid (SCM) muscles bilaterally during an
isometric neck flexor endurance test. The spectral median frequency (MF) change
during the total endurance time (TMF) and the initial time of 30s (IMF) was
calculated. The intensity of discomfort in the neck area was assessed with the
visual analogue scale (VAS). RESULTS: The rate of decline in TMF of both SCM
muscles was significantly increased in the tension-type headache group compared
with controls (right SCM, P=0.030, OR 2.0, 95% 1.2-3.7; left SCM, P=0.009, OR
2.5, 95% 1.4-4.9), while no significant differences were found between controls
and subjects with migraine. The rate of decline in IMF, the total endurance time 
(P=0.050), and VAS did not differ significantly among the study groups.
CONCLUSIONS: This preliminary finding shows that increased neck flexor muscle
fatigue in adolescents seems to be associated with tension-type headache.

PMID: 17291797 [PubMed - indexed for MEDLINE]

902: Mayo Clin Proc. 2007 Jan;82(1):61-8.

Twelve-month tolerability and safety of sumatriptan-naproxen sodium for the
treatment of acute migraine.

Winner P, Cady RK, Ruoff GE, Frishberg BM, Alexander WJ, Zhang Y, Kori SH, Lener 
SE.

Palm Beach Headache Center, 4631 N Congress Ave, Suite 200, West Palm Beach, FL
33407, USA. eneuro@aol.com

OBJECTIVES: To evaluate the long-term safety and tolerability of
sumatriptan-naproxen sodium for the treatment of moderate to severe acute
migraines and to assess the safety of administration of an optional second dose. 
PATIENTS AND METHODS: A 12-month, multicenter, open-label safety study was
conducted in adults treated for migraine attacks of moderate to severe intensity 
from April 14, 2004, to August 18, 2005. Safety evaluations included adverse
events and laboratory tests. RESULTS: Of 600 patients enrolled, 565 (94%) were
treated for at least 1 migraine. Of treated patients, 414 (73%) and 362 (64%)
completed 6 and 12 months of treatment, respectively. Of the 24,485 attacks
treated, 17,144 (70%) were treated with only 1 dose. On average, patients treated
5 migraine attacks per month, with a median of 6 days between attacks. The most
common treatment-related adverse events were nausea, muscle tightness, and
dizziness. Fourteen patients reported 1 or more serious adverse event with only 1
judged probably related to treatment. No deaths occurred. Eight percent of
patients discontinued participation in the study because of adverse events or
pregnancy. The rates of adverse events reported were no higher after treatment
with 2 tablets (at least 2 hours apart) compared with 1 tablet. CONCLUSIONS: In
this 12-month data set of more than 24,000 migraine attacks in 565 patients,
sumatriptan-naproxen sodium formulated in a single tablet was well tolerated when
used episodically for the treatment of acute migraine. The adverse events did not
differ from those expected for the individual components alone, and no new or
unexpected findings occurred.

Publication Types: 
    Clinical Trial
    Multicenter Study
    Research Support, Non-U.S. Gov't

PMID: 17285787 [PubMed - indexed for MEDLINE]

903: Exp Brain Res. 2007 Jul;180(3):517-23. Epub 2007 Feb 6.

Preserved dynamic cerebral autoregulation in the middle cerebral artery among
persons with migraine.

Reinhard M, Wehrle-Wieland E, Roth M, Niesen WD, Timmer J, Weiller C, Hetzel A.

Department of Neurology and Clinical Neurophysiology, University of Freiburg,
Neurocenter, Breisacherstr. 64, 79106 Freiburg, Germany.
matthias.reinhard@uniklinik-freiburg.de

Migraine affects the autonomous nervous system and a recent investigation has
also proposed a severe disturbance of dynamic cerebral blood flow regulation in
the middle cerebral artery during spontaneous blood pressure oscillations. This
study investigates whether dynamic cerebral autoregulation is impaired in persons
with migraine among a normal cohort. Out of 94 adults studied to establish normal
values for dynamic autoregulation, 19 suffered from migraine according to IHS
criteria (10 of them with aura). Transcranial Doppler sonography and
fingerplethysmography were used to determine dynamic autoregulation of both
middle cerebral arteries following spontaneous low frequency (0.06-0.12 Hz) blood
pressure fluctuations (phase and gain of transfer function, correlation
coefficient indices Dx and Mx). No significant differences were found for the low
frequency variability of blood pressure (power spectral density) and various
indices of dynamic cerebral autoregulation between persons with and without
migraine. Moreover, no differences were observed between persons with migraine,
with and without aura. This study based on a normal cohort does not support the
presence of generally impaired cerebral autoregulation dynamics in persons with
migraine. Future studies should focus on posterior circulation and particular
cerebellar autoregulation.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17279380 [PubMed - indexed for MEDLINE]

904: Neuro Endocrinol Lett. 2007 Feb;28(1):59-64.

Safety and efficacy of intravenous sodium valproate in the treatment of acute
migraine.

Waberzinek G, Marková J, Mastík J.

Medical Faculty, Charles University Prague, Hradec Králové, Czech Republic.
waberzinekg@fnhk.cz

This multicenter study investigated the safety and efficacy of intravenous
valproate in acute migraine attacks and the possible impact of prophylactic
valproate pre-treatment. Thirty-six patients established on migraine prophylaxis 
were administered 500 mg sodium valproate intravenously against acute migraine
attacks. Pain development was assessed by visual analogue scale up to a 24 hours 
follow up interview to detect e.g. possible relapse symptoms. A subgroup analysis
examined whether prophylactic treatment with valproate affected its acute
anti-migraine efficacy. A meaningful headache reduction within two hours was
achieved in all 12 patients with and in 20 out of 24 patients without valproate
prophylaxis. Headache-associated signs and symptoms were substantially reduced.
No serious side-effects were reported. The results confirm the therapeutic value 
of intravenous valproate in acute migraine attacks described in literature and
show a beneficial effect on all investigated efficacy parameters with a trend to 
even better response in patients receiving valproate prophylaxis.

Publication Types: 
    Clinical Trial
    Multicenter Study

PMID: 17277725 [PubMed - indexed for MEDLINE]

905: Manag Care Interface. 2006 Dec;19(12):31-8.

Cost effectiveness of topiramate in the prevention of migraines in the United
States: an update.

Brown JS, Rupnow MF, Neumann P, Friedman M, Menzin J.

Boston Health Economics, Inc., Waltham, Massachusetts 02451, USA.

A previously published decision-analytic model assessing the clinical and
economic consequences of topiramate versus no preventive treatment in migraineurs
was updated with new published literature and unpublished clinical trial data.
The model captured baseline migraine days, treatment discontinuation, treatment
response (i.e., > or = 75%, 50%-74%, and < 50% reduction in migraine frequency), 
hours of disability, cost of preventive therapy, cost of acute treatment
(pharmacy and medical service), and wages. Topiramate was associated with 29
fewer migraine-days and 78 fewer hours of disability per year, compared with no
preventive treatment. The incremental cost per migraine-day averted for
topiramate versus no preventive treatment was dollar 29 when only direct medical 
costs were considered and dollar 2 when total costs were included. Model results 
were sensitive to baseline migraine-days, response probability, and probability
of an attack being treated with a triptan. Topiramate may be a cost-effective
treatment for the prevention of migraine.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17274479 [PubMed - indexed for MEDLINE]

906: J Psychosom Res. 2007 Feb;62(2):139-43.

Childhood adversities experienced by working-age migraine patients.

Sumanen M, Rantala A, Sillanmäki LH, Mattila KJ.

University of Tampere, Medical School, Tampere, Finland.
markku.sumanen@kolumbus.fi <markku.sumanen@kolumbus.fi>

OBJECTIVE: The objective of this work was to study associations between childhood
adversities and migraine. METHODS: This is a case-control study of individuals
drawn from the Finnish Population Register comprising four age groups: 20-24,
30-34, 40-44, and 50-54 years. Altogether, 21,101 individuals responded to postal
questionnaire (response rate=40%). The subjects were asked whether a doctor had
told them that they have or have had migraine. They were then requested (through 
six questions) to think about their childhood adversities. One randomly selected 
age-matched and sex-matched control for comparison was selected for every patient
(n=4046). RESULTS: Among migraine patients, 76.8% were women. Each of the six
childhood adversities was more common among migraine patients than among
controls. In conditional logistic regression analysis for matched-pairs data,
long-lasting financial difficulties in the family, a family member having been
seriously or chronically ill, serious conflicts in the family, and parents having
divorced remained statistically significant after adjusting for education, state 
of health, and depression. Odds ratios varied between 1.22 and 1.29. CONCLUSION: 
Our findings suggest that social factors during childhood are associated with
migraine.

PMID: 17270571 [PubMed - indexed for MEDLINE]

907: J Pharmacol Exp Ther. 2007 May;321(2):564-72. Epub 2007 Jan 31.

Effects of pan- and subtype-selective N-methyl-D-aspartate receptor antagonists
on cortical spreading depression in the rat: therapeutic potential for migraine.

Peeters M, Gunthorpe MJ, Strijbos PJ, Goldsmith P, Upton N, James MF.

MRI Group, Neurology and GI Centre of Excellence in Drug Discovery,
GlaxoSmithKline, New Frontiers Science Park (North), Third Ave., Harlow, Essex
CM19 5AW, UK.

Spreading depression (SD) has long been associated with the underlying
pathophysiology of migraine. Evidence that the N-methyl-D-aspartate (NMDA)
glutamate receptor (NMDA-R) is implicated in the generation and propagation of SD
has itself been available for more than 15 years. However, to date, there are no 
reports of NMDA-R antagonists being developed for migraine therapy. In this
study, an uncompetitive, pan-NMDA-R blocker, memantine, approved for clinical
use, and two antagonists with selectivity for NMDA-R containing the NR2B subunit,
(1S,2S)-1-(4-hydroxyphenyl)-2-(4-hydroxy-4-phenylpiperidino)-1-propanol
(CP-101,606) and
(+/-)-(R*,S*)-alpha-(4-hydroxyphenyl)-beta-methyl-4-(phenylmethyl)-1-piperidine
propanol (Ro 25-6981), were investigated to assess their protective effects
against SD in the rat. Under isoflurane anesthesia, d.c. potential and the
related cortical blood flow and partial pressure of O2 (pO2) were recorded
simultaneously at separate cortical sites. Drugs (1, 3, and 10 mg/kg i.p.) were
given 1 h or 30 min before KCl application to the brain surface. Core temperature
and arterial pCO2,pO2, and pH measurements confirmed physiological stability. KCl
induced 7.7+/-1.8 (mean+/-S.D.) SD events with d.c. amplitude of 14.9+/-2.8 mV.
Memantine and CP-101,606 dose-dependently decreased SD event number (to 2.0+/-1.8
and 2.3+/-2.9, respectively) and SD amplitude at doses relevant for therapeutic
use. Ro 25-6981 also decreased SD events significantly, but less effectively (to 
4.5+/-1.6), without affecting amplitude. These results indicate that
NR2B-containing NMDA receptors are key mediators of SD, and as such, memantine-
and NR2B-selective antagonists may be useful new therapeutic agents for the
treatment of migraine and other SD-related disorders (e.g., stroke and brain
injury). Whether chronic, rather than acute, treatment may improve their efficacy
remains to be determined.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17267580 [PubMed - indexed for MEDLINE]

908: Brain. 2007 Jun;130(Pt 6):1690-703. Epub 2007 Jan 30.

Exploring the visual hallucinations of migraine aura: the tacit contribution of
illustration.

Schott GD.

The National Hospital for Neurology and Neurosurgery, Queen Square, London, UK.
geoffrey.schott@uclh.nhs.uk

The visual aura of migraine is a subjective phenomenon, and what the migraineur
experiences is necessarily inaccessible to others. Fortunately, however, the
sufferer can occasionally reveal what is being seen by means of graphic
representation, enabling an otherwise closed 'window' to be opened on the
transiently dysfunctioning brain. This article explores the unique contribution
that illustration has made to understanding mechanisms subserving the visual
aura. The most revealing illustrations are those made by the very few scientists 
who have recorded and analysed the scotomas, and in particular the expanding
fortification spectra, experienced during their migraine attacks. It is solely
through illustrations such as these that the uniform nature of many of these
hallucinations has been demonstrated. As a result, it follows that there is
likely to be a similarly uniform repertoire of processes that generate the
hallucinations in the occipital cortex. The precise form of the zigzags that
comprise the fortification spectrum, their shimmering appearance, and in
particular the speed of the peripheral spread, all of which are entirely
dependent on graphic display for their elucidation, enable conclusions to be
reached about a number of the underlying pathophysiological mechanisms, including
the involvement of spreading cortical depression, that likely occur. Illustration
has been pivotal too in revealing uncommon and sometimes curious, if not bizarre,
visual hallucinations, the forms of which suggest that extrastriate and temporal 
lobe involvement contributes to migraine aura in some instances. Illustration can
also be valuable in differential diagnosis, depicting other forms of visual
hallucination which result from a variety of non-migrainous causes. Illustration,
particularly when made during the attack, provides an unusual, little used but
powerful tool which uniquely allows the sufferer's subjective visual experiences 
to inform objective analysis. In turn, this analysis leads to insights into some 
of the cerebral disturbances which subserve migraine aura.

Publication Types: 
    Review

PMID: 17264093 [PubMed - indexed for MEDLINE]

909: Cephalalgia. 2007 Mar;27(3):220-34.

Probable migraine in the United States: results of the American Migraine
Prevalence and Prevention (AMPP) study.

Silberstein S, Loder E, Diamond S, Reed ML, Bigal ME, Lipton RB; AMPP Advisory
Group.

Jefferson Headache Center, Philadelphia, PA, USA.

Probable migraine (PM) is a prevalent migraine subtype fulfilling all but one
criterion for migraine with or without aura. The aims of this study were: (i) to 
describe the epidemiology, medical recognition and patterns of treatment for PM
in the USA; (ii) to compare the patterns of preventive PM treatment in the
population with expert panel guidelines for preventive treatment. A validated
self-administered headache questionnaire was mailed to a random sample of 120,000
US households. Subjects were classified as PM according to the second edition of 
the International Classification of Headache Disorders (ICHD-2). The
questionnaire also assessed patterns of migraine treatment. Guidelines for
preventive medication use were developed by a panel of headache experts, who used
headache frequency and impairment to assess the need for preventive therapy and
the gap between current and ideal use. Our sample consisted of 162 576
individuals aged > or = 12 years. The 1-year period prevalence of PM was 4.5%
(3.9% in men and 5.1% in women). In women and men, prevalence was higher in
middle life, between the ages of 30 and 59 years. The prevalence of PM was
significantly higher in African-Americans than in Whites (female 7.4% vs. 4.8%;
male 4.8% vs. 3.7%) and inversely related to household income. During their
headaches, most (48.2%) had at least some impairment, while 22.1% were severely
disabled. The vast majority (97%) of PM sufferers used acute treatments, although
71% usually treated with over-the-counter medication. Most PM sufferers (52.8%)
never used a migraine-preventive treatment and only 7.9% were currently using
preventive medication. According to the expert panel guidelines, prevention
should be offered (16.9%) or considered (11.5%) for 28.4% of the PM sufferers in 
the survey. We conclude that PM is a frequent, undertreated, sometimes disabling 
disorder. It has an epidemiological profile similar to migraine. In contrast to
migraine, which is less prevalent in African-Americans than in Whites, PM is more
prevalent in African-Americans than in Whites. In the USA, many with PM do not
receive adequate treatment.

PMID: 17263769 [PubMed - indexed for MEDLINE]

910: Neurology. 2007 Jan 30;68(5):343-9.

Migraine prevalence, disease burden, and the need for preventive therapy.

Lipton RB, Bigal ME, Diamond M, Freitag F, Reed ML, Stewart WF; AMPP Advisory
Group.

Department of Neurology, The Albert Einstein College of Medicine, 1300 Morris
Park Avenue, Bronx, NY 10461, USA. rlipton@aecom.yu.edu

OBJECTIVES: 1) To reassess the prevalence of migraine in the United States; 2) to
assess patterns of migraine treatment in the population; and 3) to contrast
current patterns of preventive treatment use with recommendations for use from an
expert headache panel. METHODS: A validated self-administered headache
questionnaire was mailed to 120,000 US households, representative of the US
population. Migraineurs were identified according to the criteria of the second
edition of the International Classification of Headache Disorders. Guidelines for
preventive medication use were developed by a panel of headache experts. Criteria
for consider or offer prevention were based on headache frequency and impairment.
RESULTS: We assessed 162,576 individuals aged 12 years or older. The 1-year
period prevalence for migraine was 11.7% (17.1% in women and 5.6% in men).
Prevalence peaked in middle life and was lower in adolescents and those older
than age 60 years. Of all migraineurs, 31.3% had an attack frequency of three or 
more per month, and 53.7% reported severe impairment or the need for bed rest. In
total, 25.7% met criteria for "offer prevention," and in an additional 13.1%,
prevention should be considered. Just 13.0% reported current use of daily
preventive migraine medication. CONCLUSIONS: Compared with previous studies, the 
epidemiologic profile of migraine has remained stable in the United States during
the past 15 years. More than one in four migraineurs are candidates for
preventive therapy, and a substantial proportion of those who might benefit from 
prevention do not receive it.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17261680 [PubMed - indexed for MEDLINE]

911: Med Hypotheses. 2007;69(1):64-6. Epub 2007 Jan 26.

Possible joint origin of restless leg syndrome (RLS) and migraine.

Sabayan B, Bagheri M, Borhani Haghighi A.

Student Research Committee, Nemazee Hospital, Shiraz University of Medical
Sciences, Shiraz, Iran.

Sleep disorders have been described in migraine patients. Among sleep disorders
RLS has been reported in up to one-third of migraineurs. Adverse effects of anti 
migraine therapy by dopamine antagonists can not fully explain this association. 
Therefore we present the hypothesis that RLS and migraine may have a joint
origin. The hypothesis is supported by: (1) the same genetic origin for migraine 
without aura and RLS in single Italian family on chromosome 14q21; this gene
codes survival motor neuron-interacting protein 1 (SIP1) which can play role in
both diseases. (2) Correlation of both RLS and migraine with fibromyalgia. (3)
Alteration of cortical excitability in both migraine and RLS.

PMID: 17258401 [PubMed - indexed for MEDLINE]

912: Cephalalgia. 2007 Feb;27(2):177-81.

An adenosine A2A receptor gene haplotype is associated with migraine with aura.

Hohoff C, Marziniak M, Lesch KP, Deckert J, Sommer C, Mössner R.

Department of Psychiatry and Psychotherapy, University of Münster, Münster,
Germany. hohoffch@uni-muenster.de

The adenosine A2A receptor A2AR facilitates effects of calcitonin gene-related
peptide and vasoactive intestinal peptide, two important neuropeptides in
migraine pathophysiology, and is the molecular target of caffeine, which is used 
in migraine treatment. We therefore determined whether A2AR gene variation might 
influence migraine susceptibility. Migraine patients (n = 265) with or without
aura and migraine-free controls (n = 154) were assessed and genotyped for six
genetic variants spanning the A2AR gene. A six-marker haplotype was more frequent
in migraine patients with aura (P < 0.01) but not in patients without aura,
compared with the control group. This indicates that A2AR gene variation may
contribute to the pathogenesis of migraine with aura.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17257240 [PubMed - indexed for MEDLINE]

913: Cephalalgia. 2007 Feb;27(2):165-72.

Sumatriptan and corneal reflexes in headache-free migraine patients: a randomized
and placebo-controlled crossover study.

Busch V, Kaube S, Schulte-Mattler W, Kaube H, May A.

Department of Neurology, University of Regensburg, Universitätsstr. 84, 93053
Regensburg, Germany.

A temporary sensitization of central trigeminal neurones in migraine patients
during acute attacks has been described in previous studies using the
electrically evoked nociceptive blink reflex. The cornea is innervated by small
myelinated A-delta and unmyelinated C-fibres only. Stimulation with air puffs
activates peripheral nociceptors and allows the investigation of peripheral
trigeminal nerve structures. Our objective was to investigate whether corneal
reflex examinations with air puff stimulation detect abnormalities in migraineurs
during their pain-free interval and if the corneal reflex may be modulated by the
administration of an oral triptan. After validation of the nociceptive air puff
technique by investigating the corneal reflexes before and after a local
anaesthesia of the cornea, we recorded corneal reflexes in 25 migraineurs during 
their pain-free period and 25 healthy controls before and after the oral
administration of 100 mg sumatriptan in a randomized, placebo-controlled,
crossover study. Baseline response areas under the curve (AUCs) and latencies of 
the R2 components of the corneal reflexes did not show any significant
differences between patients and controls. Patients did not show any significant 
differences regarding their headache and non-headache side. The use of an oral
triptan had no significant influence on latencies or AUCs in both patients and
controls. Our data suggest that there is no facilitation of the trigeminal system
in the headache-free interval among patients with migraine. The stable corneal
reflexes after the oral administration of 100 mg sumatriptan suggest that there
was no inhibition of the trigeminal system, both in patients during their
headache-free period and in healthy controls.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial

PMID: 17257238 [PubMed - indexed for MEDLINE]

914: Cephalalgia. 2007 Feb;27(2):139-44.

Passive paradigm single-tone elicited ERPs in tension-type headaches and
migraine.

Chen W, Shen X, Liu X, Luo B, Liu Y, Yu R, Sun G, Shen M, Wang W.

Department of Clinical Psychology and Psychiatry, Zhejiang University, Hangzhou, 
China.

The active 'oddball' event-related potential (ERP) P3 is elongated or reduced in 
migraine and tension-type headaches, indicating a deficit of active attention in 
these primary headaches. It is then reasonable to study the passive attention
function in these headaches through the technology of passive paradigm
single-tone elicited ERPs. We invited 32 patients suffering from chronic
tension-type headache (CTTH), 17 from frequent episodic tension-type headache
(FETH) and 32 from interictal migraine without aura, as well as 28 healthy
subjects to undergo passive paradigm single-tone ERPs. There were no
statistically significant differences when the mean latencies and amplitudes of
N1, P2, N2 or the mean latencies of P3 of the four groups were considered. In
contrast, the P3 amplitudes were significantly reduced in the patient groups when
compared with healthy controls. However, no further significant difference was
found between patient groups when considering P3 amplitude. Our study
demonstrated a deficit of passive attention in CTTH, FETH and migraine, but could
not separate these headache types in this regard. The reduced P3 in patients
might be due to the head pain experienced.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17257234 [PubMed - indexed for MEDLINE]

915: Cephalalgia. 2007 Feb;27(2):128-32.

Abnormalities of Na/K ATPase in migraine with aura.

Scarrone S, Podestà M, Cupello A, Finocchi C, Frassoni F, Gandolfo C, Balestrino 
M.

University of Genova, Italy, Department of Neuroscience, Ophthalmology and
Genetics, Genova, Italy.

It has been previously shown from our laboratory that abnormal functioning of
Na/K ATPase can cause spreading depression, the likely mechanism of migraine
aura. We used lymphocytes to investigate whether or not membrane Na/K ATPase is
altered in migraine with aura patients. Lymphocytes were prepared from such
patients, aged 20-45 years, and from age-matched healthy volunteers (controls).
The binding of 3H- ouabain was studied using increasing concentrations (0.5-25
nm) of this radioligand, specific for Na/K-ATPase. We studied 19 migraine with
aura patients and 22 healthy volunteers, matched for age and sex. B(max) (fmol/mg
protein) and K(D) (nM) were not different between patients and controls. However,
their ratio (B(max)/K(D)) was higher in patients than in controls. B(max) was
(mean +/- SD) 270 +/- 110 fmol/mg protein in controls, and 360 +/- 230 in
migraine with aura patients (P = 0.10, t-test). K(D) was (mean +/- SD) 2.8 +/-
1.5 nm in controls, and 2.9 +/- 3.2 nm in migraine with aura patients (P = 0.88, 
t-test). B(max)/K(D) was (mean +/- SD) 120 +/- 78 in controls, and 210 +/- 190 in
migraine patients (P = 0.046, t-test). Moreover, no control patient had a
B(max)/K(D) ratio greater than 398, while three migraine patients had ratios of
417, 572 and 722, respectively. Ouabain binding is affected by Na/K ATPase
structure (K(D)) and expression (B(max)). While these parameters were not altered
in migraine with aura patients, the difference in their ratio suggests an
imbalance between the enzyme's ouabain affinity and its expression, with
higher-affinity subtypes being more expressed than normal. Moreover, single
patients had values quite different from the control population. Our data suggest
that (i) ouabain binding to lymphocyte membranes may be a useful tool in the
diagnosis of migraine with aura and (ii) Na/K ATPase abnormalities may be
involved in migraine aura.

PMID: 17257232 [PubMed - indexed for MEDLINE]

916: Cephalalgia. 2007 Feb;27(2):111-7.

Identifying cutaneous allodynia in chronic migraine using a practical clinical
method.

Ashkenazi A, Sholtzow M, Shaw JW, Burstein R, Young WB.

Department of Neurology, Thomas Jefferson University, Jefferson Headache Center, 
Jefferson University Hospital, Philadelphia, PA 19107, USA.
avi.ashkenazi@jefferson.edu

Cutaneous allodynia is common in migraine. In the majority of previous studies on
allodynia in migraine, only patients with episodic migraine (EM) were included.
Little is known on patterns of allodynia in chronic migraine (CM). Since the
presence of allodynia is associated with a poor response to triptans, a
clinically practical method to test migraine patients for allodynia would be
useful to the clinician. The aim of this study was to assess the prevalence of
dynamic mechanical (brush) allodynia (BA) in CM, using a clinically practical
method. Eighty-nine CM patients were prospectively recruited. Patients were given
a structured questionnaire regarding demographic data and migraine
characteristics. Allodynia was tested using a 10 x 10-cm gauze pad to brush
various areas of the skin lightly. The prevalence of BA in the entire study
population and in different patient subgroups was calculated. BA was present in
42.7% (38/89) of the patients. The presence of allodynia was unrelated to age,
disease duration or to the occurrence of an acute headache exacerbation at the
time of testing. Allodynia was positively associated with a history of migraine
aura. BA was most common in the cephalic area, but was also seen in cervical
dermatomes. BA is common in CM and, unlike in EM, is not significantly affected
by the occurrence of an acute headache exacerbation. This suggests that central
trigeminovascular neurons are chronically sensitized in patients experiencing
migraine headache >15 days per month. The testing of BA in the clinical setting
is possible using a simple and brief approach. It allows the clinician to
determine whether the patient is sensitized, a diagnosis that affects treatment
decisions.

PMID: 17257230 [PubMed - indexed for MEDLINE]

917: Cephalalgia. 2007 Feb;27(2):97-106.

Migraine in the elderly: a review.

Haan J, Hollander J, Ferrari MD.

Department of Neurology, Leiden University Medical Centre, Leiden, The
Netherlands. jhaan@rijnland.nl

Although migraine is less prevalent in older than in younger age groups, the
absolute increase in the number of subjects in older age groups may lead to an
increase in the total number of migraine patients. Consequently, more elderly
migraine patients may seek medical attention. In this review, the epidemiology
and clinical aspects of migraine in the age group of > or =60 years are
summarized, with special attention to comorbidity. The review will focus on
treatment choices in elderly migraine patients. These must be based on knowledge 
of mechanisms of physiological and pathological ageing.

Publication Types: 
    Review

PMID: 17257228 [PubMed - indexed for MEDLINE]

918: Catheter Cardiovasc Interv. 2007 Feb 1;69(2):277-84.

Patent foramen ovale closure: a new therapy for migraine.

Schwerzmann M, Nedeltchev K, Meier B.

Department of Cardiology, University Hospital, Bern, Switzerland.

Migraine is a recurrent disabling disorder predominantly affecting middle-aged
women. Migraine occurs with or without aura symptoms. Several studies have shown 
an increased prevalence of right-to-left shunts (RLSs) in migraine with aura. The
overwhelming majority of these shunts were due to a patent foramen ovale (PFO).
Furthermore, migraine with aura is more prevalent in clinical entities associated
with a RLS, e.g. cryptogenic stroke, decompression illness in divers, or in
patients with hereditary hemorrhagic teleangiectasia and pulmonary arteriovenous 
fistulas. Retrospective studies have consistently shown that shunt closure was
associated with a significant reduction in migraine frequency. Its beneficial
effect seemed to exceed the efficacy of conventional migraine therapy. Several
randomized clinical trials to prospectively assess the benefit of shunt closure
in migraine patients have been initiated. The only one completed, the MIST trial 
(Migraine Intervention with STARFLEX Technology), showed a significant reduction 
of migraine with aura after device implantation, compared with controls. However,
the benefit of PFO closure was more modest than expected. This review
recapitulates the current data regarding PFO closure and migraine with aura and
summarizes in brief the current knowledge regarding migraine pathophysiology and 
the link to a RLS. (c) 2006 Wiley-Liss, Inc.

Publication Types: 
    Review

PMID: 17253601 [PubMed - indexed for MEDLINE]

919: Brain. 2007 Mar;130(Pt 3):765-70. Epub 2007 Jan 24.

Interictal habituation deficit of the nociceptive blink reflex: an endophenotypic
marker for presymptomatic migraine?

Di Clemente L, Coppola G, Magis D, Fumal A, De Pasqua V, Di Piero V, Schoenen J.

Headache Research Unit, University Department of Neurology, University of Liège, 
Liège, Belgium.

Habituation of the nociception-specific blink reflex (nBR) is reduced
interictally in migraine patients. This could be related to the habituation
deficit of evoked cortical responses, a reproducible abnormality in migraine
which has a familial character, or to central trigeminal sensitization due to
repeated attacks. We compared nBR habituation in healthy volunteers devoid of
personal or family history of migraine (HV), in migraine without aura patients
(MO) and in healthy volunteers with a family history of migraine in first degree 
relatives (HV-F). We elicited the nBR by stimulating the right supraorbital
region with a custom-built electrode in 16 MO between attacks, 15 HV and 14 HV-F.
Habituation was measured as the percentage area-under-the-curve decrease in 10
consecutive blocks of five averaged rectified responses. nBR habituation was
clearly reduced in MO and HV-F compared to HV. Percentage area under the curve
decreased between the 1st and the 10th block by 55.01% in HV, 25.71% in MO (P =
0.001) and 26.73% in HV-F (P = 0.043). HV-F had the most pronounced abnormality
with potentiation instead of habituation in the second block. We found a positive
intraindividual correlation between attack frequency and habituation in MO (r =
0.621; P = 0.010). Migraine patients have interictally a deficient habituation of
the nBR which is inversely related to attack frequency, suggesting that it is not
due to trigeminal sensitization. Surprisingly, the most pronounced habituation
deficit is found in asymptomatic individuals with a family history of migraine.
Deficient nBR habituation could thus be a trait marker for the genetic
predisposition to migraine.

Publication Types: 
    Comparative Study

PMID: 17251239 [PubMed - indexed for MEDLINE]

920: Pain Med. 2007 Jan-Feb;8(1):65-70.

Effectiveness of ropivacaine trigger points inactivation in the prophylactic
management of patients with severe migraine.

García-Leiva JM, Hidalgo J, Rico-Villademoros F, Moreno V, Calandre EP.

Instituto de Neurociencias, Universidad de Granada, Granada, Spain.

OBJECTIVE: Tenderness and referred pain have been described in migraine and
involved in its pathogenesis. The present study was performed to evaluate the
prophylactic effectiveness of ropivacaine injections during a 12-week period.
INTERVENTIONS: A total of 52 patients agreed to participate in the study. Trigger
points were explored by manual palpation and injected weekly with 10 mg
ropivacaine. The frequencies of migraine attacks were recorded from 4 weeks
before the beginning of injections until 4 weeks after the last one, and a
Clinical Global Impression improvement scale was completed in the final visit.
RESULTS: All of the subjects had one or more trigger points, located in temporal 
and/or suboccipital areas in most of the cases. In nine (17.3%) patients the
frequency of attacks was reduced >or=50%, and in 19 (36.5%) cases the reduction
was comprised between 11% and 49%. A total of 31 (59.6%) patients reported to be 
much or very much improved after finishing the injection period. In 11 cases
rescue medication intake was reduced >or=50% in comparison with baseline period, 
and the attacks of severe intensity decreased significantly. Eight (26.6%) out of
30 patients suffering chronic migraine reverted to episodic migraine. Local pain 
in injection sites was reported by 14 patients, and 13 subjects (25.5%)
experienced postinjection soreness. CONCLUSIONS: Trigger points inactivation can 
be an effective palliative measure in the prophylactic management of severe
refractory migraine.

Publication Types: 
    Clinical Trial

PMID: 17244105 [PubMed - indexed for MEDLINE]

921: Helicobacter. 2007 Feb;12(1):59-62.

Migraine, Helicobacter pylori, and oxidative stress.

Tunca A, Ardiçoğlu Y, Kargili A, Adam B.

Department of Neurology, Private Zafer Hospital, Ankara, Turkey.
etunca@e-kolay.net

BACKGROUND: The aim of this study was to ascertain whether oxidative stress is a 
causative factor of migraine attacks for Helicobacter pylori-infected
migraineurs. MATERIALS AND METHODS: A total of 35 consecutive migraine patients
without aura who came to gastroenterology polyclinic with various complaints and 
diagnosed H. pylori infection were included in the study group and compared with 
a group of 29 patients (control group) without migraine and H. infection. H.
pylori infection was diagnosed by histopathological biopsies, which were taken by
endoscopy (Olympus-GIFXQ240 endoscope). Both the diagnosis and the classification
of migraine were made according to the International Headache Society criteria.
Blood samples for nitric oxide were taken from patients with migraine during
headache-free period as well as the control group. The interaction of nitric
oxide was measured by the determination of both nitrite and nitrate
concentrations in the sample. RESULTS: The study group included 31 women and 4
men (mean age 49 +/- 8 years) and the control group included 25 women and 4 men
(mean age 52.6 +/- 11 years). The mean frequency of migraine attacks was 2.94 +/-
1.58 days/month and the mean duration of attacks was 21.2 +/- 3 hours. It was
found that the study group has lower nitrate levels than the control group.
CONCLUSIONS: Our results do not support the role of oxidative stress in patients 
suffering from H. pylori infection and migraine.

PMID: 17241302 [PubMed - indexed for MEDLINE]

922: Psychother Psychosom. 2007;76(2):122-8.

Anger, depression and personality dimensions in patients with migraine without
aura.

Abbate-Daga G, Fassino S, Lo Giudice R, Rainero I, Gramaglia C, Marech L, Amianto
F, Gentile S, Pinessi L.

Psychiatry Section, Department of Neuroscience, Ospedale San Giovanni Battista,
Psichiatria Universitaria CPR DCA, Turin, Italy.

BACKGROUND: Migraine without aura causes acute and chronic pain and partially
compromises patients' social functioning and work performance. Over the past
years, psychiatric comorbidities were frequently observed in these patients,
together with coping difficulties and typical personality traits. The aim of this
study was to identify whether migraine patients and controls share distinctive
personality traits. METHODS: 105 consecutive patients suffering from migraine
without aura referred to the Headache Center of Turin University were enrolled in
the study and compared to a control group of 79 healthy subjects. Patients and
controls completed several psychometric questionnaires, including the Temperament
and Character Inventory, the Beck Depression Inventory and the State-Trait Anger 
Expression Inventory. RESULTS: Patients suffering from migraine show more
depressive symptoms, difficult anger management with a tendency to hypercontrol, 
and a distinctive personality profile with high harm avoidance, high persistence 
and low self-directedness. When a logistic regression was performed, the only
significant predictors of migraine were temperament variables. CONCLUSIONS: The
results suggest that the personality traits and psychosomatic mechanisms of
migraine patients may make them vulnerable to stress and less skilled in coping
with pain. These traits correlate with dysregulated neurotransmitter systems
which may also be part of the psychobiological components of personality,
depressive disorders and migraine itself. Copyright 2007 S. Karger AG, Basel.

PMID: 17230053 [PubMed - indexed for MEDLINE]

923: Neuroradiology. 2007 May;49(5):419-26. Epub 2007 Jan 16.

Erratum in:
    Neuroradiology. 2007 Apr;49(4):387. Yucel, Aylin [added].

Cerebral and cerebellar ADC values during a migraine attack.

Degirmenci B, Yaman M, Haktanir A, Albayrak R, Acar M, Yucel A.

Department of Radiology, Faculty of Medicine, University of Kocatepe, Afyon
03200, Turkey. bdegirmenci@aku.edu.tr

INTRODUCTION: We investigated the diffusion-weighted MRI changes, apparent
diffusion coefficient (ADC) values, and conventional MRI findings in specific
brain areas during migraine attacks in patients with and without aura. METHODS:
Included in the study were 22 patients (2 male, 20 female) aged between 17 and 49
years who were diagnosed as having migraine according to the diagnostic criteria 
of the International Headache Society. Also included in the study were 18 age-
and sex-matched healthy volunteers. Hyperintense lesions were evaluated in
conventional MR images. Heavily diffusion-weighted images, ADC maps, and
segmented ADC maps generated for regional ADC (rADC) measurements, were also
studied. ADC values from specific brain areas were used with appropriate region
of interests (ROI). RESULTS: Migraine with aura was diagnosed in 13 patients and 
migraine without aura was diagnosed in 9 patients. A total of 23 hyperintense
lesions within the periventricular white matter and deep white matter were
detected in five patients (21.8%). All of these hyperintense lesions were seen in
migraine patients with aura. In only one patient did a hyperintense lesion show
an increased diffusion pattern on diffusion-weighted images and ADC maps. One
hyperintense lesion was detected in the control group (5.5%). There was no
significant difference in ADC values between the migraine and control groups.
CONCLUSION: T2-weighted hyperintense lesions were significantly more frequent in 
migraine patients especially in those with aura than in the control group. No
diffusion alterations in diffusion-weighted images were detected in the infra-
and supratentorial brain areas during migraine attacks in patients with and
without aura.

PMID: 17225143 [PubMed - indexed for MEDLINE]

924: J Headache Pain. 2007 Feb;8(1):35-42. Epub 2007 Jan 15.

Present and previous psychopathology of juvenile onset migraine: a pilot
investigation by Child Behavior Checklist.

Salvadori F, Gelmi V, Muratori F.

Division of Child Neurology and Psychiatry, Scientific Institute Stella Maris,
Department of Neurosciences, University of Pisa, Via dei Giacinti 2, I-56018,
Calambrone, Pisa, Italy. francesco.salvadori@inpe.unipi.it

The objective was to describe the premorbid state of migraine with juvenile
onset. Thirty subjects with migraine and 30 healthy subjects were enrolled in a
case-control study. A structured questionnaire (Child Behavior Checklist, CBCL)
was administered to the mothers and ratings were obtained for the past two age
periods (0-3 and 4-6 years) and for the present state. CBCL scores of the
migraine group (MG) were compared to those of the control group (CG) during the
three periods. A longitudinal study was performed to evaluate the evolution of
psychopathology comparing CBCL scores of MG in the three age periods. During the 
premorbid period MG showed significantly higher mean scores on total,
internalising, anxious-depressive scales. In the longitudinal perspective,
internalising traits were present in the premorbid period in MG. Children later
diagnosed as having migraine differ from CG in several scales during different
age periods. Migraine could be considered as the expression of a previous
vulnerability.

Publication Types: 
    Comparative Study

PMID: 17221344 [PubMed - indexed for MEDLINE]

925: J Headache Pain. 2007 Apr;8(2):90-3. Epub 2007 Jan 15.

How many migraine patients need prolonged (>1 year) preventive treatment?
Experience with topiramate.

Pascual J, El Berdei Y, Gómez-Sánchez JC.

Service of Neurology, University Hospital, Paseo de San Vicente 58-132, 37007,
Salamanca, Spain. juliopascual@telefonica.net

The usual recommended duration of preventive treatment for migraine is 3-6
months. Our aim was to explore how many patients attending a specialised clinic
need prolonged preventive treatment for longer than one year. Eighty consecutive 
migraine patients who received preventive treatment with topiramate for 3 months 
with good response and tolerability were included in this observational study.
All patients continued on topiramate until they had completed 6 months, when this
drug was stopped. Topiramate was reintroduced if there was a worsening.
Topiramate was kept for 6 more months and then discontinued again. Those patients
whose headaches became worse after this second withdrawal received topiramate
again and were followed-up for at least half a year. Headaches did not worsen
after the first withdrawal at 6 months in 40 patients (50%), while they clearly
worsened in the remaining 40 patients. At the end of the first year only two
patients out of these 40 (5%) discontinued topiramate and did not notice an
increase in headache frequency after two months. In conclusion, around half of
the patients attending a specialised clinic due to frequent headache need
preventive treatment for more than one year. Our data suggest that the current
practice recommending periods of preventive treatment of 3-6 months should be
reconsidered for many patients.

Publication Types: 
    Clinical Trial

PMID: 17221343 [PubMed - indexed for MEDLINE]

926: J Headache Pain. 2007 Apr;8(2):94-104. Epub 2007 Jan 15.

Personality in patients with migraine evaluated with the "Temperament and
Character Inventory".

Sánchez-Román S, Téllez-Zenteno JF, Zermeño-Phols F, García-Ramos G, Velázquez A,
Derry P, Hernández M, Resendiz A, Guevara-López UM.

Department of Neurology and Psychiatry, National Institute of Medical Sciences
and Nutrition "Salvador Zubirán", Vasco de Quiroga 15, Colonia Sección XVI,
Delegación Tlalpan, México, DF. CP 14000, México. sofiasan@yahoo.com

The objective of this study was to assess the personality profile of a sample of 
Mexican patients with migraine using the Temperament and Character Inventory
(TCI). A cross-sectional study was performed including adult migraine patients
identified from the outpatient neurology clinics of two large teaching hospitals 
in Mexico City. Patients were asked to voluntarily participate in the study. A
physician conducted a standardised diagnostic interview adhering to the criteria 
of the International Headache Society (IHS). Patients were interviewed and
administered the TCI. We used two healthy controls groups and a third group of
non-migraine pain controls. One hundred and fortytwo subjects with migraine, 108 
healthy blood donors, 269 young healthy controls and 30 patients with
non-migraine pain (NMP) were included in the study. Patients with migraine had
higher scores in the dimension harm avoidance (HA) and all its sub-dimensions
(p<0.05) than healthy patients. Patients with non-migraine pain had high scores
in HA and low scores in novelty seeking, self-directedness and cooperativeness.
Blood donors had high scores in the following subdimensions: HA1, HA4 and C3
(Cooperativeness). Personality features consistent with migraine are avoidance,
rigidity, reserve and obsessivity. Our study shows that patients with chronic
pain share some of the personality features of patients with migraine but their
TCI profile could be indicative of cluster C avoidant personality. Blood donors
were shown to have more energy, with a tendency to help other people and be more 
optimistic. The results support serotoninergic involvement as explaining the
physiopathology of migraine.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17221342 [PubMed - indexed for MEDLINE]

927: J Headache Pain. 2007 Feb;8(1):13-8. Epub 2007 Jan 15.

Sumatriptan 6 mg subcutaneous as an effective migraine treatment in patients with
cutaneous allodynia who historically fail to respond to oral triptans.

Diamond S, Freitag FG, Feoktistov A, Nissan G.

Diamond Headache Clinic, 467 West Deming Place, Suite 500, Chicago, IL 60614,
USA. MACF48@aol.com

The objective of the study was to assess the efficacy of 6 mg subcutaneous (s.c.)
sumatriptan to treat migraine and the relationship between response of migraine
and cutaneous allodynia in a population of migraine patients who historically
failed to respond to oral triptan medications. This was an open-label study
consisting of patients with migraines who historically failed to respond to oral 
triptan medications. Forty-three patients were asked to treat three migraine
attacks with 6 mg s.c. sumatriptan. The primary efficacy endpoint was the
percentage of patients achieving relief of headache at 2 h. Ninety-one percent of
the patients responded to a single dose of s.c. sumatriptan 6 mg. Fifty percent
of all patients were pain-free by 2 h and over 30% had a 24-h sustained pain-free
response. When administered within 90 min from the onset of migraine (i.e.,
during the developing phase of cutaneous allodynia), s.c. 6 mg sumatriptan proved
to be effective despite the occurrence of allodynia in a group of patients, who
historically had failed to respond to oral triptan medications. These findings
suggest that the window of opportunity to treat allodynic patients with
injectable triptans may be longer (up to 2 h) than with oral triptans (up to 1
h).

Publication Types: 
    Controlled Clinical Trial

PMID: 17221340 [PubMed - indexed for MEDLINE]

928: Arq Neuropsiquiatr. 2006 Dec;64(4):954-7.

Prevalence and impact of headache and migraine among Pomeranians in Espirito
Santo, Brazil.

Domingues RB, Aquino CC, Santos JG, da Silva AL, Kuster GW.

IProjeto de Extensão em Cefaléias (Headache Program), Escola Superior de Ciências
da Santa Casa de Misericórdia (EMESCAM), Vitória ES - Brasil. renan-domingues@
uol.com.br

This is the first study to assess the prevalence of headache and migraine among
Pomeranian descendents in Brazil. A high prevalence of headache in the last 6
months was found (53.2%). Most headache sufferers were diagnosed as having
migraine (55%). More women reported to have headache than men (65% and 33.8%,
respectively). Migraine was the most common headache found among women (62.2%).
Among men migraine was responsible for only 37.8% of the cases of headache. A
high impact of headache was found, especially among migraineurs. Most of the
headache sufferers declared to seek medical assistance for headache (67%) and
most of them used to take common analgesics for headache relief. None of them was
under prophylactic therapy.

PMID: 17221003 [PubMed - indexed for MEDLINE]

929: Arq Neuropsiquiatr. 2006 Dec;64(4):950-3.

Phobias, other psychiatric comorbidities and chronic migraine.

Corchs F, Mercante JP, Guendler VZ, Vieira DS, Masruha MR, Moreira FR, Bernik M, 
Zukerman E, Peres MF.

Instituto Israelita de Ensino e Pesquisa Albert Einstein, São Paulo, SP, Brazil.

BACKGROUND: Comorbidity of chronic migraine (CM) with psychiatric disorders,
mostly anxiety and mood disorders, is a well-recognized phenomenon. Phobias are
one of the most common anxiety disorders in the general population. Phobias are
more common in migraineurs than non-migraineurs. The clinical profile of phobias 
in CM has never been studied. METHOD: We investigated the psychiatric profile in 
56 patients with CM using the SCID I/P interview. RESULTS: Lifetime criteria for 
at least one mental disorder was found in 87.5% of the sample; 75% met criteria
for at least one lifetime anxiety disorder and 60.7% of our sample fulfilled
DSM-IV criteria for lifetime phobic avoidant disorders. Mood and anxiety scores
were higher in phobic patients than in non-phobic CM controls. Number of phobias 
correlated with higher levels of anxiety and depression. CONCLUSION: Phobias are 
common in CM. Its recognition may influence its management. Early treatment may
lead to better prognosis.

PMID: 17221002 [PubMed - indexed for MEDLINE]

930: Minerva Med. 2006 Dec;97(6):467-77.

A pharmacoeconomic evaluation of oral triptans in the treatment of migraine in
Italy.

Gori S, Morelli N, Acuto G, Caiola F, Iudice A, Murri L.

Unit of Neurology, Department of Neuroscience, University of Pisa, Pisa, Italy.
s.gori@med.unipi.it

AIM: The goal of this economic evaluation was to compare the cost-efficacy of
oral triptans currently used in the treatment of migraine in Italy. METHODS: The 
cost analysis of drugs was conducted through a structured decision tree, built up
taking into account the National Healthcare System perspective. Data on the
clinical efficacy and tolerability of oral triptans were derived from a published
meta-analysis of 53 randomized, controlled trials. Drug cost-allocation included 
either the oral triptans price and costs related to management of
treatment-associated chest and central nervous system (CNS) adverse events.
Necessary resources for management of the unwanted events were identified by
asking an experienced panel of experts how they would treat patients with
triptan-related chest and CNS adverse events. To further improve the economic
scenario and to allow a broader inference of pharmacoeconomic analysis, the
number needed to treat (NNT) to attain 100 sustained pain free (SPF) patients,
and 100 patients with SPF and no adverse events (SNAE) were also calculated.
RESULTS: Study results show cost-effective differences among oral triptans. The
best cost-efficacy ratios were attained by almotriptan 12.5 mg and rizatriptan 5 
mg, with 18.47 Euro and 26.37 Euro respectively per patient successfully treated 
(SPF). Similarly, the NNT analysis favoured almotriptan, which requires 386
patients to attain 100 SPF patients, and 393 patients to attain 100 SNAE
patients. Rizatriptan 10 mg resulted the closest competitor, requiring 395 and
457 patients, respectively. CONCLUSIONS: On the basis of published data and
within the limitations of this model analysis that included several assumptions, 
results suggest the economical advantage of almotriptan 12.5 mg among the oral
triptans approved for the treatment of migraine in Italy. This evidence could
drive selection of the most appropriate oral treatment for acute migraine attacks
based on both individual patient's needs and cost-effective drugs.

PMID: 17213783 [PubMed - indexed for MEDLINE]

931: Cephalalgia. 2007 Jan;27(1):63-7.

Sympathy for Pontius Pilate. Hemicrania in M. A. Bulgakov's The Master and
Margarita.

Zayas V, Mainardi F, Maggioni F, Zanchin G.

Department of Neurosciences, Brown University, Providence, RI 02914, USA.
vladislav_zayas@brown.edu

The aim of this study was to explore the description of the migraine attack of
Pontius Pilate (a character in the novel The Master and Margarita by M. A.
Bulgakov). Some of its features are analysed in light of current migraine
literature. It is hypothesized that, at least in part, this description is based 
on the personal experience of the novel's author. We studied and analysed the
text of the novel, other works by Bulgakov, his biography, including his medical 
training and practice, and the recently published diaries of Bulgakov and his
wife E. S. Bulgakova. The novel contains a comprehensive description of a
migraine attack. It includes a prodrome/aura of osmophobia. Olfactory perception 
during or shortly before the migraine attack is altered to the point where
neutral or even pleasant odours become unbearable. Bulgakov's extensive history
of migraines is seen in his diary, the diary of his wife, letters and other
literary works. This is one of the most detailed and extensive depictions of a
migraine attack in literature, with osmophobia described with great emphasis. It 
is likely that Pilate's migraine is described based on the personal history of
the novel's author.

Publication Types: 
    Biography
    Historical Article
    Portraits

Personal Name as Subject: 
    Bulgakov MA

PMID: 17212685 [PubMed - indexed for MEDLINE]

932: Cephalalgia. 2007 Jan;27(1):54-62.

The cost-effectiveness of oral triptan therapy in Sweden.

Ramsberg J, Henriksson M.

Pharmaceutical Benefits Board, Solna, Sweden. joakim.ramsberg@lfn.se

The literature suggests that triptans are cost effective compared with older
types of migraine treatment. However, which of the triptans that is most cost
effective has not been established. We compared the costs and effects of triptan 
treatment from a Swedish societal perspective, using evidence from the
literature. A probabilistic cost-effectiveness model was constructed to
investigate the costs and effects of treating a single attack in a typical
migraine patient. The end-point used in the base-case analysis was sustained pain
free without any adverse events (SNAE). We searched the scientific literature for
meta-analyses reporting the efficacy of oral triptans. All treatments except
rizatriptan 10 mg and eletriptan 40 mg were dominated. The incremental cost per
SNAE of rizatriptan 10 mg compared with eletriptan 40 mg was approximately 100
euro. There was substantial uncertainty concerning the results, but probabilistic
analysis showed that rizatriptan 10 mg and eletriptan 40 mg had the highest
probability of being cost-effective.

Publication Types: 
    Meta-Analysis

PMID: 17212684 [PubMed - indexed for MEDLINE]

933: Cephalalgia. 2007 Jan;27(1):41-5.

The impact of education on the diagnostic accuracy of tension-type headache and
migraine: a prospective study.

Karli N, Zarifoglu M, Erer S, Pala K, Akis N.

Department of Neurology, School of Medicine, Uludag University, Bursa, Turkey.
nkarli@yahoo.com

General practitioners (GPs) diagnose and treat headache in primary care settings.
The objective of this study was to investigate the effect of a 2-day headache
education programme for GPs primarily on diagnostic accuracy. The education
programme included theoretical lectures and face-to-face patient evaluation with 
headache specialists. Three GPs evaluated headache patients before and after the 
programme. Each GP was planned to interview a total of 60 patients (30 before, 30
after the programme). All patients were evaluated by headache specialists
following evaluation by the GPs. A total of 189 patients were included in this
study. Diagnostic accuracy increased from 56.3% to 81.0% after the headache
education programme (P < 0.001), which also significantly improved the choice of 
proper treatment (P = 0.043). The headache education programme for GPs
significantly improved diagnostic accuracy in patients with tension-type headache
and the choice of proper treatment. Such education programmes can be standardized
and given to GPs working in the primary care setting. These programmes can be
arranged locally by the universities and might have a favourable impact on the
diagnosis and treatment of headache.

PMID: 17212682 [PubMed - indexed for MEDLINE]

934: Cephalalgia. 2007 Jan;27(1):35-40.

Platelet glutamate uptake and release in migraine with and without aura.

Vaccaro M, Riva C, Tremolizzo L, Longoni M, Aliprandi A, Agostoni E, Rigamonti A,
Leone M, Bussone G, Ferrarese C.

Department of Neurology, S. Gerardo Hospital, University of Milano-Bicocca,
Milan, Italy.

Glutamate may play an important role in the pathogenesis of migraine: glutamate
release in the brain may be involved in the development of spreading depression
and increased concentrations of this amino acid have been reported in plasma and 
platelets from migraine patients. Here we assessed platelet glutamate uptake and 
release in 25 patients affected by migraine with aura (MA) and 25 patients
affected by migraine without aura (MoA), comparing the results with a group of 20
healthy matched controls. Both glutamate release from stimulated platelets and
plasma concentrations of the amino acid were assessed by high-performance liquid 
chromatography, and were increased in both types of migraine, although more
markedly in MA. Platelet glutamate uptake, assessed as 3H-glutamate intake, was
increased in MA, while it was reduced in MoA with respect to the control group.
These results support the view that MA might involve different pathophysiological
mechanisms from MoA and, specifically, up-regulation of the glutamatergic
metabolism. Understanding these dysfunctional pathways could lead to new,
possibly more successful therapeutic approaches to the management of migraine.

PMID: 17212681 [PubMed - indexed for MEDLINE]

935: Cephalalgia. 2007 Jan;27(1):29-34.

Diclofenac epolamine is effective in the treatment of acute migraine attacks. A
randomized, crossover, double blind, placebo-controlled, clinical study.

Vécsei L, Gallacchi G, Sági I, Semjén J, Tajti J, Szok D, Müller M, Vadass P,
Kerékgyártó M.

Department of Neurology, Albert Szent-Györgyi Medical and Pharmaceutical Centre, 
University of Szeged and Neurology Research Group of the Hungarian Academy of
Sciences and University of Szeged, Szeged, Hungary. giuseppe.mautone@ibsa.ch

Hydrosoluble diclofenac epolamine (DHEP) represents an interesting approach to
acute migraine attacks, where gastrointestinal motility and drug absorption are
often reduced. Its efficacy was investigated in a randomized, crossover,
double-blind trial on 155 patients who treated four consecutive mild-to-moderate 
migraine attacks, either with DHEP (65-mg sachet) or placebo. If pain was not
relieved within 1 h, a second dose was given. The total number of treated attacks
was 481. A pain-free condition was achieved within 2 h in 45.8% and 25.1% of
attacks treated, respectively, with DHEP or placebo (P < 0.0001), with a
therapeutic gain of 20.7%. Time to attack resolution, light and noise sensitivity
and impact on working ability were significantly reduced by DHEP compared with
placebo. Moreover, significantly fewer patients required a second drug dose or a 
rescue medication when treated with DHEP than with placebo. No adverse reaction
was recorded. In conclusion, DHEP was effective and safe for pain relief in
patients with an acute mild-to-moderate migraine attack.

Publication Types: 
    Multicenter Study
    Randomized Controlled Trial

PMID: 17212680 [PubMed - indexed for MEDLINE]

936: Cephalalgia. 2007 Jan;27(1):22-8.

A report of cranial autonomic symptoms in migraineurs.

Gupta R, Bhatia MS.

Department of Psychiatry, University College of Medical Sciences and GTB
Hospital, Shahdara, Delhi, India. guptaravi_2003@yahoo.co.in

The presence of cranial autonomic symptoms in migraine is well known and thought 
to represent activation of the trigeminal parasympathetic reflex pathway similar 
to trigeminal autonomic cephalalgias. However, studies regarding the prevalence
of these symptoms are few. The characteristics of migraineurs with cranial
autonomic symptoms and the association of cranial autonomic symptoms with
laterality of headache have never been studied in a clinic population.
Seventy-eight consecutive subjects with migraine were recruited from the Headache
Clinic of the Department of Psychiatry after exclusion of subjects with secondary
headache. Their demographic data and detailed history of headache were noted and 
leading questions were asked regarding cranial autonomic symptoms. chi(2) test
and Fisher's exact test was used for categorical variables, whereas an
independent sample t-test was applied on numerical data. Spearman's correlation
was used for correlational analysis of categorical variables. Female subjects
(78.2%) outnumbered males and the average duration of illness in the whole sample
was 3.81 years. Migraine without aura (53.8%) was the commonest diagnosis,
followed by migraine with aura (24.4%). Cranial autonomic symptoms were present
in 73.1% of subjects and, commonly, they were ipsilateral to headache. Moreover, 
strictly unilateral cranial autonomic symptoms were reported by only 32% of
patients. The anatomical side of headache did not affect the presence of
autonomic symptoms. Those with or without autonomic symptoms did not differ with 
respect to gender, diagnosis, laterality of headache or associated symptoms
except phonophobia, which was more common in subjects with autonomic symptoms (P 
= 0.05). Those with autonomic symptoms had longer duration of illness (P = 0.03) 
and longer headache episodes (P = 0.04). In addition, sleep was ineffective in
relieving their headache (P = 0.02). Cranial autonomic symptoms are frequent in
migraineurs and are common in subjects with long duration of illness and longer
headache episodes. Clinical evidence in the present study suggests that subjects 
with cranial autonomic symptoms have a hyperactive efferent arm of trigeminal
autonomic reflex. The connections of trigeminal nucleus with the locus coeruleus 
and dorsal raphe nucleus may account for the observed phenotypic differences
between the two groups. Further research, however, is required to elucidate the
underlying neural mechanisms of cranial autonomic symptoms in migraine.

PMID: 17212679 [PubMed - indexed for MEDLINE]

937: Cephalalgia. 2007 Jan;27(1):9-13.

Haemochromatosis gene (HFE) polymorphisms and migraine: an association study.

Rainero I, Rubino E, Rivoiro C, Valfrè W, Binello E, Zampella E, De Martino P,
Gentile S, Fenoglio P, Savi L, Gallone S, Pinessi L.

Neurology II, Headache Centre, Department of Neuroscience, University of Torino, 
Torino, Italy. irainero@molinette.piemonte.it

Several studies have suggested that iron metabolism may be involved in the
pathogenesis of migraine. Using a case-control design, we performed an
association study in a cohort of Italian migraine patients to evaluate whether a 
particular allele or genotype of the haemochromatosis gene (HFE) would modify the
occurrence and clinical features of the disease. We genotyped 256 migraine
patients and 237 healthy age-, sex- and ethnicity-matched controls for the C282Y 
and H63D polymorphisms of the HFE gene. Phenotype and allele frequencies of both 
polymorphisms were similarly distributed in migraine patients and controls. The
patients carrying the DD genotype of the H63D polymorphism showed a later age at 
onset of the disease and an increased number of migraine attacks. Our data
suggest that the HFE gene is not a major disease gene for migraine. However, the 
H63D polymorphism of the HFE gene may be considered a modifying genetic factor in
migraine.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17212677 [PubMed - indexed for MEDLINE]

938: Acta Neurol Scand. 2007 Feb;115(2):81-3.

Testing the combination beta-blocker plus topiramate in refractory migraine.

Pascual J, Rivas MT, Leira R.

Service of Neurology, University Hospital, Salamanca, Spain.
juliopascual@telefonica.net

OBJECTIVE: To test treatment combining a beta-blocker plus topiramate in migraine
patients previously resistant to the two medications in monotherapy. PATIENTS AND
METHODS: Those patients who had not responded to a beta-blocker and topiramate
received combined treatment. RESULTS: Fifty-eight patients (47 women, age 25-76
years) received the combined treatment. Thirty-three (57%) met criteria for
chronic migraine/medication overuse headache, 18 (31%) for migraine without aura 
and seven (12%) with aura. Ten (17%) discontinued due to adverse events. Among
the 48 patients who tolerated the combination, 36 (75%, 62% of the total series) 
showed response (>50% reduction in frequency), while 12 (25%) did not. The number
of days with headache/month decreased from 15.1 to 6.5 (-57%). Sixteen (44% of
responders) showed an excellent (>75%) response. Eighteen patients (38%)
experienced a total of 26 adverse events (mild-moderate). CONCLUSIONS: The
combination of beta-blocker plus topiramate showed a benefit in around 60% of
patients who had not previously responded to monotherapy. Adverse events led to
discontinuation in one out of six patients. From these open results, it seems
reasonable to recommend this combination, complementary in terms of mechanism of 
action, as a potential strategy in patients with refractory migraine.

Publication Types: 
    Clinical Trial

PMID: 17212609 [PubMed - indexed for MEDLINE]

939: Tohoku J Exp Med. 2007 Jan;211(1):23-30.

Increased nitrosative and oxidative stress in platelets of migraine patients.

Yilmaz G, Sürer H, Inan LE, Coskun O, Yücel D.

Clinical Biochemistry Laboratory, Ankara Education and Research Hospital,
Ministry of Health, Ankara 06340, Turkey.

The molecular mechanisms of migraine have not been fully clarified yet. Increased
nitrosative and oxidative stress may be associated with migraine attacks.
Platelets may play an important role in migraine patients and they can reflect
the lability of tissues to nitrosative/oxidative stress. In the present study, we
aimed to determine the levels of nitrosative and oxidative stress markers in
platelets of migraine patients during headache-free and attack periods. A total
of 56 subjects (22 migraine without aura, 14 migraine with aura, and 20 age- and 
sex-matched healthy controls) were included in the study and nitric oxide (NO)
metabolites, malondialdehyde (MDA), and thiol (SH) groups were measured in
platelets. During migraine attacks, platelet levels of nitrate, nitrite and MDA
were significantly higher in migraineurs than these in control subjects (p =
0.042, p = 0.005 and p = 0.042, respectively). By contrast, during headache-free 
period, no statistically significant differences were found in the platelet
levels of nitrate, nitrite and MDA between migraineurs and controls (p > 0.05),
although the marginal increases were detected in migraineurs. These results
suggest that increased biomarkers of nitrosative and oxidative stress in
platelets may be important in migraine patients, especially during attacks;
increase of NO metabolites in platelets during attacks supports the opinion that 
NO may play a modulatory role in biological processes particularly by
vasodilatation in migraine attacks. Therefore, MDA and NO metabolites may serve
as useful markers to show the increased vulnerability to nitrosative and
oxidative stress in migraine patients.

PMID: 17202769 [PubMed - indexed for MEDLINE]

940: J Clin Neurosci. 2007 Mar;14(3):249-51. Epub 2006 Dec 27.

The A218C polymorphism of tryptophan hydroxylase gene and migraine.

Erdal N, Herken H, Yilmaz M, Erdal E, Bayazit YA.

Department of Biophysics, Mersin University, Mersin, Turkey.

OBJECTIVE: To determine the significance of the A218C polymorphism of the
tryptophan hydroxylase (TPH) gene in migraine. METHODS: Fifty-nine migraineurs
and 62 healthy controls were included in the study, and polymerase chain reaction
- restriction fragment length polymorphism assays were used to determine TPH
A218C polymorphism. RESULTS: There was no association between TPH gene
polymorphism and gender, family history of migraine and epilepsy, or aura. There 
was no significant difference between the allele frequencies of both groups
(p>0.05). A significant difference was found between the genotypes of the
migraineurs and controls regarding the AA genotype. Homozygosity for the C allele
or heterozygosity for the A or C was not associated with the occurrence of
migraine (p>0.05), but homozygosity for the A allele was less frequent in the
migraineurs (p=0.02). CONCLUSION: Since it is unlikely that TPH polymorphism
alters serotonin biosynthesis, its association with migraine may be attributed to
linkage disequilibrium with a functional variant within the TPH gene or a nearby 
gene.

PMID: 17194593 [PubMed - indexed for MEDLINE]

941: Neurology. 2006 Dec 26;67(12):2159-63.

Prevention of menstrual attacks of migraine: a double-blind placebo-controlled
crossover study.

MacGregor EA, Frith A, Ellis J, Aspinall L, Hackshaw A.

The City of London Migraine Clinic, 22 Charterhouse Square, London, EC1M 6DX, UK.
anne.macgregor@bartsandthelondon.nhs.uk

OBJECTIVE: To assess the effect of perimenstrual estradiol supplements on
menstrual attacks of migraine associated with estrogen withdrawal. METHODS: Women
with regular menstrual cycles and menstrual migraine or menstrually related
migraine completed an initial three-cycle assessment confirming eligibility for a
six-cycle crossover study using estradiol or placebo to prevent menstrual attacks
of migraine. Women collected early morning samples of urine daily for laboratory 
assay and used a fertility monitor to identify peak fertility associated with
ovulation. Estradiol gel or placebo was first applied on the tenth day following 
the first day of peak fertility and continued daily until, and including, the
second full day of menstruation. Women kept a daily migraine diary and continued 
their usual treatment for migraine. The main outcome was the number of days
during gel use on which a migraine occurred. RESULTS: Data from 35 women were
available for a paired analysis. Percutaneous estradiol was associated with a 22%
reduction in migraine days (RR 0.78, 95% CI 0.62 to 0.99, p = 0.04); these
migraines were less severe and less likely to be associated with nausea. This
was, however, followed by a 40% increase in migraine in the 5 days following
estradiol vs placebo (RR 1.40, 95% CI 1.03 to 1.92, p = 0.03). CONCLUSION:
Although perimenstrual percutaneous estradiol showed benefit during treatment,
this was offset by deferred estrogen withdrawal, triggering post-dosing migraine 
immediately after the gel was stopped. Further work could assess if this could be
avoided by extending the duration of treatment with estradiol.

Publication Types: 
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 17190936 [PubMed - indexed for MEDLINE]

942: CNS Drugs. 2007;21(1):73-82.

Use of the sustained pain-free plus no adverse events endpoint in clinical trials
of triptans in acute migraine.

Dodick DW, Sandrini G, Williams P.

Department of Neurology, Mayo Clinic, Scottsdale, Arizona 85259, USA.
Dodick.David@mayo.edu

OBJECTIVE: To assess the relationship between the sustained pain free (SPF) and
adverse event (AE) rates associated with six oral serotonin 5-HT(1B/1D) receptor 
agonists (triptans) used for the treatment of acute migraine, employing data from
a previous meta-analysis (that included almotriptan, eletriptan, naratriptan,
rizatriptan, sumatriptan and zolmitriptan, but not frovatriptan) in order to
provide a rationale for the use of the rate of patients who are SPF plus no AE
(SNAE) as an endpoint in trials of medications for acute migraine. BACKGROUND:
The attributes of drug treatment for acute migraine that are most important to
people who experience them are complete pain relief, lack of recurrence, rapid
onset and lack of AEs. The endpoints used to assess therapy for acute migraine do
not always address these elements. METHODS: The relationship between SPF and AE
rates was explored using nonparametric regression techniques, and the box-plot
method was used to identify outliers. The estimated SNAE rate for each triptan
was calculated with and without assuming independence between efficacy and
tolerability. RESULTS: At the level of the individual agent, there was a
significant relationship between the efficacy and tolerability of each triptan,
with the exception of almotriptan 12.5 mg, which had an AE rate approximately 30%
lower than would be expected, and eletriptan 20 mg, which had an AE rate
approximately 20% higher than would be expected, on the basis of their efficacy. 
Almotriptan 12.5 mg and eletriptan 20 mg had the highest and lowest base-case
values for SNAE, respectively, and both qualified statistically as outliers to
the distribution of SNAE values obtained with the other triptans. The probability
that each triptan was superior to the reference agent (sumatriptan 100 mg) in
terms of SNAE was calculated across all possible values (at the level of the
individual patient) for the relationship between efficacy and tolerability.
Again, almotriptan 12.5 mg and eletriptan 20 mg had the highest and lowest values
for their SNAE rates, respectively, and almotriptan 12.5 mg qualified
statistically as an outlier from the distribution of the probabilities obtained
for the other triptans. CONCLUSION: This analysis determined that higher SPF
rates were strongly associated with higher AE rates, with the notable exception
of almotriptan 12.5 mg, which had a lower than expected AE rate, resulting in the
highest SNAE rate of the included triptans and doses. SNAE is a useful measure
that can be used to discriminate between therapies and this endpoint incorporates
the attributes that are most relevant to patient satisfaction with treatment. We 
recommend calculation of the SNAE rate at the level of the individual patient in 
future clinical trials of medication for the treatment of acute migraine to
facilitate selection of a treatment for acute migraine that offers the best
chance for effective management.

Publication Types: 
    Evaluation Studies

PMID: 17190530 [PubMed - indexed for MEDLINE]

943: Cell Mol Life Sci. 2007 Feb;64(3):331-44.

The search for migraine genes: an overview of current knowledge.

Colson NJ, Fernandez F, Lea RA, Griffiths LR.

Genomics Research Centre, School of Medical Science, Griffith University, Gold
Coast, Queensland, Australia.

Migraine is a complex familial condition that imparts a significant burden on
society. There is evidence for a role of genetic factors in migraine, and
elucidating the genetic basis of this disabling condition remains the focus of
much research. In this review we discuss results of genetic studies to date, from
the discovery of the role of neural ion channel gene mutations in familial
hemiplegic migraine (FHM) to linkage analyses and candidate gene studies in the
more common forms of migraine. The success of FHM regarding discovery of genetic 
defects associated with the disorder remains elusive in common migraine, and
causative genes have not yet been identified. Thus we suggest additional
approaches for analysing the genetic basis of this disorder. The continuing
search for migraine genes may aid in a greater understanding of the mechanisms
that underlie the disorder and potentially lead to significant diagnostic and
therapeutic applications.

Publication Types: 
    Review

PMID: 17187176 [PubMed - indexed for MEDLINE]

944: Neurology. 2007 Feb 20;68(8):591-6. Epub 2006 Dec 20.

Outcomes and predictors of chronic daily headache in adolescents: a 2-year
longitudinal study.

Wang SJ, Fuh JL, Lu SR, Juang KD.

Department of Neurology, National Yang-Ming University School of Medicine,
Taiwan. sjwang@vghtpe.gov.tw

OBJECTIVES: To assess the outcomes and predictors of chronic daily headache (CDH)
in a community-based cohort of adolescents. METHODS: We established a field
sample of 122 adolescents (32 M/90 F, ages 12 to 14) with CDH in 2000. These
adolescents received annual follow-up by neurologists for 2 years via a
semistructured telephone interview. CDH was defined as > or =15 headache
days/month, average > or =2 h/day for >3 months; subtypes were classified based
on the original and appendix criteria of the International Classification of
Headache Disorders (2nd ed.; ICHD-2). Poor outcome was defined as persistence of 
CDH at 2 years. RESULTS: Follow-up response rates were 92% in 2001 and 84% in
2002. Average monthly headache frequency was 11.0 +/- 9.7 days in 2001 and 7.7
+/- 6.5 days in 2002. CDH persistence rates were 40% in 2001 and 25% in 2002.
Medication overuse declined from 20% (baseline) to 6% at 2 years. The prevalence 
of migraine did not change throughout the follow-up (67 to 60%), whereas that of 
tension-type headache deceased from 86 to 46% (p < 0.001). Chronic migraine
prevalence increased markedly at baseline and became the most common CDH subtype 
at follow-up when using the ICHD-2 appendix criteria. During follow-up, seven
subjects (6%) dropped out of school. Independent predictors for CDH persistence
were medication overuse and major depression. CONCLUSIONS: Most adolescents with 
chronic daily headache (CDH) continued to have frequent headaches, although the
incidence of CDH declined at follow-up. Migraine diagnosis gained prominence as
headache frequency decreased. The percentages of chronic migraine in adolescents 
with CDH increased obviously if the appendix criteria were applied.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17182975 [PubMed - indexed for MEDLINE]

945: Nat Clin Pract Cardiovasc Med. 2007 Jan;4(1):55-8.

Migraine with aura following atrial septostomy for pulmonary arterial
hypertension.

Rogan MP, Walsh KP, Gaine SP.

Department of Respiratory Medicine, Mater Misericordiae University Hospital,
Dublin, Ireland.

BACKGROUND: A 34-year-old woman with known familial pulmonary arterial
hypertension presented with syncope. Despite medical therapy with an
endothelin-receptor antagonist and a phosphodiesterase inhibitor, the patient had
NYHA class III symptoms, with exertional dyspnea. Right heart catheterization
revealed severe pulmonary hypertension (right atrial pressure 15 mmHg, right
ventricular pressure 80/15 mmHg, pulmonary artery pressure 80/35 mmHg, mean
pulmonary artery pressure 52 mmHg). The patient underwent balloon atrial
septostomy, creating a right-to-left shunt. Although she had no history of
headaches or migraine attacks, the patient developed a migraine headache with
aura on the third day after the procedure. Migraine attacks recurred for the next
2 days, but symptoms were relieved with simple analgesia. INVESTIGATIONS:
Physical examination, electrocardiography, laboratory testing, 6-min-walk test,
right heart catheterization, chest radiography, transesophageal echocardiography,
transthoracic echocardiography. DIAGNOSIS: Migraine with aura following atrial
septostomy. MANAGEMENT: Bosentan, sildenafil, furosemide, spironolactone and
warfarin therapy, atrial septostomy, and paracetamol therapy for migraine.

Publication Types: 
    Case Reports

PMID: 17180151 [PubMed - indexed for MEDLINE]

946: Clin Drug Investig. 2007;27(1):59-66.

Effectiveness and satisfaction with zolmitriptan 5 mg nasal spray for treatment
of migraine in real-life practice: results of a postmarketing surveillance study.

Diener HC, Evers S.

Department of Neurology, University of Duisburg-Essen, Essen, Germany.
hans.diener@uni-duisburg-essen.de

OBJECTIVE: Addressing the needs of migraineurs by actively seeking patient
feedback on disease-related disability and treatment satisfaction may lead to
improved management and treatment outcomes. Patient feedback can be collected in 
postmarketing surveillance (PMS) studies. The objective of this PMS study was to 
evaluate the efficacy and tolerability of zolmitriptan 5 mg nasal spray in the
acute treatment of migraine attacks. PATIENTS AND METHODS: Patients received
zolmitriptan 5 mg nasal spray to treat migraine attacks of any severity and were 
followed up after a maximum of 4 months. Patients evaluated the efficacy and
tolerability of zolmitriptan nasal spray, and were asked whether they wished to
continue using zolmitriptan nasal spray and their preference compared with
previous treatments. Physicians also assessed the efficacy and tolerability of
zolmitriptan nasal spray. RESULTS: A total of 1838 patients (84.8% females)
participated in the study. Within 30 minutes of administration of zolmitriptan
nasal spray, 85.0% of patients reported improvements in headache pain, with 25.1%
reporting an improvement within 10 minutes. At 1 hour post-dose, 57.9% of
patients were pain free and 61.7% were able to resume usual daily activities.
Most patients (72.9%) rated zolmitriptan nasal spray as 'better' than previous
therapy. The majority (88.8%) expressed a wish to continue using zolmitriptan
nasal spray. Physicians evaluated the efficacy of zolmitriptan nasal spray as
'excellent' or 'good' in 89.4% of patients. Tolerability was evaluated as
'excellent' or 'good' in 91.6% of patients. CONCLUSIONS: Zolmitriptan 5 mg nasal 
spray provides favourable efficacy and tolerability in the acute treatment of
migraine attacks. Most patients assessed zolmitriptan nasal spray as 'better'
than previous treatment, with nearly all wishing to continue using it.

Publication Types: 
    Clinical Trial
    Multicenter Study
    Research Support, Non-U.S. Gov't

PMID: 17177580 [PubMed - indexed for MEDLINE]

947: Int J Cardiol. 2007 Sep 3;120(3):357-62. Epub 2006 Dec 12.

Spontaneous large right-to-left shunt and migraine headache with aura are risk
factors for recurrent stroke in patients with a patent foramen ovale.

Giardini A, Donti A, Formigari R, Salomone L, Palareti G, Guidetti D, Picchio FM.

Pediatric Cardiology and Adult Congenital Unit, University of Bologna, Italy.
alessandro5574@iol.it

BACKGROUND: We sought to determine whether migraine headache with aura (MHA) and 
spontaneous large right-to-left (R-L) shunt are risk factors for recurrent
cerebral ischemic events in cryptogenic stroke patients with a patent foramen
ovale (PFO). METHODS: 140 patients with a PFO and cryptogenic stroke underwent
transcatheter defect closure at our institution at a mean age of 45+/-13 years.
We retrospectively analyzed follow-up data from the first cerebral ischemic event
to the time of PFO closure. Before the procedure, all patients underwent
transesophageal echocardiography (TEE); Transcranial Doppler scanning (TCD) was
additionally performed on the last 59 patients. We analyzed the impact of MHA,
thrombophilia, spontaneous large R-L shunt, and atrial septal aneurysm (ASA) on
the risk of recurrent cerebral ischemic events. RESULTS: 44 patients (31%) had
had at least 1 recurrent event during a follow-up of 2.2+/-2.6 years. Patients
with recurrent events were more commonly females (p=0.0001), had more often an
associated thrombophilia (p=0.0077), and had a higher prevalence of spontaneously
large R-L shunt both at TEE and at TCD (p<0.05). They also had more commonly a
history of MHA (p=0.0009) and more frequent episodes of MHA (p=0.0048). Patients 
with MHA had a higher risk of recurrent events when compared to patients without 
(odds ratio 3.87, 95% CI 1.75 to 8.50). Thrombophilia (p=0.001) and spontaneous
large R-L shunt (p=0.02) were independent predictors of recurrent stroke.
CONCLUSIONS: In cryptogenic stroke patients with a PFO, a history of MHA, large
spontaneous large R-L shunt, and thrombophilia are all associated with a higher
risk of recurrent events.

PMID: 17166607 [PubMed - indexed for MEDLINE]

948: J Headache Pain. 2006 Dec;7(6):389-94. Epub 2006 Dec 13.

Treatment with sumatriptan 50 mg in the mild phase of migraine attacks in
patients with infrequent attacks: a randomised, double-blind, placebo-controlled 
study.

Tfelt-Hansen P, Bach FW, Daugaard D, Tsiropoulos I, Riddersholm B.

Danish Headache Center, Department of Neurology, University of Copenhagen,
Glostrup Hospital, DK-2600, Glostrup, Denmark. tfelt@inet.uni2.dk

Most migraine patients with infrequent attacks are currently not treated with
migrainespecific medication such as triptans. The response of these patients to
triptans is unknown. The objective of this study was to investigate the efficacy 
and tolerability of sumatriptan 50 mg vs. placebo in migraine patents with
infrequent migraine attacks when medication is taken during the mild phase of an 
attack. The study design was double-blind, placebocontrolled, parallel-group and 
randomised. Migraine patients were recruited by general practitioners and
referred to one of 4 study centres. Additional patients were recruited by
advertising. The patients were eligible for the study if they had between 6 and
12 migraine attacks with or without aura per year. The patients were instructed
to take the medication during the mild phase of a single attack. The primary
efficacy measure was the percentage of patients pain-free after 2 h. Fortysix
percent of treated attacks were moderate or severe. In the intention-to-treat
analysis, sumatriptan was superior (20/51 patients were pain-free) to placebo
(8/47 patients pain-free) (p=0.03). Adverse events (AEs) occurred more frequently
after sumatriptan (40%) than after placebo (13%) (p=0.003) and most AEs were mild
or moderate. In this migraine population with infrequent attacks, sumatriptan was
superior to placebo and was generally well tolerated.

Publication Types: 
    Comparative Study
    Evaluation Studies
    Randomized Controlled Trial

PMID: 17164991 [PubMed - indexed for MEDLINE]

949: J Headache Pain. 2006 Dec;7(6):377-88. Epub 2006 Dec 13.

Electrophysiological response patterns of primary sensory cortices in migraine.

Ambrosini A, Schoenen J.

Headache Clinic, INM Neuromed, IRCCS, Via Atinense 18, I-86077, Pozzilli (IS),
Italy. anna.ambrosini@neuromed.it

Migraine is an ictal disorder characterised by a particular vulnerability of
patients to sensory overload, both during and outside of the attack. Central
nervous system dysfunctions are supposed to play a pivotal role in migraine.
Electroneurophysiological methods, which aim to investigate sensory processing,
seem thus particularly appropriate to study the pathophysiology of migraine. We
have thus reviewed evoked potential studies performed in migraine patients.
Although results are in part contradictory, these studies nonetheless demonstrate
an interictal dysfunction of sensory cortices, and possibly of subcortical
structures, in migraine with and without aura. The predominant abnormality is a
deficient habituation of evoked responses to repeated stimuli, probably due to
cortical, and possibly widespread neural, "dysexcitability".

Publication Types: 
    Review

PMID: 17164990 [PubMed - indexed for MEDLINE]

950: Clin Drug Investig. 2006;26(5):287-96.

Tanacetum parthenium and Salix alba (Mig-RL) combination in migraine prophylaxis:
a prospective, open-label study.

Shrivastava R, Pechadre JC, John GW.

Naturveda - Vitro-Bio Research Institute, ZAC de Lavaur, Issoire, France.

BACKGROUND: Tanacetum parthenium (feverfew) has been used traditionally to treat 
migraine, and although its mechanism of action is not fully understood, serotonin
5-HT receptor blocking effects have been suggested. T. parthenium and Salix alba 
(white willow) either alone or in combination (Mig-RL) were recently shown to
inhibit binding to 5-HT(2A/2C) receptors; T. parthenium failed to recognise
5-HT(1D) receptors, whereas S. alba or the combination did. It was hypothesised
that S. alba in combination with T. parthenium may provide superior migraine
prophylactic activity compared with T. parthenium alone. METHODS: A prospective, 
open-label study was performed in 12 patients diagnosed with migraine without
aura. Twelve weeks' treatment with T. parthenium 300 mg plus S. alba 300 mg
(Mig-RL) twice daily was administered to determine the effects of therapy on
migraine attack frequency (primary efficacy criterion), intensity and duration
(secondary efficacy criteria), and quality of life, together with tolerability
for patients. RESULTS: Attack frequency was reduced by 57.2% at 6 weeks (p <
0.029) and by 61.7% at 12 weeks (p < 0.025) in nine of ten patients, with 70%
patients having a reduction of at least 50%. Attack intensity was reduced by
38.7% at 6 weeks (p < 0.005) and by 62.6% at 12 weeks (p < 0.004) in ten of ten
patients, with 70% of patients having a reduction of at least 50%. Attack
duration decreased by 67.2% at 6 weeks (p < 0.001) and by 76.2% at 12 weeks (p < 
0.001) in ten of ten patients. Two patients were excluded for reasons unrelated
to treatment. Self-assessed general health, physical performance, memory and
anxiety also improved by the end of the study. Mig-RL treatment was well
tolerated and no adverse events occurred. CONCLUSION: The remarkable efficacy of 
Mig-RL in not only reducing the frequency of migraine attacks but also their pain
intensity and duration in this trial warrants further investigation of this
therapy in a double-blind, randomised, placebo-controlled investigation involving
a larger patient population.

Publication Types: 
    Clinical Trial
    Meta-Analysis
    Research Support, Non-U.S. Gov't

PMID: 17163262 [PubMed - indexed for MEDLINE]

951: Med Hypotheses. 2007;68(6):1318-27. Epub 2006 Dec 11.

Comment in:
    Med Hypotheses. 2007;69(3):704-5.

From the nutcracker-phenomenon of the left renal vein to the midline congestion
syndrome as a cause of migraine, headache, back and abdominal pain and functional
disorders of pelvic organs.

Scholbach T.

Authorized Outpatient Ultrasound Department of the Saxonian Association of CHI
Physicians Delitzscher Strasse 141, D - 04129 Leipzig, Germany.
thomas.scholbach@sanktgeorg.de

This paper presents the hypothesis, that pain and functional disturbances of
organs which lie on the midline of the body might be caused by a venous
congestion of these organs. Cause of their congestion is the participation of
these organs (vertebral column, skull, brain, spinal medullary, uterus, prostate,
left ovary/testis, urinary bladder rectum, vagina, urethra) in the collateral
circulation of the left renal vein. In many patients with complaints of the above
mentioned organs the left renal vein is compressed inside the fork formed by the 
superior mesenteric artery and the aorta. This so called nutcracker phenomenon is
incompletely understood today. It can lead to a marked reduction of left renal
perfusion and forces the left renal blood to bypass the venous compression site
via abundant collaterals. These collaterals are often not sufficient. Their walls
become stretched and distorted - varices with inflamed walls are formed. These
dilated veins are painful, interfere with the normal organ's function and demand 
more space than usual. This way pain in the midline organs and functional
derangement of the midline organs can occur. The term "midline congestion
syndrome" seems appropriate to reflect the comprehensive nature of this frequent 
disorder. The rationale for this hypothesis is based on the novel
PixelFlux-technique (www.chameleon-software.de) of renal tissue perfusion
measurement. With this method a relevant decline of left renal cortical perfusion
was measured in 16 affected patients before therapy (left/right ratio: 0.79).
After a treatment with acetylsalicylic acid in doses from 15 to 200mg/d within
14-200 days a complete relief of so far long lasting therapy-resistant midline
organ symptoms was achieved. Simultaneously the left/right renal perfusion ratio 
increased significantly to 1.24 (p=0.021). This improvement of left renal
perfusion can be explained by a better drainage of collateral veins, diminution
of their wall distension, thereby decline of their intramural inflammation,
reduction of their mass effects (especially by the replaced spinal fluid inside
the spinal canal and the skull), and altogether a reduction of pain and
functional derangement in the affected midline organs. The proposed theory might 
influence the current understanding of such frequent and difficult to treat
diseases as chronic back pain, headaches, frequent cystitis, enuresis, abdominal 
pain, flank pain and might spur new theories of arterial hypertension, placental 
insufficiency, prostate diseases and myelopathies.

PMID: 17161550 [PubMed - indexed for MEDLINE]

952: Am J Emerg Med. 2007 Jan;25(1):60-4.

Sumatriptan for the treatment of undifferentiated primary headaches in the ED.

Miner JR, Smith SW, Moore J, Biros M.

Department of Emergency Medicine, Hennepin County Medical Center, Minneapolis, MN
55415, USA. miner015@umn.edu

OBJECTIVE: In this study, we determine the effectiveness and adverse effects of
sumatriptan when used in the emergency department (ED) as a first-line treatment 
for benign undifferentiated headaches, and determine if the International
Headache Society (IHS) classification of migraine, probable migraine, or
tension-type headache has any effect on the effectiveness of the treatment. We
hypothesize that there is no difference in the effectiveness of pain relief or
frequency and severity of adverse effects between patients with migraine,
probable migraine, or tension-type headaches when treated with sumatriptan.
METHODS: This was a prospective observational study of adult ED patients
undergoing treatment for primary headaches (ie, patients in whom head trauma,
vascular disorders, infection, or disorders of facial or cranial structures have 
been clinically excluded). Other exclusions were renal impairment, hepatic
impairment, and risk factors for coronary artery disease. Consenting patients
then were asked to complete a 100-mm visual analog scale (VAS) representing their
perceived pain, after which they were interviewed by a research assistant who
completed a headache diagnosis worksheet, which differentiates the headache by
IHS criteria. The patient repeated the VAS score at 30 and 60 minutes. Data were 
analyzed using descriptive statistics and chi squared tests. RESULTS: One hundred
forty-seven patients were enrolled: 84 (57.1%) patients with migraine headache,
45 (30.7%) with a probable migraine headache, and 18 (12.2%) with a tension
headache. A 50% reduction in VAS scores 60 minutes postdose was seen in 87 (59%) 
of 147 patients; 50 (60%) of 84 of migraine patients, 25 (56%) of 45 of probable 
migraine patients, and 12 (67%) of 18 tension patients (P = .72). There were no
serious adverse events reported. Forty-seven patients (32%) received rescue
medications after the 60-minute VAS score: 29 (34.5%) patients in the migraine
group, 15 (33.3%) patients in the probable migraine group, and 3 (15.8%) patients
in the tension-type headache group (P = .26). CONCLUSIONS: Most of the patients
presenting with primary headaches had migraine or probable migraine headaches.
There was no difference in sumatriptan's effectiveness based on the
classification of the headache using IHS criteria.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17157685 [PubMed - indexed for MEDLINE]

953: Acta Neurol Scand. 2007 Jan;115(1):34-40.

Almotriptan and zolmitriptan in the acute treatment of migraine.

Goadsby PJ, Massiou H, Pascual J, Diener HC, Dahlöf CG, Mateos V, Dowson AJ,
Raets I, Cunha L, Färkkilä M, Manzoni GC.

Headache Group, Institute of Neurology, Queen Square, London, UK.
peterg@ion.ucl.ac.uk

OBJECTIVE: To compare almotriptan and zolmitriptan in the treatment of acute
migraine. METHODS: This multicentre, double-blind trial randomized adult
migraineurs to almotriptan 12.5 mg (n = 532) or zolmitriptan 2.5 mg (n = 530) for
the treatment of a single migraine attack. The primary end point was sustained
pain free plus no adverse events (SNAE); other end points included pain relief
and pain free at several time points, sustained pain free, headache recurrence,
use of rescue medication, functional impairment, time lost because of migraine,
treatment acceptability, and overall treatment satisfaction. RESULTS: No
significant difference was seen in SNAE (almotriptan 29.2% vs zolmitriptan 31.8%)
or the other efficacy end points measured. The incidence of triptan-associated
AEs and triptan-associated central nervous system AEs was significantly lower for
patients receiving almotriptan compared to zolmitriptan. CONCLUSIONS: Almotriptan
and zolmitriptan were associated with similar efficacy and overall tolerability
in the treatment of acute migraine. Almotriptan was associated with a
significantly lower rate of triptan-associated AEs.

Publication Types: 
    Comparative Study
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 17156263 [PubMed - indexed for MEDLINE]

954: J Headache Pain. 2006 Dec;7(6):403-6. Epub 2006 Dec 10.

The broad treatment expectations of migraine patients.

Kelman L.

Headache Center of Atlanta, 5671 Peachtree Dunwoody Road, Suite 620, Atlanta, GA 
30342, USA. lkelman@mindspring.com

The objective was to define the overall treatment expectations of migraineurs.
Many studies have defined the expectations of patients regarding their acute
migraine treatment but little information is available regarding overall
expectations. During routine first visits to the author's headache clinic
patients were asked about their expectations of treatment as well as demographics
and headache characteristics. Demographics were recorded and expectations were
compared between different forms of migraine and between females and males. One
thousand seven hundreds and fifty patients were diagnosed with ICHD-II 1.1, 1.2, 
1.5.1 and 1.6, 1207 with migraine and 543 with probable migraine. A percentage of
27.8 expected a cure from their treatment, 79.7% to be symptom free, 95.2% a
reduction in frequency of headaches, 95.6% a reduction in severity of headaches
and 95.5% an improved quality of life. Males had greater expectations for
reduction in severity of migraines than females. Patients with migraine were more
likely to expect a cure and a reduction in headache severity than patients with
probable migraine. Patients with aura with every headache were more likely to
expect reduced frequency of headache than patients with no aura. Some patients
did expect a cure for their headaches and knowing patients' expectations may
facilitate headache management and education, and achieve more realistic
outcomes.

PMID: 17149569 [PubMed - indexed for MEDLINE]

955: J Headache Pain. 2006 Dec;7(6):413-5. Epub 2006 Dec 10.

Narcotic analgesics for acute migraine in the emergency room: are we meeting
Headache Societies' guidelines?

Wasay M, Zaki KS, Khan SU, Rehmani R.

Department of Neurology, The Aga Khan University, and Department of Medicine,
Abbasi Shaheed Hospital, Karachi, 74800, Pakistan. mohammad.wasay@aku.edu

We analysed 161 patients with acute migraine in our emergency room (ER) to
identify the use of narcotic analgesics as first-line treatment. Twenty-four
percent of patients were treated with opioid analgesics and 76% patients were
treated with non-opioid analgesics. Pain was completely relieved in 100 (62%)
patients, partially relieved in 50 (31%) patients and was not relieved in 11 (7%)
patients at the time of discharge. Pain relief was not related to the use of
opioids vs. non-opioids. The treatment of acute migraine in our ER is in line
with the guidelines of the Headache Societies and needs further improvement.

Publication Types: 
    Clinical Trial
    Comparative Study

PMID: 17149566 [PubMed - indexed for MEDLINE]

956: J Headache Pain. 2006 Dec;7(6):433-7. Epub 2006 Dec 10.

Migraine--the forgotten epidemic: development of the EHF/WHA Rome Declaration on 
Migraine.

Diener HC, Steiner TJ, Tepper SJ.

Department of Neurology, University of Duisburg-Essen, Hufelandstr. 55, 45147,
Essen, Germany. hans.diener@uni-duisburg-essen.de

Despite the availability of effective treatments, many migraine sufferers in
Europe still do not receive optimal treatment. A panel of specialists,
primary-care physicians and patient-group representatives met in Rome on 10-11
June 2005, under the auspices of the European Headache Federation (EHF), the
World Headache Alliance (WHA) and the University of Duisburg-Essen, to review the
scientific background, management issues, and physician, patient and government
perspectives on migraine. The goal of the meeting was to produce the EHF/WHA Rome
Declaration on Migraine, a statement of the actions required to improve migraine 
care and the quality of life of people with migraine. The key recommendation of
the EHF/WHA Rome Declaration on Migraine is education of migraine sufferers,
health professionals and health-policy makers.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17149560 [PubMed - indexed for MEDLINE]

957: Catheter Cardiovasc Interv. 2007 Jan;69(1):9-14.

Patent foramen ovale and migraine.

Post MC, Luermans JG, Plokker HW, Budts W.

Department of Cardiology, St. Antonius Hospital, Nieuwegein, the Netherlands, and
University Hospital Gasthuisberg, Leuven, Belgium. m.post@antonius.net

Migraine is a common neurological disorder with a great impact on the quality of 
life and social activities. The patent foramen ovale (PFO) is an intra-atrial
right-to-left shunt with a prevalence of 25% in the general population. An
increased prevalence is found in patients with migraine, especially in migraine
with aura. Percutaneous PFO closure might decrease the prevalence of migraine.
However, most of these observational studies were retrospective without a
randomized design and the results need to be interpreted with caution. In this
review we describe the association between PFO and migraine and the different
pathophysiological hypotheses, which have been proposed to explain this
relationship. Copyright (c) 2006 Wiley-Liss, Inc.

Publication Types: 
    Review

PMID: 17143907 [PubMed - indexed for MEDLINE]

958: Brain. 2007 Feb;130(Pt 2):346-56. Epub 2006 Dec 2.

Comment in:
    Brain. 2007 Feb;130(Pt 2):312-3.

The genetic spectrum of a population-based sample of familial hemiplegic
migraine.

Thomsen LL, Kirchmann M, Bjornsson A, Stefansson H, Jensen RM, Fasquel AC,
Petursson H, Stefansson M, Frigge ML, Kong A, Gulcher J, Stefansson K, Olesen J.

Danish Headache Center, University of Copenhagen, Department of Neurology
Glostrup Hospital, Copenhagen, Denmark. llt@dadlnet.dk

Familial hemiplegic migraine (FHM) is a rare subtype of migraine with aura and
transient hemiplegia. FHM mutations are known in three genes, the CACNA1A (FHM1) 
gene, the ATP1A2 (FHM2) and the SCN1A (FHM3) gene and seem to have an
autosomal-dominant mode of inheritance. The aim of this study was to search for
FHM mutations in FHM families identified through a screen of the Danish
population of 5.2 million people. FHM patients were diagnosed according to the
International Classification of Headache Disorders and all FHM patients had a
physical and neurological examination by a physician. A total of 147 FHM patients
from 44 different families were identified; 43 FHM families participated in this 
study. Linkage analysis of these families shows clear linkage to the FHM locus
(FHM1) on chromosome 19, supportive linkage to the FHM2 locus whereas no linkage 
was found to the FHM3 locus. Furthermore, we sequenced all exons and promoter
regions of the CACNA1A and ATP1A2 genes and screened for the Q1489K mutation in
the SCN1A gene. CACNA1A gene mutations were identified in three of the FHM
families, two known FHM mutations, R583Q and T666M and one novel C1369Y mutation.
Three FHM families were identified with novel mutations in the ATP1A2 gene; a
family with a V138A mutation, a family with a R202Q mutation and a family with a 
R763C mutation. None of the Danish FHM families have the Q1489K mutation in the
SCN1A gene. Our study shows that only 14% (6/42) of FHM families in the general
Danish population have exonic FHM mutations in the CACNA1A or ATP1A2 gene. The
families we identified with FHM mutations in the CACNA1A and ATP1A2 genes were
extended, multiple affected families whereas the remaining FHM families were
smaller. The existence of many small families in the Danish FHM cohort may
reflect less bias in FHM family ascertainment and/or more locus heterogeneity
than described previously.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17142831 [PubMed - indexed for MEDLINE]

959: Trends Mol Med. 2007 Jan;13(1):39-44. Epub 2006 Dec 1.

Recent advances in understanding migraine mechanisms, molecules and therapeutics.

Goadsby PJ.

Institute of Neurology, The National Hospital for Neurology and Neurosurgery,
Queen Square, London WC1N 3BG, UK. peterg@ion.ucl.ac.uk

Migraine is a complex, disabling disorder of the brain that manifests itself as
attacks of often severe, throbbing head pain with sensory sensitivity to light,
sound and head movement. There is a clear familial tendency to migraine, which
has been well defined in a rare autosomal dominant form of familial hemiplegic
migraine (FHM). FHM mutations so far identified include those in CACNA1A (P/Q
voltage-gated Ca(2+) channel), ATP1A2 (N(+)-K(+)-ATPase) and SCN1A (Na(+)
channel) genes. Physiological studies in humans and studies of the experimental
correlate--cortical spreading depression (CSD)--provide understanding of aura,
and have explored in recent years the effect of migraine preventives in CSD.
Therapeutic developments in migraine have come by targeting the trigeminovascular
system, with the most-recent being the proof-of-principle study of calcitonin
gene-related peptide (CGRP) receptor antagonists in acute migraine. To understand
the basic pathophysiology of migraine, brain imaging studies have firmly
established reproducible changes in the brainstem in regions that include areas
that are involved in sensory modulation. These data lead to the view that
migraine is a form of sensory dysmodulatio--a system failure of normal sensory
processing.

Publication Types: 
    Review

PMID: 17141570 [PubMed - indexed for MEDLINE]

960: Clin Neurophysiol. 2007 Feb;118(2):457-63. Epub 2006 Dec 1.

The blink reflex in "chronic migraine".

De Marinis M, Pujia A, Colaizzo E, Accornero N.

Department of Neurological Sciences, La Sapienza University, Rome, Italy.
m.de.marinis@mclink.it

OBJECTIVES: Activation of the trigeminovascular system and sensitisation of
brainstem trigeminal nuclei are thought to play an important role in migraine.
The aim of this study was to investigate the blink reflex and its habituation in 
patients with "chronic migraine". METHODS: We studied 35 patients suffering from 
"chronic migraine" (IHS classification criteria) outside and during a spontaneous
attack, and 35 control subjects. An EMG device with a specific habituation test
program was used to elicit and record blink reflex responses and to randomly
repeat stimulations at different time intervals so as to induce habituation.
RESULTS: The R(1) and R(2) latencies, amplitudes and areas of the basal blink
reflex were similar in patients studied both outside and during an attack as well
as in control subjects, whereas the blink reflex habituation responses were
markedly reduced in patients studied outside an attack. The percent changes in
the R(2) areas from the baseline values, obtained when stimuli were delivered at 
time intervals of 10, 5, 4, 3, 2 and 1s, were statistically different
(p<0.01-p<0.001) from those of the same patients studied during a migraine attack
and of those of control subjects. There was a significant correlation between
decreased habituation of the blink reflex and a higher frequency of attacks. The 
stimulus intensities of the blink reflex (multiples of the detection threshold
intensities) were significantly lower (p<0.001) on the side affected, or more
severely affected, by headache in patients studied during a migraine attack.
CONCLUSIONS: The decreased habituation of the blink reflex outside an attack
reflects abnormal excitability in "chronic migraine", which normalizes during the
attacks. The inverse correlation between the frequency of attacks and habituation
responses confirms the abnormal excitability induced by the high frequency of
attacks. Central sensitisation mechanisms (allodynia) may explain the lower
detection thresholds observed on the side affected by headache in patients during
the attacks. SIGNIFICANCE: The blink reflex and its habituation may help shed
light on the subtle neurophysiological changes that occur in migraine patients
between and during attacks.

PMID: 17141567 [PubMed - indexed for MEDLINE]

961: CNS Drugs. 2006;20(12):1019-26.

Efficacy and tolerability of zolmitriptan oral tablet in the acute treatment of
menstrual migraine.

Tuchman M, Hee A, Emeribe U, Silberstein S.

Palm Beach Neurological Center, Palm Beach Gardens, FL 33418, USA.
mmtuchman@aol.com

OBJECTIVE: To determine the efficacy and tolerability of zolmitriptan 2.5 mg oral
tablet as an acute treatment for menstrual migraine attacks. METHODS: This was a 
two-phase, multicentre, randomised, double-blind, placebo-controlled,
parallel-group outpatient study (Phase I is reported here). The study was
conducted at 27 sites in the USA. Eligible women were randomised (1 : 1) to
receive either zolmitriptan 2.5 mg oral tablet or placebo, and instructed to
acutely treat up to two menstrual migraine attacks per menstrual period for up to
three menstrual cycles with a single dose of study medication. Menstrual migraine
was operationally defined as an attack occurring within the time period of 2 days
prior to the expected onset of menses to 5 days after the onset of menses.
Participants were asked to treat migraine headaches of moderate or severe
intensity only that occurred >24 hours after the end of the last migraine attack 
and that had not been acutely treated with other medications. Information
regarding each migraine attack was recorded by patients in treatment diary cards.
The primary efficacy variable was 2-hour headache response (defined as a 2-point 
drop on a 4-point scale) for all attacks treated. Secondary variables included 1-
and 4-hour headache response rate; 1-, 2- and 4-hour headache response based on a
100 mm visual analogue scale (VAS); pain-free rate at 1, 2 and 4 hours; use of
escape medication; the proportion of patients with recurrence within 24 hours of 
initial treatment; and tolerability. RESULTS: The intention-to-treat population
comprised 334 patients (zolmitriptan [n = 174]; placebo [n = 160]). Patients
treated 625 attacks with zolmitriptan and 529 attacks with placebo. Twice as many
patients who took zolmitriptan achieved a 2-hour headache response compared with 
placebo recipients (65.7% vs 32.8%; p < 0.0001). Furthermore, a significantly
higher headache response was observed with zolmitriptan than placebo at all
timepoints assessed. Significantly more zolmitriptan recipients were pain-free 2 
hours post-dose compared with placebo recipients (p < 0.0001). The use of escape 
medication was considerably lower in zolmitriptan recipients (42.6% vs 71.3%; p <
0.0001). Based on the reduction in VAS score of > or = 30 mm from baseline,
significantly more zolmitriptan recipients achieved headache response compared
with placebo recipients at 1, 2 and 4 hours post-dose (all p < 0.0001).
Recurrence was reported in 29.1% of zolmitriptan-treated attacks versus 45.1% of 
placebo-treated attacks (p = 0.0009), with median time to recurrence of 8.5 and
4.0 hours, respectively. Zolmitriptan was well tolerated. CONCLUSION: Oral
zolmitriptan is effective and well tolerated for the acute treatment of menstrual
migraine attacks. The results are similar to those seen with zolmitriptan in
studies of the general migraine population.

Publication Types: 
    Clinical Trial, Phase I
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 17140280 [PubMed - indexed for MEDLINE]

962: Med Pregl. 2006 Jul-Aug;59(7-8):299-304.

The impact of headache severity on quality of life of patients with migraine.

[Article in English, Serbian]

Simić S, Slankamenac P, Cvijanović M, Ilin M, Kopitović A.

Institut za neurologiju, Klinicki centar "Novi Sad", Novi Sad. dsimic@eunet.yu

Migraine is a chronic disease characterized by episodic headache attacks, most
often on one side of the head with pulsating, moderate to severe pain. We
conducted an assessment of headache severity by using the MIGSEV questionnaire,
and the quality of life assessment by using the QVM questionnaire, on a sample of
30 patients suffering from migraine. Afterwards, the research results were
compared. The research results indicate that the majority of patients suffer from
severe and moderate headaches. The quality of life is poorer in patients
suffering from severe headaches.

PMID: 17140027 [PubMed - indexed for MEDLINE]

963: J Fam Pract. 2006 Dec;55(12):1057-62.

Do family physicians fail to provide triptans for patients with migraine?

Walling A, Woolley DC, Molgaard C, Kallail KJ.

Department of Family and Community Medicine, University of Kansas School of
Medicine-Wichita, 1010 North Kansas, Wichita, KS 67214, USA. awalling@kumc.edu

While continuing to improve recognition of migraine in your patient population,
pay particular attention to the adherence rate among those for whom you have
prescribed a triptan. Ask patients who discontinue triptan therapy why they made 
that decision. Besides adverse effects from the agent, reasons may include
medication cost, influence of comorbidities, or triptan interaction with
medications you may not have known about.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17137542 [PubMed - indexed for MEDLINE]

964: J Fam Pract. 2006 Dec;55(12):1038-47.

Migraine: a better way to recognize and treat it.

Landy SH, Kwong WJ, Hutchinson S, Roselli A, Burch SP.

Wesley Headache Clinic, 8974 Bridge Forest Drive, Memphis, TN 38138, USA.
wesleyhead@aol.com

Consider using the Headache Assessment Quiz, which 76% of providers in this study
said enabled patients to adequately convey headache severity/symptoms, compared
with just 20% of providers at baseline who thought patients communicated clearly.
Use the quiz also to better understand the impact of migraine on a patient's
life, and to help determine which patients need migraine-specific therapy.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17137539 [PubMed - indexed for MEDLINE]

965: Prescrire Int. 2006 Oct;15(85):184-8.

Pharmacological prevention of migraine: to be considered case by case.

[No authors listed]

(1) Migraines are characterized by recurrent headaches generally lasting between 
4 and 72 hours and disappearing without complication. They can be incapacitating,
owing to their frequency and/or intensity. (2) Many drugs have been used to
prevent migraines. One of the most common outcome measures used in clinical
trials is the proportion of responder patients, defined as those in whom the
monthly frequency of migraines is at least halved. On average, about one-third of
patients respond to placebo in clinical trials. (3) Propranolol is the
betablocker with the best-documented efficacy: in absolute terms the response
rate is about 30% higher than with placebo. The adverse effects of betablockers
are mainly cardiovascular and neuropsychological. (4) Valproic acid, an
anticonvulsant, is about as effective as propranolol, and its adverse effects are
generally acceptable. (5) Amitriptyline is the antidepressant with the
best-documented preventive effects, with a response rate about 20% higher than
placebo. Its principal adverse effects are due to its atropinic action.
Amitriptyline can also have a sedative effect. (6) Flunarizine also has
documented efficacy, but this "hidden neuroleptic" can cause extrapyramidal
disorders and weight gain. (7) Among the serotonergic antagonists, methysergide
has documented efficacy but long-term treatment can lead to serious
retroperitoneal, pulmonary or cardiac fibrosis. Pizotifen causes drowsiness or
weight gain in about 50% of patients. (8) The choice of preventive treatment for 
migraine must be based on the balance between efficacy (compared to placebo) and 
adverse effects. In practice, the first choice drug is propranolol. (9) Because
the frequency of migraines fluctuates over time, withdrawal of prophylaxis should
be attempted on a regular basis, with the patient's consent.

PMID: 17128528 [PubMed - indexed for MEDLINE]

966: Neurosci Res. 2007 Feb;57(2):179-83. Epub 2006 Nov 27.

Altered levels of serotonin in lymphoblasts derived from migraine patients.

Nagata E, Hamada J, Shimizu T, Shibata M, Suzuki S, Osada T, Takaoka R, Kuwana M,
Suzuki N.

Department of Neurology, Saitama City Hospital, 2560 Mimuro, Saitama City, Japan.
e-nagata@umin.ac.jp

We previously reported that dysfunctions in the autonomic nervous systems of
patients with migraines occur not only in the brain, but throughout the whole
body. Serotonin and neuropeptides are also known to have important roles in the
pathophysiology of migraine. With this background in mind, we analyzed human
lymphoblast cell lines from migraine with aura (MwA) patients to investigate the 
pathophysiology of migraine. The characteristics of these lymphoblasts and the
involvement of the lymphoblasts in serotonin metabolism were examined. The
lymphoblasts expressed serotonin receptors as well as some enzymes related to
serotonin metabolism. The serotonin level in the MwA lymphoblasts was higher than
that in the control cells. However, serotonin uptake into the lymphoblasts in MwA
patients was similar to that in the control subjects. These findings suggest that
lymphoblasts in MwA patients have altered levels of serotonin metabolism.
Moreover, we propose that this lymphoblast cell system could serve as a novel
modality for migraine research.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17125868 [PubMed - indexed for MEDLINE]

967: Pain. 2007 Apr;128(3):209-14. Epub 2006 Nov 22.

Increased plasma substance P and CGRP levels, and high ACE activity in
migraineurs during headache-free periods.

Fusayasu E, Kowa H, Takeshima T, Nakaso K, Nakashima K.

Department of Neurology, Institute of Neurological Sciences, Faculty of Medicine,
Tottori University, 36-1 Nishi-cho, Yonago 683-8504, Japan. piala@mx5.tiki.ne.jp 
<piala@mx5.tiki.ne.jp>

Substance P (SP), calcitonin gene-related peptide (CGRP), and angiotensin
converting enzyme (ACE) may have roles in trigeminovascular nociceptive
mechanisms. We investigated interictal levels of SP, CGRP, ACE activity, and
their correlation, in a sample of migraineurs. Forty-one patients suffering from 
migraine with aura (MA), 54 without aura (MO), and 52 non-headache subjects
(controls) participated in this study. Blood samples were collected from cubital 
veins. Plasma levels of SP and CGRP were measured by enzyme immunoassay. Plasma
ACE activities were measured spectrophotometrically. SP levels in MA (6.6+/-3.7
pg/ml; mean+/-SD) and MO (6.6+/-3.2 pg/ml) were significantly higher than in
controls (4.8+/-2.4 pg/ml) (P<0.01). CGRP levels in MA (18.8+/-8.8 pg/ml) and MO 
(19.1+/-9.4 pg/ml) were also significantly higher than in controls (13.4+/-4.4
pg/ml) (P<0.01). ACE activities in MA (34.6+/-19.0 U/l) were significantly higher
than in MO (25.3+/-13.2 U/l) and controls (27.0+/-20.4 U/l) (P<0.05). There was a
significant correlation between SP and CGRP levels (P<0.05). In MA, SP and CGRP
showed a tendency toward positive correlation, which was not significant. There
was a weak, but significant positive correlation between SP levels and ACE
activities (P<0.01). However, a relationship between ACE activities and CGRP
levels was not observed. The data suggest that SP, CGRP, and ACE are relevant to 
migraine pathophysiology, and that they may interact.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17123735 [PubMed - indexed for MEDLINE]

968: Invest Ophthalmol Vis Sci. 2006 Dec;47(12):5599-604.

Orientation discrimination and contrast detection thresholds in migraine for
cardinal and oblique angles.

Tibber MS, Guedes A, Shepherd AJ.

School of Psychology, Birkbeck College, University of London, London, United
Kingdom.

PURPOSE: To determine whether orientation discrimination deficits in migraine,
which have been found to depend on the spatial frequency of the stimulus, are due
to precortical dysfunction or to abnormal patterns of orientation tuning at
cortical loci. Further, to assess whether any cortical involvement is restricted 
to the striate cortex or whether higher cortical areas are also involved.
Orientation-specific abnormalities would provide evidence of cortical
dysfunction. METHODS: Orientation-discrimination and contrast-detection
thresholds were assessed at cardinal (0 degrees) and oblique (45 degrees)
orientations using explicit lines defined by Gabor patches. To test for
extrastriate dysfunction, participants made orientation judgments using virtual
lines defined by two widely spaced circles. Migraine history, migraine triggers, 
and pattern sensitivity were also assessed. Twenty migraineurs (10 with visual
aura, 10 without) and 20 control participants were tested. RESULTS:
Orientation-discrimination thresholds were lower for discriminations made about
the cardinal axis than for discriminations made about the oblique axis, a
well-documented phenomenon known as the oblique effect. Relative to the control
group, the migraine group exhibited orientation-specific sensitivity losses on
explicit and virtual judgments. Orientation-discrimination thresholds about the
oblique axis were significantly elevated in the migraine group. In contrast, the 
migraine and control groups' detection thresholds did not differ. CONCLUSIONS:
These findings reflect abnormal function of striate and extrastriate cortex in
migraine. In addition, the discrimination data are consistent with wider
orientation-tuning curves for orientation-sensitive cells in migraine, whereas
the detection data suggest peak sensitivity does not differ between the groups.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17122154 [PubMed - indexed for MEDLINE]

969: Arq Neuropsiquiatr. 2006 Sep;64(3A):549-52.

Mutation analysis of CACNA1A and ATP1A2 genes in Brazilian FHM families.

Lopes LR, Peres MF, Vanmolkot KR, Tobo PR, Zukerman E, Frants RR, van den
Maagdenberg AM, Moreira-Filho CA.

Instituto de Ensino e Pesquisa, Hospital Israelita Albert Einstein, São Paulo,
SP, Brazil, and Leiden University Medical Center, The Netherlands.
lucianarl@einstein.br

Familial hemiplegic migraine (FHM) is a rare autosomal dominant form of migraine 
with aura. This disease has been associated with missense mutations in the
CACNA1A and ATP1A2 genes. The aim of this study was to identify whether CACNA1A
and ATP1A2 are or not related to Brazilian FHM. Here we screened four Brazilian
FHM families (total of 26 individuals--13 affected and 13 asymptomatic or normal)
for mutations in both genes. We found an amino acid change in a member of family 
FHM-D (Arg2206Gly). However since this alteration is not present in all affected 
individuals and is present in one asymptomatic individual it should be considered
a polymorphism. Further studies with additional families will be necessary to
reveal the importance of both CACNA1A and ATP1A2 genes on the pathogeneses of FHM
in Brazil and to test the third gene (SCN1A) in these FHM families.

PMID: 17119788 [PubMed - indexed for MEDLINE]

970: Neuropsychopharmacology. 2007 Jun;32(6):1384-90. Epub 2006 Nov 22.

Erratum in:
    Neuropsychopharmacology. 2007 Jun;32(6):1432.

Endocannabinoids in chronic migraine: CSF findings suggest a system failure.

Sarchielli P, Pini LA, Coppola F, Rossi C, Baldi A, Mancini ML, Calabresi P.

Neurologic Clinic, Department of Medical and Surgical Specialties and Public
Health, University of Perugia, Perugia, Italy. neuro.pg@tiscalinet.it

Based on experimental evidence of the antinociceptive action of endocannabinoids 
and their role in the modulation of trigeminovascular system activation, we
hypothesized that the endocannabinoid system may be dysfunctional in chronic
migraine (CM). We examined whether the concentrations of
N-arachidonoylethanolamide (anandamide, AEA), palmitoylethanolamide (PEA), and
2-arachidonoylglycerol (2-AG) in the CSF of patients with CM and with probable CM
and probable analgesic-overuse headache (PCM+PAOH) are altered compared with
control subjects. The above endocannabinoids were measured by high-performance
liquid chromatography (HPLC), and quantified by isotope dilution
gas-chromatography/mass-spectrometry. Calcitonin gene-related peptide (CGRP)
levels were also determined by RIA method and the end products of nitric oxide
(NO), the nitrites, by HPLC. CSF concentrations of AEA were significantly lower
and those of PEA slightly but significantly higher both in patients with CM and
PCM+PAOH than in nonmigraineur controls (p<0.01 and p<0.02, respectively). A
negative correlation was found between AEA and CGRP levels in CM and PCM+PAOH
patients (r=0.59, p<0.01 and r=-0.65, p<0.007; respectively). A similar trend was
observed between this endocannabinoid and nitrite levels. Reduced levels of AEA
in the CSF of CM and PCM+PAOH patients may reflect an impairment of the
endocannabinoid system in these patients, which may contribute to chronic head
pain and seem to be related to increased CGRP and NO production. These findings
support the potential role of the cannabinoid (CB)1 receptor as a possible
therapeutic target in CM.

PMID: 17119542 [PubMed - indexed for MEDLINE]

971: Eur J Neurol. 2006 Dec;13(12):1370-3.

Is uncertain diagnosis a more frequent reason for referring migraine patients to 
neurologist than other headache syndromes?

Bekkelund SI, Salvesen R.

Department of Neurology, The University Hospital of North Norway, Tromsø, Norway.
svein.ivar.bekkelund@unn.no

The objective was to assess whether the physician's uncertainty of diagnosis was 
a more frequent motivation for referring migraine patients than other headache
patients to a neurologist. In this population based survey we included 846
consecutive patients referred to and examined at a specialist centre for headache
during a period of 2 years. As primary outcome we compared cross-sectionally
frequency of referring patients with migraine and other headaches to neurologist.
According to the patients, uncertainty of diagnosis was the main reason for
referral to a neurological specialist consultation, i.e. in 51% of cases.
Thirty-nine per cent of patients classified as having migraine were referred
because of an uncertain diagnosis, compared with 62% in patient with other
headaches (95 CI 0.13-0.33), (P < 0.0001). Headache subtypes other than migraine 
and younger age were associated to more uncertainty of diagnosis. We conclude
that diagnostic uncertainty was an important factor amongst half the headache
patients seen by neurologists and uncertain diagnoses as reason for referral was 
more important amongst patients with non-migrainous headache.

PMID: 17116222 [PubMed - indexed for MEDLINE]

972: Eur J Neurol. 2006 Dec;13(12):1364-9.

Brain MRI white matter lesions in migraine patients: is there a relationship with
antiphospholipid antibodies and coagulation parameters?

Intiso D, Di Rienzo F, Rinaldi G, Zarrelli MM, Giannatempo GM, Crociani P, Di
Viesti P, Simone P.

Department of Neurology and Rehabilitation, Scientific Institute, Casa Sollievo
della Sofferenza, S. Giovanni Rotondo (FG), Italy. do.intiso@tiscali.it

Brain magnetic resonance imaging (MRI) studies in migraine patients have
demonstrated lesions consisting of focal regions of increased signal intensity
within the white matter. Antiphospholipid antibodies are known to have a role in 
many diseases including migraine. The aim of the present study was to ascertain
the relationship between MRI-visualized cerebral focal hyperintense lesions and
serum antiphospholipid antibody levels, as well as blood coagulation parameters
in migraine patients. One hundred and two (77 females, 25 males, mean age 33.8
+/- 11.1) consecutive migraine patients and a control group of 94 (70 females, 24
males, mean age 33.2 +/- 10.8) healthy subjects were enrolled. All individuals
underwent brain MRI. Complete blood examinations, autoantibodies,
antiphospholipids antibodies including anticardiolipin and lupus anticoagulant
(aCL, LAC), antithrombin III, Protein C and S serum levels were ascertained in
the subjects who presented white matter lesions on MRI. Twenty-seven (26.4%)
migraine patients and six (6.3%) healthy subjects in the control group showed
focal regions of increased intensity signal within cerebral white matter (odds
ratio 5.3, 95% CI: 1.98-16.36). In migraine patients with white matter lesions,
antiphospholipid antibodies were not detected and serum levels of antithrombin
III, and proteins C and S were normal. White matter lesions in migraine patients 
are fairly common. This finding is not associated with antiphospholipid
antibodies or abnormal coagulation parameters. The significance of such lesions
at present remains unclear.

Publication Types: 
    Comparative Study

PMID: 17116221 [PubMed - indexed for MEDLINE]

973: Eur J Neurol. 2006 Dec;13(12):1346-51.

Increased urinary excretion of nitric oxide metabolites in longitudinally
monitored migraine patients.

Rejdak K, Empl M, Giffin NJ, Afridi SK, Petzold A, Stelmasiak Z, Thompson EJ,
Goadsby PJ, Kaube H, Giovannoni G.

Department of Neuroinflammation, Institute of Neurology, London, UK.
krejdak@europe.com

This study evaluated a relationship between nitric oxide (NO) and migraine
attacks in order to gain insight into migraine pathomechanism. The study groups
consisted of 12 migraineurs and eight controls. All subjects collected morning
urine samples for 40 consecutive days. Urinary NO metabolites, nitrite/nitrate
(NO(x)) levels were measured with the vanadium-based assay, whilst creatinine
(Cr) and neopterin were determined with high-performance liquid chromatography.
The mean urinary NO(x)/Cr ratio and number of NO(x) peaks was significantly
greater in the migraine group compared with controls (P = 0.01 and P = 0.007,
respectively). In the second approach, high NO(x) values were re-assessed in
relation to raised neopterin, a marker of systemic infection or inflammation, and
were excluded. The excretion of NO(x) persisted being pulsatile, and migraineurs 
had more peaks compared with controls (P = 0.01). In seven patients, NO(x) peaks 
coincided with headache days. This was more frequent than expected by random
association in four patients (Monte-Carlo simulation; odds ratios: 2.16-7.77; no 
overlap of 95% CI). In four patients, NO(x) peaks preceded or followed headache
days. Although there is a difference in the pattern of urinary NO(x) excretion
between control and migraine populations, the variable temporal association of
NO(x) peaks and headaches suggests a complex role of NO in this condition.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 17116218 [PubMed - indexed for MEDLINE]

974: Cephalalgia. 2006 Dec;26(12):1473-82.

Cost-effectiveness of migraine prevention: the case of topiramate in the UK.

Brown JS, Papadopoulos G, Neumann PJ, Price M, Friedman M, Menzin J.

Harvard Medical School/Harvard Pilgrim Health Care, Department of Ambulatory Care
& Prevention, Boston, MA, USA.

The aim of this study was to assess the cost-effectiveness of topiramate vs. no
preventive treatment in the UK. Model inputs included baseline migraine
frequency, treatment discontinuation and response, preventive and acute medical
cost per attack [2005 GBP ( pound)] and gain in health utility. Outcomes included
monthly migraines averted, acute and preventive treatment costs and cost per
quality-adjusted life year (QALY). Topiramate was associated with 1.8 fewer
monthly migraines and a QALY gain of 0.0384. The incremental cost of topiramate
vs. no preventive treatment was about 10 UK pounds per migraine averted and 5700 
UK pounds per QALY. Results are sensitive to baseline monthly migraine frequency,
triptan use rate and the gain in utility. Incorporating savings from reduced work
loss (about 36 UK pounds per month) suggests that topiramate would be cost saving
compared with no preventive treatment. This analysis suggests that topiramate is 
a cost-effective treatment for migraine prevention compared with no preventive
treatment.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17116098 [PubMed - indexed for MEDLINE]

975: Cephalalgia. 2006 Dec;26(12):1462-72.

Testing of variants of the MTHFR and ESR1 genes in 1798 Finnish individuals fails
to confirm the association with migraine with aura.

Kaunisto MA, Kallela M, Hämäläinen E, Kilpikari R, Havanka H, Harno H, Nissilä M,
Säkö E, Ilmavirta M, Liukkonen J, Teirmaa H, Törnwall O, Jussila M, Terwilliger
J, Färkkilä M, Kaprio J, Palotie A, Wessman M.

Biomedicum Helsinki, Research Program in Molecular Medicine and Department of
Clinical Chemistry, University of Helsinki, 00029 HUS, Helsinki, Finland.

Among the few independently replicated genetic associations in migraine are
polymorphisms in the methylenetetrahydrofolate reductase (MTHFR) and oestrogen
receptor (ESR1) genes. We studied the contribution of these genes to migraine
susceptibility by genotyping six MTHFR and 26 ESR1 polymorphisms in 898 unrelated
migraine with aura (MA) patients and in 900 unrelated healthy controls. There
were no differences in the genotype distributions of the previously
migraine-associated SNPs C677T (MTHFR) and G2014A (ESR1) between cases and
controls (P-values 0.83 and 0.55, respectively). Thus, we were not able to
replicate the previous findings, although our study had considerable power.
However, five of the ESR1 SNPs (rs6557170, rs2347867, rs6557171, rs4870062 and
rs1801132) that were in strong linkage disequilibrium were nominally associated
with MA (uncorrected P-values 0.007-0.034). These results did not, however,
remain significant after taking multiple testing into account. Thus it seems
unlikely that the studied genes are involved in migraine susceptibility, at least
in this sample.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 17116097 [PubMed - indexed for MEDLINE]

976: Headache. 2006 Nov-Dec;46(10):1575-9.

Comment in:
    Headache. 2007 Sep;47(8):1227; author reply 1227-8.

Endothelial nitric oxide synthase (Glu298Asp) polymorphism is an independent risk
factor for migraine with aura.

Borroni B, Rao R, Liberini P, Venturelli E, Cossandi M, Archetti S, Caimi L,
Padovani A.

Department of Medical Sciences, Neurological Clinic, University of Brescia,
Brescia, Italy.

OBJECTIVE: The aim of the present study was to evaluate whether the functional
endothelial nitric oxide synthase (eNOS) Glu298Asp polymorphism, which has been
demonstrated to decrease the endothelial NOS activity, might be a risk factor for
migraine. BACKGROUND: It has widely demonstrated that nitric oxide (NO) is
involved in migraine pathogenesis. Several genetic risk factors have been
associated with migraine, but no study has unraveled a possible relationship
between migraine and eNOS Glu298Asp. Methods.-One hundred fifty-six migraine
patients and 125 healthy nonheadache volunteers entered the study. Demographic
and clinical characteristics were carefully recorded, and a neurological workup
was performed. RESULTS: eNOS AspAsp homozygous patients had a 3-fold time risk
for migraine with aura (MA) when compared to migraine without aura (MO) patients 
(OR-3.02, 95% CI-1.21 to 7.51), and more than 2-fold time increased risk when
compared to control subjects (OR-2.21, 95% CI-1.00 to 5.04). In migraine
patients, no difference in age at onset, mean attack's intensity, family history 
for any of the studied comorbidities, or the presence of comorbidities was found 
in eNOS AspAsp homozygous compared to eNOS GluGlu or eNOS GluAs carriers.
CONCLUSIONS: Homozygous Asp298, a common variant of the eNOS gene, is an
independent risk factor for MA in this study population.

PMID: 17115991 [PubMed - indexed for MEDLINE]

977: Headache. 2006 Nov-Dec;46(10):1571-4.

Circadian and seasonal variation of migraine attacks in children.

Soriani S, Fiumana E, Manfredini R, Boari B, Battistella PA, Canetta E, Pedretti 
S, Borgna-Pignatti C.

Department of Clinical and Experimental Medicine--Pediatrics, University of
Ferrara, 44100 Ferrara, Italy.

OBJECT: To investigate the rhythmicity of migraine episodes without aura in a
pediatric population. METHODS: Time of occurrence of 2517 migraine attacks in 115
children was recorded, by means of a diary, both by hourly and monthly intervals.
RESULTS: A significant circadian variation, characterized by a peak in the
afternoon (P < .001) and one in the early morning (P= .002) was found. A seasonal
peak was also observed between November and January, while a nadir was observed
in July. CONCLUSIONS: The clustering of attacks in the morning and midday and in 
autumn-winter, with a minimum frequency in July, suggests that school activities 
may represent an important cause of migraine.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17115990 [PubMed - indexed for MEDLINE]

978: Headache. 2006 Nov-Dec;46(10):1535-44.

Change of excitability in brainstem and cortical visual processing in migraine
exhibiting allodynia.

Shibata K, Yamane K, Iwata M.

Department of Medicine, Tokyo Women's Medical University, Medical Center East,
2-1-10 Nishiogu, Arakawa-ku, Tokyo 116-8567, Japan.

BACKGROUND: Clinical and neurophysiological manifestations of information
processing associated with central sensitization are little known. Allodynic
migraine (AM) can be caused by the sensitization of trigeminal neuron, but no
study has reported on AM between attacks using blink reflex (BR) and
pattern-reversal visual evoked potentials (PVEPs). OBJECTIVE: We explored the
characteristics of AM between attacks associated with central sensitization using
BR and PVEP. METHODS: We recruited 13 patients with interictal AM and 15 patients
with nonallodynic migraine (NA), and 30 healthy subjects (HS). BRs were obtained 
using paired pulses delivered at the interstimulus interval (ISI) of 150, 300,
and 500 ms. The ratio of the area in the R2 of the second to R2 of the first
shock was measured for each ISI. PVEP were recorded with 2 spatial frequencies
(0.5 and 4.0 cpd) and 2 low and high contrasts (29% and 98%, respectively).
Amplitudes of P100 were measured. RESULTS: For BR, there were no significant
differences in the ratio of the area of the R2 between the sides of stimulation, 
and the sides of headache. AM patients had less suppression of the R2 at the ISI 
of 150 and 300 ms when compared with the NA patients and HS. For PVEP, at 0.5,
there were significant differences of amplitude between AM patients and HS, and
between NA patients and HS in low and high contrast. At 4.0 cpd, there were
significant differences of amplitude between AM patients and HS in low contrast, 
and between AM patients and HS, and NA patients and HS in high contrast. In AM
patients, there was a significant difference of amplitude ratio between 0.5 and
4.0 cpd. Conclusions.-Our BR and PVEP study showed that migraine patients
exhibiting allodynia may show central sensitization of brainstem trigeminal
neuron and have contrast modulating dysfunction during the cortical visual
processing of striate and extrastriate on visual cortex in-between attacks.

PMID: 17115986 [PubMed - indexed for MEDLINE]

979: Headache. 2006 Nov-Dec;46(10):1503-10.

Topiramate for migraine prevention in adolescents: a pooled analysis of efficacy 
and safety.

Winner P, Gendolla A, Stayer C, Wang S, Yuen E, Battisti WP, Nye JS.

Palm Beach Headache Center, West Palm Beach, FL, USA.

OBJECTIVE: To characterize the efficacy and safety of topiramate for migraine
prevention in adolescents from 3 randomized, 26-week, double-blind,
placebo-controlled trials. BACKGROUND: Limited information is available regarding
the efficacy and safety of prophylactic medications for treatment of adolescent
migraine, a significant health problem. In studies that included adults and
children, topiramate 100 and 200 mg/day were effective and generally
well-tolerated in the prevention of migraine headache. METHODS: We performed a
post hoc subset analysis of the efficacy and safety data from the 51 patients,
ages 12-17 years, enrolled in 3 pivotal trials of topiramate for migraine
prophylaxis. RESULTS: Daily treatment with topiramate 50, 100, and 200 mg for 26 
weeks reduced monthly migraine frequency from baseline 46% (P= .07), 63% (P=
.02), and 65% (P= .04), respectively, compared with placebo (16%). Similarly,
topiramate reduced both the monthly mean number of migraine days (1, 4, and 5
days for topiramate 50, 100, and 200 mg/day, respectively, vs 1 day for placebo) 
and percentage of days during which acute migraine medications were administered 
(59%, 54%, and 67% for topiramate 50, 100, and 200 mg/day, respectively, vs 42%
for placebo), although the treatment differences did not reach nominal
statistical significance. Topiramate 200 mg/day did not appear to offer greater
efficacy than 100 mg/day. Treatment was generally well-tolerated, although
adverse events were most frequent in the 200 mg/day dose group. CONCLUSIONS: This
post hoc subset analysis suggests that topiramate 100 and 200 mg/day, and
possibly 50 mg/day, administered prophylactically for 26 weeks may reduce
migraine in adolescents.

Publication Types: 
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 17115983 [PubMed - indexed for MEDLINE]

980: Headache. 2006 Nov-Dec;46(10):1492-502.

Effectiveness and tolerability of acupuncture compared with metoprolol in
migraine prophylaxis.

Streng A, Linde K, Hoppe A, Pfaffenrath V, Hammes M, Wagenpfeil S, Weidenhammer
W, Melchart D.

Centre for Complementary Medicine Research, Department of Internal Medicine II,
Technische Universität München, Munich, Germany.

OBJECTIVES: In a randomized controlled multicenter trial extending over 24 weeks,
we investigated whether acupuncture is as effective and safe as metoprolol in the
prophylactic treatment of migraine under conditions similar to routine care.
METHODS: One hundred fourteen migraine patients could be randomized to treatment 
over 12 weeks either with acupuncture (8 to 15 sessions) or metoprolol (100 to
200 mg daily). Main outcome measure was the difference in the number of migraine 
days between baseline and the weeks 9 to 12 after randomization (derived from a
headache diary). RESULTS: Two of 59 patients randomized to acupuncture withdrew
prematurely from the study compared to 18 of 55 randomized to metoprolol. The
number of migraine days decreased by 2.5 +/- 2.9 days (baseline 5.8 +/- 2.5 days)
in the acupuncture group compared to 2.2 +/- 2.7 days (baseline 5.8 +/- 2.9 days)
in the metoprolol group (P= .721). The proportion of responders (reduction of
migraine attacks by > or =50%) was 61% for acupuncture and 49% for metoprolol.
Both physicians and patients reported fewer adverse effects in the acupuncture
group. CONCLUSIONS: Due to missing the recruitment target (480 patients) and the 
high drop-out in the metoprolol group the results must be interpreted with
caution. Still, they suggest that acupuncture might be an effective and safe
treatment option for patients unwilling or unable to use drug prophylaxis.

Publication Types: 
    Comparative Study
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 17115982 [PubMed - indexed for MEDLINE]

981: Headache. 2006 Nov-Dec;46(10):1480-6.

Comment in:
    Headache. 2007 Sep;47(8):1228-9; author reply 1229.

A clinical study of migraine evolution.

Pryse-Phillips W, Aubé M, Bailey P, Becker WJ, Bellavance A, Gawel M, Giammarco
R, Mackie G, Purdy RA, Robinson G, Shapero G, Wilson K.

Memorial University, St. John's, Newfoundland, Canada.

BACKGROUND: The buildup time of migraine headaches has not been well delineated
in publications to date and we are aware of patients whose migraines last well
over 72 hours. More concentration on these factors in the assessment of patients 
might lead to more appropriate therapeutic choices. METHOD: Prospective
ascertainment of such data through a questionnaire completed by 253 informed and 
willing patients with IHS migraine with or without aura consulting Canadian
headache specialists. Data were electronically sent to a central computer from
each center, tabulated and analyzed using standard statistical parameters.
RESULTS: In 253 patients with migraine ascertained using applied IHS criteria,
nausea was a feature in over 90% of cases, especially in those with aura. This
inhibited the ingestion of oral medications in about a quarter of all subjects.
The time to build from no pain to moderate/severe pain was shorter in subjects
with auras and was less than 2 hours in 97% of those with and 86% of those
without auras. However, we also identified a group of subjects with migraine
(over 10% of all) in whom the build time to maximum pain is delayed for over 2
hours. Nausea was experienced by 91.7% of subjects, slightly but significantly
later in those without auras. While most headaches in each group lasted from 4 to
72 hours, 24.3% of those with and 20.6% of those without aura expected to
experience pain for more than 72 hours, while in untreated cases disability due
to pain, nausea, or malaise usually persisted for over 3 days in 24.3% and 16.7% 
of those with and without aura, respectively. One-fifth of migraineurs may be in 
pain and/or disabled by accompanying symptoms for over 3 days in a typical
migraine attack. Over half of our subjects reported that their medications worked
well or excellently. CONCLUSIONS: Attacks of migraine in real-life clinical
situations vary somewhat from the IHS criteria in that they are more often
associated with nausea that interferes with oral therapy; can persist for over 72
hours; may have slow (>2 hours) buildup to maximum pain in 10% of cases; and may 
cause disability for over 3 days. Nevertheless, current therapeutic regimens
(including prescribed medications) work well for a substantial majority.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17115980 [PubMed - indexed for MEDLINE]

982: Psychiatry Res. 2007 Jan 15;149(1-3):261-6. Epub 2006 Nov 17.

High anxiety and migraine are associated with the s allele of the 5HTTLPR gene
polymorphism.

Gonda X, Rihmer Z, Juhasz G, Zsombok T, Bagdy G.

Laboratory of Neurochemistry and Experimental Medicine, National Institute of
Psychiatry and Neurology, Huvosvolgyi ut 116, H-1021 Budapest, Hungary.

The 5HTTLPR polymorphism of the serotonin transporter gene has been associated
with anxiety disorders and also migraine, suggesting a common etiological
background of these disorders. This association is further supported by the high 
comorbidity of these disorders. In our study Spielberger's State-Trait Anxiety
Inventory and the 5HTTLPR genotype were investigated in a cohort of 97
psychiatrically healthy females also including 45 migraineurs. Higher state
anxiety scores were significantly associated with the s allele either in the
whole sample or when the group was separated into migraineurs and
non-migraineurs. Migraineurs also had a significantly higher frequency of the s
allele. Our results indicate that even in a healthy population the s allele is
associated with a high anxiety endophenotype. The association of migraine with
anxiety may be explained by the higher rate of individuals carrying the s allele 
among migraineurs.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17113652 [PubMed - indexed for MEDLINE]

983: Int J Clin Pract. 2006 Dec;60(12):1530-5.

Comment in:
    Int J Clin Pract. 2006 Dec;60(12):1519-21.

Improved migraine management in primary care: results of a patient treatment
experience study using zolmitriptan orally disintegrating tablet.

Shapero G, Dowson A, Lacoste JP, Almqvist P.

Markham Headache and Pain Treatment Centre, Markham, ON, Canada.
shapero1@on.aibn.com

The 'Zomig Appropriate for Primary care' programme was developed to address the
needs of primary care physicians (PCPs) to improve migraine management. As part
of the programme, an international, open-label, 6-month clinical study was
performed. The study included new and tangible outcome variables relevant to PCPs
and recruited patients presenting in primary care with an established migraine
diagnosis. Patients treated up to three migraine attacks per month with
zolmitriptan orally disintegrating tablet (ODT) 2.5 mg. All other migraine
attacks occurring during the study period were treated with the patient's usual
migraine medication (including other triptans). Questionnaires were used to
record patient treatment experiences at the study end. The primary end-point was 
the proportion of patients wanting to continue using zolmitriptan ODT. Some 595
patients treated 7171 migraine attacks with zolmitriptan ODT. Of the 504 patients
who completed the 6-month questionnaire, 380 (75.4%) wished to continue using
zolmitriptan ODT. The results of the study indicate that patient-orientated
end-points are more motivational and meaningful to physicians than traditional
end-points used in controlled clinical trials, allowing them to make informed
decisions regarding migraine management.

Publication Types: 
    Multicenter Study
    Research Support, Non-U.S. Gov't

PMID: 17109663 [PubMed - indexed for MEDLINE]

984: J Interv Cardiol. 2006 Dec;19(6):552-7.

Transcatheter closure of patent foramen ovale in patients with migraine headache.

Spies C, Schräder R.

Rush University Medical Center, Section of Cardiology, Chicago, Illinois, USA.

Our objective is to review the epidemiology and pathophysiology of migraine
headache, its association with patent foramen ovale (PFO), and the impact of PFO 
closure on migraine. Upon reviewing English-language publications listed in
MEDLINE relating to migraine headache, PFO, and transcatheter closure of PFO, we 
selected case series, retrospective and prospective studies relevant to the
topic.Primarily retrospective case-control studies demonstrate a link between PFO
closure and improvement of migraine headache. Few prospective data confirm the
initial results. However, the only randomized, controlled trial finished to date 
analyzing the effect of PFO closure on migraine failed to reach its primary
outcome of resolution of migraine following the intervention. The evidence of a
benefit on migraine headache following PFO closure is not convincing, but
certainly intriguing. With currently ongoing trials, more information related to 
this topic can be expected.

Publication Types: 
    Review

PMID: 17107372 [PubMed - indexed for MEDLINE]

985: Neurology. 2006 Nov 14;67(9):1707-9.

Variation of the serotonin transporter gene SLC6A4 in the susceptibility to
migraine with aura.

Todt U, Freudenberg J, Goebel I, Heinze A, Heinze-Kuhn K, Rietschel M, Göbel H,
Kubisch C.

Institute of Human Genetics, Center for Molecular Medicine Cologne, University of
Cologne, Cologne, Germany.

To replicate a reported association between migraine with aura (MA) and a
promoter polymorphism in the serotonin transporter gene (SLC6A4), we performed a 
case-control study in a large German sample comprising 472 patients with MA and
506 controls. Neither this polymorphism nor a systematic analysis with single
nucleotide polymorphisms capturing the main haplotype diversity of the SLC6A4
locus provided evidence for a contribution of SLC6A4 to the predisposition of
complex inherited MA.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17101915 [PubMed - indexed for MEDLINE]

986: Eur J Obstet Gynecol Reprod Biol. 2007 Oct;134(2):157-63. Epub 2006 Nov 9.

Pregnancy complications and delivery outcomes in pregnant women with severe
migraine.

Bánhidy F, Acs N, Horváth-Puhó E, Czeizel AE.

Second Department of Obstetrics and Gynecology, Semmelweis University, School of 
Medicine, Budapest, Hungary.

OBJECTIVE: The objective was to study the possible association among maternal
migraine during pregnancy, pregnancy complications, and the delivery outcomes:
sex ratio, gestational age/birth weight and preterm birth/low birth weight. STUDY
DESIGN: The population-based large data set of newborn infants without any
defects of the Hungarian Case-Control Surveillance System of Congenital
Abnormalities, 1980-1996 was analyzed. RESULTS: Out of 38,151 newborn infants,
713 (1.9%) had mothers who had severe migraine during pregnancy; 68% were
medically recorded. Pregnant women with severe migraine had a higher prevalence
of preeclampsia and severe nausea/vomiting, but a lower occurrence of threatened 
abortion and preterm delivery. However, mean gestational age and birth weight, as
well as the proportion of low birth weight and preterm births, were similar in
newborn infants born to mothers with or without migraine. CONCLUSION: Severe
maternal migraine and its related drug treatment may increase the occurrence of
preeclampsia and severe nausea/vomiting during pregnancy, but is not associated
with unfavorable delivery outcomes.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17097212 [PubMed - indexed for MEDLINE]

987: Clin Neuropharmacol. 2006 Nov-Dec;29(6):338-42.

Levetiracetam in the prophylaxis of migraine with aura: a 6-month open-label
study.

Brighina F, Palermo A, Aloisio A, Francolini M, Giglia G, Fierro B.

Neurophysiology Unit, Department of Neurology, University of Palermo, Palermo,
Italy.

OBJECTIVE: To evaluate the efficacy of levetiracetam as prophylactic treatment
for migraine with aura with high frequency of attacks. BACKGROUND: Migraine with 
aura with high frequency of attacks could represent a very demanding therapeutic 
problem. Efficacy of the antiepileptic drug, lamotrigine, has been reported in
this form of migraine. Levetiracetam is a new antiepileptic drug with an
excellent tolerability profile. Mechanisms of action of this drug remain largely 
unknown, but recently, it has been shown to exert inhibitory effects on
neuronal-type calcium channels. METHODS: We performed a small open-label trial
treating 16 patients affected by migraine with aura with high frequency of
attacks. After a 1-month run-in period, patients were treated with levetiracetam 
at a dosage of 1000 mg/d for 6 months. RESULTS: The number of attacks per month
was significantly reduced during the first month (compared with run-in; P <
0.001), and it was reduced further during the second (second month vs first
month; P < 0.001) and the third months (third month vs second month; P < 0.001)
of the treatment. This improvement persisted unchanged for the remaining 3 months
of treatment. In 7 (44%) of the 16 patients, the attacks were completely
abolished after 3 months of treatment. Severity of headache and duration of
headache and aura were also significantly reduced at the third and sixth months
of treatment (P < 0.001). Levetiracetam was well tolerated (6 patients complained
of slight dizziness, nervousness, and somnolence). CONCLUSIONS: Levetiracetam
seems to be a safe and effective treatment for migraine with aura. Controlled
trials are needed to confirm the observed results.

Publication Types: 
    Comparative Study
    Evaluation Studies

PMID: 17095897 [PubMed - indexed for MEDLINE]

988: J Neurol Sci. 2006 Dec 21;251(1-2):118-23. Epub 2006 Nov 7.

Association between a 19 bp deletion polymorphism at the dopamine
beta-hydroxylase (DBH) locus and migraine with aura.

Fernandez F, Lea RA, Colson NJ, Bellis C, Quinlan S, Griffiths LR.

Genomics Research Centre, School of Medical Science, Griffith University, Gold
Coast, Queensland, Australia.

Migraine is a debilitating neurological disorder, affecting 12% of Caucasian
populations. It is well known that migraine has a strong genetic component,
although the type and number of genes involved is unclear. Our previous work has 
investigated dopamine related migraine candidate genes and has reported a
significant allelic association with migraine of a microsatellite localised to
the promoter region of the dopamine beta-hydroxylase (DBH) gene. The present
study performed an association analysis in a larger population of case-controls
(275 unrelated Caucasian migraineurs versus 275 controls) examining two different
genetic DBH polymorphisms (a functional insertion/deletion promoter and a coding 
SNP A444G polymorphism). Although no significant association was found for the
SNP polymorphism, the results showed a significant association between the
insertion/deletion variant and disease (chi(2)=8.92, P=0.011), in particular in
migraine with aura (chi(2)=11.53, P=0.003) compared to the control group.
Furthermore, the analysis of this polymorphism stratified by gender, revealed
that male individuals with the homozygote deletion genotype had three times the
risk of developing migraine, compared to females. The DBH insertion/deletion
polymorphism is in linkage disequilibrium with the previously reported migraine
associated DBH microsatellite and this insertion/deletion polymorphism is
functional, which may explain a potential role in susceptibility to migraine.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 17095019 [PubMed - indexed for MEDLINE]

989: Handb Exp Pharmacol. 2007;(177):129-43.

Serotonin receptor ligands: treatments of acute migraine and cluster headache.

Goadsby PJ.

Institute of Neurology, Queen Square, London WC1N 3BG, UK. peterg@ion.ucl.ac.uk

Fuelled by the development of the serotonin 5-HT(1B/1D) receptor agonists, the
triptans, the last 15 years has seen an explosion of interest in the treatment of
acute migraine and cluster headache. Sumatriptan was the first of these agonists,
and it launched a wave of therapeutic advances. These medicines are effective and
safe. Triptans were developed as cranial vasoconstrictors to mimic the desirable 
effects of serotonin, while avoiding its side-effects. It has subsequently been
shown that the triptans' major action is neuronal, with both peripheral and
central trigeminal inhibitory effects, as well as actions in the thalamus and at 
central modulatory sites, such as the periaqueductal grey matter. Further
refinements may be possible as the 5-HT(1D) and 5-HT(1F) receptor agonists are
explored. Serotonin receptor pharmacology has contributed much to the better
management of patients with primary headache disorders.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 17087122 [PubMed - indexed for MEDLINE]

990: J Rheumatol. 2006 Nov;33(11):2184-91.

Comment in:
    Nat Clin Pract Rheumatol. 2007 Apr;3(4):200-1.

Migraine during systemic lupus erythematosus: findings from brain single photon
emission computed tomography.

Nobili F, Mignone A, Rossi E, Morbelli S, Piccardo A, Puppo F, Indiveri F,
Sambuceti G, Rodriguez G.

Department of Clinical Neurophysiology, Azienda Ospedale-Universita S. Martino,
Viale Benedetto XV 6, I-16132 Genoa, Italy. flaviomariano.nobili@hsanmartino.it

OBJECTIVE: Headache in systemic lupus erythematosus (SLE) is controversial, as is
evidence of brain impairment in patients with SLE and headache. Perfusion single 
photon emission computed tomography (SPECT) was performed to investigate brain
impairment in SLE patients with migraine-like headache either from the period of 
diagnosis or later in the course of disease. METHODS: Eighteen patients with SLE 
(mean age 40.8 +/- 13.6 yrs) matching these characteristics underwent brain SPECT
with 99mTc-HMPAO in the interictal period. Electroencephalography (EEG) and
magnetic resonance imaging (MRI) were performed in 12 and 10 patients,
respectively. SPECT was analyzed through visual and asymmetry combined analysis
as well as by voxel-based statistical analysis compared to a control group of
matched healthy subjects (statistical threshold: p = 0.01). RESULTS: Focal
hypoperfusion was evidenced in 15 (83%) patients, often matching the main side of
pain location, whereas EEG and MRI each gave a positive result in 50% of cases.
Using voxel-based analysis, significant hypoperfusion was found in 8 (44%)
patients, either lateralized to one side or localized to the anterior cingulate
cortex, independent of pain location. CONCLUSION: Brain perfusion SPECT is a
sensitive tool for identifying brain impairment in SLE-related migraine, although
the mechanisms of brain damage remain to be elucidated. Besides confirming focal 
hypoperfusion in some patients, in 4 patients statistical analysis revealed
interictal hypofunction of the anterior cingulate cortex, a key structure for
cortical elaboration of pain in the midline network.

PMID: 17086605 [PubMed - indexed for MEDLINE]

991: Pain. 2007 Mar;128(1-2):111-27. Epub 2006 Nov 2.

Efficacy of biofeedback for migraine: a meta-analysis.

Nestoriuc Y, Martin A.

Philipps-University of Marburg, Section for Clinical Psychology and
Psychotherapy, Gutenbergstr. 18, 35032 Marburg, Germany.
yvonne.nestoriuc@staff.uni-marburg.de <yvonne.nestoriuc@staff.uni-marburg.de>

In this article, we meta-analytically examined the efficacy of biofeedback (BFB) 
in treating migraine. A computerized literature search of the databases Medline, 
PsycInfo, Psyndex and the Cochrane library, enhanced by a hand search, identified
86 outcome studies. A total of 55 studies, including randomized controlled trials
as well as pre-post trials, met our inclusion criteria and were integrated. A
medium effect size (d =0.58, 95% CI=0.52, 0.64) resulted for all BFB
interventions and proved stable over an average follow-up phase of 17 months.
Also, BFB was more effective than control conditions. Frequency of migraine
attacks and perceived self-efficacy demonstrated the strongest improvements.
Blood-volume-pulse feedback yielded higher effect sizes than peripheral skin
temperature feedback and electromyography feedback. Moderator analyses revealed
BFB in combination with home training to be more effective than therapies without
home training. The influence of the meta-analytical methods on the effect sizes
was systematically explored and the results proved to be robust across different 
methods of effect size calculation. Furthermore, there was no substantial
relation between the validity of the integrated studies and the direct treatment 
effects. Finally, an intention-to-treat analysis showed that the treatment
effects remained stable, even when drop-outs were considered as nonresponders.

Publication Types: 
    Meta-Analysis
    Review

PMID: 17084028 [PubMed - indexed for MEDLINE]

992: Headache. 2006 Nov;46 Suppl 4:S212-20.

DHE in the pharmacotherapy of migraine: potential for a larger role.

Saper JR, Silberstein S, Dodick D, Rapoport A.

Michigan Head Pain and Neurological Institute, Ann Arbor, USA.

Despite a large array of currently marketed, frequently effective drugs for the
acute treatment of migraine headache, comprising various classes and
formulations, predictably reliable treatment for most headache types is often
lacking. Dihydroergotamine mesylate (DHE) is a comparatively safe and effective
therapy for migraine headache that could potentially be used for a broader range 
of headache types than occurs at present. The features of DHE supporting this
assertion include (1) effectiveness in terminating severe, long-lasting
headaches, (2) rapid onset of action, (3) very low rates of headache recurrence, 
(4) minimal risk of medication-overuse headache, and (5) in the nasal spray
formulation, suitability for outpatients (especially patients who are very
nauseated or vomiting, potentially obviating the need for an office or hospital
visit for acute care). Conditions or circumstances for which there are data
supporting the expanded use of DHE include menstrual migraine, migraine with
central sensitization and cutaneous allodynia, medication-overuse headache,
migraine recurrence, and status migrainosus. The introduction of the intranasal
formulation of DHE provides both pharmacologic and patient-convenience advantages
for use in migraine therapy. This article reviews the rationale for the use of
DHE in these common, often difficult-to-treat migraine forms.

Publication Types: 
    Review

PMID: 17078853 [PubMed - indexed for MEDLINE]

993: Headache. 2006 Nov;46 Suppl 4:S192-201.

Nasal delivery of antimigraine drugs: clinical rationale and evidence base.

Rapoport A, Winner P.

New England Center for Headache, Stanford, CT 06092-1251, USA.

The intranasal route of administration for antimigraine drugs offers many
theoretical and practical advantages. A drug that is administered intranasally is
absorbed by the highly vascular mucous membranes of the nose, which allows for
rapid delivery of un-metabolized drug to the central nervous system. The onset of
action is thus considerably earlier than with oral administration requiring
gastrointestinal absorption. The intranasal route also provides several practical
advantages, such as greater acceptability to patients because of the noninvasive 
mode of delivery, the ability to take medication when severe nausea or vomiting
is present, and a better adverse event profile. Three antimigraine drugs are
available in intranasal formulation: dihydroergotamine, sumatriptan, and
zolmitriptan. This article reviews the pharmacology, efficacy, safety, and
tolerability of these agents. All are well tolerated by patients and have
demonstrated efficacy in the treatment of migraine headache. Each of these drugs 
has a unique pharmacokinetic and pharmacodynamic profile, which may support a
clinical preference for one intranasal agent over another in treating patients
with specific headache features.

Publication Types: 
    Review

PMID: 17078851 [PubMed - indexed for MEDLINE]

994: Headache. 2006 Nov;46 Suppl 4:S182-91.

Central sensitization theory of migraine: clinical implications.

Dodick D, Silberstein S.

Mayo Clinic, Scottsdale, AZ 85255, USA.

The clinical science of migraine headache continues to evolve. Theories of the
pathophysiology of migraine have progressed from the early vascular basis of
migraine to more complex current theories that emphasize the centrality of
neuronal dysfunction. The most recently articulated theory of migraine is the
central sensitization hypothesis, which proposes that altered processing of
sensory input in the brainstem, principally the trigeminal nucleus caudalis,
could account for many of the temporal and symptomatic features of migraine, as
well as its poor response to triptan therapy when such treatment is initiated
hours after the onset of pain. Both preclinical and clinical data support the
central sensitization theory. A critical clinical implication of this theory is
that drugs that are capable of either aborting or arresting the process of
central sensitization, most prominently dihydroergotamine, may have a unique role
in the treatment of migraine. An additional, and highly practical, implication is
based upon the finding that cutaneous allodynia-pain arising from innocuous
stimulation of the skin, as in hair brushing or the application of cosmetics-is
an easily identifiable marker of central sensitization. Thus, the presence or
absence of cutaneous allodynia can be integrated into the routine clinical
assessment of migraine and utilized as a determinant of treatment. Future basic
and clinical research on central sensitization is likely to be of ongoing
importance to the field.

Publication Types: 
    Review

PMID: 17078850 [PubMed - indexed for MEDLINE]

995: Headache. 2006 Nov;46 Suppl 4:S171-81.

Pharmacology of dihydroergotamine and evidence for efficacy and safety in
migraine.

Saper JR, Silberstein S.

Michigan Head Pain and Neurological Institute, Ann Arbor 48104, USA.

Dihydroergotamine mesylate (DHE), an ergot alkaloid, has been extensively
utilized and studied in the treatment of episodic and chronic migraine. This
article reviews the pharmacokinetics, pharmacodynamics, and clinical efficacy and
safety of DHE, particularly in comparison to ergotamine tartrate (ET), a similar 
ergot alkaloid with a long history of use in the treatment of migraine.
Structural differences between these 2 compounds account for clinically important
distinctions in their pharmacokinetic, pharmacodynamic, and adverse event
profiles. DHE is a significantly less potent arterioconstrictor than is ET, which
makes it a potentially much safer drug. In addition, DHE is associated with a
markedly lower incidence of medication-withdrawal headache, nausea, and vomiting 
than is ET. The safety and efficacy data presented here are derived from clinical
trials and case series involving DHE administered by intravenous infusion,
intramuscular or subcutaneous injection, or intranasal spray.

Publication Types: 
    Review

PMID: 17078849 [PubMed - indexed for MEDLINE]

996: Pain. 2006 Dec 5;125(3):286-95. Epub 2006 Oct 25.

Comment in:
    Pain. 2006 Dec 5;125(3):206-7.    Pain. 2007 Jun;129(3):363-4; author reply 364-5.

Exploding vs. imploding headache in migraine prophylaxis with Botulinum Toxin A.

Jakubowski M, McAllister PJ, Bajwa ZH, Ward TN, Smith P, Burstein R.

Departments of Anesthesia and Critical Care, Beth Israel Deaconess Medical
Center, Harvard Medical School, Boston, MA 02115, USA.

Migraine headache is routinely managed using medications that abort attacks as
they occur. An alternative approach to migraine management is based on
prophylactic medications that reduce attack frequency. One approach has been
based on local intramuscular injections of Botulinum Toxin Type A (BTX-A). Here, 
we explored for neurological markers that might distinguish migraine patients who
benefit from BTX-A treatment (100 units divided into 21 injections sites across
pericranial and neck muscles). Responders and non-responders to BTX-A treatment
were compared prospectively (n=27) and retrospectively (n=36) for a host of
neurological symptoms associated with their migraine. Data pooled from all 63
patients are summarized below. The number of migraine days per month dropped from
16.0+/-1.7 before BTX-A to 0.8+/-0.3 after BTX-A (down 95.3+/-1.0%) in 39
responders, and remained unchanged (11.3+/-1.9 vs. 11.7+/-1.8) in 24
non-responders. The prevalence of aura, photophobia, phonophobia, osmophobia,
nausea, and throbbing was similar between responders and non-responders. However,
the two groups offered different accounts of their pain. Among non-responders,
92% described a buildup of pressure inside their head (exploding headache). Among
responders, 74% perceived their head to be crushed, clamped or stubbed by
external forces (imploding headache), and 13% attested to an eye-popping pain
(ocular headache). The finding that exploding headache was impervious to
extracranial BTX-A injections is consistent with the prevailing view that
migraine pain is mediated by intracranial innervation. The amenability of
imploding and ocular headaches to BTX-A treatment suggests that these types of
migraine pain involve extracranial innervation as well.

Publication Types: 
    Clinical Trial
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 17069972 [PubMed - indexed for MEDLINE]

997: Pharmacol Ther. 2007 Feb;113(2):321-40. Epub 2006 Oct 25.

Potential role of female sex hormones in the pathophysiology of migraine.

Gupta S, Mehrotra S, Villalón CM, Perusquía M, Saxena PR, MaassenVanDenBrink A.

Department of Pharmacology, Erasmus MC, University Medical Center Rotterdam, P.O.
Box 1738, 3000 DR Rotterdam, The Netherlands.

Clinical evidence indicates that female sex steroids may contribute to the high
prevalence of migraine in women, as well as changes in the frequency or severity 
of migraine attacks that are in tandem with various reproductive milestones in
women's life. While female sex steroids do not seem to be involved in the
pathogenesis of migraine per se, they may modulate several mediators and/or
receptor systems via both genomic and non-genomic mechanisms; these actions may
be perpetuated at the central nervous system, as well as at the peripheral
(neuro)vascular level. For example, female sex steroids have been shown to
enhance: (i) neuronal excitability by elevating Ca(2+) and decreasing Mg(2+)
concentrations, an action that may occur with other mechanisms triggering
migraine; (ii) the synthesis and release of nitric oxide (NO) and neuropeptides, 
such as calcitonin gene-related peptide CGRP, a mechanism that reinforces
vasodilatation and activates trigeminal sensory afferents with a subsequent
stimulation of pain centres; and (iii) the function of receptors mediating
vasodilatation, while the responses of receptors inducing vasoconstriction are
attenuated. The serotonergic, adrenergic and gamma-aminobutyric acid (GABA)-ergic
systems are also modulated by sex steroids, albeit to a varying degree and with
potentially contrasting effects on migraine outcome. Taken together, female sex
steroids seem to be involved in an array of components implicated in migraine
pathogenesis. Future studies will further delineate the extent and the clinical
relevance of each of these mechanisms, and will thus expand the knowledge on the 
femininity of migraine.

Publication Types: 
    Review

PMID: 17069890 [PubMed - indexed for MEDLINE]

998: Invest Ophthalmol Vis Sci. 2006 Nov;47(11):5125-31.

Transient tritanopia in migraine: evidence for a large-field retinal abnormality 
in blue-yellow opponent pathways.

Tibber MS, Shepherd AJ.

School of Psychology, Birkbeck College, University of London, London, United
Kingdom.

PURPOSE: To determine whether the magnitude of transient tritanopia (TT) differs 
between migraine and control groups. TT is a retinal phenomenon characterized by 
a paradoxical reduction in sensitivity to short-wavelength (purple) stimuli after
extinction of long-wavelength (yellow) adapting displays. A group difference in
the magnitude of TT would provide evidence for a retinal contribution to the
S-cone-specific color-processing abnormalities that have been reported in
migraine. METHODS: Thirty-two migraineurs and 32 age- and sex-matched control
participants were tested with a four-alternative, forced-choice procedure to
determine S-cone increment and decrement detection thresholds before and after
adaptation to a long-wavelength (yellow) display and a neutral (white) display.
Migraine history, migraine triggers, and pattern sensitivity were also assessed. 
RESULTS: Both groups' detection thresholds for increment (purple) S-cone stimuli 
were increased after extinction of the long-wavelength adapting display compared 
with the neutral display, demonstrating TT. This loss of sensitivity was
significantly greater in the migraine group. In contrast, loss of sensitivity to 
decrement (yellow) S-cone stimuli was less marked and did not differ between the 
groups. The magnitude of TT correlated positively with indices of pattern
sensitivity and susceptibility to visually triggered migraines but not with
migraine history. CONCLUSIONS: These results demonstrate that abnormalities in a 
specific retinal circuit contribute to decreased short-wavelength sensitivity
after adaptation in migraine. As thresholds did not correlate with indices of
migraine history, it is unlikely that this finding reflects cumulative damage
induced by repeated migraine episodes.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17065534 [PubMed - indexed for MEDLINE]

999: J Neurol. 2006 Dec;253(12):1589-93. Epub 2006 Oct 24.

The G-308A promoter variant of the tumor necrosis factor-alpha gene is associated
with migraine without aura.

Mazaheri S, Hajilooi M, Rafiei A.

Department of Neurology, Sina Hospital, Hamadan University of Medical Sciences,
Hamadan, Iran.

Migraine is considered to be a polygenic multifactorial disease with various
environmental and genetic etiologies. Tumor necrosis factor-alpha (TNF-alpha), a 
potent immunomodulator and pro-inflammatory cytokine, has been implicated in many
pathological processes in brain. The hypothesis of this study was that migraine
without aura (MWA) might be associated with TNF-alpha (-308) polymorphism,
resulting in increased TNF-alpha production. Genotyping was performed on DNA
extracted from peripheral leukocytes by PCR-SSP method in 221 patients with WMA
and 183 healthy control subjects from Iranian population. The results showed that
the frequency of -308 A variant allele was higher in MWA than in the control
group (40.6% versus 22.3%, OR 3.73, 95% CI 2.4-5.82, p<0.0001). TNF-alpha GA
heterozygous genotype, high producer, was significantly more prevalent in
patients with MWA than controls (74% versus 44.7%, p<0.0001) whilst the low
producer GG homozygous genotype was less frequent in patients compared with
controls (22.4% versus 55.3%, p<0.0001). The logistic regression analysis showed 
a significant association for TNF-alpha (-308A) female allele carriers with MWA
at reproductive ages (OR 2.56; 95% CI, 1.57-4.16, p<0.0001) when compared with
their matched control subjects.In conclusion, this study demonstrates an
association of tumor necrosis factor-alpha (-308A) carriage with MWA, suggesting 
that carrying a high responder TNF-alpha-308A allele may be a genetic factor in
increasing the susceptibility to develop MWA.

PMID: 17063315 [PubMed - indexed for MEDLINE]

1000: Br J Clin Pharmacol. 2006 Nov;62(5):591-600.

A model-based approach to treatment comparison in acute migraine.

Maas HJ, Danhof M, Della Pasqua O.

Division of Pharmacology, Leiden/Amsterdam Center for Drug Research, the
Netherlands.

AIMS: Currently, direct comparisons between 5-HT(1B/d) receptor agonists are used
to assess differences and similarities in antimigraine response. Such comparisons
depend on the selected sampling time and do not allow evaluation of entire
response profiles. A thorough evaluation of drug properties requires that the
time course of the response be taken into account. In this investigation we show 
the advantages of a model-based approach to compare the efficacy of two triptans 
(sumatriptan vs. naratriptan). METHODS: A Markov model was used to describe the
course of a migraine attack over three clinically identified stages. Drug effects
were modelled as concentration-dependent increases in transition rates and were
parameterised as potency (EC(50)) and maximum effect (E(max)). Parameters were
estimated using headache measurements from efficacy studies. Model estimates were
then used to compare the pharmacodynamics of the two drugs in a time-independent 
manner. RESULTS: Efficacy parameters could be derived, allowing for comparison
between compounds. The potency ratio (EC50(suma)/EC50(nara)) for headache relief 
was 3.3 (0.9, 12). The ratio of maximum effects (Emax(suma)/Emax(nara)) for this 
endpoint was 0.74 (0.55, 0.97). To interpret these efficacy measures and explore 
their value for the development of antimigraine drugs, results were evaluated
against the reported in vitro potency at 5-HT(1B) and 5-HT(1D) receptors.
CONCLUSIONS: Comparison of the effects of two or more drugs based on preset
sampling times does not allow proper assessment of the antimigraine properties in
vivo. Disease dynamics must be considered to evaluate treatment response
adequately and optimise the dosing regimen in migraine.

PMID: 17061965 [PubMed - indexed for MEDLINE]

1001: Neurology. 2006 Oct 24;67(8):1353-6.

Prognosis of migraine headaches in adolescents: a 10-year follow-up study.

Monastero R, Camarda C, Pipia C, Camarda R.

Adult Headache Centre, Section of Neurology and Psychiatry, DiNOP, University of 
Palermo, Italy.

OBJECTIVE: To determine the long-term outcome of migraine headaches in
adolescents and to identify possible predictors of prognosis. METHODS: Fifty-five
of 80 subjects with migraine headaches (ages 11 to 14 years), who attended the
baseline examination of a population-based study conducted in southern Italy in
1989, were eligible for follow-up in 1999. All interviews and examinations were
conducted by neurologists, and migraine diagnoses were based on the International
Headache Society (IHS) criteria. The association between possible prognostic
factors and the long-term persistence of migraine headaches was explored using
logistic regression analysis. RESULTS: Of 55 subjects with migraine headaches at 
baseline, 41.8% had persistent migraine, 38.2% had experienced remission, and
20.0% transformed to tension-type headache. Only migraine without aura persisted 
in the same IHS code after 10 years, whereas migrainous disorder and
nonclassifiable headache did not. The family history of migraine significantly
predicted the 10-year persistence of migraine headaches (odds ratio [OR] = 7.0;
95% CI: 1.7 to 26.8). The risk persisted when only subjects with migraine with or
without aura were evaluated (OR = 5.0; 95% CI: 1.2 to 20.9). CONCLUSIONS:
Migraine headaches in adolescents have a favorable long-term prognosis. Familial 
disposition for migraine predicted a poorer outcome, especially in subjects with 
migraine without aura.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17060559 [PubMed - indexed for MEDLINE]

1002: Cephalalgia. 2006 Nov;26(11):1330-4.

'Hair wash' or 'head bath' triggering migraine - observations in 94 Indian
patients.

Ravishankar K.

The Headache and Migraine Clinic, Jaslok Hospital, Lilavati Hospital, Mumbai,
India. dr_k_ravishankar@vsnl.com

Identification of trigger factors is helpful in the diagnosis and management of
migraine. Common triggers of migraine are well established but 'hair wash or head
bath' as a trigger for migraine has so far not been reported. This prospective
study analysed this unusual trigger link in 94 out of 1500 Indian patients who
fulfilled the International Headache Society criteria for migraine. In 11
patients, hair wash was the only trigger; in 45 patients hair wash was one of the
triggers and in 38 patients hair wash was a trigger concurrently and in
combination with another common trigger. The effect of episodic and long-term
prophylaxis in preventing this trigger-like headache has been analysed. The
underlying pathophysiological basis is not established but it is important for
this unusual regional trigger to be identified and incorporated in the management
strategy.

Publication Types: 
    Case Reports

PMID: 17059440 [PubMed - indexed for MEDLINE]

1003: Cephalalgia. 2006 Nov;26(11):1310-9.

Serotonin-induced plasma extravasation in the murine inner ear: possible
mechanism of migraine-associated inner ear dysfunction.

Koo JW, Balaban CD.

Department of Otolaryngology, Seoul National University College of Medicine,
Seoul National University Bundang Hospital, Seongnam, Korea.

Sensitivity to sound and vertigo are often components of migraine. Recent studies
suggest that plasma extravasation from intradural blood vessels may contribute to
migraine pain. This study documented plasma extravasation in the mouse inner ear 
after intravenous administration of serotonin (5-HT). Horseradish peroxidase
(HRP) was injected intravenously to trace protein extravasation in mice, followed
15 min later by intravenous 5-HT or saline. Forty-five minutes later, mice were
euthanized. HRP extravasation was visualized immunohistochemically and quantified
densitometrically. Baseline and evoked extravasation in stria vascularis and
tectorial membrane were indistinguishable from skin, dura mater and tympanic
membrane. Brain parenchyma, Scarpa's ganglion, basal spiral ganglion and
modiolus, and the central vestibular nerve segment showed no significant
5-HT-induced extravasation. In contrast, 5-HT produced extravasation in the
apical spiral ganglion, modiolus, and intralabyrinthine superior and inferior
vestibular nerve. Thus, inner ear plasma extravasation is a potential mechanism
for migraine-associated vertigo and sound sensitivity.

PMID: 17059438 [PubMed - indexed for MEDLINE]

1004: Cephalalgia. 2006 Nov;26(11):1294-303.

Intravital microscopy on a closed cranial window in mice: a model to study
trigeminovascular mechanisms involved in migraine.

Gupta S, Akerman S, van den Maagdenberg AM, Saxena PR, Goadsby PJ, van den Brink 
AM.

Department of Pharmacology, Erasmus Medical Centre, Rotterdam, the Netherlands.

The purpose of the study was to develop a mouse model to study trigeminovascular 
mechanisms using intravital microscopy on a closed cranial window. In addition,
we studied exogenous and endogenous calcitonin gene-related peptide
(CGRP)-mediated vasodilation in dural arteries. Arteries in C57BL/6Jico mice were
constricted with endothelin-1, which reduced the baseline diameter by 65-75%.
Subsequently, vasodilation was induced by alpha-CGRP, capsaicin or transcranial
electrical stimulation of perivascular trigeminal nerves in the absence or
presence of different concentrations of BIBN4096BS or sumatriptan. Both
alpha-CGRP and capsaicin induced vasodilation in preconstricted arteries.
Transcranial electrical stimulation also induced current-dependent relaxation of 
dural arteries with 100 microA producing maximal dilation in the control group.
BIBN4096BS blocked the responses evoked by alpha-CGRP and capsaicin, as well as
electrical stimulation, whereas sumatriptan attenuated only vasodilation induced 
by electrical stimulation. This model is likely to prove useful in dissecting
elements of the trigeminovascular system and for exploring pathophysiological
aspects of migraine, especially in future studies using transgenic mice with
mutations relevant to those observed in patients with migraine.

PMID: 17059436 [PubMed - indexed for MEDLINE]

1005: Cephalalgia. 2006 Nov;26(11):1275-86.

Retinal migraine reappraised.

Grosberg BM, Solomon S, Friedman DI, Lipton RB.

Department of Neurology, Albert Einstein College of Medicine, Bronx, New York,
NY, USA. bgrosber@montefiore.org

Retinal migraine is usually characterized by attacks of fully reversible
monocular visual loss associated with migraine headache. Herein we summarize the 
clinical features and prognosis of 46 patients (six new cases and 40 from the
literature) with retinal migraine based upon the International Classification of 
Headache Disorders-2 (ICHD-2) criteria. In our review, retinal migraine is most
common in women in the second to third decade of life. Contrary to ICHD-2
criteria, most have a history of migraine with aura. In the typical attack
monocular visual features consist of partial or complete visual loss lasting <1
h, ipsilateral to the headache. Nearly half of reported cases with recurrent
transient monocular visual loss subsequently experienced permanent monocular
visual loss. Although the ICHD-2 diagnostic criteria for retinal migraine require
reversible visual loss, our findings suggest that irreversible visual loss is
part of the retinal migraine spectrum, perhaps representing an ocular form of
migrainous infarction. Based on this observation, the authors recommend migraine 
prophylactic treatment in an attempt to prevent permanent visual loss, even if
attacks are infrequent. We also propose a revision to the ICHD-2 diagnostic
criteria for retinal migraine.

Publication Types: 
    Case Reports
    Research Support, N.I.H., Extramural

PMID: 17059434 [PubMed - indexed for MEDLINE]

1006: Cephalalgia. 2006 Nov;26(11):1265-74.

Comment in:
    Cephalalgia. 2007 Jul;27(7):862-3; author reply 863.

A review of evidence-based medicine and meta-analytic reviews in migraine.

Tfelt-Hansen P.

Danish Headache Centre, Department of Neurology, University of Copenhagen,
Glostrup Hospital, Glostrup, Denmark. tfelt@inet.uni2.dk

The following systematic reviews and meta-analyses are presented and the results 
discussed: the evidence-based American guidelines, five systematic reviews on
naratriptan, rizatriptan, eletriptan, sumatriptan and propranolol; a
meta-analysis of sumatriptan, a meta-analysis of acute migraine therapy, a
meta-analysis of triptans available in Canada and a large meta-analysis of oral
triptans. The systematic reviews of several randomized trials of one drug
overcome random effects in estimating treatment effect of the reviewed drug. The 
results from the large meta-analysis of several drugs are compared with
head-to-head comparative trials. Results are generally the same in the
meta-analysis and in the comparative trials, with some exceptions. Head-to-head
comparisons should remain the 'gold standard' and meta-analyses are a useful
supplement in cases when comparative trials are relatively small and when no
comparative trials exist.

Publication Types: 
    Comparative Study
    Review

PMID: 17059433 [PubMed - indexed for MEDLINE]

1007: J Neurol Neurosurg Psychiatry. 2007 Jun;78(6):600-4. Epub 2006 Oct 20.

Comment in:
    J Neurol Neurosurg Psychiatry. 2007 Jun;78(6):553.

Migraine with unilateral motor symptoms: a case-control study.

Young WB, Gangal KS, Aponte RJ, Kaiser RS.

Thomas Jefferson University, Philadelphia, Pennsylvania, USA.
william.b.young@jefferson.edu

OBJECTIVE: To characterise the clinical features of non-familial migraine with
unilateral motor symptoms (MUMS) and compare these features with those of
migraine without weakness. METHODS: 24 patients with MUMS and 48 matched controls
were identified from a tertiary care headache centre. Using a structured
interview, the migraine symptoms of both groups were characterised. Results of
previously administered Beck Depression Inventories (BDI), Minnesota Multiphasic 
Personality Inventories and psychiatric diagnoses were collected, when available,
and compared between groups. RESULTS: 9 patients had episodic migraine and 15 had
chronic migraine. Patients with MUMS always had weakness involving the arm
subjectively, and both arm and leg objectively. A give-way character was always
present. Only 17% of patients with MUMS reported facial weakness; 58% reported
persistent interictal weakness; 92% reported sensory symptoms. A rostrocaudal
march of sensory and motor symptoms was frequently reported. Weakness was
ipsilateral to unilateral headache in two thirds of the patients. Compared with
controls, patients with MUMS had had similar pain intensities, but were more
likely to report other migrainous symptoms, including allodynia. 38% of patients 
with MUMS were told they had had a stroke, and 17% believed they had had a stroke
despite normal brain imaging. Patients with MUMS reported fewer affective
disorders and more adjustment disorders than controls, and had similar BDI
scores. CONCLUSIONS: A syndrome of severe migraine with accompanying give-way
weakness is common in tertiary care headache centres. It is accompanied by other 
neurological symptoms.

Publication Types: 
    Comparative Study

PMID: 17056632 [PubMed - indexed for MEDLINE]

1008: Epilepsia. 2006 Oct;47(10):1674-81.

Do children with benign rolandic epilepsy have a higher prevalence of migraine
than those with other partial epilepsies or nonepilepsy controls?

Wirrell EC, Hamiwka LD.

Department of Pediatrics and Clinical Neurosciences, University of Calgary,
Calgary, Alberta, Canada. elaine.wirrell@calgaryhealthregion.ca

PURPOSE: Prior studies have given conflicting data concerning the association of 
benign rolandic epilepsy of childhood (BREC) and migraine but were limited by
lack of sensitive, diagnostic criteria for childhood migraine. By using revised
International Headache Society (IHS-R) criteria, we compared the prevalence of
migraine in children with BREC with that of those (a) with
cryptogenic/symptomatic partial epilepsy and (b) without epilepsy. METHODS: Three
cohorts of children, gender and age matched (within 1 year) were identified: (a) 
BREC, (b) cryptogenic/symptomatic partial epilepsy, and (c) no history of
seizures. Parents were queried in a standardized interview about migraine and
migraine equivalents in their child, and in either biologic parent. Migraine was 
defined by using the IHS-R (for children) and IHS criteria (for parents).
Children with headache were divided into definite (meeting IHS-R criteria),
probable (recurrent, throbbing headaches with nausea, vomiting, photophobia or
phonophobia, not meeting IHS-R criteria), possible (recurrent headaches with
throbbing character or associated nausea/vomiting), or nonmigraine groups. chi(2)
analysis was used to determine whether the cohort with BREC had a higher
prevalence of definite, definite or probable, or definite, probable, or possible 
migraines or migraine equivalents than the other two cohorts. RESULTS: Each
cohort consisted of 53 children (mean age, 9.8-9.9 years, M/F ratio, 35:18).
Those with BREC had higher rates of definite and probable (p = 0.05), of
definite, probable, and possible migraine (p = 0.05), and of migraine equivalents
excluding motion sickness (p < 0.005) than did those without seizures; however,
they did not differ significantly from the cryptogenic/symptomatic partial
epilepsy cohort. CONCLUSIONS: Partial epilepsy, regardless of etiology, is
associated with higher rates of migraine in children. The pathophysiologic link
between epilepsy and migraine is unknown.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 17054690 [PubMed - indexed for MEDLINE]

1009: PLoS Med. 2006 Oct;3(10):e402.

Comment in:
    PLoS Med. 2006 Oct;3(10):e404.

Anatomical alterations of the visual motion processing network in migraine with
and without aura.

Granziera C, DaSilva AF, Snyder J, Tuch DS, Hadjikhani N.

Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General
Hospital, Harvard Medical School, Charlestown, Massachusetts, United States of
America.

BACKGROUND: Patients suffering from migraine with aura (MWA) and migraine without
aura (MWoA) show abnormalities in visual motion perception during and between
attacks. Whether this represents the consequences of structural changes in
motion-processing networks in migraineurs is unknown. Moreover, the diagnosis of 
migraine relies on patient's history, and finding differences in the brain of
migraineurs might help to contribute to basic research aimed at better
understanding the pathophysiology of migraine. METHODS AND FINDINGS: To
investigate a common potential anatomical basis for these disturbances, we used
high-resolution cortical thickness measurement and diffusion tensor imaging (DTI)
to examine the motion-processing network in 24 migraine patients (12 with MWA and
12 MWoA) and 15 age-matched healthy controls (HCs). We found increased cortical
thickness of motion-processing visual areas MT+ and V3A in migraineurs compared
to HCs. Cortical thickness increases were accompanied by abnormalities of the
subjacent white matter. In addition, DTI revealed that migraineurs have
alterations in superior colliculus and the lateral geniculate nucleus, which are 
also involved in visual processing. CONCLUSIONS: A structural abnormality in the 
network of motion-processing areas could account for, or be the result of, the
cortical hyperexcitability observed in migraineurs. The finding in patients with 
both MWA and MWoA of thickness abnormalities in area V3A, previously described as
a source in spreading changes involved in visual aura, raises the question as to 
whether a "silent" cortical spreading depression develops as well in MWoA. In
addition, these experimental data may provide clinicians and researchers with a
noninvasively acquirable migraine biomarker.

Publication Types: 
    Comparative Study
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 17048979 [PubMed - indexed for MEDLINE]

1010: Headache. 2006 Oct;46 Suppl 2:S61-8.

Tailoring management strategies for the patient with menstrual migraine: focus on
prevention and treatment.

Tepper SJ.

Yale University School of Medicine, New Haven, CT, USA.

Many women report an increased frequency of headaches around the time of menses. 
For some women, these headaches are more severe, of longer duration, and lead to 
greater disability than those occurring at other times in the menstrual cycle. A 
headache diary is critical to properly diagnose menstrual migraine (MM) by
prospectively documenting headache days, severity of headache, and the headaches'
relationship to menses. In women with diagnosed MM, acute treatment has been
proven to be effective in randomized clinical trials. For those women who have
predictable periods and may require preventive therapy, short-term prevention is 
a reasonable approach due to the predictability of MM. Although several agents
(eg, naproxen sodium, magnesium, triptans) have been evaluated for prevention of 
MM, all but triptans have been assessed in small trials of between 20 and 35
women. Naratriptan, frovatriptan, and, most recently, zolmitriptan have been
proven effective in preventing MM. Triptans are generally well tolerated, and the
long-term safety of these agents is currently being evaluated. The flexibility of
using acute and preventive therapy allows physicians to tailor treatment of MM
and meet the needs of individual patients.

Publication Types: 
    Review

PMID: 17044843 [PubMed - indexed for MEDLINE]

1011: Headache. 2006 Oct;46 Suppl 2:S55-60.

Menstrual migraine: pathophysiology, diagnosis, and impact.

Loder EW.

Harvard Medical School, Graham Headache Centre, Boston, MA 02130, USA.

The incidence of migraine varies over the course of the menstrual cycle. In the
general population, approximately 60% of women with migraine report an increased 
frequency of headache during menses. The estrogen withdrawal that occurs just
prior to the onset of menses and that leads to loss of serotonergic tone is
thought to be the trigger for headaches that arise at this time of the menstrual 
cycle. The ability of triptans, specific serotonin receptor agonists, to prevent 
menstrual migraine is consistent with this hypothesis. Moreover, compared with
headaches that occur during other times in the cycle, menstrual migraines are
more severe in most women and may be of longer duration, as well as more
resistant to treatment in a subset of women.

Publication Types: 
    Review

PMID: 17044842 [PubMed - indexed for MEDLINE]

1012: Headache. 2006 Oct;46 Suppl 2:S49-54.

Hormonal changes throughout life in women.

Zacur HA.

Theodore and Ingrid Baramki Reproductive Endocrinology and Infertility, Johns
Hopkins University School of Medicine, Department of Gynecology and Obstetrics,
Baltimore, MD 21093, USA.

The changes in hormonal milieu associated with menarche, pregnancy, lactation,
and menopause are frequently accompanied by changes in the patterns and frequency
of migraine. Migraine headache is more common in females and, for many women, the
onset of this condition occurs at menarche. As many as 60% of women migraineurs
report an association between migraine and menstruation, and evidence suggests
that estrogen withdrawal may be a trigger for menstrual migraine in susceptible
women. Moreover, in the majority of women, migraine frequency increases during
the pill-free interval with oral contraceptive use and during the postpartum
period, which are other times of decreasing estrogen levels. Migraine frequency
tends to decrease during periods of increasing or stable estrogen levels. For
these reasons, the numerous neuroendocrine effects elicited by estrogen have been
evaluated to explain its role in migraine. Overall, estrogen appears to be a key 
factor in menstrual migraine, but it is likely to be only one of several factors 
that act in concert to trigger migraine in susceptible women. Understanding the
relationship of the different hormonal milieus through the natural course of
women's lives can guide diagnosis and treatment.

Publication Types: 
    Review

PMID: 17044841 [PubMed - indexed for MEDLINE]

1013: CNS Drugs. 2006;20(11):961-4.

Spotlight on eletriptan in migraine.

McCormack PL, Keating GM.

Wolters Kluwer Health, Adis, Auckland, New Zealand. demail@adis.co.nz

Eletriptan (Relpax) is an orally administered, lipophilic, highly selective
serotonin 5-HT(1B/1D) receptor agonist ('triptan') that is effective in the acute
treatment of moderate to severe migraine attacks in adults. It has a rapid onset 
of action and demonstrates superiority over placebo as early as 30 minutes after 
the administration of a single 40 or 80 mg oral dose. The efficacy of eletriptan 
20 mg was similar to that of sumatriptan 100 mg, while eletriptan 40 and 80 mg
displayed greater efficacy than sumatriptan 50 or 100 mg for most endpoints.
Eletriptan 40 mg was generally superior to naratriptan 2.5 mg and equivalent to
almotriptan 12.5 mg, rizatriptan 10 mg and zolmitriptan 2.5 mg, while eletriptan 
80 mg was superior to zolmitriptan 2.5 mg for most efficacy parameters.
Eletriptan 40 and 80 mg were consistently superior to ergotamine/caffeine.
Eletriptan is generally well tolerated, reduces time lost from normal activities,
improves patients' health-related quality of life and appears to be at least as, 
if not more, cost effective than sumatriptan. Eletriptan is therefore a useful
addition to the triptan family and a first-line treatment option in the acute
management of migraine attacks.

Publication Types: 
    Review

PMID: 17044732 [PubMed - indexed for MEDLINE]

1014: J Emerg Med. 2006 Aug;31(2):169-71.

Unusual visual symptoms in a patient with bilateral vertebral artery dissection: 
a case report.

Nagurney JT, Feldman D, Cahill DP, Gatha NM, Koroshetz WJ.

Department of Emergency Medicine, Massachusetts General Hospital, Boston,
Massachusetts, 02115, USA.

We present a previously unreported set of symptoms in a patient found to have
bilateral vertebral dissections. Although visual symptoms are common in vertebral
dissection, their pattern does not typically mimic those that commonly precede or
accompany migraine headache. When they do occur, they usually take the form of
diplopia or blurred vision. The patient we describe had visual symptoms that
varied over three episodes of headache and included transient visual field loss
and scintillations ("lightning bolts"), both common in migraine. However, our
patient's new visual symptoms represented a change in pattern from those that had
accompanied her previous migraines. This detailed history-taking prompted an
evaluation for an etiology other than migraine and prevented a further delay in
diagnosis and treatment.

Publication Types: 
    Case Reports

PMID: 17044579 [PubMed - indexed for MEDLINE]

1015: J Nurs Scholarsh. 2006;38(3):278-85.

Comment in:
    J Nurs Scholarsh. 2007;39(1):3.

The experiences of midlife women with migraines.

Moloney MF, Strickland OL, DeRossett SE, Melby MK, Dietrich AS.

Byrdine F Lewis School of Nursing, Georgia State University, Atlanta 30302-4019, 
USA. mmoloney@gsu.edu

PURPOSE: To describe the experiences of midlife women with migraines. DESIGN AND 
METHODS: Qualitative data were collected in two consecutive studies, using
open-ended interviews, focus groups, and online discussion boards. Interpretive
methods were used for analysis. FINDINGS: Three patterns were identified:
Changing Headache Patterns; Predicting, Preventing, and Controlling Headaches;
and Keeping on the Move. These patterns indicated how women's headaches changed
over time, how headaches were envisioned within the context of their lives, what 
strategies were used to meet work and home responsibilities, and how women
controlled their headaches while maintaining a sense of perspective. CONCLUSIONS:
Many midlife women with migraines receive inadequate or inappropriate treatment, 
and better dissemination of current diagnostic and treatment guidelines is
necessary. Ongoing research is needed to increase understanding of how this
problem affects midlife women's lives and of what interventions might prevent or 
alleviate migraine discomfort.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 17044346 [PubMed - indexed for MEDLINE]

1016: Headache. 2006 Oct;46(9):1441-9.

Treatment of headaches in the ED with lower cervical intramuscular bupivacaine
injections: a 1-year retrospective review of 417 patients.

Mellick LB, McIlrath ST, Mellick GA.

Department of Emergency Medicine, Medical Colleg of Georgia, Augusta, GA, USA.

OBJECTIVE: The primary objective of this retrospective chart review is to
describe 1 year's experience of an academic emergency department (ED) in treating
a wide spectrum of headache classifications with intramuscular injections of 0.5%
bupivacaine bilateral to the spinous process of the lower cervical vertebrae.
BACKGROUND: Headache is a common reason that patients present to an ED. While
there are a number of effective therapeutic interventions available for the
management of headache pain, there clearly remains a need for other treatment
options. The intramuscular injection of 1.5 mL of 0.5% bupivacaine bilateral to
the sixth or seventh cervical vertebrae has been used to treat headache pain in
our facility since July 2002. The clinical setting for the study was an academic 
ED with an annual volume of over 75,000 patients. METHODS: We performed a
retrospective review of over 2805 ED patients with the discharge diagnosis of
headache and over 771 patients who were coded as having had an anesthetic
injection between June 30, 2003 and July 1, 2004. All adult patients who had
undergone paraspinous intramuscular injection with bupivacaine for the treatment 
of their headache were gleaned from these 2 larger databases and were included in
this retrospective chart review. A systematic review of the medical records was
accomplished for these patients. RESULTS: Lower cervical paraspinous
intramuscular injections with bupivacaine were performed in 417 patients.
Complete headache relief occurred in 271 (65.1%) and partial headache relief in
85 patients (20.4%). No significant relief was reported in 57 patients (13.7%)
and headache worsening was described in 4 patients (1%). Overall a therapeutic
response was reported in 356 of 417 patients (85.4%). Headache relief was
typically rapid with many patients reporting complete headache relief in 5 to 10 
minutes. Associated signs and symptoms such as nausea, vomiting, photophobia,
phonophobia, and allodynia were also commonly relieved. CONCLUSION: Our
observations suggest that the intramuscular injection of small amounts of 0.5%
bupivacaine bilateral to the sixth or seventh cervical spinous process appears to
be an effective therapeutic intervention for the treatment of headache pain in
the outpatient setting.

Publication Types: 
    Clinical Trial

PMID: 17040341 [PubMed - indexed for MEDLINE]

1017: Headache. 2006 Oct;46(9):1431-40.

Visual stimuli are common triggers of migraine and are associated with pattern
glare.

Harle DE, Shepherd AJ, Evans BJ.

The Neville Chappell Research Clinic, The Institute of Optometry, London, UK.

OBJECTIVE: To investigate the associations between interictal pattern glare,
visual stress, and visual triggers of migraine. BACKGROUND: There has been
relatively little research on the visual stimuli that can trigger migraine
episodes. This is surprising, since if practitioners can obviate such triggers,
then some attacks may be prevented. The existing literature suggests that
patients who are prone to visually triggered migraines report more illusions on
viewing striped patterns ("pattern glare") and that colored filters may be an
effective intervention for these people. METHODS: Headache symptoms and headache 
triggers were investigated in migraine and control groups in 2 separate
experiments. In one experiment, we also determined, for each participant, pattern
glare, whether it was reduced by colored filters and, if so, what the optimum
color of filter was. Color vision was also assessed with the D15 test. RESULTS:
People with migraine saw significantly more illusions on viewing each striped
pattern and experienced greater pattern glare. They were also more likely to
select a colored filter to aid visual comfort, particularly colors in the
blue-to-green sector of the spectrum. Color vision was impaired subtly but
significantly in migraine. Principal component analyses grouped common headache
triggers into 5 broadly equal components: food, visual triggers, alcohol, stress 
and tiredness, and the environment. In a second analysis, the overall number of
illusions seen in striped patterns was associated with visual triggers while
pattern glare, use of colored filters, and interictal light sensitivity together 
formed a sixth component interpreted as visual stress. CONCLUSIONS: It is
suggested that clinicians should ask migraine patients whether visual stimuli
trigger their migraine, about interictal visual symptoms, and use the pattern
glare test to ensure that those who may benefit from optometric interventions are
appropriately managed.

Publication Types: 
    Clinical Conference
    Multicenter Study
    Research Support, Non-U.S. Gov't

PMID: 17040340 [PubMed - indexed for MEDLINE]

1018: Headache. 2006 Oct;46(9):1344-63.

Headache and sleep disorders: review and clinical implications for headache
management.

Rains JC, Poceta JS.

Center for Sleep Evaluation, Elliot Hospital, Manchester, NH 03103, USA.

Review of epidemiological and clinical studies suggests that sleep disorders are 
disproportionately observed in specific headache diagnoses (eg, migraine,
tension-type, cluster) and other nonspecific headache patterns (ie, chronic daily
headache, "awakening" or morning headache). Interestingly, the sleep disorders
associated with headache are of varied types, including obstructive sleep apnea
(OSA), periodic limb movement disorder, circadian rhythm disorder, insomnia, and 
hypersomnia. Headache, particularly morning headache and chronic headache, may be
consequent to, or aggravated by, a sleep disorder, and management of the sleep
disorder may improve or resolve the headache. Sleep-disordered breathing is the
best example of this relationship. Insomnia is the sleep disorder most often
cited by clinical headache populations. Depression and anxiety are comorbid with 
both headache and sleep disorders (especially insomnia) and consideration of the 
full headache-sleep-affective symptom constellation may yield opportunities to
maximize treatment. This paper reviews the comorbidity of headache and sleep
disorders (including coexisting psychiatric symptoms where available). Clinical
implications for headache evaluation are presented. Sleep screening strategies
conducive to headache practice are described. Consideration of the spectrum of
sleep-disordered breathing is encouraged in the headache population, including
awareness of potential upper airway resistance syndrome in headache patients
lacking traditional risk factors for OSA. Pharmacologic and behavioral sleep
regulation strategies are offered that are also compatible with treatment of
primary headache.

Publication Types: 
    Review

PMID: 17040332 [PubMed - indexed for MEDLINE]

1019: Headache. 2006 Oct;46(9):1334-43.

Modifiable risk factors for migraine progression.

Bigal ME, Lipton RB.

Department of Neurology, Albert Einstein College of Medicine, Bronx, NY 10461,
USA.

Migraine is a chronic-recurrent disorder that progresses in some individuals.
Transformed migraine is the result of this progression. Since migraine does not
progress in most patients, identifying the risk factors for progression has
emerged as a very important public health priority. If risk factors can be
identified, that might provide a foundation for more aggressive preventive
intervention. Risk factors for progression may be divided into non-remediable
(gender, age, race) and remediable categories. In this paper, we focus on several
already identified remediable risk factors, including frequency of migraine
attacks, obesity, acute medication overuse, caffeine overuse, stressful life
events, depression, and sleep disorders. We present the evidence for each risk
factor and discuss possible interventions to address them.

Publication Types: 
    Review

PMID: 17040331 [PubMed - indexed for MEDLINE]

1020: Eur J Neurol. 2006 Nov;13(11):1239-44.

Validation of the deCODE Migraine Questionnaire (DMQ3) for use in genetic
studies.

Kirchmann M, Seven E, Björnsson A, Björnssdóttir G, Gulcher JR, Stefánsson K,
Olesen J.

Danish Headache Center, Department of Neurology, University of Copenhagen,
Glostrup Hospital, Copenhagen, Denmark. kirchmann@dadlnet.dk

We assessed the reliability of the diagnosis of migraine with aura (MA) and
migraine without aura (MO) based on the third edition of the deCODE Migraine
Questionnaire (DMQ3) using a physician-conducted interview as an empirical index 
of validity. Amongst Danish migraine families recruited from specialist practice 
we selected 200 cases diagnosed according to the International Classification of 
Headache Disorders 2nd Edition in a validated physician-conducted telephone
interview: 50 patients with exclusively MA, 50 with both MA and MO, 50 with
exclusively MO and 50 controls. A written copy of the DMQ3 was mailed to the
participant. The DMQ3-based diagnosis was compared with the interview-based
diagnosis. Overall, the DMQ3 diagnosed migraine (MA, MO or both) with a
sensitivity of 99% (109/110), a specificity of 86% (32/37) and a kappa statistic 
of 0.89. The most reliable subtype of migraine was MA (with or without
co-occurring attacks of MO) which was diagnosed with a sensitivity of 92%
(71/77), a specificity of 93% (65/70) and a kappa statistic of 0.85. Exclusively 
MO was diagnosed with a sensitivity of 91% (30/33), a specificity of 93%
(106/114) and a kappa statistic of 0.80. Weakest was the diagnosis of both MO and
MA which was diagnosed with a sensitivity of 63% (24/38), a specificity of 92%
(100/109) and a kappa statistic of 0.57. In conclusion, the DMQ3 is a valid tool 
for diagnosing patients with migraine for genetic studies.

Publication Types: 
    Comparative Study
    Validation Studies

PMID: 17038039 [PubMed - indexed for MEDLINE]

1021: Mayo Clin Proc. 2006 Oct;81(10):1387-91; quiz 1392.

Answers to frequently asked questions about migraine.

Garza I, Swanson JW.

Department of Neurology, Mayo Clinic College of Medicine, 200 First St SW,
Rochester, MN 55905, USA. garzaurdiales.ivan@mayo.edu

Migraine is a common primary headache disorder associated with pronounced
disability and hence marked economic and public health Implications. Appropriate 
treatment is warranted to limit the associated disability migraineurs experience.
Because of the heterogeneity of migraine, treatment plans must be individualized.
The purpose of this article is to provide answers to frequently asked questions
regarding the management of migraine.

Publication Types: 
    Review

PMID: 17036564 [PubMed - indexed for MEDLINE]

1022: Mayo Clin Proc. 2006 Oct;81(10):1311-9.

Assessing the ability of topiramate to improve the daily activities of patients
with migraine.

Brandes JL, Kudrow DB, Rothrock JF, Rupnow MF, Fairclough DL, Greenberg SJ.

Nashville Neuroscience Group, 300 20th Ave N, Suite 603, Nashville, TN 37203,
USA. jbrandes@nashvilleneuroscience.com

OBJECTIVE: To assess the impact of topiramate on the daily activities of patients
with migraine. PATIENTS AND METHODS: We performed a randomized, double-blind,
placebo-controlled multicenter trial Initiated on March 1, 2001, and completed on
April 4, 2002. Patient-reported data from the Migraine Specific Questionnaire
(MSQ) and the Medical Outcomes Study 36-item Short-Form Health Survey (SF-36)
were collected at baseline and at weeks 8, 16, and 26 from an intent-to-treat
population receiving either topiramate, 50, 100, or 200 mg/d, or placebo. Two
activity-related MSQ domains (role restrictive [MSQ-RR] and role prevention
[MSQ-RP]) and 2 activity-related SF-36 domains (role physical [SF36-RP] and
vitality [SF36-VT]) were the prospectively designated secondary outcome measures.
The changes in MSQ and SF-36 scores for each treatment group were calculated by
measuring the area under the curve from week 8 (the beginning of the maintenance 
period) through week 26 of the double-blind phase, relative to the prospective
baseline. A mixed-effect piecewise linear regression model was used to estimate
average domain score over time. RESULTS: Patients receiving topiramate, 100 or
200 mg/d, had significantly reduced mean monthly (28-day) migraine frequency (P =
.008 and P < .001, respectively) compared with placebo, but not patients
receiving topiramate, 50 mg/d (P = .48). Topiramate significantly improved mean
MSQ-RR domain scores (50 mg/d [P = .02], 100 mg/d [P< .001], and 200 mg/d [P <
.001]) and mean MSQ-RP domain scores (50 mg/d [P = .007], 100 mg/d [P = .001],
and 200 mg/d [P= .002]) vs placebo. Topiramate, 100 and 200 mg/d, significantly
improved mean SF36-RP domain scores vs placebo (P = .02). Topiramate (all doses) 
improved SF36-VT domain scores, although not significantly vs placebo. Changes in
prospectively designated domain scores were significantly correlated with changes
in mean monthly migraine frequency (P < or = .001 [MSQ domains], P < or = .002
[SF-36 domains]). CONCLUSION: Patient-reported migraine-specific outcomes
measured by the MSQ-RR and MSQ-RP domains improved significantly for those
receiving topiramate (all doses) vs placebo. The SF36-RP domain scores improved
significantly for patients receiving 100 or 200 mg/d of topiramate. Improvements 
in all 4 prospectively selected MSQ and SF-36 domains were significantly
correlated with decreases in mean monthly migraine frequency.

Publication Types: 
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 17036556 [PubMed - indexed for MEDLINE]

1023: Headache. 2006 Oct;46 Suppl 3:S144-6.

Modifiable risk factors for migraine progression (or for chronic daily
headaches)--clinical lessons.

Bigal ME, Lipton RB.

Department of Neurology, Albert Einstein College of Medicine, Bronx, NY 10461,
USA.

Herein we summarize clinical issues gleaned from a full peer-reviewed article on 
modifiable risk factors for migraine. Since migraine is progressive in some but
not in most individuals, identifying patients at risk for progression is crucial.
Key interventions include: (1) Decrease headache frequency with behavioral and
pharmacologic interventions; (2) Monitor the body mass index and encourage
maintenance of normal weight; (3) Avoid medication overuse; (4) Avoid caffeine
overuse; (5) Investigate and treat sleep problems and snoring; (6) Screen and
treat depression and other psychiatric comorbidities. These recommendations have 
not been demonstrated to improve outcomes in longitudinal studies.

Publication Types: 
    Review

PMID: 17034393 [PubMed - indexed for MEDLINE]

1024: Complement Ther Clin Pract. 2006 Nov;12(4):276-80. Epub 2006 Sep 28.

Kampo medicines as alternatives for treatment of migraine: six case studies.

Ishida K, Sato H.

Department of Internal Medicine, Metropolitan Aoyama Hospital, 5-53-3 Jingumae,
Shibuya-ku, Tokyo 150-0001, Japan. k-ishida@iom.twmu.ac.jp

Kampo is a well-recognized form of traditional medicine in Japan. This paper
reports upon six cases of successful use of Kampo medicines, herbal medicine
preparations, for the treatment of migraine. Most of the patients had been
treated with conventional medicines, such as non-steroidal anti-inflammatory
drugs or triptans, but were not satisfied with the outcomes of these conventional
treatments with regard to their effectiveness or feelings of discomfort after
administration. We administered two Kampo medicines, goshuyuto for prevention of 
migraine and senkyuchachosan as a painkiller. Both Kampo medicines worked
successfully in the treatment of migraine and the patients were satisfied with
their effects. Kampo medicine seems a favorable candidate for alternative therapy
of migraine.

Publication Types: 
    Case Reports

PMID: 17030300 [PubMed - indexed for MEDLINE]

1025: Pain. 2007 Feb;127(3):221-33. Epub 2006 Oct 4.

Stereotyped topography of different elevated contingent negative variation
components in children with migraine without aura points towards a subcortical
dysfunction.

Bender S, Weisbrod M, Resch F, Oelkers-Ax R.

Department for Child and Adolescent Psychiatry, University of Heidelberg,
Blumenstrasse 8, D-69115 Heidelberg, Germany.
Stephan.Bender@med.uni-heidelberg.de

Increased negativity during contingent negative variation (CNV) is thought to
reflect abnormal neural activation in adult migraineurs' attention related
processing. Findings in childhood and adolescence have yielded less clear
results. This study characterizes the age-dependent development of CNV topography
in migraine during childhood in order to elucidate the origin and cerebral
generators of described CNV elevations. A large sample of children with primary
headache (migraine with/without aura, tension type headache) and healthy controls
aged 6-18 years was examined in a CNV paradigm using 64-channel high resolution
DC-EEG. Patients were tested for diagnose-related topographic group differences
of initial CNV (iCNV), late CNV (lCNV) and postimperative negative variation
(PINV). All three CNV components of 6-11-year-old migraineurs without aura showed
elevated negativity over the supplementary motor area (SMA) and around the
vertex. Migraine children lacked age-dependent development of late CNV around Cz 
as previously reported. However, they showed a normal development of late CNV
over pre-/primary motor cortex (MI). There was no marked elevation of iCNV
amplitude over frontal areas (orienting reaction) nor specific amplitude
elevations over "motor" or "sensory" areas during sustained attention (late CNV).
Additional "pre-mature" activation e.g., in the locus coeruleus (leading to
diffuse cortical activation summing up to a maximum over the vertex) or the basal
ganglia (interacting with SMA) explained the rather stereotyped CNV elevation
around the vertex better than a specific implication of the cortical systems
responsible for orienting, motor preparation or sensory attention.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 17027155 [PubMed - indexed for MEDLINE]

1026: J Pain. 2006 Oct;7(10):688-96.

A series of three sequential, randomized, controlled studies of repeated
treatments with botulinum toxin type A for migraine prophylaxis.

Elkind AH, O'Carroll P, Blumenfeld A, DeGryse R, Dimitrova R; BoNTA-024-026-036
Study Group.

Elkind Headache Center, Mount Vernon, New York, USA.

We examined the effects of multiple treatments with low doses of botulinum toxin 
type A (BoNTA; BOTOX(R), Allergan Inc., Irvine, CA) versus placebo for
prophylaxis of episodic migraine. This was a series of 3 sequential, randomized, 
controlled studies of 418 patients with a history of 4 to 8 moderate to severe
migraines per month. In study I, patients were randomized to treatment with
placebo or BoNTA (7.5 U, 25 U, or 50 U) in predetermined fixed injection sites on
the front and sides of the head only. In study II, patients continued to receive,
or were randomized to, 2 consecutive treatments with 25 U or 50 U. In study III, 
patients were randomized to placebo or continuation of 25 U or 50 U. Injection
cycles were each 4 months long. BoNTA and placebo produced comparable decreases
from baseline in the frequency of migraines at each time point examined (P >or=
.201). No consistent, statistically significant differences were observed for any
efficacy variable. Adverse events were similar among the groups within each
study. In these exploratory studies of episodic migraine patients, repeated
injections of low doses of BoNTA into fixed frontal, temporal, and glabellar
sites were not more effective than placebo. BoNTA was safe and well tolerated.
PERSPECTIVE: Beneficial effects of BoNTA in the treatment of migraine have been
reported, but positive results are not universal, possibly because the optimal
patient population and regimen are not yet definitively established. This study
explores the effects of multiple injections of low BoNTA doses into fixed sites
for episodic migraine.

Publication Types: 
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 17018329 [PubMed - indexed for MEDLINE]

1027: J Headache Pain. 2006 Sep;7(4):185-7. Epub 2006 Sep 4.

Comment in:
    J Headache Pain. 2006 Sep;7(4):169-71.

Chronic migraine prevention with topiramate.

Peres MF, Mercante JP, Tanuri FC, Nunes M, Zukerman E.

Instituto Israelita de Ensino e Pesquisa Albert Einstein, UNIFESP - EPM FMABC,
Department of Neurology, Brazil. marioperes@yahoo.com

Chronic migraine (CM) is a disabling condition with not many treatment strategies
available. Topiramate is effective in episodic migraine prevention, however
little is known about its effect in CM. An open label study was performed.
Sixty-four patients diagnosed with CM or probable CM according to the IHS
diagnostic criteria were enrolled, 50 patients were available for analysis and an
intention-to-treat methodology was applied. The primary endpoint considered was
the number of patients with a decrease in headache frequency higher than 50%. The
median dose was 100 mg, a reduction in frequency higher than 50% occurred in 33
patients (66%) and 14 (28%) presented a complete response, defined as a frequency
reduction higher than 95%. The medication was well tolerated. The most common
side effects found were weight loss, paraesthesias, nausea, cognitive
dysfunction, fatigue, somnolence, insomnia and depression. Our findings suggest
that topiramate is effective in CM prophylaxis.

Publication Types: 
    Clinical Trial
    Research Support, Non-U.S. Gov't

PMID: 17016684 [PubMed - indexed for MEDLINE]

1028: Pain Med. 2006 Sep-Oct;7(5):386-94.

Botulinum toxin--a treatment for migraine? A systematic review.

Gupta VK.

Dubai Police Medical Services, Dubai, United Arab Emirates. dr_vkgupta@yahoo.com

Scalp injection of botulinum toxin type A (BT-A) into the superficial musculature
has evoked interest in the management of migraine headache. In clinical trials,
prevention of migraine attacks for 3 months or more has been seen in some
patients following BT-A scalp injections. In the majority of pain syndromes where
BT-A is effective, inhibition of muscle spasms appears to be an important
component of its activity. A direct or independent and prolonged analgesic action
unrelated to skeletal muscle relaxation is believed to underlie the prophylactic 
efficacy of BT-A in migraine; peripheral and central modulation of pain impulses 
by BT-A has also been proposed. A direct peripheral antinociceptive effect was
not seen in three controlled studies of BT-A in normal human volunteers.
Experimental evidence for BT-A-induced analgesia in rats is suggestive but
dose-dependent and lasts only 2 weeks. In migraine patients, a consistent or
dose-dependent response to BT-A treatment has not been seen. Peak responses to
BT-A in migraine patients are seen at 8-12 weeks, whereas BT-A-affected nerve
endings in mice fully recover function between 63 and 91 days; the difference in 
species limits the interpretation of this dissonance. As BT-A does not normally
cross the intact blood-brain barrier, meningeal nociceptors appear unlikely to be
influenced by scalp injections of BT-A; the possibility of antidromic transfer of
BT-A in the trigeminovascular system should be considered. The extended period
for which migraine prophylaxis might be required, the antigenic and
headache-provoking potential of BT-A, the inability of BT-A to affect central
neuronal processes significantly, including the aura of migraine, the possible
placebo effect of needling, and purely subjective outcome measures in headache
studies are additional concerns in evaluating this treatment strategy. The
clinical utility of BT-A has not been compared against established migraine
prophylactic agents. The efficacy of BT-A in preventing migraine headache attacks
remains controversial and the underlying scientific rationale is debatable.

Publication Types: 
    Review

PMID: 17014596 [PubMed - indexed for MEDLINE]

1029: J Psychosom Res. 2006 Oct;61(4):447-51.

Accompanying symptoms and psychiatric comorbidity in migraine and tension-type
headache patients.

Mongini F, Rota E, Deregibus A, Ferrero L, Migliaretti G, Cavallo F, Mongini T,
Novello A.

Department of Clinical Pathophysiology, Unit of Headache-Facial Pain, University 
of Turin, Turin, Italy. franco.mongini@unito.it

OBJECTIVE: Our objective was to assess the prevalence of accompanying symptoms of
migraine and tension-type headache in patients with such conditions (both
episodic and chronic) and in headache-free controls, and their relationship with 
depression and anxiety. METHOD: A psychological assessment (Axis I, DSM-IV) was
performed, and 21 accompanying symptoms were investigated in 506 patients with
episodic migraine (231), chronic migraine (102), episodic tension-type headache
(83), and chronic tension-type headache (90) and in 80 controls. The relationship
between symptoms, headache type, and psychiatric comorbidity was analyzed.
RESULTS: The mean number of symptoms was significantly higher in patients
(n=10.3) than in controls (n=3.4). Most symptoms were significantly associated
with depression and anxiety, while only some of them were significantly
associated with headache, with no relevant difference among groups. CONCLUSION:
In headache patients, psychiatric comorbidity (compared with headache type or
chronicity) seems to be more strictly associated with an increased burden of
accompanying symptoms.

PMID: 17011351 [PubMed - indexed for MEDLINE]

1030: BMC Gastroenterol. 2006 Sep 28;6:26.

Migraine, fibromyalgia, and depression among people with IBS: a prevalence study.

Cole JA, Rothman KJ, Cabral HJ, Zhang Y, Farraye FA.

Department of Epidemiology, Boston University School of Public Health, Boston MA,
USA. jalexcole@comcast.net

BACKGROUND: Case descriptions suggest IBS patients are more likely to have other 
disorders, including migraine, fibromyalgia, and depression. We sought to examine
the prevalence of these conditions in cohorts of people with and without IBS.
METHODS: The source of data was a large U.S. health plan from January 1, 1996
though June 30, 2002. We identified all people with a medical claim associated
with an ICD-9 code for IBS. A non-IBS cohort was a random sample of people with
an ICD-9 code for routine medical care. In the cohorts, we identified all claims 
for migraine, depression, and fibromyalgia. We estimated the prevalence odds
ratios (PORs) of each of the three conditions using the Mantel-Haenszel method.
We conducted quantitative sensitivity analyses to quantify the impact of residual
confounding and in differential outcome identification. RESULTS: We identified
97,593 people in the IBS cohort, and a random sample of 27,402 people to compose 
the non-IBS comparison cohort. With adjustment, there was a 60% higher odds in
the IBS cohort of having any one of the three disorders relative to the
comparison cohort (POR 1.6, 95% CI 1.5 - 1.7). There was a 40% higher odds of
depression in the IBS cohort (POR 1.4, 95% CI 1.3 - 1.4). The PORs for
fibromyalgia and migraine were similar (POR for fibromyalgia 1.8, 95% CI 1.7 -
1.9; POR for migraine 1.6, 95% CI 1.4 - 1.7). Differential prevalence of an
unmeasured confounder, or imperfect sensitivity or specificity of outcome
detection would have impacted the observed results. CONCLUSION: People in the IBS
cohort had a 40% to 80% higher prevalence odds of migraine, fibromyalgia, and
depression.

Publication Types: 
    Comparative Study

PMID: 17007634 [PubMed - indexed for MEDLINE]

1031: Eur J Neurosci. 2006 Sep;24(6):1517-34.

Animal models of migraine: looking at the component parts of a complex disorder.

Bergerot A, Holland PR, Akerman S, Bartsch T, Ahn AH, MaassenVanDenBrink A,
Reuter U, Tassorelli C, Schoenen J, Mitsikostas DD, van den Maagdenberg AM,
Goadsby PJ.

Headache Group, Institute of Neurology, and The National Hospital for Neurology
and Neurosurgery, Queen Square, London, UK.

Animal models of human disease have been extremely helpful both in advancing the 
understanding of brain disorders and in developing new therapeutic approaches.
Models for studying headache mechanisms, particularly those directed at migraine,
have been developed and exploited efficiently in the last decade, leading to
better understanding of the potential mechanisms of the disorder and of the
action for antimigraine treatments. Model systems employed have focused on the
pain-producing cranial structures, the large vessels and dura mater, in order to 
provide reproducible physiological measures that could be subject to
pharmacological exploration. A wide range of methods using both in vivo and in
vitro approaches are now employed; these range from manipulation of the mouse
genome in order to produce animals with human disease-producing mutations,
through sensitive immunohistochemical methods to vascular, neurovascular and
electrophysiological studies. No one model system in experimental animals can
explain all the features of migraine; however, the systems available have begun
to offer ways to dissect migraine's component parts to allow a better
understanding of the problem and the development of new treatment strategies.

Publication Types: 
    In Vitro
    Review

PMID: 17004916 [PubMed - indexed for MEDLINE]

1032: Laryngoscope. 2006 Oct;116(10):1782-6.

Migraine-related vertigo: diagnostic criteria and prophylactic treatment.

Maione A.

Department of Otolaryngology, Azienda Ospedaliera of Pordenone, Pordenone, Italy.
aeturomaione@libero.it

OBJECTIVE/HYPOTHESIS: The objective of this prospective, observational study was 
to evaluate the efficacy of migraine pharmacologic prophylaxis on a group of
vertiginous patients considered affected by migraine-related vertigo on the basis
of precise criteria of inclusion. METHODS: Fifty-three patients affected by
migraine-related vertigo were selected from a cohort of 652 vertiginous patients 
referred to our Dizziness Unit from March 2001 to June 2005. Inclusion criteria
were at least five vertigo attacks occurred in any period of time or dizziness
and/or positional vertigo for at least 6 months; migraine, past or present,
and/or a family history of migraine and/or motion intolerance; and exclusion of
other causes. Patients were submitted to migraine pharmacologic prophylaxis
selected on the basis of the characteristics of the patients and of the drug side
effects. The efficacy of the treatment was evaluated after 6 months by
questionnaire divided into five outcome categories (resolution, substantial
control, moderate control, minimal control, no improvement or worsening) and, for
the patients with recurrent vertiginous attacks, also reporting the percentage
reduction of the attack frequency. RESULTS: Thirty-six patients completed the
study and were submitted to analysis of the results: 10 reported complete
resolution of symptoms, 15 substantial control, 7 moderate control, one minimum
control and 3 no improvement. Thirty-three of them had recurrent vertigo: 19
reported complete disappearance of the attacks, 8 reduction of the frequency
>50%, 5 reduction <50%, and one no reduction. CONCLUSIONS: Migraine prophylactic 
treatment shows encouraging results in patients with migraine-related vertigo
selected with our criteria of inclusion: 69.3% reported satisfactory control of
symptoms (sum of complete resolutions and substantial controls) and 81.8% had at 
least a 50% reduction of the vertiginous episodes frequency.

PMID: 17003732 [PubMed - indexed for MEDLINE]

1033: Neurology. 2006 Sep 26;67(6):1028-33.

Migrainous vertigo: prevalence and impact on quality of life.

Neuhauser HK, Radtke A, von Brevern M, Feldmann M, Lezius F, Ziese T, Lempert T.

Department of Epidemiology, Robert Koch Institute, Berlin, Germany.
neuhauserh@rki.de

OBJECTIVE: To investigate the epidemiology of migrainous vertigo (MV) in the
general population by assessing prevalence, clinical features, comorbid
conditions, quality of life, and health care utilization. METHODS: We screened a 
representative sample of the adult population in Germany (n = 4,869) for moderate
or severe dizziness/vertigo and followed up with validated neurotologic telephone
interviews (n = 1,003). Diagnostic criteria for MV were as follows: 1) recurrent 
vestibular vertigo; 2) migraine according to the International Headache Society; 
3) migrainous symptoms during at least two vertiginous attacks (migrainous
headache, photophobia, phonophobia, or aura symptoms); and 4) vertigo not
attributed to another disorder. In a concurrent validation study (n = 61) the
interviews had a sensitivity of 84% and a specificity of 94% for vestibular
vertigo and 81% and 100% for migraine. RESULTS: The lifetime prevalence of MV was
0.98% (95% CI 0.70 to 1.37), the 12-month prevalence 0.89% (95% CI 0.62 to 1.27).
Spontaneous rotational vertigo was reported by 67% of participants with MV while 
24% had positional vertigo. Twenty-four percent always experienced headaches with
their vertigo. Logistic regression analysis comparing participants with MV with
dizziness-free migraineurs showed an independent association with coronary heart 
disease but not with sex, age, migrainous aura, education, stroke, hypertension, 
hyperlipidemia, body mass index, or depression. Age-adjusted health-related
quality of life scores (SF-8 Health Survey) were consistently lower in
participants with MV compared to dizziness-free controls. Two thirds of
participants with MV had consulted a doctor but only 20% of these were diagnosed 
with MV. CONCLUSIONS: Migrainous vertigo is relatively common but underdiagnosed 
in the general population and has considerable personal and healthcare impact.

Publication Types: 
    Comparative Study

PMID: 17000973 [PubMed - indexed for MEDLINE]

1034: CNS Drugs. 2006;20(10):813-20.

Migraine in children and adolescents: a guide to drug treatment.

Hämäläinen ML.

Department of Pediatric Neurology, Hospital for Children and Adolescents,
Helsinki University Central Hospital, Helsinki, Finland. mirja.hamalainen@hus.fi

Migraine is a common disorder in children and adolescents, with a prevalence of 5
and 10%, respectively. Some patients may have recognisable factors that trigger
or aggravate migraine attacks, such as flickering or bright lights, strong smells
and noise, and where possible these should be avoided. It is also wise to
maintain a lifestyle where children receive regular meals and get sufficient
sleep. If used, acute pharmacological treatment should be given at the onset of
an attack, followed by a rest or sleep. According to recent literature,
paracetamol (acetaminophen) and ibuprofen can be recommended for the acute
treatment of migraine attacks in children and adolescents, and sumatriptan nasal 
spray can be recommended for adolescents. The oral formulation of sumatriptan has
not shown efficacy in paediatric patients, and the subcutaneous injection,
although somewhat effective, is not an ideal formulation for this patient group. 
There are too few data on the efficacy of the other 'triptans' to recommend their
use in children and adolescents. There are less data on the use of prophylactic
drugs in paediatric patients. In systematic studies, only flunarizine, which is
not available in many countries, and propranolol have been found to be effective.
A pilot placebo-controlled study suggests that topiramate might also be
effective. Several other agents are commonly used to prevent migraine attacks in 
children (e.g. amitriptyline, valproic acid [sodium valproate]) despite a lack of
robust research into their efficacy.

Publication Types: 
    Review

PMID: 16999452 [PubMed - indexed for MEDLINE]

1035: Clin Ther. 2006 Jul;28(7):1002-11.

Erratum in:
    Clin Ther. 2006 Sep;28(9):1482.

Efficacy and tolerability of topiramate 200 mg/d in the prevention of migraine
with/without aura in adults: a randomized, placebo-controlled, double-blind,
12-week pilot study.

Silberstein SD, Hulihan J, Karim MR, Wu SC, Jordan D, Karvois D, Kamin M.

Jefferson Headache Center, Thomas Jefferson University Hospital, Philadelphia, PA
19107, USA. stephen.silberstein@jefferson.edu

BACKGROUND: Several large, randomized, double-blind, placebo-controlled trials
have found topiramate (TPM) to be effective and generally well tolerated as a
preventive therapy for migraine. OBJECTIVE: This paper evaluates efficacy and
safety data from a pilot study of TPM 200 mg/d as preventive therapy in adult
subjects with a history of migraine with or without aura. METHODS: The pilot
study had a randomized, double-blind, placebo-controlled design. Subjects were
randomized in a 2:1 ratio to receive TPM 200 mg/d or placebo. The double-blind
treatment phase consisted of an 8-week titration period (25 mg/d for the first
week, followed by weekly increases of 25 mg) and a 12-week maintenance period.
The primary efficacy measure was the change in mean monthly migraine frequency.
Additional measures were the median percent reduction in monthly migraine
frequency and the proportion of responders (those with > or =50%, > or =75%, or
100% reduction in monthly migraine frequency). RESULTS: The intent-to-treat (ITT)
population included 211 subjects (138 TPM, 73 placebo; mean [SD] mean weight,
76.7 [18.7] kg). Of 45 subjects who discontinued the study in the TPM group, 21
discontinued during the titration period, compared with 3 of 13 subjects who
discontinued in the placebo group. When the efficacy data were assessed using the
per-protocol, analysis-of-covariance model, TPM 200 mg/d was not associated with 
a significant reduction in mean monthly migraine frequency compared with placebo.
A post hoc analysis using a Poisson regression model in the ITT population
suggested that TPM significantly reduced mean monthly migraine frequency compared
with placebo (P=0.04). A significantly larger proportion of TPM-treated subjects 
had a > or =75% reduction in monthly migraine frequency compared with placebo
(P=0.03). At least 1 adverse event was reported by 90.0% and 69.9% of the TPM and
placebo groups, respectively. Treatment-emergent adverse events (AEs) occurring
in > or =10% of subjects in the TPM group were paresthesia (45%), dizziness
(16%), fatigue (16%), nausea (14%), and weight loss (14%). Most
treatment-emergent AEs were rated mild or moderate in severity. Of 3 serious AEs 
(depression, abdominal pain, leg pain) occurring during the trial, none were
considered related to either TPM or placebo. CONCLUSION: In this pilot study,
mean monthly migraine frequency did not differ significantly between TPM and
placebo.

Publication Types: 
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 16990078 [PubMed - indexed for MEDLINE]

1036: Prescrire Int. 2006 Aug;15(84):132-3.

Topiramate: new indication. Migraine prevention: best avoided.

[No authors listed]

(1) The first-line drug for prevention of migraines is propranolol: it is the
most thoroughly evaluated treatment, and thus far no other drug has been found to
be more effective. (2) Topiramate, an antiepileptic drug, is now also approved
for migraine prevention. Only 3 out of 4 double-blind placebo-controlled trials
showed that topiramate 100 mg/day was effective: on average, 46% of patients had 
a reduction of at least 50% in the frequency of migraines, compared to 23% of
patients on placebo. Increasing the dose to 200 mg did not lead to better
efficacy. (3) A double-blind trial versus propranolol failed to show that
topiramate was as effective or better than propranolol. (4) Topiramate has
numerous, frequent and sometimes serious adverse effects, mainly including
neurosensory disorders (paraesthesias, language disorders, confusion) and
gastrointestinal disturbances. (5) Topiramate treatment costs nearly 5 times more
than propranolol. (6) In practice, the adverse effects of topiramate outweigh its
efficacy in the prevention of migraine attacks.

Publication Types: 
    Comparative Study

PMID: 16989025 [PubMed - indexed for MEDLINE]

1037: Am J Ther. 2006 Sep-Oct;13(5):411-7.

Using patient-centered endpoints to determine the cost-effectiveness of triptans 
for acute migraine therapy.

Kelman L, Von Seggern RL.

Headache Center of Atlanta, Atlanta, GA 30342, USA. lkelman@mindspring.com

The objective of this study was to use the patient-centered efficacy measurements
of sustained pain free and sustained pain free with no adverse events to compare 
the relative cost-effectiveness of 6 oral triptans in the treatment of acute
migraine. Adverse event and sustained pain-free rates were obtained from a
comprehensive meta-analysis of 53 clinical trials of oral triptans. Efficacy and 
tolerability were assumed to be independent. Average wholesale prices were in US 
dollars as of May 10, 2004. The meta-analysis of oral triptans reported that
almotriptan 12.5 mg (Axert) exhibited the highest sustained pain-free rate
(25.9%), with the lowest rate associated with eletriptan 20 mg (Relpax) (10.6%). 
In addition, almotriptan 12.5 mg possessed the lowest overall absolute adverse
event rate (14.2%), with the highest adverse event rate exhibited by eletriptan
80 mg (53.9%). To attain 100 sustained pain-free patients, almotriptan 12.5 mg
and rizatriptan 10 mg (Maxalt) proved to be the most cost-effective triptans,
costing $7120 and $7427, respectively; the least cost-effective were naratriptan 
2.5 mg (Amerge) ($13,736) and eletriptan 20 mg ($16,104). To attain 100 sustained
pain-free with no adverse events patients, almotriptan 12.5 mg was the most
cost-effective triptan ($8298) and the least cost-effective were eletriptan 20 mg
($25,521) and eletriptan 80 mg ($29,614). At average wholesale prices as of May
10, 2004, almotriptan 12.5 mg achieved the highest level of cost-effectiveness
using either sustained pain free or sustained pain free with no adverse events as
endpoints.

Publication Types: 
    Comparative Study
    Meta-Analysis
    Research Support, Non-U.S. Gov't
    Review

PMID: 16988536 [PubMed - indexed for MEDLINE]

1038: Phytomedicine. 2006 Nov;13(9-10):743-6. Epub 2006 Sep 20.

Effectiveness of Petasites hybridus preparations in the prophylaxis of migraine: 
a systematic review.

Agosti R, Duke RK, Chrubasik JE, Chrubasik S.

Headache Center Hirslanden, Münchhaldenstr. 33, 8008 Zürich, Switzerland.
reto.agosti@kopfwww.ch

The objective of this review was to evaluate the strength of evidence of
effectiveness for Petasites hybridus in the prophylaxis of migraine. Several
databases and other sources were searched to identify randomised-controlled
trials investigating P. hybridus preparations. Two trials totalling 293 patients 
(60 and 233 patients) were included in this review. Both trials investigated the 
proprietary Petasites root extract Petadolex. The trials were described in
narrative way, taking into consideration methodological quality scores. Pooling
of data was not carried out due to the heterogeneity of the results. The extract 
at higher dose (150 mg) showed a greater decreased frequency of migraine attacks 
and a greater number of responders (improvement>50%) after treatment over 3-4
months than the extract at lower dose (100 mg) and placebo. Moderate evidence of 
effectiveness is, thus, available for a higher than the recommended dose of the
proprietary Petasites root extract Petadolex in the prophylaxis of migraine.
Further rigorous studies are required to confirm effectiveness and safety in
long-term use before treatment with Petasites root extract can be recommended as 
an alternative option in the treatment schedule for the prophylaxis of migraine.

Publication Types: 
    Review

PMID: 16987643 [PubMed - indexed for MEDLINE]

1039: Clin Ther. 2006 Aug;28(8):1107-15.

Comparative sensitivity of stopwatch methodology and conventional pain assessment
measures for detecting early response to triptans in migraine: results of a
randomized, open-label pilot study.

Sunshine A, Mulhern SA, Olson N, Elkind A, Almas M, Sikes C.

Analgesic Development Ltd., 635 Madison Avenue, New York, NY 10022, USA.
analgesicdevel@att.net

BACKGROUND: The standard measure of efficacy used in migraine trials is a 4-point
patient-rated headache pain intensity (HPI) scale. However, it has been suggested
that using a stopwatch to measure the time to meaningful pain relief can provide 
a more precise measurement of treatment response. OBJECTIVE: This study evaluated
the sensitivity of a stopwatch method for detecting meaningful relief of headache
pain and the correlation of this method with the HPI scale and a 5-point pain
relief scale. METHODS: In this open-label, parallel-group pilot study, patients
were randomized to receive oral eletriptan 40 mg, eletriptan 80 mg, or
rizatriptan 10 mg for the treatment of a single acute migraine attack. The effect
of study treatment on migraine pain was assessed immediately before dosing and at
0.5, 1, 1.5, 2, 3, and 4 hours after dosing. At each time point, patients
recorded the 3 types of pain assessment in a patient diary. HPI was rated using
the standard 4-point International Headache Society pain intensity scale (from 0 
= no pain to 3 = severe pain). Pain relief was rated on a 5-point pain relief
scale (from 4 = no relief to 0 = complete relief). The time to the onset of
meaningful pain relief was measured using a stopwatch. At 4 hours after dosing,
patients provided a global rating of the overall efficacy of study medication on 
a 5-point scale (from 0 = poor to 4 = excellent). RESULTS: Seventy-nine patients 
participated in the trial (78.5% female; mean [SD] age, 37.7 [9.8] years; 58.2%
white). The median times to meaningful pain relief measured by stopwatch were 84,
72, and 93 minutes for eletriptan 40 mg, eletriptan 80 mg, and rizatriptan 10 mg,
respectively (log-rank P = 0.029, eletriptan 80 mg vs rizatriptan 10 mg). At 90
minutes (approximating the median time to meaningful pain relief on the
stopwatch), headache response rates using HPI scoring (mild to no pain) were 65%,
68%, and 52% in the respective treatment groups, with no significant difference
between groups. On the pain relief scale, the corresponding mean (SD) scores at
90 minutes were 1.6 (1.2), 1.4 (1.3), and 2.0 (1.4) (P = NS). The pain
relief-defined response (> or = 75% pain relief) at 90 minutes did not differ
significantly between the 3 treatment groups (62%, 56%, and 48%). Detection of
early improvement (0.5 and 1 hour) was similar with the HPI and pain relief
scales. CONCLUSION: The results of this open-label pilot study suggest the
convergent validity of 3 pain-assessment methods in migraine, but indicate that
the use of a stopwatch may be a more sensitive method for detecting between-group
differences.

Publication Types: 
    Comparative Study
    Randomized Controlled Trial

PMID: 16982287 [PubMed - indexed for MEDLINE]

1040: Brain Dev. 2007 Apr;29(3):178-81. Epub 2006 Sep 14.

The efficacy of sodium valproate and a MRA finding in confusional migraine.

Fujita M, Fujiwara J, Maki T, Shigeta M, Shibasaki K, Takahashi N, Takahashi M.

Department of Pediatrics, Tsukuba Gakuen Hospital, 2573-1, Kamiyokoba, Tsukuba,
Ibaraki, 305-0854, Japan. mitfujita@tulip.sannet.ne.jp

Confusional migraine (CM) is recognized as a kind of pediatric migraine
equivalent. We report that a 10-year-old girl had repeated attacks of confusional
state and of migraine with aura. She suffered from total of six CM attacks and
migraine attacks with aura almost once a month. Therefore, sodium valproate (VPA)
was initiated to prevent these attacks. They have been controlled after
increasing her dosage to 600mg/day. The intracranial magnetic resonance
angiography (MRA) during the last CM attack indicated narrowing of left middle
and posterior cerebral arteries. However, MRA during the attack free period at
41-day follow-up showed normal vessels. Electroencephalograms showed severe
slowing without seizure discharges during the CM attacks. This case indicates
that VPA is an effective treatment for the prophylaxis of CM and migraine with
aura. MRA is considered helpful for the diagnosis of this kind of migraine in
children because of noninvasive neuroimaging.

Publication Types: 
    Case Reports

PMID: 16973324 [PubMed - indexed for MEDLINE]

1041: Neurology. 2006 Dec 26;67(12):2154-8. Epub 2006 Sep 13.

Incidence of migraine relative to menstrual cycle phases of rising and falling
estrogen.

MacGregor EA, Frith A, Ellis J, Aspinall L, Hackshaw A.

City of London Migraine Clinic, 22 Charterhouse Square, London, EC1M 6DX, UK.
anne.macgregor@bartsandthelondon.nhs.uk

OBJECTIVE: To investigate the association between urinary hormone levels and
migraine, with particular reference to rising and falling levels of estrogen
across the menstrual cycle in women with menstrual and menstrually related
migraine. METHODS: Women with regular menstrual cycles, who were not using
hormonal contraception or treatments and who experienced between one and four
migraine attacks per month, one of which regularly occurred on or between days 1 
+/- 2 of menstruation, were studied for three cycles. Women used a fertility
monitor to identify ovulation, conducting a test each day as requested by the
monitor, using a sample of early morning urine. Urine samples were collected
daily for assay of estrone-3-glucuronide, pregnanediol 3-glucuronide,
follicle-stimulating hormone, and luteinizing hormone. All women kept a daily
migraine diary and continued their usual treatment for migraine. RESULTS: Of 40
women recruited, data from 38 women were available for analysis. Compared with
the expected number of attacks, there was a significantly higher number of
migraine attacks during the late luteal/early follicular phase of falling
estrogen and lower number of attacks during rising phases of estrogen.
CONCLUSION: These findings confirm a relationship between migraine and changing
levels of estrogen, supporting the hypothesis of perimenstrual but not
postovulatory estrogen "withdrawal" migraine. In addition, rising levels of
estrogen appear to offer some protection against migraine.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16971700 [PubMed - indexed for MEDLINE]

1042: J Child Neurol. 2006 Sep;21(9):761-6.

Sleep disturbance in children with migraine.

Heng K, Wirrell E.

Department of Pediatrics and Clinical Neurosciences, University of Calgary,
Alberta Children's Hospital, 1820 Richmond Road SW, Calgary, Alberta, Canada.

The objectives of this study were to determine if (1) children with migraine
experience greater sleep disturbances than their siblings, (2) those with more
severe migraine have greater levels of sleep disruption, and (3) these sleep
disturbances lead to greater behavioral problems and more missed school. Children
aged 6 to 18 years with a diagnosis of migraine for > 6 months, who had at least 
one sibling without migraine in the same age range, were identified through our
neurology clinic database or at the time of the clinic visit. Parents completed
the (1) demographic, general health, and migraine information questionnaire; (2) 
Child Sleep Habits Questionnaire; and (3) Behavior Assessment System for
Children: Second Edition (BASC-2) Parent Rating Scales for each child. Cases with
migraine had higher total sleep (P < .02), sleep delay (P < .03), and daytime
sleepiness scores (P < .001) than controls. Cases with more severe migraines had 
higher total sleep (P < .01) and sleep duration scores (P < .03) than those with 
milder headaches. In cases, higher total sleep scores predicted greater behavior 
problems on all four composite scales on the Behavior Assessment System for
Children: Second Edition (Externalizing Problems, P < .05; Internalizing
Problems, P < .005; Behavior Systems Index, P < .003; and Adaptability Skills, P 
< .006). We conclude that children with migraine are prone to greater sleep and
behavioral disturbances than children without headache. Sleep disorders should be
routinely queried and appropriate advice on sleep hygiene provided.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16970882 [PubMed - indexed for MEDLINE]

1043: Cleve Clin J Med. 2006 Sep;73(9):793-4, 797, 800-1 passim.

Migraine prophylaxis: who, why, and how.

Loj J, Solomon GD.

Department of Medicine, Advocate Lutheran General Hospital, Park Ridge, IL 60068,
USA.

If a patient has frequent, severely debilitating migraine headaches, prophylactic
treatment may help. Beta-blockers, tricyclic antidepressants, and anticonvulsants
have the best evidence of efficacy; calcium channel blockers and nonsteroidal
anti-inflammatory drugs are also popular because they are well tolerated and
inexpensive. We review migraine treatment with emphasis on prophylaxis.

Publication Types: 
    Review

PMID: 16970133 [PubMed - indexed for MEDLINE]

1044: JAMA. 2006 Sep 13;296(10):1274-83.

Comment in:
    ACP J Club. 2007 Jan-Feb;146(1):23.    Aust J Physiother. 2006;52(4):304.    Evid Based Med. 2007 Feb;12(1):25.    J Fam Pract. 2006 Dec;55(12):1033-4.    JAMA. 2007 Jan 3;297(1):42; author reply 42.

Does this patient with headache have a migraine or need neuroimaging?

Detsky ME, McDonald DR, Baerlocher MO, Tomlinson GA, McCrory DC, Booth CM.

Faculty of Medicine, Medicine, University of Toronto, Toronto, Ontario.

CONTEXT: In assessing the patient with headache, clinicians are often faced with 
2 important questions: Is this headache a migraine? Does this patient require
neuroimaging? The diagnosis of migraine can direct therapy, and information
obtained from the history and physical examination is used by physicians to
determine which patients require neuroimaging. OBJECTIVE: To determine the
usefulness of the history and physical examination that distinguish patients with
migraine from those with other headache types and that identify those patients
who should undergo neuroimaging. DATA SOURCES AND STUDY SELECTION: A systematic
review was performed using articles from MEDLINE (1966-November 2005) that
assessed the performance characteristics of screening questions in diagnosing
migraine (with the International Headache Society diagnostic criteria as a gold
standard) and addressed the accuracy of the clinical examination in predicting
the presence of underlying intracranial pathology (with computed
tomography/magnetic resonance imaging as the reference standard). DATA
EXTRACTION: Two authors independently reviewed each study to determine
eligibility, abstract data, and classify methodological quality using
predetermined criteria. Disagreement was resolved by consensus with a third
author. DATA SYNTHESIS: Four studies of screening questions for migraine (n =
1745 patients) and 11 neuroimaging studies (n = 3725 patients) met inclusion
criteria. All 4 of the migraine studies illustrated high sensitivity and
specificity if 3 or 4 criteria were met. The best predictors can be summarized by
the mnemonic POUNDing (Pulsating, duration of 4-72 hOurs, Unilateral, Nausea,
Disabling). If 4 of the 5 criteria are met, the likelihood ratio (LR) for
definite or possible migraine is 24 (95% confidence interval [CI], 1.5-388); if 3
are met, the LR is 3.5 (95% CI, 1.3-9.2), and if 2 or fewer are met, the LR is
0.41 (95% CI, 0.32-0.52). For the neuroimaging question, several clinical
features were found on pooled analysis to predict the presence of a serious
intracranial abnormality: cluster-type headache (LR, 10.7; 95% CI, 2.2-52);
abnormal findings on neurologic examination (LR, 5.3; 95% CI, 2.4-12); undefined 
headache (ie, not cluster-, migraine-, or tension-type) (LR, 3.8; 95% CI,
2.0-7.1); headache with aura (LR, 3.2; 95% CI, 1.6-6.6); headache aggravated by
exertion or a valsalva-like maneuver (LR, 2.3; 95% CI, 1.4-3.8); and headache
with vomiting (LR, 1.8; 95% CI, 1.2-2.6). No clinical features were useful in
ruling out significant pathologic conditions. CONCLUSIONS: The presence of 4
simple historical features can accurately diagnose migraine. Several individual
clinical features were found to be associated with a significant intracranial
abnormality, and patients with these features should undergo neuroimaging.

Publication Types: 
    Review

PMID: 16968852 [PubMed - indexed for MEDLINE]

1045: Chest. 2006 Sep;130(3):896-901.

The relationship between migraine and right-to-left shunt: Fact or fiction?

Post MC, Budts W.

Department of Cardiology, St Antonius Hospital, Koekoekslaan 1, 3435 CM
Nieuwegein, the Netherlands. m.post@antonius.net

The prevalence of a right-to-left shunt, both cardiac and pulmonary, is high in
patients with migraines, especially migraine with aura. Percutaneous closure of a
right-to-left shunt seems to be associated with a pronounced decrease in the
number of migraine attacks or its prevalence. In this review, the relationship
between migraine and right-to-left shunting is described by highlighting the
different pathophysiologic hypotheses.

Publication Types: 
    Review

PMID: 16963692 [PubMed - indexed for MEDLINE]

1046: Cephalalgia. 2006 Oct;26(10):1225-33.

Tryptophan depletion increases nausea, headache and photophobia in migraine
sufferers.

Drummond PD.

School of Psychology, Murdoch University, Perth, Western Australia, Australia.
p.drummond@murdock.edu.au

Sensitivity to light was investigated 5 and 8 h after consumption of an amino
acid drink which contained L-tryptophan (balanced amino acid condition: 19
controls and 22 migraine sufferers) or which produced a short-term reduction in
brain serotonin synthesis by omitting L-tryptophan (tryptophan depletion
condition: 16 controls and 16 migraine sufferers). Migraine sufferers reported
more intense nausea, headache, glare- and light-induced pain than controls. In
addition, glare- and light-induced pain were greater in the tryptophan depletion 
condition than in the balanced amino acid condition, in both migraine sufferers
and controls. Eight hours after the amino acid drink, after participants had
completed tests of pain sensitivity and motion sickness provocation, tryptophan
depletion augmented headache in migraine sufferers and aggravated nausea in
migraine sufferers and controls. These findings suggest that a reduction in brain
synthesis of serotonin intensifies photophobia and other migrainous symptoms and 
thus might contribute to the pathogenesis of migraine.

Publication Types: 
    Controlled Clinical Trial
    Research Support, Non-U.S. Gov't

PMID: 16961791 [PubMed - indexed for MEDLINE]

1047: Cephalalgia. 2006 Oct;26(10):1214-9.

Functional gastrointestinal disorders in migrainous children: efficacy of
flunarizine.

Boccia G, Del Giudice E, Crisanti AF, Strisciuglio C, Romano A, Staiano A.

Department of Paediatrics, University of Naples Federico II, Naples, Italy.

The aim of this study was to evaluate the prevalence of functional
gastrointestinal disorders (FGIDs) in children with migraine headache and the
effects of flunarizine on gastrointestinal manifestations. We studied 50
migrainous children (mean age 8.63 years). The clinical pattern and the diagnosis
of FGIDs were obtained from structured questionnaires. All subjects underwent
measurement of total gastric emptying time (TGEt) performed by real-time
ultrasonography of the gastric antrum at baseline (T0). In the second part of the
study, we evaluated 10 migrainous children (mean age 9.8 years) with associated
FGIDs. In these 10 patients, repeated TGEt evaluation together with a detailed
symptom history was obtained after 1 (T1) and 2 months (T2) of treatment with
flunarizine. Control groups were composed of 10 migrainous children without FGIDs
(mean age 9.2 years) and nine sex- and age-matched healthy children.
Gastrointestinal disorders were present in 70% of the patients. Migrainous
children with FGIDs had significantly (P < 0.01) more prolonged TGEt than
subjects without FGIDs. Prior to therapy, all migrainous children with FGIDs had 
prolongation of TGEt compared with controls (P < 0.05). Patients on flunarizine
had a significant decrease in TGEt at both 1 (P < 0.01) and 2 months (P = 0.002) 
of therapy. The mean frequency of abdominal pain per month was significantly (P <
0.001) reduced at T1 compared with T0. The mean frequency of vomiting per month
was significantly decreased at T1 (P < 0.05) and even more so at T2 (P < 0.01).
Finally, the mean frequency of headache per month was significantly reduced only 
at T2 (P < 0.05), whereas the mean duration of headache was significantly
decreased at T1 (P < 0.01) with no difference between T1 and T2. Most children
with migraine report FGIDs, associated with a delayed gastric emptying.
Flunarizine decreases the frequency and duration of migrainous episodes as well
as the gastrointestinal symptoms.

Publication Types: 
    Controlled Clinical Trial

PMID: 16961789 [PubMed - indexed for MEDLINE]

1048: Cephalalgia. 2006 Oct;26(10):1209-13.

The prevalence of premonitory symptoms in migraine: a questionnaire study in 461 
patients.

Schoonman GG, Evers DJ, Terwindt GM, van Dijk JG, Ferrari MD.

Department of Neurology, Leiden University Medical Centre, Leiden, The
Netherlands. g.g.schoonman@lumc.nl

Migraine attacks are often preceded by premonitory symptoms. Prevalence rates of 
migraine patients reporting one or more premonitory symptoms show considerable
variability and rates range between 12% and 79%. Sources of variability might be 
differences in study population or research design. Using a questionnaire, we
retrospectively studied the prevalence of 12 predefined premonitory symptoms in a
clinic-based population. Of 461 migraine patients, 374 (81%) responded. At least 
one premonitory symptom was reported by 86.9% and 71.1% reported two or more. The
most frequently reported premonitory symptoms were fatigue (46.5%), phonophobia
(36.4%) and yawning (35.8%). The mean number of premonitory symptoms per person
was 3.2 (+/- 2.5). Women reported 3.3 premonitory symptoms compared with 2.5
symptoms in men (P = 0.01). Age, education, migraine subtype (with or without
aura) and mean attack frequency had no effect on the mean number of symptoms per 
individual. In conclusion, premonitory symptoms are frequently reported by
migraine patients. Sensitivity and specificity of premonitory symptoms for
migraine need to be assessed using prospective methods.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16961788 [PubMed - indexed for MEDLINE]

1049: Cephalalgia. 2006 Oct;26(10):1199-202.

Zonisamide for migraine prophylaxis in refractory patients.

Ashkenazi A, Benlifer A, Korenblit J, Silberstein SD.

Jefferson Headache Center, Philadelphia, PA 19107, USA.
avi.ashkenazi@jefferson.edu

Zonisamide is a new antiepileptic drug with multiple mechanisms of action and a
favourable pharmacokinetic profile. Preliminary data suggest that zonisamide may 
be effective in migraine prophylaxis. We evaluated the efficacy and tolerability 
of zonisamide for migraine prophylaxis in refractory patients. We reviewed the
charts of adult patients with International Headache Society-defined episodic
migraine (EM) or with transformed migraine (TM) according to the
Silberstein-Lipton criteria, who had been treated with zonisamide at our
out-patient clinic for at least 60 days. Demographic data, zonisamide dosage and 
duration of treatment were collected and analysed. Headache frequency, attack
duration, headache severity and headache-related disability before and after
treatment initiation with zonisamide were compared. Thirty-three patients were
included in the study (average age 43.9 +/- 8.4 years; 23 (70%) with TM and 10
(30%) with EM). The patients had failed an average of 6.2 migraine prophylactic
drugs prior to zonisamide. The average zonisamide daily dose was 337.9 +/- 146.3 
mg and the average duration of treatment was 186.4 +/- 174.0 days. The average
number of days with headache per month was reduced in the entire study population
from 20.7 +/- 9.5 before zonisamide treatment to 18.0 +/- 11.3 after its
initiation (P = 0.06) [in TM from 24.7 +/- 7.3 to 21.0 +/- 10.7 (P = 0.06); in EM
from 11.6 +/- 7.6 to 11.0 +/- 9.7 (P = NS)]. No significant changes in other
headache parameters were found. Fourteen patients (42.4%) reported adverse events
(AEs), the most common of which was fatigue. Most patients (12/14, 85.7%) rated
AEs as mild or moderate. In this group of refractory migraine patients,
zonisamide therapy did not result in a statistically significant beneficial
effect on headache or on associated symptoms.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16961786 [PubMed - indexed for MEDLINE]

1050: Clin Neuropharmacol. 2006 Sep-Oct;29(5):269-75.

Topiramate and triptans revert chronic migraine with medication overuse to
episodic migraine.

Mei D, Ferraro D, Zelano G, Capuano A, Vollono C, Gabriele C, Di Trapani G.

Department of Neuroscience, Headache Centre, Catholic University, Rome, Italy.
dmei@rm.unicatt.it

OBJECTIVE: This is a randomized, double-blind versus placebo study aimed at
evaluating the efficacy of topiramate (TPM) in reducing the number of days with
headache and the amount of acute medication taken monthly in patients with
chronic migraine with medication overuse. We also studied the efficacy of single 
triptans available in Italy in interrupting headache crises during preventive
treatment. METHODS: The studied sample was made up of 50 subjects: 30 patients
were randomized for treatment with TPM, 100 mg/d, and 20 for placebo. Subjects
treated with TPM were further randomized to evaluate, in double-blind versus
placebo, the efficacy of single triptans available in Italy. The double-blind
phase consisted of a titration phase (4 weeks) and of a maintenance phase (8
weeks). OUTCOME MEASURES: The reduction in the number of days with headache per
28 days and the reduction in the amount of acute medication taken per 28 days
throughout the clinical trial in the TPM group were compared with those of the
placebo group; the number of patients who were pain-free at 2 hours after the
triptan intake and the headache recurrence rate in the 22 hours after the
pain-free condition in the triptan group were compared with those of the placebo 
group. We also looked at tolerability profile. RESULTS: The group treated with
TPM had a significant reduction in the number of days with headache (P < 0.0001
vs placebo) and in the mean amount of acute medication taken (P < 0.0001 vs
placebo); all triptans were superior to placebo; there were no significant
differences between different triptans; the analgesic effect of triptans
increased throughout the trial. CONCLUSIONS: Topiramate proved to be well
tolerated and effective in reverting chronic migraine with medication overuse to 
episodic migraine.

Publication Types: 
    Clinical Trial
    Comparative Study
    Randomized Controlled Trial

PMID: 16960472 [PubMed - indexed for MEDLINE]

1051: Birth Defects Res A Clin Mol Teratol. 2006 Aug;76(8):592-601.

Maternal severe migraine and risk of congenital limb deficiencies.

Bánhidy F, Acs N, Horváth-Puhó E, Czeizel AE.

Second Department of Obstetrics and Gynecology, Semmelweis University, School of 
Medicine, Budapest, Hungary.

BACKGROUND: Migraines occurs frequently during pregnancy; however, there are no
published data on their possible teratogenic potential in a controlled
epidemiological study. Therefore, we examined the risk of congenital
abnormalities in infants born to women who had migraines and other headaches
during pregnancy. METHODS: Between 1980 and 1996, the Hungarian Case-Control
Surveillance of Congenital Abnormalities evaluated 22,843 cases (newborns or
fetuses) with congenital abnormalities, 38,151 control newborn infants without
any abnormalities, and 834 malformed controls with Down syndrome. RESULTS:
Migraines anytime during pregnancy occurred in 565 (2.5%) mothers of the case
group compared with 713 (1.9%) mothers in the control group (crude prevalence
odds ratio [POR], 1.3; 95% confidence interval [CI], 1.2-1.5) and 24 (2.9%)
pregnant women in the malformed control group (crude POR, 0.9; 95% CI, 0.6-1.3)
The mothers of 247 cases, 533 controls, and 21 malformed controls had severe
migraines during the second and/or third months of pregnancy. There was only 1
congenital abnormality group: limb deficiencies, which had a higher rate of
maternal migraines during the second and third months of pregnancy both at the
comparison of cases and matched controls (adjusted POR, 2.5; 95% CI, 1.1-5.8) and
of cases and malformed controls (adjusted POR, 1.7; 95% CI, 1.3-3.0). There was
no association between other headaches and different congenital abnormalities at 
the comparison of cases and controls. CONCLUSIONS: Our data showed that maternal 
severe migraines during the second and/or third months of pregnancy were
associated with an increased risk of congenital limb deficiencies. A similar
association was not detected between congenital anomalies and other headaches
during pregnancy. Our study was not based on a prior hypothesis; therefore, these
data can be considered only as a signal that needs confirmation by independent
data sets. 2006 Wiley-Liss, Inc.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16955495 [PubMed - indexed for MEDLINE]

1052: Laryngoscope. 2006 Sep;116(9):1577-9.

Visually enhanced vestibulo-ocular reflex: a diagnostic tool for migraine
vestibulopathy.

Arriaga MA, Chen DA, Hillman TA, Kunschner L, Arriaga RY.

Pittsburgh Ear Associates, Pittsburgh, Pennsylvania, USA. tec8lote@aol.com

OBJECTIVES: 1) To compare the incidence of elevated visually enhanced
vestibular-ocular reflex (VVOR) rotational gain during rotational chair testing
in a normal control group versus a group of patients diagnosed with migraine
vestibulopathy; 2) to discuss the possible application of VVOR gain during
rotational chair testing for diagnosing migraine vestibulopathy. STUDY DESIGN:
Prospective normal control group and retrospective cohort comparison. METHODS: 1)
Prospective rotational chair studies including VVOR in 20 normal control
patients; 2) retrospective review of vestibular studies including VVOR in 100
consecutive patients with migraine vestibulopathy. RESULTS: Twenty of the normal 
controls and 69 of the migraine vestibulopathy patients met all inclusion
criteria. One of 20 (5%) normal control patients had elevated VVOR gain, whereas 
49 of 69 (71%) of migraine vestibulopathy patients had elevated VVOR gain.
CONCLUSIONS: VVOR gain normal criteria were appropriate in 95% of our normal
control test group. VVOR gain was more frequently elevated in migraine
vestibulopathy patients than in the normal controls, and the difference was
significant (P < .001). VVOR gain elevation was the most common vestibular test
abnormality in this cohort of patients with migraine vestibulopathy. Because VVOR
measures visual-vestibular interaction and its central connections, this
parameter may be a useful diagnostic tool for migraine vestibulopathy in patients
manifesting disequilibrium and motion sensitivity.

PMID: 16954982 [PubMed - indexed for MEDLINE]

1053: J Br Menopause Soc. 2006 Sep;12(3):104-8.

Migraine and the menopause.

MacGregor EA.

City of London Migraine Clinic, London, UK.
anne.macgregor@bartsandthelondon.nhs.uk

The prevalence of migraine peaks during the 40s and an increased association
between migraine and menstruation is often noted. Migraine generally improves
after the menopause. Although menstrual irregularity, hot flushes and other
climacteric symptoms may warrant management with hormone replacement therapy
(HRT), there has been some concern that HRT may aggravate migraine and
potentially increase the risk of ischaemic stroke. This evidence-based review
concludes that migraine is not a contraindication for HRT but continuous-release 
transdermal estrogen, in the lowest effective dose, is recommended.

Publication Types: 
    Review

PMID: 16953983 [PubMed - indexed for MEDLINE]

1054: Aust N Z J Obstet Gynaecol. 2006 Oct;46(5):395-401.

Comment in:
    Aust N Z J Obstet Gynaecol. 2007 Apr;47(2):155.

Intrapartum analgesia and its association with post-partum back pain and headache
in nulliparous women.

Orlikowski CE, Dickinson JE, Paech MJ, McDonald SJ, Nathan E.

Staff Specialist Anaesthetist, Royal Hobart Hospital, Perth, Western Australia,
Australia.

BACKGROUND: The effect of intrapartum analgesia on post-partum maternal back and 
neck pain, headache and migraine, is uncertain. AIMS: To determine if nulliparous
women having epidural analgesia during labour have a similar incidence of the
above-mentioned post-partum symptoms compared with women managed using other
forms of pain relief. METHODS: Secondary analysis of cohort data from a
randomised trial in which nulliparous women intending to deliver vaginally were
randomised to either epidural analgesia (EPI) or continuous midwifery support
(CMS) at admission for delivery. Because of high cross-over rates, groups were
initially defined by the randomised treatment allocation and the actual treatment
received (CMS-CMS n = 185, EPI-CMS n = 117, EPI-EPI n = 376 and CMS-EPI n = 314).
Univariate analysis showed no difference between groups, so final analysis was
based on the actual treatment received. RESULTS: Six hundred and ninety women
received epidural analgesia (EPIDURAL) and 302 received other methods of pain
relief including CMS. Back pain was common before, during and after pregnancy,
and risk factors for post-partum back pain at six months were back pain prior to 
pregnancy or at two months post-partum. Epidural analgesia, mode of delivery,
spontaneous or induced labour, birthweight and back pain during pregnancy had no 
significant relationship with post-partum back pain at six months. Headache was
significantly more common in the EPIDURAL group during pregnancy and at two
months post-partum, but not at six months. Migraine was not associated with
intrapartum analgesia. CONCLUSIONS: This analysis supports previous research
suggesting that epidural analgesia is not a significant risk factor for
persisting post-partum back pain, headache or migraine.

Publication Types: 
    Comparative Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 16953853 [PubMed - indexed for MEDLINE]

1055: Am J Cardiol. 2006 Sep 15;98(6):831-3. Epub 2006 Aug 2.

Relation of atrial shunts to migraine in patients with ischemic stroke and
peripheral emboli.

Wilmshurst P, Nightingale S, Pearson M, Morrison L, Walsh K.

Royal Shrewsbury Hospital, Shrewsbury, United Kingdom.
peter.wilmshurst@rsh.nhs.uk

This study investigated whether the increased incidence of stroke in young
subjects with migraine is because they have an increased prevalence of atrial
right-to-left shunts. The investigators report the prevalence of clinically
relevant atrial shunts in those with stroke and migraine compared with those with
stroke but without migraine and also in historic control groups of subjects who
had migraine with aura but no stroke and in population controls. Of 60
consecutive stroke patients, 42 (70%) had large- or medium-sized atrial shunts.
Transcatheter shunt closure was performed in 39 patients, of whom 35 had patent
foramen ovales (mean diameter 9.8 +/- 4.1 mm) and 4 had atrial septal defects. If
atrial shunts were unrelated to stroke in patients with migraines, shunt
prevalence in those with migraine and stroke would be the same as in those with
migraine but without stroke. However, a much greater shunt prevalence was found
in those with stroke and migraine with aura (84%) than in those with migraine
with aura but no stroke (38.1%, p <0.001), population controls (12.2%, p <0.001),
and those with stroke but no migraine (55.6%, p <0.05). Shunt prevalence was also
significantly greater in patients who had stroke and migraine without aura (75%) 
than in population controls (p <0.001) and in those with migraine with aura but
no stroke (p <0.05). In conclusion, the increased incidence of stroke in subjects
with migraine compared with the general population is because they have a higher 
prevalence of large atrial shunts and hence an increased risk for paradoxic
embolism.

PMID: 16950197 [PubMed - indexed for MEDLINE]

1056: Curr Pain Headache Rep. 2006 Oct;10(5):377-81.

Pharmacologic treatment of migraine.

Yonker ME.

Pediatric Headache Program, Division of Neurology, AI DuPont Hospital for
Children, 1600 Rockland Road, PO Box 269, Wilmington, DE 19899, USA.
myonker@nemours.org

Nonsteroidal anti-inflammatory drugs are the mainstay of migraine treatment for
children and adolescents by most primary care physicians. Not all patients
respond to these readily available agents. Triptans have been studied in children
and adolescents, and there is reasonable evidence to support the use of these
agents in these populations. Other agents, such as combination preparations and
ergot compounds, are also used in clinical practice, although there has been
little scientific study. Prophylactic agents have been less well studied in those
under 18 years of age. Agents such as antidepressants, anticonvulsants, and
antihypertensives are commonly used in clinical practice. Safety issues are
fairly well understood because of historical use and use for other conditions.
Efficacy and optimal dosing have yet to be established for the treatment of
migraine in children and adolescents in double-blind, randomized,
placebo-controlled trials.

Publication Types: 
    Review

PMID: 16945255 [PubMed - indexed for MEDLINE]

1057: Curr Pain Headache Rep. 2006 Oct;10(5):363-9.

Diagnosing migraine in the pediatric population.

Winner P, Hershey AD.

Palm Beach Headache Center, Premiere Research Institute at Palm Beach Neurology, 
West Palm Beach, FL 33407, USA. eneuro@aol.com

Migraine in the pediatric population remains substantially underdiagnosed and
undertreated. The recently revised International Classification of Headache
Disorders is a step in the right direction to improve our diagnostic accuracy.
This article reviews the practical diagnostic issues related to migraine in the
pediatric population.

Publication Types: 
    Review

PMID: 16945253 [PubMed - indexed for MEDLINE]

1058: Curr Pain Headache Rep. 2006 Oct;10(5):350-4.

The physical examination of migraine.

Sorrell MR.

Springfield Neurology Associates, LLC, 300 Carew Street, Suite 2, Springfield, MA
01104, USA. mrsorrell@pol.net

Patients and physicians are frequently unaware that pain coming from the muscles 
of the head and neck is probably the cause of the most frequent forms of
migraine. Identifying the extracranial origins of the patient's headache by
physical examination should reassure patient and examiner that the headache is
benign and treatable. The results of the examination should lead to physical
treatment, reducing headache frequency and severity. This paper describes
techniques of the physical examination to identify the extracranial causes of
migraine headache.

Publication Types: 
    Review

PMID: 16945251 [PubMed - indexed for MEDLINE]

1059: Ann Otol Rhinol Laryngol. 2006 Aug;115(8):587-94.

Prospective study of positional nystagmus in 100 consecutive patients.

Bertholon P, Tringali S, Faye MB, Antoine JC, Martin C.

Department of Otorhinolaryngology-Head and Neck Surgery, Bellevue Hospital,
Saint-Etienne, France.

OBJECTIVES: The purpose of this study was to investigate the various diagnoses of
patients who present with positional nystagmus. METHODS: Positional maneuvers
were systematically performed in the plane of the posterior canal (PC;
Dix-Hallpike maneuver) and the horizontal canal (HC; patients were rolled to
either side in a supine position) on 490 consecutive patients essentially
referred for vertigo and/or gait unsteadiness. RESULTS: One hundred patients
(20%) presented positional nystagmus. This nystagmus had a peripheral origin in
83 patients, including 80 patients with benign paroxysmal positional vertigo
(BPPV). In BPPV, the PC was involved in 61 patients, the HC in 18 patients
(geotropic horizontal nystagmus in 11 and ageotropic in 7; changing from
geotropic to ageotropic or the reverse in 4 patients), and both the PC and HC in 
1 patient. There was evidence of central positional nystagmus in 12 patients,
including positional downbeat nystagmus during the Dix-Hallpike maneuver in 7
patients with various neurologic disorders, and ageotropic horizontal nystagmus
during the HC maneuver in 2 patients with, respectively, cerebellar ischemia and 
definite migrainous vertigo. The peripheral or central origin of the positional
nystagmus could not be ascertained in 5 patients, including 1 patient with
probable migrainous vertigo and another with possible anterior canal BPPV.
CONCLUSIONS: A rotatory-upbeat nystagmus in the context of PC BPPV, a horizontal 
nystagmus, whether geotropic or ageotropic, due to HC BPPV, and a positional
downbeat nystagmus related to various central disorders are the 3 most common
types of positional nystagmus. Geotropic horizontal positional nystagmus and,
most certainly, horizontal positional nystagmus changing from geotropic to
ageotropic or the reverse point to HC BPPV. In contrast, an ageotropic horizontal
positional nystagmus that is not changing (from ageotropic to geotropic) may
indicate a central lesion.

Publication Types: 
    Case Reports

PMID: 16944657 [PubMed - indexed for MEDLINE]

1060: Neurology. 2006 Oct 10;67(7):1135-40. Epub 2006 Aug 30.

Comment in:
    Nat Clin Pract Neurol. 2007 Apr;3(4):196-7.

A randomized trial of rizatriptan in migraine attacks in children.

Ahonen K, Hämäläinen ML, Eerola M, Hoppu K.

Hospital for Children and Adolescents, Department of Clinical Pharmacology,
University of Helsinki, Finland.. Kati.Ahonen@fimnet.fi

OBJECTIVE: To examine the efficacy of rizatriptan and the consistency of
treatment response in migraine attacks of children and adolescents. METHODS: We
conducted a double-blind, placebo-controlled three-way crossover trial in
patients ages 6 to 17 years diagnosed with migraine in two pediatric hospital
outpatient clinics. Two doses of rizatriptan and a matching placebo were
administered at home during three attacks. Rizatriptan dose was 5 mg for those
with a body weight of 20 to 39 kg, and 10 mg for those with a body weight of 40
kg or more. The primary efficacy endpoint was headache relief by two grades on a 
five-grade face scale at 2 hours. RESULTS: Ninety-six patients used all three
treatments, 10 used two, and 10 only the first. At 2 hours, the primary endpoint 
was reached twice as often after both treatments of rizatriptan (first 74%, n =
71/96; second 73%, n = 70/96) as after placebo (36%, n = 35/96) (p < 0.001).
Already at 1 hour, rizatriptan was clearly more effective as headache relief was 
reported by 50% (n = 48/96) and 55% (n = 53/96) of children after the first and
the second dose of rizatriptan, compared to 29% (n = 28/96) after placebo (p =
0.004). Rizatriptan was superior at 3 and 4 hours, and the other endpoints also
favored rizatriptan. Efficacy of rizatriptan was constant over the two treated
attacks, and the findings were similar in children using the dose of 5 and 10 mg.
No serious adverse effects were observed. CONCLUSIONS: Oral rizatriptan is
effective and well-tolerated for migraine attacks in children over age 6 years.

Publication Types: 
    Randomized Controlled Trial

PMID: 16943370 [PubMed - indexed for MEDLINE]

1061: Acta Neurol Scand. 2006 Oct;114(4):281-6.

Increased risk of migraine in Marfan's syndrome?

Knudsen S, Russell MB.

Department of Neurofysiology, Glostrup University Hospital, Glostrup, Denmark.

OBJECTIVE: To study the prevalence of migraine in Marfan's syndrome. MATERIAL AND
METHODS: Patients were recruited from Landsforeningen (a patient organization)
for Marfan's syndrome. A total of 46 persons were eligible for a validated
semi-structured telephone interview by a physician trained in headache
diagnostics. RESULTS: The prevalence of migraine without aura was 13% among men
and 40% among women. The prevalence of migraine with aura was 44% among men and
37% among women. The overall prevalence of migraine was 63% with an equal sex
ratio. This corresponds to a 3.6- and 2.0-fold significant increased risk among
men and women, respectively, compared with the general population. CONCLUSION:
The high prevalence and equal sex ratio of migraine is puzzling and likely to be 
secondary to Marfan's syndrome. It might be associated with dural ectasia, as the
prevalence of dural ectasia is similar to that of migraine in Marfan's syndrome.

PMID: 16942549 [PubMed - indexed for MEDLINE]

1062: Headache. 2006 Sep;46(8):1303-4.

Comment in:
    Headache. 2008 Jan;48(1):164-5.

Popular sweetner sucralose as a migraine trigger.

Patel RM, Sarma R, Grimsley E.

Department of Internal Medicine, Mercer University School of Medicine, Macon, GA,
USA.

Sucralose (trichlorogalactosucrose, or better known as Splenda) is an artificial 
sweetener from native sucrose that was approved by the FDA on April 1, 1998
(April Fool's Day). This observation of a potential causal relationship between
sucralose and migraines may be important for physicians to remember this can be a
possible trigger during dietary history taking. Identifying further triggers for 
migraine headaches, in this case sucralose, may help alleviate some of the cost
burden (through expensive medical therapy or missed work opportunity) as well as 
provide relief to migraineurs.

Publication Types: 
    Case Reports

PMID: 16942478 [PubMed - indexed for MEDLINE]

1063: Headache. 2006 Sep;46(8):1261-3.

Triptans--why once?

Ifergane G, Wirguin I, Shvartzman P.

Headache Clinic, Department of Neurology, Soroka Medical Center, Beer-Sheva,
Israel.

OBJECTIVE: To evaluate triptan use patterns in a large Israeli HMO district.
BACKGROUND: Triptans, 5HT(1B/1D) agonists, provide an effective and safe relief
of headache and accompanying symptoms during an acute migraine attack. METHOD: We
retrospectively reviewed the computerized prescription filling data of 1498
patients who filled a first triptan prescription between July 2003 and June 2004.
RESULTS: During a 1-year follow-up period, 841 patients (56.1%) purchased
triptans only once. Single-time users were significantly more prevalent among men
and in patients younger than 30 or older than 70 years. CONCLUSIONS: It seems
that many migraine patients choose not to use triptans after their first
experience with the drug.

PMID: 16942470 [PubMed - indexed for MEDLINE]

1064: Headache. 2006 Sep;46(8):1230-45.

Serotonin in trigeminal ganglia of female rodents: relevance to menstrual
migraine.

Berman NE, Puri V, Chandrala S, Puri S, Macgregor R, Liverman CS, Klein RM.

Department of Anatomy and Cell Biology, University of Kansas Medical Center,
Kansas City, KS, USA.

OBJECTIVES: We examined changes in the serotonin system across the estrous cycle 
in trigeminal ganglia of female rodents to determine which components are present
and which are regulated by the variations in levels of ovarian steroids that
occur during the estrous cycle. BACKGROUND: Migraine is 2-3 times more prevalent 
in women than in men and attacks are often timed with the menstrual cycle,
suggesting a mechanistic link with ovarian steroids. Serotonin has been
implicated in the pathogenesis of migraine, and the effectiveness of triptans,
selective 5HT-1B/D/F agonists, has provided further support for this concept. It 
is not known whether serotonin, its rate-limiting enzyme tryptophan hydroxylase
(TPH), or its receptors are regulated by ovarian steroids in trigeminal ganglia. 
METHODS: We used reverse transcription-polymerase chain reaction to examine gene 
expression in cycling mice, Western blots to examine protein expression,
double-labeling immunohistochemistry using markers of nociceptors and
nonnociceptors and confocal microscopy to identify specific types of neurons, and
primary tissue culture to examine effects of estrogen on trigeminal neurons in
vitro. RESULTS: In C57/BL6 mice mRNA levels of TPH-1, the rate-limiting enzyme in
serotonin synthesis, were over 2-fold higher and protein levels were 1.4-fold
higher at proestrus, the high estrogen stage of the cycle than at diestrus, the
low estrogen stage. TPH protein also was present in primary trigeminal cultures
obtained from female Sprague-Dawley rats, but levels were not affected by 24-hour
treatment with physiological levels (10(-9) M) of 17beta-estradiol. Gene
expression of 5HT-1B and 5HT-1D receptors in trigeminal ganglia was not regulated
by the estrous cycle. Serotonin was present in trigeminal neurons containing
CGRP, a potent vasoactive neuropeptide, peripherin, an intermediate filament
present in neurons with unmyelinated axons, neurofilament H, which is present in 
neurons with myelinated axons, and in neurons binding IB4, a marker of
nonpeptidergic nociceptors. Serotonin was also present in neurons containing
5HT-1B. The serotonin-positive population was significantly larger in diameter
than the serotonin-negative population. Conclusions.-Expression of the
rate-limiting enzyme required for serotonin synthesis is regulated during the
natural estrous cycle, and serotonin is present in larger trigeminal neurons of
all the major subtypes. Colocalization of serotonin with 5HT-1B suggests that
this receptor functions as an autoreceptor to regulate serotonin release.
Cyclical changes in serotonin levels in trigeminal ganglia could contribute to
the pathogenesis of menstrual migraine.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 16942467 [PubMed - indexed for MEDLINE]

1065: Expert Opin Emerg Drugs. 2006 Sep;11(3):419-27.

Migraine: emerging treatment options for preventive and acute attack therapy.

Goadsby PJ.

Institute of Neurology, Headache Group, The National Hospital for Neurology and
Neurosurgery, Queen Square, London WC1N 3BG, UK. peterg@ion.ucl.ac.uk

This review discusses emerging treatments of migraine in the context of what is
now available. At present, patients are treated with a range of acute attack
medicines or preventive treatments, with many having significant drawbacks.
Important unmet needs are acute attack treatments that act by exclusively neural 
mechanisms with no vascular effects, and effective, well tolerated preventive
medicines. Calcitonin gene-related peptide receptor antagonist, vanilloid
receptor antagonists and nitric oxide synthase inhibitors are all in clinical
trials for acute migraine. Tonaberset (a gap-junction blocker), an inducible
nitric oxide synthase inhibitor and botulinum toxin A are in clinical trials for 
preventive therapy. Device-based approaches using neurostimulation of the
occipital nerve are being studied, although the first study of patent foramen
ovale closure for migraine prevention failed.

Publication Types: 
    Review

PMID: 16939382 [PubMed - indexed for MEDLINE]

1066: Ann Allergy Asthma Immunol. 2006 Aug;97(2):226-30.

Prevalence of migraine headaches in patients with allergic rhinitis.

Ku M, Silverman B, Prifti N, Ying W, Persaud Y, Schneider A.

Allergy & Asthma Care PA, Haddonfield, New Jersey 08033, USA. mku72@hotmail.com

BACKGROUND: Histamine has been implicated in the pathogenesis of migraine
headaches. Because allergic rhinitis (AR) is a histamine-driven syndrome and the 
nasal passage is in close proximity to the central nervous system, we hypothesize
that AR may trigger migraine headaches. OBJECTIVE: To determine the prevalence of
migraine headaches in patients with and without AR. METHODS: Allergic rhinitis
was diagnosed based on skin or radioallergosorbent test results, clinical
history, and physical examination findings. The diagnosis of migraine headache
was made if patients fulfilled the International Headache Society criteria.
Surveys were obtained from hospital-based allergy, pediatric, and internal
medicine clinics, all serving the same inner-city population. RESULTS: A total of
294 surveys were completed. Of 76 patients in the AR group, 26 (34%) had
headaches meeting the International Headache Society criteria for migraines, and 
of the 57 patients in the non-AR group, only 2 (4%) had headaches that met the
criteria. A Fisher exact test showed P = 8.2 x 10(-6). The odds ratio was 14.3,
which signifies that the odds of having migraine headaches is 14.3 times higher
in the AR group than in the non-AR group. CONCLUSIONS: There is a high prevalence
of migraine headaches in patients with AR compared with those without AR. We
propose that histamine plays a key role in triggering migraines by means of
vasodilation and inflammation in the pathogenesis of migraine headaches.

Publication Types: 
    Historical Article

PMID: 16937756 [PubMed - indexed for MEDLINE]

1067: J Clin Psychol. 2006 Nov;62(11):1367-78.

Treating chronic migraine headaches: an evidence-based practice approach.

Walker BB, Seay SJ, Solomon AC, Spring B.

Indiana University, Department of Psychological and Brain Sciences, Bloomington, 
IN 47405, USA. bbwalker@indiana.edu

Psychologists and other mental health care professionals are generally trained to
incorporate empirical evidence into clinical practice, but few have been taught
formal techniques for doing so. Given the rapidity of progress in the clinical
sciences, there is a growing need among practitioners to access current,
clinically relevant research and have strategies for integrating these research
findings into the clinic. In the field of medicine, evidence-based medicine took 
hold in the early 1990s to provide a framework and skill set for translating
research into practice. This method is now widely known as evidence-based
practice (EBP) to reflect its applicability to multiple disciplines. In this
article, we present a general overview of EBP, illustrate how we used this
approach to develop a treatment plan for a patient who had chronic migraine
headaches, and discuss some of the opportunities and challenges EBP presents to
mental health professionals.

Publication Types: 
    Case Reports

PMID: 16937349 [PubMed - indexed for MEDLINE]

1068: J Pain Palliat Care Pharmacother. 2006;20(3):25-8.

Relief of acute migraine headache with intravenous oxytocin: report of two cases.

Phillips WJ, Ostrovsky O, Galli RL, Dickey S.

Department of Emergency Medicine, University of Mississippi Medical Center, 2500 
North State St, Jackson, MS 39216, USA. wphillips@emergmed.umsmed.edu

We present 2 cases, one adult and one pediatric, of acute migraine headache
promptly relieved by intravenous oxytocin. Both cases were typical flares of a
chronic intermittent headache pattern with classic vascular symptoms. Pain relief
in both cases was rapid and temporally related to oxytocin administration.
Vascular headache pathophysiology and possible oxytocin mechanisms of action are 
discussed.

Publication Types: 
    Case Reports

PMID: 16931475 [PubMed - indexed for MEDLINE]

1069: Headache. 2006 Jun;46 Suppl 1:S39-44.

Neurochemistry of trigeminal activation in an animal model of migraine.

Oshinsky ML, Luo J.

Department of Neurology, Thomas Jefferson University, 1020 Locust Street, Suite
398 JAH, Philadelphia, PA 19107, USA.

Research techniques such as electrophysiology, cFos protein expression, and other
measurements of neuronal activation provide insights into the pathophysiology of 
pain processing in migraine, but they do not indicate the specific
neurotransmitter systems involved. This paper summarizes data from microdialysis 
experiments in which changes in the neurochemistry of the trigeminal nucleus
caudalis (TNC) were monitored during dural stimulation. Microdialysis allows the 
measurement of extracellular concentrations of neurotransmitters in a small area 
of the brain, in vivo, by means of a probe equipped with a semipermeable
membrane. Microdialysis enables direct measurement of changes in extracellular
concentrations of neurotransmitters in the intact animal over time in response to
dural inflammation. Following the activation of the dural nociceptors, changes in
the extracellular amino acid neurotransmitters in the deep lamina of the TNC were
tracked. A 5-minute application of inflammatory soup when compared with saline to
the dura of rats induced a transient decrease in extracellular glutamate in the
TNC at approximately 30 minutes postapplication. This short-lived decrease was
followed by a continuous increase in extracellular glutamate to a level of
approximately 3 times the baseline value at 3 hours after application of the
inflammatory soup. The time course of this increase in extracellular glutamate
correlated with changes in sensory thresholds on the face of the rat from
electrophysiological recordings of secondary sensory neurons in the TNC. No
significant differences between the inflammatory soup and saline conditions were 
observed for extracellular concentrations of aspartate (an excitatory amino acid)
or the inhibitory neurotransmitters gamma-aminobutyric acid or glutamine. Results
of these experiments support an integral role for glutamate in central
sensitization of neurons in the TNC, and suggest an important contribution of
glutamate to allodynia and hyperalgia in this animal model of migraine.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16927963 [PubMed - indexed for MEDLINE]

1070: Headache. 2006 Jun;46 Suppl 1:S32-8.

Functional imaging of the trigeminal system: applications to migraine
pathophysiology.

Borsook D, Burstein R, Moulton E, Becerra L.

P.A.I.N. Group, Brain Imaging Center, McLean Hospital, 115 Mill Street, Belmont, 
MA 02478-9106, USA.

BACKGROUND: Based largely on data from animal models, migraine is hypothesized to
involve changes in neural function in brain areas that mediate
nociception--specifically, the trigeminal nerve, spinal trigeminal nucleus, and
thalamus. These hypotheses about migraine pathophysiology can be tested directly 
in humans for the first time, with recent advances in functional neuroimaging
techniques, which allow assessment of functional activity of specific brain
areas. This article discusses the hypothesized role of the trigeminovascular pain
system in migraine, reviews recent findings involving functional imaging of the
human trigeminal system, and considers applications of functional imaging in the 
study of migraine pathophysiology. Functional neuroimaging is the only
noninvasive approach for the objective measurement of changes in neural activity 
in humans. Functional magnetic resonance imaging has been applied to the
measurement of neural activation of the trigeminal nociceptive system in healthy 
volunteers, and in patients with pain syndromes such as trigeminal pain.
CONCLUSIONS: The demonstrated utility of functional magnetic resonance imaging at
elucidating, in a regionally specific manner, the functional and temporal changes
in neural activity in the trigeminal nociceptive system, promises to make it a
useful tool for the study of migraine pathophysiology and the evaluation of
therapeutic interventions.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't
    Review

PMID: 16927962 [PubMed - indexed for MEDLINE]

1071: Headache. 2006 Jun;46 Suppl 1:S25-31.

Invertebrate modeling of a migraine channelopathy.

Estevez M.

Veterans Administration Hospital and University of Pittsburgh School of Medicine,
Pittsburgh, PA 15213, USA.

Migraine is a chronic episodic disorder that has been linked to abnormalities in 
serotonin signaling and abnormal function of a presynaptic voltage-gated calcium 
channel, CACNA1A. Although the importance of serotonin to migraine tendency
suggests a link between serotonergic signaling and CACNA1A function, the nature
of this connection remains unclear in vertebrate studies. This article reviews
findings, based on an invertebrate model of CACNA1A dysfunction, which suggest a 
potential connection between serotonergic and calcium channel abnormalities in
migraine. Neurons of the invertebrate species Caenorhabditis elegans express a
voltage-gated calcium channel, UNC-2, which is the closest ortholog in C. elegans
of human CACNA1A. Mutations in unc-2, the gene that encodes this invertebrate
channel, cause the animals to be lethargic and uncoordinated. By identifying the 
genes that could be altered in such a way as to suppress the lethargic phenotype 
of unc-2, a signaling pathway has been identified through which UNC-2 calcium
channel function antagonizes a transforming growth factor-beta (TGF-beta) pathway
modulating locomotion. In C. elegans, serotonergic signaling can inhibit the rate
of movement. The UNC-2/transforming growth factor-beta pathway identified
regulates the expression of a gene encoding the rate-limiting enzyme for
serotonin synthesis, tryptophan hydroxylase. The evolutionary and functional
relationship between the UNC-2 channel and the migraine-associated CACNA1A
channel was further confirmed through experiments showing that transgenic
expression of human CACNA1A can suppress the lethargic and serotonin-deficient
phenotypes of unc-2 mutant animals. The findings in this invertebrate model
constitute the first direct demonstration of how CACNA1A function might affect
the levels of serotonin, a neurotransmitter known to be important in migraine.

Publication Types: 
    Review

PMID: 16927961 [PubMed - indexed for MEDLINE]

1072: Headache. 2006 Jun;46 Suppl 1:S19-24.

Genetics of migraine: an update.

Gardner KL.

Department of Neurology, Veterans Administration Hospital and University of
Pittsburgh Medical Center, Pittsburgh, PA, USA.

Observations including the long-recognized tendency of migraine to run in
families, the high concordance rates for migraine in twins reared together or
apart, and the association of specific mutations with a rare migraine form are
consistent with a genetic contribution to the disorder. This paper summarizes
major findings to date on the genetics of migraine. Study of the heritability of 
migraine, particularly the common forms of migraine, is beset by several
challenges including the absence of easily measurable biological markers,
uncertainty about the etiologic and clinical overlap among migraine types, and
the apparently complex interplay of environmental and genetic factors in
determining migraine phenotype. Nevertheless, significant progress has been
realized in recent years. Familial hemiplegic migraine, a rare migraine variant, 
appears to be transmitted by a Mendelian, autosomal dominant mode of inheritance 
involving mutations in at least 2 genes. These genes do not seem to be critically
involved in the other forms of migraine; however, several other susceptibility
loci for more common forms of migraine have been identified in recent genome-wide
screens and candidate-locus studies. These and other data suggest that the
genetic contribution to migraine is complex, multifactorial, and subject to
significant modification by environmental factors.

Publication Types: 
    Review

PMID: 16927960 [PubMed - indexed for MEDLINE]

1073: Headache. 2006 Jun;46 Suppl 1:S13-8.

Mast cell involvement in the pathophysiology of migraine headache: A hypothesis.

Levy D, Burstein R, Strassman AM.

Department of Anesthesia and Critical Care, Headache Research Laboratory, Beth
Israel Deaconess Medical Center, Harvard Institutes of Medicine, 77 Avenue Louis 
Pasteur, Boston, MA 02115, USA.

Migraine attacks are triggered by a variety of conditions including endogenous
and exogenous factors. Evidence suggests that activation and sensitization of
primary afferent meningeal nociceptive neurons, the peripheral arm of the
trigeminovascular system, constitutes one of the earliest events promoting the
intracranial pain of migraine. However, the link between the varied triggering
factors and activation of meningeal nociceptive neurons is not completely
understood. Local inflammation with release of mediators from local
immune/inflammatory cells is thought to play a critical role in such neuronal
response. Meningeal mast cells may play such a role by virtue of their proximity 
both to meningeal blood vessels and nociceptive axons and their ability to
release a host of proinflammatory/algesic mediators. This paper reviews data
relevant to the hypothesis that mast cells, upon activation by migraine triggers,
contribute to the genesis of migraine headache. Epidemiologic findings, clinical 
data, and observations on anatomical and physiological characteristics of mast
cells converge to suggest an important role of these immune cells in the
pathogenesis of migraine. Migraine triggers might directly or indirectly promote 
mediator secretion from meningeal mast cells, and thereby cause inflammation and 
activation of the trigeminovascular system. While consistent, the evidence
supporting mast cell involvement in the genesis of migraine is largely
circumstantial to date. Further studies are needed to test directly the nature of
mast cell involvement in the pathogenesis of migraine headache.

Publication Types: 
    Review

PMID: 16927959 [PubMed - indexed for MEDLINE]

1074: Headache. 2006 Jun;46 Suppl 1:S9-12.

Erratum in:
    Headache. 2006 Jul-Aug;46(7):1227.

Cerebrospinal profiling of proteins, lipids, small molecules, and elements:
application to the study of migraine pathophysiology.

Harrington MG.

Huntington Medical Research Institutes, 99 North El Molino Avenue, Pasadena, CA
91101, USA.

BACKGROUND AND OBJECTIVES: The fundamental reason that the migraine phenotype is 
experienced by sufferers and not by the more fortunate populace is not known. We 
believe a common biochemical pathway is involved, and are attempting to reveal
this by using an objective and broad survey of molecular composition, rather than
the conventional hypothesis-driven approaches that are narrowly focused and
subjective. METHODS: This article discusses the application of CSF bioanalysis in
a clinical sample and summarizes preliminary findings, which are described more
fully in papers currently in press. RESULTS: In migraineurs during a migraine
attack, compared with a migraine-free period, changes have been documented in the
concentrations of specific proteins, lipids, small molecules, and elements in the
CSF The degree to which these changes are specific to migraine remains to be
determined. CONCLUSIONS: As the CSF profiles for proteins, lipids, small
molecules, and elements become better delineated in both healthy individuals and 
in disease states such as migraine, measurement of changes in CSF composition
will provide the potential for improving diagnosis, correlating molecular events 
with symptoms, developing new therapeutic strategies, and enhancing the ability
to monitor the results of therapy.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 16927958 [PubMed - indexed for MEDLINE]

1075: Headache. 2006 Jun;46 Suppl 1:S3-8.

Calcitonin gene-related peptide (CGRP) and migraine.

Durham PL.

Department of Biology, Missouri State University, 231 Temple Hall, Springfield,
MO 65897, USA.

The neuropeptide calcitonin gene-related peptide (CGRP) has long been postulated 
to play an integral role in the pathophysiology of migraine. While clinical
findings are consistent with such a role, the specific pathogenic mechanisms of
CGRP in migraine have remained speculative until recently. Through advances in
molecular neuroscience, the pathogenic mechanisms of CGRP in migraine have begun 
to be elucidated. This paper discusses the hypothesized role of CGRP in migraine 
and reviews recent findings on the molecular mechanisms of this neuropeptide in
migraine pathophysiology. Studies in cultured trigeminal neurons demonstrate that
CGRP is released from trigeminal ganglia cells, that CGRP transcription is
increased under conditions mimicking neurogenic inflammation, that migraine
pharmacotherapies can both reduce CGRP release and inhibit CGRP transcription,
and that tumor necrosis factor-alpha (TNF-alpha), an endogenous inflammatory
mediator implicated in migraine, can stimulate CGRP transcription. Together, the 
results suggest that, in migraine, activation of trigeminal nerves release CGRP
and other peptides that cause the release of proinflammatory mediators. These
mediators further increase CGRP synthesis and release over hours to days in
correspondence with the 4- to 72-hour duration of a typical migraine episode. The
increased CGRP synthesis and release might be mediated by activation of
mitogen-activated protein kinase pathways, which, in turn, can be modulated by
endogenous inflammatory substances such as TNF-alpha and affected by drugs such
as sumatriptan.

Publication Types: 
    Review

PMID: 16927957 [PubMed - indexed for MEDLINE]

1076: MedGenMed. 2006 May 4;8(2):31.

Comment in:
    MedGenMed. 2006;8(2):89.

Emerging drugs for migraine prophylaxis and treatment.

Bigal ME, Krymchantowski AV.

The New England Center for Headache, P.C., Stamford, Connecticut, USA.

Migraine is a chronic neurologic disorder with heterogeneous characteristics
resulting in a range of symptom profiles, burden, and disability. Migraine
affects nearly 12% of the adult population in occidental countries, imposing
considerable economic and social losses. The pharmacologic treatment of migraine 
includes preventive and acute strategies. A better understanding of the migraine 
pathophysiology along with the discovery of novel molecular targets has lead to a
growing number of upcoming therapeutic proposals. This review focuses on new and 
emerging agents for the treatment of migraine.

Publication Types: 
    Review

PMID: 16926770 [PubMed - indexed for MEDLINE]

1077: Indian J Ophthalmol. 2006 Sep;54(3):195-7.

Comment in:
    Indian J Ophthalmol. 2006 Sep;54(3):147-8.

Acute myopia and angle closure caused by topiramate, a drug used for prophylaxis 
of migraine.

Desai CM, Ramchandani SJ, Bhopale SG, Ramchandani SS.

Department of Ophthalmology, MGM Hospital, Kamothe, Navi Mumbai, Maharashtra,
India.

Acute transient myopia with shallowing of the anterior chamber is a rare
idiosyncratic response to many systemic and topical medications, including
sulfonamides. Several such cases have been reported in the past, but are less
frequently reported in recent times. We report a case of acute progressive myopia
and bilateral angle closure due to Topiramate--a drug used for epilepsy and
migraine prophylaxis.

Publication Types: 
    Case Reports

PMID: 16921218 [PubMed - indexed for MEDLINE]

1078: Physiother Theory Pract. 2006 Sep;22(4):163-74.

Strength and mobility of the neck-shoulder region in adolescent headache.

Oksanen A, Metsähonkala L, Viander S, Jäppilä E, Aromaa M, Anttila P, Salminen J,
Sillanpää M.

Department of Physical Medicine and Rehabilitation, Turku University Central
Hospital, Turku, Finland. airi.oksanen@tyks.fi

The significance of the musculoskeletal function of the neck-shoulder region in
different headache types in children and adolescents is not clear. The purpose of
this study was to investigate the association between different types of headache
and the strength and mobility of the neck-shoulder region in 13-year-old
schoolchildren. A structured questionnaire on headache was sent to all 1,409
children in the sixth grade in the city of Turku. Of the 1,135 (81%) children who
completed the questionnaire, a sample from different headache groups was randomly
selected for clinical examination. The study consisted of 59 children with
migraine, 65 with episodic tension-type headache (TTHA), and 59 headache-free
controls. Dynamic muscle strength of the upper extremities (UE endurance),
mobility of both shoulders (UE mobility), and the cervical range of motion (CROM)
were measured. Girls with episodic TTHA had lower UE endurance of both dominant
and nondominant sides than girls in the other study groups. Girls with migraine
had lower UE endurance of nondominant side than girls in the control group. In
boys, no significant differences were observed. An interesting association
between the function of the neck-shoulder region and headache complaints in
adolescents was ascertained.

PMID: 16920676 [PubMed - indexed for MEDLINE]

1079: Cephalalgia. 2006 Sep;26(9):1137-42.

SMART: stroke-like migraine attacks after radiation therapy.

Black DF, Bartleson JD, Bell ML, Lachance DH.

Mayo Clinic College of Medicine, Department of Neurology, Rochester, MN 55905,
USA. black.david@mayo.edu

We describe two adults with stroke-like migraine attacks after radiation therapy 
(SMART syndrome), propose revised diagnostic criteria, and review the previously 
reported patients. 'SMART' is an acronym for a newly recognized syndrome which
occurs as a delayed consequence of cerebral irradiation and consists of
prolonged, unilateral, migrainous neurological symptoms with transient, dramatic 
cortical gadolinium enhancement of the affected cerebral hemisphere and is
sometimes punctuated by generalized seizures and ipsilateral EEG slowing.
Although the neurological symptoms can last for weeks, full recovery occurs. An
appropriate evaluation should exclude alternative explanations.

Publication Types: 
    Case Reports

PMID: 16919065 [PubMed - indexed for MEDLINE]

1080: Cephalalgia. 2006 Sep;26(9):1131-6.

Motion perception in migraineurs: abnormalities are not related to attention.

McKendrick AM, Badcock DR, Badcock JC, Gurgone M.

Department of Optometry and Vision Sciences, University of Melbourne, Carlton,
and Centre for Clinical Research in Neuropsychiatry/Graylands Hospital, Nedlands,
Australia. allisonm@unimelb.edu.au

Migraine groups have impaired ability to identify global motion direction in
noisy random dot stimuli, an observation that has been used as evidence for
cortical hyperexcitability. Several studies have also suggested abnormalities in 
cognitive processing, particularly in the domains of attention, visuo-spatial
processing and memory. This study aimed to determine whether poor performance by 
migraineurs in motion coherence tasks could be explained by non-visual cognitive 
factors such as attention. Twenty-nine migraineurs and 27 non-headache controls
participated. Global motion coherence thresholds were measured along with
measures of neuropsychological function, using the Repeatable Battery for the
Assessment of Neuropsychological Status (RBANS). The migraine group had
significantly higher motion coherence thresholds than controls. No significant
difference in attention or any other RBANS index score was found between groups. 
Index scores did not correlate with motion perception thresholds. This study does
not support inattention or other cognitive abnormality as an explanation for
motion perception anomalies in migraine.

Publication Types: 
    Controlled Clinical Trial
    Research Support, Non-U.S. Gov't

PMID: 16919064 [PubMed - indexed for MEDLINE]

1081: Cephalalgia. 2006 Sep;26(9):1123-30.

Rating of olfactory judgements in migraine patients.

Demarquay G, Royet JP, Giraud P, Chazot G, Valade D, Ryvlin P.

Unité de Neurologie Fonctionnelle et d'Epileptologie, Hôpital Neurologique Pierre
Wertheimer, and Neuroscience and Sensory Systems, Claude-Bernard University,
Lyon, France. genevieve.demarquay@chu-lyon.fr

The aim of this study was to evaluate olfactory hypersensitivity (OHS) between
attacks in migraine patients. Seventy-four migraine patients and 30 controls were
enrolled. The presence of OHS was evaluated using an oral questionnaire and a
chemical odour intolerance index. Subjects had to rate the intensity and
hedonicity of 12 odourants using a linear rating scale. Twenty-six patients
(35.2%) but no control subjects reported an interictal OHS (P<0.001). Logistic
regression analysis showed that patients with OHS presented a greater attack
frequency, a higher number of odour-induced migraines and visual hypersensitivity
when compared with other patients. Disease duration, age, gender and auditory
hypersensitivity were not associated with OHS. OHS patients judged odours less
pleasant than did other patients and controls, whereas the intensity scores were 
identical in both groups. OHS between attacks was significantly associated with
odour-triggered migraine and an alteration of hedonic judgement.

Publication Types: 
    Controlled Clinical Trial
    Research Support, Non-U.S. Gov't

PMID: 16919063 [PubMed - indexed for MEDLINE]

1082: Cephalalgia. 2006 Sep;26(9):1097-105.

Advice alone vs. structured detoxification programmes for medication overuse
headache: a prospective, randomized, open-label trial in transformed migraine
patients with low medical needs.

Rossi P, Di Lorenzo C, Faroni J, Cesarino F, Nappi G.

Headache Clinic, INI Grottaferrata, Grottaferrata, Italy. paolo.rossi90@alice.it

The aim of this study was to compare the effectiveness of strong advice to
withdraw the overused medication with the effectiveness of two structured
pharmacological detoxification strategies in a cohort of patients diagnosed with 
probable migraine overuse headache (MOH) plus migraine and presenting low medical
needs. One hundred and twenty patients participated in the study. Exclusion
criteria included: previous detoxification treatments, coexistent medical or
psychiatric illnesses and overuse of agents containing opioids, benzodiazepines
and barbiturates. Group A received only intensive advice to withdraw the overused
medication. Group B underwent a standard out-patient detoxification programme
(advice+prednisone+preventive treatment). Group C underwent a standard in-patient
withdrawal programme (as in group B + fluid replacement and antiemetics).
Withdrawal therapy was considered successful if, after 2 months, the patient had 
reverted to an episodic pattern of headache and to an intake of symptomatic
medication on fewer than 10 days/month. We were able to detoxify 75.4% of the
whole cohort, 77.5% of patients in group A, 71.7% of patients in group B and
76.9% of those in group C (P>0.05). In patients with migraine plus MOH and low
medical needs, effective drug withdrawal may be obtained through the imparting of
advice alone.

Publication Types: 
    Randomized Controlled Trial

PMID: 16919060 [PubMed - indexed for MEDLINE]

1083: Cephalalgia. 2006 Sep;26(9):1089-96.

Prevalence and correlates of migraine among women attending a prenatal care
clinic in Lima, Peru.

Adeney KL, Flores JL, Perez JC, Sanchez SE, Williams MA.

Department of Epidemiology, University of Washington School of Public Health and 
Community Medicine, Seattle, Washington 98122, USA, and Dos de Mayo Hospital,
Lima, Peru. kathryn7@u.washington.edu

Migraine headaches are among the leading causes of disability in the world. The
burden of migraines is highest in women of reproductive age. This cross-sectional
study characterized the prevalence, symptoms and correlates of migrainous
headaches in 154 pregnant women attending a prenatal care clinic in Lima, Peru.
Lifetime prevalence of migraine defined by modified IHS criteria was 9.1% (95% CI
4.6-13.6). When probable migraines were included, the lifetime prevalence of
migraine in this population was 29.2% (95% CI 22.0-36.4). Migraine headaches were
associated with a maternal history of headache, childhood carsickness, a
diagnosis of allergies, and a high frequency of fatigue. Although
headache-related disability was low in terms of missed work and recreation, high 
rates of headache pain and medicinal use reflect the true impact on this
population.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 16919059 [PubMed - indexed for MEDLINE]

1084: Cephalalgia. 2006 Sep;26(9):1071-9.

NF-kappaB activity and iNOS expression in monocytes from internal jugular blood
of migraine without aura patients during attacks.

Sarchielli P, Floridi A, Mancini ML, Rossi C, Coppola F, Baldi A, Pini LA,
Calabresi P.

Neurologic Clinic, Department of Medical Specialties and Public Health,
University of Perugia, Perugia, Italy. neuro.pg@tiscalinet.it

This study investigated nuclear factor-kappa B (NF-kappaB) activity by
electrophoresis mobility gel shift assay and IkappaBalpha expression by Western
blot analysis in monocytes obtained from serial samples of internal jugular
venous blood taken from seven migraine patients without aura during attacks.
Inducible nitric oxide synthase (iNOS) expression was also assessed by reverse
transcription-polymerase chain reaction. An increase in NF-kappaB activity peaked
2 h after attack onset. This was accompanied by a transient reduction in
IkappaBalpha expression. Up-regulation of iNOS was evident at 4 h, maintained at 
6 h and reduced at the end of the attack. These findings substantiate the
hypothesis of transitory delayed inflammation, as suggested by the animal model, 
and suggest the possibility of using therapeutic approaches to target NF-kappaB
transcription in the treatment of migraine.

Publication Types: 
    Clinical Trial

PMID: 16919057 [PubMed - indexed for MEDLINE]

1085: Cephalalgia. 2006 Sep;26(9):1061-70.

Myofascial trigger points, neck mobility and forward head posture in unilateral
migraine.

Fernández-de-Las-Peñas C, Cuadrado ML, Pareja JA.

Department of Physical Therapy, Occupational Therapy, Physical Medicine and
Rehabilitation, Universidad Rey Juan Carlos, and Department of Neurology,
Fundación Hospital Alcorcón, Madrid, Spain. cesarfdlp@yahoo.es

This paper describes the differences in the presence of myofascial trigger points
(TrPs) in the upper trapezius, sternocleidomastoid, temporalis and suboccipital
muscles between unilateral migraine subjects and healthy controls, and the
differences in the presence of TrPs between the symptomatic side and the
non-symptomatic side in migraine subjects. In addition, we assess the differences
in the presence of both forward head posture (FHP) and active neck mobility
between migraine subjects and healthy controls and the relationship between FHP
and neck mobility. Twenty subjects with unilateral migraine without side-shift
and 20 matched controls participated. TrPs were identified when there was a
hypersensible tender spot in a palpable taut band, local twitch response elicited
by the snapping palpation of the taut band and reproduction of the referred pain 
typical of each TrP. Side-view pictures were taken in both sitting and standing
positions to measure the cranio-vertebral angle. A cervical goniometer was
employed to measure neck mobility. Migraine subjects showed a significantly
greater number of active TrPs (P<0.001), but not latent TrPs, than healthy
controls. Active TrPs were mostly located ipsilateral to migraine headaches
(P<0.01). Migraine subjects showed a smaller cranio-vertebral angle than controls
(P<0.001), thus presenting a greater FHP. Neck mobility in migraine subjects was 
less than in controls only for extension (P=0.02) and the total range of motion
in flexion/extension (P=0.01). However, there was a positive correlation between 
the cranio-vertebral angle and neck mobility. Nociceptive inputs from TrPs in
head and neck muscles may produce continuous afferent bombardment of the
trigeminal nerve nucleus caudalis and, thence, activation of the
trigeminovascular system. Active TrPs located ipsilateral to migraine headaches
might be a contributing factor in the initiation or perpetuation of migraine.

Publication Types: 
    Controlled Clinical Trial

PMID: 16919056 [PubMed - indexed for MEDLINE]

1086: Cephalalgia. 2006 Sep;26(9):1051-60.

Premonitory and resolution symptoms in migraine: a prospective study in 100
unselected patients.

Quintela E, Castillo J, Muñoz P, Pascual J.

Health Centre of Astillero, University Hospital, Salamanca, Spain.

The nosology of migraine premonitory (PS) and resolution (RS) symptoms was
studied in 100 migraineurs consulting their general physician. They were asked to
fill in, for three attacks, a PS and RS questionnaire. 'True' PS/RS were those
experienced the day before (or the day after) the headache had started only if
they were not present in a questionnaire completed in a pain-free period. True PS
and RS were experienced by 84% and 80%, respectively, of subjects for the first
attack. The mean and range (per patient) of PS were 6.8 and 0-21 and of RS 4.7
and 0-15. Anxiety, phonophobia, irritability, unhappiness and yawning were the
commonest PS, whereas asthenia, tiredness, somnolence and concentration
difficulties were the most common RS. Gender, age and Migraine Disability
Assessment scores did not influence PS and RS. Both PS and RS were more frequent 
in migraine with aura subjects. Patients on preventatives showed a decreased
frequency of PS and, to a lesser degree, of RS. Severity of headache was
associated with a higher frequency of RS. Individual RS and especially PS were
quite consistent after three attacks. Almost two-thirds of the symptoms were
noticed in at least two out of three attacks, while more than a half of PS and
more than a quarter of RS repeated in three out of three attacks. In conclusion, 
around 80% of unselected migraineurs experience RS and PS. Migraine with aura and
severe pain are risk factors for experiencing PS and RS, while preventatives were
protective, especially for PS.

Publication Types: 
    Clinical Trial

PMID: 16919055 [PubMed - indexed for MEDLINE]

1087: J Electromyogr Kinesiol. 2007 Aug;17(4):493-503. Epub 2006 Sep 5.

Repeatability of electromyography and force measurements of the neck muscles in
adolescents with and without headache.

Oksanen A, Ylinen JJ, Pöyhönen T, Anttila P, Laimi K, Hiekkanen H, Salminen JJ.

Department of Physical and Rehabilitation Medicine, Turku University Central
Hospital, P.O. Box 52, FIN-20521 Turku, Finland. airi.oksanen@tyks.fi

BACKGROUND: Reliable measurements are needed to study the dysfunction of the neck
muscles. The aim of this study was to determine the intra-tester repeatability of
EMG and isometric force measurements of the neck muscles in adolescents with
headache and headache-free controls. METHODS: A group of 30 adolescents with
migraine-type headache, 29 with tension-type headache, and 30 headache-free
controls were recruited. Maximal isometric neck muscle force with simultaneous
recording of surface EMG from the cervical erector spinae and the
sternocleidomastoideus muscles was measured twice during one day. FINDINGS: For
all groups, intra-class correlation coefficients (ICC) and coefficients of
variation (CV) showed acceptable repeatability of all measurements. (Force
measurements: ICC 0.98-0.99, CV 0.7-3.7%; EMG measurements: ICC 0.95-0.99, CV
4.9-10.1%.) On the individual level, variation between the consecutive
measurements was found to be low in all groups. INTERPRETATION: The present EMG
and force measurements of neck muscles indicate acceptable intra-tester
repeatability in adolescents. The repeatability was comparable in migraine- and
tension-type headache and headache-free groups. The EMG and the force
measurements offer the possibility to investigate neck muscle dysfunction in
adolescent headache.

PMID: 16908197 [PubMed - indexed for MEDLINE]

1088: Drug Ther Bull. 2006 Aug;44(8):62-4.

Topiramate for migraine prophylaxis.

[No authors listed]

About 14% of adults in the UK have migraines. Drugs used in migraine prophylaxis 
include beta-blockers (e.g. propranolol), 5HT antagonists (e.g. pizotifen),
antidepressants (e.g. amitriptyline), antiepileptics (e.g. sodium valproate) and 
NSAIDs. The antiepileptic topiramate (Topamax-Janssen-Cilag) is licensed for the 
prophylaxis of migraine headache in patients aged over 16 years. Here we discuss 
the place of topiramate in migraine prophylaxis.

Publication Types: 
    Review

PMID: 16903488 [PubMed - indexed for MEDLINE]

1089: J Child Neurol. 2006 May;21(5):423-5.

Meningismus is a commonly overlooked finding in tension-type headache in children
and adolescents.

Almazov I, Brand N.

Meuhedet Healthcare Services, Tel Aviv, Israel. almazov@netvision.net.il

At present, both migraine and tension-type headaches in children are believed to 
be chronic primary headaches. Meningeal signs in both cases are ignored or not
examined, and the neurologic status is considered normal. This is the first study
that focuses on meningeal signs in children with chronic headaches. The study
population comprised 1738 patients aged 5 to 17 years who were examined in an
outpatient neurologic clinic over a 6-year period. Particular attention was paid 
to examination of meningeal signs, including nuchal rigidity, Kernig's sign,
Brudzinski's three signs (upper, middle, and lower), the "tripod" sign, and
Guillain's and facial signs; the presence of these signs was regarded as
meningismus syndrome. Some meningeal signs were found in 12% of 1007 children
suffering from migraine, whereas 97% of 731 children with tension-type headaches 
had the whole set of meningeal signs. This suggested that meningismus is the
major clinical syndrome in chronic tension-type headaches in children and
adolescents. Chronic mild sterile (possibly autoimmune) inflammation of meninges 
(dura mater) can be caused by a preceding infection, as well as minor trauma of
the head and/or back. Prolonged rest in a recumbent position usually resulted in 
relief or complete disappearance of both headache and meningeal signs. Monitoring
of the meningeal signs is helpful for evaluation of the patient's condition in
the course of treatment.

Publication Types: 
    Comparative Study

PMID: 16901450 [PubMed - indexed for MEDLINE]

1090: Mayo Clin Proc. 2006 Aug;81(8):1086-91; quiz 1092.

Prevention of migraine in women throughout the life span.

Tozer BS, Boatwright EA, David PS, Verma DP, Blair JE, Mayer AP, Files JA.

Division of Women's Health Internal Medicine, Mayo Clinic College of Medicine,
13400 E Shea Blvd, Scottsdale, AZ 85259, USA.

Migraine is a common disorder in women. The 1-year prevalence of migraine is 18% 
in women compared with 6% in men. Migraine most commonly occurs during the
reproductive years, affecting 27% of women 30 to 49 years of age. The
predominance of this disorder and its social, functional, and economic
consequences make migraine an important issue in women's health. The hormonal
milieu has a substantial effect on migraine in women. An understanding of these
hormonal influences in the various stages of life in females is essential to the 
management and prevention of migraines. This article reviews migraine prevention 
strategies with an emphasis on specific therapies for each stage of a woman's
life.

Publication Types: 
    Review

PMID: 16901031 [PubMed - indexed for MEDLINE]

1091: J Neurosci. 2006 Aug 9;26(32):8332-8.

Tissue injury regulates serotonin 1D receptor expression: implications for the
control of migraine and inflammatory pain.

Ahn AH, Basbaum AI.

Department of Neurology, University of California, San Francisco, San Francisco, 
California 94158, USA. andrew.ahn@ucsf.edu

The anti-migraine action of "triptan" drugs involves the activation of serotonin 
subtype 1D (5-HT1D) receptors expressed on "pain-responsive" trigeminal primary
afferents. In the central terminals of these nociceptors, the receptor is
concentrated on peptidergic dense core vesicles (DCVs) and is notably absent from
the plasma membrane. Based on this arrangement, we hypothesized that in the
resting state the receptor is not available for binding by a triptan, but that
noxious stimulation of these afferents could trigger vesicular release of DCVs,
thus externalizing the receptor. Here we report that within 5 min of an acute
mechanical stimulus to the hindpaw of the rat, there is a significant increase of
5-HT1D-immunoreactivity (IR) in the ipsilateral dorsal horn of the spinal cord.
We suggest that these rapid immunohistochemical changes reflect redistribution of
sequestered receptor to the plasma membrane, where it is more readily detected.
We also observed divergent changes in 5-HT1D-IR in inflammatory and nerve-injury 
models of persistent pain, occurring at least in part through the regulation of
5-HT1D-receptor gene expression. Finally, we found that 5-HT1D-IR is unchanged in
the spinal cord dorsal horn of mice with a deletion of the gene encoding the
neuropeptide substance P. This result differs from that reported for the partial 
differential-opioid receptor, which is also sorted to DCVs, but is greatly
reduced in preprotachykinin mutant mice. We suggest that a "pain"-triggered
regulation of 5-HT1D-receptor expression underlies the effectiveness of triptans 
for the treatment of migraine. Moreover, the widespread expression of 5-HT1D
receptor in somatic nociceptive afferents suggests that triptans could, in
certain circumstances, treat pain in nontrigeminal regions of the body.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 16899728 [PubMed - indexed for MEDLINE]

1092: Man Ther. 2007 May;12(2):153-60. Epub 2006 Aug 8.

Neurodynamic responses in children with migraine or cervicogenic headache versus 
a control group. A comparative study.

von Piekartz HJ, Schouten S, Aufdemkampe G.

Department of Rehabilitation Science and Physiotherapy for Craniofacial
Dysfunction and Pain, Stobbenkamp 10, 7631 CP Ootmarsum, The Netherlands.
harryvonpiekartz@home.nl

Headache in children with unknown aetiology is an increasing phenomenon in
industrial countries, especially during growth spurts. During this growth phase, 
the Long Sitting Slump (LSS) can be a useful tool for measurement of
neurodynamics and management. This study investigated the difference in cervical 
flexion and sensory responses (intensity and location) during the LSS tests in
children (n=123) aged 6-12 years, between a migraine (primary headache group=PG),
cervicogenic headache (secondary headache group=SG) and control group (CG). The
results indicated that the intensities of the sensory response rate were highest 
in the PG and SG when compared to CG. The responses in the legs were
predominantly found in the PG (81.9%) and responses in the spine in the SG (80%).
The sacrum position varied significantly between both headache groups (PG and SG)
and the CG (p<0.0001), but there was no significant difference between the CG and
the PG (p>0.05). No significant difference in the neck flexion range was measured
in LSS, nor in standardized knee flexion between the PG and CG (p>0.05). The
cervical flexion ranges differed significantly (p<0.0001) between the SG on the
one hand and the PG and CG on the other. The biggest difference in neck flexion
during knee extension was between the SG and CG.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 16899387 [PubMed - indexed for MEDLINE]

1093: J Headache Pain. 2006 Sep;7(4):188-95. Epub 2006 Aug 11.

Comment in:
    J Headache Pain. 2006 Sep;7(4):172-3.

Trigger factors of migraine and tension-type headache: experience and knowledge
of the patients.

Wöber C, Holzhammer J, Zeitlhofer J, Wessely P, Wöber-Bingöl C.

Department of Neurology, Medical University of Vienna, Währinger Gürtel 18-20,
A-1090, Vienna, Austria. christian.woeber@meduniwien.ac.at

The objective was to examine potential trigger factors of migraine and
tension-type headache (TTH) in clinic patients and in subjects from the
population and to compare the patients' personal experience with their
theoretical knowledge. A cross-sectional study was carried out in a headache
centre. There were 120 subjects comprising 66 patients with migraine and 22 with 
TTH from a headache outpatient clinic and 32 persons with headache (migraine or
TTH) from the population. A semistructured interview covering biographic data,
lifestyle, medical history, headache characteristics and 25 potential trigger
factors differentiating between the patients' personal experience and their
theoretical knowledge was used. The most common trigger factors experienced by
the patients were weather (82.5%), stress (66.7%), menstruation (51.4%) and
relaxation after stress (50%). The vast majority of triggers occurred
occasionally and not consistently. The patients experienced 8.9+/-4.3 trigger
factors (range 0-20) and they knew 13.2+/-6.0 (range 1-27). The number of
experienced triggers was smallest in the population group (p=0.002), whereas the 
number of triggers known did not differ in the three study groups. Comparing
theoretical knowledge with personal experience showed the largest differences for
oral contraceptives (65.0 vs. 14.7%, p<0.001), chocolate (61.7 vs. 14.3%,
p>0.001) and cheese (52.5 vs. 8.4%, p<0.001). In conclusion, almost all trigger
factors are experienced occasionally and not consistently by the majority of
patients. Subjects from the population experience trigger factors less often than
clinic patients. The difference between theoretical knowledge and personal
experience is largest for oral contraceptives, chocolate and cheese.

PMID: 16897622 [PubMed - indexed for MEDLINE]

1094: J Headache Pain. 2006 Sep;7(4):206-10. Epub 2006 Aug 11.

Specific features of migraine syndrome in children.

Knezevic-Pogancev M.

Institute of Child and Youth Health Care, Novi Sad, Hajduk Veljkova 10, 21000,
Novi Sad, Serbia & Montenegro. godipo@eunet.yu

The aim of the study was to define factors that can be used to distinguish
migraine headaches from primary non-migraine headaches. Specific characteristics 
of headaches were analysed in 30,636 children aged 3-17; 18.97% had recurrent
primary non-migraine headaches, whereas 8.63% had migraine headaches. Migraine
attacks follow identical patterns (94.9%): occurring monthly (78.0%), occurring
in morning hours (58.5%), lasting for several hours (45.1%) and ending after
sleep (76.7%). Nausea, vomiting impulse and vomiting are basic present elements
of migraine attacks in children. Canonical discriminate analysis defined the
following statistically significant factors, which can distinguish migraine
headaches from primary non-migraine headaches in children: relief after sleep
(0.945), vomiting impulse (0.945), photophobia (0.523), nausea (0.379),
phonophobia (0.354) and vomiting (0.330).

PMID: 16897615 [PubMed - indexed for MEDLINE]

1095: J Neural Transm. 2007;114(4):417-21. Epub 2006 Aug 10.

Kynurenine in combination with probenecid mitigates the stimulation-induced
increase of c-fos immunoreactivity of the rat caudal trigeminal nucleus in an
experimental migraine model.

Knyihár-Csillik E, Toldi J, Mihály A, Krisztin-Péva B, Chadaide Z, Németh H,
Fenyo R, Vécsei L.

Department of Neurology, Albert Szent-Györgyi Medical and Pharmaceutical Center, 
University of Szeged, Szeged, Hungary. knyihar@nepsy.szote.u-szeged.hu

Nitroglycerin, often used as a migraine model, results in increased number of
c-fos immunoreactive secondary sensory neurons in the caudal trigeminal nucleus. 
Since synapses between first- and second-order trigeminal neurons are mediated by
excitatory amino acids, NMDA receptors are presumably inhibited by kynurenic
acid, the only known endogeneous NMDA receptor antagonist. Although kynurenic
acid does not cross the BBB, its precursor, kynurenine, if combined with
probenecid, crosses it readily. Systemic kynurenine + probenecid treatment
significantly diminishes nitroglycerin-induced increase of c-fos immunoreactivity
in the brainstem.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16897600 [PubMed - indexed for MEDLINE]

1096: Neurology. 2006 Aug 8;67(3):419-23.

Comment in:
    Nat Clin Pract Neurol. 2007 May;3(5):254-5.

Bilateral transverse sinus stenosis predicts IIH without papilledema in patients 
with migraine.

Bono F, Messina D, Giliberto C, Cristiano D, Broussard G, Fera F, Condino F,
Lavano A, Quattrone A.

Institute of Neurology, University Magna Graecia, Catanzaro, Italy.

BACKGROUND: The headache profile of patients with idiopathic intracranial
hypertension without papilledema (IIHWOP) may be indistinguishable from that of
migraine. Bilateral transverse sinus stenosis (BTSS) has been found in the
majority of patients with IIHWOP. The frequency of BTSS associated with IIHWOP in
patients with migraine is unknown. OBJECTIVE: To detect the frequency of BTSS in 
adult patients with migraine and to investigate whether the presence of BTSS
identifies patients with IIHWOP. METHODS: In a prospective study from December
2000 to November 2005, 724 consecutive patients with recurrent headaches who
fulfilled International Headache Society diagnostic criteria for migraine
underwent cerebral MR venography (MRV). A portion of these patients underwent a
lumbar puncture (LP) to measure CSF pressure. MRV and LP were also performed in
70 age-matched control subjects. RESULTS: Six hundred seventy-five of the 724
patients with migraines had normal MRV. Seventy of these 675 patients underwent
LP, and all of them had normal CSF pressure. Forty-nine (6.7%) of the 724
patients with migraine had BTSS. Twenty-eight of these 49 patients with BTSS
underwent LP, and 19 (67.8%) had IIHWOP. The headache profiles of patients with
BTSS and IIHWOP did not differ from those of patients with normal MRVs and CSF
pressures within normal limits. CSF pressure was normal in both patients and
controls with normal MRV. CONCLUSIONS: Of patients with migraine, 6.7% had
bilateral transverse sinus stenosis; 67.8% of these patients had idiopathic
intracranial hypertension without papilledema (IIHWOP). These results suggest
that patients with migraine who present bilateral transverse sinus stenosis on
cerebral MR venography should undergo lumbar puncture to exclude IIHWOP.

PMID: 16894101 [PubMed - indexed for MEDLINE]

1097: Expert Rev Neurother. 2006 Aug;6(8):1147-57.

Migraine preventive therapy: selection of appropriate patients and general
principles of management.

D'Amico D, Lanteri-Minet M.

C. Besta National Neurological Institute, Via Celoria 11, 20133 Milano, Italy.
damicodo@tiscali.it

The goal of this review is to communicate the rationale and the possible benefits
of migraine preventive treatments to clinicians and patients, and to address the 
many problematic issues created by missed diagnosis or misdiagnoses and
inadequate migraine management. Successful implementation of migraine preventive 
treatment requires appropriate patient selection based on several factors,
including the frequency of migraine attacks (> or =2-3 attacks/month), the level 
of disability incurred and the frequency of acute medication usage.
Unfortunately, several epidemiologic surveys indicate that preventive therapies
are significantly underutilized, which supports the need for greater dialog
concerning migraine prevention between consumers and physicians. Effective
migraine preventive therapy should reduce the frequency, duration, and severity
of migraine, and also improve function, reduce disability, and possibly reduce
the risk of worsening the headache syndrome, through acute medication overuse.

Publication Types: 
    Review

PMID: 16893343 [PubMed - indexed for MEDLINE]

1098: Bioorg Med Chem Lett. 2006 Oct 1;16(19):5052-6. Epub 2006 Aug 2.

Benzodiazepine calcitonin gene-related peptide (CGRP) receptor antagonists:
optimization of the 4-substituted piperidine.

Burgey CS, Stump CA, Nguyen DN, Deng JZ, Quigley AG, Norton BR, Bell IM, Mosser
SD, Salvatore CA, Rutledge RZ, Kane SA, Koblan KS, Vacca JP, Graham SL, Williams 
TM.

Department of Medicinal Chemistry, Merck Research Laboratories, West Point, PA
19486, USA. christopher_burgey@merck.com

In our continuing effort to identify CGRP receptor antagonists for the acute
treatment of migraine, we have undertaken a study to evaluate alternative
4-substituted piperidines to the lead dihydroquinazolinone 1. In this regard, we 
have identified the piperidinyl-azabenzimidazolone and phenylimidazolinone
structures which, when incorporated into the benzodiazepine core, afford potent
CGRP receptor antagonists (e.g., 18 and 29). These studies produced a potent
analog (18) which overcomes the instability issues associated with the lead
structure 1. A general pharmacophore for the 4-substituted piperidine component
of these CGRP receptor antagonists is also presented.

PMID: 16889959 [PubMed - indexed for MEDLINE]

1099: Am J Med. 2006 Aug;119(8):670-5.

Migraines, angiographic coronary artery disease and cardiovascular outcomes in
women.

Ahmed B, Bairey Merz CN, McClure C, Johnson BD, Reis SE, Bittner V, Pepine CJ,
Sharaf BL, Sopko G, Kelsey SF, Shaw L; WISE Study Group.

Division of Cardiology, Department of Medicine, Cedars-Sinai Research Institute, 
Cedars-Sinai Medical Center, Los Angeles, Calif, USA.

PURPOSE: There are conflicting data regarding the association between migraines
and cardiovascular events. We evaluated the relationship between migraine
headaches, angiographic coronary artery disease, and cardiovascular events in
women. SUBJECTS AND METHODS: The Women's Ischemia Syndrome Evaluation (WISE)
study is a National Heart, Lung and Blood Institute (NHLBI)-sponsored
prospective, multicenter study aiming to improve ischemia evaluation in women. A 
total of 944 women presenting with chest pain or symptoms suggestive of
myocardial ischemia were enrolled and underwent complete demographic, medical,
and psychosocial history, physical examination, and coronary angiography testing.
A smaller subset of 905 women, representing a mean age of 58 years, answered
questions regarding a history of migraines. We prospectively followed 873 women
for 4.4 years for cardiovascular events and all-cause mortality. RESULTS: Women
reporting a history of migraines (n=220) had lower angiographic coronary severity
scores, and less severe (> or = 70% luminal stenosis) angiographic coronary
artery disease compared to women without a history of migraines (n=685). These
differences remained statistically significant after adjustment for age and other
important cardiac risk factors. On prospective follow-up of a median of 4.4
years, women with a history of migraines were not more likely to have a
cardiovascular event (hazard ratio [HR] 1.2; 95% confidence interval [CI],
0.93-1.58) and migraines did not predict all-cause mortality (HR 0.96; 95% CI,
0.49-1.99). CONCLUSION: Among women undergoing coronary angiography for suspected
ischemia, those reporting migraines had less severe angiographic coronary artery 
disease. We could not support an association between migraines and cardiovascular
events or death. Further research studying the common pathophysiology underlying 
migraines and cardiovascular disease is warranted.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 16887413 [PubMed - indexed for MEDLINE]

1100: Int J Cardiol. 2006 Oct 26;113(1):E7-8. Epub 2006 Aug 2.

Acute coronary syndrome associated with myocardial bridging due to ergotamine
treatment for migraine.

Shimony A, Romem A, Horowitz S, Boehm R, Horowitz J.

A 48-year-old woman presented with acute coronary syndrome and underwent coronary
angiography which revealed myocardial bridging at the distal end of the left
anterior descending artery with otherwise normal coronary arteries. The patient
used to take ergotamine for her chronic migraine. Possible association with
myocardial bridging which was found in this patient is discussed.

Publication Types: 
    Case Reports
    Letter

PMID: 16887217 [PubMed - indexed for MEDLINE]

1101: Cephalalgia. 2006 Aug;26(8):1004-9.

Imaging abnormalities in sporadic hemiplegic migraine on conventional MRI,
diffusion and perfusion MRI and MRS.

Jacob A, Mahavish K, Bowden A, Smith ET, Enevoldson P, White RP.

The Walton Centre for Neurology and Neurosurgery, Liverpool, UK.
anujacob@liv.ac.uk

Prolonged hemiparetic migraine aura can cause diagnostic confusion and be
mistaken for ischaemic stroke occurring during the course of a
migraine--'migrainous infarction'. We report a case of prolonged hemiparesis
occurring during the course of a migraine attack. Though initially confused with 
migrainous infarction, we suggest with sequential magnetic resonance imaging,
magnetic resonance angiography, diffusion, perfusion images and magnetic
resonance spectroscopy that the hemiplegia was not of vascular origin and that
the patient had sporadic hemiplegic migraine. We hypothesize that the mechanisms 
of sporadic hemiplegic migraine probably lie at a cellular level, similiar to
familial hemiplegic migraine.

Publication Types: 
    Case Reports

PMID: 16886937 [PubMed - indexed for MEDLINE]

1102: Cephalalgia. 2006 Aug;26(8):968-72.

Abnormal platelet trace amine profiles in migraine with and without aura.

D'Andrea G, Granella F, Leone M, Perini F, Farruggio A, Bussone G.

Headache Centre, Villa Margherita Hospital, Arcugnano (VI), Italy.

Trace amines, including tyramine, octopamine and synephrine, are closely related 
to classic biogenic amines. In one study, where these substances were found
elevated in plasma of migraineurs, it was hypothesized that trace amine
metabolism is deranged in migraine. To confirm these findings, we studied, using 
a multichannel electrochemical high-performance liquid chromatography system, the
concentrations of trace amines in platelets of migraine without aura (MoA) and
migraine with aura (MA) patients in headache-free period, compared with controls.
Platelet concentrations of trace amines, although elevated in both migraine
types, showed a different profile in MoA and MA. Octopamine was significantly
higher in MoA sufferers (0.69 +/- 0.43 ng/10(8) platelets) compared with both
control subjects (0.22 +/- 0.16 ng/10(8) platelets) and MA patients (0.39 +/-
0.37 ng/10(8) platelets). Synephrine was significantly higher in MA patients
(0.72 +/- 0.44 ng/10(8) platelets) with respect to both controls (0.33 +/- 0.25
ng/10(8) platelets) and MoA sufferers (0.37 +/- 0.29 ng/10(8) platelets). These
results strengthen the hypothesis that tyrosine metabolism is deranged in
migraine and may participate in its pathophysiology.

Publication Types: 
    Controlled Clinical Trial

PMID: 16886933 [PubMed - indexed for MEDLINE]

1103: Cephalalgia. 2006 Aug;26(8):960-7.

Sick leave is related to frequencies of migraine and non-migrainous headache--The
HUNT Study.

Fiane I, Haugland ME, Stovner LJ, Zwart JA, Bovim G, Hagen K.

Department of Clinical Neuroscience, Section of Neurology, Norwegian University
of Science and Technology, Trondheim, Norway.

The aim of this large, cross-sectional, population-based study was to examine the
association between sick leave and headache. Between 1995 and 1997, all 92 566
adults in Nord-Trøndelag County in Norway were invited to participate in a health
survey. Out of 73 327 invited individuals <67 years old, a total of 38 192 (52%) 
responded to questions about headache, work situation and sick leave during the
past year. Associations between sick leave, headache and migraine included were
assessed in multivariate analyses, estimating prevalence odds ratios (ORs) with
95% confidence intervals (CIs). There was an increasing prevalence of sick leave 
with increasing frequency of migraine and non-migrainous headache. The prevalence
of sick leave >8 weeks during the past year was more than three times higher
among individuals with headache >14 days per month (20%) compared with those
without headache (6%). The results may indicate that better treatment of
individuals with chronic headache may have beneficial economic implications.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16886932 [PubMed - indexed for MEDLINE]

1104: Cephalalgia. 2006 Aug;26(8):949-59.

Do migraineurs have difficulty judging direction of simulated heading?

McKendrick AM, Turpin A, Webb S, Badcock DR.

School of Psychology, University of Western Australia, Crawley.
allisonw@unimelb.edu.au

Some migraineurs have increased thresholds for the detection of global dot
motion. We investigated whether migraineurs show consequential abnormalities in
the determination of direction of self-motion (heading) from simulated optic
flow. The ability to determine heading from optic flow is likely to be necessary 
for optimal determination of self-motion through the environment. Twenty-five
migraineurs and 25 controls participated. Global dot motion coherence thresholds 
were assessed, in addition to performance on two simulated heading tasks: one
with a symmetrical flow field, and the second with differing velocity of optic
flow on the left and right sides of the participant. While some migraineurs
demonstrated abnormal global motion coherence thresholds, there was no difference
in performance on the heading tasks at either simulated walking (5 km/h) or
driving (50 km/h) speeds. Increased global motion coherence thresholds in
migraineurs do not result in abnormal judgements of heading from 100% coherent
optic flow.

Publication Types: 
    Controlled Clinical Trial
    Research Support, Non-U.S. Gov't

PMID: 16886931 [PubMed - indexed for MEDLINE]

1105: Cephalalgia. 2006 Aug;26(8):934-9.

Prevalence of patent foramen ovale in migraine patients with and without aura
compared with stroke patients. A transcranial Doppler study.

Carod-Artal FJ, da Silveira Ribeiro L, Braga H, Kummer W, Mesquita HM, Vargas AP.

Department of Neurology, The Sarah Network of Rehabilitation Hospitals, Sarah
Hospital, Brazilia DF, Brazil.

The aim of this study was to investigate the prevalence of patent foramen ovale
(PFO) in a consecutive unselected cohort of migraine patients (with and without
aura) and compare it with a group of ischaemic young and elderly stroke patients.
One hundred and forty-one migraine patients were compared with 330 stroke
patients (130 young patients; 200 elderly patients) selected from our hospital
stroke data bank. PFO was assessed with transcranial Doppler sonography with i.v.
injection of agitated saline. The prevalence of PFO was 51.7% in migraine with
aura (MA) patients, 33.7% in migraine without aura (MoA) patients, 33.8% in young
stroke patients and 20.5% in elderly stroke patients (P < 0.001). The prevalence 
of PFO in cryptogenic stroke in young and elderly stroke patients was,
respectively, 41.1% and 25% (P = 0.04). The difference between MA and MoA
patients was significant (odds ratio = 2.1). The prevalence of PFO in MA patients
is higher than in MoA patients and in young cryptogenic stroke patients.

Publication Types: 
    Comparative Study
    Controlled Clinical Trial

PMID: 16886929 [PubMed - indexed for MEDLINE]

1106: Cephalalgia. 2006 Aug;26(8):925-33.

Dipyridamole may induce migraine in patients with migraine without aura.

Kruuse C, Lassen LH, Iversen HK, Oestergaard S, Olesen J.

Danish Headache Centre and Department of Neurology, University of Copenhagen,
Glostrup Hospital, Denmark.

Dipyridamole inhibits phosphodiesterase 5 (PDE5) and adenosine re-uptake. The
most prominent side-effect is headache. We examined the migraine-generating
effects of dipyridamole as well as the cerebral blood velocity response in a
single-blind study, including 10 patients with migraine without aura and 10
healthy subjects. Dipyridamole 0.142 mg/kg per min was administered
intravenously. Headache intensity was scored on a verbal rating scale along with 
pain characteristics and accompanying symptoms. Blood velocity in the middle
cerebral artery (V(mca)), blood pressure and heart rate were recorded repeatedly.
Headache was induced in all migraine patients and in eight of 10 healthy subjects
(P = 0.47) with no significant difference in headache intensity (P = 0.53).
However, five patients but only one healthy subject experienced the symptoms of
migraine without aura, according to ICHD-2 criteria, within 12 h (P = 0.14). Four
patients reported photophobia after dipyridamole compared with no healthy
subjects (P = 0.087). V(mca) decreased (P < 0.001) during and after dipyridamole 
infusion with no difference between groups (P = 0.15) coinciding with initiation,
but not cessation of immediate headache. Thus, dipyridamole induces symptoms of
migraine and an initial decrease in V(mca) in migraine patients, but not
significantly more than in healthy subjects. This relatively low frequency of
migraine induction, compared with nitric oxide donors and sildenafil, is probably
due to the less specific action of dipyridamole on the cGMP signalling pathway as
well as a possible bidirectional effect of adenosine on migraine induction.

Publication Types: 
    Controlled Clinical Trial
    Research Support, Non-U.S. Gov't

PMID: 16886928 [PubMed - indexed for MEDLINE]

1107: Cephalalgia. 2006 Aug;26(8):920-4.

Comment in:
    Cephalalgia. 2007 Feb;27(2):190; author reply 190.

The impact of different antimigraine compounds on platelet and erythrocyte
aggregation.

Evers S, Heuel T, Frese A, Akova-Oztürk E, Husstedt IW.

Department of Neurology, University of Münster, Germany. everss@uni-muenster.de

Clinical and experimental data suggest that ergotamine compounds and triptans may
contribute to vascular events such as myocardial infarction and stroke. The role 
of blood cell aggregation in this context is, however, not clarified. We aimed to
evaluate the impact of different acute antimigraine compounds on platelet and
erythrocyte aggregation in a human ex vivo experimental design. In 20 healthy
subjects without migraine and in 20 healthy subjects with migraine without aura, 
platelet and erythrocyte aggregation were measured before and after intake of
placebo, acetylsalicylic acid, ergotamine tartrate, zolmitriptan and sumatriptan.
Platelet aggregation was measured by the so-called platelet reactivity index.
Erythrocyte aggregation was measured by photometric assessment in an
aggregometer. Ergotamine tartrate induced a significant increase of platelet
aggregation, whereas acetylsalicylic acid induced a significant decrease in both 
subject groups. After placebo, after sumatriptan and after zolmitriptan, no
significant changes of platelet aggregation were noted. Erythrocyte aggregation
was affected by neither compound. We can conclude that platelet aggregation, but 
not erythrocyte aggregation, is increased after intake of ergotamine tartrate.
This may in part contribute to vascular side-effects of this compound.
Acetylsalicylic acid and the triptans appeared to be safe with respect to
platelet and erythrocyte aggregation.

Publication Types: 
    Comparative Study
    Controlled Clinical Trial

PMID: 16886927 [PubMed - indexed for MEDLINE]

1108: Cephalalgia. 2006 Aug;26(8):917-9.

Side-shifting hemicrania continua with aura (migraine with aura with autonomic
symptoms responsive to indomethacin?).

Peres MF, Masruha MR, Young WB.

Instituto Israelita de Ensino e Pesquisa Albert Einstein, São Paulo, Brazil.
marioperes@yahoo.com

Atypical features of hemicrania continua (HC), including both visual aura and
side shifting, have been reported previously. However, auras and variable
unilaterality have never been reported together in HC. We report two patients
with side-shifting HC with aura. These patients' symptoms are unilateral
headaches, visual aura, autonomic features, throbbing pain, nausea and
photo/phonophobia. One could speculate that the unilaterality and/or the
autonomic symptom modules are indomethacin responsive. The patients can also be
classified as chronic migraine with aura, with autonomic symptoms, responsive to 
indomethacin. Neither migraine subtype nor side-shifting HC with aura is included
in the current International Headache Society (IHS) classification, so these
patients are not classifiable. Side-shifting HC with aura implies the need to
revisit the traditional IHS categorization of headaches into unique diagnostic
groups. The modular headache theory may be a tool for the understanding of these 
rare and complex cases.

Publication Types: 
    Case Reports

PMID: 16886926 [PubMed - indexed for MEDLINE]

1109: Cephalalgia. 2006 Aug;26(8):905-16.

Diaries and calendars for migraine. A review.

Nappi G, Jensen R, Nappi RE, Sances G, Torelli P, Olesen J.

University Centre for Adaptive Disorders and Headache (UCADH), IRCCS C. Mondino
Foundation Institute of Neurology, Pavia, Italy.

Headache is one of the most common types of pain and, in the absence of
biological markers, headache diagnosis depends only on information obtained from 
clinical interviews and physical and neurological examinations. Headache diaries 
make it possible to record prospectively the characteristics of every attack and 
the use of headache calendars is indicated for evaluating the time pattern of
headache, identifying aggravating factors and evaluating the efficacy of
preventive treatment. This may reduce the recall bias and increase accuracy in
the description. The use of diagnostic headache diaries does have some
limitations because the patient's general acceptance is still limited and some
subjects are not able to fill in a diary. In this review, we considered diaries
and calendars especially designed for migraine and, in particular, we aimed at:
(i) determining what instruments are available in clinical practice for diagnosis
and follow-up of treatments; and (ii) describing the tools that have been
developed for research and their main applications in the headache field. In
addition to the literature review, we added two paragraphs concerning the
authors' experience of the use of diaries and calendars in headache centres and
their proposals for future areas of research.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 16886925 [PubMed - indexed for MEDLINE]

1110: Pediatrics. 2006 Aug;118(2):704-9.

Mimics of childhood stroke: characteristics of a prospective cohort.

Shellhaas RA, Smith SE, O'Tool E, Licht DJ, Ichord RN.

Division of Neurology, Wood 6th Floor, Children's Hospital of Philadelphia,
University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, 
USA.

BACKGROUND: Little is known about the clinical features and spectrum of diagnoses
in children with "stroke mimics," those with acute neurologic deficits but
without cerebrovascular diseases. OBJECTIVES: Our goal was to describe patients
with stroke mimics and to determine if clinical features predict benign
diagnoses. METHODS: Our stroke consult team registered a prospective consecutive 
cohort of 143 patients with acute presentations suspicious for cerebrovascular
disease from November 2003 to November 2004. Cases in which stroke was ruled out 
(stroke mimics) were reviewed for clinical features and diagnostic test results
and were classified "benign" if there was no structural brain lesion and there
was an expectation of complete recovery. RESULTS: Of the 143 cases evaluated for 
suspected stroke, 30 (21%) had stroke mimics. Presenting signs included seizure
(n = 11), headache (n = 9), mental status change (n = 6), focal weakness (n =
14), and focal sensory change (n = 7). Eleven patients had "benign" diagnoses (3 
migraine, 3 psychogenic diagnoses, 3 musculoskeletal abnormalities, 1 delirium,
and 1 episodic vital sign changes). Nineteen patients had "not-benign" diagnoses 
(3 reversible posterior leukoencephalopathy syndrome, 3 neonatal seizures, 2
vascular anomalies, 2 inflammatory disease, 2 intracranial infection, 2 epilepsy,
2 metabolic stroke, 1 tumor, 1 drug toxicity, and 1 idiopathic intracranial
hypertension). Except for the presence of seizures, there were no significant
differences in presentation or risk factors between benign and not-benign cases. 
CONCLUSIONS: Many disorders mimic childhood stroke. History and clinical
presentation often do not distinguish the one third of patients with benign
disorders from the two thirds with more serious problems, necessitating timely
comprehensive investigations, especially brain MRI.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16882826 [PubMed - indexed for MEDLINE]

1111: J Formos Med Assoc. 2006 Jul;105(7):563-8.

Validity, reliability and application of the taiwan version of the migraine
disability assessment questionnaire.

Hung PH, Fuh JL, Wang SJ.

The Neurological Institute, Taipei Veterans General Hospital and Department of
Neurology, National Yang-Ming University School of Medicine, Taipei, Taiwan.

BACKGROUND/PURPOSE: The seven-item Migraine Disability Assessment (MIDAS)
questionnaire is a simple and useful tool for evaluating migraine-related
disability. The goals of this study were: (1) to test the reliability and
validity of the Taiwan version of the MIDAS (MIDAS-T) questionnaire, and (2) to
measure the impact of migraine among Taiwanese patients in a headache clinic.
METHODS: Consecutive migraine patients, aged 20-50 years, visiting the headache
clinic at the Taipei Veterans General Hospital were invited to participate in the
study. They completed the MIDAS-T and a form, which collected headache-related
information including characteristics and impact on their lives. Of them, about
30 patients were randomly invited to repeat the MIDAS-T 3 weeks later. RESULTS: A
total of 281 migraine patients (M/F, 63/218; mean age, 35.27 +/- 8.21 years)
participated in the study. Of them, 31 completed the MIDAS-T again 3 weeks later.
MIDAS-T showed acceptable internal consistency (Cronbach alpha = 0.79),
test-retest reliability (r = 0.67) and criterion validity (r = 0.37 for question 
A [headache frequency] and r = 0.34 for question B [headache intensity], p <
0.001). The mean score of migraine patients on MIDAS-T was 34.21 +/- 45.90,
ranging from 0 to 265. MIDAS grade I (score 0-5) was found in 22% of patients,
grade II (6-10) in 15%, grade III (11-20) in 17%, and grade IV (>or=21) in 46%.
CONCLUSION: This study supports the reliability and validity of MIDAS-T for use
in Taiwanese patients. Almost half of the migraine patients were classified as
having severe disability (grade IV).

Publication Types: 
    Research Support, Non-U.S. Gov't
    Validation Studies

PMID: 16877236 [PubMed - indexed for MEDLINE]

1112: Pediatr Neurol. 2006 Aug;35(2):119-21.

Activity levels among adolescents with migraine.

Dooley JM, Gordon KE, Wood EP, Brna PM.

Pediatric Neurology Division, Dalhousie University and the IWK Health Centre,
Halifax, Nova Scotia, Canada. jdooley@dal.ca

Data was analyzed from the nationally representative Canadian Community Health
Survey. A total of 17,549 adolescents reported whether they had "migraine
headaches" (response rate 99.9%) and in what exercise activities they
participated. Those with migraine reported more daily activity than migraine-free
peers when corrected for age and sex. They were as likely to play contact sports 
but were more involved in other noncompetitive activities, such as walking
(P<0.001), gardening and yard work (P=0.008), jogging and running (P=0.002), and 
fishing (P=0.03). Canadian adolescents with migraine are therefore overall more
active than their peers without migraine.

PMID: 16876008 [PubMed - indexed for MEDLINE]

1113: Neurobiol Dis. 2006 Sep;23(3):491-501. Epub 2006 Jul 26.

Serotonin receptors modulate trigeminovascular responses in ventroposteromedial
nucleus of thalamus: a migraine target?

Shields KG, Goadsby PJ.

Headache Group, Institute of Neurology, London, UK.

Triptans, serotonin 5-HT(1B/1D), receptor agonists, which are so effective in
acute migraine, are considered to act directly on the trigeminovascular system.
Using an in vivo model of trigeminovascular nociception, we report a potentially 
novel action for the triptans within the somatosensory thalamus. Both
microiontophoretically applied and intravenous naratriptans potently and
reversibly modulate nociceptive neurotransmission by trigeminovascular thalamic
neurons in the ventroposteromedial nucleus (VPM) driven by stimulation of the
superior sagittal sinus. Naratriptan also suppresses l-glutamate activated
trigeminovascular VPM neurons. Co-ejection of naratriptan with the 5-HT(1B/1D)
receptor antagonist GR127935 antagonized this effect. (S)-WAY 100135 the 5-HT(1A)
receptor antagonist also partially inhibited the effect of naratriptan in the VPM
when co-ejected with it. Taken together, the new data suggest a potential effect 
of triptans in the VPM nucleus of the thalamus acting through 5-HT(1A/1B/1D)
mechanisms, and offer an entirely new direction for the development of and
understanding of the effects of anti-migraine medicines.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16875831 [PubMed - indexed for MEDLINE]

1114: Drugs Aging. 2006;23(6):461-89.

Practical considerations for the treatment of elderly patients with migraine.

Sarchielli P, Mancini ML, Calabresi P.

Department of Medical and Surgical Specialties and Public Health, Neurologic
Clinic, University of Perugia, Perugia, Italy. headache@unipg.it

Treatment of migraine presents special problems in the elderly. Co-morbid
diseases may prohibit the use of some medications. Moreover, even when these
contraindications do not exist, older patients are more likely than younger ones 
to develop adverse events. Managing older migraine patients, therefore,
necessitates particular caution, including taking into account possible
pharmacological interactions associated with the greater use of drugs for
concomitant diseases in the elderly. Paracetamol (acetaminophen) is the safest
drug for symptomatic treatment of migraine in the elderly. Use of selective
serotonin 5-HT(1B/1D) receptor agonists ('triptans') is not recommended, even in 
the absence of cardiovascular or cerebrovascular risk, and NSAID use should be
limited because of potential gastrointestinal adverse effects. Prophylactic
treatments include antidepressants, beta-adrenoceptor antagonists, calcium
channel antagonists and antiepileptics. Selection of a drug from one of these
classes should be dictated by the patient's co-morbidities. Beta-adrenoceptor
antagonists are appropriate in patients with hypertension but are contraindicated
in those with chronic obstructive pulmonary disease, diabetes mellitus, heart
failure and peripheral vascular disease. Use of antidepressants in low doses is, 
in general, well tolerated by elderly people and as effective, overall, as in
young adults. This approach is preferred in patients with concomitant mood
disorders. However, prostatism, glaucoma and heart disease make the use of
tricyclic antidepressants more difficult. Fewer efficacy data in the elderly are 
available for selective serotonin reuptake inhibitors, which can be tried in
particular cases because of their good tolerability profile. Calcium channel
antagonists are contraindicated in patients with hypotension, heart failure,
atrioventricular block, Parkinson's disease or depression (flunarizine), and in
those taking beta-adrenoceptor antagonists and monoamine oxidase inhibitors
(verapamil). Antiepileptic drug use should be limited to migraine with high
frequency of attacks and refractoriness to other treatments. Promising additional
strategies include ACE inhibitors and angiotensin II type 1 receptor antagonists 
because of their effectiveness and good tolerability in patients with migraine,
particularly in those with hypertension. Because of its favourable compliance and
safety profile, botulinum toxin type A can be considered an alternative treatment
in elderly migraine patients who have not responded to other currently available 
migraine prophylactic agents. Pharmacological treatment of migraine poses special
problems in regard to both symptomatic and prophylactic treatment.
Contraindications to triptan use, adverse effects of NSAIDs, and unwanted
reactions to some antiemetics reduce the list of drugs available for the
treatment of migraine attacks in elderly patients. The choice of prophylactic
treatment (beta-adrenoceptor antagonists, calcium channel antagonists,
antiepileptics, and more recently, some antihypertensive drugs) is influenced by 
co-morbidities and should be directed at those drugs that are believed to have
fewer adverse effects and a better safety profile. Unfortunately, for most of
these drugs, efficacy studies are lacking in the elderly.

Publication Types: 
    Review

PMID: 16872231 [PubMed - indexed for MEDLINE]

1115: Curr Med Res Opin. 2006 Aug;22(8):1535-44.

Prevalence of migraine and response to sumatriptan in patients self-reporting
tension/stress headache.

Kaniecki R, Ruoff G, Smith T, Barrett PS, Ames MH, Byrd S, Kori S.

University of Pittsburgh Headache Center, 120 Lytton Avenue, Pittsburgh, PA
15213, USA. kanieckirg@upmc.edu

OBJECTIVE: This study was conducted to evaluate the prevalence of migraine and
its responsiveness to migraine-specific therapy in patients with self-reported
tension-type headache. METHODS: Patients were adults (n = 423) consulting one of 
54 North American study sites including primary care clinics, neurology clinics, 
and headache clinics. The study comprised an initial diagnosis phase to determine
the headache diagnosis of patients entering the study with self-reported
tension/stress headache, including that previously diagnosed by a health care
provider. Patients reporting tension/stress headache were evaluated and diagnosed
as having migraine with or without aura, probable migraine, tension-type
headache, or another headache type. Exclusion criteria included prior diagnosis
of migraine or probable migraine and the presence of headache for at least 15
days monthly during either of the 2 months before screening. The initial phase
was followed by a randomized, double-blind treatment phase to evaluate the
efficacy of sumatriptan 100 mg tablets for the treatment of a single migraine
attack in those meeting International Headache Society (IHS) criteria for
migraine during the diagnosis phase. RESULTS: Of 423 patients reporting
tension/stress headache at study entry, 84% (n = 357) were diagnosed at the
clinic visit as fulfilling IHS criteria for migraine without aura or migraine
with aura, and 65% (n = 276) were diagnosed with migraine only (i.e., with no
other concurrent headache diagnosis). Three hundred thirty-two (332) patients
entered the double-blind treatment phase. Headache relief rates 2h post-dose, the
primary efficacy endpoint, did not significantly differ between sumatriptan and
placebo (p = 0.099). However, improvements were significantly (p < 0.05) greater 
with sumatriptan than placebo on several other headache-related efficacy
measures. CONCLUSIONS: Migraine headache may go unrecognized in patients with
self-reported tension headache. Among patients having self-reported tension
headache and diagnosed with migraine during the study, response to acute
treatment with sumatriptan was inconclusive. Improvement with sumatriptan versus 
placebo was observed for some measures and not for others. The results should be 
interpreted in the context of study limitations including use of patient
self-reports to assess headache diagnosis and possible lack of representativeness
arising from the predominantly white sample.

Publication Types: 
    Multicenter Study
    Randomized Controlled Trial

PMID: 16870078 [PubMed - indexed for MEDLINE]

1116: Otol Neurotol. 2006 Aug;27(5):713-5.

New surgical approach for migraine.

Fan Z, Fan Z, Wang H.

Department of Otolaryngology-Head and Neck Surgery, Shandong Provincial Hospital,
Jinan, Shandong, PR China.

OBJECTIVE: To introduce a new procedure for the treatment of intractable cases of
migraine. STUDY DESIGN: To eliminate the excessive vascular and nervous effect by
ligation of superficial temporal artery and middle meningeal artery and severance
of greater superficial petrosal nerve. RESULTS: A total of 10 patients with cases
of severe migraine underwent the surgery. A follow-up of 2 to 18 years showed no 
recurrences. Among the patients, three were living and well for more than 10
years. CONCLUSION: With an extradural approach, the procedure is relatively safe 
and simple. It stands as a good alternative for the treatment of intractable
cases of migraine.

Publication Types: 
    Case Reports

PMID: 16868520 [PubMed - indexed for MEDLINE]

1117: Acta Neurol Scand. 2006 Aug;114(2):71-83.

Migraine: a review and future directions for treatment.

Linde M.

Cephalea Headache Centre and Institute of Neuroscience and Physiology,
Sahlgrenska Academy, Göteborg University, Gothenburg, Sweden.
mattias.linde@neuro.gu.se

Migraine is a chronic, neurological disorder generally manifesting itself in
attacks with severe headache, nausea and an increased reactivity to sensory
stimuli. A low migraine threshold is set by genetic factors, although the
phenotype also modulates the manifestations. The 1-year prevalence is
approximately 13% and is higher among women. Patients usually experience
neuropsychological dysfunction, and sometimes also reversible focal neurological 
symptoms. The trajectories of the characteristic symptoms of acute migraine
usually follow a similar time course, indicating a reciprocal underlying
mechanism. A central nervous system hyperexcitability has been demonstrated in
neurophysiological studies. The dibilitating effects of migraine are not confined
to the attacks per se. Many individuals do not recover completely between the
attacks and most report a negative impact on the most important life domains, and
an interest in testing other treatments. Young persons have a higher frequency of
attacks. Acute treatment should routinely be initiated with an analgesic plus a
prokinetic anti-emetic. Triptans must not be provided early during the attack to 
ensure their efficacy. The natural course of attacks is commonly only temporarily
altered by acute treatment. Non-pharmacological treatment and drugs may be
equally viable in prophylaxis for migraine. In more complicated cases, conjoint
therapy should be considered. New strategies to improve adherence with existing
therapeutic regimens might yield greater benefits than will new pharmacological
agents.

Publication Types: 
    Review

PMID: 16867028 [PubMed - indexed for MEDLINE]

1118: Headache. 2006 Jul-Aug;46(7):1191-4.

Cerebral vasoreactivity is influenced by the prandial state among migraineurs.

Coelho Rde S, Gomes CM, Teixeira RA.

Universidade Católica de Brasília, Brasilia, Distrito Federal, Brazil.

OBJECTIVE: To test if the cerebral vasoreactivity among migraineurs is influenced
by the prandial state. DESIGN AND METHODS: Eight patients with migraine without
aura were studied (mean age = 23.75 years; range = 19 to 32 years; 6 women). We
also studied 8 healthy controls (mean age = 20.63 years; range = 18 to 22 years; 
3 women), with no history of migraine. Cerebral vasoreactivity was measured on
the right side by the breath holding index (BHI) using an EZ-Dop transcranial
Doppler instrument, with a 2-MHz transducer fitted on a headband. Serum glucose
levels were measured after a 10-hour fasting period and then 10 minutes after a
standardized breakfast. RESULTS: In both groups, we found a postprandial (PP)
glycemia enhancement (P < .02). Migraineurs showed enhanced PP cerebral
vasoreactivity when compared to the fasting state (FS) (BHI-PP = 1.46; BHI-FS =
1.16; P= .02). Among controls, we found a trade to enhancement, but without
statistic significance (BHI-PP = 1.28; BHI-FS = 1.11; P= .30). Glucose levels
were not significantly correlated to cerebral vasoreactivity in any of the groups
(P > .05). CONCLUSION: Our findings suggest that migraineurs have a higher
reactivity to hypercapnia during the PP period.

Publication Types: 
    Comparative Study

PMID: 16866724 [PubMed - indexed for MEDLINE]

1119: Headache. 2006 Jul-Aug;46(7):1186-90.

From transformed migraine to episodic migraine: reversion factors.

Seok JI, Cho HI, Chung CS.

Samsung Medical Center, Neurology, Seoul, Republic of Korea.

OBJECTIVE: To identify the factors contributing to the reversion of transformed
migraine (TM) into episodic migraine. BACKGROUND: TM, the most common and
important subtype of chronic daily headache (CDH), has a great effect on a
patient's quality of life. However, its clinical course and outcome predictors
have rarely been studied prospectively. METHOD: Of 1142 consecutive headache
patients seen at the Headache Clinic of the Samsung Medical Center, the patients 
with TM (frequency >15/month for >6 months and a history of migraine meeting the 
ICHD-II diagnostic criteria) were followed for at least 1 year. We analyzed the
demographic data, clinical course, and compliance factors, such as those of the
physician's management protocol and recommended lifestyle modification. RESULTS: 
A total of 136 patients finished the final follow-up assessment 1 year after the 
initial evaluation. Ninety-five patients (70%) converted from TM to episodic
migraine. Forty-one patients (30%) continued to suffer daily headaches without a 
period of improvement. The demographic and clinical information collected before 
the treatment was not significantly related to outcome, except for chronic use of
analgesics for other medical conditions (P= .01). Of the compliance factors, good
compliance with preventive medication (P < .001), withdrawal from continuous use 
of analgesics for headache relief (P < .001), and regular exercise (P= .04) were 
significant positive contributors to the reversion of TM into episodic migraine. 
CONCLUSION: Compliance factors are the most important factors that determine the 
reversion of TM into episodic migraine.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16866723 [PubMed - indexed for MEDLINE]

1120: Headache. 2006 Jul-Aug;46(7):1161-71.

Migraine changes with age: IMPACT on migraine classification.

Kelman L.

Headache Center of Atlanta, 5671 Peachtree Dunwoody Road, Suite 620, Atlanta, GA 
30342, USA.

OBJECTIVE: To establish if criteria for the diagnosis of migraine change with age
and to document the influence of age on the full spectrum of migraine features.
Also to define the clinical spectrum and provide a prognostic profile of migraine
stratified by age. BACKGROUND: Few studies have formally analyzed migraine
characteristics stratified by age in a large cohort of patients. METHODS: One
thousand nine consecutive patients meeting ICHD-2, 1.1, 1.2, and 1.5.1 at their
initial office visit were studied. Patients were stratified by age into 3 groups:
group I, 16 to 29, group II, 30 to 49, and group III, 50 years or older.
Variables studied included gender, headache duration in years, prodrome, aura,
postdrome, headache triggers, headache characteristics, associated symptoms,
headache location, headache frequency, headache days, and disability. Ordinal
variables were graded from 0 to 3 but only grades greater than grade 1 (more than
occasional) were used in the study. RESULTS: A total of 86.3% patients were
female and mean age was 37.7 years +/- 11.7 years (range 16 to 80), headache
duration 15.0 years, and headache frequency 10 headaches per month. STUDY
RESULTS: No significant age differences were seen in gender, or frequency of
prodrome, aura, or postdrome. In patients with aura the percentage of headaches
with aura significantly decreased with age. Headache triggers, in general, showed
no age differences; specific triggers showed statistical differences: stress as a
trigger decreased with age; alcohol, smoke, and neck pain triggers increased with
age, while in women hormones as a trigger peaked markedly in the 30- to
49-year-old age group compared with the other ages. Exercise, food, not eating,
heat, lights, perfume, sex, sleep disturbance, sleeping late, and weather
triggers showed no significant differences in age. Headache location showed no
differences except for neck location, which significantly increased with age.
Associated symptoms of photophobia, phonophobia, dizziness decreased with age and
running of the nose/tearing of the eyes increased with age. Nausea, vomiting,
osmophobia, taste abnormalities, and diarrhea showed no significant differences. 
Headache quality showed decreasing throbbing, pressure, and stabbing with age,
but aching showed no statistical difference. Being forced to sleep or rest with
headache showed a significant decrease with age, but no significant differences
were seen in other acute migraine characteristics, including choose to sleep or
rest with headache, function during headache, average intensity and duration of
headache, recurrence rate of headache, headache aggravation by activity, response
to acute medication, and acute medication satisfaction. The 50+ age group tended 
to have less dizziness, photophobia, phonophobia, nausea, vomiting, temporal
location, throbbing, pressure, stabbing, headache days, moderate days, severe
days, aggravation of headache by activity, and recurrence but tended to have more
mild days, greater ability to function during headache, and greatest response to 
acute medication. Despite no difference from other groups in headache intensity
and duration of headache, these findings taken together seem to reflect a "lesser
migraine" in the 50+ age group. CONCLUSIONS: This study highlights specific age
differences in migraineurs, in most instances showing an age decline in frequency
of variables, such as stress as a trigger, photophobia, phonophobia, dizziness,
throbbing, pressure, stabbing, and being forced to sleep or rest with headache.
Hormones as a trigger peaked in women in the 30- to 49-year-old age group.
Increases with age were seen with alcohol, smoke, and neck pain triggers, neck
location, and running of the nose/tearing of the eyes. The 50+ age group showed
trends suggesting a "lesser acute migraine attack." These findings support the
concept of lessening features of migraine over time resulting in a lower
prevalence of migraine in older patients.

PMID: 16866720 [PubMed - indexed for MEDLINE]

1121: Headache. 2006 Jul-Aug;46(7):1151-60.

Long-term migraine prevention with topiramate: open-label extension of pivotal
trials.

Rapoport A, Mauskop A, Diener HC, Schwalen S, Pfeil J.

The New England Center for Headache, PC, Stamford, CT 06902, USA.

OBJECTIVE: To demonstrate that topiramate is an effective and generally
well-tolerated migraine preventive therapy when used for up to 14 months.
BACKGROUND: Topiramate 100 and 200 mg/d significantly reduced mean monthly
migraine frequency during 2 large, 26-week, randomized, placebo-controlled
trials. Only a small number of clinical trials have examined the long-term (> or 
=1 year) effectiveness and safety of migraine preventive therapies. METHODS: Five
hundred sixty-seven patients with an established history of migraine with or
without aura were enrolled in this 8-month, open-label extension of 2 large (49
US and 52 US and Canadian medical centers), randomized, double-blind,
placebo-controlled, parallel group, 26-week trials of identical design. To be
eligible for the open-label extension, patients were required to have either
completed the double-blind phase of the 2 pivotal migraine prevention trials or
withdrew after 4 weeks due to lack of efficacy. All eligible patients, regardless
of type or dose of study medication (topiramate or placebo) received in the
double-blind phase, were titrated to a clinically effective dose of open-label
topiramate based on physician judgment of patient response. Efficacy of
topiramate was measured as the change in mean monthly migraine frequency.
RESULTS: The mean topiramate dose during the open-label extension phase was 124.7
mg/d and 150.3 mg/d for patients on placebo (n = 159) or topiramate (n = 408),
respectively, during the double-blind phase (N = 567, 91% female, mean age 39.4
years). Patients on topiramate for up to 14 months had 2.2 +/- 2.4 (mean +/- SD) 
migraines per month after completion of the open-label extension phase (3.4 +/-
2.6 at double-blind endpoint). Patients on topiramate during the open-label
extension phase only (placebo during the double-blind phase) had 3.0 +/- 2.9
migraines per month at open-label extension endpoint (4.9 +/- 3.0 migraines per
month at double-blind endpoint). Discontinuation rates due to adverse events
during the double-blind phase were 22.2% for patients on topiramate and 11.0% for
patients on placebo. Discontinuation rates due to adverse events during the
open-label extension phase were 8.6% for those patients who had already received 
topiramate during the double-blind phase and 20.9% for those patients who had
previously received placebo. CONCLUSIONS: Patients receiving topiramate
experienced a sustained reduction in migraine frequency for up to 14 months. The 
effectiveness and safety of topiramate was consistent with that observed during 2
26-week pivotal trials.

Publication Types: 
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 16866719 [PubMed - indexed for MEDLINE]

1122: Headache. 2006 Jul-Aug;46(7):1142-50.

Comment in:
    Headache. 2007 Mar;47(3):452; author reply 452-3.

Eletriptan in migraine patients reporting unsatisfactory response to rizatriptan.

Goldstein J, Tiseo PT, Albert KS, Li C, Sikes CR.

San Francisco Headache Clinic, 909 Hyde Street, Suite 322, San Francisco, CA
94109, USA.

OBJECTIVE: The objective of this open-label study was to evaluate the efficacy of
switching patients who had a previous unsatisfactory response to rizatriptan to
eletriptan 40 mg. Background.-The characteristics of individual migraine patients
can vary tremendously and can have a significant impact on treatment outcomes. In
addition, clinical experience has demonstrated that the triptans are not
identical or interchangeable and that patients who respond poorly or who are
dissatisfied with one agent can derive benefit by being switched to another agent
within the triptan class. METHODS: Patients were eligible if they met
International Headache Society criteria for migraine, with a frequency of 1 to 6 
migraine attacks per month, and had documented "unsatisfactory treatment
response" to rizatriptan within the past year (54% on the melt formulation; 46%
on tablets). Reasons for dissatisfaction with rizatriptan (>1 could be cited)
included inadequate (84%) or slow onset (50%) of pain relief, high recurrence
rate (69%), and lack of improvement in associated symptoms (60%). One hundred
twenty-three patients were eligible for treatment. Patients were instructed to
take eletriptan 40 mg as soon as they were certain that their headache was a
migraine, regardless of level of pain severity (8% treated headaches that were
mild). RESULTS: Headache response at 2 hours (first-attack data) was 64%. Absence
of nausea (from baseline to 2 hours) increased from 50% to 78%, absence of
photophobia from 30% to 72%, and absence of phonophobia from 39% to 77%.
Functional response at 2 hours was 63%, with 41% of patients reporting normal
functioning. Treatment with eletriptan 40 mg was associated with a 27% to 40%
reduction in migraine attack-related functional impairment, as measured by the
PQ-7. Recurrence rates were 36.6%. Overall, 72% of patients rated eletriptan as a
"good-to-excellent" treatment, and 78% reported overall satisfaction with the
degree of headache relief. CONCLUSION: The results of this study suggest that
eletriptan is an efficacious treatment option for patients who are dissatisfied
with their response to rizatriptan.

Publication Types: 
    Clinical Trial
    Multicenter Study
    Research Support, Non-U.S. Gov't

PMID: 16866718 [PubMed - indexed for MEDLINE]

1123: Headache. 2006 Jul-Aug;46(7):1136-41.

Migrainous vertigo: mutation analysis of the candidate genes CACNA1A, ATP1A2,
SCN1A, and CACNB4.

von Brevern M, Ta N, Shankar A, Wiste A, Siegel A, Radtke A, Sander T, Escayg A.

Department of Human Genetics, Emory University, Atlanta, Georgia 30322, USA.

BACKGROUND: Migrainous vertigo (MV) is increasingly recognized as a common cause 
of episodic vertigo. MV displays several clinical similarities with familial
hemiplegic migraine (FHM) and episodic ataxia type 2 (EA-2), which have been
linked to mutations in 3 genes, CACNA1A, encoding a neuronal calcium channel
alpha subunit, ATP1A2, encoding a catalytic subunit of a Na(+)/K(+)-ATPase, and
most recently the voltage-gated sodium channel SCN1A. The present study explored 
the hypothesis that mutations in CACNA1A, ATP1A2, SCN1A, and the calcium channel 
beta(4) subunit CACNB4 confer susceptibility to MV. METHODS: Mutation analysis of
the coding exons and exon/intron junctions of CACNA1A, ATP1A2, SCN1A, and CACNB4 
was performed in 14 unrelated MV patients by conformation sensitive gel
electrophoresis and automated sequence analysis. RESULTS: Analysis of the 4
candidate genes in the 14 MV patients resulted in the identification of a total
of 26 sequence variants. The silent substitution D29D in CACNB4 was observed in 2
MV patients and was not present in 46 ethnically matched control DNA samples. The
remaining variants were also observed in control DNA samples and the allele
frequencies of variants that resulted in amino acid substitutions were not
significantly different between patients and controls. CONCLUSIONS: Based on this
group of patients there is no evidence that the genes causing FHM and EA-2
represent major susceptibility loci for MV.

PMID: 16866717 [PubMed - indexed for MEDLINE]

1124: Headache. 2006 Jul-Aug;46(7):1128-35.

Cerebrospinal fluid sodium increases in migraine.

Harrington MG, Fonteh AN, Cowan RP, Perrine K, Pogoda JM, Biringer RG, Hühmer AF.

Huntington Medical Research Institutes, Molecular Neurology, Pasadena, CA 91101, 
USA.

BACKGROUND: Pharmaceuticals with calcium- or sodium-channel-blocking activity
have proven useful for migraine prophylaxis, and calcium channel, sodium
transporter, and sodium channel gene mutations have been found in familial
hemiplegic migraine. However, it is not known whether calcium or sodium
homeostasis is altered in migraine. OBJECTIVE: To compare levels of sodium,
calcium, potassium, and magnesium in cerebrospinal fluid (CSF) and blood plasma
between migraineurs and controls. METHODS: We recruited 20 migraineurs without
aura and 11 controls prospectively, and studied migraineurs in sick (MH(+)) and
well (MH(-)) states. We collected lumbar CSF and venous blood plasma, quantified 
elements with ion-selective electrodes or colorimetry, and determined osmolality 
by depression of freezing point. We compared levels of Na(+), Ca(2+), K(+), and
Mg among and also within subjects who were studied in both MH(+) and MH(-)
states. RESULTS: Mean CSF Na(+) levels were increased by 3 mmol/L in MH(+)
compared with MH(-) and by 4 mmol/L compared to controls (P < 0.005). In 4
subjects who were sampled in both MH(+) and MH(-) states, mean CSF Na(+)
concentration increased by 2 mmol/L in the MH(+) state compared with the MH(-)
state (P < 0.05). Simultaneous plasma Na(+) levels did not differ among the 3
clinical groups, nor did osmolality, total Ca and Ca(2+), K(+), and total Mg
levels in CSF. CONCLUSIONS: Compared to both controls and the MH(-) state, CSF
Na(+) concentration increased in MH(+) independently from other clinical or
pharmacological fluctuations, CSF concentrations of Ca(2+), Mg, and K(+), and
blood plasma Na(+) levels. These results implicate a deviation of Na(+)
homeostasis in migraine. The modestly elevated extracellular Na(+) in MH(+) may
cause the neural changes that underlie clinical features of migraine.

Publication Types: 
    Comparative Study
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 16866716 [PubMed - indexed for MEDLINE]

1125: Headache. 2006 Jul-Aug;46(7):1095-107.

Erratum in:
    Headache. 2006 Nov-Dec;46(10):1597.

Imaging findings of migraine.

Cutrer FM, Black DF.

Division of Headache, Mayo Clinic, Rochester, MN 55905, USA.

Increasingly sophisticated neuroimaging techniques have allowed researchers to
begin to define functional and anatomical characteristics of migraine. This paper
reviews current knowledge and techniques employed. Assessing present-day
knowledge limitations it concludes that with parallel advances in the technology 
of imaging and the pathophysiologic understanding of migraine, a reliable
biomarker may be discovered in the future.

Publication Types: 
    Review

PMID: 16866714 [PubMed - indexed for MEDLINE]

1126: Headache. 2006 Jul-Aug;46(7):1088-94.

Neuronal signal substances as biomarkers of migraine.

Edvinsson L.

Department of Medicine, Clinical Sciences, University Hospital, S-221 85 Lund,
Sweden.

Of the sensory nervous system associated signal substances it is only calcitonin 
generelated peptide (CGRP) that is reliably associated with the degree of pain in
the acute attacks of primary headaches. The treatment with triptans alleviates
both the pain and the associated CGRP release, putatively via a presynaptic
effect on the sensory nerves. The studies of opoids and other sensory
neuropeptides are inconsistent and require further analysis. Initial positive
data on endothelin and its receptors have turned out negative. Nitric oxide
mechanisms are still debated both in terms of initiation of attacks and for the
treatment.

Publication Types: 
    Review

PMID: 16866713 [PubMed - indexed for MEDLINE]

1127: Headache. 2006 Jul-Aug;46(7):1069-74.

Physiological parameters as biomarkers of migraine.

Gantenbein AR, Sándor PS.

Headache and Pain Unit, Neurology Department, University Hospital Zurich, Zurich,
Switzerland.

We review physical signs and measurements from neurophysiological research, which
may be considered biomarkers of migraine. Most studies show that information
processing is abnormal in migraineurs. Studies of trigeminal nociception are in
line with a central sensitization during the attack. The best documented
abnormality is an interictal lack of habituation in migraineurs, with a
normalization during the headache state, which has been shown using evoked and
event-related potentials. Together with a diminished energy reserve found in
MR-spectroscopy studies, these results suggest a possible role of increased
energy consumption in attack generation. Importantly, to date, no
neurophysiological marker has a high enough sensitivity and specificity to point 
out the single migraine patient. Therefore, these biomarkers are to be understood
as tools for research and are not to be used for diagnostic purposes.

Publication Types: 
    Review

PMID: 16866711 [PubMed - indexed for MEDLINE]

1128: Headache. 2006 Jul-Aug;46(7):1059-68.

Genetic biomarkers for migraine.

De Vries B, Haan J, Frants RR, Van den Maagdenberg AM, Ferrari MD.

Department of Human Genetics, Leiden University Medical Centre, Leiden, The
Netherlands.

Biomarkers are physical signs or laboratory measurements that occur in
association with a pathological process and have putative diagnostic and/or
prognostic utility. In migraine, clinical, radiological, and biochemical
biomarkers might be helpful to improve diagnosis, get insight in pathophysiology,
and facilitate treatment choices. Genetic biomarkers are defined as genetic
variations (mutations or polymorphisms) that can predict disease susceptibility, 
disease outcome, or treatment response. As yet, only a few genetic biomarkers for
migraine are available. Mutations in 3 different genes responsible for familial
hemiplegic migraine, a monogenetic subtype of migraine with aura, and the MTHFR
C677T polymorphism in common forms of migraine are clear examples. Many positive 
findings from linkage studies and association studies in common forms of migraine
have not been replicated, and are therefore of less clinical use. In this review,
we will discuss genetic biomarkers in migraine.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 16866710 [PubMed - indexed for MEDLINE]

1129: Headache. 2006 Jul-Aug;46(7):1046-58.

Biomarkers in migraine: their promise, problems, and practical applications.

Loder E, Rizzoli P.

Harvard Medical School and the John R. Graham Headache Centre, Brigham and
Women's/Faulkner Hospital, Boston, MA, USA.

Biomarkers are physical signs or laboratory measurements that "occur in
association with a pathological process and have putative diagnostic and/or
prognostic utility." Biomarkers hold considerable promise for understanding and
intervening in the disease process of migraine. They may permit recognition of
individuals at risk of developing migraine, improve the timing, accuracy, and
precision of migraine diagnosis, and serve as indicators of treatment response
and disease progression. Furthermore, they hold great promise for research. At
the same time, there are important limitations to the use of biomarkers in
migraine, including problems with validity, reliability, accuracy, and precision.
Legal, ethical, and cost considerations are also important. This review describes
the potential uses and limitations of biomarkers in migraine diagnosis,
treatment, and research.

Publication Types: 
    Review

PMID: 16866709 [PubMed - indexed for MEDLINE]

1130: Neurology. 2006 Jul 25;67(2):252-7.

Obesity is a risk factor for transformed migraine but not chronic tension-type
headache.

Bigal ME, Lipton RB.

Department of Neurology, Albert Einstein College of Medicine, Bronx, NY, USA.
mbigal@aecom.yu.edu

OBJECTIVE: To assess the influence of the body mass index (BMI) on the prevalence
and severity of chronic daily headache (CDH) and its most frequent subtypes,
transformed migraine (TM) and chronic tension-type headache (CTTH). METHODS: The 
authors gathered information on headache, medical features, height, and weight
using a computer-assisted telephone interview. Participants were divided into
five categories, based on BMI: underweight (<18.5), normal weight (18.5 to 24.9),
overweight (25 to 29.9), obese (30 to 34.9), and morbidly obese (>35). The
prevalence and severity of CDH, TM, and CTTH were assessed. Multivariate analyses
modeling these diagnoses as a function of BMI were conducted. RESULTS: Among
30,215 participants, the prevalence of CDH was 4.1%; 1.3% had TM and 2.8% CTTH.
In contrast with the normal weight group (3.9%), the prevalence of CDH was higher
in obese (5.0% [odds ratio (OR) = 1.3, 95% CI = 1.1-1.6]) and morbidly obese
(6.8% [OR = 1.8, 95% CI = 1.4 to 2.2]). BMI had a strong influence on the
prevalence of TM, which ranged from 0.9% of the normal weighted to 1.2% of the
overweight (OR = 1.4 [1.1 to 1.8]), 1.6% of the obese (OR = 1.7 [1.2 to 2.43]),
and 2.5% of the morbidly obese (OR = 2.2 [1.5 to 3.2]). The effects of the BMI on
the prevalence of CTTH were just significant in the morbidly obese group.
Adjusted analyses showed that obesity was associated with CDH and TM but not
CTTH. CONCLUSIONS: Chronic daily headache and obesity are associated. Obesity is 
a stronger risk factor for transformed migraine than for chronic tension-type
headache.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16864817 [PubMed - indexed for MEDLINE]

1131: Neurology. 2006 Jul 25;67(2):246-51.

Age-dependent prevalence and clinical features of migraine.

Bigal ME, Liberman JN, Lipton RB.

Department of Neurology, Albert Einstein College of Medicine, Bronx, NY, USA.
mbigal@aecom.yu.edu

BACKGROUND: Available data suggest two seemingly opposite trends with regard to
the natural history of migraine. Migraine prevalence decreases with age. In some 
individuals, migraine progresses to chronic daily headache. OBJECTIVE: To
contrast the clinical features of migraine across the life span. METHODS: A
validated computer-assisted telephone interview (CATI) was used to identify a
population sample in three urban centers in the United States. Eligible
participants were older than 18 years. The CATI covered the International
Classification of Headache Disorders criteria for migraine and probable migraine 
(PM). Prevalence and clinical features of migraine and PM were examined by age.
RESULTS: This sample consists of 145,335 participants. The overall prevalence of 
migraine was 15%, whereas the overall prevalence of PM was 14.6%. Migraine
prevalence was highest between ages 30 and 39 years. In older ages, PM was more
prevalent than migraine. Among those with migraine, the prevalence of unilateral 
and throbbing pain peaked at intermediate ages and declined after that. The
prevalence of photophobia and phonophobia related to the attacks declined with
ages, whereas the prevalence of aura increased. The proportion of those with 10
to 14 headache days per month also increased, from 12.5% in those ages 18 to 29
to 41.0% (odds ratio = 4.8, 95% CI = 3.9 to 7.1) in those older than 70.
CONCLUSION: The profile of migraine changes over the life span and suggests three
nonexclusive profiles. In many, migraine remits. In some patients with migraine, 
attacks get less typical, resembling probable migraine instead of full migraine. 
In some, migraine progresses.

PMID: 16864816 [PubMed - indexed for MEDLINE]

1132: Clin Ther. 2006 Jun;28(6):872-80.

Time to pain freedom and onset of pain relief with rizatriptan 10 mg and
prescription usual-care oral medications in the acute treatment of migraine
headaches: a multicenter, prospective, open-label, two-attack, crossover study.

Bell CF, Foley KA, Barlas S, Solomon G, Hu XH.

Outcomes Research and Management, Merck & Co., Inc., West Point, Pennsylvania
19486, USA.

BACKGROUND: Patients and physicians consider rapid onset of pain relief and pain 
freedom among the most important attributes of migraine therapy. OBJECTIVE: This 
study compared the effectiveness of rizatriptan 10 mg and usual-care oral
migraine medications in everyday clinical practice settings. METHODS: This was a 
multicenter, prospective, open-label study. Adult patients treated 2 sequential
migraine attacks with rizatriptan 10 mg and a usual-care prescription migraine
medication in a crossover manner. Patients chose which medication to take first. 
They recorded the treatment outcomes using a stopwatch and a treatment diary. End
points included time to pain freedom (length of time from dosing to no pain) and 
time to onset of pain relief (mean time to onset of pain relief and proportion of
patients reporting onset of pain relief at 30 minutes), satisfaction with
treatment, and medication preference. Information on adverse events was collected
through the normal post-marketing reporting mechanism. Comparisons were made
using the paired t test and McNemar test for continuous and categorical
variables, respectively. A mixed model, accounting for multiple observations per 
patient, was fitted for the time to pain freedom, controlling for age, sex,
treatment period, medication, and headache severity. RESULTS: Of 2346 enrolled
patients, 1489 treated 2 migraines in a crossover manner and were included in the
analysis (86.8% women, 13.2% men; mean age, 41.7 years). A majority of patients
(80.6%) treated both migraines with oral triptans. The most commonly used
nontriptans were NSAIDs (5.4%), butalbital-containing combinations (4.3%), and
isometheptene (3.4%). Over-the-counter medications were used by 22.3% of patients
during rizatriptan-treated attacks and by 28.9% of patients during attacks
treated with usual-care medications. The mean time to pain freedom was
significantly shorter when an attack was treated with rizatriptan compared with
usual-care medications (222 vs 298 minutes, respectively; P<0.001), and the onset
of pain relief was significantly more rapid (85 vs 107 minutes; P=0.003), with
significant differences noted as early as 15 minutes after dosing (P<0.001). The 
findings remained similar after adjustment for potential confounding factors. No 
significant sequence effect was detected. Significantly more patients reported
being very satisfied or satisfied with rizatriptan compared with usual-care
medications (65.4% vs 57.7%; P<0.001) and preferred rizatriptan (58.0% vs 42.0%; 
P<0.001). One female patient reported having hives and itchy skin the day after
taking rizatriptan; the symptoms subsided after treatment with
methylprednisolone. CONCLUSIONS: In this selected population, treatment of a
migraine attack with rizatriptan 10 mg was associated with a faster time to pain 
freedom and onset of pain relief compared with treatment with usual-care oral
migraine medications. Patients reported greater satisfaction with and preference 
for rizatriptan.

Publication Types: 
    Clinical Trial
    Comparative Study
    Multicenter Study

PMID: 16860170 [PubMed - indexed for MEDLINE]

1133: JAMA. 2006 Jul 19;296(3):283-91.

Erratum in:
    JAMA. 2006 Aug 9;296(6):654.    JAMA. 2006 Jul 19;296(3):1 p following 291.

Comment in:
    JAMA. 2006 Aug 9;296(6):653-4; author reply 654.    JAMA. 2006 Dec 13;296(22):2677; author reply 2677-8.    JAMA. 2006 Jul 19;296(3):332-3.    Nat Clin Pract Cardiovasc Med. 2007 Mar;4(3):126-7.    Nat Clin Pract Neurol. 2007 Feb;3(2):74-5.

Migraine and risk of cardiovascular disease in women.

Kurth T, Gaziano JM, Cook NR, Logroscino G, Diener HC, Buring JE.

Division of Preventive Medicine, Brigham and Women's Hospital, Harvard Medical
School, Boston, Mass 02215-1204, USA. tkurth@rics.bwh.harvard.edu

CONTEXT: Migraine with aura has been associated with an adverse cardiovascular
risk profile and prothrombotic factors that, along with migraine-specific
physiology, may increase the risk of vascular events. Although migraine with aura
has been associated with increased risk of ischemic stroke, an association with
cardiovascular disease (CVD) and, specifically, coronary events remains unclear. 
OBJECTIVE: To evaluate the association between migraine with and without aura and
subsequent risk of overall and specific CVD. DESIGN, SETTING, AND PARTICIPANTS:
Prospective cohort study of 27,840 US women aged 45 years or older who were
participating in the Women's Health Study, were free of CVD and angina at study
entry (1992-1995), and who had information on self-reported migraine and aura
status, and lipid measurements. This report is based on follow-up data through
March 31, 2004. MAIN OUTCOME MEASURES: The primary outcome measure was the
combined end point of major CVD (first instance of nonfatal ischemic stroke,
nonfatal myocardial infarction, or death due to ischemic CVD); other measures
were first ischemic stroke, myocardial infarction, coronary revascularization,
angina, and death due to ischemic CVD. RESULTS: At baseline, 5125 women (18.4%)
reported any history of migraine; of the 3610 with active migraine (migraine in
the prior year), 1434 (39.7%) indicated aura symptoms. During a mean of 10 years 
of follow-up, 580 major CVD events occurred. Compared with women with no migraine
history, women who reported active migraine with aura had multivariable-adjusted 
hazard ratios of 2.15 (95% confidence interval [CI], 1.58-2.92; P<.001) for major
CVD, 1.91 (95% CI, 1.17-3.10; P = .01) for ischemic stroke, 2.08 (95% CI,
1.30-3.31; P = .002) for myocardial infarction, 1.74 (95% CI, 1.23-2.46; P =
.002) for coronary revascularization, 1.71 (95% CI, 1.16-2.53; P = .007) for
angina, and 2.33 (95% CI, 1.21-4.51; P = .01) for ischemic CVD death. After
adjusting for age, there were 18 additional major CVD events attributable to
migraine with aura per 10 000 women per year. Women who reported active migraine 
without aura did not have increased risk of any vascular events or angina.
CONCLUSIONS: In this large, prospective cohort of women, active migraine with
aura was associated with increased risk of major CVD, myocardial infarction,
ischemic stroke, and death due to ischemic CVD, as well as with coronary
revascularization and angina. Active migraine without aura was not associated
with increased risk of any CVD event.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 16849661 [PubMed - indexed for MEDLINE]

1134: Neuroepidemiology. 2006;27(2):61-6. Epub 2006 Jul 14.

Frequency of headache and migraine in Qatar.

Bener A.

Department of Medical Statistics and Epidemiology, Hamad General Hospital, Hamad 
Medical Corporation, Doha, Qatar. abener@hmc.org.qa

BACKGROUND: Headache is a worldwide problem that affects all ages. To date there 
are no epidemiological data regarding headaches in Qatar. AIM: The aim of this
study was to use the International Headache Society (IHS) diagnostic criteria to 
estimate the prevalence of migraine and headache in an adult population. DESIGN: 
This is a cross-sectional population-based study. SETTING: The study was carried 
out at 12 Primary Health Care Centers during the period from October to December 
2004 in Qatar. SUBJECTS: Of the 1,200 subjects who were approached to participate
in this study, 913 gave their consent, representing a response rate of 76.1%.
METHODS: Subjects were selected by a multistage stratified sampling procedure. We
used the IHS criteria for migraine. Face-to-face interviews were based on a
questionnaire that included variables such as age, sex, socioeconomic status,
lifestyle habits, exacerbating factors, warning symptoms, associated features,
family history and associated factors. RESULTS: Of the studied subjects, 54.9%
were males and 45.1% females. The prevalence of headache and migraine among men
was 67.9%, 7.8%, and among women 78.2%, 8.0%, respectively. Subjects aged 25-34
years had higher prevalence of headache comparing to other age groups (27.3%).
Prevalence of headache was higher in women. Subjects with less than a high school
education had higher frequency of headache (49.1%). The most common warning
symptoms prior to headache were abnormal vision (53.0%) and weakness (30.4%).
Stress (71.8%) and weather (49.5%) made headache worse in subjects. The majority 
of the headache sufferers looked for a dark (33.7%) and quiet place (74.5%) to
rest. CONCLUSION: Headachedisorders constitute a public health problem in a newly
developed Qatari society, due to fast urbanization. More women suffered from
headache and migraine than men. The study revealed that there was a strong
association between hemoglobin level and headache and its severity. Furthermore, 
the prevalence of headache and migraine in Qatar is higher than in Western and
African countries.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16847389 [PubMed - indexed for MEDLINE]

1135: Curr Med Res Opin. 2006 Jun;22(6):1021-9.

The impact of migraine on daily activities: effect of topiramate compared with
placebo.

Silberstein SD, Loder E, Forde G, Papadopoulos G, Fairclough D, Greenberg S.

Jefferson Headache Center, Philadelphia, PA 19107, USA.

OBJECTIVE: Assess the impact of migraine preventive therapy on patient-reported
routine daily activities using the Migraine Specific Questionnaire (MSQ) and the 
Medical Outcomes Study Short Form-36 (SF-36) in patients with migraine who
participated in a 26-week, randomized, double-blind, placebo-controlled trial of 
topiramate for migraine prevention. METHODS: Patients were required to have 3-12 
migraines and < or = 15 headache days/month during the baseline phase. Patients
who failed > 2 adequate regimens of migraine preventive therapy were excluded.
MSQ and SF-36 data were collected at baseline, weeks 8, 16, and 26 from 469
patients receiving either topiramate 50, 100, or 200 mg/day or placebo. Patients 
entered a double-blind, 8-week titration period followed by an 18-week
maintenance period. Two activity-related MSQ domains (Role Restrictive [RR] and
Role Prevention [RP]) and two activity-related SF-36 domains (Role Physical
[SF-36-RP] and Vitality [SF-36-VT]) were prospectively designated as the outcome 
measures. Changes in MSQ and SF-36 scores during the double-blind phase relative 
to prospective baseline scores were compared between topiramate- and
placebo-treated groups. Specifically, a mixed-effect piecewise linear regression 
model was used to estimate average domain score over time, and areas under the
domain-over-time curve (AUC) were compared using a 2-sided t-test, with
multiplicity adjustment. RESULTS: In the intent-to-treat population (N = 469),
topiramate (all doses) significantly improved mean MSQ-RR domain scores versus
placebo (topiramate 50 mg/day, p = 0.035; topiramate 100 mg/day; p < 0.001;
topiramate 200 mg/day, p = 0.001). Topiramate-associated improvements in mean
MSQ-RP domain scores were significant versus placebo only for topiramate 100
mg/day (p = 0.045). SF-36-RP and SF-36-VT domain scores improved (not significant
versus placebo) for topiramate 100 and 200 mg/day. Changes in these MSQ and SF-36
domain scores significantly correlated with changes in mean monthly migraine
frequency. CONCLUSION: Improvements in patient-reported outcomes specific for
migraine (measured by the MSQ) were significantly better for patients receiving
topiramate than for those receiving placebo. Improvements in the prospectively
selected MSQ and SF-36 domains were significantly correlated with the decrease in
mean monthly migraine frequency observed with topiramate treatment.

Publication Types: 
    Comparative Study
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 16846536 [PubMed - indexed for MEDLINE]

1136: Curr Pain Headache Rep. 2006 Aug;10(4):312-5.

Migraine and intranasal contact point headache: is there any connection?

Behin F, Lipton RB, Bigal M.

Division of Otolaryngology, Christ Hospital, Jersey City, NJ 07306, USA.
fbehin@yahoo.com

It has been suggested that contact point can trigger headache in individuals with
migraine. In this article, we review the anatomy of the sinonasal cavity. We then
define contact points and discuss the pathophysiology of contact point headaches.
We propose a theory to explain the relationship between migraines and contact
points. We close by presenting our personal casuistic in the surgical treatment
of patients with contact point and refractory headaches. In migraineurs with
contact point, surgery may improve the headaches.

Publication Types: 
    Review

PMID: 16834948 [PubMed - indexed for MEDLINE]

1137: Clin Exp Hypertens. 2006 Apr-May;28(3-4):233-42.

Complications of migraine: migrainous infarction.

Bono G, Minonzio G, Mauri M, Clerici AM.

Universitary Center for Adaptive Disorders and Headache, Dipartimento di Medicina
Clinica, Università degli Studi dell'Insubria, Varese, Italy. neurova@tin.it

Migraine and cerebrovascular disorders are comorbid diseases and the overlap of
their clinical symptoms has relevant diagnostic and therapeutic implications. The
prototypic condition of this relationship is reproduced by a clinical event named
migrainous infarction (MI), listed by the ICHD-II among the "complication of
migraine." We discuss the diagnostic criteria proposed for this rare condition
with regard to the epidemiological studies and the clinicopathogenetic
implications. In the clinical setting therefore, "possible" cases of migrainous
infarction should undergo an extended diagnostic workup to rule out symptomatic
migraine due to extra/intra-cranial vascular pathology (artery
dissection/malformations, venous thrombosis) and to exclude a causal role for
other conditions. These include patent foramen ovale and thrombophylic status
that may become critical risk factors for stroke, particularly among migraineurs,
in coincidence with precipitating factors that should be more accurately
considered in each single case.

Publication Types: 
    Review

PMID: 16833029 [PubMed - indexed for MEDLINE]

1138: Neurologist. 2006 Jul;12(4):204-13.

The preventive treatment of migraine.

Bigal ME, Lipton RB.

Departments of Neurology, Albert Einstein College of Medicine, Bronx, New York,
USA. mbigal@aecom.yu.edu

BACKGROUND: Migraine is a common, chronic, and disabling disorder. The treatment 
of migraine includes a combination of nonpharmacologic and pharmacologic
techniques. Pharmacologic approaches are subdivided in preventive therapies and
acute care. REVIEW SUMMARY: In this review article, we review the current
approaches to the preventive treatment of migraine. Preventive treatment should
be initiated in those with frequent or disabling headaches. The goals include (1)
reducing attack frequency, intensity, and duration; (2) minimizing
headache-related disability; (3) improving health-related quality of life; (4)
avoiding headache escalation and medication misuse. In this article, we also
discuss the principles of migraine prevention, as well as drugs available for
this goal. We divide preventive medications on those of common use, nutraceutical
compounds, and medications less frequently used. We close by briefly discussing
some in-development potential preventive drugs. CONCLUSION: Preventive therapies 
are well suitable for migraineurs with attack-related disability despite
appropriate acute care.

Publication Types: 
    Review

PMID: 16832239 [PubMed - indexed for MEDLINE]

1139: Expert Rev Neurother. 2006 Jul;6(7):1087-97.

Early treatment of migraine attacks with triptans: a strategy to enhance outcomes
and patient satisfaction?

D'Amico D, Moschiano F, Bussone G.

C. Besta National Neurological Institute, Clinical Neurosciences Department, Via 
Celoria 11, 20133 Milano, Italy. damicodo@tiscali.it

Treating migraine attacks early with triptans may be more effective than late
triptan administration. However, in published studies, the definition of 'early' 
varied (in terms of time, pain intensity or presence of allodynia) or was
unclear. Therefore, clear clinical indications have not been established.
Appropriately designed trials to address this issue remain a priority. Early
triptan treatment may also have disadvantages, including inadvertent treatment of
tension-type headaches and danger of medication overuse. At present, only those
migraineurs with rapid pain worsening, high pain recurrence rate and clinical
indications of allodynia should be encouraged to take triptans as quickly as
possible. This recommendation implies a requirement for patient education and the
need to carefully tailor treatment to individual needs.

Publication Types: 
    Review

PMID: 16831121 [PubMed - indexed for MEDLINE]

1140: Ann Behav Med. 2006 Aug;32(1):50-9.

A randomized, controlled trial of massage therapy as a treatment for migraine.

Lawler SP, Cameron LD.

Department of Psychology, The University of Auckland. s.lawler@uq.edu.au

BACKGROUND: Migraine is a distressing disorder that is often triggered by stress 
and poor sleep. Only one randomized controlled trial (RCT) has assessed the
effects of massage therapy on migraine experiences, which yielded some promising 
findings. PURPOSE: An RCT was designed to replicate and extend the earlier
findings using a larger sample, additional stress-related indicators, and
assessments past the final session to identify longer-term effects of massage
therapy on stress and migraine experiences. METHODS: Migraine sufferers (N = 47) 
who were randomly assigned to massage or control conditions completed daily
assessments of migraine experiences and sleep patterns for 13 weeks. Massage
participants attended weekly massage sessions during Weeks 5 to 10. State
anxiety, heart rates, and salivary cortisol were assessed before and after the
sessions. Perceived stress and coping efficacy were assessed at Weeks 4, 10, and 
13. RESULTS: Compared to control participants, massage participants exhibited
greater improvements in migraine frequency and sleep quality during the
intervention weeks and the 3 follow-up weeks. Trends for beneficial effects of
massage therapy on perceived stress and coping efficacy were observed. During
sessions, massage induced decreases in state anxiety, heart rate, and cortisol.
CONCLUSIONS: The findings provide preliminary support for the utility of massage 
therapy as a nonpharmacologic treatment for individuals suffering from migraines.

Publication Types: 
    Randomized Controlled Trial

PMID: 16827629 [PubMed - indexed for MEDLINE]

1141: Brain Res. 2006 Aug 30;1107(1):206-14. Epub 2006 Jul 5.

Cerebrovascular reactivity to hypercapnia in migraine patients measured with
near-infrared spectroscopy.

Akin A, Bilensoy D.

Institute of Biomedical Engineering, Boĝaziçi University, Bebek, Istanbul 34342, 
Turkey. ata.akin@boun.edu.tr

Migraine pain is considered to manifest itself as a result of an impaired
cerebrovascular reactivity. Hence, proper quantification and diagnosis of this
problem without causing more disturbance has always been a challenge in
investigating migraine pathogenesis. Functional near-infrared spectroscopy system
(fNIRS) is being proposed as an inexpensive, rapid, safe and accurate technique
to monitor cerebrovascular dynamics. We have developed NIROXCOPE 201, a novel
multi source and detector device of fNIRS, and attempted to investigate the
cerebrovascular reactivity of migraine patients to a breath hold task which
produces a metabolic perturbation. Six normals and six migraine patients
performed four consecutive breath holding task. A typical brain hemodynamic
response (BHR) is observed both for controls and migraineurs with an initial
phase, main response and a recovery phase. Hence, fitting to a sum of three
sequentially arranged gaussian curves proved that amplitudes of [Hb] and [HbO2]
signals acquired by fNIRS are approximately two to five times higher in controls 
than migraine patients (P<0.01) for all phases. Moreover, amplitude change
between successive breath holds tends to converge to a steady value for controls 
whereas an uncontrolled percent change is observed for migraineurs. Our results
confirm an impaired cerebrovascular reactivity in the frontal cortex of migraine 
patients interictally.

Publication Types: 
    Comparative Study

PMID: 16822486 [PubMed - indexed for MEDLINE]

1142: Trends Pharmacol Sci. 2006 Aug;27(8):410-5. Epub 2006 Jul 3.

Preventive treatment of migraine.

Silberstein SD.

Jefferson Headache Center, 111 South 11th Street, Suite 8130, Philadelphia, PA
19107, USA. stephen.silberstein@jefferson.edu

Migraine is a common episodic pain disorder, the treatment of which can be acute 
to stop an attack or preventive to reduce the frequency, duration or severity of 
attacks. Preventive treatment is used when attacks are frequent or disabling.
Many different medication groups are used for preventive treatment, including
beta-blockers, antidepressants and antiepileptic drugs. Their mechanisms of
action include raising the threshold to migraine activation, enhancing
antinociception, inhibiting cortical spreading depression, inhibiting peripheral 
and central sensitization, blocking neurogenic inflammation and modulating
sympathetic, parasympathetic or 5-HT tone. In this article, I review evidence of 
the effectiveness of migraine preventive drugs. I also discuss the setting of
treatment priorities.

Publication Types: 
    Review

PMID: 16820222 [PubMed - indexed for MEDLINE]

1143: Eur J Emerg Med. 2006 Aug;13(4):247-8.

Comment in:
    Eur J Emerg Med. 2007 Aug;14(4):243-4.

Nicotine gum withdrawal and migraine headaches.

Stalnikowicz R.

Department of Emergency Medicine, Hadassah University Hospital, Mount Scopus,
Jerusalem, Israel. darvasi@md.huji.ac.il

Some abstinent smokers develop withdrawal symptoms when they stop using nicotine 
gum or when placebo is substituted. The present report describes a patient who
suffered from severe migraine headaches after sudden discontinuation of nicotine 
gum. It has been suggested that physical dependence may be a cause of behavioral 
dependence on nicotine gum. Physicians should emphasize the need for gradual
reduction of nicotine gum.

PMID: 16816594 [PubMed - indexed for MEDLINE]

1144: Int J Clin Pract. 2006 Jun;60(6):698-706.

Comment in:
    Int J Clin Pract. 2007 Feb;61(2):350-2.

Review of clinical trials using early acute intervention with oral triptans for
migraine management.

Dowson AJ, Mathew NT, Pascual J.

King's Headache Services, King's College Hospital, London, UK.
drandydowson@dowsona.fsnet.co.uk

Most of the data on triptan use are from clinical trials in which patients were
instructed to wait until migraine headache pain was moderate/severe in intensity.
In the real world, patients may hesitate to use a triptan until headache pain is 
moderate/severe because of the cost of these agents or limited supply allowed by 
their health service organisation. However, accumulating data indicate that early
intervention with an oral triptan when headache pain is still mild may be the
most effective acute treatment strategy. Economic analyses also support early
triptan intervention in migraine attacks. Tolerability is expected to be
particularly important in early intervention, as patients treating mild migraine 
pain may be more reluctant to risk adverse events. Thus, an agent selected for
use as early intervention should have both a demonstrated efficacy in treating
mild migraine headache and placebo-like tolerability. This article reviews
retrospective and prospective clinical trials which investigated the use of
triptans for early acute migraine therapy.

Publication Types: 
    Meta-Analysis
    Review

PMID: 16805756 [PubMed - indexed for MEDLINE]

1145: Neurol India. 2006 Jun;54(2):205-6.

Hypomania as an aura in migraine.

Datta SS, Kumar S.

Department of Psychiatry, Royal Cornhill Hospital, Aberdeen, UK.

We report a 19-year-old man presenting to the department of Psychiatry for the
evaluation of prominent behavioral symptoms associated with episodic headaches,
with normal inter-episodic periods. A diagnosis of classic migraine with
hypomanic aura was made. Other possible co-morbid or causative illnesses were
excluded and preventive therapy with valproate was started due to the prominent
affective symptoms as a part of the migranous aura. With this the frequency of
headaches gradually decreased over the next four months. He was followed up for 2
years when he was found to be symptom-free. Recent research into the mechanisms
of migraine has identified that the cortical hyperexcitability and an imbalance
between neuronal inhibition and excitement mediated by gamma-aminobutyric acid
and excitatory amino acids respectively may be the underlying mechanism. The high
rate of affective disorders in patients with migraine, association of migraine
with an aura comprising of mood symptoms and good response to treatment with
mood-stabilisers might give newer insights into the pathophysiology of mood
disorder as well.

Publication Types: 
    Case Reports

PMID: 16804272 [PubMed - indexed for MEDLINE]

1146: Clin Pharmacokinet. 2006;45(7):715-28.

Modelling the anti-migraine effects of BIBN 4096 BS: a new calcitonin
gene-related peptide receptor antagonist.

Trocóniz IF, Wolters JM, Tillmann C, Schaefer HG, Roth W.

Department of Pharmacy and Pharmaceutical Technology, School of Pharmacy,
University of Navarra, Pamplona, Spain.

BACKGROUND AND OBJECTIVE: Migraine attacks are associated with release of the
calcitonin gene-related peptide (CGRP) from trigeminal nerves. BIBN 4096 BS is
the first CGRP receptor antagonist tested in humans showing response rates
similar to those reported for triptans, together with very good safety and
tolerability profiles. The objective of the current study is to develop a
population pharmacokinetic/pharmacodynamic model resembling the mechanism of
action of BIBN 4096 BS, and to extract by model-based simulations dosage
formulations and pharmacodynamic properties that can assist in the development of
CGRP receptor antagonists. METHODS: 126 patients with an acute moderate to severe
migraine attack lasting not more than 6 hours were enrolled in this phase IIa
study. BIBN 4096 BS was given as a single intravenous 10-minute infusion at
different dose levels ranging from 0.25 to 10 mg. Severity of headache was
measured up to 24 hours. Patients who did not show pain relief by 2 hours were
allowed to take rescue medication. Severity of headache and time to rescue
medication measurements were fitted simultaneously using logistic regression and 
time-to-event analysis with nonlinear mixed-effect modelling software NONMEM
version V. RESULTS: Severity of headache and time to rescue medication were
described as a function of the fraction of the CGRP receptors blocked by BIBN
4096 BS, and controlled by the second- and first-order rate constants
representing the onset (k(on)) and offset (k(off)) of the anti-migraine effects. 
The model predicted a slow rate of offset of the anti-migraine effect (half-life 
of k(off) = 21 hours). The model developed described the data well and was
validated properly. DISCUSSION: A semi-mechanistic population
pharmacokinetic/pharmacodynamic model has been developed for the anti-migraine
effects of BIBN 4096 BS, characterised by the severity of headache and time to
rescue medication. Simulations exploring the effect of the rate of absorption,
bioavailability after an extravascular administration and the rate of
activation/inactivation of the anti-migraine effect were performed. The rate of
absorption seems to play a minor role; however, at least bioavailability
fractions of 0.2-0.3 should be obtained. With regard to the kinetics of the
anti-migraine effect, and to achieve a response rate of 60% at 2 hours, values of
k(on) should be > 0.081 mL/ng/h. At later times after administration higher
values of k(off) are associated with faster offset of the response. The
simulations showed that molecules with high k(on) and low k(off) values are the
most promising.

Publication Types: 
    Clinical Trial, Phase II
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 16802852 [PubMed - indexed for MEDLINE]

1147: Chin J Integr Med. 2006 Jun;12(2):112-7.

Clinical study on effect of Xiaoyao Nose Drops in stopping episode of migraine.

Hu HQ, Zhou YH, Wang XL.

Shandong University of TCM, Jinan 250014, China. huhaiqiang@126.com

OBJECTIVE: To observe the effect of Xiaoyao Nose Drops (XYND) in stopping episode
of migraine. METHODS: Adopted was the randomized double-blinded placebo-controled
method, with the 126 patients equally assigned to two groups, the treated group
treated with XYND and the control group with placebo, and the therapeutic course 
was 30 days for all. The clinical total effective rate and effect in alleviating 
headache were observed. And hemorrheological parameters as well as the blood flow
of the anterior cerebral artery (ACA), median cerebral artery (MCA) and posterior
cerebral artery (PCA) were measured before and after treatment. RESULTS: The
clinical total effective rate and headache alleviating rate in the treated group 
were 93.33% and 96.67% respectively, while those in the control group were 18.33%
and 20.00% respectively, and comparison between the two groups showed significant
difference (all P < 0.01). The blood viscosity (high, middle and low shear),
plasma viscosity and fibrinogen got lowered significantly in the treated group
after treatment, showing significant difference in comparison either with those
before treatment or with those in the control group after treatment (P < 0.05 or 
P < 0.01). The velocity of blood flow in all cerebral arteries lowered
significantly, also showing significant difference in comparison either with
those before treatment or with those in the control group after treatment (P <
0.05 or P < 0.01). CONCLUSION: XYND is effective in stopping the headache of
patients with migraine, and worth applying in clinical practice.

Publication Types: 
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 16800989 [PubMed - indexed for MEDLINE]

1148: Invest Ophthalmol Vis Sci. 2006 Jul;47(7):3213-9.

Vernier acuity is normal in migraine, whereas global form and global motion
perception are not.

McKendrick AM, Badcock DR, Gurgone M.

School of Psychology, University of Western Australia, Crawley, Australia.
allisonm@unimelb.edu.au

PURPOSE: A recent study has demonstrated that some people with migraine display
impairments of intermediate stages of motion and form processing. Deficits were
identified by using tasks that required that local stimulus attributes be
integrated into global percepts. Neurons capable of global processing of form and
motion are known to be present in extrastriate cortical areas V4 and V5,
respectively. It is not clear from the literature whether deficits of global
processing in migraineurs are likely to arise from reduced input to extrastriate 
cortex from primary visual cortex (V1). The purpose of the study was to compare
presumed measures of V1 performance (vernier acuity) to measures of global form
and motion perception in migraineurs. METHODS: Thirty migraineurs (17 with aura, 
and 13 without) and 20 age-matched nonheadache control subjects participated.
Intermediate level motion and form perceptions were measured using global dot
motion stimuli and Glass patterns, respectively. Vernier stimuli were broad
vertical bars composed of small dot elements. Both a static luminance stimulus
and a motion defined form vernier stimulus were used. RESULTS: Mean migraine and 
control group performance were not significantly different for either vernier
task (static: t(48)=0.39, P=0.70; motion: t(48)=0.29, P=0.77). Mean migraine
group performance was significantly worse than in control subjects for both the
global form (t(48)=2.06, P=0.04) and global motion (t(48)=2.87, P<0.01) tasks.
CONCLUSIONS: On average, migraineurs demonstrate abnormalities of intermediate
stages of both motion and form processing. These abnormalities do not appear to
arise from dropout of performance at V1, as vernier acuity was normal in the same
individuals.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16799069 [PubMed - indexed for MEDLINE]

1149: Pharmacol Ther. 2006 Oct;112(1):199-212. Epub 2006 Jun 23.

New and future migraine therapy.

Ramadan NM, Buchanan TM.

Department of Neurology, Rosalind Franklin University of Medicine and Science,
North Chicago, IL 60064, USA. nabih.ramadan@rosalindfranklin.edu

Modern neuroscience advanced our understanding of putative migraine mechanisms,
which led to improved therapeutics. Indeed, mechanism-based acute migraine
therapy gained steam in the early 1990s after the introduction of the triptans
(5-HT1B,D agonists). Post-triptans, novel targets such as calcitonin gene-related
peptide (CGRP) antagonists, inhibitors of excitatory glutamatergic receptors, and
nitric oxide synthase (NOS) inhibitors are leading the pack in this exploding
field of discovery research. In contrast, novel therapeutic targets for migraine 
prevention are lacking despite a hugely unmet need. To date, migraine
prophylactic drugs are advanced based on expanded indications for already
approved pharmaceuticals (e.g., topiramate, valproate, propranolol, and timolol).
An improved understanding of the predisposition to an attack, genomic
discoveries, valid and reliable biomarkers and surrogates, and predictive
preclinical models likely will unravel the neuronal substrates for central
hyperexcitability and nociceptive dysmodulation, hopefully leading us to better
mechanism-based targets for prevention, and ultimately yielding drugs with
optimal therapeutic ratios or indices.

Publication Types: 
    Review

PMID: 16797716 [PubMed - indexed for MEDLINE]

1150: Eur J Neurol. 2006 Jun;13(6):560-72.

EFNS guideline on the drug treatment of migraine - report of an EFNS task force.

Members of the task force:, Evers S, Afra J, Frese A, Goadsby PJ, Linde M, May A,
Sándor PS.

Department of Neurology, University of Münster, Germany. everss@uni-muenster.de
European Federation of NeurologicalSocieties

Migraine is one of the most frequent disabling neurological conditions with a
major impact on the patients' quality of life. To give evidence-based or expert
recommendations for the different drug treatment procedures of the different
migraine syndromes based on a literature search and an consensus in an expert
panel. All available medical reference systems were screened for all kinds of
clinical studies on migraine with and without aura and on migraine-like
syndromes. The findings in these studies were evaluated according to the
recommendations of the EFNS resulting in level A,B, or C recommendations and good
practice points. For the acute treatment of migraine attacks, oral non-steroidal 
anti-inflammatory drugs (NSAIDs) and triptans are recommended. The administration
should follow the concept of stratified treatment. Before intake of NSAIDs and
triptans, oral metoclopramide or domperidon is recommended. In very severe
attacks, intravenous acetylsalicylic acid or subcutaneous sumatriptan are drugs
of first choice. A status migrainosus can probably be treated by steroids. For
the prophylaxis of migraine, betablockers (propranolol and metoprolol),
flunarizine, valproic acid, and topiramate are drugs of first choice. Drugs of
second choice for migraine prophylaxis are amitriptyline, naproxen, petasites,
and bisoprolol.

Publication Types: 
    Practice Guideline
    Research Support, Non-U.S. Gov't

PMID: 16796580 [PubMed - indexed for MEDLINE]

1151: Soc Sci Med. 2006 Oct;63(8):1986-97. Epub 2006 Jun 21.

Gendering the migraine market: do representations of illness matter?

Kempner J.

University of Michigan, Ann Arbor, MI, USA. jkempner@umich.edu

Migraine is a common, debilitating and costly disorder. Yet help-seeking for and 
rates of diagnosis of migraine are low. Drawing on ethnographic observations of
pharmaceutical marketing practices at professional headache conferences and a
content analysis of migraine advertising, principally in the USA, this paper
demonstrates: (1) that the pharmaceutical industry directs its marketing of
migraine medication to women; and (2) as part of this strategy, pharmaceutical
advertisements portray women as the prototypical migraine sufferer, through
representations that elicit hegemonic femininity. This strategy creates the
impression that migraine is a "women's disorder", which, in turn, exacerbates
gender bias in help seeking and diagnosis of migraine and reifies presumptions
about the epidemiology of the disorder. I conclude that these pharmaceutical
marketing practices have a paradoxical effect: even as they educate and raise
awareness about migraine, they also create barriers to help seeking and
diagnosis.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16790309 [PubMed - indexed for MEDLINE]

1152: Drugs. 2006;66(8):1129-49.

Eletriptan: a review of its use in the acute treatment of migraine.

McCormack PL, Keating GM.

Adis International Limited, Auckland, New Zealand. demail@adis.co.nz

Eletriptan (Relpax) is an orally administered, lipophilic, highly selective
serotonin 5-HT(1B/1D) receptor agonist ('triptan') that is effective in the acute
treatment of moderate to severe migraine attacks in adults. It has a rapid onset 
of action and demonstrates superiority over placebo as early as 30 minutes after 
the administration of a single 40 or 80 mg oral dose. The efficacy of eletriptan 
20 mg was similar to that of sumatriptan 100 mg, while eletriptan 40 and 80 mg
displayed greater efficacy than sumatriptan 50 or 100 mg for most endpoints.
Eletriptan 40 mg was generally superior to naratriptan 2.5 mg and equivalent to
almotriptan 12.5 mg, rizatriptan 10 mg and zolmitriptan 2.5 mg, while eletriptan 
80 mg was superior to zolmitriptan 2.5 mg for most efficacy parameters.
Eletriptan 40 and 80 mg were consistently superior to ergotamine/caffeine.
Eletriptan is generally well tolerated, reduces time lost from normal activities,
improves patients' health-related quality of life and appears to be at least as, 
if not more, cost effective than sumatriptan. Eletriptan is therefore a useful
addition to the triptan family and a first-line treatment option in the acute
management of migraine attacks.

Publication Types: 
    Review

PMID: 16789799 [PubMed - indexed for MEDLINE]

1153: Clin J Pain. 2006 Jul-Aug;22(6):564-8.

Comparison of Short Form-36 and Migraine Disability Assessment questionnaire in
patients with migraine.

Fuh JL, Wang SJ.

Neurological Institute, Taipei Veterans General Hospital and Department of
Neurology, National Yang-Ming University School of Medicine, Taipei, Taiwan.

BACKGROUND: The Short Form-36 (SF-36) and Migraine Disability Assessment (MIDAS) 
questionnaires are two of the most commonly used tools to measure outcomes in
people suffering from headaches. Nevertheless, little is known about their
interrelationship in patients with headache. OBJECTIVES: The aim of this study
was to investigate the interrelationship between SF-36 and MIDAS questionnaires
in patients with migraine. METHODS: We enrolled 231 patients with migraine
(male/female: 43/188, mean age 35.3+/-8.1) who visited our headache clinic. They 
completed the SF-36, MIDAS, and a headache intake form. RESULTS: The correlation 
coefficients between the MIDAS score and 8 domains of the SF-36 ranged from -0.30
for the mental health domain to -0.53 for the social functioning domain (P<0.01).
Canonical correlation analysis showed that the overall overlap between the 2
instruments was moderately strong (canonical correlation coefficients r=0.707 and
0.572). The overall measured redundancies for MIDAS and SF-36 scales in this
study were 35.4% and 11.5%, respectively. The stepwise linear regression model
showed that the social functioning domain alone explained 27.9% of variance in
the MIDAS scores. Bodily pain, physical functioning, and general health domains
added an additional 11.4% of the explained variance in the regression model.
CONCLUSION: Despite the fact that these two measures were considerably
correlated, the MIDAS and SF-36 were found to measure different aspects of the
impact of headache for the sample investigated. The MIDAS questionnaire does not 
cover the emotional domain; therefore, an accompanying psychological
questionnaire might help assess the outcome for headache studies.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 16788344 [PubMed - indexed for MEDLINE]

1154: Clin J Pain. 2006 Jul-Aug;22(6):548-53.

Myofascial disorders in the trochlear region in unilateral migraine: a possible
initiating or perpetuating factor.

Fernández-de-Las-Peñas C, Cuadrado ML, Gerwin RD, Pareja JA.

Department of Physical Therapy, Occupational Therapy, Physical Medicine and
Rehabilitation of Universidad Rey Juan Carlos, Alcorcón, Madrid, Spain.
cesarfdlp@yahoo.es

OBJECTIVE: Some patients with trochlear disorders have been found to suffer from 
concurrent migraine. However, a trochlear examination is not systematically done 
in patients with migraine. Moreover, a search for myofascial trigger points in
the superior oblique muscle has never been reported in these patients. METHODS:
The trochlear region was examined in 20 participants with strictly unilateral
migraine without side-shift and in 20 controls. Referred pain elicited by
different maneuvers during manual palpation (ie, maintained pressure, active
muscle contraction, and stretching of the superior oblique muscle) was assessed
with a visual analog scale. All participants were headache free on the day of
evaluation. RESULTS: Sixteen participants with migraine (80%) perceived referred 
pain on examination of the trochlear area. It was described as a tightening
sensation in the retro-orbital region, sometimes extending to the supraorbital
region and the homolateral forehead. In 15 participants with migraine, both the
active contraction and the stretching of the muscle increased the referred pain, 
which was consistent with definite myofascial trigger points. All the definite
trigger points were ipsilateral to the side of the headache. Conversely, only 5
controls (20%) had referred pain. None of them had definite myofascial trigger
points because muscle stretching did not increase the intensity of pain. The
intensity of referred pain at each stage of the trochlear examination was greater
in subjects with migraine than in controls (P<0.001). CONCLUSION: Patients with
unilateral migraine commonly perceive referred pain from the trochlear area that 
probably comes from the myofascial trigger points. Myofascial disorders in the
trochlear region might contribute to the perpetuation of concomitant migraine.

Publication Types: 
    Comparative Study

PMID: 16788342 [PubMed - indexed for MEDLINE]

1155: Expert Rev Neurother. 2006 Jun;6(6):911-9.

Optimizing migraine therapy: evidence-based and patient-centered care.

Diamond ML, Wenzel RG, Nissan GR.

Diamond Headache Clinic, Inpatient Unit, 2900 North Lake Shore Drive Chicago, IL 
60657, USA. clinic@diamondheadache.com

Migraine is a chronic, intermittently debilitating neurovascular condition that
affects the physical, mental and social aspects of health-related quality of
life. Primary care provider interactions with migraine sufferers are common,
highlighting the need for clinicians to provide optimal therapy. A comprehensive 
therapy plan should encompass the whole patient, via a patient-physician
partnership where goals and strategies are mutually established. Key treatments
include nondrug approaches, such as education and lifestyle modifications, to
reduce the occurrence of attacks, as well as acute medications to address the
immediate need for relief during an attack. Routine assessment and adjustment of 
therapy based on data recorded by patient diaries is paramount. Clinical trials
support the use of triptans and dihydroergotamine for moderate-to-severe migraine
and nonsteroidal anti-inflammatory drugs (alone or in combination with
antiemetics or caffeine) for mild-to-moderate migraine, as the treatments of
choice to reduce pain and disability time in a cost-effective manner. Published
evidence also endorses stratified care, where medication selection is geared
towards disease severity, instead of step care, where nonspecific mediations are 
given to all patients. Thus, patients with significant migraine-induced
debilitation, as assessed by tools, such as the Migraine Disability Assessment
Scale or the Headache Impact Test, are prescribed migraine-specific agents from
the onset of therapy, thereby avoiding the inherent failures of step care. For
individuals experiencing a high frequency of attacks or routine debilitation,
preventive medications are warranted.

Publication Types: 
    Review

PMID: 16784413 [PubMed - indexed for MEDLINE]

1156: Cephalalgia. 2006 Jul;26(7):871-4.

Rizatriptan vs. rizatriptan plus trimebutine for the acute treatment of migraine:
a double-blind, randomized, cross-over, placebo-controlled study.

Krymchantowski AV, Filho PF, Bigal ME.

Instituto de Neurologia Deolindo Couto, Rio de Janeiro, Brazil.
abouchkrym@globo.com

Gastroparesis frequently happens during migraine attacks, postponing the onset of
action of orally administered drugs. Furthermore, triptans seem to work better in
the earlier phases of the migraine attacks. Therefore, associating a
gastrokinetic drug with a triptan may translate into better efficacy and higher
consistency of response. Trimebutine is an opioid derivative with exclusive
action on receptors of the Meissner and Auerbach plexus throughout the digestive 
tube. It has no absorption or central penetration. Herein we contrast the
combination of rizatriptan plus trimebutine with rizatriptan alone in the acute
treatment of migraine. Forty patients with migraine consecutively seen in our
clinic were randomized to treat two consecutive moderate or severe attacks with
one tablet of 10 mg rizatriptan plus one capsule of 200 mg trimebutine and two
attacks with the same triptan and placebo, in counterbalanced order. We collected
information on the severity of the attack, as well as presence of nausea and
photophobia at the time of drug intake, and after 1, 2 and 4 h. Recurrence and
adverse events were also contrasted. Sixty-four attacks were treated with each
drug regimen. At 1 h postdose, 30 (46.8%) of 64 attacks treated with the
combination resolved completely, vs. eight (12.5%) of the rizatriptan-treated
attacks, a difference of 34% (P < 0.01). At 2 h postdose, 47 (73.4%) attacks
treated with the combination vs. 20 (31.2%) of those treated with rizatriptan
alone resolved completely, a difference of 42% (95% confidence interval 26, 58, P
< 0.001). Regarding nausea and photophobia, the combination was also associated
with significantly better response. Recurrence was similar among the two drug
regimens, as well as adverse events. The combination rizatriptan and trimebutine 
is more effective than rizatriptan alone. The combination does not increase
adverse events or recurrence of pain.

Publication Types: 
    Comparative Study
    Randomized Controlled Trial

PMID: 16776704 [PubMed - indexed for MEDLINE]

1157: Cephalalgia. 2006 Jul;26(7):857-64.

Dysfunction of arousal systems in sleep-related migraine without aura.

Della Marca G, Vollono C, Rubino M, Di Trapani G, Mariotti P, Tonali PA.

Department of Neuroscience, Catholic University. Rome, Italy.
dellamarca@rm.unicatt.it

Primary headaches are closely related to sleep. Modifications in the patterns of 
arousal during sleep have been reported in migraine, especially in the nights
preceding a headache attack. We aimed at evaluating the pattern of arousal from
sleep in a group of patients affected by sleep-related migraine. We enrolled 10
consecutive patients, three males and seven females, aged between 20 and 62
years, who presented frequent attacks of migraine without aura (more than five
per month), closely related to sleep (more than one-half of the attacks occurred 
during sleep, causing an awakening). A control group was studied, matched for age
and sex. Patients and controls underwent a full-night polysomnographic study,
following adaptation; arousal pattern was studied by the scoring of the
high-frequency EEG arousal and by the cyclic alternating pattern (CAP).
Migraineurs showed a lower CAP rate in non-rapid eye movement (NREM) sleep and,
in particular, a lower number of A1 phases (low-frequency, high-amplitude EEG
bursts) compared with the controls. Migraineurs also showed a lower index of
high-frequency EEG arousals during rapid eye movement (REM) sleep. The reduction 
in the CAP rate indicates a lower level of arousal fluctuation in NREM sleep. The
reduced arousal index in REM suggests a dysfunction in neural structures involved
in both the control of REM sleep and the pathophysiology of migraine, such as the
hypothalamus and the brainstem.

Publication Types: 
    Controlled Clinical Trial

PMID: 16776702 [PubMed - indexed for MEDLINE]

1158: Cephalalgia. 2006 Jul;26(7):852-6.

Comparison of dynamic (brush) and static (pressure) mechanical allodynia in
migraine.

LoPinto C, Young WB, Ashkenazi A.

New York University School of Medicine, New York, NY, USA.

Allodynia has been described in migraine but has not been fully investigated for 
the different sensory modalities. The aim of this study was to compare the
prevalence of dynamic (brush) and static (pressure) mechanical allodynia in
migraine patients and to suggest a practical method of testing them in a clinical
setting. Patients with International Headache Society-defined episodic migraine
(EM) or with transformed migraine (TM) as defined by Silberstein and Lipton were 
prospectively recruited from the Jefferson Headache Center out-patient clinic. A 
questionnaire of migraine features and symptoms of allodynia was administered.
Brush allodynia (BA) was tested by cutaneous stimulation with a gauze pad and
pressure allodynia (PA) was tested using von Frey hairs (VFH). The prevalence of 
BA and PA in all patients and in the different subgroups was calculated and
correlated with migraine features. We recruited 55 migraine patients. Twenty-five
had EM and 30 had TM. BA was present in 18 (32.7%) patients and PA in 18-24
(32.7-43.6%). Allodynia to both brush and pressure was found in 13-17
(23.6-30.9%) patients. If a patient had allodynia to one modality only, it was
more likely to be PA than BA. Both BA and PA were more common in patients with TM
compared with those with EM [BA 46.7% vs. 16.0%; PA (differences significant for 
the medium and thick VFHs) 50% vs. 20% and 50% vs. 12%, respectively]. Both types
of allodynia were also more common in patients with migraine with aura compared
with those with migraine without aura (BA 57.1% vs. 17.6%; PA 57.1-61.9% vs.
17.6-32.7%). There was a positive correlation between allodynia score (as
obtained by examination) and allodynia index (as obtained by history) for both BA
and PA. The incomplete, although considerable, overlap between BA and PA suggests
that allodynia to different sensory modalities is associated with sensitization
of different neuronal populations. Because PA was more common than BA, it may be 
a more sensitive indicator of allodynia in migraine. PA can be tested clinically 
in a practical and systematic manner.

Publication Types: 
    Controlled Clinical Trial

PMID: 16776701 [PubMed - indexed for MEDLINE]

1159: Cephalalgia. 2006 Jul;26(7):820-30.

Clinical features, classification and prognosis of migraine and tension-type
headache in children and adolescents: a long-term follow-up study.

Kienbacher C, Wöber C, Zesch HE, Hafferl-Gattermayer A, Posch M, Karwautz A,
Zormann A, Berger G, Zebenholzer K, Konrad A, Wöber-Bingöl C.

Headache Unit, Department of Neuropsychiatry of Childhood and Adolescents,
Medical University of Vienna, Vienna, Austria.
christian.kienbacher@meduniwien.ac.at

We performed a long-term follow-up examination in children and adolescents with
migraine and tension-type headache (TTH) in order to investigate the evolution of
clinical features and headache diagnoses, to compare International Classification
of Headache Disorders (ICHD)-I and ICHD-II criteria and to identify prognostic
factors. We re-examined 227 patients (52.4% female, age 17.6 +/- 3.1 years) 6.6
+/- 1.6 years after their first presentation to a headache centre using identical
semistructured questionnaires. Of 140 patients initially diagnosed with migraine,
25.7% were headache free, 48.6% still had migraine and 25.7% had TTH at
follow-up. Of 87 patients with TTH, 37.9% were headache free, 41.4% still had TTH
and 20.7% had migraine. The number of subjects with definite migraine was higher 
in ICHD-II than in ICHD-I at baseline and at follow-up. The likelihood of a
decrease in headache frequency decreased with a changing headache location at
baseline (P < 0.0001), with the time between baseline and follow-up (P = 0.0019),
and with an initial diagnosis of migraine (P = 0.014). Female gender and a longer
time between headache onset and first examination tended to have an unfavourable 
impact. In conclusion, 30% of the children and adolescents presenting to a
headache centre because of migraine or TTH become headache-free in the long-term.
Another 20-25% shift from migraine to TTH or vice versa. ICHD-II criteria are
superior to those of ICHD-I in identifying definite migraine in children and
adolescents presenting to a headache centre. The prognosis is adversely affected 
by an initial diagnosis of migraine and by changing headache location, and it
tends to be affected by an increasing time between headache onset and first
presentation.

PMID: 16776697 [PubMed - indexed for MEDLINE]

1160: Cephalalgia. 2006 Jul;26(7):816-9.

Normobaric hypoxia and nitroglycerin as trigger factors for migraine.

Schoonman GG, Sándor PS, Agosti RM, Siccoli M, Bärtsch P, Ferrari MD, Baumgartner
RW.

Department of Neurology, Leiden University Medical Centre, the Netherlands.
g.g.schoonman@lumc.nl

Migraine prevalence is increased in high-altitude populations and symptoms of
acute mountain sickness mimic migraine symptoms. Here we tested whether
normobaric hypoxia may trigger migraine attacks. As positive control we used
nitrolgycerin (NTG), which has been shown to induce migraine attacks in up to 80%
of migraineurs. Sixteen patients (12 females, mean age 28.9 +/- 7.2 years)
suffering from migraine with (n = 8) and without aura (n = 8) underwent three
different provocations (normobaric hypoxia, NTG and placebo) in a randomized,
cross-over, double dummy design. Each provocation was performed on a separate
day. The primary outcome measure was the proportion of patients developing a
migraine attack according to the criteria of the International Headache Society
within 8 h after provocation onset. Fourteen patients completed all three
provocations. Migraine was provoked in six (42%) patients by hypoxia, in three
(21%) by NTG and in two (14%) by placebo. The differences among groups were not
significant (P = 0.197). The median time to attacks was 5 h. In conclusion, the
(remarkably) low response rate to NTG is surprising in view of previous data.
Further studies are required to establish fully the potency of hypoxia in
triggering migraine attacks.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 16776696 [PubMed - indexed for MEDLINE]

1161: Cephalalgia. 2006 Jul;26(7):809-15.

A 3-year follow-up of headache diagnoses and symptoms in Swedish schoolchildren.

Laurell K, Larsson B, Mattsson P, Eeg-Olofsson O.

Department of Neuroscience, Uppsala University, Uppsala, Sweden.
katarina.laurell@akademiska.se

Information is sparse concerning the incidence and prognosis of headache in
children from the general population, especially of tension-type headache. In
this study, headache diagnoses and symptoms were reassessed in 122 out of 130
schoolchildren after 3 years. Nearly 80% of those with headache at first
evaluation still reported headache at follow-up. Although the likelihood of
experiencing the same headache diagnosis and symptoms was high, about one-fifth
of children with tension-type headache developed migraine and vice versa. Female 
gender predicted migraine and frequent headache episodes predicted overall
headache at follow-up. The estimated average annual incidence was 81 and 65 per
1000 children, for tension-type headache and migraine, respectively. We conclude 
that there is a considerable risk of developing and maintaining headache during
childhood. Headache diagnoses should be reassessed regularly and treatment
adjusted. Girls and children with frequent headache have a poorer prognosis and
therefore intervention is particularly important in these groups.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16776695 [PubMed - indexed for MEDLINE]

1162: Cephalalgia. 2006 Jul;26(7):801-8.

Objective assessment of cortical excitability in migraine with and without aura.

Chronicle EP, Pearson AJ, Mulleners WM.

Department of Psychology, University of Hawaii at Manoa, Honolulu, HI 96822, USA.
chronicl@hawaii.edu

Recent progress in the genetics of migraine has refocused attention on cortical
dysfunction as an important component of the pathophysiology of this disorder. In
previous work, we have demonstrated functional changes in the visual cortex of
migraine patients, using an objective transcranial magnetic stimulation
technique, termed magnetic suppression of perceptual accuracy (MSPA). This study 
aimed to replicate previous findings in migraine with aura (MA) and to use the
technique to examine migraine without aura (MoA). Eight MA patients, 14 MoA
patients and 13 migraine-free controls participated. MSPA assessments were
undertaken using a standardized protocol in which computer-presented letter
targets were followed at a variable delay interval by a single magnetic pulse
delivered over the occiput. MSPA performance is expressed as a profile of
response accuracy across target-pulse delay intervals. The profiles of
migraine-free controls exhibited a normal U-shape. MA patients had significantly 
shallower profiles, showing little or no suppression at intermediate delay
intervals. MoA patients had profiles that were similar to controls. Recent animal
evidence strongly indicates that the U-shape of the normal MSPA function is
caused by preferential activation of inhibitory neurons. Shallower MPSA profiles 
in MA patients are therefore likely to indicate a functional hyperexcitability
caused by impaired inhibition. The finding of normal MPSA profiles in MoA
patients is novel and will require further investigation.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16776694 [PubMed - indexed for MEDLINE]

1163: Cephalalgia. 2006 Jul;26(7):782-9.

Abnormal modulatory influence of diffuse noxious inhibitory controls in migraine 
and chronic tension-type headache patients.

Sandrini G, Rossi P, Milanov I, Serrao M, Cecchini AP, Nappi G.

University Centre for Adaptive Disorders and Headache, IRCCS 'C. Mondino'
Foundation, University of Pavia, Pavia, Italy. gsandrin@unipv.it

The aim of this study was to evaluate the function of pain modulating systems
subserving diffuse noxious inhibitory controls (DNICs) in primary headaches.
DNICs were examined in 24 migraineurs, 17 patients with chronic tension-type
headache (CTTH) and 20 healthy subjects by means of nociceptive flexion RIII
reflex and the cold pressor test (CPT) as heterotopic noxious conditioning
stimulation (HNCS). The subjective pain thresholds (Tp) and the RIII reflex
threshold (Tr) were significantly lower in CTTH vs. controls. In controls a
significant inhibition of the RIII reflex was observed during the CPT (-30%, P < 
0.05). Conversely, migraine and CTTH patients showed facilitation (+31%, P < 0.05
and +40%, P < 0.01, respectively) of the RIII reflex during the HNCS. This study 
demonstrates a dysfunction in systems subserving DNICs in both migraine and CTTH.
Impairment of endogenous supraspinal pain modulation systems may contribute to
the development and/or maintenance of central sensitization in primary headaches.

Publication Types: 
    Controlled Clinical Trial

PMID: 16776692 [PubMed - indexed for MEDLINE]

1164: Neurology. 2006 Aug 8;67(3):497-9. Epub 2006 Jun 14.

Comment in:
    Neurology. 2007 Apr 24;68(17):1441.

Treatment of childhood migraine attacks with oral zolmitriptan and ibuprofen.

Evers S, Rahmann A, Kraemer C, Kurlemann G, Debus O, Husstedt IW, Frese A.

Department of Neurology, University of Münster, Germany. everss@uni-muenster.de

The authors conducted a double-blind, placebo-controlled, crossover study to
investigate the efficacy of oral zolmitriptan in the treatment of migraine in
children and adolescents. Patients (n = 32) received placebo, zolmitriptan 2.5
mg, and ibuprofen 200 to 400 mg to treat three consecutive migraine attacks. Pain
relief rates after 2 hours were 28% for placebo, 62% for zolmitriptan, and 69%
for ibuprofen (p < 0.05). Both drugs are well tolerated with only mild side
effects.

Publication Types: 
    Randomized Controlled Trial

PMID: 16775229 [PubMed - indexed for MEDLINE]

1165: Acta Neurol Scand. 2006 Jul;114(1):13-6.

Prothrombotic risk factors in ischemic stroke and migraine in children.

Pilarska E, Lemka M, Bakowska A.

Department of Developmental Neurology, Medical University of Gdansk, Gdansk,
Poland. pilar@amg.gda.pl

OBJECTIVE: To evaluate the contribution of antiphospholipid antibodies (aPL) and 
thrombomodulin (Thm) in the pathogenesis of stroke and migraine in children.
MATERIALS AND METHODS: Ninety children were included in the study: 30 children
(4-15 years) after an ischemic stroke of an unknown etiology; 30 migrainous
patients (8-15 years), who were hospitalized in the Department of Developmental
Neurology, Medical University of Gdansk, Poland, and 30 healthy children of the
same age. RESULTS: The statistical analysis showed an increase in the values of
anticardiolipin antibodies (aCL), anti beta2-glycoprotein 1 (beta2-GP1) and Thm
in children with stroke and migraine than in the control group. The resultant
values were higher, but stayed at standard. CONCLUSION: The possible role of
prothrombotic factors in individual cases of pediatric stroke and migraine cannot
be excluded.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16774621 [PubMed - indexed for MEDLINE]

1166: Am J Hum Genet. 2006 Jul;79(1):85-99. Epub 2006 May 10.

Trait components provide tools to dissect the genetic susceptibility of migraine.

Anttila V, Kallela M, Oswell G, Kaunisto MA, Nyholt DR, Hamalainen E, Havanka H, 
Ilmavirta M, Terwilliger J, Sobel E, Peltonen L, Kaprio J, Farkkila M, Wessman M,
Palotie A.

Finnish Genome Center, Helsinki, Finland.

The commonly used "end diagnosis" phenotype that is adopted in linkage and
association studies of complex traits is likely to represent an oversimplified
model of the genetic background of a disease. This is also likely to be the case 
for common types of migraine, for which no convincingly associated genetic
variants have been reported. In headache disorders, most genetic studies have
used end diagnoses of the International Headache Society (IHS) classification as 
phenotypes. Here, we introduce an alternative strategy; we use trait
components--individual clinical symptoms of migraine--to determine affection
status in genomewide linkage analyses of migraine-affected families. We
identified linkage between several traits and markers on chromosome 4q24 (highest
LOD score under locus heterogeneity [HLOD] 4.52), a locus we previously reported 
to be linked to the end diagnosis migraine with aura. The pulsation trait
identified a novel locus on 17p13 (HLOD 4.65). Additionally, a trait combination 
phenotype (IHS full criteria) revealed a locus on 18q12 (HLOD 3.29), and the age 
at onset trait revealed a locus on 4q28 (HLOD 2.99). Furthermore, suggestive or
nearly suggestive evidence of linkage to four additional loci was observed with
the traits phonophobia (10q22) and aggravation by physical exercise (12q21,
15q14, and Xp21), and, interestingly, these loci have been linked to migraine in 
previous studies. Our findings suggest that the use of symptom components of
migraine instead of the end diagnosis provides a useful tool in stratifying the
sample for genetic studies.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16773568 [PubMed - indexed for MEDLINE]

1167: Clin Neuropharmacol. 2006 May-Jun;29(3):157-9.

Reversible tremor, myoclonus, and fasciculations associated with topiramate use
for migraine.

Alonso-Navarro H, Jiménez-Jiménez FJ.

Servicio de Neurología, Hospital Virgen de la Concha, Zamora, Spain.

OBJECTIVE: To report a patient with tremor, multifocal myoclonus, and
fasciculations, possibly induced by the antiepileptic drug topiramate. CASE
REPORT: A 46-year-old woman with frequent episodes of migraine without aura that 
were not controlled with other prophylactic drug, developed a reversible clinical
picture of postural tremor, multifocal myoclonus, weight loss, amyotrophia, and
fasciculations after exposure to topiramate. These symptoms disappeared after
topiramate withdrawal. CONCLUSIONS: Tremor, myoclonus, and fasciculations should 
be considered as a possible adverse effect of topiramate.

Publication Types: 
    Case Reports

PMID: 16772816 [PubMed - indexed for MEDLINE]

1168: Am J Ther. 2006 May-Jun;13(3):183-7.

Botulinum toxin type A in prophylactic treatment of migraine.

Anand KS, Prasad A, Singh MM, Sharma S, Bala K.

Ram Manohar Lohia Hospital, New Delhi, India. kuljeet_anand@rediffmail.com

Current migraine preventive therapies are often unsatisfactory because of their
limited efficacy, adverse effects, and drug interactions. An open-label,
non-controlled study of botulinum toxin type A (BTX-A) suggested some benefits
for patients with migraine. To assess the efficacy and safety of BTX-A, a
randomized, double-blind, vehicle-controlled, parallel group study was conducted 
in 32 patients with a history of 2 to 8 migraine attacks per month, with or
without aura. The patients were randomized to receive single administrations of
50-U BTX-A or vehicle injected into multiple sites of pericranial muscles at the 
same visit. Patients kept daily diaries in which they recorded outcome measures
like migraine frequency, migraine severity, and the occurrence of
migraine-associated symptoms. Patients graded symptoms on a 4-point scale ranging
from grades 0 to 3 before and up to 3-months after treatment. The assessments
were made at 0, 1, and 3 months. The primary efficacy parameters included number 
of headaches resolved (grade 3/2 to grade 0) and alleviation of other
accompanying symptoms of migraine. The supplementary end point included
improvement in quality of life (QOL). About 75% of patients reported complete
relief to mild headache (grade 0-1) by BTX-A and none by placebo group. Patient' 
QOL parameters like energy/vitality and feelings and concerns about the treatment
had shown considerable improvement. However, normal day-to-day work functioning
and social interactions deteriorated. No adverse effects were reported in any of 
the patients in either of the groups during the study. It is evident from the
study that pericranial injection of 50-U BTX-A showed good efficacy and
tolerability as a prophylactic agent. However, this therapy will be expensive to 
the patients, but it is far superior in providing relief to the patients compared
with existing therapies.

Publication Types: 
    Randomized Controlled Trial

PMID: 16772757 [PubMed - indexed for MEDLINE]

1169: Eur Neurol. 2006;55(4):198-203. Epub 2006 Jun 13.

Evaluation of efficacy, tolerability, and treatment satisfaction with almotriptan
in 3 consecutive migraine attacks. The migraine--satisfaction with treatment:
reality with Almogran study.

Massiou H, Pradalier A, Donnet A, Lanteri-Minet M, Allaf B.

Service de Neurologie, Hôpital Lariboisière, Paris, France. hmassiou@wanadoo.fr

The objective of the open-label, multicenter Migraine--Satisfaction with
Treatment: Reality with Almogran study was to assess efficacy, tolerability, and 
satisfaction with almotriptan 12.5 mg among migraineurs who were not achieving
adequate results with their current acute therapy. Data from 434 patients (342
evaluable), were obtained for 929 attacks by 154 neurologists in France. Using a 
questionnaire developed by the National Agency for Accreditation and Evaluation
in Health (ANAES), almotriptan was associated with an increased proportion of
patients experiencing significant relief at 2 h (69.3 vs. 26.6%), tolerating the 
medication well (91.2 vs. 76.0%), able to resume activities (70.5 vs. 24.9%), and
taking only 1 dose (59.4 vs. 28.1%) compared with previous therapies. At 2 h,
headache pain had disappeared in 33.4% of attacks and was mild in 26.9%.
Recurrence rate was 28.4% and rescue analgesics were used in 20.9% of attacks.
The rate of adverse event-related discontinuations was 2.6%. The proportion of
patients who were very satisfied/satisfied overall with almotriptan treatment was
69%. Almotriptan 12.5 mg was effective, well-tolerated and associated with a high
rate of treatment satisfaction in patients whose previous acute migraine therapy 
was inadequate according to the ANAES recommendations.

Publication Types: 
    Clinical Trial
    Multicenter Study

PMID: 16772716 [PubMed - indexed for MEDLINE]

1170: J Headache Pain. 2006 Jun;7(3):160-4. Epub 2006 Jun 15.

Reading data in migraine acute treatment studies: from clinical trials to reviews
and meta-analyses.

Buzzi MG.

Headache Centre, IRCCS Fondazione Santa Lucia, Via Ardeatina 306, I-00179 Rome,
Italy. mg.buzzi@hsantalucia.it

The huge amount of data regarding triptans in clinical practice provides a great 
opportunity to learn about their efficacy, tolerability and adverse events and
offers to the clinician the background for the best treatment option in any
patient, given that the patient is suitable for being treated with any of those
compounds. A detailed clinical history is necessary in order to make a
preliminary selection of triptan-suitable or -unsuitable migraine patients. Among
the former, a secondary selection may be made, to recognise different attacks
that can be successfully treated with different triptans, according to attack
presentation and progression, within the same patient. Reading single original
articles has become very difficult. Therefore, data are often presented in review
form, which may be too partial or oriented. Systematic reviews or meta-analyses
better serve to comment on data as they follow an analytic method that is based
upon pooling data from original articles and comparing them using statistical
aids.

Publication Types: 
    Review

PMID: 16767534 [PubMed - indexed for MEDLINE]

1171: J Headache Pain. 2006 Sep;7(4):222-30. Epub 2006 Jun 15.

Comorbid neuropathologies in migraine.

Sacco S, Olivieri L, Bastianello S, Carolei A.

Department of Neurology, University of L'Aquila, 67100, L'Aquila, Italy.

The identification of comorbid disorders in migraineurs is important since it may
impose therapeutic challenges and limit treatment options. Moreover, the study of
comorbidity might lead to improve our knowledge about causes and consequences of 
migraine. Comorbid neuropathologies in migraine may involve mood disorders
(depression, mania, anxiety, panic attacks), epilepsy, essential tremor, stroke, 
and white matter abnormalities. Particularly, a complex bidirectional relation
exists between migraine and stroke, including migraine as a risk factor for
cerebral ischemia, migraine caused by cerebral ischemia, migraine as a cause of
stroke, migraine mimicking cerebral ischemia, migraine and cerebral ischemia
sharing a common cause, and migraine associated with subclinical vascular brain
lesions.

Publication Types: 
    Review

PMID: 16767530 [PubMed - indexed for MEDLINE]

1172: J Headache Pain. 2006 Jun;7(3):127-35. Epub 2006 Jun 15.

Migraine with aura: visual disturbances and interrelationship with the pain
phase. Vågå study of headache epidemiology.

Sjaastad O, Bakketeig LS, Petersen HC.

Department of Neurology, St. Olavs Hospital, Trondheim University Hospitals
(NTNU), Trondheim, Norway. tora.rui@ntnu.no

In the Vågå study of headache epidemiology, 1838 or 88.6% of the available
18-65-year-old inhabitants of the commune were included. Everyone was questioned 
and examined personally by the principal investigator (OS). There were 178 cases 
of various types of visual disturbances during the migraine attack, which
corresponds to 9.7% of the study group. The prevalence among females was 11.9%
and among males 7.4%; female/male ratio was 1.70, as against 1.05 in the total
Vågå study population. By far the most frequently occurring visual disturbance
pattern was (A) 1. Visual disturbances --> 2. pain-free interlude --> 3. pain
phase (in 78% of the cases). Other frequent patterns were: (B). Visual
disturbances, but no pain phase (24%); and: (C) 1. Pain phase --> 2. visual
disturbances (23%). Evidently, in the solitary case, there might be more than one
visual disturbance pattern. The most frequently occurring solitary visual
disturbances were: scintillating scotoma (62%) and obscuration (33%); but also
more rare ones were identified, like anopsia, autokinesis (movement of stationary
objects), tunnel vision and micropsia. Among the non-visual aura disturbances,
paraesthesias and speech disturbances were the most frequent ones. The prevalence
of migraine with aura seemed to be considerably higher than in similar studies.
This also includes studies that have been carried out with a face-to-face
interview technique.

PMID: 16767529 [PubMed - indexed for MEDLINE]

1173: Pediatr Neurol. 2006 Jun;34(6):421-32.

Nonepileptic uses of antiepileptic drugs in children and adolescents.

Golden AS, Haut SR, Moshé SL.

Department of Neurology and the Comprehensive Epilepsy Management Center, Bronx, 
New York, USA. agolden@u.washington.edu

Antiepileptic drugs are often prescribed for nonepileptic neurologic and
psychiatric conditions. The United States Food and Drug Administration has
approved several antiepileptic drugs for the treatment of neuropathic pain,
migraine, and mania in adults. For pediatric patients, use of antiepileptic drugs
for non-seizure-related purposes is supported mainly by adult studies, open-label
trials, and case reports. Summarized here is the published literature for or
against the use of antiepileptic drugs for neuropathic pain, migraine, movement
disorders, bipolar disorder, aggressive behavior, and pervasive developmental
disorders in children and adolescents. Using the American Academy of Neurology's 
four-tiered classification scheme for a therapeutic article and translation to a 
recommendation rating, there are no nonepileptic disorders for which
antiepileptic drugs have been established as effective for pediatric patients.
Valproate and carbamazepine are "possibly effective" in the treatment of Sydenham
chorea, and valproate is "probably effective" in decreasing aggressive behavior. 
Carbamazepine is "probably ineffective" in the treatment of aggression, and
lamotrigine is "possibly ineffective" in improving the core symptom of pervasive 
developmental disorders. Despite the frequent use of antiepileptic drugs in the
treatment of juvenile bipolar disorder, migraine, and neuropathic pain, the data 
are insufficient to make recommendations regarding the efficacy of antiepileptics
in these conditions in children and adolescents.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't
    Review

PMID: 16765818 [PubMed - indexed for MEDLINE]

1174: Brain Dev. 2006 Nov;28(10):660-2. Epub 2006 Jun 12.

Familial limb pain in childhood: unusual manifestation of migraine?

Saito Y, Fusayasu E, Iitsuka T, Takeshima T, Ohno K.

Divisions of Child Neurology, Faculty of Medicine, Tottori University, Japan.
saitoyo@grape.med.tottori-u.ac.jp

A familial case of limb pain is described. Frequent vascular pain appeared during
early childhood in affected individuals, often with predominance in the lower
extremities. This pain subsided in patients during adolescence, when they began
to suffer from typical migraine. The limb pain was moderate to severe, and
refractory to analgesic and anti-migraine medications. Limb temperature was cold 
at the onset of pain, and became warm during the painful attacks. Plasma
substance P and calcitonin gene-related peptide were elevated during the episodic
pain. We propose this condition is a new precursor etiology of migraine, with
possible autosomal dominant inheritance.

Publication Types: 
    Case Reports
    Comparative Study

PMID: 16765548 [PubMed - indexed for MEDLINE]

1175: J Pain. 2006 Jun;7(6):445-51.

Kinesiophobia in migraine.

Martins IP, Gouveia RG, Parreira E.

Centro de Estudos Egas Moniz, Instituto de Medicina Molecular, Lisbon Faculty of 
Medicine, Lisboa, Portugal. labling@fm.ul.pt

Pain aggravation by movement and avoidance of movement (kinesiophobia) is often
reported by patients during migraine attacks. Yet its specific contribution to
migraine diagnosis is undetermined. To characterize the frequency and severity of
kinesiophobia during migraine and its role in the diagnosis of primary headaches,
we questioned 150 patients (126 women and 24 men, average age 38.5 yrs) with
migraine (n = 111) or tension-type headache (TTH) (n = 39) about aggravation of
pain by bending forward, brisk head movements (jolt), and avoidance of movement
during the attacks. The degree of pain worsening by each stimulus was measured
through a visual analog scale and compared to worsening produced by other sensory
stimuli such as light, sound, and smell. The discrimination power of
kinesiophobia between migraine and TTH was calculated, using the International
Classification of Headache Disorders criteria as gold standard.
Sensitivity/specificity of studied symptoms was high in differentiating the 2
headache types: bending forward: 98%/85.7%; jolt: 96.3%/81.6%; and immobility
during the attacks: 100%/70%. The degree of kinesiophobia was identical to photo-
and phonophobia in migraine patients. We conclude that kinesiophobia
discriminates between migraine and TTH. Bending forward and jolt may be useful
additional questions to ask patients for the differentiation of headache attacks.
PERSPECTIVE: This article evaluates the specific role of movement
(movement-induced pain aggravation and avoidance of movement) in primary
headaches. Kinesophobia is an easy symptom to screen, explained by migraine
pathophysiology, and proved to be a sensitive and specific measure to identify
migraine attacks when compared to tension-type headache.

PMID: 16750801 [PubMed - indexed for MEDLINE]

1176: Clin Ther. 2006 Apr;28(4):517-26.

A randomized, double-blind, placebo-controlled trial of the efficacy and
tolerability of a 4-mg dose of subcutaneous sumatriptan for the treatment of
acute migraine attacks in adults.

Wendt J, Cady R, Singer R, Peters K, Webster C, Kori S, Byrd S.

Northwest Neurospecialists, Tucson, Arizona 85750-1805, USA.
jwendt@neuroresearch.com

OBJECTIVE: The aim of this study was to evaluate the efficacy and tolerability of
a single 4-mg dose of sumatriptan SC for the acute treatment of adult patients
experiencing a migraine attack with moderate to severe pain. METHODS: In this
randomized, double-blind, placebo-controlled study, subjects included men and
women aged 18 to 60 years who had migraine with or without aura, as defined by
the 1988 International Headache Society criteria. Subjects received either
sumatriptan 4 mg SC or placebo SC for a migraine attack with headache pain of
moderate to severe intensity. The primary efficacy measurement was pain relief at
2 hours. Secondary efficacy measures included the severity of headache pain at
10, 20, 30, 40, 50, 60, and 90 minutes postadministration. Clinical assessments
of pain severity and adverse events were made by way of questioning and
observation of subjects and were completed at 10, 20, 30, 40, 50, 60, 90, and 120
minutes postadministration. RESULTS: Five hundred seventy-seven subjects (87%
female and 94% white) participated in this study. Three hundred eighty-four
received sumatriptan and 193 received placebo. At 120 minutes postadministration,
sumatriptan 4 mg SC was associated with greater proportions of patients who
experienced pain relief (70% vs 22%; P<0.001) or were pain free (50% vs 11%;
P<0.001). In addition, there were statistically significant differences between
sumatriptan 4 mg SC and placebo for multiple secondary end points, including pain
relief as early as 10 minutes postadministration (11% vs 6%; P=0.039), pain-free 
status as early as 30 minutes postadministration (10% vs 3%; P<0.001), nausea as 
early as 30 minutes postadministration (39% vs 49%; P=0.021), and photophobia as 
early as 10 minutes postadministration (80% vs 87%; P=0.046). The most common
adverse events in the sumatriptan 4-mg SC and placebo groups, respectively, were 
injection-site reactions (43% and 15%), tingling (12% and 3%), dizziness or
vertigo (10% and 5%), and warm or hot sensation (8% and 2%). Treatment groups
were not statistically compared for adverse events. CONCLUSIONS: Sumatriptan 4 mg
SC was effective for the acute treatment of migraine attacks and was generally
well tolerated in these patients.

Publication Types: 
    Randomized Controlled Trial

PMID: 16750463 [PubMed - indexed for MEDLINE]

1177: Can J Neurol Sci. 2006 May;33(2):195-9.

Nalpha-methyl histamine safety and efficacy in migraine prophylaxis: phase III
study.

Millán-Guerrero RO, Isais-Millán R, Benjamín TH, Tene CE.

Department of Neurology, Unidad de Investigación Medica en Epidemiología Clínica,
Hospital General de Zona UMF No 1 IMSS. Colima.

BACKGROUND: The histamine catabolite, Nalpha-methylhistamine, possesses a
selective affinity for H3 receptors. For this reason, we considered evaluating
the efficacy of this histaminergic H3 agonist in migraine prophylactic treatment.
OBJECTIVE: To study the therapeutic potential of the subcutaneous administration 
of Nalpha-methylhistamine in migraine prophylaxis, in a Phase III clinical
pharmacological study. METHODS: Using a controlled double-blind, placebo
controlled clinical trial for 12 weeks, 60 patients with migraine, who fit the
criteria established by the International Headache Society, were selected. The
efficacy of subcutaneous administration of Nalpha-methylhistamine 1 to 3 ng twice
a week against placebo was studied, evaluating the outcome of headache intensity,
frequency, duration, and analgesic intake. RESULTS: Comparison between the groups
treated with placebo (n=30) and Nalpha-methylhistamine (n=30), on data collected 
for the 4th, 8th and 12th weeks of treatment, revealed that
Nalpha-methylhistamine exerted a significant (p<0.0001) reduction (compared to
placebo) in intensity, frequency, and duration of migraine attacks, as well as on
the use of analgesic intake. No significant (p>0.05) adverse experiences or side 
effects developed in either group. CONCLUSIONS: The present study provides
evidence of the efficacy of Nalpha-methylhistamine, given subcutaneously at doses
of 1 to 3 ng twice a week, offering a new therapeutic alternative and laying the 
clinical and pharmacological groundwork for the use of histaminergic H3-agonists 
in migraine prophylaxis, which may specifically inhibit the neurogenic edema
response involved in migraine pathophysiology.

Publication Types: 
    Clinical Trial, Phase III
    Randomized Controlled Trial

PMID: 16736729 [PubMed - indexed for MEDLINE]

1178: Headache. 2006 Jun;46(6):1005-10.

Tremor in patients with migraine.

Duval C, Norton L.

Département de Kianthropologie, Université du Québec in Montréal, Canada.

BACKGROUND: It has been suggested that patients with migraine are at a higher
risk of developing essential tremor (ET). In addition, it was shown that patients
with migraine are at higher risk of subclinical vascular infarcts in the
cerebellum, a structure believed to be implicated in ET. OBJECTIVE: Determine
whether patients with migraine who do not show clinically detectable ET have
subtle alteration in their physiological tremor characteristics that may serve as
a predictor for the eventual appearance of ET. METHODS: The physiological tremor 
of 30 patients with migraine (25 women, mean age: 41 +/- 8 years) was examined
using a laser displacement sensor. Tremor was recorded in 5 conditions:
hand-rest, hand-postural, finger-rest, finger-postural, and finger-loading (70
g). We also recorded tremor in healthy controls who never experienced migraine.
Amplitude, median power frequency, power dispersion (width of a frequency band
containing 68% of the power), and power distribution within 3 predetermined
frequency bands of interest (3.5 to 7.5, 7.5 to 12.5, and 16 to 30 Hz) were
assessed in each condition. RESULTS: All tremor characteristics described above
were very similar between the migraine group and controls. These results were
supported by the lack of correlation between tremor characteristics and the
number of years of experiencing migraine (ranging from 3 to 41 years; mean: 20
+/- 10). Patients with aura (N = 21) had tremor characteristics similar to that
of patients without aura (N = 9) and controls. CONCLUSION: These results suggest 
that, if a link exists between migraine and ET, the latter might be the result of
an "acute event" (eg, stroke) rather than a progressive alteration of
tremorogenic mechanisms.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16732847 [PubMed - indexed for MEDLINE]

1179: Headache. 2006 Jun;46(6):997-1004.

Retinal vascular caliber and migraine: the Blue Mountains Eye Study.

Liew G, Mitchell P, Wong TY, Wang JJ.

Department of Ophthalmology, Centre for Vision Research, University of Sydney,
Sydney, Australia.

OBJECTIVE: To assess whether migraine is associated with retinal microvascular
caliber. BACKGROUND: Migraine is believed to be associated with vascular disease,
but few studies have investigated the relationship between structural
microvascular changes and migraine. DESIGN: Population-based cross-sectional
study. METHODS: Participants in the Blue Mountains Eye Study follow-up (1997 to
1999, n = 2,335, aged 54+) had retinal photographs taken. A computer-assisted
method was used to measure average retinal arteriolar and venular diameters and
calculate the arteriole-to-venule ratio. History of migraine was recorded by
interview using International Headache Society criteria (1988). RESULTS: Subjects
giving a history of migraine without aura (n = 128) had narrower retinal
arterioles than subjects giving a history of migraine with aura (n = 182) or
subjects with no migraine history (n = 1619). After multivariate adjustment, mean
retinal arteriolar diameter was 4.3 microm (95% confidence interval 0.5, 8.1)
narrower in subjects reporting migraine without aura as compared to subjects with
no migraine. CONCLUSIONS: Individuals with a history of migraine without aura
were more likely to have slightly narrower retinal arteriolar caliber than
individuals without migraine. This relationship was not present for migraine with
aura. These data support the hypothesis that microvascular disease may be
associated with certain types of migraine.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16732846 [PubMed - indexed for MEDLINE]

1180: Headache. 2006 Jun;46(6):991-6.

Serotonin transporter protein polymorphism and harm avoidance personality in
migraine without aura.

Park JW, Han SR, Yang DW, Kim YI, Lee KS.

Department of Neurology, Catholic University of Korea, Seoul, Korea.

OBJECTIVE: To investigate polymorphisms in the serotonin transporter protein gene
and harm avoidance personality dimension in patients with migraine without aura
(MWOA). BACKGROUND: The serotonin transporter protein is a key modulator of
serotonergic synaptic neurotransmission. Two polymorphic regions of the gene for 
serotonin transporter protein have been found, and are associated with variations
in the functional activity of serotonin caused by differing transcriptional
efficiency. The harm avoidance (HA) personality trait may also be heritable and
associated with altered serotonergic neurotransmitter activity. DESIGN: We
amplified the polymorphism in the promoter of serotonin transporter protein
(5-HTTLPR) and the variable number of tandem repeats polymorphism within intron 2
(VNTR) using the polymerase chain reaction and performed genotype polymorphism
analyses in 97 patients with MWOA and 100 healthy controls. We investigated
serotonin-related personality traits by evaluating the HA personality dimension
using a tridimensional questionnaire. RESULTS: The genotype frequencies and
allele distributions of 5-HTTLPR did not differ between patients with MWOA and
controls. The VNTR genotype STin2.12/STin2.12 was significantly more common in
patients with MWOA (90%) than in controls (77%; P= .017). Patients with MWOA also
had HA scores (21.9 +/- 6.4) significantly higher than those of controls (16.3
+/- 6.1; P < .001). CONCLUSIONS: Serotonergic activity might be involved in the
development of MWOA and VNTR of serotonin transporter gene might be one of the
genetically contributing factors.

PMID: 16732845 [PubMed - indexed for MEDLINE]

1181: Headache. 2006 Jun;46(6):983-90.

Not tonight, I have a headache?

Houle TT, Dhingra LK, Remble TA, Rokicki LA, Penzien DB.

Department of Anesthesiology, Wake Forest University School of Medicine, Medical 
Center Boulevard, Winston-Salem, NC 27157-1009, USA.

OBJECTIVE: The present study examined the relationship between the diagnosis of
migraine and self-reported sexual desire. BACKGROUND: There is evidence for a
complex relationship between sexual activity and headache, particularly migraine.
The current headache diagnostic criteria even distinguish between several types
of primary headaches associated with sexual activity. METHODS: Members of the
community or students at the Illinois Institute of Technology (N = 68) were
administered the Brief Headache Diagnostic Interview and the Sexual Desire
Inventory (SDI). Based on the revised diagnostic criteria established by the
International Headache Society (ICHD-II), participants were placed in 1 of the 2 
headache diagnostic groups: migraine (n = 23) or tension-type (n = 36). RESULTS: 
Migraine subjects reported higher SDI scores, and rated their own perceived level
of desire higher than those suffering from tension-type headache. The presence of
the symptom "headache aggravated by routine physical activity" significantly
predicted an elevated SDI score. CONCLUSIONS: Migraine headaches and sexual
desire both appear to be at least partially modulated by serotonin (5-HT). The
metabolism of 5-HT has been shown to covary with the onset of a migraine attack, 
and migraineurs appear to have chronically low systemic 5-HT. As sexual desire
also has been linked to serotonin levels, the results are consistent with the
hypothesis that migraine and sexual desire both may be modulated by similar
serotonergic phenomena.

PMID: 16732844 [PubMed - indexed for MEDLINE]

1182: Headache. 2006 Jun;46(6):973-82.

The prevalence and impact of migraine headache in bipolar disorder: results from 
the Canadian Community Health Survey.

McIntyre RS, Konarski JZ, Wilkins K, Bouffard B, Soczynska JK, Kennedy SH.

Department of Psychiatry, University of Toronto, Mood Disorders
Psychopharmacology Unit, University Health Network, 399 Bathurst Street, Toronto,
ON, Canada M5T 2S8.

OBJECTIVE: To report on the prevalence of comorbid migraine in bipolar disorder
and the implications for bipolar age of onset, psychiatric comorbidity, illness
course, functional outcome, and medical service utilization. BACKGROUND: Migraine
comorbidity is differentially reported in bipolar versus unipolar depressed
clinical samples. The bipolar disorder-migraine association and its consequences 
have been infrequently reported in epidemiological studies. METHODS: Data for
this analysis were derived from respondents (n = 36 984) to the Canadian
Community Health Survey - Mental Health and Well-Being (CCHS). Respondents
reporting a lifetime WHO-CIDI-defined manic episode and physician-diagnosed
migraine (lifetime) were compared to respondents without migraine on
sociodemography, course of illness, and medical service utilization indices.
RESULTS: An estimated 2.4% of the sample met criteria for bipolar disorder.
Persons with bipolar disorder had a relatively higher prevalence of migraine
versus the general population (24.8% vs. 10.3%; P < .05). The sex-specific
prevalence of comorbid migraine in bipolar disorder was 14.9% for males and 34.7%
for females. Bipolar males with comorbid migraine were more likely to live in a
low income household (P < .05); receive welfare and social assistance (P < .05); 
report an earlier age of onset of bipolar disorder (P < .05); and have a higher
lifetime prevalence of comorbid anxiety disorders (P < .05). Bipolar males with
comorbid migraine were also more likely to utilize primary (P < .05) and mental
health care services (P < .05) . Bipolar females with comorbid migraine had more 
comorbid medical disorders (P < .05) and were more likely to require help with
personal or instrumental activities of daily living when compared to bipolar
females without migraine. CONCLUSION: Bipolar disorder with comorbid migraine is 
prevalent and associated with greater dysfunction and medical service
utilization, notable in males. Opportunistic screening and surveillance for
bipolar and comorbid migraine is warranted.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16732843 [PubMed - indexed for MEDLINE]

1183: Headache. 2006 Jun;46(6):942-53.

Pain characteristics of the acute migraine attack.

Kelman L.

Headache Center of Atlanta, 5671 Peachtree Dunwoody Road, Suite 620, GA 30342,
USA.

OBJECTIVES: This study describes the pain characteristics of the acute migraine
attack, including time of onset, time to peak, duration, intensity, quality,
aggravation by activity, as well as recurrence frequency and time to recurrence, 
in a tertiary care practice. BACKGROUND: The literature documenting the
characteristics of the pain of the acute attack of migraine is sparse. METHODS: A
total of 1,283 migraine patients (ICHD 1.1, 1.2, 1.5.1, and ICHD 1.6 [total
migraine population]) were evaluated at first visit. Headache character
(throbbing, aching, pressure, stabbing scaled grade 0 to 3; 0 = none; 1 = mild; 2
= moderate; 3 = severe), intensity (for average, minimum, and maximum intensity
headaches, scaled 0 to 10), lifetime duration, frequency per month, duration in
minutes (for average, minimum, maximum duration headaches), time of onset of
headache (morning, afternoon, evening, night, anytime), aggravation of headache
with activity (scaled 0 to 3), percentage recurrence, time to recurrence, were
recorded. Patients were stratified into different groups; ICHD 1.1, 1.2, and
1.5.1 (migraine) ICHD 1.1 and 1.2 (episodic migraine), ICHD 1.5.1 (chronic
migraine), and ICHD 1.6 (probable migraine). Patients with unremitting daily
headache were excluded. RESULTS: Demographics: A total of 84.3% patients were
female, and the mean age was 37.7, ranging from 13.0 to 80.5 years. Eight hundred
seventy-four patients were classified as ICHD 1.1, 1.2, and 1.5.1 (migraine), 524
with ICHD 1.1 and 1.2 (episodic migraine), 350 with ICHD 1.5.1 (chronic
migraine), and 409 with ICHD 1.6 (probable migraine). Study Results: Time of
onset of headache was mostly in the morning in 18.7%, afternoon 13.5%, evening
4.0%, during night 9.4%, and "anytime" 54.3%, with minor differences seen in
different headache types, gender, presence of aura, and headache frequency. The
median time to peak of the headache was greater in migraine than probable
migraine (90 minutes vs. 60 minutes; P < .01). Headache duration medians were
reported as minimum of 12 hours, maximum of 48 hours with an average of 24 hours,
females being greater than males in average headache (24.0 vs. 12.0; P < .01),
minimum (24.0 vs. 8; P < .05), and maximum (48.0 vs. 24.0; P < .01). Only the
minimum duration differed between migraine and atypical migraine (12.0 vs. 4.0; P
< .01). Headache intensity medians were as follows: average intensity 7/10,
minimum 4/10, and maximum 10/10, with no differences in migraine versus probable 
migraine, gender, or headache frequency. Headache intensity median was
consistently greater in migraine episodic than chronic migraine (average 8.0 vs. 
6.5, minimum 4.5 vs. 3.0, maximum 10.0 vs. 9.0, all P < .05). Headache character 
(greater than grade 1) was throbbing (73.5%), aching (73.8%), pressure (75.4%),
and stabbing (42.6%) with significantly more throbbing in migraine than in
probable migraine (73.5% vs. 63.2%; P < .01) and more aching in chronic than in
episodic migraine (65.4% vs. 63.1%; P < .05). Headache increased by activity was 
present in 90.2% of patients, grade 1 in 13.8%, grade 2 in 30.8%, and grade 3 in 
45.5% of patients. The presence of activity aggravating headache was more likely 
to be associated with headache triggers, maximum headache severity, longer time
to 50% reduction of headache, and longer time to absent headache with triptans,
and more headache-associated symptoms, and longer postdrome duration (all P <
.05). Recurrence rate was 43.8% with the median time to recurrence being 8 hours.
Significantly less recurrence occurred with episodic than chronic migraine (30.0%
vs. 50.0%; P < .01). CONCLUSIONS: This study provides an in-depth description of 
pain features in the acute migraine attack. It was found that a significant
number of patients need to be provided with the means of treating headache
rapidly in at least some of their headaches and that headache recurrence needs to
be addressed in a large number of patients.

PMID: 16732840 [PubMed - indexed for MEDLINE]

1184: Headache. 2006 Jun;46(6):934-41.

A clinical trial of trimethobenzamide/diphenhydramine versus sumatriptan for
acute migraines.

Friedman BW, Hochberg M, Esses D, Bijur PE, Corbo J, Paternoster J, Solorzano C, 
Toosi B, Lipton RB, Gallagher EJ.

Department of Emergency Medicine, Albert Einstein College of Medicine, Bronx, NY,
USA.

BACKGROUND: Although various classes of medication are used to treat acute
migraine in the emergency department (ED), no treatment offers complete pain
relief without side effects or recurrence of headache. Consequently, even though 
several antiemetic medications as well as SQ sumatriptan have demonstrated
efficacy and tolerability for the ED treatment of migraine, there remains a need 
for more effective parenteral therapies. Open-label studies suggest that the
combination of trimethobenzamide and diphenhydramine (TMB/DPH) may provide
effective relief in a high proportion of migraineurs. OBJECTIVE: To test the
hypothesis that ED patients with acute migraine, given intramuscular TMB/DPH,
would have a larger reduction in their pain scores than patients given SQ
sumatriptan. METHODS: This was an ED-based, randomized, double-blind,
"double-dummy" clinical trial comparing 2 parenteral treatments for acute
migraine headaches. Subjects received a combination of TMB 200 mg and DPH 25 mg
as a single intramuscular injection or 6 mg of SQ sumatriptan. Pain scores,
disability scores, associated symptoms, and adverse effects were assessed for 2
hours in the ED and by telephone 24 hours after medication administration. The
primary outcome was the between-group difference in reduction of pain intensity
as measured by a validated numerical rating scale 2 hours after medication
administration. This study was designed to detect superiority of TMB/DPH;
therefore, a 1-tailed t-test was used. An interim analysis was planned to
terminate the trial if predetermined endpoints in the primary outcome variable
were reached. RESULTS: The trial was stopped by the data monitoring committee
after 40 subjects were enrolled because a substantial benefit in the primary
outcome was found favoring sumatriptan. Baseline pain scores were comparable
between the 2 groups. By 2 hours, sumatriptan subjects had improved by a mean of 
6.1 and the TMB/DPH subjects had improved by a mean of 4.4 (95% CI for difference
of 1.7: -0.1 to 3.4). By 24 hours after medication administration, sumatriptan
subjects had a mean improvement from baseline of 4.9 as compared to 5.3 for TMB
(95% CI for difference of -0.4: -2.4 to 1.6). The need for rescue medication was 
comparable between the groups. No serious or frequent adverse effects were noted 
in either group. CONCLUSIONS: SQ sumatriptan is probably superior to TMB/DPH for 
treating the pain of acute migraine at 2 hours. However, TMB/DPH was
well-tolerated, efficacious, and relieved pain comparably to sumatriptan at 24
hours. TMB/DPH might have a role in select populations in which sumatriptan is
contraindicated or likely to be ineffective.

Publication Types: 
    Comparative Study
    Randomized Controlled Trial

PMID: 16732839 [PubMed - indexed for MEDLINE]

1185: Headache. 2006 Jun;46(6):914-24.

Efficacy of Rizatriptan 10 mg administered early in a migraine attack.

Cady R, Martin V, Mauskop A, Rodgers A, Hustad CM, Ramsey KE, Skobieranda F.

Primary Care Network, 3805 S. Kansas Expressway, Springfield, MO 65807, USA.

OBJECTIVE: To determine if administration of rizatriptan 10 mg is superior to
placebo for the early treatment of acute migraine, while the pain is mild.
BACKGROUND: Past studies have suggested that treatment outcomes can be improved
if a triptan is administered early in the time course of a migraine attack.
METHODS: Two randomized, parallel, placebo-controlled, double-blind studies. TAME
(Treat A Migraine Early)1 was conducted at 46 centers in the United States;
TAME2, at 48 centers in the United States. Totally, 1030 adult patients with at
least a 6-month history of migraine were studied. Patients were instructed to
treat within 1 hour of migraine onset, while pain was mild. Patients maintained a
headache diary in which they rated their levels of pain and disability, and
recorded other symptoms of migraine. Primary endpoints were pain freedom at 2
hours and sustained pain freedom at 24 hours post-dose. RESULTS: In TAME1, 57.3% 
versus 31.1% of patients reported pain freedom at 2 hours post-dose and 42.6%
versus 23.2% reported 24-hour sustained pain freedom with rizatriptan versus
placebo, respectively (P < .001 for both). In TAME2, 58.9% versus 31.1% of
patients reported pain freedom at 2 hours post-dose and 48.0% versus 24.6%
reported 24-hour sustained pain freedom with rizatriptan versus placebo,
respectively (P < .001 for both). All other efficacy endpoints favored
rizatriptan. Repeat doses of the medicine were not allowed; patients may have
delayed treatment; non-migraine headaches may have been treated. CONCLUSIONS:
Rizatriptan 10 mg was superior to placebo when treating migraine early, while
pain is mild, as measured by pain freedom at 2 hours and 24-hour sustained pain
freedom.

Publication Types: 
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 16732837 [PubMed - indexed for MEDLINE]

1186: Stroke. 2006 Jul;37(7):1765-70. Epub 2006 May 25.

Brain gray matter changes in migraine patients with T2-visible lesions: a 3-T MRI
study.

Rocca MA, Ceccarelli A, Falini A, Colombo B, Tortorella P, Bernasconi L, Comi G, 
Scotti G, Filippi M.

Neuroimaging Research Unit, Scientific Institute and University Ospedale San
Raffaele, Milan, Italy.

BACKGROUND AND PURPOSE: In migraine patients, functional imaging studies have
shown changes in several brain gray matter (GM) regions. However, 1.5-T MRI has
failed to detect any structural abnormality of these regions. We used a 3-T MRI
scanner and voxel-based morphometry (VBM) to assess whether GM density
abnormalities can be seen in patients with migraine with T2-visible abnormalities
and to grade their extent. METHODS: In 16 migraine patients with T2-visible
abnormalities and 15 matched controls, we acquired a T2-weighted and a
high-resolution T1-weighted sequence. Lesion loads were measured on T2-weighted
images. An optimized version of VBM analysis was used to assess regional
differences in GM densities on T1-weighted scans of patients versus controls.
Statistical parametric maps were thresholded at P<0.001, uncorrected for multiple
comparisons. RESULTS: Compared with controls, migraine patients had areas of
reduced GM density, mainly located in the frontal and temporal lobes. Conversely,
patients showed increased periacqueductal GM (PAG) density. Compared with
patients without aura, migraine patients with aura had increased density of the
PAG and of the dorsolateral pons. In migraine patients, reduced GM density was
strongly related to age, disease duration, and T2-visible lesion load (r ranging 
from -0.84 to -0.73). CONCLUSIONS: Structural GM abnormalities can be detected in
migraine patients with brain T2-visible lesions using VBM and a high-field MRI
scanner. Such GM changes comprise areas with reduced and increased density and
are likely related to the pathological substrates associated with this disease.

PMID: 16728687 [PubMed - indexed for MEDLINE]

1187: Eur J Neurol. 2006 May;13(5):533-5.

No association of C-1019G promoter polymorphism of 5-HT1A receptor gene with
migraine.

Yang XS, Xu XP, Yang QD.

Department of Neurology, Xiangya Hospital, Central South University, Changsha,
Hunan, China. xiaosuy2004@163.com

It is well known that migraine has a strong genetic component, although the type 
and number of genes involved remains unclear. There is evidence to suggest that
serotonin-related genes may be involved in the pathogenesis of migraine. To
investigate whether the 5-HT1A receptor gene contributes to the risk of migraine 
we performed an association study of C-1019G promoter polymorphism of the gene in
102 migraineurs and 93 controls. Subjects were of Han Chinese origin. No
significant differences in allele (P=0.82) or genotype frequencies (P=0.71) were 
seen in migraineurs compared with the controls. When migraine with aura, without 
aura, with family history, without family history were analyzed separately, the
frequencies did not vary significantly. Our results suggest that C-1019G in
5-HT1A is not a major genetic risk factor for migraine.

Publication Types: 
    Comparative Study

PMID: 16722981 [PubMed - indexed for MEDLINE]

1188: Expert Opin Pharmacother. 2006 Jun;7(8):1085-95.

Botulinum toxin type A for the treatment of migraine.

Aurora S.

Swedish Headache Center, University of Washington, Seattle, WA 98104, USA.
Sheena.Aurora@Swedish.org

Migraine is a common and debilitating disorder that often requires prophylactic
therapy, particularly for those migraine patients who meet the diagnostic
criteria for chronic daily headache (chronic migraine). Existing prophylactic
treatments for migraine are inadequate for many patients due to their modest
efficacy and/or systemic side effects. Alternative treatment strategies are
needed, particularly in those with chronic migraine. Botulinum toxin type A is a 
locally injected protein complex that has been investigated as a treatment for
episodic migraine and chronic daily headache. A systematic series of controlled
trials has led to the identification of a subset of migraineurs with chronic
daily headache who obtain demonstrated benefits of botulinum toxin type A over
placebo that is maintained with repeated treatments.

Publication Types: 
    Review

PMID: 16722818 [PubMed - indexed for MEDLINE]

1189: Pediatr Ann. 2006 May;35(5):345-53.

Headaches in children.

Rubin DH, Suecoff SA, Knupp KG.

Department of Pediatrics, St Barnabas Hospital, Bronx, NY 10457, USA.
david_rubin@stbarnabas-ny.org

Headache is an incredibly common complaint, but a detailed evaluation is
necessary to diagnose some life-threatening diseases that may have their initial 
presentation in this manner. The evaluation and management of pediatric headaches
requires close attention to a detailed "headache history," physical,
neurological, and ophthalmologic examinations, and, when indicated, specific
neuroimaging studies. Close follow-up of those patients with headaches is
mandatory, whether they are placed on long-term or short-term medications. It
also is important to appreciate the potential co-existence of headaches with
other chronic disorders, such as asthma or diabetes.

Publication Types: 
    Review

PMID: 16722293 [PubMed - indexed for MEDLINE]

1190: Neurology. 2006 Jun 27;66(12):1894-8. Epub 2006 May 17.

Comment in:
    Neurology. 2006 Jun 27;66(12):E43-4.    Neurology. 2007 Feb 13;68(7):536; author reply 536.

Probable medication-overuse headache: the effect of a 2-month drug-free period.

Zeeberg P, Olesen J, Jensen R.

Danish Headache Center, Department of Neurology, University of Copenhagen,
Glostrup Hospital, Nordre Ringvej 57, DK-2600 Glostrup, Denmark.
peter.zeeberg@dadlnet.dk

OBJECTIVE: To describe the emerging profile of headache frequency following a
2-month drug-free period in patients with medication overuse. METHODS: All
patients treated and discharged from Danish Headache Center in 2002 and 2003 had 
prospectively filled out a diagnostic headache diary on a daily basis. For
patients with probable medication-overuse headache (MOH), the authors determined 
headache frequencies before and after medication withdrawal from these
prospective recordings. RESULTS: Among 1,326 patients, 337 had probable MOH. Two 
hundred sixteen patients who stayed medication-free for 2 months were eligible.
Overall, 45% of the patients improved, 48% had no change, and 7% had more
headaches. Median age was 48 years, and male/female ratio 1:2.7. The relative
reduction in headache frequency varied considerably with a 67% median reduction
in migraine, 0% in tension-type headache (TTH), and 37% in patients with both
migraine and TTH (MT). Comparing the diagnostic groups, the relative reduction in
frequency differed between migraine and TTH (p < 0.001) and between MT and TTH (p
< 0.01). Triptan/ergot overusers improved the most (p < 0.0001). The difference
between MT and TTH remained significant when triptan/ergot overuse was controlled
(p < 0.05). CONCLUSION: These data demonstrate the benefit of withdrawal in
already established medication overuse and support the existence of
medication-overuse headache as a clinical entity.

Publication Types: 
    Clinical Trial
    Research Support, Non-U.S. Gov't

PMID: 16707727 [PubMed - indexed for MEDLINE]

1191: Neurology. 2006 Aug 22;67(4):676-8. Epub 2006 May 17.

Episodic neurologic dysfunction with migraine and reversible imaging findings
after radiation.

Pruitt A, Dalmau J, Detre J, Alavi A, Rosenfeld MR.

Division of Neuro-oncology, Department of Radiology, Hospital of the University
of Pennsylvania, Philadelphia, USA.

Reported are three adults who developed frequent episodes of a complex neurologic
syndrome years after radiation therapy for a brain tumor. MRI and
[(18)F]fluorodeoxyglucose PET performed during the episodes demonstrated dramatic
gyral thickening with enhancement and intense hypermetabolism in symptomatic
regions that resolved on follow-up studies. EEG during episodes showed only
slowing. The differential diagnosis and imaging findings are reviewed.

Publication Types: 
    Case Reports

PMID: 16707725 [PubMed - indexed for MEDLINE]

1192: Drugs. 2006;66(6):883-90.

Comment in:
    Drugs. 2006;66(6):891-2.

Sumatriptan fast-disintegrating/rapid-release tablets.

Moen MD, Keating GM.

Adis International Limited, 41 Centorian Drive, Mairangi Bay, Auckland 1311, New 
Zealand. demail@adis.co.nz

Sumatriptan is a serotonin 5-HT(1B/1D) receptor agonist that is used for the
acute treatment of migraine attacks. A new fast-disintegrating/rapid-release
sumatriptan tablet (sumatriptan FDT/RRT) has been developed with the goal of
speeding absorption and onset of effect compared with standard sumatriptan
tablets. Bioequivalence of sumatriptan FDT/RRT tablets to standard sumatriptan
tablets was established in healthy volunteers. Initial data suggest that
sumatriptan FDT/RRT tablets may disintegrate faster and get emptied from the
stomach faster than standard sumatriptan tablets. In a randomised, double-blind, 
multicentre, early intervention trial in adults with mild migraine, significantly
more sumatriptan FDT/RRT 50 and 100mg recipients than placebo recipients were
pain free or migraine free 2 hours after receiving study medication. Compared
with placebo, pain relief was significantly greater with sumatriptan FDT/RRT
100mg at 25 and 17 minutes following administration, and with sumatriptan FDT/RRT
50mg at 50 and 30 minutes following administration, in two randomised,
double-blind, multicentre trials in adults with moderate to severe migraine.
Sumatriptan FDT/RRT tablets were generally well tolerated; the tolerability
profile was similar to that reported for standard sumatriptan tablets in other
studies.

PMID: 16706565 [PubMed - indexed for MEDLINE]

1193: Curr Opin Neurol. 2006 Jun;19(3):294-8.

New insights into migraine pathophysiology.

Sanchez-Del-Rio M, Reuter U, Moskowitz MA.

Department of Neurology, Hospital Ruber Internacional, Madrid, Spain.

PURPOSE OF REVIEW: This article will review new and exciting developments in
migraine research, with particular emphasis on mutations associated with familial
hemiplegic migraine and the role of cortical spreading depression in its
pathophysiology and treatment. RECENT FINDINGS: The recent discovery of multiple 
point mutations in familial hemiplegic migraine has led to the suggestion that
migraine and its variants may be due to a paroxysmal disturbance in
ion-translocating mechanisms. Mutations associated with familial hemiplegic
migraine render the brain more susceptible to prolonged cortical spreading
depression caused by either excessive synaptic glutamate release or decreased
removal of glutamate and potassium from the synaptic cleft, or persistent sodium 
influx. Suppression of cortical spreading depression has become an interesting
target for preventive migraine treatment. Prolonged treatment with beta-blockers,
valproate, topiramate, methysergide or amitriptyline reduced the number of
potassium-evoked cortical spreading depressions and elevated the electrical
stimulation threshold for the induction of cortical spreading depression in rats.
Recent imaging studies in patients suffering from migraine without aura also
point to the presence of silent cortical spreading depression as an underlying
mechanism. Repeated waves of cortical spreading depression may have deleterious
effects on brain function, and perhaps cause silent ischaemic lesions in
vulnerable brain regions such as the cerebellum in susceptible individuals.
SUMMARY: This review emphasizes several neurobiological aspects of migraine that 
reveal paroxysmal disturbances in neuronal and vascular function, that in turn
reflect disturbances in the maintenance of ionic gradients.

Publication Types: 
    Review

PMID: 16702838 [PubMed - indexed for MEDLINE]

1194: Curr Opin Neurol. 2006 Jun;19(3):286-93.

Migraine with aura: new understanding from clinical epidemiologic studies.

Kirchmann M.

Danish Headache Center, Department of Neurology, Glostrup Hospital, University of
Copenhagen, Copenhagen, Denmark. Kirchmann@dadlnet.dk

PURPOSE OF REVIEW: To discuss the consequences of recent clinical data on
migraine with aura for clinical practice and future research in the light of new 
diagnostic criteria for migraine with aura. RECENT FINDINGS: Migraine with aura
is now distinguished from hemiplegic migraine and from basilar migraine. Migraine
with typical aura has an aura consisting of visual, sensory, or speech symptoms. 
The aura symptoms typically develop gradually over 5 or more minutes, last
between 5 and 60 minutes and, when more than one symptom is present, they occur
in succession. Half-sidedness is typical of visual and sensory symptoms, whereas 
speech symptoms are typically aphasic, primarily of the Broca type. A visual aura
rating scale with a high sensitivity and specificity has been developed to
standardize the diagnosis of visual aura. The new classification, the new
criteria, and the new knowledge about clinical features of migraine with aura are
important both for routine clinical diagnosis and for future research studies.
SUMMARY: Recent studies of the clinical features of migraine with aura allow a
more precise diagnosis and classification than previously possible. A clear
distinction between migraine with typical aura, hemiplegic migraine, and basilar 
migraine is important for genetic and other research studies.

Publication Types: 
    Review

PMID: 16702837 [PubMed - indexed for MEDLINE]

1195: Int J Clin Pract. 2006 May;60(5):604-5.

Metoclopramide for migraine-associated hiccup.

Gupta VK.

Dubai Police Medical Services, Dubai, United Arab Emirates. dr_vkgupta@yahoo.com

Persistent hiccup can be a distressing disorder. I present a case of
migraine-attack-associated sustained hiccup. Metoclopramide can swiftly control
both hiccup and migraine headache. Vasopressin release probably underlies
migraine-aborting action of metoclopramide while restoration of oesophageal
smooth muscle function involves competitive dopaminergic antagonism and a
prominent cholinergic agonist activity. Episodic prolonged hiccup associated with
nausea is an unusual presenting feature of migraine.

Publication Types: 
    Case Reports

PMID: 16700863 [PubMed - indexed for MEDLINE]

1196: CNS Drugs. 2006;20(5):343-50.

Role of melatonin in the pathophysiology of migraine: implications for treatment.

Vogler B, Rapoport AM, Tepper SJ, Sheftell F, Bigal ME.

Jefferson Headache Center, Thomas Jefferson University, Philadelphia,
Pennsylvania, USA.

The pineal gland and its secretory product, melatonin, have been implicated in
the pathophysiology of migraine, as well as some of its comorbid disorders.
Supporting this view, many migraineurs are susceptible to various environmental
triggers that influence the secretion of melatonin from the pineal gland, and
many prodromal symptoms are probably generated in the hypothalamus, a brain
region that provides input into the pineal gland to modulate the secretion of
melatonin. In addition, studies have shown abnormalities in melatonin secretion
in patients who experience migraine and an improvement in migraine following
administration of melatonin. However, the dysfunction in melatonin secretion in
migraineurs may simply be a marker of hypothalamic dysfunction or neuronal
hyperexcitability, leading to migraine susceptibility. It is also possible that
abnormal melatonin secretion leads to decreased inhibitory neurotransmitter
activity, decreased inhibition of the release of calcitonin gene-related peptide 
(CGRP) from activation of the trigeminal system, or less analgesia.Whatever its
role in the pathogenesis of migraine, melatonin may prove to be a useful therapy.
Future studies are necessary to further elucidate whether melatonin is a well
tolerated, beneficial therapy, and to determine the optimal dose and formulation 
of melatonin for use in migraine therapy.

Publication Types: 
    Review

PMID: 16696576 [PubMed - indexed for MEDLINE]

1197: Neurol Sci. 2006 May;27 Suppl 2:S96-9.

Treatment of aura: solving the puzzle.

D'Andrea G, Nordera GP, Allais G.

Headache and Cerebrovascular Center, Villa Margherita Neurological Clinic,
Arcugnano (VI), Italy.

Migraine with aura (MwA) sufferers, at times, need specific treatments. This is
the case when the auras are frequent, prolonged and cause anxiety and distress.
Abnormal release of glutamate, which may trigger auras, and abnormal platelet
behaviour, which constitutes a possible predisposing factor to MwA, are possible 
targets for MwA-specific prophylactic therapy. Here we present results obtained
using lamotrigine (two open trials), an agent known to inhibit glutamate release,
and picotamide, an antiplatelet drug, in the prophylactic treatment of MwA
sufferers. Lamotrigine significantly reduced the frequency of MwA attacks, and
picotamide together with lamotrigine reduced the duration and/or the occurrence
of auras. In comparison to lamotrigine, the therapy with picotamide may have some
advantages such as the use of the therapeutic dose from the first day of
treatment (lamotrigine needs one month or more to reach such a dose) and the
possibility to prevent cerebral ischaemic events and migraine stroke, a rare but 
severe complication of MwA attacks.

Publication Types: 
    Clinical Trial

PMID: 16688638 [PubMed - indexed for MEDLINE]

1198: Neurol Sci. 2006 May;27 Suppl 2:S91-5.

The complications of migraine with aura.

Agostoni E, Aliprandi A.

Department of Neurosciences, Manzoni Hospital, Lecco, Italy. e.agostoni@libero.it

Migraine with aura is a common disorder in industrialised countries, affecting up
to 5% of the adult population. Although migraine aura is usually a benign
disorder, in rare instances it can be the cause of serious neurologic
complications. The most common is migrainous stroke, defined as a persistent
neurologic deficit following the aura with evidence of brain infarction at
neuroimaging and lack of alternative explanations. The most likely pathogenic
mechanism is brain ischaemia induced by cortical spreading depression, but other 
possibilities, such as intracranic arterial dissection or embolism through patent
foramen ovale need to be considered. Other complications are migraine-related
seizures, which are probably caused by neuronal hyperexcitability in migraineurs,
and persistent auras without infarction. These disorders are of both clinical and
scientific interest, as they throw light on the complex and not yet fully
understood relationship between migraine with aura, stroke and epilepsy.

Publication Types: 
    Review

PMID: 16688637 [PubMed - indexed for MEDLINE]

1199: Neurol Sci. 2006 May;27 Suppl 2:S86-90.

From spreading depression to the trigeminovascular system.

Dalkara T, Zervas NT, Moskowitz MA.

Department of Neurology, Faculty of Medicine, Hacettepe University, Ankara,
Turkey.

Migraine headaches have a complex pathophysiology; both vascular and neuronal
mechanisms have been proposed. One possible scenario begins with brain-initiated 
events evolving to cortical spreading depression (CSD), which in turn activates
the trigeminal nerve to cause headaches. Experimental evidence supports a
relationship between CSD as a cause of migraine aura as well as CSD as a cause of
trigeminal activation. Susceptibility to CSD and to migraine appears to be
genetically determined. In some migraine subtypes, genes controlling
translocation of calcium, sodium and potassium have been implicated, perhaps
altering the susceptibility to CSD. This chapter briefly reviews current
knowledge pertaining to migraine pathophysiology with emphasis on current notions
linking disturbances in ion flux to the genesis of headache.

Publication Types: 
    Review

PMID: 16688636 [PubMed - indexed for MEDLINE]

1200: Neurol Sci. 2006 May;27 Suppl 2:S82-5.

Energy metabolism in migraine.

Lodi R, Tonon C, Testa C, Manners D, Barbiroli B.

Dipartimento di Medicina, Clinica e Biotecnologia Applicata "D. Campanacci",
Università di Bologna, Policlinico S. Orsola, Via Massarenti 9, I-40138, Bologna,
Italy. raffaele.lodi@unibo.it

Over the last two decades magnetic resonance spectroscopy has been extensively
used to investigate the role of energy metabolism impairment in the
physiopathology of migraine. In this paper we review the studies performed on
migraine sufferers during headache attacks as well as interictally. Overall there
is currently evidence that migraine is associated with a generalised disorder of 
energy metabolism and that this, in association with other susceptibility
factors, may be an important feature that lowers the threshold for triggering
migraine attacks.

Publication Types: 
    Review

PMID: 16688635 [PubMed - indexed for MEDLINE]

1201: Neurol Sci. 2006 May;27 Suppl 2:S77-81.

Neurophysiological features of the migrainous brain.

Schoenen J.

Department of Neurology-Headache Research Unit and Research Center for Cellular
and Molecular Neurobiology, University of Liège, Liège, Belgium.
jschoenen@ulg.ac.be

Migraine is a disorder in which central nervous system (CNS) dysfunction might
play a pivotal role. As there are no consistent structural disturbances, clinical
neurophysiology methods seem particularly suited to study its pathophysiology.
This chapter will focus on a review of neurophysiological studies that have
provided an insight into migraine pathogenesis. The results are in part
contradictory, which may be due to the methodology, patient selection or timing
of study. Nonetheless, quantitative electroencephalography and
magnetoencephalography recordings during migraine attacks provide strong, though 
indirect, evidence favouring the occurrence of spreading cortical depression
during attacks of migraine with, and possibly without, aura. Evoked cortical
potential and nociceptive blink reflex studies demonstrate that lack of
habituation during repetitive stimulation is a reproducible CNS dysfunction
interictally in both migraine with and without aura. Transcranial magnetic
stimulations show excitability changes of the visual cortex. The interictal
migrainous CNS dysfunction is likely to play a role in migraine pathogenesis, has
a familial character and undergoes periodic modulations with quasi-normalisation 
just before, during an attack and after treatment with certain prophylactic
agents. In addition, neurophysiological methods have revealed subclinical
abnormalities of cerebellar function and neuromuscular transmission, which may
improve phenotyping of migraineurs for genetic and therapeutic studies.

Publication Types: 
    Review

PMID: 16688634 [PubMed - indexed for MEDLINE]

1202: Neurol Sci. 2006 May;27 Suppl 2:S193-7.

Efficacy and tolerability of almotriptan versus zolmitriptan for the acute
treatment of menstrual migraine.

Allais G, Acuto G, Cabarrocas X, Esbri R, Benedetto C, Bussone G.

Woman's Headache Center, Department of Gynecology and Obstetrics, University of
Turin, Via Ventimiglia 3, I-10126, Turin, Italy. gb.allais@tiscali.it

Menstrual migraine (MM) attacks are a challenge for the headache specialist,
because they are particularly difficult to treat. Almotriptan is a
second-generation triptan successfully used for the acute treatment of migraine. 
No data on the efficacy and safety of almotriptan in MM treatment have been
published previously. The objective was to evaluate the efficacy and tolerability
of almotriptan in the symptomatic treatment of MM attacks and to compare these
parameters to those obtained with zolmitriptan, another second-generation
triptan. Data from a multicentre, multinational, randomised, double-blind,
parallel clinical trial, conducted at 118 centres in 9 European countries, to
evaluate the efficacy and tolerability of almotriptan 12.5 mg vs. zolmitriptan
2.5 mg in the acute treatment of migraine were analysed retrospectively. Of the
1061 patients included, 902 were women and 255 of these treated a MM attack: 136 
with almotriptan and 119 with zolmitriptan. No significant difference between the
two treatments was found. Two hours after dosing, 67.9% of almotriptan-treated
and 68.6% of zolmitriptan-treated patients had obtained pain relief; while 44.9% 
and 41.2%, respectively, were pain free. Recurrence rates 2-24 h after dosing
were 32.8% for almotriptan and 34.7% for zolmitriptan. Adverse events in the 24 h
after dosing were reported by 19.8% of those taking almotriptan and 23.1% of
those taking zolmitriptan. In conclusion, almotriptan is effective and safe in
the treatment of MM attacks.

Publication Types: 
    Comparative Study
    Evaluation Studies
    Multicenter Study
    Randomized Controlled Trial

PMID: 16688629 [PubMed - indexed for MEDLINE]

1203: Neurol Sci. 2006 May;27 Suppl 2:S190-2.

Mismatch in how oestrogen modulates molecular and neuronal function may explain
menstrual migraine.

Welch KM, Brandes JL, Berman NE.

Rosalind Franklin University of Medicine and Science, North Chicago, USA.
michael.welch@rosalindfranklin.edu

This paper is designed to provide concepts and stimulate directions for further
investigation of menstrual migraine. On the basis of experimental studies and
literature review, we propose that abnormalities in how estrogen modulates
neuronal function in migraine are due to a mismatch between its gene-regulation
and membrane effects. In the interictal phase when estrogen levels peak,
increased neuronal excitability is balanced by homeostatic gene regulation in
brain cortex, and nociceptive systems. When levels fall at menses, mismatch in
homeostatic gene regulation by estrogen unmasks non-nuclear mitogen-activated
hyperexcitability of cell membranes, sensitizing neurons to triggers that
activate migraine attacks. At the trough of estrogen levels, the down-regulating 
effect on inflammatory genes is lost and peptide modulated central sensitization 
is increased as is pain and disability of the migraine attack.

Publication Types: 
    Review

PMID: 16688628 [PubMed - indexed for MEDLINE]

1204: Neurol Sci. 2006 May;27 Suppl 2:S159-63.

Topiramate in migraine prophylaxis: data from a pooled analysis and open-label
extension study.

Bussone G, Usai S, D'Amico D.

Headaches and Cerebrovascular Disorders Unit, C. Besta National Neurological
Institute, Via Celoria 11, I-20133, Milan, Italy. bussone@istituto-besta.it

Topiramate is approved for the preventive treatment of migraine in several
countries based on the results of three large randomised, double-blind studies
that showed that this compound was significantly more effective than placebo in
migraine prophylaxis. We review the results of two studies: one which pooled data
from the three controlled double-blind trials using 100 mg/day of topiramate, and
an open-label extension of two of these trials in which patients received
different topiramate doses for an eight-month maintenance period. The overall
results confirm that topiramate is effective in reducing migraine frequency, and 
has a satisfactory tolerability profile.

Publication Types: 
    Review

PMID: 16688622 [PubMed - indexed for MEDLINE]

1205: Neurol Sci. 2006 May;27 Suppl 2:S153-8.

Which therapy for which patient?

Pierangeli G, Cevoli S, Sancisi E, Grimaldi D, Zanigni S, Montagna P, Cortelli P.

Dipartimento di Scienze Neurologiche, Università di Bologna, Via U. Foscolo 7,
I-40123, Bologna, Italy. giulia.pierangeli@unibo.it

Prophylactic treatment is mainly intended to reduce the frequency of migraine
attacks, enhance response to acute medications, improve patient function and
reduce disability. Sufficient evidence and consensus exist to recommend
propranolol, timolol, amitriptyline, pizotifen, divalproex, sodium valproate and 
topiramate as first line agents for migraine prevention. These drugs can halve
the frequency of attacks in 50% of patients. The anticipated benefit must be
weighed against the adverse effects associated with each agent in determining the
optimal preventive regimen for individual patients considering any comorbid
conditions that are often present. The decision to treat and the choice of
prophylactic drug must be taken with the patient. It is important to balance
expectations and therapeutic realities for each particular drug. Recent data on
the effect of prophylactic treatment on trigeminovascular activation and on
cortical spreading depression emphasise the importance of developing research on 
migraine-preventive drugs.

Publication Types: 
    Review

PMID: 16688621 [PubMed - indexed for MEDLINE]

1206: Neurol Sci. 2006 May;27 Suppl 2:S123-9.

Which triptan for which patient?

Rapoport AM, Tepper SJ, Sheftell FD, Kung E, Bigal ME.

Department of Neurology, Columbia University, New York, NY, USA.
alanrapoport@nech.net

The triptans were developed for the acute treatment of a migraine attack and have
revolutionised the treatment of this disorder since their introduction in the
early 1990s. Although their mechanisms of actions are similar and based on the
stimulation of specific serotonin (5-hydroxytryptamine) receptors including
peripheral 1B and central and peripheral 1D subtypes, each triptan has its own
distinctive pK properties that result in different profiles of efficacy and
tolerability. Triptans work by decreasing neurogenic inflammation peripherally in
the meninges, vasoconstriction of meningeal vessels and by modulating
secondary-order neurons in the brain stem. Studies of patient attitudes towards
their acute care regimens reveal that they are often unhappy with some aspect of 
their treatment-usually the speed of action, degree of efficacy, presence of
adverse events and the need for additional doses due to frequent and/or rapid
recurrence. The majority of patients, when asked in a clinical trial performed at
tertiary care headache centres, are willing to try another triptan. The aim of
this article is to review the pK and clinical characteristics of these acute
care, migraine-specific triptan medications and discuss how their individual
characteristics lead to their preferred choice in various clinical scenarios. The
pK and clinical efficacy data presented are taken from older published studies in
which triptans were compared to placebo or each other, but the patients were
asked to wait till the headache reached moderate or severe intensity prior to
taking study medication. New studies have looked at early treatment paradigms and
result in better efficacy data, but are difficult to compare due to different
endpoints.

Publication Types: 
    Case Reports
    Review

PMID: 16688615 [PubMed - indexed for MEDLINE]

1207: Neurol Sci. 2006 May;27 Suppl 2:S117-22.

Treatment strategies in the acute therapy of migraine: stratified care and early 
intervention.

D'Amico D, Moschiano F, Usai S, Bussone G.

Headaches and Cerebrovascular Disorders Unit, C. Besta National Neurological
Institute, Via Celoria 11, I-20133, Milan, Italy. damicodo@tiscali.it.

Various treatment strategies have been proposed to help clinicians provide the
most effective acute treatment for migraine patients. Stratified care is based on
the concept that the most appropriate initial treatment can be prescribed after
evaluation of each patient's headache characteristics. The results of a large
multicentre trial showed that when patients were stratified according to
disability grade, clinical outcomes were significantly better than with step-care
approaches. Prospective studies have shown that treating migraines with triptans 
when pain is mild (early intervention) considerably increases success rates for
endpoints (pain-free at 2 h, sustained pain-free state) for which triptans had
relatively poor efficacy in pivotal trials, and which contribute most to patient 
satisfaction. Stratified care and early treatment are also cost-effective.
However these strategies are not suitable for all patients. Stratified care may
be rendered difficult by medication contraindications and changes in attack
characteristics over time. Early triptan intervention carries a risk of
medication overuse and might not be indicated in patients with lack of pain
progression. Successful implementation of both strategies requires that
physicians are well informed, and that they elicit an exhaustive headache history
from each patient.

Publication Types: 
    Review

PMID: 16688614 [PubMed - indexed for MEDLINE]

1208: Neurol Sci. 2006 May;27 Suppl 2:S107-10.

Inflammation and excitotoxicity: role in migraine pathogenesis.

Longoni M, Ferrarese C.

Department of Neuroscience and Biomedical Technologies, University of
Milano-Bicocca, Ospedale S. Gerardo, Monza, Italy.

The pathogenesis of migraine is still unclear, but much evidence suggests a role 
of inflammation in pain generation. Calcitonin gene related peptide, nitric oxide
and cytokines are all molecules shown to be involved both in animal and human
studies. The glutamatergic system is also described as a possible mechanism
leading to neuronal hyperexcitability and cortical spreading depression (CSD).
Excitotoxic neural death, due to excessive release of the amino acid in the
extracellular space, may represent a consequence of protracted CSD and oligaemia 
and may be involved in migrainous infarction and aspecific lesions seen on
T2-weighted NMR imaging.

Publication Types: 
    Review

PMID: 16688611 [PubMed - indexed for MEDLINE]

1209: Neurol Sci. 2006 Apr;27(1):47-50.

Gender ratio of migraine without aura: observations over time.

Cucurachi L, Devetak M, Torelli P, Lambru G, Manzoni GC.

Headache Centre, Department of Neurology, University of Parma Ospedale Maggiore, 
via Gramsci 14, I-43100 Parma, Italy. cucurachi77@yahoo.com

Migraine without aura is typically considered a female condition. The purpose of 
this study was to determine if there have been any changes in the female-to-male 
ratio of the disease over time. We included in the study all patients with
migraine without aura (n = 3457) referred to the Parma University Headache Centre
between 1976 and 1995. They were divided into subgroups with respect to gender
and year-range of onset of migraine (before 1960, in the 1960s, in the 1970s, in 
the 1980s, and between 1990 and 1995). Gender ratio ranged from 3.6:1 (in
patients with onset before 1960) to 2.8:1 (in patients with onset in the 1980s), 
with no statistically significant changes during the observation period.

PMID: 16688599 [PubMed - indexed for MEDLINE]

1210: Neurol Sci. 2006 Apr;27(1):14-7.

The extent of right-to-left shunt fails to correlate with severity of clinical
picture in migraine with aura.

Gori S, Morelli N, Fanucchi S, Gallerini S, Manca ML, Orlandi G, Murri L.

Department of Neurosciences, Institute of Neurology, Universitary Centre for
Adaptive Disorders and Headaches, Section of Pisa 1, University of Pisa, I-56100 
Pisa, Italy. s.gori@med.unipi.it

Several investigations have documented an increased incidence of right-to-left
shunt (RLS) in migraine with aura (MA) and have emphasised its role in the
physiopathology of aura; so far, however, no data are available concerning a
possible correlation between the extent of the RLS and the clinical picture of MA
patients. To investigate the possible relationship between the extent of the RLS,
revealed by the number of microbubbles (MB) detected during transcranial Doppler 
with IV injection of ultrasound contrast (TCDc), and the clinical characteristics
of MA (age at first onset of migraine, mean annual frequency of attacks and mean 
duration of the aura phase), 30 consecutive patients with typical aura and
migraine headache positive on TCDc evaluation for RLS were enrolled. Permanent
RLS was found in 12 patients and latent RLS was found in 18 patients; of these, 6
had a high-grade RLS, 5 medium-grade RLS and 7 low-grade RLS. No correlation has 
been documented between the number of MBs and the clinical parameters of both
patients with latent shunts and those with permanent ones, nor between the
clinical parameters of the two groups of patients. These data show that RLS does 
not seem to affect the clinical manifestation of MA and that the extent of RLS
fails to correlate with the severity of the clinical picture of the disorder.

PMID: 16688594 [PubMed - indexed for MEDLINE]

1211: J Headache Pain. 2006 Apr;7(2):95-7. Epub 2006 Apr 26.

Almotriptan in the acute treatment of migraine in patients 11-17 years old: an
open-label pilot study of efficacy and safety.

Charles JA.

Department of Neurosciences, New Jersey Medical School, 185 S Orange Ave, Newark,
NJ 07103-2714, USA. jamesacharlesmd@aol.com

The objective was to investigate the safety and efficacy of almotriptan in
patients aged 11-17 years old with acute migraine. Fifteen patients aged 11-17
with a history of migraine with or without aura were treated with almotriptan.
Reduction in headache severity, disability and adverse effects were studied.
Almotriptan in doses ranging from 6.25 to 12.5 mg was well tolerated. There were 
virtually no adverse effects except for one case of transient mild stiffness. Of 
the 15 patients, only 2 demonstrated no efficacy without adverse effects. In the 
other 13 patients, not only was almotriptan effective, but again, no significant 
adverse effects were reported. Almotriptan is probably safe and effective in
patients aged 11-17. This small open-label pilot study should support the
feasibility of a large randomised controlled study to demonstrate tolerability
and efficacy of almotriptan in children and adolescents with episodic migraine.

Publication Types: 
    Comparative Study
    Controlled Clinical Trial

PMID: 16688412 [PubMed - indexed for MEDLINE]

1212: Cephalalgia. 2006 Jun;26(6):742-6.

Comment in:
    Cephalalgia. 2007 May;27(5):469; author reply 469-70.

New appendix criteria open for a broader concept of chronic migraine.

Headache Classification Committee, Olesen J, Bousser MG, Diener HC, Dodick D,
First M, Goadsby PJ, Göbel H, Lainez MJ, Lance JW, Lipton RB, Nappi G, Sakai F,
Schoenen J, Silberstein SD, Steiner TJ.

Department of Neurology, University of Copenhagen, Glostrup Hospital, Demark.
jeol@glostruphosp.kbhamt.dk

After the introduction of chronic migraine and medication overuse headache as
diagnostic entities in The International Classification of Headache Disorders,
Second Edition, ICHD-2, it has been shown that very few patients fit into the
diagnostic criteria for chronic migraine (CM). The system of being able to use CM
and the medication overuse headache (MOH) diagnosis only after discontinuation of
overuse has proven highly unpractical and new data have suggested a much more
liberal use of these diagnoses. The International Headache Classification
Committee has, therefore, worked out the more inclusive criteria for CM and MOH
presented in this paper. These criteria are included in the appendix of ICHD-2
and are meant primarily for further scientific evaluation but may be used already
now for inclusion into drug trials, etc. It is now recommended that the MOH
diagnosis should no longer request improvement after discontinuation of
medication overuse but should be given to patients if they have a primary
headache plus ongoing medication overuse. The latter is defined as previously,
i.e. 10 days or more of intake of triptans, ergot alkaloids mixed analgesics or
opioids and 15 days or more of analgesics/NSAIDs or the combined use of more than
one substance. If these new criteria for CM and MOH prove useful in future
testing, the plan is to include them in a future revised version of ICHD-2.

Publication Types: 
    Practice Guideline

PMID: 16686915 [PubMed - indexed for MEDLINE]

1213: Cephalalgia. 2006 Jun;26(6):731-7.

Metabolic and genetic risk factors for migraine in children.

Bottini F, Celle ME, Calevo MG, Amato S, Minniti G, Montaldi L, Di Pasquale D,
Cerone R, Veneselli E, Molinari AC.

Thrombosis and Haemostasis Unit, Department of Paediatric Haematology and
Oncology, Giannina Gaslini Children's Hospital, Genoa, Italy.

Migraine can induce ischaemic stroke, and is considered an independent risk
factor for stroke in the young. To date, the nature of the link between migraine 
and stroke is essentially unknown. Forty-five children were studied. Homocysteine
levels (fasting and post methionine load), vitamin B12 and plasma folate levels, 
factor V Leiden, factor II G20210A, methylenetetrahydrofolate reductase (MTHFR)
C677T and A1298C mutations were examined. Compared with controls, patients with
migraine had higher levels of post-methionine load homocysteine values (19.5 +/- 
4.9 vs. 16.9 +/- 1.9; P = 0.025) and significantly lower folate levels (5.8 +/-
2.6 vs. 7.5 +/- 2.1; P = 0.002). We found a trend toward an increased risk of
migraine in subjects carrying a homozygous mutant genotype for MTHFR C677T and
MTHFR A1298C polymorphisms. Genetic prothrombotic conditions do not seem to be
related to migraine in the young, whereas the biochemical differences between
migrainous patients and controls are an appealing topic for further
investigation.

Publication Types: 
    Controlled Clinical Trial

PMID: 16686913 [PubMed - indexed for MEDLINE]

1214: Cephalalgia. 2006 Jun;26(6):722-30.

Exteroceptive suppression of masseter muscle activity in juvenile migraineurs.

Ebinger F.

University Paediatric Hospital, Department of Child Neurology, University of
Heidelberg, Heidelberg, Germany. friedrich_ebinger@med.uni-heidelberg.de

The second exteroceptive suppression period (ES2) of masseter or temporalis
muscle activity may be reduced in adults with chronic tension-type headache. In
adults with migraine, ES2 was found normal or tended to be protracted. To date,
no studies on exteroceptive suppression in children and adolescents with
headaches have been published. We investigated the exteroceptive suppression of
masseter muscle activity in 14 migraineurs and 19 controls between 6 and 18 years
of age. It was elicited by electrical stimulation at the labial commissure. No
differences were found regarding the first suppression period, but ES2 was
significantly longer in the migraine group than in controls. The results of the
migraine group suggest overactivity of the interneurons of the reflex loop due to
impaired inhibitory control from superior antinociceptive systems already at the 
beginning of this headache disorder.

Publication Types: 
    Controlled Clinical Trial
    Research Support, Non-U.S. Gov't

PMID: 16686912 [PubMed - indexed for MEDLINE]

1215: Cephalalgia. 2006 Jun;26(6):712-21.

The natural course of migraine attacks. A prospective analysis of untreated
attacks compared with attacks treated with a triptan.

Linde M, Mellberg A, Dahlöf C.

Gothenburg Migraine Clinic, Gothenberg, Sweden. mattias.linde@neuro.gu.se

This study was designed to document prospectively and explore scientifically the 
natural course of untreated migraine attacks in detail. A new, integrated,
time-intensity method for self-assessment of the intensity of symptoms was tested
on 18 adult International Headache Society migraineurs who volunteered to refrain
from treatment during one attack. The area under the curves (AUC) during 72 h of 
untreated attacks was compared with attacks treated with a triptan. Migraine
attacks are heterogeneous both inter- and intra-individually. In untreated
attacks, the pain can stabilize and fluctuate around a plateau with a wavelength 
of hours. In general, the symptoms of each separate migraine attack follow a
similar temporal course, with only moderate deviations. In some cases photo-
and/or phonophobia (hyperexcitability) were not experienced at all, despite
severe pain and nausea. Moreover, there was sometimes no nausea despite severe
pain and hyperexcitability. Vomiting does not always correlate to the intensity
of nausea and is not always followed by decreased headache intensity. Treatment
with a triptan usually only temporarily distorts the basic pattern of attacks.
Hyperexcitability can respond before pain to treatment. These genuine findings of
the classic symptoms of migraine attacks support the notion of a mutual
underlying pathophysiological mechanism.

Publication Types: 
    Comparative Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 16686911 [PubMed - indexed for MEDLINE]

1216: Cephalalgia. 2006 Jun;26(6):691-6.

Improvement in quality of life and activity limitations in migraine patients
after prophylaxis. A prospective longitudinal multicentre study.

D'Amico D, Solari A, Usai S, Santoro P, Bernardoni P, Frediani F, De Marco R,
Massetto N, Bussone G; Progetto Cefalee Lombardia Group.

C. Besta National Neurological Institute, Milan, Italy. damicodo@tiscalinet.it

Improved health-related quality of life (HRQOL) and reduced activity limitations 
are prime objectives of migraine therapy, but no data on the effect of preventive
treatments on these outcomes are available. We monitored changes in HRQOL using
the Short Form 36 (SF-36) and headache-related activity limitations using the
Migraine Disability Assessment Score (MIDAS) in 141 consecutive migraine without 
aura patients on prophylaxis. A total of 102 patients completed the 3-month
study. Mean (SD) number of headache days/month dropped from 8.0 (3.7) to 5.0
(2.3) (P < 0.001). Mean monthly consumption of acute drugs reduced from 7.4 (3.5)
to 4.4 (3.1) (P < 0.001). MIDAS total score reduced (improved) significantly. All
SF-36 scale scores increased (improved), most significantly. This first study to 
assess prospectively the impact of prophylaxis on HRQOL and daily activities in a
large series indicates that migraine prophylaxis has the potential to reduce the 
global burden of migraine on individuals and society.

Publication Types: 
    Comparative Study
    Controlled Clinical Trial

PMID: 16686908 [PubMed - indexed for MEDLINE]

1217: Cephalalgia. 2006 Jun;26(6):678-83.

Migraine-mimicking headache and sickle cell disease: a transcranial Doppler
study.

Silva GS, Vicari P, Figueiredo MS, Junior HC, Idagawa MH, Massaro AR.

Department of Neurology, Universidade Federal de Sao Paulo, São Paulo, Brazil.

Headache occurs in sickle cell disease (SCD), but its characteristics and
frequency have not previously been studied. Our aim was to study patterns of
headache in adults with SCD and to correlate its presence with blood flow
velocities measured by transcranial Doppler (TCD) and with brain magnetic
resonance imaging (MRI) abnormalities. We studied 56 adults with SCD.
Twenty-eight patients (50%) had severe and frequent headaches. In 20 patients
(35.7%) the headache met the International Headache Society criteria for migraine
without aura. Patients with frequent and severe headache presented TCD velocities
significantly higher than those without headache, or with milder headache. No
correlation was found between headache and abnormalities in brain MRI. A
migraine-mimicking headache occurs in SCD but we should not understand it as a
primary headache because the blood flow abnormalities secondary to SCD detected
by TCD seem to play an important role in these patients.

Publication Types: 
    Controlled Clinical Trial

PMID: 16686906 [PubMed - indexed for MEDLINE]

1218: Cephalalgia. 2006 Jun;26(6):672-7.

QTc dispersion and P-wave dispersion during migraine attacks.

Duru M, Melek I, Seyfeli E, Duman T, Kuvandik G, Kaya H, Yalçin F.

Mustafa Kemal University Faculty of Medicine, Department of Emergency Medicine,
Antakya/Hatay, Turkey. mduru@mku.edu.tr

The aim of this study was to investigate increase of QTc dispersion and P-wave
dispersion during migraine attacks. Fifty-five patients (16-65 years of age, 49
women, six men) with migraine were included in our study. Heart rate, QTc
interval, maximum and minimum QTc interval, QTc dispersion, maximum and minimum
P-wave duration and P-wave dispersion were measured from 12-lead ECG recording
during migraine attacks and pain-free periods. ECGs were transferred to a
personal computer via a scanner and then used for magnification of x400 by Adobe 
Photoshop software. Maximum QTc interval (454 +/- 24 ms vs. 429 +/- 23 ms, P <
0.001), QTc interval (443 +/- 26 ms vs. 408 +/- 22 ms, P < 0.001) and QTc
dispersion (63 +/- 18 ms vs. 43 +/- 14 ms, P < 0.001) were found significantly
higher during migraine attacks compared with pain-free periods. Maximum P-wave
duration (107 +/- 11 ms vs. 100 +/- 11 ms, P < 0.001) and P-wave dispersion (45
+/- 13 ms vs. 35 +/- 13 ms, P < 0.001) were found higher during migraine attacks 
than pain-free periods. We concluded that migraine attacks are associated with
increased QTc and P-wave dispersion compared with pain-free periods.

Publication Types: 
    Clinical Trial

PMID: 16686905 [PubMed - indexed for MEDLINE]

1219: Cephalalgia. 2006 Jun;26(6):660-71.

Ocular motor measures in migraine with and without aura.

Wilkinson F, Karanovic O, Ross EC, Lillakas L, Steinbach MJ.

Department of Psychology, York University, Toronto, ON, Canada. franw@yorku.ca

The purpose of this study was to examine basic ocular motor function in
individuals with migraine. We used an infrared eye-tracking system to measure
horizontal smooth pursuit to a sinusoidal target, saccades to horizontal target
displacements of 5-20 degrees , and the stability of fixation in 19 migraine
without aura (MoA), 19 migraine with aura (MA) and 19 headache-free control (C)
subjects. Eye movement measurements were made at two target displacement rates
and against both homogeneous grey and patterned backgrounds. We found no
statistically significant differences between migraine and control subjects in
any of the eye movement parameters measured, but did find highly significant
effects of both target speed and background pattern in all groups. Our results do
not provide support for subclinical cerebellar impairment in migraineurs, and do 
provide evidence that previously described visual abnormalities in migraine are
not artefacts of abnormal fixation or eye movements.

Publication Types: 
    Clinical Trial
    Research Support, Non-U.S. Gov't

PMID: 16686904 [PubMed - indexed for MEDLINE]

1220: Cephalalgia. 2006 Jun;26(6):642-59.

Experimental migraine models and their relevance in migraine therapy.

Arulmani U, Gupta S, VanDenBrink AM, Centurión D, Villalón CM, Saxena PR.

Department of Pharmacology, Cardiovascular Research Institute COEUR, Erasmus MC, 
University Medical Centre Rotterdam, Rotterdam, the Netherlands.

Although the understanding of migraine pathophysiology is incomplete, it is now
well accepted that this neurovascular syndrome is mainly due to a cranial
vasodilation with activation of the trigeminal system. Several experimental
migraine models, based on vascular and neuronal involvement, have been developed.
Obviously, the migraine models do not entail all facets of this clinically
heterogeneous disorder, but their contribution at several levels (molecular, in
vitro, in vivo) has been crucial in the development of novel antimigraine drugs
and in the understanding of migraine pathophysiology. One important vascular in
vivo model, based on an assumption that migraine headache involves cranial
vasodilation, determines porcine arteriovenous anastomotic blood flow. Other
models utilize electrical stimulation of the trigeminal ganglion/nerve to study
neurogenic dural inflammation, while the superior sagittal sinus stimulation
model takes into account the transmission of trigeminal nociceptive input in the 
brainstem. More recently, the introduction of integrated models, namely
electrical stimulation of the trigeminal ganglion or systemic administration of
capsaicin, allows studying the activation of the trigeminal system and its effect
on the cranial vasculature. Studies using in vitro models have contributed
enormously during the preclinical stage to characterizing the receptors in
cranial blood vessels and to studying the effects of several putative
antimigraine agents. The aforementioned migraine models have advantages as well
as some limitations. The present review is devoted to discussing various migraine
models and their relevance to antimigraine therapy.

Publication Types: 
    Review

PMID: 16686903 [PubMed - indexed for MEDLINE]

1221: Cerebrovasc Dis. 2006;22(2-3):91-100. Epub 2006 May 9.

Migraine and patent foramen ovale: A residual coincidence or a pathophysiological
intrigue?

Piechowski-Jozwiak B, Devuyst G, Bogousslavsky J.

Department of Neurology, Centre Hospitalier Universitaire Vaudois, Lausanne,
Switzerland.

Migraine is one of the most common neurological disorders and one of the most
frequent primary headaches. It imposes a significant burden on the affected
individuals, society and health care system. As the etiology and pathophysiology 
of migraine are not well understood, treatment is largely symptomatic. Patent
foramen ovale is a remnant of a fetal circulation and is highly prevalent in the 
general population. Its presence was linked to several disorders including
migraine. The aim of this review was to search in the available data the answer
to the question whether the link between migraine and patent foramen ovale is
coincidental or whether they represent a pathophysiological entity. Copyright
2006 S. Karger AG, Basel.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 16685120 [PubMed - indexed for MEDLINE]

1222: Brain. 2006 Jul;129(Pt 7):1833-43. Epub 2006 May 9.

Local and global motion after-effects are both enhanced in migraine, and the
underlying mechanisms differ across cortical areas.

Shepherd AJ.

School of Psychology, Birkbeck College, University of London, London, UK.
a.shepherd@bbk.ac.uk

Visual after-effects are illusions that occur after prolonged viewing of visual
displays (pattern adaptation). The motion after-effect (MAE), for example, is an 
illusory impression of motion that is seen after viewing moving displays.
After-effects have been used extensively in basic vision research as well as in
clinical settings, and have been reported to be enhanced in migraine. Pattern
adaptation is a cortical phenomenon that reflects both cellular mechanisms acting
within individual neurons and specific interactions between groups of neurons
activated by the adapting display. A remarkable feature of the MAE is that its
duration is only slightly reduced if a delay is inserted between the end of the
adaptation and the test display ('storage'). The reduction is consistent with
recovery of the cellular component, and the residual with network changes that
are maintained during the delay. This study aimed (i) to assess explanations for 
prolonged MAEs in migraine by teasing apart the proposed cellular and network
components of adaptation using storage; (ii) to determine the extent of cortical 
abnormality in migraine using local and global MAEs, which reflect adaptation at 
different stages of the visual system. Fifty migraine (22 with, 28 without aura) 
and 50 control participants adapted to motion before viewing a stationary or
dynamic (random motion) test, which consequently appeared to move in the opposite
direction (local and global MAEs, respectively). Half of the trials included a
delay between the adapting and test displays. The results extend those reported
previously, as both local and global MAEs lasted longer in migraine compared with
the control group. Global MAEs survived delays almost completely for both groups,
whereas local MAEs were reduced to a greater extent in migraine. There were no
significant differences between migraine subgroups classified according to the
presence or absence of visual aura. These results suggest that cellular recovery 
is slowed in migraine for early but not later visual cortical areas. Sustained
network changes following adaptation are implicated across cortical areas.
Differences between people with and without migraine on various measures of
visual perception have been attributed to abnormal cortical processing in
migraine, variously described by hyperexcitability, heightened responsiveness
and/or a lack of intra-cortical inhibition. The results are not consistent with
hyperexcitability resulting from a lack of inhibition in migraine, but are
consistent with extended suppression of intra-cortical excitation. The
implications of these results for alternative models of hyperexcitability are
discussed.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16684787 [PubMed - indexed for MEDLINE]

1223: Int J Audiol. 2006 Apr;45(4):224-6.

Differentiation of migrainous positional vertigo (MPV) from horizontal canal
benign paroxysmal positional vertigo (HC-BPPV).

Roberts RA, Gans RE, Kastner AH.

The American Institute of Balance, 11290 Park Boulevard, Seminole, FL 33772, USA.
rroberts@dizzy.com

This article presents an approach to differentiation of migrainous positional
vertigo (MPV) from horizontal canal benign paroxysmal positional vertigo
(HC-BPPV). Such an approach is essential because of the difference in
intervention between the two disorders in question. Results from evaluation of
the case study presented here revealed a persistent ageotropic positional
nystagmus consistent with MPV or a cupulolithiasis variant of HC-BPPV. The
patient was treated with liberatory maneuvers to remove possible otoconial debris
from the horizontal canal in an attempt, in turn, to provide further diagnostic
information. There was no change in symptoms following treatment for HC-BPPV.
This case was diagnosed subsequently as MPV, and the patient was referred for
medical intervention. Treatment has been successful for 22 months. Incorporation 
of HC-BPPV treatment, therefore, may provide useful information in the
differential diagnosis of MPV and the cupulolithiasis variant of HC-BPPV.

Publication Types: 
    Case Reports

PMID: 16684703 [PubMed - indexed for MEDLINE]

1224: J Pediatr Health Care. 2006 May-Jun;20(3):167-71.

Epilepsy and migraine headache: is there a connection?

Stevenson SB.

Arkansas Children's Hospital, 800 Marshall St, Slot #512-15, Little Rock, AR
72202, USA. stevensonsharon@uams.edu

INTRODUCTION: This study investigated the prevalence of migraine headache in
pediatric patients with epilepsy and the incidence of these two disorders in the 
family history. METHOD: A retrospective chart review was conducted on 475
patients with a primary diagnosis of epilepsy between January 2003 and June 2004.
The patients were managed in a pediatric neurology outpatient clinic at a major
teaching hospital. Cases were selected using the ICD-9-CM definition for
epilepsy. Data collected included age, sex, headache, migraine, and family
history. RESULTS: The study revealed a higher prevalence of migraine in epilepsy 
patients (14.7%) than in the general population (2.7% to 11%). Only 4.7% had a
family history of migraine, but 20.6% had a positive family history of epilepsy, 
supporting current ideas of the genetic etiology of some epilepsies. DISCUSSION: 
This study specifically addressed epilepsy and migraine in children, but whenever
a primary diagnosis is made, the potential for a coexisting disorder should be
investigated.

PMID: 16675377 [PubMed - indexed for MEDLINE]

1225: Cephalalgia. 2006 May;26(5):596-603.

Cognitive and behavioural effects of migraine in childhood and adolescence.

Riva D, Aggio F, Vago C, Nichelli F, Andreucci E, Paruta N, D'Arrigo S,
Pantaleoni C, Bulgheroni S.

Developmental Neurology Division, Istituto Nazionale Neurologico C. Besta,
Milano, Italy. driva@istituto-besta.it

Since cognitive and behavioural characteristics of paediatric migraine sufferers 
have yet to be adequately defined, in this study we assessed the effect of
migraine on the interictal functioning of children and adolescents by comparing
the performance of two patient groups, 17 migraine sufferers with aura (MA) and
31 without aura (MoA) and by correlating the duration of the disorder, the
frequency of attacks and interictal period with neuropsychological and
behavioural findings. Both patient groups had cognitive performance within normal
range except for a significant delay in the reaction time (RT) task. Both MA and 
MoA revealed a behavioural phenotype characterized by internalizing problems on
Child Behaviour Check List (CBCL) scales. Slower RT to simple visual stimuli may 
be an early sign of a subclinical neuropsychological dysfunction, significantly
correlated with the frequency of headache attacks and interictal period. The lack
of a control group and other methodological limitations, such as patient
selection bias and unadjusted P-value for multiple testing, make it difficult to 
give this finding a clearcut meaning. Further studies are needed on larger
samples compared with a control group.

Publication Types: 
    Comparative Study

PMID: 16674769 [PubMed - indexed for MEDLINE]

1226: Cephalalgia. 2006 May;26(5):578-88.

Clinical features and pharmacological treatment of migraine patients referred to 
headache specialists in Canada.

Jelinski SE, Becker WJ, Christie SN, Giammarco R, Mackie GF, Gawel MJ, Eloff AG, 
Magnusson JE.

Department of Clinical Neurosciences, University of Calgary, Calgary, Alberta,
and Richmond Hospital, British Columbia, Canada.

We set out to examine selected clinical characteristics of migraine patients
referred to neurologists specializing in headache in Canada, and to document
their pharmacological therapy both before and after consultation with the
neurologist. Demographic, clinical and pharmacotherapy data were collected at the
time of consultation for 606 patients referred to five headache clinics and who
were given a migraine diagnosis by the neurologist. Data were analysed as part of
the Canadian Headache Outpatient Registry and Database (CHORD) Project. The mean 
age of the migraine patients was 39.7 years; and 82.5% were female. The majority 
of patients suffered severe impact from their headaches. Prior to consultation,
48.7% were taking a triptan; after consultation, 97.2% were on a triptan. Before 
consultation, 30.9% were on a prophylactic drug; after consultation, 70.4% were. 
20.8% of patients were medication overusers. Of these medication overusers, 42.4%
were overusing an opiate, usually in combination with other analgesics; 21.6%
were overusing a triptan. Medication changes made by the neurologists at
consultation included a large increase in the use of both triptans and
prophylactic medications. Medication overuse, particularly opiate overuse,
remains a significant problem in patients with migraine in Canada.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16674767 [PubMed - indexed for MEDLINE]

1227: Cephalalgia. 2006 May;26(5):554-60.

Visual cortical inhibitory function in migraine is not generally impaired:
evidence from a combined psychophysical test with an fMRI study.

Huang J, DeLano M, Cao Y.

Department of Radiology, Michigan State University, East Lansing, MI 48824, USA. 
jie@rad.msu.edu

A robust, visual masking test that was developed to be feasible with functional
magnetic resonance imaging (fMRI) was used to examine the visual cortical
inhibitory function in migraine patients with visual aura at both psychophysical 
and cortical levels. The study showed that the decreased visibility of a visual
target was associated with a reduction in cortical activation in the primary
visual cortex. The suppression of the transient on-response and after-discharge
of neurons to the target was most likely to be responsible for reducing cortical 
activation, rendering the target less visible or invisible. The migraine patients
were equally susceptible to visual masking and showed no difference in cortical
activation when compared with age- and sex-matched non-headache controls,
demonstrating that visual cortical inhibitory function was not impaired under the
experimental conditions. Although these results are not in conflict with the
general cortical hyperexcitability theory in migraine, they provide evidence to
show the limitation to the theory.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 16674764 [PubMed - indexed for MEDLINE]

1228: Cephalalgia. 2006 May;26(5):548-53.

The relationship between migraine pain and other associated symptoms.

Kelman L, Tanis D.

Headache Center of Atlanta, Atlanta, GA 30342, USA. lkelman@mindspring.com

This study explores the relationship of the pain of the migraine headache and the
associated features of migraine. Migraineurs (n=1025) (ICHD-2, 1.1-1.2 and 1.5.1)
were evaluated retrospectively using a detailed database (daily unremitting
excluded). Variables studied included headache intensity and duration, associated
symptoms and pain characteristics. Non-parametric correlations were used to
evaluate relationships among variables. Headache intensity correlated with
nausea, vomiting, photophobia, phonophobia, dizziness (all P=0.000), running of
the nose/tearing of the eyes (P=0.007), and osmophobia (P=0.044), but not with
diarrhoea or taste abnormality. Headache duration correlated only with osmophobia
(P=0.002) and taste abnormality (P=0.005). Throbbing, pressure and stabbing pain 
correlated with most of the associated symptoms. Aching correlated only with
taste abnormality. This correlational study demonstrates that migraine pain is
clearly related to nausea, but is also correlated with other associated migraine 
symptoms. Taste abnormality and osmophobia are better correlated with headache
duration rather than headache intensity.

PMID: 16674763 [PubMed - indexed for MEDLINE]

1229: Cephalalgia. 2006 May;26(5):537-47.

Efficacy and tolerability of diclofenac potassium sachets in migraine: a
randomized, double-blind, cross-over study in comparison with diclofenac
potassium tablets and placebo.

Diener HC, Montagna P, Gács G, Lyczak P, Schumann G, Zöller B, Mulder LJ, Siegel 
J, Edson K.

Department of Neurology, University of Essen, Essen, Germany, and Péterfy Sandor 
Hospital, Budapest, Hungary. h.diener@uni-essen.de

A randomized, controlled, cross-over trial compared single doses of 50 mg
diclofenac potassium sachets and tablets with placebo in 328 patients with
migraine pain, treating 888 attacks. For the primary endpoint 24.7% of the
patients were pain free at 2 h postdose with sachets, 18.5% for tablets and 11.7%
for placebo. Treatment differences were significant for sachets vs. placebo
(P<0.0001), tablets vs. placebo (P=0.0040) and for sachets vs. tablets
(P=0.0035). The numbers needed to treat compared with placebo to achieve pain
free at 2 h were 7.75 [95% confidence interval (CI) 5.46, 13.35] for sachets and 
15.83 (95% CI 8.63, 96.20) for tablets. Sachets were also statistically superior 
to tablets for sustained headache response, sustained pain free and reduction in 
headache intensity within the first 2 h postdose measured on a visual analogue
scale (P<0.05). Onset of analgesic effect was 15 min for sachets and 60 min for
tablets. Fewer patients needed rescue medication, and there were marked
improvements in accompanying symptoms and working ability with both sachets and
tablets vs. placebo. No safety issues were identified. This study demonstrates
that sachets offer patients suffering from migraine pain a more effective
treatment with a faster onset of analgesia when compared with tablets.

Publication Types: 
    Comparative Study
    Multicenter Study
    Randomized Controlled Trial

PMID: 16674762 [PubMed - indexed for MEDLINE]

1230: Cephalalgia. 2006 May;26(5):520-9.

Acupuncture in migraine prophylaxis: a randomized sham-controlled trial.

Alecrim-Andrade J, Maciel-Júnior JA, Cladellas XC, Correa-Filho HR, Machado HC.

Universitat Autonòma de Barcelona, Medicina Interna, and Hospital Clinic,
Clinical Pharmacology Unit, Barcelona, Catalunya, Spain. jalecrim@uol.com.br

The purpose of the present trial was to evaluate semi-standardized acupuncture
efficacy in migraine prophylaxis. Twenty-eight subjects with migraine were
randomized to the real or sham acupuncture groups. Semi-standardized and
standardized minimal acupuncture were used, respectively, in the two groups of
patients. They were all treated with 16 acupuncture sessions in 12 weeks. Both
groups exhibited similar reductions in: percentage of patients with reduction of 
migraine>or=40% and >or=50% regarding frequency of migraine attacks, days with
migraine, frequency of migraine attacks, average duration of a migraine attack,
rate of rescue medication used, average headache severity rate and other
parameters compared with the baseline period. Associated symptoms, such as nausea
and vomiting, also showed equal estimates in both groups. These findings showed
that semi-standardized acupuncture shows no difference from sham acupuncture in
preventing migraine attacks.

Publication Types: 
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 16674760 [PubMed - indexed for MEDLINE]

1231: Cephalalgia. 2006 May;26(5):506-10.

Prevalence of unexplained upper abdominal symptoms in patients with migraine.

Kurth T, Holtmann G, Neufang-Hüber J, Gerken G, Diener HC.

Department of Neurology, University Duisburg-Essen, Essen, Germany, and Division 
of Preventive Medicine, Brigham and Women's Hospital, Harvard Medical School,
Boston, MA 02120, USA. tkurth@rics.bwh.harvard.edu

Patients with functional gastrointestinal disorders frequently report migraine.
We aimed to determine the prevalence of idiopathic upper abdominal symptoms in
patients with migraine and compare it with a control population of healthy blood 
donors. We assessed abdominal symptoms using the Bowel Disease Questionnaire in a
series of 488 consecutive blood donors without migraine and 99 patients with
migraine. Upper abdominal symptoms were reported by 38%[95% confidence interval
(CI) 32, 44] of blood donors compared with 81% (67, 91, P<0.001) of migraine
patients. Of the blood donors, 23% (18, 28) reported frequent dyspepsia compared 
with 60% (44, 74, P<0.001) of the migraine patients. Migraine was associated with
frequent upper abdominal symptoms (odds ratio 2.7, 95% CI 1.2, 6.1) after
adjusting for age, gender, smoking and consumption of analgesics and alcohol.
Upper abdominal symptoms are significantly more frequent in patients with
migraine compared with healthy controls. The association between migraine and
idiopathic upper abdominal symptoms may suggest common pathophysiological
mechanisms.

PMID: 16674758 [PubMed - indexed for MEDLINE]

1232: Cephalalgia. 2006 May;26(5):497-505.

Prophylactic treatment of migraine in children. Part 2. A systematic review of
pharmacological trials.

Damen L, Bruijn J, Verhagen AP, Berger MY, Passchier J, Koes BW.

Department of General Practice, Erasmus Medical Centre, Rotterdam, the
Netherlands.

The aim of this study was to assess the efficacy of pharmacological prophylactic 
treatments of migraine in children. Databases were searched from inception to
June 2004 and references were checked. We selected controlled trials on the
effects of pharmacological prophylactic treatments in children with migraine. We 
assessed trial quality using the Delphi list and extracted data. Analyses were
carried out according to type of intervention. A total of 20 trials were
included. Headache improvement was significantly higher for flunarizine compared 
with placebo (relative risk 4.00, 95% confidence interval 1.60, 9.97). There is
conflicting evidence for the use of propranolol. Nimodipine, clonidine, L-5HTP,
trazodone and papaverine showed no effect when compared with placebo. All
medications were well tolerated and adverse events showed no significant
differences. Flunarizine may be effective as prophylactic treatment for migraine 
in children. Because of the small number of studies and the methodological
shortcomings, conclusions regarding effectiveness have to be drawn with caution.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 16674757 [PubMed - indexed for MEDLINE]

1233: J Adv Nurs. 2006 May;54(4):491-501.

Effectiveness of acupuncture for migraine: critical literature review.

Griggs C, Jensen J.

Shepway Primary Care Trust, Kent, UK. cg67@kent.ac.uk

AIM: The aim of this paper is to evaluate previous research studies on
acupuncture for migraine with reference to the Standards for Reporting
Interventions in Controlled Trials of Acupuncture guidelines. BACKGROUND: It is
estimated that around 2-15% of the world's population are affected by migraine
headaches. Thirteen per cent of adults in the United Kingdom suffer with chronic 
pain, migraine headaches accounting for 7% of cases. Migraine pain relief is
grounded in pharmacology. Acupuncture for migraine has been widely researched.
However, inconsistent and low quality results have been produced. Recently,
published Standards for Reporting Interventions in Controlled Randomized Trials
of Acupuncture guidelines recommend important information that must be included
in research in order to be valid and reliable. METHODS: Searches were conducted
between September 2003 and May 2004 using the Ovid Medline 1966-2004, British
Medical Journal, Blackwell Synergy, Science Direct, The Lancet and Cochrane
Library Issue 1 databases. Searches were limited to the previous 20 years and to 
publications in the English language only. FINDINGS: Thirteen randomized
controlled trials met the inclusion criteria and were critically reviewed for
methodological quality, reporting of acupuncture needling details, practitioner
background, control interventions and use of a diagnostic criterion. Findings
agreed with previous literature reviews that the majority of studies of
acupuncture for migraine research are of poor quality, with conflicting results. 
Few studies met the criteria of the Standards for Reporting Interventions in
Controlled Trials of Acupuncture recommendations. Overall, the quality of
research in this area must be questioned. CONCLUSIONS: In the light of these
findings, practitioners may face a dilemma when considering the use of
acupuncture for migraine. Therefore, large, high quality randomized controlled
trials of acupuncture for migraine are needed. Until better quality research is
published, with verification of the benefits of acupuncture for migraine,
provision of this alternative therapy should not be expanded or withdrawn.

Publication Types: 
    Review

PMID: 16671978 [PubMed - indexed for MEDLINE]

1234: J Midwifery Womens Health. 2006 May-Jun;51(3):174-84.

Management of migraine headaches.

Graves BW.

Midwifery Education Program, Baystate Medical Center, Springfield, MA 01199, USA.
Barbara.graves@bhs.org

With 17% to 18% of women suffering from migraine headaches, clinicians will often
be asked by their patients to prescribe medication. Migraine is an episodic
chronic disease that is best managed with an overall treatment plan, rather than 
treated as an acute illness that is managed with sporadic medications. Realistic 
goals for the long-term management of migraine are based on patient education and
an ongoing discussion between patient and provider. This article reviews the
clinical presentation of migraine and recommendations for both acute and
preventive treatment, including complementary therapies. "Red flags" that could
be signs of more serious neurologic illness are presented. The management of
migraine in pregnancy is also reviewed.

Publication Types: 
    Review

PMID: 16647669 [PubMed - indexed for MEDLINE]

1235: J Altern Complement Med. 2006 Apr;12(3):237-45.

Designing an acupuncture study: the nationwide, randomized, controlled, German
acupuncture trials on migraine and tension-type headache.

Molsberger AF, Boewing G, Diener HC, Endres HG, Kraehmer N, Kronfeld K, Zenz M.

Forschungsgruppe Akupunktur und Chinesische Medizin, Duesseldorf, Germany.
a.molsberger@facm.de

BACKGROUND: In the nationwide German Acupuncture Trials (GERAC) verum
acupuncture, based on Traditional Chinese Medicine (TCM), was to be tested
against sham acupuncture for the entities classified in the West as "migraine"
(MIG) and "tension-type headache" (TTH). However, there were no generally
accepted guidelines on how to perform a consistent verum or sham treatment.
OBJECTIVE: To design broadly consensual verum and sham acupuncture treatment
protocols for MIG and TTH for the GERAC. METHODOLOGY: Extensive literature study 
and consultation with acupuncture experts. Personal interviews, both free and
structured, e-mail discussions, and phone conferences were used. RESULTS: Broadly
consensual acupuncture protocols for MIG and TTH for verum and sham acupuncture
were developed. They included semi-standardized point combinations with clearly
described point selection rules based on TCM acupuncture diagnoses. A procedure
was developed to help ensure homogenous treatment quality in a large multicenter 
trial. CONCLUSIONS: The GERAC study design allowed acupuncture to be tested in a 
naturalistic environment. The rigorous study design and the large number of
physician investigators guaranteed a high external validity for the results. The 
results will help determine the significance of Chinese acupuncture in the
context of Western medicine for the treatment of MIG and TTH.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16646722 [PubMed - indexed for MEDLINE]

1236: Forsch Komplementmed. 2006 Apr;13(2):101-8. Epub 2006 Apr 19.

Treatment in a randomized multicenter trial of acupuncture for migraine (ART
migraine).

Linde K, Streng A, Hoppe A, Brinkhaus B, Witt CM, Hammes M, Irnich D,
Hummelsberger J, Willich SN, Melchart D.

Centre for Complementary Medicine Research, Department of Internal Medicine II,
Technical University of Munich, Germany. Klaus.Linde@lrz.tum.de

BACKGROUND: This paper aims to describe the characteristics of physicians and
interventions of a large, multicenter randomized trial of acupuncture for
migraine (ART Migraine) in order to enable acupuncturists to assess the study
interventions. PATIENTS AND METHODS: 302 patients suffering from migraine were
randomized to 12 sessions of semi-standardized acupuncture (6 predefined basic
points, recommendations for optional individual choice of additional points
given), standardized minimal acupuncture (superficial needling of at least 5 of
10 predefined, distant non-acupuncture points) or a waiting list. 30 physicians
trained and experienced in acupuncture from 18 centers in Germany participated in
the trial. RESULTS: The median duration of acupuncture training of trial
physicians was 500 h (range 140-1350). Physicians had acupuncture experience for 
10 (<1 to 25) years and had treated 200 (60 to >1000) patients with acupuncture
in the year preceding trial participation. The 6 basic points were needled in
76-93% of sessions. Compliance with treatment instructions varied considerably
among centers in the acupuncture group. In contrast, compliance with the minimal 
acupuncture protocol was very good. 6 of the 30 physicians stated that they would
have treated patients somewhat differently outside the trial, 1 completely
differently. The trial found a significant effect of those treated with
acupuncture compared to those on the waiting list for treatment, but minimal
acupuncture was as effective as acupuncture. CONCLUSIONS: The treatment protocols
for acupuncture and minimal acupuncture in ART Migraine appeared an adequate
compromise in the specific situation and for the predefined purposes. However, a 
relevant minority of participating physicians would have treated patients
differently outside the trial.

Publication Types: 
    Comparative Study
    Multicenter Study
    Randomized Controlled Trial

PMID: 16645290 [PubMed - indexed for MEDLINE]

1237: Headache. 2006 May;46(5):815-8.

Reversible palinopsia and the Alice in Wonderland syndrome associated with
topiramate use in migraineurs.

Evans RW.

Weill Medical College of Cornell University and The Methodist Hospital,
Neurology, Houston, TX 77004, USA.

Two patients are reported who developed palinopsia while taking topiramate for
migraine prevention which resolved or decreased in frequency or duration on lower
doses, but recurred or increased in frequency or duration on higher doses. Both
patients had complete resolution of palinopsia when topiramate was discontinued. 
A third patient is described who developed the "Alice in Wonderland" syndrome
about 1 week after starting topiramate for migraine prevention with complete
resolution of symptoms about 1 month after stopping. Topiramate use may cause
palinopsia and may be associated with the Alice in Wonderland syndrome through an
unknown mechanism.

PMID: 16643588 [PubMed - indexed for MEDLINE]

1238: Headache. 2006 May;46(5):804-7.

Zonisamide prophylaxis in refractory pediatric headache.

Pakalnis A, Kring D.

Neurology Division, Children's Hospital, Columbus, OH 43205, USA.

INTRODUCTION: Currently, no medications are approved for pediatric headache
prophylaxis in the United States. Zonisamide is an antiepileptic drug with
preliminary studies suggesting some efficacy in the adult headache population.
METHODS: A retrospective chart review was conducted on refractory headache
patients in our multidisciplinary Headache Clinic who were treated with
zonisamide, an antiepileptic drug, for headache prophylaxis. Records were
reviewed for pertinent data including patient history, diagnosis, prior treatment
regimens, and zonisamide response, along with headache frequency. RESULTS: Twelve
patients were identified (8 girls); mean age was 13.5 years. Eight of the 12
patients had a positive response to zonisamide with greater than 50% reduction in
headaches from pretreatment values. CONCLUSION: Zonisamide had some efficacy in
headache reduction. It was well tolerated with only minor side effects. Further
prospective studies with zonisamide are warranted in refractory pediatric
headache patients.

PMID: 16643584 [PubMed - indexed for MEDLINE]

1239: Headache. 2006 May;46(5):794-803.

Migraine headaches and preeclampsia: an epidemiologic review.

Adeney KL, Williams MA.

Center for Perinatal Studies, Swedish Medical Center, Seattle, WA 98122, USA.

OBJECTIVE: To summarize and evaluate available empirical research on the
relationship between migraines and gestational hypertension or preeclampsia and
to provide direction for future research in this area. BACKGROUND: Migraines
affect a substantial proportion of reproductive-aged women and have been
associated with cardiovascular risk factors and ischemic disease in this
population. Preeclampsia is a vascular disorder of pregnancy, also linked to
adverse cardiovascular outcomes. METHODS: Publications were identified by a
MEDLINE search using keywords "migraine,""preeclampsia," and "gestational
hypertension," and by examination of the reference lists of identified articles. 
RESULTS: The literature review yielded 10 studies addressing the association
between migraines and preeclampsia or gestational hypertension. Of the 10
studies, 8 reported a positive association between the syndromes. CONCLUSIONS:
Available evidence suggests that migraines and preeclampsia may reflect an
underlying predisposition toward ischemic injury. More rigorous epidemiologic
research is warranted, after consideration of several important methodologic
issues.

Publication Types: 
    Research Support, N.I.H., Extramural
    Review

PMID: 16643583 [PubMed - indexed for MEDLINE]

1240: Headache. 2006 May;46(5):788-93.

Use of a pine bark extract and antioxidant vitamin combination product as therapy
for migraine in patients refractory to pharmacologic medication.

Chayasirisobhon S.

Department of Neurology, Kaiser Permanente Medical Center, Anaheim, CA 92807,
USA.

OBJECTIVE: To evaluate the potential benefit of a pine bark extract and
antioxidant vitamin combination product in the treatment of migraine headache.
BACKGROUND: This was an uncontrolled preliminary study to investigate the
potential of an antioxidant formulation as therapy for migraine headache.
METHODS: Twelve patients with a long-term history of migraine with and without
aura who had failed to respond to multiple treatments with beta-blockers,
antidepressants, anticonvulsants, and 5-hydroxytryptamine receptor agonists were 
selected for the study. They were treated with 10 capsules of an antioxidant
formulation of 120 mg pine bark extract, 60 mg vitamin C, and 30 IU vitamin E in 
each capsule daily for 3 months. Following enrollment patients completed a
migraine disability assessment (MIDAS) questionnaire to give a baseline measure
of migraine impact on work, school, domestic, and social activities over the
previous 3 months. Patients were then treated for 3 months with the antioxidant
formulation while continuing to receive existing pharmacologic medications. A
second MIDAS was given at the conclusion of the treatment period. RESULTS: There 
was a significant mean improvement in MIDAS score of 50.6% for the 3-month
treatment period compared with the 3 months prior to baseline (P < .005). The
treatment was also associated with significant reductions in number of headache
days and headache severity score. Mean number of headache days was reduced from
44.4 days at baseline (95% CI 28.9 to 59.8) to 26.0 days (95% CI 5.3 to 46.7; P <
.005) after 3 months' therapy and mean headache severity was reduced from 7.5 of 
10 (95% CI 6.7 to 8.4) to 5.5 (95% CI 4.1 to 7.0; P < .005). CONCLUSION: These
data suggest that the antioxidant therapy used in this study may be beneficial in
the treatment of migraine possibly reducing headache frequency and severity.
Further clinical investigation into the efficacy of antioxidant as therapy for
chronic migraine is warranted.

Publication Types: 
    Clinical Trial

PMID: 16643582 [PubMed - indexed for MEDLINE]

1241: Headache. 2006 May;46(5):781-7.

Haloperidol in the acute treatment of migraine: a randomized, double-blind,
placebo-controlled study.

Honkaniemi J, Liimatainen S, Rainesalo S, Sulavuori S.

Department of Neurology, University of Tampere, Finland.

OBJECTIVE: To assess the efficacy and safety of i.v. haloperidol in treatment of 
acute migraine headache in a double-blind, randomized, placebo-controlled study
design. BACKGROUND: Neuroleptics are mainly used as antiemetics in acute
migraine. In a previous open trial haloperidol was effective in relieving
migraine pain. DESIGN: Patients were randomized into 2 groups receiving
intravenously either 5 mg haloperidol in 500 mL of normal saline or 500 mL of
normal saline alone. Pain was assessed by visual analogue scale (VAS) before and 
1 to 3 hours after the infusion. If the patient felt no relief in pain intensity 
1 to 3 hours after the infusion and had received placebo, he/she then received
haloperidol infusion as an open trial. The open trial also included 7 patients
who refused from the placebo-controlled trial. About 1 month after the infusion
the patients were contacted by telephone and interviewed about the side effects
of the treatment. RESULTS: Forty patients were enrolled into the double-blind,
placebo-controlled study. Before the infusion the VAS values were 7.7 in the
haloperidol and 7.2 in the placebo group. After the infusion the VAS values were 
2.2 in the haloperidol and 6.3 in the placebo group (P < .0001). Significant pain
relief was achieved in 80% of the patients treated with haloperidol, whereas only
3 patients (15%) responded to placebo (P < .0001). Seventeen patients treated
with placebo without response together with 7 patients who refused from the
placebo-controlled study participated in the open trial. In this group VAS
declined from 6.7 to 2.4 and 79% of these patients felt significant pain relief. 
The most common side effects caused by haloperidol were sedation and akathisia,
the latter being more troublesome. These effects were very common in patients
participating in the double-blind (80%) and open (88%) trials. Sixteen percent of
the patients considered the side effects intolerable and would not like the
migraine attacks to be treated with haloperidol in the future. Three patients
(7%) returned to the emergency ward because of a relapse. CONCLUSIONS: This study
shows that i.v. haloperidol is very effective in relieving migraine-associated
pain. Because the majority of the patients had taken other medication without
response, haloperidol appears to be an effective rescue medication even when
other types of treatment have failed. Relapses are rare, but side effects are
common, limiting the use of haloperidol in some patients.

Publication Types: 
    Randomized Controlled Trial

PMID: 16643581 [PubMed - indexed for MEDLINE]

1242: Headache. 2006 May;46(5):773-80.

Acute migraine treatment: patterns of use and satisfaction in a clinical
population.

Malik SN, Hopkins M, Young WB, Silberstein SD.

Thomas Jefferson University, Jefferson Headache Center, Philadelphia, PA 19107,
USA.

BACKGROUND: The sequence and timing of taking migraine medications, whether
prescription or over-the-counter, and the patient's response to their treatment, 
is unknown. OBJECTIVE: To describe the use of, response to, and satisfaction with
acute medications for 1 migraine attack. METHODS: We performed a clinic-based
survey of 127 patients at Jefferson Headache Center, Philadelphia. Adult patients
who met the International Headache Society criteria for migraine with or without 
aura were included in the study. Patients were asked to complete a questionnaire.
RESULTS: Of 109 participants who met the inclusion criteria, most waited 1 hour
or more after the onset of symptoms to take medication. Triptans were most
commonly used as first, second, and third medications. Triptan use was associated
with higher 2-hour pain-free response rates compared with other agents, whether
the triptan was used as the first, second, or third medication. Patients who were
treated with medications other than triptans were more likely to have pain at 2
hours (P = .36). NSAIDs had relatively low pain-free and headache relief response
rates at 2 hours. Sixty-two participants (56.9%) had to treat a second time and
31 (28.4%) had to treat a third time. Some participants (17.6%) had headache
recurrence within 24 hours after becoming headache free following initial
medication and some (23.5%) had recurrence after becoming headache free following
their second medication. Sixty-six percent of participants reported being very
satisfied/satisfied with their initial medication and 33% were somewhat
dissatisfied/dissatisfied to some degree. Even though most patients were
satisfied with their medication, 88% reported that they would be willing to try a
new antimigraine medication. Most patients (60 [55%]) preferred a long-acting
agent versus a rapid-onset, short-acting agent (which was preferred by 49 [45%]
patients). CONCLUSION: Migraine patients have treatment preferences. They
generally want a drug that provides complete headache relief, and they are often 
satisfied with the current treatment options.

PMID: 16643580 [PubMed - indexed for MEDLINE]

1243: Headache. 2006 May;46(5):766-72.

Medications associated with probable medication overuse headache reported in a
tertiary care headache center over a 15-year period.

Meskunas CA, Tepper SJ, Rapoport AM, Sheftell FD, Bigal ME.

Princeton University, Molecular Biology, NJ, USA.

OBJECTIVES: To evaluate the substances associated with medication overuse
headache (MOH) in a headache center, over the course of the past 15 years.
BACKGROUND: The acute treatment of migraine has substantially changed over the
past 15 years, and therefore, the substances associated with MOH may have changed
as well. METHODS: We randomly reviewed charts of subjects seen during the years
of 2005, 2000, 1995, and 1990, to identify substances associated with MOH. Since 
the criteria proposed by the second edition of the International Classification
of Headache Disorders require causal attribution, demonstrated by improvement
after withdrawal (and this was not assessed in this study), herein we refer to
probable MOH (PMOH). We contrasted the substances associated with PMOH over the
studied years. RESULTS: Our sample consists of 1200 individuals, 300 per year of 
interest. The proportions of subjects with a diagnosis of PMOH remained stable
over the years, varying from 64% of all cases seen in the center in 1990, to
59.3% in 2005. We found a significant decrease in the relative frequency of
probable ergotamine overuse headache (from 18.6% to 0%, P < .0001), and in
probable combination analgesic overuse headache (from 42.2% to 13.6%, P < .0001).
The differences were not significant for opioid overuse headache. The relative
frequency increased significantly for the triptans (from 0% to 21.6%, P < .0001),
simple analgesics (from 8.8% to 31.8%, P < .05), and for combinations of acute
medications (from 9.8% to 22.7%, P = .01). CONCLUSION: While overuse of acute
medications remains an important problem in the tertiary care arena, the
substances associated with the overuse have dramatically changed over the past 15
years. Educational initiatives should emphasize that the newer specific acute
migraine medications (triptans) may also be associated with PMOH.

PMID: 16643579 [PubMed - indexed for MEDLINE]

1244: Headache. 2006 May;46(5):754-65.

Migraine care among different ethnicities: do disparities exist?

Nicholson RA, Rooney M, Vo K, O'Laughlin E, Gordon M.

Department of Family Medicine, Saint Louis University School of Medicine, MO
63104, USA.

OBJECTIVE: Evaluate whether, in a primary care setting, Caucasians (C) and
African Americans (AA) with moderately to severely disabling migraines differed
in regards to: utilizing the health-care system for migraine care, migraine
diagnosis and treatment, level of mistrust in the health-care system, perceived
communication with their physician, and perceived migraine triggers. BACKGROUND: 
Research has documented ethnic disparities in pain management. However, almost no
research has been published concerning potential disparities in utilization,
diagnosis, and/or treatment of migraine. It is also important to consider whether
ethnic differences exist for trust and communication between patients and
physicians, as these are essential when diagnosing and treating migraine.
METHODS: Adult patients with headache (n = 313) were recruited from primary care 
waiting rooms. Of these, 131 (AA = 77; C = 54) had migraine, moderate to severe
headache-related disability, and provided socioeconomic status (SES) data.
Participants completed measures of migraine disability (MIDAS), migraine
health-care utilization, diagnosis and treatment history, mistrust of the medical
community, patient-physician communication (PPC), and migraine triggers. Analysis
of covariance (controlling for SES and recruitment site), chi-square, and Pearson
product moment correlations were conducted. RESULTS: African Americans were less 
likely to utilize the health-care setting for migraine treatment (AA = 46% vs. C 
= 72%, P < .001), to have been given a headache diagnosis (AA = 47% vs. C = 70%, 
P < .001), and to have been prescribed acute migraine medication (AA = 14% vs. C 
= 37%, P < .001). Migraine diagnosis was low for both groups, and <15% of all
participants had been prescribed a migraine-specific medication or a migraine
preventive medication despite suffering moderate to severe levels of migraine
disability. African Americans had less trust in the medical community (P < .001, 
eta2 = 0.26) and less positive PPC (P < .001, eta2 = 0.11). Also, the lower the
trust and communication, the less likely they were to have ever seen (or
currently be seeing) a doctor for migraine care or to have been prescribed
medication. CONCLUSIONS: Migraine utilization, diagnosis, and treatment were low 
for both groups. However, this was especially true for African Americans, who
also reported lower levels of trust and communication with doctors relative to
Caucasians. The findings highlight the need for improved physician and patient
education about migraine diagnosis and treatment, the importance of cultural
variation in pain presentation, and the importance of communication when
diagnosing and treating migraine.

Publication Types: 
    Comparative Study

PMID: 16643578 [PubMed - indexed for MEDLINE]

1245: Headache. 2006 May;46(5):750-3.

Comment in:
    Headache. 2006 Oct;46(9):1462-3.

Migraine prevention: what patients want from medication and their physicians (a
headache specialty clinic perspective).

Rozen TD.

Michigan Head Pain & Neurological Institute, Ann Arbor 48104, USA.

OBJECTIVE: To document the results of a migraine patients survey, from a headache
specialty clinic, in which patients were asked to rank, in order of importance,
certain characteristics of migraine preventive treatment. METHODS: A 10-question 
survey was completed by 150 patients (114 females and 36 males) with a history of
migraine who presented to the Michigan Head Pain & Neurological Institute. The
patients were asked to rank, in order of importance, characteristics of migraine 
preventive treatment. Each characteristic was rated individually on a 1 to 10
scale (1 being of little importance and 10 being extremely important). The mean
rating of each characteristic was then calculated and the results analyzed.
RESULTS/DISCUSSION: From this migraine preventive treatment survey, the most
important thing to migraineurs, from a headache specialty clinic population, is
that the prescribing physician involves them in the decision making of choosing a
preventive agent. The physician taking time to explain the possible medication
side effects is the second most highly ranked characteristic. Migraine
preventives with published efficacy in the medical literature are also deemed
very important. Migraineurs do not mind using more than 1 preventive agent at one
time if greater efficacy can be achieved. Agents that may affect weight and/or
cause sedation may be important factors as to why patients (especially females)
may not want to take a preventive medication. Natural therapies and once-daily
dosing are ranked lower overall but still are important characteristics of
preventive treatment. Some gender differences are noted in the ranking of
migraine preventive characteristics.

PMID: 16643577 [PubMed - indexed for MEDLINE]

1246: Headache. 2006 May;46(5):742-9.

Factors influencing migraineur-consulting behavior in a university population.

Skomo ML, Desselle SP, Berdine HJ.

Duquesne University, Mylan School of Pharmacy, Pittsburgh, PA, USA.

OBJECTIVE: The purpose of this study was to identify factors that contribute to
treatment-seeking behavior in migraineurs in a large employer population.
Specifically, the impact of psychographic variables, such as social support,
attitudes toward medication, locus of control, and migraine-associated
disability, are considered concomitantly with demographic and disease severity
variables. BACKGROUND: Migraine remains an underconsulted condition. Previous
explorations of demographic factors and headache characteristics have not
adequately predicted migraineur physician-consulting behavior. METHODS:
University employees and students experiencing headaches were interviewed by
pharmacists to determine whether they suffer from migraine using the
International Headache Society (IHS) criteria for migraine. Identified
migraineurs were categorized into 3 groups: (1) never-consulter, (2)
lapsed-consulter, and (3) current-consulter. Each group was asked to complete an 
instrument that assesses perceived social support (Headache Social Support
Questionnaire), medication attitudes (Beliefs about Medicines Questionnaire),
locus of control (Headache-Specific Locus of Control Scale), and
migraine-associated disability (Migraine Disability Assessment Questionnaire).
Univariate (ANOVA) and multivariate (logistic regression) approaches were used to
identify factors associated with migraineur-consulting behavior. RESULTS: A total
of 100 subjects participated in the study. Eighty-two participants met IHS
criteria for migraine, of whom 22 were never-consulters, 20 were
lapsed-consulters, and 40 were current-consulters. The consulter groups differed 
on scores acquired from the Social Support Active Involvement subscale (P= .04)
and the Healthcare Professional Locus of Control subscale (P= .010). The logistic
regression procedures confirmed the contributions of social support and
healthcare locus of control in predicting migraineur-consulting behavior.
CONCLUSION: Results suggest that attitudes concerning the role of healthcare
professionals and the presence of a supportive social network have greater
influence on migraineur-consulting behavior than do patient demographic
characteristics, beliefs about medications, and migraine frequency and severity. 
With an understanding of the link between psychosocial variables and consulting
behavior, healthcare professionals may be able to positively impact migraineur
physician consultation rates, drug therapy, and quality of life.

PMID: 16643576 [PubMed - indexed for MEDLINE]

1247: Headache. 2006 May;46(5):732-41.

Comment in:
    Headache. 2007 Mar;47(3):448.

Changing physician knowledge, attitudes, and beliefs about migraine: evaluation
of a new educational intervention.

Patwardhan MB, Samsa GP, Lipton RB, Matchar DB.

Center for Clinical Health Policy Research, Duke University Medical Center,
Durham, NC 27705, USA.

OBJECTIVE: Use a presurvey of primary care providers (PCPs) enrolled in a
continuing medical education (CME) program on headache management to ascertain
their existing knowledge, attitudes, and beliefs regarding migraine and use a
postsurvey to determine the extent to which the CME program has brought
participant knowledge, attitudes, and skills closer to conformance with best
evidence. BACKGROUND: Migraine is a common and debilitating condition, which PCPs
may not always manage satisfactorily. In an effort to improve management, the
American Headache Society has developed a CME program called BRAINSTORM that
encourages PCPs to adopt the US Headache Consortium Guidelines for headache care.
METHODS: A 20-item questionnaire was developed that covered the essential
elements of migraine care. The questionnaire was administered before and after a 
BRAINSTORM presentation to 254 consenting primary care clinicians attending a
medical meeting at 1 of 6 sites. A control group of 112 comparable physicians who
did not attend the presentation completed the same questionnaire. Prepresentation
scores of attendees were compared to scores of nonattendees to assess the
generalizability of results. Prepresentation scores on selected questions were
used to assess participant baseline knowledge, attitudes, and beliefs. Pre- and
postpresentation scores for attendees at all sites were compared using the
Mantel-Haenszel statistic to assess the effectiveness of the BRAINSTORM CME. Pre-
and postpresentation scores were compared by site using the Breslow-Day test to
evaluate any differential impact based on CME location. RESULTS: Prepresentation 
scores of attendees and nonattendees were found to be similar. No significant
difference in performance was noted across sites. A chi-square analysis revealed 
a statistically significant difference between pre- and postpresentation scores
for 16 of the test's 20 questions. In the pretest, all participants scored <66%
on 2 questions related to prevalence, impact, and pathophysiology of migraine, 2 
questions pertaining to history taking/physical examination, and 3 migraine
management questions. Attendee scores improved to >66% posttest on all except 2
questions related to prevalence, impact, and pathophysiology of migraine.
CONCLUSION: Our results indicate that PCPs need to acquire greater understanding 
about the epidemiology and pathophysiology of migraine and may require guidance
in history taking and physical examination of migraine patients. Improvement in
scores posttest confirms that the BRAINSTORM program has a significant immediate 
impact on the knowledge, beliefs, and attitudes of participants. The program
could be strengthened to improve emphasis in some areas where posttest scores
showed no improvement.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16643575 [PubMed - indexed for MEDLINE]

1248: Headache. 2006 May;46(5):726-31.

Erratum in:
    Headache. 2006 Jul-Aug;46(7):1227.

Comment in:
    Nat Clin Pract Neurol. 2006 Oct;2(10):526-7.

The impact of intensive patient education on clinical outcome in a clinic-based
migraine population.

Rothrock JF, Parada VA, Sims C, Key K, Walters NS, Zweifler RM.

Department of Neurology, University of South Alabama, Mobile 36693, USA.

OBJECTIVE: To determine whether the addition of patient education to routine
medical management improves the clinical status of migraine patients and reduces 
their utilization of healthcare resources. BACKGROUND: Optimal migraine
management typically requires effective patient education. Such education often
is difficult to accomplish in the busy clinic setting. METHODS: One hundred
consecutive patients with migraine presenting to an university-based headache
clinic were randomized to receive or not receive a standardized course of
didactic instruction regarding migraine biogenesis and management. The course
consisted of 3 classes taught by lay migraineurs who themselves previously had
undergone intensive training. All patients were evaluated initially and at 1, 3, 
and 6 months by a neurologist blinded as to the results of randomization.
Clinical variables examined included headache frequency/severity, migraine
disability assessment (MIDAS) scores, patient compliance, presence versus absence
of analgesic use/overuse, and headache-related unscheduled visits or phone calls.
Comparisons were made between baseline findings and findings at the 6-month
follow-up visit, with the change in mean MIDAS score serving as the primary
outcome variable. RESULTS: At 6 months the group randomized to receive intensive 
education exhibited a significantly greater reduction in mean MIDAS score than
the group randomized to routine medical management only (24 vs. 14 points; P <
.05). Those patients also experienced a reduction in mean headache days per month
and a greater reduction in functionally incapacitating headache days per month,
exhibited less analgesic overuse and need for abortive therapy, were more
compliant with prophylactic therapy prescribed, and made fewer headache-related
calls to the clinic or unscheduled visits. CONCLUSION: Intensive education of
migraine patients by trained lay instructors may convey significant benefit to
those patients and reduce their utilization of healthcare resources.

Publication Types: 
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 16643574 [PubMed - indexed for MEDLINE]

1249: Headache. 2006 May;46(5):715-25.

Recognition and therapeutic management of migraine in 2004, in France: results of
FRAMIG 3, a French nationwide population-based survey.

Lucas C, Géraud G, Valade D, Chautard MH, Lantéri-Minet M.

Neurological Clinic, Hospital Salengro, Lille, France.

OBJECTIVE: To evaluate the proportion of migraineurs who are self-aware of their 
disease in France, to determine the factors (disability, quality of life,
psychiatric comorbidities, and medical consultation) that may promote
self-awareness of migraine, and to assess the influence of these factors on
migraine attacks. BACKGROUND: New recommendations for migraine diagnosis and
medical management were released in 2003 by the French medicoeconomic evaluation 
service (ANAES). In addition, the revised classification of headache disorders
recently issued by the International Headache Society includes probable migraine 
as a form of migraine. However, strict and probable migraine now appear to be
part of the same spectrum of disease. METHODS: Subjects with migraine (strict or 
probable) according to the revised classification were identified by a postal
questionnaire from a large representative sample of the French adult population. 
Migraine-related disability was assessed using the MIDAS questionnaire, anxiety
and depression by the Hospital Anxiety and Depression scale (HADS), and
health-related quality of life (HRQoL) by the 8 concepts of the Short-Form 12
(SF-12) questionnaire. Migraine management was assessed according to the use of
recommended or nonrecommended treatments, and treatment efficacy according to the
set of 4 questions designed by the ANAES. RESULTS: Of the 10,532 subjects
interviewed, 1,179 subjects (21.3%) were identified as migraineurs. Sixty percent
of all migraine subjects were not self-aware that they had migraine. Medical
consultation, duration of migraine history, severe intensity of attacks, impact
on daily living, and female gender promoted self-awareness of migraine. On the
other hand, HRQoL and anxiety and depression scores were not different between
subjects self-aware or not self-aware of migraine. Only 20% of all migraine
subjects were medically followed-up. Quality of the first medical consultation
appears determinant for continued consulting. Subjects self-aware of migraine
more frequently used recommended acute treatments of migraine, which proved more 
effective than nonrecommended treatments as assessed according to the ANAES set
of questions. CONCLUSIONS: Migraine medical diagnosis and follow-up remain low in
France. Careful medical consultation is a prime factor for migraine subject
self-awareness of migraine, continued consultation, and use of recommended
medications for the treatment of migraine attacks.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16643573 [PubMed - indexed for MEDLINE]

1250: Headache. 2006 Apr;46(4):682-3.

Exploding head syndrome followed by sleep paralysis: a rare migraine aura.

Evans RW.

Neurology, Park Plaza Hospital, Houston, Texas, USA.

A 26-year-old patient is described with a unique migraine aura. She described an 
8-year history of episodes occurring 1 to 2 times yearly of exploding head
syndrome followed by sleep paralysis followed by a migraine headache. She also
had identical headaches without aura about once per week. Both aura symptoms,
which may occur in the brainstem, resulted in activation of the trigeminovascular
system through an unknown mechanism.

Publication Types: 
    Case Reports

PMID: 16643566 [PubMed - indexed for MEDLINE]

1251: Headache. 2006 Apr;46(4):672-5.

Comment in:
    Headache. 2007 Mar;47(3):448-50.

Could statins be useful in the treatment of patients with migraine?

Liberopoulos EN, Mikhailidis DP.

Department of Clinical Biochemistry, Royal Free Hospital and University College
Medical School, Pond Street, London NW3 2QG, UK.

Migraine is a common and disabling neurological disorder. Studies have shown that
patients with migraine (especially those with typical aura with migraine) have an
unfavorable cardiovascular risk profile and an increased risk of early-onset (<45
years) ischemic stroke. Statins are effective hypolipidemic drugs that reduce
cardiovascular-related morbidity and death in patients with or without
established atherosclerotic vascular disease. We report a patient whose frequent 
attacks of typical aura with migraine completely resolved after the initiation of
treatment with a statin. In this context, we comment on the possible effects of
statins on the pathophysiology of migraine. We suggest that statins may be useful
drugs in the treatment of migraine because they could reduce the increased
cardiovascular risk in these patients and also attenuate migraine attacks. Only a
randomized prospective study in this population could provide a definite answer
to these speculations.

Publication Types: 
    Case Reports

PMID: 16643563 [PubMed - indexed for MEDLINE]

1252: Headache. 2006 Apr;46(4):663-71.

Patent foramen ovale and migraine--bringing closure to the subject.

Schwedt TJ, Dodick DW.

Department of Neurology, Mayo Clinic College of Medicine, 13400 E. Shea Blvd,
Scottsdale, AZ 85259, USA.

There is increasing interest in the relationship between migraine and patent
foramen ovale (PFO). PFO is more common in migraineurs with aura, and migraine
with aura is more prevalent in patients with PFO. Retrospective analyses of PFO
closure for stroke prevention and decompression illness in divers have suggested 
that migraineurs with and without aura may derive significant benefit from PFO
closure, but to date no prospective, randomized, sham-controlled study to confirm
this has been completed. Herein we review published data regarding the
relationship between migraine and PFO and discuss the rationale, justification,
and important factors to consider in the conduct of prospective, controlled,
clinical trials designed to evaluate the efficacy and safety of percutaneous
device closure of PFO for migraine prevention.

Publication Types: 
    Review

PMID: 16643562 [PubMed - indexed for MEDLINE]

1253: Headache. 2006 Apr;46(4):642-8.

Comparison of the effect of topiramate and sodium valporate in migraine
prevention: a randomized blinded crossover study.

Shaygannejad V, Janghorbani M, Ghorbani A, Ashtary F, Zakizade N, Nasr V.

Department of Neurology, Isfahan University of Medical Sciences and Health
Services, Isfahan, Iran.

BACKGROUND: Topiramate and sodium valporate are anticonvulsants, demonstrated to 
be effective as monotherapy for migraine prevention in placebo-controlled trials.
OBJECTIVES: To compare the relative efficacy of topiramate and sodium valporate
in the prevention of migraine. PATIENTS AND METHODS: A 24-week, randomized,
double-blind, crossover, clinical trial was conducted from October 2003 to
September 2004. A total of 64 patients with migraine headache, aged 14 to 57
years, were randomly allocated to the 2 treatment groups. The first group
received topiramate (25 mg daily increment over 1 week to 50 mg) for a total of 2
months. The second group received sodium valporate (200 mg daily increment over 1
week to 400 mg) for 2 months. Response to treatment was assessed at 0, 1, 8, 16, 
and 24 weeks after start of therapy. RESULTS: Topiramate appeared to be
equivalent in efficacy and safety to sodium valporate. A significant decrease in 
duration, monthly frequency, and intensity of headache occurred in both groups.
Of the 32 patients treated with sodium valporate, the mean standard deviation
(SD) of monthly migraine frequency decreased from 5.4 (2.5) to 4.0 (2.8) episode 
per month, headache intensity from 7.7 (1.2) to 5.8 (1.7) by visual analog scale 
(VAS), and headache duration from 21.3 (14.6) to 12.3 (10.7) hours (P < .001).
Correspondingly, in the 32 patients treated with topiramate, the mean SD of
monthly headache frequency decreased from 5.4 (2.0) to 3.2 (1.9) per month,
headache intensity from 6.9 (1.2) to 3.7 (1.3), and headache duration from 17.3
(8.4) to 3.9 (2.7) hours (P < .001). CONCLUSION: This study demonstrates that
treatment with topiramate and sodium valporate both significantly reduce migraine
headache. This effect of topiramate and sodium valporate has previously been
shown to reduce migraine headache, and we postulate that treatment with
topiramate and sodium valporate may have a similar benefit.

Publication Types: 
    Comparative Study
    Randomized Controlled Trial

PMID: 16643559 [PubMed - indexed for MEDLINE]

1254: Headache. 2006 Apr;46(4):611-21.

Color vision but not visual attention is altered in migraine.

Shepherd AJ.

School of Psychology, Birbeck College, University of London, Malet St, London,
WC1E 7HX, UK.

OBJECTIVE: To examine visual search performance in migraine and headache-free
control groups and to determine whether reports of selective color vision
deficits in migraine occur preattentively. BACKGROUND: Visual search is a classic
technique to measure certain components of visual attention. The technique can be
manipulated to measure both preattentive (automatic) and attentive processes.
Here, visual search for colored targets was employed to extend earlier reports
that the detection or discrimination of colors selective for the short-wavelength
sensitive cone photoreceptors in the retina (S or "blue" cones) is impaired in
migraine. METHOD: Visual search performance for small and large color differences
was measured in 34 migraine and 34 control participants. Small and large color
differences were included to assess attentive and preattentive processing,
respectively. In separate conditions, colored stimuli were chosen that would be
detected selectively by either the S-, or by the long- (L or "red") and middle (M
or "green")-wavelength sensitive cone photoreceptors. RESULTS: The results showed
no preattentive differences between the migraine and control groups. For active, 
or attentive, search, differences between the migraine and control groups
occurred for colors detected by the S-cones only, there were no differences for
colors detected by the L- and M-cones. The migraine group responded significantly
more slowly than the control group for the S-cone colors. CONCLUSIONS: The
pattern of results indicates that there are no overall differences in search
performance between migraine and control groups. The differences found for the
S-cone colors are attributed to impaired discrimination of these colors in
migraine and not to differences in attention.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 16643556 [PubMed - indexed for MEDLINE]

1255: Headache. 2006 Apr;46(4):604-10.

Erratum in:
    Headache. 2006 Jun;46(6):1039.

The prevalence and spectrum of sleep problems in women with transformed migraine.

Calhoun AH, Ford S, Finkel AG, Kahn KA, Mann JD.

Neurology, University of North Carolina, Chapel Hill, 27599-7025, USA.

OBJECTIVES: It is our clinical observation that patients with transformed
migraine (TM) almost invariably report nonrestorative sleep. In this study we
sought first to validate that clinical observation, then to describe the
prevalence and spectrum of factors that might contribute to nonrestorative sleep 
in a TM population. BACKGROUND: Although headaches have been linked with sleep
problems for over a century, there is little information about the spectrum or
prevalence of specific sleep problems associated with TM in adults. METHODS: We
conducted a detailed sleep interview on 147 consecutive women with TM. Subjective
sleep quality was assessed by asking patients to describe their state upon
awakening as "refreshed" or "tired." RESULTS: None of the 147 patients reported
awakening "refreshed," and 83.7% stated that they awakened "tired." Sleep
complaints were prevalent and varied in this population. CONCLUSIONS: Although
the relationship between pain and sleep is complex and ill understood, we found a
very high prevalence of nonrestorative sleep and a similarly high prevalence of
modifiable poor sleep habits in patients with TM. Since behavioral approaches
have been found effective in improving sleep quality in patients with poor sleep 
hygiene, we propose that studies be undertaken to assess the impact of such
treatment on TM.

PMID: 16643555 [PubMed - indexed for MEDLINE]

1256: Headache. 2006 Apr;46(4):597-603.

Comment in:
    Headache. 2006 Sep;46(8):1309-10.

Endocrine function is altered in chronic migraine patients with
medication-overuse.

Rainero I, Ferrero M, Rubino E, Valfrè W, Pellegrino M, Arvat E, Giordano R,
Ghigo E, Limone P, Pinessi L.

Department of Neuroscience, Neurology III--Headache Center, University of Turin, 
Via Cherasco 15, 10126 Torino, Italy.

OBJECTIVE: To evaluate the effects of analgesic overuse on endocrine function in 
patients with chronic migraine and medication-overuse headache (CM-MOH).
BACKGROUND: Chronic migraine is frequently associated with an overuse of
symptomatic medications. Drugs currently used in acute migraine attacks are
associated with several endocrine effects. At present, the endocrine effects of
medication overuse in chronic migraine patients are unknown. METHODS: Eighteen
patients with CM-MOH, diagnosed according to the ICHD-II criteria, and 18 healthy
controls received an intravenous administration of GHRH, hCRH, and TRH. Plasma
concentrations of GH, TSH, ACTH, and cortisol were measured for a 90-minute
period after administration of the specific releasing hormones. RESULTS: Hormonal
basal concentrations were similar in both groups. GH response to GHRH was
significantly reduced in patients with CM-MOH in comparison with controls. TRH
induced a reduction of TSH concentrations only at the end of the test. After hCRH
administration, ACTH and cortisol concentrations were significantly higher in
cases than in controls. A significant correlation between duration of the disease
and altered hormonal response was found. CONCLUSIONS: Our study shows that both
corticotropic and somatotropic functions are significantly impaired in CM-MOH
patients and suggests a role for hormones in the development of chronic migraine.

Publication Types: 
    Clinical Trial
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 16643554 [PubMed - indexed for MEDLINE]

1257: Headache. 2006 Apr;46(4):592-6.

Plasma 5-hydroxytryptamine (5-HT) in migraine during an attack-free period.

Nagata E, Shibata M, Hamada J, Shimizu T, Katoh Y, Gotoh K, Suzuki N.

Department of Neurology, Saitama City Hospital, Saitama, Japan.

OBJECTIVE: We measured the plasma 5-HT, 5-hydroxytryptophan (5-HTP), and
tryptophan levels in controls, migraine patients with aura (MWA), and migraine
patients without aura (MWoA) during an attack-free period. BACKGROUND: Serotonin 
(5-hydroxytryptamine, 5-HT) has been implicated in the pathophysiology of
migraine. The precise relationship between 5-HT and migraine, however, remains
unclear. METHODS: Blood samples in controls, MWA, and MWoA patients during an
attack-free period were collected from brachial arteries and analyzed using HPLC.
RESULTS: The plasma tryptophan and 5-HTP levels were not significantly different 
between the controls and migraine patients (either MWA or MWoA). However, the
plasma 5-HT level in the MWA patients was significantly lower than that in the
controls and MWoA patients. CONCLUSIONS: The present data suggest that reduced
levels of 5-HT in MWA may result from either a dysfunction in the enzymes
involved in serotonin biosynthesis or a dysfunction in 5-HT release or uptake
from platelets and lymphocytes. These findings indicate the existence of a
serotonin metabolism dysfunction in MWA patients that may differ from the state
of serotonin metabolism in MWoA patients.

PMID: 16643553 [PubMed - indexed for MEDLINE]

1258: Headache. 2006 Apr;46(4):585-91.

Platelet levels of dopamine are increased in migraine and cluster headache.

D'Andrea G, Granella F, Perini F, Farruggio A, Leone M, Bussone G.

Headache Centre, Villa Margherita Hospital, Arcugnano, VI, Italy.

OBJECTIVE: To measure plasma and platelet levels of dopamine in patients with
migraine with aura, migraine without aura, and cluster headache. BACKGROUND:
Clinical, genetic, and pharmacological evidences suggest that an abnormality of
dopaminergic system plays a role in migraine pathogenesis. Direct evidence of an 
abnormal metabolism of dopamine in migraine, however, is lacking. METHODS: Plasma
and platelet levels of dopamine were measured in patients with migraine with aura
or migraine without aura during headache-free periods and in patients with
cluster headache during the remission and active periods, as compared with
healthy control subjects, using a multichannel electrochemical high-performance
liquid chromatography system. RESULTS: Plasma levels of dopamine were not
detectable with our methodology. Platelet levels of dopamine were higher in both 
types of migraine (migraine without aura = .20 +/- .17 ng/10(8) platelets;
migraine with aura = .16 +/- .19 ng/10(8) platelets) than in control subjects
(.10 +/- .11 ng/10(8) platelets), although in migraine with aura patients the
difference was not significant. Patients with cluster headache showed the highest
levels of platelet dopamine (.34 +/- .36 ng/10(8) platelets). CONCLUSIONS: Our
results support the hypothesis that the dopaminergic system is impaired in
migraine and cluster headache and suggest that high platelet levels of dopamine
may represent an abnormal biochemical phenotypic trait of these primary
headaches.

PMID: 16643552 [PubMed - indexed for MEDLINE]

1259: Headache. 2006 Apr;46(4):563-76.

Workplace absenteeism and aspects of access to health care for individuals with
migraine headache.

Lofland JH, Frick KD.

Health Policy, Thomas Jefferson University, Philadelphia, PA, USA.

OBJECTIVES: (1) To examine the relationship between access to care and the number
of missed workdays, and (2) to determine how this relationship is confounded by
the presence of having health insurance and health care use among migraineurs.
DESIGN/METHODS: This retrospective, pooled, cross-sectional study used 1996 to
1999 Medical Expenditure Panel Survey data. Employed migraineurs who were between
18 and 65 years of age were included. Individuals reporting a neoplastic or an
acute pain condition were excluded. An access to care index was developed using
Rasch Partial Credit Analysis. A 2-part model was used to estimate the annual
number of missed workdays. RESULTS: Of the 703 migraineurs, 538 (77%) reported
missing work time. Of those who missed work, the mean (SE) annual number of
missed workdays was 4.4 (.39). A higher level of access to care (P= .025) and
presence of depression (P= .033) were significantly associated with missing a
greater number of workdays. We created a proxy for migraine severity based on
migraine-related prophylactic medication use and hospitalization(s). Severe
migraines were significantly (OR = 2.01, SE = .51, P= .006) associated with an
increased likelihood to miss workdays. When health insurance was included in the 
model, a higher level of access to care was significantly associated with the
increased likelihood to miss workdays (OR = 1.04, SE = .021, P= .05). From the
original model, the odds ratio (1.035 to 1.040) and the SE (.020 to .021)
increased slightly. When health care use was included in the model and health
insurance was removed, (1) emergency department visits were significantly (P=
.006) associated with missing a greater number of workdays, and (2) access to
care was significantly associated with missing a greater number of workdays (P=
.028). When having health insurance and health care use were simultaneously
included in the model, a higher level of access to care was significantly
associated with greater likelihood to miss work (OR = 1.040, SE = .0212, P= .05) 
and missing a greater number of workdays (P= .005). However, a change of 1
standard deviation in the score would be associated with a 12% change in the odds
to miss work and only 8 percentage points change in the number of missed
workdays. CONCLUSIONS: Contrary to expectations, a higher level of access to care
is significantly associated with an increased likelihood to miss work and with
missing a greater number of workdays. Depression, migraine severity, and health
care use are important explanatory variables. Having health insurance may be a
confounder between access to care and workplace absenteeism.

PMID: 16643549 [PubMed - indexed for MEDLINE]

1260: Headache. 2006 Apr;46(4):553-62.

Reliability, validity, and clinical utility of the Migraine-ACT questionnaire.

Kilminster SG, Dowson AJ, Tepper SJ, Baos V, Baudet F, D'Amico D.

Institute of Naval Medicine, Alverstoke, Hampshire, UK.

BACKGROUND: The 4-item Migraine-ACT questionnaire is an assessment tool for use
by primary care physicians to identify patients who require a change in their
current acute migraine treatment. It has been shown to be easy to use, and to be 
reliable and accurate in its assessments. OBJECTIVES: To further analyze the
Migraine-ACT study database, providing additional information on the reliability,
validity, and potential clinical utility of the questionnaire. METHODS:
Reliability was assessed by recording the distribution of Migraine-ACT scores
recorded at baseline and 1 week later (test-retest reliability). Analyses of
consistency of Migraine-ACT scores were conducted on the total sample of patients
and for the separate centers, using Pearson and Spearman correlations. Validity
was assessed by comparing the t-discrimination values for clinically relevant
questions within domains of the original 27-item questionnaire. Reliability and
validity were also assessed by constructing an "alternative" (Form B)
Migraine-ACT questionnaire, derived from an analysis of the second-best items in 
each domain in the original study data. Clinical utility was assessed using
Pearson pairwise correlations to compare Migraine-ACT scores with clinically
defined criteria as analyzed by the SF-36 Quality of Life questionnaire, the
Migraine Disability Assessment (MIDAS) questionnaire, and the Migraine Therapy
Assessment (MTAQ) questionnaire. RESULTS: The distribution of Migraine-ACT scores
between the 2 completions of the questionnaire was consistent for the total
sample (test-retest reliability, r= .81) and between the individual countries (r=
.61 to .92). In this study, the validity (assessed as t-discrimination) of the
Migraine-ACT "impact" and "global assessment of relief" questions were markedly
higher than those of other endpoints used in migraine clinical studies. The Form 
B Migraine-ACT questionnaire was almost as reliable and accurate as the original 
Form A questionnaire. The distribution of Migraine-ACT scores was: 0 = 12.6%, 1 =
13.7%, 2 = 14.7%, 3 = 20.5%, and 4 = 38.4%. The change in Migraine-ACT score
correlated with, and had a linear relationship with changes in SF-36, MIDAS, and 
MTAQ scores, and indicated that a Migraine-ACT score of <or=2 corresponded with a
need to consider changing the patient's acute medication. About 40% of the
migraine patients in the study scored <or=2 and may have had significant unmet
treatment needs. CONCLUSIONS: These data confirm the excellent reliability and
validity of the Migraine-ACT questionnaire and provide further evidence for its
utility in clinical practice.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Validation Studies

PMID: 16643548 [PubMed - indexed for MEDLINE]

1261: J Am Acad Audiol. 2006 Jan;17(1):69-80.

Differentiation of Ménière's disease and migraine-associated dizziness: a review.

Shepard NT.

Department of Special Education and Communication Disorders, College of Education
and Human Services, University of Nebraska, Lincoln 68583-0738, USA.
nshepard2@unl.edu

A significant body of literature exists demonstrating a relationship between
migraine disorders and dizziness. In the characterizations of the
migraine-associated dizziness, the signs and symptoms show overlap with those
characterizing Meniere's disease. There has been literature, beginning with
Ménière himself, suggesting a relationship between Ménière's disease and
migraine-associated dizziness. This implicates a possible underlying link in
pathogenesis. This review article presents a discussion of the overlap in signs
and symptoms between the two disorders. Suggestions for differentiating between
the disorders based on recent literature protocols and use of test results are
also discussed. Vestibular and balance rehabilitation programs have a role in
both of the disorders but differ in the overall management aspects of the
disorders. The distinction in the use of vestibular rehabilitation is discussed.

Publication Types: 
    Review

PMID: 16640061 [PubMed - indexed for MEDLINE]

1262: Brain Res. 2006 May 23;1090(1):197-201. Epub 2006 Apr 25.

Cerebrospinal fluid GABA levels in chronic migraine with and without depression.

Vieira DS, Naffah-Mazacoratti MG, Zukerman E, Senne Soares CA, Alonso EO,
Faulhaber MH, Cavalheiro EA, Peres MF.

Instituto Israelita de Ensino e Pesquisa Albert Einstein, Universidade Federal de
São Paulo-Escola Paulista de Medicina, Brazil.

Psychiatric comorbidity is one of the key elements in chronic migraine (CM)
management. Depression is particularly common in these patients, occurring in up 
to 85%. Preclinical studies have suggested that gamma-aminobutyric acid (GABA)
levels may be decreased in animal models of depression. Also, clinical studies
have reported low level in mood disorder patients for both plasma and
cerebrospinal fluid (CSF) GABA. We hypothesized that low GABA levels in the brain
might be related to the depression associated with CM. We studied 14 chronic
migraine patients, with or without depression, compared to age-and sex-matched
controls. CSF GABA levels were measured by HPLC. CSF GABA levels showed
significant lower levels in depressed patients than those without depression. No 
difference was found when comparing patients versus controls. A GABA deficiency
may be the underlying mechanism of depression in CM. Hence, preventive therapies 
modulating GABA neurotransmission could be used in CM associated with depression.

PMID: 16638608 [PubMed - indexed for MEDLINE]

1263: Pediatr Neurol. 2006 Apr;34(4):329-32.

Minor head trauma-induced sporadic hemiplegic migraine coma.

Curtain RP, Smith RL, Ovcaric M, Griffiths LR.

Genomics Research Centre, School of Medical Science, Griffith University, Gold
Coast, Queensland, Australia.

Familial hemiplegic migraine is a severe, rare subtype of migraine. Gene
mutations on chromosome 19 have been identified in the calcium channel,
voltage-dependent, P/Q type, alpha-1A subunit gene (chromosome 19p13) for
familial hemiplegic migraine. Recently a gene mutation (Serine-218-Leucine) for a
dramatic syndrome associated with familial hemiplegic migraine, commonly named
"migraine coma", has implicated exon 5 of this gene. The occurrence of trivial
head trauma, in such familial hemiplegic migraine patients, may also be
complicated by severe, sometimes even fatal, cerebral edema and coma occurring
after a lucid interval. Sporadic hemiplegic migraine shares a similar spectrum of
clinical presentation and genetic heterogeneity. The case report presented in
this article implicates the involvement of the Serine-218-Leucine mutation in the
extremely rare disorder of minor head trauma-induced migraine coma. We conclude
that the Serine-218-Leucine mutation in the calcium channel, voltage-dependent,
P/Q type, alpha-1A subunit gene is involved in sporadic hemiplegic migraine,
delayed cerebral edema and coma after minor head trauma.

Publication Types: 
    Case Reports

PMID: 16638514 [PubMed - indexed for MEDLINE]

1264: Semin Neurol. 2006 Apr;26(2):260-70.

Paroxysmal hemicrania, SUNCT, and hemicrania continua.

Boes CJ, Swanson JW.

Department of Neurology, Mayo Clinic College of Medicine, 200 First Street SW,
Rochester, MN 55905, USA.

The trigeminal autonomic cephalalgias (TACs) are a group of primary headache
disorders characterized by unilateral pain in the somatic distribution of the
trigeminal nerve and ipsilateral autonomic signs, which reflect activation of the
cranial parasympathetic pathway. The group includes cluster headache, paroxysmal 
hemicrania, and short-lasting unilateral neuralgiform headache with conjunctival 
injection and tearing. Hemicrania continua was previously classified as one of
the TACs. Despite their common elements, individually these headaches differ with
respect to attack duration, frequency, and response to indomethacin.

Publication Types: 
    Historical Article
    Review

PMID: 16628536 [PubMed - indexed for MEDLINE]

1265: Semin Neurol. 2006 Apr;26(2):232-41.

Pathophysiology and management of transformed migraine and medication overuse
headache.

Boes CJ, Black DF, Dodick DW.

Department of Neurology, Mayo Clinic College of Medicine, 200 First Street SW,
Rochester, MN 55905, USA.

There is considerable overlap in the mechanisms mediating migraine headache pain 
and sustained opioid-induced paradoxical pain. Both involve upregulation of
calcitonin gene-related peptide and increased excitability of dorsal horn
neurons. Descending facilitation from the rostral ventromedial medulla may
contribute to this increased excitability. Using special magnetic resonance
imaging techniques, high iron levels were found in the periaqueductal gray of
patients with chronic daily headache with medication overuse. The periaqueductal 
gray is the center of a powerful descending antinociceptive neuronal network and 
projects to the rostral ventromedial medulla and subsequently to the dorsal horn.
The periaqueductal gray is also involved in the behavioral response to opiate
withdrawal. Dysfunction in the periaqueductal gray may explain why frequent
analgesic use can result in medication overuse headache in migraineurs.
Management of transformed migraine with medication overuse involves patient
education, biobehavioral therapy, withdrawal of overused acute medications,
bridge therapy for withdrawal headache, initiation of preventive medication, and 
close follow-up.

Publication Types: 
    Review

PMID: 16628534 [PubMed - indexed for MEDLINE]

1266: Semin Neurol. 2006 Apr;26(2):223-31.

Episodic and chronic migraine in children.

Mack KJ.

Child and Adolescent Neurology, Mayo Clinic College of Medicine, 200 First Street
SW, Rochester, MN 55905, USA.

Migraine headaches occur frequently in both preschool and school-aged children.
Although some symptoms of migraines may change with age, they are typically
characterized by severe headaches in an ill-appearing child associated with
photophobia and nausea and are relieved by sleep. In late childhood and
adolescence, the headaches of some patients will transform into a chronic daily
headache or chronic migraine. Treatment consists of identifying environmental
triggers, providing appropriate pain relief, and the judicious use of
preventative medications.

PMID: 16628533 [PubMed - indexed for MEDLINE]

1267: Semin Neurol. 2006 Apr;26(2):217-22.

Special considerations in the treatment of migraine in women.

Lay CL, Broner SW.

The Headache Institute, St. Luke's-Roosevelt Hospital Center, 1000 Tenth Avenue, 
New York, NY 10019, USA.

Nearly 32 million Americans have migraine, 24 million of whom are women who
suffer with migraine throughout their lifetimes. Prior to puberty, girls are
afflicted with migraine at approximately the same rate as boys, but after puberty
there is an emerging female predominance. Although hormones do not entirely
explain the epidemiological variation seen in migraine, estrogen certainly plays 
an important role. Given the hormonal changes occurring throughout a woman's
life, there are many opportunities for a hormonal impact on migraine, including
menarche, oral contraceptive use, pregnancy, perimenopause, and menopause. The
special considerations of migraine in women will be reviewed including
epidemiology, pathophysiology, diagnosis, and therapy.

Publication Types: 
    Review

PMID: 16628532 [PubMed - indexed for MEDLINE]

1268: Semin Neurol. 2006 Apr;26(2):208-16.

Sporadic and familial hemiplegic migraine: diagnosis and treatment.

Black DF.

Department of Neurology, Mayo Clinic College of Medicine, Mayo Clinic-W8A, 200
First Street SW, Rochester, MN 55905, USA.

Hemiplegic migraine is a rare subtype of migraine with aura associated with
transient hemiplegia. The weakness is caused by motor aura. Hemiplegic migraine
is the only headache syndrome associated with known genetic mutations and serves 
as a model for understanding more common varieties of migraine. Because the
phenotype includes striking yet transient neurological signs and symptoms, it is 
imperative that clinicians know the differential diagnosis to rule out possible
secondary etiologies when treating patients with hemiplegic spells. Hemiplegic
migraine occurs with equal prevalence in either a sporadic or familial form
differentiated only by family history. Thus far, treatment trials are anecdotal, 
although verapamil and acetazolamide have shown promise.

Publication Types: 
    Review

PMID: 16628531 [PubMed - indexed for MEDLINE]

1269: Semin Neurol. 2006 Apr;26(2):199-207.

Behavioral approaches to the treatment of migraine.

Holroyd KA, Drew JB.

Department of Psychology, Ohio University, 225 Porter Hall, Athens, OH 45701,
USA.

Behavioral interventions such as biofeedback training, relaxation training, and
cognitive-behavior stress management therapy have been identified as efficacious 
treatments for migraine headache. These treatments, and the formats
(clinic-based, limited-contact, and home-based) in which they are taught, are
described in this article. Information about public health interventions (school,
work, Internet, and mass media) is also briefly addressed. Results of studies
examining the efficacy of behavioral treatments, how behavioral treatments
compare in effectiveness, and how they can be integrated with pharmacotherapy are
reviewed for both adult and pediatric populations. Finally, the role of
behavioral treatments in migraine treatment guidelines is discussed, and factors 
that are associated with response to behavioral treatments are reviewed.

Publication Types: 
    Research Support, N.I.H., Extramural
    Review

PMID: 16628530 [PubMed - indexed for MEDLINE]

1270: Semin Neurol. 2006 Apr;26(2):188-98.

Prophylactic pharmacotherapy for migraine headaches.

Buchanan TM, Ramadan NM.

Department of Neurology, The Chicago Medical School at Rosalind Franklin
University of Medicine and Science, 3333 Green Bay Road, North Chicago, IL 60064,
USA.

Migraine therapeutics are pharmacological, including acute and preventive,
nonpharmacological and/or both. Preventive pharmacological strategies
serendipitously were discovered to be effective and include drugs from various
pharmacological classes (e.g., beta-adrenergic blocker, anticonvulsant, tricyclic
antidepressants, serotonin receptor antagonist). Converging level I evidence and 
clinical experience support the use of the antidepressant amitriptyline, the
anticonvulsants divalproex and topiramate, and the beta-adrenergic blockers
propranolol, timolol, and metoprolol in migraine prevention. Other options for
migraine prophylaxis exist, but the level of evidence in support of their use is 
not as robust. All of these drugs have varying degrees of adverse effects, some
of which can limit their use. Balancing potential efficacy with risk of adverse
effects, addressing patients' expectations and desires, complying with management
recommendations, adequate follow up, and accurate assessment of treatment goals
are key to migraine prevention. Finally, future migraine-preventive drugs likely 
will target migraine mechanisms more specifically, which undoubtedly will enhance
the therapeutic index.

Publication Types: 
    Review

PMID: 16628529 [PubMed - indexed for MEDLINE]

1271: Semin Neurol. 2006 Apr;26(2):181-7.

Acute therapy for migraine headaches.

Rozen TD.

Michigan Head-Pain and Neurological Institute, 3120 Professional Drive, Ann
Arbor, MI 48104, USA.

The migraine attack is made up of phases, which include the prodrome, aura, and
the headache itself. Not every migraineur experiences each phase. Each phase has 
its own distinct pathogenesis and its own unique acute therapy. The acute therapy
for each phase of the migraine attack will be discussed.

Publication Types: 
    Review

PMID: 16628528 [PubMed - indexed for MEDLINE]

1272: Semin Neurol. 2006 Apr;26(2):171-80.

Pathophysiology of migraine.

Cutrer FM.

Department of Neurology, Mayo Clinic College of Medicine, 200 First Street SW,
Rochester, MN 55905, USA.

The cause and pathophysiology of migraine are not well understood. Over the years
research into migraine pathophysiology has focused on the physiology and
pharmacology of the headache, the changes in cerebral cortex associated with the 
symptoms of the aura, and more recently the genetics underlying the migraine
syndromes. In this discussion, the neuroanatomical structures activated during
migraine attacks, the traditional theories of migraine that serve as the
foundation for current research, and the essential findings from current migraine
pathophysiological research will be reviewed. Investigations in migraine can be
divided into those related to the brain events initiating a migraine attack,
those examining the mechanisms of activation and transmission within trigeminal
afferent neurons, and those focused on the effect of and the modulation of
nociception trigeminal input within the central nervous system.

Publication Types: 
    Review

PMID: 16628527 [PubMed - indexed for MEDLINE]

1273: Expert Rev Neurother. 2006 Apr;6(4):563-73.

Aspirin in the treatment of acute migraine attacks.

Diener HC, Lampl C, Reimnitz P, Voelker M.

Department of Neurology, University Duisburg-Essen, Hufelandstrasse 55, 45122,
Essen, Germany. h.diener@uni-essen.de

Acetylsalicylic acid (aspirin or ASA) has been used for many years as an
analgesic, antipyretic and anti-inflammatory drug. In recent years, evidence for 
its effectiveness in migraine headache has been demonstrated in several clinical 
trials. The effervescent highly buffered preparation of aspirin was shown to be
effective, safe and well tolerated compared with placebo or other treatment
options. The effervescent aspirin preparation is at least as effective as the
combination of aspirin plus metoclopramide, but has fewer side effects. This
review summarizes and analyzes clinical data of aspirin in the treatment of acute
migraine attacks with respect to the different galenic formulations.

Publication Types: 
    Comparative Study
    Review

PMID: 16623655 [PubMed - indexed for MEDLINE]

1274: J Manag Care Pharm. 2006 Apr;12(3):246-53.

Assessment of clinical, service, and cost outcomes of a conversion program of
sumatriptan to rizatriptan ODT in primary care patients with migraine headaches.

Gershovich OE, Billups SJ, Delate T, Hoffman CK, Carroll N.

Kaiser Permanente Colorado, 8383 W. Alameda Ave., Lakewood, CO 80226, USA.
olga.gershovich@kp.org

OBJECTIVE: Managed care organizations can increase the value of drug therapy by
negotiating discounts on drug acquisition costs with pharmaceutical manufacturers
and promoting use of preferred drugs, including the conversion of patients to
preferred medications. This investigation was designed to assess conversion
success, migraine drug utilizations, and patient satisfaction with a clinical
pharmacist-managed conversion program from sumatriptan to rizatriptan ODT, both
formulary drugs. METHODS: This was a retrospective cohort study conducted in a
managed care organization for patients aged 18 years or older who had picked up
at least one outpatient prescription for any sumatriptan dosage form at the
pharmacy between January 2002 and June 2002. Patients. pharmacy and medical data 
were reviewed to assess eligibility (e.g., no history of rizatriptan failure) for
conversion from sumatriptan to rizatriptan orally disintegrating tablet (ODT).
There was no copayment difference for members for rizatriptan ODT versus
sumatriptan. A questionnaire was developed to assess 2 domains: (1) patient
satisfaction with the medication conversion process and (2) preference for
rizatriptan ODT or sumatriptan. A random sample of 315 patients who initiated
conversion to rizatriptan ODT was surveyed. Electronic pharmacy claims were
reviewed to determine the number of patients who were successfully converted from
sumatriptan to rizatriptan ODT. Pharmacy expenditures and total health care
utilization and expenditures in the 180 days prior to (baseline) and after the
conversion (followup) to rizatriptan ODT were compared for the cohorts of
subjects who were successfully converted and those patients who were not
successfully converted. RESULTS: Therapeutic conversion from sumatriptan to
rizatriptan ODT was attempted in 457 patients; 214 (47%) were successfully
converted. The only difference between the 2 cohorts at baseline for the 6 months
prior to attempted conversion was a higher mean number of sumatriptan doses per
patient per month (PPPM) in the 243 failed conversions (mean 3.5, SD 2.9)
compared with the 214 successful conversions (mean 2.8, SD 2.8, P =0.003). The
median triptan doses increased by 1.0 PPPM in both cohorts (P =0.882), from 2.0
to 3.0 doses PPPM in the group of successful conversions and from 2.7 to 4.0 in
the group of unsuccessful conversions. The survey response rate was 55% for both 
successful and for unsuccessful conversions. More than 90% of the patients in
both cohorts were satisfied with the level of care provided by the clinical
pharmacy staff during medication conversion, and there was no difference between 
the 2 cohorts in patient satisfaction (P=0.761). Rizatriptan ODT was preferred by
68.0% and 8.5% of successful and failed conversion subjects, respectively (P
<0.001). Using representative group purchase prices, triptan expenditures for
successful conversion subjects were reduced by a median of -2 dollars (6 %) PPPM 
while triptan expenditures for unsuccessful conversions increased by a median of 
8 dollars (P <0.001). There were no differences for either cohort in median PPPM 
changes in migraine-related office visits (0.0 median change in office visits, P 
=0.748) or office-visit costs (0 dollars median change, P =0.861) for
preconversion versus postconversion attempts Regression modeling identified that 
lower total counts of sumatriptan doses filled during baseline period was an
independent predictor of successful conversion to rizatriptan ODT (P <0.001).
There was an average of 3.5 triptan medication fills per patient for successful
conversion during the 6-month follow-up period, with 78% of these subjects
filling at least 2 prescriptions for rizatriptan ODT during this period.
CONCLUSIONS: This conversion program for sumatriptan to rizatriptan ODT was
successful in converting almost half of primary care patients to the preferred
product despite the absence of a copayment incentive for members to agree to the 
conversion. There were no measurable medical or economic consequences of the
conversion, and patient satisfaction with the quality of care was maintained.
Future efforts are likely to have a higher success rate if focused on converting 
patients with less-severe migraine headaches, as measured by the need for
baseline rescue medication, since lower acuity was the only independent predictor
of successful conversion in this conversion program for 2 triptan drugs.

PMID: 16623609 [PubMed - indexed for MEDLINE]

1275: Rev Neurol Dis. 2005 Fall;2(4):167-75.

Preventive treatment of migraine.

Silberstein SD.

Department of Neurology, Jefferson Medical College of Thomas Jefferson
University, Philadelphia, PA, USA.

Migraine preventive therapy, even in the absence of a headache, is given in an
attempt to reduce the frequency, duration, or severity of attacks. Circumstances 
that might warrant preventive treatment include disabling migraine attacks, the
overuse of acute medications or failure of or contraindication to acute
medications, troublesome side effects from medication, hemiplegic migraine, or
very frequent headaches (more than 2 a week). The major medication groups for
preventive treatment include anticonvulsants, antidepressants, b-adrenergic
blockers, calcium channel antagonists, serotonin antagonists, neurotoxins,
nonsteroidal anti-inflammatory drugs, and others. If preventive medication is
indicated, the agent preferentially should be chosen from one of the first-line
categories, based on the drug's side-effect profile and the patient's coexistent 
and comorbid conditions.

Publication Types: 
    Review

PMID: 16622394 [PubMed - indexed for MEDLINE]

1276: JAMA. 2006 Apr 19;295(15):1824-30.

The influence of estrogen on migraine: a systematic review.

Brandes JL.

Department of Neurology, Vanderbilt University School of Medicine, Nashville,
Tenn, USA. jbrandes@nashvilleneuroscience.com

CONTEXT: Menstrual migraine affects approximately 50% to 60% of female
migraineurs, but knowledge regarding the role of hormones, especially estrogen,
appears incomplete. OBJECTIVE: To conduct a systematic review to determine the
role of hormones on menstrual migraine. EVIDENCE ACQUISITION: MEDLINE (January
1966 through September 1, 2005) and EMBASE Drugs and Pharmacology (January 1991
through September 1, 2005) were searched for articles published in the English
language using the keywords migraine, estrogen, menstrual migraine, pure
menstrual migraine, true menstrual migraine, menstrually-associated migraine,
menstrually-related migraine, pregnancy, breast-feeding, perimenopause,
menopause, nitric oxide, and estrogen receptors. A total of 643 unique articles
were reviewed for relevance, scientific rigor, and generalizability. For each
relevant citation, the bibliography was reviewed to identify additional sources
of pertinent data. EVIDENCE SYNTHESIS: The influence of estrogen on migraine is
evident by a 3-fold greater prevalence among women compared with men, and by
significant changes in migraine incidence with changes in female reproductive
status. Menstrual migraines are usually more resistant to treatment, generally
not associated with aura, of longer duration, and associated with more functional
disability compared with attacks at other times of the month. Biochemical and
genetic evidence suggest central and peripheral roles for estrogen in the
pathophysiology of menstrual migraine, with potential interactions with
excitatory circuits, including serotonergic components. Although evidence for
estrogen as a preventive treatment for menstrual migraine is inconsistent,
serotonin receptor agonists (triptans) provide acute relief and also may have a
role in prevention. CONCLUSIONS: Epidemiological, pathophysiological, and
clinical evidence link estrogen to migraine headaches. Triptans appear to provide
acute relief and also may be useful for headache prevention. Clear, focused, and 
evidence-based treatment algorithms are needed to support primary care
physicians, neurologists, and gynecologists in the treatment of this common
condition.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 16622144 [PubMed - indexed for MEDLINE]

1277: Eur J Neurol. 2006 Mar;13(3):244-9.

Trigger point evaluation in migraine patients: an indication of peripheral
sensitization linked to migraine predisposition?

Calandre EP, Hidalgo J, García-Leiva JM, Rico-Villademoros F.

Instituto de Neurociencias, Universidad de Granada, Granada, Spain. epita@ugr.es

Although migraine is a neurovascular disorder, both scalp tenderness and referred
pain have been observed in migraine patients. The present study was carried out
to investigate the presence of trigger points eliciting referred pain in 98
migraine patients and in 32 healthy subjects. Trigger points were found in 92
(93.9%) migraineurs and in nine (29%) controls (P < 0.0001). The number of
individual migraine trigger points varied from zero to 14 (modal number: 4), and 
was found to be related to both the frequency of migraine attacks (P < 0.0001),
and the duration of the disease (P = 0.017). About 74% of the total detected
trigger points were found in temporal and/or suboccipital areas; other locations 
were mainly found in patients showing more than four trigger points. Trigger
point palpation provoked a migraine attack in 30 (30.6%) patients. Pericraneal
allodynia was found in 15 (15.3%) patients. These data indicate that nociceptive 
peripheral sensitization is a usual finding in migraine, and that central
sensitization can develop in patients with frequent attacks and long-lasting
disease. Trigger points' detection in migraine patients could be useful when
applying therapies like acupuncture, needling or botulinum toxin injections
directed to reduce peripheral sensitization.

Publication Types: 
    Comparative Study
    Evaluation Studies

PMID: 16618340 [PubMed - indexed for MEDLINE]

1278: Eur J Neurol. 2006 Mar;13(3):215-9.

Migraine and stroke--why do we talk about it?

Lampl C, Marecek S.

Department of Neurology and Psychiatry, Pain and Headache Center, Linz General
Hospital, Linz, Austria. christian.lampl@akh.linz.at

Data from observational studies suggest that migraine may be a risk factor for
stroke. Furthermore, a significant association between migraine and ischemic
stroke (IS) has been demonstrated in population and case-control studies. The
risk of IS appears to be higher for migraine with aura than for migraine without 
aura. The pathogenesis is not known but several studies report some common
biochemical mechanisms in the two diseases. Meta-analysis also demonstrates that 
subjects with migraine are at higher risk of showing white matter abnormalities
on magnetic resonance images than are those without migraine.

Publication Types: 
    Review

PMID: 16618335 [PubMed - indexed for MEDLINE]

1279: Headache. 2006 Mar;46(3):515-7.

Comment in:
    Headache. 2007 Mar;47(3):447.    Headache. 2008 Jan;48(1):164-5.

Migraine triggered by sucralose--a case report.

Bigal ME, Krymchantowski AV.

Department of Neurology, The Albert Einstein College of Medicine, Bronx, NY
10461, USA.

Sucralose is the active compound of the most commonly sold sweetener in the
United States. Different than aspartame, sucralose is not considered to be a
migraine trigger. Herein we report a patient with attacks of migraine
consistently triggered by sucralose. She also suffers from menstrually related
migraine that had been well-controlled for several months since she switched her 
contraceptive from fixed estrogen to triphasic contraceptive pills. Some attacks 
triggered by sucralose were preceded by aura, and she had never experienced
migraine with aura before. Withdrawal of the compound was associated with
complete resolution of the attacks. Single-blind exposure (vs. sugar) triggered
the attacks, after an attack-free period.

Publication Types: 
    Case Reports

PMID: 16618274 [PubMed - indexed for MEDLINE]

1280: Headache. 2006 Mar;46(3):503-7.

Comment in:
    Headache. 2006 Sep;46(8):1309.

Prevention of migraine with olmesartan in patients with
hypertension/prehypertension.

Charles JA, Jotkowitz S, Byrd LH.

New Jersey Medical School, Department of Neurosciences, Newark 07103, USA.

OBJECTIVE: To explore the effects of olmesartan on frequency and severity of
migraine attacks in patients with comorbid hypertension and prehypertension.
BACKGROUND: A randomized, double-blind, placebo-controlled, crossover study with 
a total of 60 patients has demonstrated the efficacy and safety of the
angiotensin II receptor blocker candesartan in migraine prophylaxis. We study the
potential efficacy and tolerability of olmesartan in preventing migraine in
patients with hypertension and prehypertension. DESIGN/METHODS: Twenty-four
adults, aged 27 through 76, with either hypertension or prehypertension, were
included in this open-label study. Participants suffered from migraines
(diagnosed according to International Headache Society classifications) for at
least 3 months. Patients were treated with 10 to 40 mg of olmesartan per various 
observational periods of at least 3 months. Frequency and severity were recorded 
by office visits or by telephonic interview. RESULTS: Patients reported an 82.5% 
average reduction in the frequency of migraine attacks. Patients also experienced
a 45% average reduction in the severity of migraine attacks measured on a numeric
pain scale of 1 to 10. The only undesired effect was dizziness or presyncope. No 
serious adverse events occurred and no adverse event caused a premature
termination. Two patients had no reduction in headache frequency, intensity, and 
blood pressure. CONCLUSIONS: The favorable results and low rate of adverse
effects, in this open migraine prevention study in patients with hypertension or 
prehypertension, are similar to results of the randomized, double-blind,
placebo-controlled, crossover study in patients taking candesartan. Olmesartan
shows a potential as an effective and well-tolerated migraine prophylactic agent 
for patients with comorbid hypertension and prehypertension.

Publication Types: 
    Randomized Controlled Trial

PMID: 16618270 [PubMed - indexed for MEDLINE]

1281: Headache. 2006 Mar;46(3):498-502.

Open-label trial of cinnarizine in migraine prophylaxis.

Togha M, Ashrafian H, Tajik P.

Department of Neurology, Sina Hospital, Tehran University of Medical Sciences,
Iran.

OBJECTIVE: To assess the effectiveness and safety of cinnarizine as a
migraine-preventive therapy. METHODS: Sixty patients with more than 2 migraine
headache attacks during a 4-week baseline entered the study and received a 25-mg 
tablet cinnarizine twice daily for the first 3 days and then 3 times daily. They 
were assessed on weeks 2, 6, 10, and 14. Reduction from baseline in 4-week
migraine headache rate was the primary efficacy variable. Reduction in migraine
attacks duration and severity was also evaluated. RESULTS: The mean reduction in 
4-week migraine headache rate was 4.6 +/- 2.2 from the baseline of 6.2 +/- 2.2
after 14 weeks of treatment, which was statistically significant (P < 0.001).
Percent reduction in 4-week migraine frequency was 35% after 2 weeks, 74% after 6
weeks, 74% after 10 weeks, and 75% after 14 weeks of treatment. Significant
reduction in attack duration (P < 0.001) and severity (P < 0.001) was also noted.
No serious adverse events were observed in this series of patient. CONCLUSION:
Cinnarizine is an efficacious and well-tolerated prophylactic antimigraine
medication, which has early onset effectiveness.

PMID: 16618269 [PubMed - indexed for MEDLINE]

1282: Headache. 2006 Mar;46(3):492-7.

Comment in:
    Headache. 2006 Jul-Aug;46(7):1210.

Thomas Jefferson's headaches: were they migraines?

Cohen GL, Rolak LA.

Department of Neurosciences, Marshfield Clinic, WI, USA.

Thomas Jefferson had severe headaches on a number of occasions during his adult
life, as noted by most of his biographers. Some occurred during important
historical events, including the period just before the writing of the
Declaration of Independence. Historians generally have considered these headaches
to be migraines, while some physician authors have considered the alternative
diagnoses of tension-type headaches and cluster headaches. A review of the
literature, including Jefferson's many letters, suggests that they probably were 
migraines, although not all of the current diagnostic criteria can be met.

Publication Types: 
    Biography
    Historical Article

Personal Name as Subject: 
    Jefferson T

PMID: 16618268 [PubMed - indexed for MEDLINE]

1283: Headache. 2006 Mar;46(3):478-85.

Contribution of serotonin transporter gene polymorphisms to pediatric migraine.

Szilagyi A, Boor K, Orosz I, Szantai E, Szekely A, Kalasz H, Sasvari-Szekely M,
Farkas V.

Institute of Medical Chemistry, Molecular Biology and Pathobiochemistry,
Semmelweis University, Budapest, Hungary.

BACKGROUND: The serotonin transporter gene is a promising candidate locus for the
genetic susceptibility of migraine. OBJECTIVE: Two functional polymorphisms of
the serotonin transporter gene (5-HTTLPR and STin2) were analyzed to assess
whether these variants are associated with pediatric migraine. METHODS:
Eighty-seven Hungarian pediatric migraine patients and 464 controls were
genotyped using polymerase chain reaction. Patients suffering from migraine with 
(n = 38) or without aura (n = 49) were interviewed regarding the clinical
symptoms before or during the attacks. RESULTS: There was no difference between
genotype or allele distribution of 5-HTTLPR and STin2 polymorphisms in the entire
group of migraineurs and controls. Analysis of subgroups showed an association
between STin2 and migraine with aura, as the 12,12 homozygote genotype was
overrepresented in this group of patients. Furthermore, similar allele and
genotype patterns were found in cases with severe vomiting and abdominal pain.
CONCLUSIONS: These results confirm and extend the association between the STin2
polymorphism of 5-HTT gene and migraine with aura using pediatric probands. Our
data also suggest a novel endophenotype for pediatric migraine characterized by
excessive vomiting and abdominal pain during the attack.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16618266 [PubMed - indexed for MEDLINE]

1284: Headache. 2006 Mar;46(3):469-77.

The impact of migraine on patients with major depressive disorder.

Hung CI, Liu CY, Juang YY, Wang SJ.

Department of Psychiatry, Chang Gung Memorial Hospital and Chang Gung University 
School of Medicine, Taoyuan, Taiwan.

BACKGROUND: The impact of migraine and other headache types among psychiatric
outpatients with major depressive disorder (MDD) has not been fully described.
OBJECTIVE: To investigate the impact of migraine on the severity, physical, and
anxiety symptoms in patients with MDD and to examine the interaction between
headache and depression. METHODS: This clinic-based study enrolled consecutive
psychiatric outpatients meeting DSM-IV criteria for MDD. Headache types were
diagnosed based on the International Classification of Headache Disorders, 2nd
edition (2004). Three psychometric instruments were used to evaluate anxiety,
depression, and physical components: the Hamilton Depression Rating Scale, the
Beck Depression Inventory, and the Hospital Anxiety and Depression Scale. In
addition, the interactions between headache and their depressive episode were
also evaluated. RESULTS: Compared with patients without migraine, MDD patients
with comorbid migraine (n = 73, 48.3%) had higher physical and anxiety scores on 
the three psychometric instruments. Migraine accounted for 5% to 11% of the
variance of the total scores on the three psychometric scales. Approximately half
(48.5%) of patients reported headache worsening during or after a depressive
episode. CONCLUSIONS: Our study found that comorbidity of migraine in patients
with MDD was associated with more anxiety and physical symptoms. Headache should 
not be considered as only a somatic symptom of depression, but should be treated 
as an important comorbid disorder because it might exacerbate or interact with
depression during a depressive episode.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16618265 [PubMed - indexed for MEDLINE]

1285: Headache. 2006 Mar;46(3):461-8.

Characteristic and overlapping features of migraine and tension-type headache.

Turkdogan D, Cagirici S, Soylemez D, Sur H, Bilge C, Turk U.

Department of Pediatric Neurology, Institute of Neurological Sciences, Marmara
University, Istanbul, Turkey.

OBJECTIVE: This epidemiological survey was conducted to investigate comprehensive
characteristic and overlapping features of migraine and tension-type headache
(TTH) disorders classified based on International Classification of Headache
Disorders-II. METHODS: The stratified cohort of this study was composed of 2504
schoolchildren aged 10 to 17 years. A 38-item questionnaire inquiring all
characteristic features of primary headache syndromes mandatory for
classification was applied to selected 483 children with recurrent headache in
the last 6 months. RESULTS: Migraine was diagnosed in 227 (47.0%) of 483 children
and TTH in 154 (31.9%). Out of 125 children with definite migraine, 73 (58.4%)
reported tension-type symptoms and 94 (68.1%) of 138 children with definite TTH
reported migraine-type symptoms. Pressing pain (21%) and lack of aggravation of
pain by physical activity (34%) were the major tension-type features in patients 
with migraine. Throbbing quality (43%) and aggravation by physical activity (30%)
determined the main migraine-type features in patients with TTH. CONCLUSION: The 
frequent co-occurrence of migraine and TTH symptoms suggests the presence of a
common pathogenesis.

PMID: 16618264 [PubMed - indexed for MEDLINE]

1286: Headache. 2006 Mar;46(3):444-53.

Acetaminophen, aspirin, and caffeine in combination versus ibuprofen for acute
migraine: results from a multicenter, double-blind, randomized, parallel-group,
single-dose, placebo-controlled study.

Goldstein J, Silberstein SD, Saper JR, Ryan RE Jr, Lipton RB.

San Francisco Headache Clinic, CA 94109, USA.

OBJECTIVE: Compare the effectiveness of a combination analgesic containing
acetaminophen, aspirin, and caffeine to that of ibuprofen in the treatment of
migraine. METHODS: Multicenter, double-blind, randomized, parallel-group,
placebo-controlled, single-dose study. A total of 1555 migraineurs were included 
in the analysis. No patients were excluded solely because of severity of symptoms
or degree of disability. A single 2-tablet dose for each of the 3 treatment
groups: a combination product containing acetaminophen 250 mg, aspirin 250 mg,
and caffeine 65 mg per tablet (AAC); ibuprofen 200 mg per tablet (IB); or
matching placebo. The primary efficacy endpoint was the weighted sum of pain
relief (PAR) scores at 2 hours postdose (TOTPAR2) and an important secondary
endpoint was the time to onset of meaningful relief. RESULTS: There were 669
patients in the AAC group, 666 patients in the IB group, and 220 patients in the 
placebo group. The 3 treatment groups had similar demographic profiles, migraine 
histories, and baseline symptom profiles. While both active treatments were
significantly better than placebo in relieving the pain and associated symptoms
of migraine, AAC was superior to IB for TOTPAR2, as well as for PAR, time to
onset of meaningful PAR, pain intensity reduction, headache response, and pain
free. The mean TOTPAR2 scores for AAC, IB, and placebo were 2.7, 2.4, and 2.0,
respectively (AAC vs. IB, P < .03). The median time to meaningful PAR for AAC was
20 minutes earlier than that of IB (P < .036). CONCLUSION: AAC and IB are safe,
cost-effective treatments for migraine; AAC provides significantly superior
efficacy and speed of onset compared with IB.

Publication Types: 
    Comparative Study
    Multicenter Study
    Randomized Controlled Trial

PMID: 16618262 [PubMed - indexed for MEDLINE]

1287: Headache. 2006 Mar;46(3):439-43.

Migraines linked to intrapulmonary right-to-left shunt.

Thenganatt J, Schneiderman J, Hyland RH, Edmeads J, Mandzia JL, Faughnan ME.

Division of Respirology, Department of Medicine, St. Michael's Hospital,
University of Toronto, ON, Canada.

OBJECTIVE: To determine if there is an association between migraines and
intrapulmonary right-to-left shunt. BACKGROUND: Several studies have described an
association between migraines and intracardiac right-to-left shunt. METHODS:
Patients with hereditary hemorrhagic telangiectasia (HHT) were retrospectively
recruited from the Toronto Hereditary Hemorrhagic Telangiectasia Center Clinical 
Database. All patients had been prospectively, systematically asked about a
history of migraines and systematically screened for pulmonary and cerebral
arteriovenous malformations (AVMs). All patients with a definite diagnosis of
HHT, assessed during a 2-year period (February 1997 to April 1999), were
included. Univariate analyses and logistic regression were performed, for
migraine as the dependent variable and the following independent variables: age, 
sex, pulmonary AVMs, and cerebral AVMs. RESULTS: Of the 200 patients assessed
during the 2-year period, 124 (62%) had a definite diagnosis of HHT and were
included in the analysis. Eighty (65%) were females. Forty-seven (38%) of the HHT
patients had a history of migraine, of whom 38 (81%) had migraine with aura. The 
prevalence of migraine was greater in patients with pulmonary AVMs (46%) compared
to patients without pulmonary AVMs (33%), OR = 1.7 (0.8 to 3.6), though this did 
not reach statistical significance (P = .14). Pulmonary AVMs were significantly
associated with migraine (OR = 2.4, 95% CI = 1.1 to 5.5, P = .04), after
adjustment for age and sex, using logistic regression. CONCLUSIONS: There is a
significant association between intrapulmonary right-to-left shunt and migraine.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16618261 [PubMed - indexed for MEDLINE]

1288: Headache. 2006 Mar;46(3):429-34.

Comment in:
    Headache. 2006 Mar;46(3):435-8.

The role of cardiac and pulmonary pathology in migraine: a hypothesis.

Wilmshurst P, Nightingale S.

Department of Cardiology, Royal Shrewsbury Hospital, UK.

From observation of recent data linking migraine with right-to-left shunts and by
analogy with the etiologies of decompression illness, we postulate that cardiac
and pulmonary pathology can have an important effect on the cranial final common 
pathway that generates attacks of migraine. One possible mechanism is associated 
with a significant right-to-left shunt, which is usually through a persistent
foramen ovale, but is sometime through a pulmonary shunt. This allows a venous
agent, possibly 5-hydroxytryptamine, to bypass the lung filter. Migraine can
occur when there is no shunt if similar agents are liberated in the left heart
beyond the lung filter, possibly by platelet activation. Migraine could also
occur if the venous agents are produced in such large amounts that they overwhelm
the pulmonary filter or are unaffected by passage through the lungs. In some
individuals migraine may be unrelated to blood-borne triggers.

Publication Types: 
    Review

PMID: 16618259 [PubMed - indexed for MEDLINE]

1289: Headache. 2006 Mar;46(3):422-8.

Erratum in:
    Headache. 2006 Mar;46(3):548.

Comment in:
    Headache. 2007 Mar;47(3):447-8.

Migraine is associated with menorrhagia and endometriosis.

Tietjen GE, Conway A, Utley C, Gunning WT, Herial NA.

Department of Neurology, Medical College of Ohio, Toledo 43614, USA.

OBJECTIVE: To evaluate the frequency of menorrhagia and endometriosis in female
migraineurs compared to age-matched women without headache. BACKGROUND: Migraine 
predominantly affects women of childbearing age and is often associated with the 
menstrual period, yet there is a paucity of data regarding the relationship of
migraine and menstrual disorders. METHODS: Women diagnosed with migraine, using
International Headache Society criteria and an age- and sex-matched control
group, were administered a semistructured questionnaire regarding migraine and
migraine-related disability, menstrual history, other bleeding history, vascular 
event history, and vascular risk factors. RESULTS: Fifty female migraineurs
between the ages of 22 and 50 years and 52 age-matched women (mean age 37 years) 
were enrolled in the study. Similar proportions of women in each group reported
using hormone contraceptives (30% vs. 33%, P = .77) and hormone replacement
therapy (12% vs. 8%, P = .69). The proportions presently menstruating (64 % vs.
80%, P = .20) and status after hysterectomy were similar (24% vs. 14%, P = .84). 
Menorrhagia (defined as at least three consecutive heavy periods), both current
and prior, was more commonly reported in migraineurs (63% vs. 37%, P = .009),
with higher likelihood of staining clothes by menses (35% vs. 8%, P = .003), and 
significant impact of menses on activities of daily living (on a 10-point Likert 
scale) with work/school participation (P = .02), family activities (P < .0001),
sleep (P = .003), life enjoyment (P = .001), mood (P = .02), and overall quality 
of life (P = .003). Endometriosis, which may be associated with menorrhagia, was 
also more commonly diagnosed in the migraineurs (30% vs. 4%, P = .001). The
migraineurs more frequently described bruising (40% vs. 10%, P < .001) and rectal
bleeding (18% vs. 2%, P = .017) but not more serious bleeding problems.
Nonsteroidal anti-inflammatory drug (NSAID) use was more frequent in the migraine
group (28% vs. 12%, P = .036), and significance for increased menorrhagia,
endometriosis, menstrual interference, and bruising was maintained, even when
controlling for the use of NSAIDs. With logistic regression, menorrhagia was
significantly associated with migraine, adjusted odds ratio (OR) = 2.8 (95% CI
1.2 to 6.5), and with endometriosis, adjusted OR = 10.5 (95% CI 2.2 to 51.4).
There were no differences in vascular events and risk factors, except for trends 
of increased hypertension (25% vs. 10%, P = .05), transient ischemic
attack/stroke (10% vs. 2%, P = .08), and Raynaud's disease (10% vs. 2%, P = .08) 
in the migraineurs. CONCLUSION: Women with migraine have a higher frequency of
menorrhagia, endometriosis, and associated psychosocial consequences. These
findings suggest that there should be further study of factors influencing
endometriosis and menstrual blood flow, such as eicosanoids and platelet
function, in migraineurs.

PMID: 16618258 [PubMed - indexed for MEDLINE]

1290: Headache. 2006 Mar;46(3):413-21.

Relationship between migraine and epilepsy in pediatric age.

Piccinelli P, Borgatti R, Nicoli F, Calcagno P, Bassi MT, Quadrelli M, Rossi G,
Lanzi G, Balottin U.

Child Neuropsychiatry Unit, University of Insubria, Macchi Foundation Hospital,
Varese, Italy.

OBJECTIVE: Many studies have supported the hypothesis of alteration of cortical
hyperexcitability as a possible pathological mechanism underlying the onset of
migraine and epileptic attacks. Different biochemical pathways involving cellular
structures may increase or decrease the excitability of neuronal membranes. The
aim of this study was to identify a possible link between migraine and epilepsy
from a clinical and neurophysiologic point of view. METHODS: One-hundred
thirty-seven children and adolescents consecutively diagnosed for tension-type
headache and idiopathic migraine with and without aura were studied. Anamnestic, 
clinical, and instrumental data were collected by a neurological examination, a
specific questionnaire, and awake electroencephalogram (EEG) registrations. EEG
features of nonheadache and nonseizures control group were compared. RESULTS:
Fourteen cases (10.2%) had a positive history for seizures with fever, isolated
seizures, or epilepsy. Distribution differed according to headache diagnosis;
migraine with aura (MWA) was largely prevalent. Specific electroencephalographic 
abnormalities were present in 11.7% of the sample, with a significant different
distribution across the groups of children with headache and the control group:
specific interictal abnormalities were found in 10 of 23 (43.5%) children with
MWA. Two factors, seizures and specific interictal electroencephalographic
abnormalities, showed a different distribution in patients with MWA compared to
other classes of headache and control group (P < or = .01). CONCLUSION: The
present study supports the hypothesis of a possible clinical continuum between
some types of MWA and epileptic syndromes as entities due to altered neuronal
excitability with similar genetic substrates.

PMID: 16618257 [PubMed - indexed for MEDLINE]

1291: Headache. 2006 Mar;46(3):399-412.

Clinical characteristics of tension-type headache and migraine in adolescents: a 
student-based study.

Karli N, Akgöz S, Zarifoğlu M, Akiş N, Erer S.

University of Uludag, School of Medicine, Department of Neurology, Bursa, Turkey.

BACKGROUND AND OBJECTIVES: Adolescent headaches, particularly migraine, might
present with different features from adult headaches. The objectives of this
study were to investigate the characteristics of tension-type headache and
migraine, to find the sensitivity and specificity of the diagnostic criteria of
the IHS classification according to age and gender. METHODS: A multistep,
stratified, cluster sampling method was used for subject selection. The estimated
sample size was 2387. The study was conducted in two phases: the questionnaire
and the face to face interview phases. During the semistructured interview, a
clinical diagnosis has been made and clinical characteristics have been recorded.
RESULTS: All headaches fulfilled the criteria of duration. The most common
feature of migraine was moderate to severe (92.4%), pulsating pain (79.2%). For
ETTH, bilateral localization (91.3%) and mild to moderate pain intensity (90.6%) 
were the most common features. Younger adolescents showed mixed headache
characteristics. Highest sensitivities for migraine were duration (100%),
moderate to severe pain (92.4%), and pulsating quality of pain (79.2%). Vomiting,
trigger factors food and alcohol had a high specificity for migraine.
CONCLUSIONS: Our data strongly support continuum hypothesis. In early adolescence
headaches might present with mixed headache characteristics. Age and gender have 
some influence on headache characteristics, particularly on migraine. The
sensitivity and specificity of case definition criteria of ICHD-2 for adolescent 
migraine is moderate and need to be reconsidered.

PMID: 16618256 [PubMed - indexed for MEDLINE]

1292: Headache. 2006 Mar;46(3):365-86.

Ovarian hormones and migraine headache: understanding mechanisms and
pathogenesis--part 2.

Martin VT, Behbehani M.

Department of Internal Medicine, University of Cincinnati College of Medicine,
Ohio 45267-0535, USA.

Migraine headache is strongly influenced by reproductive events that occur
throughout the lifespan of women. Each of these reproductive events has a
different "hormonal milieu," which might modulate the clinical course of migraine
headache. Estrogen and progesterone can be preventative or provocative for
migraine headache under different circumstances depending on their absolute serum
levels, constancy of exposure, and types of estrogen/progesterone derivatives.
Attacks of migraine with and without aura respond differently to changes in
ovarian hormones. Clearly a greater knowledge of ovarian hormones and their
effect on migraine is essential to a greater understanding of the mechanisms and 
pathogenesis of migraine headache.

Publication Types: 
    Review

PMID: 16618254 [PubMed - indexed for MEDLINE]

1293: MedGenMed. 2005 Dec 14;7(4):69.

Lysine clonixinate vs naproxen sodium for the acute treatment of migraine: a
double-blind, randomized, crossover study.

Krymchantowski AV, Peixoto P, Higashi R, Silva A Jr, Schutz V.

Outpatient Headache Unit, Instituto de Neurologia Deolindo Couto, Department of
Neurology, Hospital Pasteur, Universidade Federal do Rio de Janeiro Rio de
Janeiro, Brazil.

BACKGROUND AND OBJECTIVES: The process of inflammation is crucial in migraine,
and several nonsteroidal anti-inflammatory drugs (NSAIDs) are effective in the
treatment of migraine attacks. Despite their efficacy, the routine use of NSAIDs 
is limited by side effects as well as incomplete efficacy in some patients. Among
the available options, lysine clonixinate (LC) and naproxen sodium (NS) have
proved effective in migraine. The aim of this study was to compare the efficacy
and tolerability of oral formulations of LC and NS in the treatment of moderate
or severe migraine attacks, with a double-blind, crossover design. METHODS:
Seventy subjects (62 women, 8 men) between ages 18 and 71 years (mean age, 41)
with migraine according to the criteria of the International Headache Society
were prospectively enrolled. The patients were randomized into 2 groups and each 
participant treated 2 migraine attacks. Group 1 treated the first attack with LC 
and the second attack with NS. Group 2 treated 2 attacks in a counterbalanced
order. Doses were 250 mg of LC or 550 mg of NS, which were encapsulated for equal
appearance. Headache intensity, nausea, photophobia, and side effects were
evaluated at baseline, 1 hour, and 2 hours after drug administration. Rescue
drugs were allowed after 2 hours for those who didn't respond, and this was also 
compared between groups. RESULTS: Sixty patients (54 women, 6 men) completed the 
study. At 1 hour, 13.6% patients who used LC were pain-free compared with 11.9%
who used NS (P = .78). At 2 hours, 35.6% patients who took LC and 32.2% who took 
NS were pain-free (P = .69). At baseline, 52.5% of the patients randomized to
group 1 reported nausea, compared with 33.9% in group 2, and both drugs
eliminated nausea: At both 1 hour and 2 hours, nausea diminished significantly
for those taking LC, but only after 2 hours for those who took NS (P < .0001).
Both drugs eliminated photophobia at 1 hour and 2 hours; however, LC was superior
to NS in reducing photophobia at 2 hours (P = .027). Ten patients who took LC and
8 who took NS required rescue drugs after 2 hours. Twelve patients who used LC
and 16 who took NS reported side effects. COMMENTS: Although this study did not
include a placebo arm, which impairs any definitive efficacy claims, we found LC 
and NS to be similarly effective and well tolerated in patients presenting
moderate or severe attacks of migraine.

Publication Types: 
    Randomized Controlled Trial

PMID: 16614691 [PubMed - indexed for MEDLINE]

1294: J Vestib Res. 2005;15(5-6):327-32.

Vestibular function in migraine-related dizziness: a pilot study.

Furman JM, Sparto PJ, Soso M, Marcus D.

Department of Otolaryngology, University of Pittsburgh School of Medicine, USA.
furman@pitt.edu

Migraine-related dizziness (MRD) refers to a disorder in which vestibular
symptoms are an integral part of migraine symptomatology. The purpose of this
study was to better define the pathophysiology of MRD, which is incompletely
understood and to generate hypotheses regarding MRD by assessing the semicircular
canal-ocular reflex, the otolith-ocular reflex, visual-vestibular interaction,
vestibulo-spinal function, and visually induced postural sway. Subjects included 
five subjects with MRD, five subjects with migraine without dizziness, and five
headache-free controls. Subjects with migraine were tested interictally. Results 
indicated that the mean gain of the semicircular canal-ocular reflex during both 
sinusoidal and constant velocity rotation was reduced in subjects with MRD. No
changes were noted in the dynamics of the semicircular canal-ocular reflex. The
otolith-ocular reflex, assessed with constant velocity OVAR, indicated that
subjects with MRD showed a larger modulation component. No group differences were
found in the bias component during constant velocity OVAR, nor in semicircular
canal-otolith interaction or visual-vestibular interaction. Computerized dynamic 
posturography indicated that subjects with MRD demonstrated a surface-dependent
pattern. Postural sway during optic flow indicated that subjects with MRD swayed 
more than the other subjects. We hypothesize that competing processes of
serotonergic excitation and inhibition alter central vestibular pathways
differently for semicircular canal vs. otolithic responses and for
vestibulo-ocular vs. vestibulo-spinal pathways.

Publication Types: 
    Controlled Clinical Trial
    Research Support, Non-U.S. Gov't

PMID: 16614477 [PubMed - indexed for MEDLINE]

1295: J Neurol Neurosurg Psychiatry. 2006 May;77(5):686-9.

Diffusion tensor magnetic resonance imaging at 3.0 tesla shows subtle cerebral
grey matter abnormalities in patients with migraine.

Rocca MA, Ceccarelli A, Falini A, Tortorella P, Colombo B, Pagani E, Comi G,
Scotti G, Filippi M.

Neuroimaging Research Unit, Scientific Institute and University Ospedale San
Raffaele, Via Olgettina, 60, 20132 Milan, Italy.

BACKGROUND AND OBJECTIVE: Diffusion tensor (DT) magnetic resonance imaging (MRI) 
has the potential to disclose subtle abnormalities in the brain of migraine
patients. This ability may be increased by the use of high field magnets. A DT
MRI on a 3.0 tesla scanner was used to measure the extent of tissue damage of the
brain normal appearing white (NAWM) and grey matter in migraine patients with T2 
visible abnormalities. METHODS: Dual echo, T1 weighted and DT MRI with diffusion 
gradients applied in 32 non-collinear directions were acquired from 16 patients
with migraine and 15 sex and age matched controls. Lesion load on T2 weighted
images was measured using a local thresholding segmentation technique, and brain 
atrophy assessed on T1 weighted images using SIENAx. Mean diffusivity and
fractional anisotropy histograms of the NAWM and mean diffusivity histograms of
the grey matter were also derived. RESULTS: Brain atrophy did not differ between 
controls and patients. Compared with healthy subjects, migraine patients had
significantly reduced mean diffusivity histogram peak height of the grey matter
(p=0.04). No diffusion changes were detected in patients' NAWM. In migraine
patients, no correlation was found between T2 weighted lesion load and brain DT
histogram derived metrics, whereas age was significantly correlated with grey
matter mean diffusivity histogram peak height (p=0.05, r=-0.52). CONCLUSIONS: DT 
MRI at high field strength discloses subtle grey matter damage in migraine
patients, which might be associated with cognitive changes in these patients.

PMID: 16614037 [PubMed - indexed for MEDLINE]

1296: J Neurol Neurosurg Psychiatry. 2006 May;77(5):658-64.

Interaction of somatoform and vestibular disorders.

Best C, Eckhardt-Henn A, Diener G, Bense S, Breuer P, Dieterich M.

Department of Neurology, Johannes-Gutenberg University, Langenbeckstrasse 1,
55101 Mainz, Germany. bestc@uni-mainz.de

BACKGROUND: The high coincidence of organic vestibular and somatoform vertigo
syndromes has appeared to support pathogenic models showing a strong linkage
between them. It was hypothesised that a persisting vestibular dysfunction causes
the development of anxiety disorders. OBJECTIVE: To determine the relation
between vestibular deficits and somatoform vertigo disorders in an
interdisciplinary prospective study. METHODS: Participants were divided into
eight diagnostic groups: healthy volunteers (n=26) and patients with benign
paroxysmal positioning vertigo (BPPV, n=11), vestibular neuritis (n=11),
Menière's disease (n=7), vestibular migraine (n=15), anxiety (n=23), depression
(n=12), or somatoform disorders (n=22). Neuro-otological diagnostic procedures
included electro-oculography with rotatory and caloric testing, orthoptic
examination with measurements of subjective visual vertical (SVV) and ocular
torsion, and a neurological examination. Psychosomatic diagnostic procedures
comprised interviews and psychometric instruments. RESULTS: Patients with BPPV
(35.3%) and with vestibular neuritis (52.2%) had pathological test values on
caloric irrigation (p<0.001). Otolith dysfunction with pathological tilts of SVV 
and ocular torsion was found only in patients with vestibular neuritis (p<0.001).
Patients with Menière's disease, vestibular migraine, and psychiatric disorders
showed normal parameters for vestibular testing but pathological values for
psychometric measures. There was no correlation between pathological neurological
and pathological psychometric parameters. CONCLUSIONS: High anxiety scores are
not a result of vestibular deficits or dysfunction. Patients with Menière's
disease and vestibular migraine but not vestibular deficits showed the highest
psychiatric comorbidity. Thus the course of vertigo syndromes and the possibility
of a pre-existing psychopathological personality should be considered pathogenic 
factors in any linkage between organic and psychometric vertigo syndromes.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16614028 [PubMed - indexed for MEDLINE]

1297: Twin Res Hum Genet. 2006 Feb;9(1):54-63.

Migraine with aura and migraine without aura are not distinct entities: further
evidence from a large Dutch population study.

Ligthart L, Boomsma DI, Martin NG, Stubbe JH, Nyholt DR.

Department of Biological Psychology, Vrije Universiteit, Amsterdam, Netherlands.

It is often debated whether migraine with aura (MA) and migraine without aura
(MO) are etiologically distinct disorders. A previous study using latent class
analysis (LCA) in Australian twins showed no evidence for separate subtypes of MO
and MA. The aim of the present study was to replicate these results in a
population of Dutch twins and their parents, siblings and partners (N = 10,144). 
Latent class analysis of International Headache Society (IHS)-based migraine
symptoms resulted in the identification of 4 classes: a class of unaffected
subjects (class 0), a mild form of nonmigrainous headache (class 1), a moderately
severe type of migraine (class 2), typically without neurological symptoms or
aura (8% reporting aura symptoms), and a severe type of migraine (class 3),
typically with neurological symptoms, and aura symptoms in approximately half of 
the cases. Given the overlap of neurological symptoms and nonmutual exclusivity
of aura symptoms, these results do not support the MO and MA subtypes as being
etiologically distinct. The heritability in female twins of migraine based on LCA
classification was estimated at .50 (95% confidence intervals [CI] .27 - .59),
similar to IHS-based migraine diagnosis (h2 = .49, 95% CI .19-.57). However,
using a dichotomous classification (affected-unaffected) decreased heritability
for the IHS-based classification (h2 = .33, 95% CI .00-.60), but not the
LCA-based classification (h2 = .51, 95% CI .23-.61). Importantly, use of the
LCA-based classification increased the number of subjects classified as affected.
The heritability of the screening question was similar to more detailed LCA and
IHS classifications, suggesting that the screening procedure is an important
determining factor in genetic studies of migraine.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16611468 [PubMed - indexed for MEDLINE]

1298: Curr Vasc Pharmacol. 2006 Apr;4(2):117-28.

Migraine: current therapeutic targets and future avenues.

Arulmozhi DK, Veeranjaneyulu A, Bodhankar SL.

New Chemical Entity Research, Lupin Research Park, Village Nande, Taluk Mulshi,
Pune, Maharashtra, India. adk_bits@yahoo.com

Migraine is characterized by attacks of intense pulsatile and throbbing headache,
typically unilateral in nature with or without aura. Migraine affects a
substantial fraction (10-20 %) of the world population (more women than men).
With regard to the pathophysiology of migraine, several theories have been
proposed; the major three are vascular (due to cerebral vasodilatation),
neurological (abnormal neurological firing) and neurogenic dural inflammation
(release of inflammatory neuropeptides). The drugs used to treat migraine can be 
divided into two groups: agents that abolish the acute migraine headache and
agents aimed at prevention. The acutely acting antimigraine agents (5-HT(1B/1D)
receptor agonists) stimulated research interest in the field of migraine.
Currently prophylactic treatments for migraine include calcium channel blockers, 
5-HT(2) receptor antagonists, beta-adrenoceptor blockers and gamma-amino butyric 
acid (GABA) agonists. Unfortunately, many of these treatments are non-specific
and not always effective. Despite progress, the complex etiology of migraine
requires further research, the condition often remains undiagnosed and available 
therapies are underused. In this review, the evidence that linked the different
theories of migraine with its pathophysiology is considered. Furthermore, the
present therapeutic targets and future approaches for the acute and prophylactic 
treatment of migraine are critically evaluated.

Publication Types: 
    Review

PMID: 16611154 [PubMed - indexed for MEDLINE]

1299: J Neurol. 2006 Aug;253(8):1000-1. Epub 2006 Apr 10.

Three patients with migraine following caloric-induced vestibular stimulation.

Seemungal B, Rudge P, Davies R, Gresty M, Bronstein A.

Department of Movement and Balance, Imperial College, Charing Cross Fulham Palace
Road, W6 8RF, UK. b.seemungal@imperial.ac.uk

The co-occurrence of migraine and dizziness is greater than would be expected by 
chance. We report 3 patients who developed migraine following acute vertigo
precipitated during caloric testing. A small proportion of the epidemiological
links between migraine and vertigo may be due to vertigo-triggered migraine.

Publication Types: 
    Case Reports

PMID: 16607475 [PubMed - indexed for MEDLINE]

1300: Neurology. 2006 Apr 11;66(7):1105-7.

Prolonged but reversible migraine-like episodes long after cranial irradiation.

Partap S, Walker M, Longstreth WT Jr, Spence AM.

Division of Pediatric Neurology, Children's Hospital and Regional Medical Center,
University of Washington, Seattle, WA, USA.

The authors describe three patients with prolonged but reversible episodes of
severe headaches and focal neurologic deficits developing years after irradiation
for cranial neoplasms. Despite extensive evaluations, etiology of episodes in
these three and eight other previously reported patients remains undetermined.
Whether they all have the same condition is uncertain. Although some had cortical
gadolinium enhancement on MRI, all 11 patients returned to baseline over hours to
weeks.

Publication Types: 
    Case Reports

PMID: 16606929 [PubMed - indexed for MEDLINE]

1301: Neurology. 2006 Apr 11;66(7):1034-7.

Comment in:
    Neurology. 2007 Mar 13;68(11):878; author reply 878-9.    Neurology. 2007 Mar 13;68(11):878; author reply 878-9.

Syncope in migraine: the population-based CAMERA study.

Thijs RD, Kruit MC, van Buchem MA, Ferrari MD, Launer LJ, van Dijk JG.

Department of Neurology and Clinical Neurophysiology, Leiden University Medical
Center, National Institute of Public Health and the Environment, Bilthoven, The
Netherlands. r.d.thijs@lumc.nl

OBJECTIVE: To examine the association between migraine and syncope-related
autonomic nervous system (ANS) symptoms. METHODS: A population-based study among 
migraineurs with and without aura (n = 323) and control subjects (n = 153) was
conducted. A systematic questionnaire and cardiovascular measurements during
rest, while standing, and after venipuncture addressed the prevalence of syncope,
orthostatic intolerance, orthostatic hypotension (OH), and the postural
tachycardia syndrome (POTS) in migraineurs and control subjects. RESULTS: The
lifetime prevalence of syncope in all participants was 41%, more often in women
(45 vs 32%; p = 0.02). Compared with control subjects, migraineurs had a higher
lifetime prevalence of syncope (46 vs 31%; p = 0.001), frequent syncope (five or 
more attacks) (13 vs 5%; p = 0.02), and orthostatic intolerance (32 vs 12%; p <
0.001). There was no association between ANS symptoms and the severity of
migraine or migraine subtype. Cardiovascular measurements and the prevalence of
POTS and OH did not differ significantly between migraineurs and control
subjects. CONCLUSION: This population-based study demonstrated an elevated
prevalence of syncope and orthostatic intolerance in migraineurs without clear
interictal signs of autonomic nervous system dysfunction.

Publication Types: 
    Research Support, N.I.H., Intramural
    Research Support, Non-U.S. Gov't

PMID: 16606915 [PubMed - indexed for MEDLINE]

1302: J Hypertens Suppl. 2006 Mar;24(1):S139-43.

Involvement of the renin-angiotensin system in migraine.

Tronvik E, Stovner LJ, Schrader H, Bovim G.

Norwegian National Headache Centre, Norwegian University of Science and
Technology, Trondheim University Hospital, Trondheim, Norway.
Erling.Trovnik@ntnu.no

Migraine is a common episodic headache that predominantly affects young adults,
particularly women in their most productive years. Many of the prophylactic
agents available today have side-effects that are not compatible with long-term
use. The discovery that drugs influencing the renin-angiotensin system (RAS),
which have few side-effects, were effective in some patients with migraine led to
several studies investigating a possible link between the angiotensin system and 
migraine pathophysiology. Clinical trials indicated that angiotensin-converting
enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) are
effective in the prophylactic treatment of migraine. These findings are further
supported by pharmacoepidemiological, genetic, and physiological studies. In
addition, it is known that the RAS has neurophysiological, chemical, and
immunological effects that are of relevance in migraine pathophysiology. On the
basis of evidence presented in this review, we find it likely that the RAS has a 
clinically important role in migraine pathophysiology. The effect of ARBs and
ACEIs on migraine is probably not attributable to their effect on blood pressure.
The RAS has several actions that may be relevant in migraine pathophysiology, but
the reason for the prophylactic effect of ARBs/ACEIs in migraine remains a matter
of speculation.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 16601567 [PubMed - indexed for MEDLINE]

1303: Ann N Y Acad Sci. 2005 Dec;1060:283-93.

Outcome research in music therapy: a step on the long road to an evidence-based
treatment.

Nickel AK, Hillecke T, Argstatter H, Bolay HV.

Deutsches Zentrum fur Musiktherapieforschung, Viktor Dulger Institut, DZM e.V.,
Maassstr. 26, 69123 Heidelberg, Germany. anne.nickel@fh-heidelberg.de

Music therapy is the therapeutic use of music and musical activities in the
treatment of somatic and mental diseases. In the last decades it has developed
from a quasi-professional working field into an increasingly evidence-based
treatment for various diseases. Selected outcome studies that were carried out in
order to give music therapy a scientific and empirical base are presented in this
article. Results show that music therapy is an effective intervention for
patients with chronic pain, children with migraine, and patients suffering from
chronic tinnitus. This positive outcome, in combination with the observed
moderate to large effect sizes in different metanalyses, provides evidence for
the use of music therapy in specific clinical fields. Future research should
focus on studies that compare well-defined music therapy interventions to
standard treatment.

Publication Types: 
    Randomized Controlled Trial

PMID: 16597777 [PubMed - indexed for MEDLINE]

1304: Can J Neurol Sci. 2006 Feb;33(1):73-9.

Pain free efficacy of sumatriptan in the early treatment of migraine.

Jelinski SE, Becker WJ, Christie SN, Ahmad FE, Pryse-Phillips W, Simpson SD.

Department of Clinical Neurosciences, University of Calgary Calgary, AB, Canada.

BACKGROUND: There is evidence that headache response rates may be higher if
triptans are used early when a migraine attack is still mild, as compared to when
it is treated after pain has reached moderate or severe intensity. METHODS: In
this randomized, double blind, placebo controlled, parallel group clinical trial,
361 patients took either placebo, sumatriptan 50 mg, or sumatriptan 100 mg in a
single attack study. The primary outcome measure was pain-free status at two
hours. RESULTS: In the intention to treat group, two hour pain free rates were
16%, 40%, and 50% in the placebo group, sumatriptan 50 mg group, and the
sumatriptan 100 mg group respectively (p < 0.001, active treatment groups vs.
placebo). CONCLUSIONS: Both sumatriptan 50 mg and 100 mg were significantly
superior to placebo for the pain-free end point at two hours. The pain-free
response rates in this trial where sumatriptan was taken while the headache was
still mild were generally higher than in older clinical trials where headache was
treated after reaching a moderate or severe intensity.

Publication Types: 
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 16583726 [PubMed - indexed for MEDLINE]

1305: Can J Neurol Sci. 2006 Feb;33(1):63-7.

Motor and occipital cortex excitability in migraine patients.

Gunaydin S, Soysal A, Atay T, Arpaci B.

Neurology Department, Bakirkoy State Hospital for Psychiatric and Neurological
Diseases, Bakirkoy, Istanbul, Turkey.

OBJECTIVE: We evaluated motor and occipital cortex excitability in migraine
patients using transcranial magnetic stimulation. METHODS: In this study, we
included 15 migraine patients with aura (MwA), 15 patients without aura (MwoA)
between attacks, and 31 normal healthy controls. Motor thresholds at rest,
amplitudes of motor evoked potentials, central motor conduction time and cortical
silent period were measured by stimulation of the motor cortex by using 13.5 cm
circular coil and recording from abductor digiti minimi muscle. Additionally,
phosphene production and the threshold of phosphene production was determined by 
stimulation of the visual cortex with the same coil. RESULTS: No significant
differences were observed between the groups with respect to the motor
thresholds, Motor evoked potential max/compound muscle action potential max
(MEPmax/Mmax) amplitudes, central motor conduction times and duration of cortical
silent period. Although not statistically significant, the proportion of the
migraineurs with phosphene generation (90%) was found to be higher than that of
normal controls (71%). Phosphene threshold levels in migraine patients, however, 
were significantly lower than those of the controls with MwA patients having the 
lowest levels. CONCLUSION: Our findings indicate that the occipital cortex, but
not the motor cortex, is hyperexcitable in migraine patients.

PMID: 16583724 [PubMed - indexed for MEDLINE]

1306: Tex Dent J. 2006 Feb;123(2):190-7.

Migraine drug therapy: dental implications.

Jeske AH.

Department of Restorative Dentistry and Biomaterials, University of Texas Dental 
Branch, Houston, USA.

Triptan drugs continue to constitute the major pharmacotherapeutic interventional
agents for migraine therapy. Interactions of dental drugs with migraine
medications are limited, but their seriousness dictates that dentists be aware of
the use of ergot alkaloids, triptans, or other migraine drugs. While many
migraine sufferers avoid dental therapy dur ing migraine attacks, the
practitioner who is treating a patient who has taken migraine medications must
carefully monitor the cardiovascular status of the patient, which may affect the 
use of vasoconstrictors. Macrolide antibiotics and azole antifungals represent
additional drug groups that are prescribed by dentists but which may potentiate
the adverse effects of migraine drugs. Migraine patients prefer agents that offer
rapid onset of relief and total relief within a couple hours of drug
administration; they also prefer therapy that prevents recurrences and does not
require "rescue" medications, and, of course, a lack of adverse effects and
interactions with other medications. Currently, no single drug or class of drugs 
offers this ideal combination of actions in all patients.

PMID: 16579506 [PubMed - indexed for MEDLINE]

1307: J Headache Pain. 2006 Apr;7(2):90-4. Epub 2006 Mar 31.

Salivary cortisol, dehydroepiandrosterone-sulphate (DHEA-S) and testosterone in
women with chronic migraine.

Patacchioli FR, Monnazzi P, Simeoni S, De Filippis S, Salvatori E, Coloprisco G, 
Martelletti P.

Department of Human Physiology and Pharmacology V. Erspamer, 2nd School of
Medicine, S. Andrea Hospital, Piazza Aldo Moro 5, I-00185, Rome, Italy.
francesca.patacchioli@uniroma1.it

Hypothalamus-pituitary-adrenal (HPA) axis activity was monitored in 20 women with
chronic migraine (CM), previously affected by medication overuse headache (MOH), 
in comparison to healthy women (20 subjects) by measuring salivary cortisol,
testosterone, dehydroepiandrosterone-sulphate (DHEA-S) levels, and their ratios, 
one week after the end of the MOH rehabilitation procedure. The participants were
instructed how to collect saliva samples at home, a procedure that was performed 
twice a day (08:00 a.m. and 8:00 p.m.). Morning and evening levels of cortisol
were significantly increased in CM patients with respect to controls. With regard
to the cortisol/DHEA-S ratio, an inverse marker of psycho-physical wellbeing, CM 
women showed significantly higher values than controls. Moreover,
testosterone/cortisol ratios (anabolic/catabolic index of physical performance)
were significantly lower in CM patients than in controls. In the present study,
CM appears not to be associated with an impairment of cortisol and DHEAS
circadian fluctuation; however, CM patients present alterations in HPA axis
function that might contribute to metabolic and psychological alterations that
have also been associated with CM.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 16575505 [PubMed - indexed for MEDLINE]

1308: J Headache Pain. 2006 Apr;7(2):109-15. Epub 2006 Mar 31.

The history of the migraine trust.

Rose FC.

Academic Unit of Neuroscience, Charing Cross & Westminster (now Imperial College)
Medical School, UK. fcliffordrose@tiscali.co.uk

The history of a medical charity founded for the purpose of initiating research
into the commonest of all human afflictions-headache. Of the 100 causes, migraine
is one of the commonest, and in spite of the lack of interest of the medical
profession, this review shows how the pace of research rapidly increased as
evidenced by the biennial International Symposia of the Migraine Trust.

Publication Types: 
    Historical Article
    Review

PMID: 16575504 [PubMed - indexed for MEDLINE]

1309: J Headache Pain. 2006 Apr;7(2):101-8. Epub 2006 Mar 31.

Understanding clinical trials in migraine.

Tfelt-Hansen P.

The Danish Headache Center, Department of Neurology, University of Copenhagen,
Glostrup Hospital, DK-2600, Glostrup, Denmark. tfelt@inet.uni2.dk

The following points are covered in this review. (1) How a randomised clinical
trial in migraine is performed. The whole process from idea to publication of an 
article is reviewed. (2) How to understand a paper on clinical trials in
migraine. The aim of the study, design of study, efficacy measures and
presentation of results are reviewed. The aim of the study is often stated
vaguely and it is suggested to look at the power calculations in order to
understand the aim of the study. The aims and the results of the trial programmes
of the triptans are reviewed. Results of the study should be presented with
95%CI. (3) How to understand meta-analyses in migraine. Relationship between
meta-analyses and head-to-head comparative trials is reviewed; and it is
concluded that head-to-head comparisons remain the "golden standard" with
meta-analyses as a useful supplement.

Publication Types: 
    Review

PMID: 16575501 [PubMed - indexed for MEDLINE]

1310: Int J Pediatr Otorhinolaryngol. 2006 Aug;70(8):1431-8. Epub 2006 Mar 30.

Auditory brainstem response in pediatric migraine: during the attack and
asymptomatic period.

Firat Y, Ozturan O, Bicak U, Yakinci C, Akarcay M.

Department of Otorhinolaryngology, Inonu University, School of Medicine, Malatya,
Turkey. yezdanf@yahoo.com

OBJECTIVE: The aim of this study was to evaluate the hearing parameters of
children with migraine during ictal and interictal period. METHOD: 16 pediatric
patients with migraine and normal otolaryngologic examination were evaluated.
Hearing parameters were assessed with auditory brainstem response (ABR) testing
between and during the migraine attacks. Binaural absolute latencies of waves I, 
III and V, interpeak latencies I-III, III-V and I-V of ABR in response to 80 dB
nHL clicks were calculated. Initial findings were compared with those of 20
healthy volunteers. RESULTS: Peak latencies of wave V and interpeak latencies of 
I-V were prolonged during the attack in migraineurs on the left. The side of
latency elongation was not affected by the side of headache. When these
parameters were separately compared for gender, they were prolonged in boys
during the attack in migraineurs; however in girls, while there was statistically
significant difference at interpeak latencies of I-V, no significant difference
was noted at peak latencies of wave V. CONCLUSIONS: ABR waves did not exceed
clinical norms in migraine patients in headache-free period. But, important
effects on sensorineural hearing parameters were detected during the attack. Our 
results indicated a transient impairment of the auditory brainstem function
during the headache in pediatric migraine patients.

PMID: 16574252 [PubMed - indexed for MEDLINE]

1311: Am Heart J. 2006 Apr;151(4):922.e1-5.

Transcatheter patent foramen ovale closure mitigates aura migraine headaches
abolishing spontaneous right-to-left shunting.

Giardini A, Donti A, Formigari R, Salomone L, Prandstraller D, Bonvicini M,
Palareti G, Guidetti D, Gaddi O, Picchio FM.

Pediatric Cardiology and Adult Congenital Unit, University of Bologna, Italy.
alessandro5574@iol.it

BACKGROUND: Patent foramen ovale (PFO) has been implicated in the etiology of
migraine headache with aura (MHA), but the mechanisms that link right-to-left
(R-to-L) shunt to MHA are unclear, and the reports on the efficacy of
transcatheter PFO closure on MHA prevention are scarce. METHODS: We reviewed the 
clinical records of 131 consecutive patients who underwent successful
transcatheter PFO closure at our institution at a mean age of 45 +/- 13 years
because of cryptogenic stroke. Of the 131 patients, 35 (27%) had a diagnosis of
MHA made by the primary care physician or the referring neurologist. Migraine
headache with aura incidence and severity were assessed by using Migraine
Disability Assessment (MIDAS) questionnaire. Presence and magnitude of R-to-L
shunt were assessed in all patients by means of transesophageal echocardiography 
and also by means of transcranial Doppler (TCD) in the last 50 patients (38%).
RESULTS: Patients with MHA had a higher prevalence of thrombophilia (P = .007), a
more complex atrial septal anatomy (P = .001), and they also had higher
prevalence of spontaneous R-to-L shunt and of spontaneous large shunt, both at
transesophageal echocardiography (P = .015, and .028, respectively) and at TCD (P
= .036, and .038, respectively). After the procedure, 32 (91%) of 35 patients had
either complete resolution or significant improvement in their MHA. At a mean
follow-up of 1.7 +/- 1.3 years, MHA disappeared completely in 29 (83%) of 35
patients. Of the remaining 6 patients, 3 patients (8%) had an improvement of > or
= 2 grades in the incidence and severity of MHA, 2 patients did not show any
improvement of their MHA, whereas 1 patient reported a severe relapse of MHA
about 1 year after the procedure. CONCLUSIONS: In patients with PFO, MHA is
associated with spontaneous large R-to-L shunt and thrombophilic conditions.
Transcatheter defect closure seems to be an effective and safe means to treat MHA
in patients with PFO.

PMID: 16569564 [PubMed - indexed for MEDLINE]

1312: Neurology. 2006 Mar 28;66(6):880-6.

Basilar-type migraine: clinical, epidemiologic, and genetic features.

Kirchmann M, Thomsen LL, Olesen J.

Danish Headache Center, Department of Neurology, Glostrup Hospital, University of
Copenhagen, Denmark. kirchmann@dadlnet.dk

BACKGROUND: It remains uncertain whether basilar-type migraine (BM) is a subtype 
of migraine with typical aura (MTA) or a distinct phenotype or genotype.
OBJECTIVE: To analyze the symptomatology, familial distribution, and genotype of 
BM. METHODS: The authors recruited 105 families comprising 362 patients with MTA 
or BM (International Classification of Headache Disorders-1 criteria). Among
these patients, 38 patients from 29 families had BM. In 12 of the families with
BM with an apparently dominant inheritance the authors sequenced all exons of the
CACNA1A (chromosome 19) and ATP1A2 (chromosome 1) genes responsible for most
cases of the autosomal dominantly inherited familial hemiplegic migraine and
performed a linkage analysis of chromosome 1 and 19 with a nonparametric or
autosomal dominant parametric model using an affected only analysis. RESULTS: BM 
occurred in 10% (38/362) of patients with MTA. The basilar-type aura had a median
duration of 60 minutes and comprised vertigo 61%, dysarthria 53%, tinnitus 45%,
diplopia 45%, bilateral visual symptoms 40%, bilateral paresthesias 24%,
decreased level of consciousness 21%, hypacusia 21%, and ataxia 5%. The relative 
frequency of the individual basilar-type symptoms was not different from patients
with hemiplegic migraine from a previous study. The patients with BM were equally
distributed among the 105 families with MTA (p = 0.37). The attacks of MTA were
identical in families with or without BM. No causative mutations and no linkage
was identified. CONCLUSIONS: Basilar-type aura seemingly may occur at times in
any patient with migraine with typical aura. There is no firm clinical,
epidemiologic, or genetic evidence that BM is an independent disease entity
different from MTA.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 16567706 [PubMed - indexed for MEDLINE]

1313: Neuroscience. 2006 Jun 30;140(2):743-51. Epub 2006 Mar 23.

Effect of eugenol on spreading depression and epileptiform discharges in rat
neocortical and hippocampal tissues.

Müller M, Pape HC, Speckmann EJ, Gorji A.

Institut für Physiologie I, Universität Münster, Robert-Koch-Strasse 27a, D-48149
Münster, Germany.

Eugenol, an aromatic molecule derived from several plants, has been receiving
examination for clinical relevance in epilepsy and headache. To investigate the
neurophysiologic properties of the action of eugenol, its effects on epileptiform
field potentials elicited by omission of extracellular Mg2+, spreading depression
induced by KCl microinjection, electrically evoked field potentials, and
long-term potentiation were tested in rat neocortical and hippocampal tissues.
Eugenol (10-100 micromol/l) dose-dependently and reversibly suppressed both
epileptiform field potentials and spreading depression Eugenol also reversibly
decreased the amplitude of the field postsynaptic potentials evoked in CA1 area
of hippocampus and the third layer of neocortex. Eugenol significantly reduced
the long-term potentiation by approximately 30% compared with controls. Thus,
eugenol can suppress epileptiform field potentials and spreading depression,
likely via inhibition of synaptic plasticity. The results indicate the potential 
for eugenol to use in the treatment of epilepsy and cephalic pain.

PMID: 16563641 [PubMed - indexed for MEDLINE]

1314: Turk J Pediatr. 2006 Jan-Mar;48(1):31-7.

Diagnostic criteria of pediatric migraine without aura.

Senbil N, Gürer YK, Aydin OF, Rezaki B, Inan L.

Department of Pediatric Neurology, Dr. Sami Ulus Children's Hospital, Ankara,
Turkey.

The objectives of this study were to assess the validity of the International
Classification of Headache Disorders-I (ICHD-I) and the International Headache
Society-Revised (IHS-R) criteria and to evaluate the other headache features that
are not included in these criteria for migraine without aura in the pediatric
population. One hundred and thirty-two children who referred to our clinic with
the complaint of chronic or recurrent headache were evaluated. Clinical diagnosis
of the pediatric neurologist was used as the gold standard in evaluating the
validity of ICHD-I and IHS-R criteria and the other headache features. After
eliminating patients with other migraine types, secondary headache, and missing
data, 92 patients were included in the study according to their records.
Sixty-one children (66.3%) were diagnosed as migraine without aura. Using the
clinical diagnosis as the gold standard, the specificity of ICHD-I criteria was
detected as 93.5%, while the sensitivity was detected as 36.1%. IHS-R criteria
had 90.3% specificity and 78.7% sensitivity. Relief of headache with sleeping or 
lying down in a dark, quiet room was found to be the highest specific and
sensitive factor of the other headache features not included in these criteria.
IHS-R criteria were found to be more valid in the diagnosis of migraine without
aura than ICHD-I criteria. IHS-R criteria are recommended both in clinical
practice and in the studies requiring migraine without aura case definitions in
the pediatric population.

Publication Types: 
    Validation Studies

PMID: 16562783 [PubMed - indexed for MEDLINE]

1315: Cephalalgia. 2006 Apr;26(4):477-82.

Field testing alternative criteria for chronic migraine.

Bigal ME, Tepper SJ, Sheftell FD, Rapoport AM, Lipton RB.

Department of Neurology, Albert Einstein College of Medicine, Bronx, NY, USA.
mbigal@aecom.yu.edu

The criteria for chronic migraine (CM), as proposed by the Second Edition of the 
International Classification of Headache Disorders (ICHD-2) is very restrictive, 
excluding most patients that evolve from episodic migraine. In this study we
empirically tested three recent proposals for revised criteria for CM. We
included individuals with transformed migraine (TM) with or without medication
overuse, according to the criteria proposed by Silberstein and Lipton. All
individuals had headache calendars for at least three consecutive months. We
assessed the proportion of subjects that fulfilled ICHD-2 criteria for CM or
probable chronic migraine with probable medication overuse (CM+). We also tested 
three proposals for making the CM criteria more inclusive. In proposal 1, CM/CM +
would require at least 15 days of migraine or probable migraine per month.
Proposal 2 suggests that CM/CM + would be classified in those with >or= 15 days
of headache per month, where at least 50% of these days are migraine or probable 
migraine. Proposal 3 suggests that CM/CM + would be classified in those with
chronic daily headache and at least 8 days of migraine or probable migraine per
month. Among TM sufferers, 399 (62.5%) had TM with medication overuse, and just
10.2% were classified as CM+ 158 (37.5%) had TM without medication overuse; just 
nine (5.6%) met current ICHD-2 criteria for CM. Using the alternative criteria,
proposal 1 included 48.7% of patients with TM without medication overuse;
proposal 2 captured 88%, and proposal 3 classified 94.9% of these patients. For
TM with medication overuse, the proportions for proposals 1-3 were, respectively,
37%, 81% and 91%. The differences were statistically significant, favouring
proposal 3. Consistently, criteria for CM and CM+ should be revised to require at
least 8 days of migraine or probable migraine per month, in individuals with 15
or more days of headache per month.

Publication Types: 
    Comparative Study

PMID: 16556250 [PubMed - indexed for MEDLINE]

1316: Cephalalgia. 2006 Apr;26(4):457-65.

Relationship between precipitating agents and neurophysiological abnormalities in
migraine.

Siniatchkin M, Averkina N, Gerber WD.

Paediatric Neurology, University of Kiel, Kiel, Germany.
m.siniatchkin@pedneuro.uni-kiel.de

The particular mechanisms of migraine anticipation by different precipitating
agents are still unknown. The contingent negative variation (CNV) was recorded in
the premenstrual and ovulation phases of the cycle in both rest and stress
conditions in 17 migraine and 15 healthy women. In migraineurs a significant
increase of amplitude of the initial CNV component in the premenstrual phase
compared with ovulation was observed. During both the ovulation and premenstrual 
phases both migraineurs and controls demonstrated a significant increase of the
CNV amplitude on stress. The increase of the amplitude on stress in the
premenstrual phase was more pronounced in migraineurs. This study shows that
stress and menstrual cycle are associated with changes of the initial CNV
amplitude, probably indicating a higher probability of migraine attacks.

Publication Types: 
    Controlled Clinical Trial

PMID: 16556248 [PubMed - indexed for MEDLINE]

1317: Cephalalgia. 2006 Apr;26(4):451-6.

Prevalence of fibromyalgia syndrome in migraine patients.

Ifergane G, Buskila D, Simiseshvely N, Zeev K, Cohen H.

Headache Clinic, Department of Neurology, Soroka Medical Centre, Ben-Gurion
University of the Negev, Beer Sheva, Israel. galif@clalit.org.il

Fibromyalgia syndrome (FMS) is a chronic pain syndrome of unknown aetiology
characterized by diffuse pain over more than 3 months and tenderness in specific 
sites named tender points. The aim of this study was to assess the prevalence and
severity of FMS among patients suffering from episodic migraine. Ninety-two
consecutive patients (20 male, 72 female) fulfilling the International Headache
Society criteria for migraine with and without aura from a tertiary headache
clinic were evaluated. A headache and generalized pain history was recorded,
tender points were evaluated by thumb palpation. The diagnosis of FMS was made
based on the 1990 American College of Rheumatology classification criteria for
FMS. Sixteen (22.2%) of the female patients and none of the male patients were
diagnosed as suffering from FMS. Migraine severity and characteristics were
similar to other female migraine patients. Patients suffering from migraine-FMS
had lower quality of life scores and higher levels of mental distress. A high
incidence of FMS was found among female migraine patients but not in males. The
coexistence of FMS should be considered when choosing a prophylactic migraine
therapy.

PMID: 16556247 [PubMed - indexed for MEDLINE]

1318: Cephalalgia. 2006 Apr;26(4):445-50.

Headache prevention outcome and body mass index.

Bigal ME, Gironda M, Tepper SJ, Feleppa M, Rapoport AM, Sheftell FD, Lipton RB.

Department of Neurology, Albert Einstein College of Medicine, Bronx, NY, USA.
mbigal@aecom.yu.edu

A population-based longitudinal study suggests that obesity is a strong risk
factor for the development of headaches on 15 or more days per month. Little is
know about the influence of weight on the response to headache preventive
treatment. Herein we prospectively assessed the influence of the baseline body
mass index (BMI) on the response to headache preventive treatment. We included
adults with episodic or chronic migraine (ICHD-2), or transformed migraine
(Silberstein and Lipton criteria) that sought care in a headache clinic. BMI was 
assessed in the first visit. Baseline information included headache frequency,
number of days with severe headache (prospectively obtained over 1 month), and
headache-related disability (HIT-6). The same information was obtained after 3
months of preventive treatment. Subjects were categorized based on BMI in: normal
weight (</=24.9), overweight (25-29.9), or obese (>/=30). We contrasted the
headache end-points using anova with post-test and Kruskal-Wallis with post-test.
We used logistic regression to model BMI and headache parameters adjusting for
covariates. Our sample consisted of 176 subjects (79.5% women, mean of 44.4
years). At baseline 40.9% had normal weight, 29.5% were overweight and 27.3% were
obese. No significant differences were observed in the number of headache days at
baseline. After treatment, frequency declined in the entire population, but no
significant differences were found by BMI group. Regarding the number of days
with severe pain per month, there were also no significant differences at
baseline (normal = 6.1, overweight = 6.5, obese = 6.7), and improvement overall
(P = 0.01). However, changes were greater in the obese (reduction in 2.7 days
with treatment) and overweight (3.9) vs. normal (1.5, P < 0.01). Finally, HIT
scores at baseline did not differ by BMI group (normal weight = 63.8, overweight 
= 64.1, obese = 63.6). However, compared with the normal weighted group, change
in HIT scores (follow-up baseline) were greater in the obese (6.4 vs. 3.5, P <
0.05) and overweight groups (6.8 vs. 3.5, P < 0.05). In the logistic regression
model, BMI did not account for changes in disability, headache frequency, or in
the number of days with severe headache per month, after adjusting for
covariates. Contrary to what we hypothesized, obesity at baseline does not seem
to be related to follow-up refractoriness to preventive treatment.

Publication Types: 
    Controlled Clinical Trial

PMID: 16556246 [PubMed - indexed for MEDLINE]

1319: Cephalalgia. 2006 Apr;26(4):436-44.

Migraine patients have lower systolic but higher diastolic blood pressure
compared with controls in a population-based study of 21,537 subjects. The
Reykjavik Study.

Gudmundsson LS, Thorgeirsson G, Sigfusson N, Sigvaldason H, Johannsson M.

Department of Pharmacology and Toxicology, University of Iceland, Reykjavik,
Iceland.

Several studies have explored a possible association between migraine and
hypertension, with contradictory results. Because of this uncertainty the
relation between blood pressure (BP) and migraine was studied in 10,366 men and
11,171 women in a population-based longitudinal study. A modified version of the 
1988 International Headache Society criteria was used for diagnosis of migraine. 
Logistic regression analysis was used. The crude 1-year prevalence of migraine
was 5.2% among men and 14.1% among women. No significant association was found
between hypertension and migraine. For a one standard deviation (SD) increase in 
diastolic BP the probability of having migraine increased 14% (P = 0.11) for men 
and 30% (P < 0.0001) for women. For a 1-SD increase in systolic BP the
probability of having migraine decreased 19% (P = 0.007) for men and 25% (P <
0.0001) for women. It was also found that for a 1-SD increase in pulse pressure
the probability of having migraine decreased 13% (P = 0.005) for men and 14% (P <
0.0001) for women. In a population-based study of men and women it was found that
subjects with migraine had lower pulse pressure, lower systolic BP and higher
diastolic BP compared with controls.

Publication Types: 
    Controlled Clinical Trial
    Research Support, Non-U.S. Gov't

PMID: 16556245 [PubMed - indexed for MEDLINE]

1320: Cephalalgia. 2006 Apr;26(4):428-35.

Does earlier headache response equate to earlier return to functioning in
patients suffering from migraine?

Pradel FG, Subedi P, Varghese AA, Mullins CD, Weis KA.

Department of Pharmaceutical Health Services Research, School of Pharmacy,
University of Maryland, Baltimore, MD 21201, USA. fpradel@rx.umaryland.edu

This study explored the association between headache response and return to
functioning, and identified migraine-associated symptoms related to functional
status and acceptability of migraine treatment as reported by patients. Data from
migraineurs enrolled in the active arms of a randomized, double-blind, parallel
group, placebo-controlled, clinical trial were analysed. The relationships
between headache response and functional response, and clinical factors and
treatment acceptability were assessed using chi(2) tests of proportions and
logistic regressions. A greater proportion of patients with headache response at 
0.5 h were functioning at 0.5, 1 and 2 h compared with patients who did not
attain a headache response at 0.5 h (P < 0.0001). These patients also were more
likely to find their treatment acceptable (P < 0.05). The results suggest a
direct temporal relationship among the key determinants of migraine resolution.
Rapid headache response is associated with faster return to functioning; rapid
headache and functional responses are significant attributes of treatment
acceptability.

Publication Types: 
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 16556244 [PubMed - indexed for MEDLINE]

1321: Cephalalgia. 2006 Apr;26(4):416-22.

Prediction of headache response in migraine treatment.

Maas HJ, Danhof M, Della Pasqua OE.

Division of Pharmacology, Leiden/Amsterdam Centre for Drug Research, the
Netherlands.

Triptans are efficacious for the acute treatment of migraine attacks. Yet,
defining a concentration-effect relation for these compounds is difficult as the 
dynamics of the migraine attack are not thoroughly understood. The objective of
this investigation was to develop a disease model to predict measures of headache
in randomized placebo-controlled clinical trials investigating oral sumatriptan
as a paradigm compound. A hidden Markov model based on the states of response (no
relief, relief, and pain free) and headache scores (observed variable) was used
in conjunction with population pharmacokinetics. Model parameters were capable of
predicting the course of headache relief, pain-free status and headache
recurrence. It was shown that sumatriptan shortens mean transit times between
states by up to 5 h. The potency of sumatriptan (EC(50)) was 9 ng/ml. These
findings demonstrate the value of combining pharmacokinetic and efficacy
information to model disease and characterize time-independent drug properties in
a population of migraineurs.

PMID: 16556242 [PubMed - indexed for MEDLINE]

1322: Cephalalgia. 2006 Apr;26(4):409-15.

Glial cell line-derived neurotrophic factor and somatostatin levels in
cerebrospinal fluid of patients affected by chronic migraine and fibromyalgia.

Sarchielli P, Alberti A, Candeliere A, Floridi A, Capocchi G, Calabresi P.

Neurologic Clinic, Department of Medical and Surgical Specialties and Public
Health, University of Perugia, Perugia, Italy. neuro.pg@tiscalinet.it

The aim of the present study was to verify cerebrospinal fluid (CSF) levels of
glial cell line-derived neurotrophic factor (GDNF) and somatostatin, both
measured by sensitive immunoassay, in: 16 chronic migraine (CM) patients, 15
patients with an antecedent history of migraine without aura diagnosed as having 
probable chronic migraine (PCM) and probable analgesic-abuse headache (PAAH), 20 
patients affected by primary fibromyalgia syndrome (PFMS), and 20 control
subjects. Significantly lower levels of GDNF and somatostatin were found in the
CSF of both CM and PCM + PAAH patients compared with controls (GDNF =P < 0.001, P
< 0.002; somatostatin = P < 0.002, P < 0.0003), without significant difference
between the two groups. PFMS patients, with and without analgesic abuse, also had
significantly lower levels of both somatostatin and GDNF (P < 0.0002, P < 0.001),
which did not differ from those of CM and PCM + PAAH patients. A significant
positive correlation emerged between CSF values of GDNF and those of somatostatin
in CM (r = 0.70, P < 0.02), PCM + PAAH (r = 0.78, P < 0.004), and PFMS patients
(r = 0.68, P < 0.008). Based on experimental findings, it can be postulated that 
reduced CSF levels of GDNF and somatostatin in both CM and PCM + PAAH patients
can contribute to sustained central sensitization underlying chronic head pain.
The abuse of simple or combination analgesics does not seem to influence the
biochemical changes investigated, which appear to be more strictly related to the
chronic pain state, as demonstrated also for fibromyalgia.

Publication Types: 
    Controlled Clinical Trial

PMID: 16556241 [PubMed - indexed for MEDLINE]

1323: Cephalalgia. 2006 Apr;26(4):400-8.

Efficacy, speed of action and tolerability of almotriptan in the acute treatment 
of migraine: pooled individual patient data from four randomized, double-blind,
placebo-controlled clinical trials.

Dahlöf CG, Pascual J, Dodick DW, Dowson AJ.

Institute of Clinical Neuroscience, Gothenburg Migraine Clinic, Gothenburg,
Sweden. carl.dahlof@migraineclinic.se

A meta-analysis of pooled individual patient data from four randomized,
placebo-controlled, double-blind trials comparing several doses of almotriptan (n
= 1,908) with placebo (n = 386) was used to investigate the efficacy, speed of
onset and tolerability of almotriptan in the acute treatment of migraine. As
early as 30 min after dosing, almotriptan 12.5 mg was significantly more
effective than placebo for pain relief (14.9% vs. 8.2%; P < 0.05) and pain free
(2.5% vs. 0.7%; P < 0.05). At 2 h, pain-relief rates were 56.0%, 63.7% and 66.0% 
for almotriptan 6.25, 12.5 and 25 mg, respectively, compared with 35% for
placebo; 2-h pain-free rates were 26.7%, 36.4% and 43.4% compared with 13.9% for 
placebo. All almotriptan dosages were significantly more effective than placebo
in eliminating migraine-associated symptoms (P < 0.05) and in achieving sustained
pain relief up to 24 h (P < 0.05). The incidence of adverse events after
almotriptan 6.25 mg and 12.5 mg was not significantly different from that of
placebo. This meta-analysis confirms the findings of individual clinical trials, 
while demonstrating for the first time, significant pain-free efficacy at 30 min 
compared with placebo.

Publication Types: 
    Meta-Analysis
    Review

PMID: 16556240 [PubMed - indexed for MEDLINE]

1324: Cephalalgia. 2006 Apr;26(4):373-83.

Prophylactic treatment of migraine in children. Part 1. A systematic review of
non-pharmacological trials.

Damen L, Bruijn J, Koes BW, Berger MY, Passchier J, Verhagen AP.

Department of General Practice, Erasmus Medical Centre, Rotterdam, the
Netherlands.

The aim of this study was to assess the efficacy of non-pharmacological
prophylactic treatments of migraine in children. Databases were searched from
inception to June 2004 and references were checked. We selected controlled trials
reporting the effects of non-pharmacological prophylactic treatments in children 
with migraine. We assessed trial quality using the Delphi list and extracted
data. Analyses were carried out according to type of intervention. A total of 19 
trials were included. Relaxation, relaxation + biofeedback, relaxation +
biofeedback + cognitive behavioural treatment were more effective compared with
waiting list controls. Relaxation + behavioural therapy was more effective than
placebo. There is conflicting evidence for the use of oligoantigenic diets. A few
non-pharmacological treatments such as relaxation may be effective as
prophylactic treatment for migraine in children. Because of the small number of
studies and the methodological shortcomings, conclusions on effectiveness have to
be drawn with caution.

Publication Types: 
    Meta-Analysis
    Research Support, Non-U.S. Gov't
    Review

PMID: 16556238 [PubMed - indexed for MEDLINE]

1325: Cephalalgia. 2006 Apr;26(4):361-72.

Mitochondrial dysfunction and migraine: evidence and hypotheses.

Sparaco M, Feleppa M, Lipton RB, Rapoport AM, Bigal ME.

Department of Neurology and Headache Centre, Hospital G. Rummo Benevento,
Benevento, Italy. marcosparaco@aliceposta.it

The molecular basis of migraine is still not completely understood. An impairment
of mitochondrial oxidative metabolism might play a role in the pathophysiology of
this disease, by influencing neuronal information processing. Biochemical assays 
of platelets and muscle biopsies performed in migraine sufferers have shown a
decreased activity of the respiratory chain enzymes. Studies with phosphorus
magnetic resonance spectroscopy ((31)P-MRS) have demonstrated an impairment of
the brain oxidative energy metabolism both during and between migraine attacks.
However, molecular genetic studies have not detected specific mitochondrial DNA
(mtDNA) mutations in patients with migraine, although other studies suggest that 
particular genetic markers (i.e. neutral polymorphisms or secondary mtDNA
mutations) might be present in some migraine sufferers. Further studies are still
needed to clarify if migraine is associated with unidentified mutations on the
mtDNA or on nuclear genes that code mitochondrial proteins. In this paper, we
review morphological, biochemical, imaging and genetic studies which bear on the 
hypothesis that migraine may be related to mitochondrial dysfunction at least in 
some individuals.

Publication Types: 
    Review

PMID: 16556237 [PubMed - indexed for MEDLINE]

1326: NeuroRx. 2006 Apr;3(2):181-91.

The pharmacological treatment options for pediatric migraine: an evidence-based
appraisal.

Lewis DW, Winner P.

Division of Pediatric Neurology, Children's Hospital of the King's Daughters,
Eastern Virginia Medical School, Norfolk, 23501, USA. dlewis@chkd.com

The treatment of children and adolescents who suffer from migraine headaches must
be individually tailored, flexible, and balanced with a blend of bio-behavioral
measures, agents for acute treatment and, if needed, daily preventive medicines. 
While controlled data is limited, there is now enough evidence available to
provide a rational framework to build treatment plans appropriate for the
pediatric population. Essentially, the pharmacological management of pediatric
migraine divides into agents for the acute attacks and agents used daily to
prevent or reduce the frequency of attacks. For the acute treatment, the most
rigorously studied agents are ibuprofen, acetaminophen, and the nasal spray forms
of sumatriptan and zolmitriptan, all of which have shown both safety and efficacy
in controlled trials. For preventive treatment the calcium channel blocker
flunarezine has the best efficacy profile in controlled trials, but is not
available in the U.S. A growing body of data, mostly uncontrolled, is emerging
regarding the use of several anti-epileptic agents (e.g. topiramate, disodium
valproate, levateracetam), as well as the antihistamine cyproheptadine and the
anti-depressant amitriptyline.

Publication Types: 
    Review

PMID: 16554256 [PubMed - indexed for MEDLINE]

1327: Catheter Cardiovasc Interv. 2006 Apr;67(4):625-9.

Long-term efficacy of transcatheter patent foramen ovale closure on migraine
headache with aura and recurrent stroke.

Giardini A, Donti A, Formigari R, Salomone L, Palareti G, Guidetti D, Picchio FM.

Pediatric Cardiology and Adult Congenital Unit, University of Bologna, Bologna,
Italy. alessandro5574@iol.it

OBJECTIVES: To assess the long-term results of transcatheter patent foramen ovale
(PFO) closure on migraine headache with aura (MHA) and on the risk of recurrent
stroke. Background: Transcatheter PFO closure is associated with an early
improvement of MHA, and a reduction or the risk of recurrent cerebral ischemia,
but the long-term outcome after the procedure is unknown. METHODS: We analyzed
follow-up data of 38 consecutive patients who had undergone transcatheter PFO
closure at our institution because of cryptogenic stroke and had been followed-up
for at least 3 years after the procedure. Mean age at closure was 43 +/- 13
years. Thirteen patients (34%) had a diagnosis of MHA made by the primary care
physician or the referring neurologist. Migraine disability assessment
questionnaire (MIDAS) was used to assess MHA incidence and severity. RESULTS:
After a mean follow-up of 4.8 +/- 1.4 years, two patients had a recurrent stroke 
(13 and 15 months after the procedure, respectively). Recurrence rate 5 years
after the procedure was 5.3%. After 4.9 +/- 1.4 years from the intervention,
12/13 patients (92%, 95% CI 65-99%) had complete resolution in their MHA.
Overall, MIDAS score decreased significantly (38.6 +/- 26.3 vs. 4.4 +/- 5.1, P < 
0.0001) after the procedure. One patient did not report any improvement of MHA
after transcatheter PFO closure, whereas one patient reported a severe relapse of
MHA about 1 year after PFO closure. Freedom from recurrent MHA 5 years after the 
procedure was 85% (95% CI 57-97%). CONCLUSIONS: The rate of recurrent cerebral
ischemia and recurrent MHA seems to be low at long-term follow-up after
transcatheter PFO closure. Recurrent cerebral ischemia and relapse of MHA seem to
be confined to the first 15 months after the procedure.

PMID: 16548006 [PubMed - indexed for MEDLINE]

1328: Genomics. 2006 Jun;87(6):693-703. Epub 2006 Mar 20.

Genomic profiles for human peripheral blood T cells, B cells, natural killer
cells, monocytes, and polymorphonuclear cells: comparisons to ischemic stroke,
migraine, and Tourette syndrome.

Du X, Tang Y, Xu H, Lit L, Walker W, Ashwood P, Gregg JP, Sharp FR.

MIND Institute, University of California at Davis, 2805 50th Street, Sacramento, 
CA 95817, USA.

Blood genomic profiling has been applied to disorders of the blood and various
organ systems including brain to elucidate disease mechanisms and identify
surrogate disease markers. Since most studies have not examined specific cell
types, we performed a preliminary genomic survey of major blood cell types from
normal individuals using microarrays. CD4+ T cells, CD8+ T cells, CD19+ B cells, 
CD56+ natural killer cells, and CD14+ monocytes were negatively selected using
the RosetteSep antibody cocktail, while polymorphonuclear leukocytes were
separated with density gradient media. Genes differentially expressed by each
cell type were identified. To demonstrate the potential use of such cell
subtype-specific genomic expression data, a number of the major genes previously 
reported to be regulated in ischemic stroke, migraine, and Tourette syndrome are 
shown to be associated with distinct cell populations in blood. These specific
gene expression, cell-type-related profiles will need to be confirmed in larger
data sets and could be used to study these and many other neurological diseases.

Publication Types: 
    Comparative Study
    Research Support, N.I.H., Extramural
    Research Support, U.S. Gov't, Non-P.H.S.

PMID: 16546348 [PubMed - indexed for MEDLINE]

1329: Lancet Neurol. 2006 Apr;5(4):310-6.

Erratum in:
    Lancet Neurol. 2008 Jun;7(6):475.

Comment in:
    Lancet Neurol. 2006 May;5(5):382-3; author reply 383.

Efficacy of acupuncture for the prophylaxis of migraine: a multicentre randomised
controlled clinical trial.

Diener HC, Kronfeld K, Boewing G, Lungenhausen M, Maier C, Molsberger A,
Tegenthoff M, Trampisch HJ, Zenz M, Meinert R; GERAC Migraine Study Group.

Department of Neurology, University Essen, Essen, Germany. h.diener@uni-essen.de

BACKGROUND: Our aim was to assess the efficacy of a part-standardised verum
acupuncture procedure, in accordance with the rules of traditional Chinese
medicine, compared with that of part-standardised sham acupuncture and standard
migraine prophylaxis with beta blockers, calcium-channel blockers, or
antiepileptic drugs in the reduction of migraine days 26 weeks after the start of
treatment. METHODS: This study was a prospective, randomised, multicentre,
double-blind, parallel-group, controlled, clinical trial, undertaken between
April 2002 and July 2005. Patients who had two to six migraine attacks per month 
were randomly assigned verum acupuncture (n=313), sham acupuncture (n=339), or
standard therapy (n=308). Patients received ten sessions of acupuncture treatment
in 6 weeks or continuous prophylaxis with drugs. Primary outcome was the
difference in migraine days between 4 weeks before randomisation and weeks 23-26 
after randomisation. This study is registered as an International Standard
Randomised Controlled Trial, number ISRCTN52683557. FINDINGS: Of 1295 patients
screened, 960 were randomly assigned to a treatment group. Immediately after
randomisation, 125 patients (106 from the standard group) withdrew their consent 
to study participation. 794 patients were analysed in the intention-to-treat
popoulation and 443 in the per-protocol population. The primary outcome showed a 
mean reduction of 2 .3 days (95% CI 1.9-2.7) in the verum acupuncture group, 1.5 
days (1.1-2.0) in the sham acupuncture group, and 2.1 days (1.5-2.7) in the
standard therapy group. These differences were statistically significant compared
with baseline (p<0.0001), but not across the treatment groups (p=0.09). The
proportion of responders, defined as patients with a reduction of migraine days
by at least 50%, 26 weeks after randomisation, was 47% in the verum group, 39% in
the sham acupuncture group, and 40% in the standard group (p=0.133).
INTERPRETATION: Treatment outcomes for migraine do not differ between patients
treated with sham acupuncture, verum acupuncture, or standard therapy.

Publication Types: 
    Clinical Trial
    Comparative Study
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 16545747 [PubMed - indexed for MEDLINE]

1330: Neurosci Lett. 2006 May 29;400(1-2):121-4. Epub 2006 Mar 15.

Neurophysiological reactivity before a migraine attack.

Siniatchkin M, Averkina N, Andrasik F, Stephani U, Gerber WD.

Pediatric Neurology, University of Kiel, Schwanenweg 20, 24105 Kiel, Germany.
m.siniatchkin@pedneuro.uni-kiel.de

Migraine patients are characterized by increased amplitudes and reduced
habituation of the contingent negative variation (CNV) response, especially
before a migraine attack. As shown previously, migraine provoking and
precipitating agents can cause CNV abnormalities. However, it is unclear whether 
the temporal relation to the migraine attack determines how the brain reacts to a
migraine precipitant. In this study, experimentally-induced achievement stress,
one of the typical precipitants for migraine, was examined for its effects upon
the CNV response. CNV was recorded during conditions of rest and stress, both
before and after a migraine attack, as well as during a headache-free interval.
The neurophysiological reactivity to stress in migraineurs was compared with
those of healthy subjects. Before a migraine attack, migraine patients
demonstrated significantly more pronounced neurophysiological reactivity to
stress: the amplitude of the early CNV component was more increased and its
habituation was more reduced in the stress condition, especially 1-3 days before 
an attack compared with changes of CNV amplitudes and habituation under stress
obtained after an attack, during the headache-free interval, or in healthy
controls. The study demonstrates that the brain of migraine patients is
characterized by increased susceptibility to migraine provoking agents before an 
actual attack.

Publication Types: 
    Comparative Study

PMID: 16540242 [PubMed - indexed for MEDLINE]

1331: J Headache Pain. 2006 Apr;7(2):83-9. Epub 2006 Mar 15.

High prolactin levels as a worsening factor for migraine.

Cavestro C, Rosatello A, Marino MP, Micca G, Asteggiano G.

Department of Neurology, S. Lazzaro Hospital A.S.L. 18 Alba - Bra, Alba (CN),
Italy. cicaves@tin.it

Many factors should be considered when an episodic migraine worsens and becomes
chronic. Prolactin (PRL) was linked to the origin of pain in patients with
microprolactinomas who developed different types of headaches. Our team carried
out studies on 27 patients with a background of episodic headaches that became
chronic. The patients were evaluated by means of a general examination, a
neurological examination and a hormonal profile. Of the 27 patients, 7 of them
had an increased level of prolactinaemia. All the patients were women, ranging
from 17 to 57 years of age. Four of them had a pure form of migraine without
aura, whereas 3 patients had both migraines without aura and tension-type
headaches. They suffered from headache for a period ranging from 3 to 32 years
and their headache became chronic 4-12 months prior to the visit. Their headache 
did not change in type, but only in severity and frequency. Two patients had no
symptoms referable to high PRL levels; 4 patients had irregular menses or
amenorrhoea. One of these patients also suffered galactorrhoea and two of these
patients had a microprolactinoma at MRI; one patient was using estroprogestinic
drugs, so her menstrual alteration could not be considered. The patients were
followed-up for a period of 6-16 months. Six patients responded favourably after 
being treated with cabergoline, although some had already tried other drugs,
which, however, had no effect on their headache. One patient improved after
ceasing to take estroprogestinic, in spite of increased levels of PRL. Therefore,
on this basis, PRL levels should always be considered when headache worsens. It
is an adjunctive worsening factor, which can be easily eliminated.

Publication Types: 
    Comparative Study

PMID: 16538425 [PubMed - indexed for MEDLINE]

1332: Eur J Hum Genet. 2006 May;14(5):555-60.

Two de novo mutations in the Na,K-ATPase gene ATP1A2 associated with pure
familial hemiplegic migraine.

Vanmolkot KR, Kors EE, Turk U, Turkdogan D, Keyser A, Broos LA, Kia SK, van den
Heuvel JJ, Black DF, Haan J, Frants RR, Barone V, Ferrari MD, Casari G,
Koenderink JB, van den Maagdenberg AM.

Department of Human Genetics, Leiden University Medical Centre, Leiden, The
Netherlands, and Department of Neurology, Dr Lütfi Kirdar State Hospital,
Maltepe, Istanbul, Turkey.

Familial hemiplegic migraine (FHM) is a rare autosomal dominantly inherited
subtype of migraine, in which hemiparesis occurs during the aura. The majority of
the families carry mutations in the CACNA1A gene on chromosome 19p13 (FHM1).
About 20% of FHM families is linked to chromosome 1q23 (FHM2), and has mutations 
in the ATP1A2 gene, encoding the alpha2-subunit of the Na,K-ATPase. Mutation
analysis in a Dutch and a Turkish family with pure FHM revealed two novel de novo
missense mutations, R593W and V628M, respectively. Cellular survival assays
support the hypothesis that both mutations are disease-causative. The
identification of the first de novo mutations underscores beyond any doubt the
involvement of the ATP1A2 gene in FHM2.

Publication Types: 
    Case Reports
    Research Support, Non-U.S. Gov't

PMID: 16538223 [PubMed - indexed for MEDLINE]

1333: J Mass Dent Soc. 2006 Winter;54(4):28-30.

Migraine with aura and dental occlusion: a case report.

Melis M, Secci S.

Craniofacial Pain Center, Tufts University School of Dental Medicine, USA.

Migraine is defined as a primary headache; however, some reports may suggest a
relationship with dental occlusion and dental parafunction (clenching or grinding
of the teeth). A patient diagnosed with migraine with aura, with concomitant
temporomandibular joint and masseter muscle pain, was treated by the use of a
dental appliance. The treatment succeeded in eliminating headache and visual
aura, and significantly reducing the other symptoms. A headache related to dental
occlusion and dental parafunctions seems to be able to mimic a primary migraine
headache. Therefore, dental evaluation is always advised for headache diagnosis.

Publication Types: 
    Case Reports

PMID: 16536161 [PubMed - indexed for MEDLINE]

1334: Neurology. 2006 Mar 14;66(5):765-7.

Comment in:
    Neurology. 2006 Sep 12;67(5):919-20; author reply 919-20.

Different degrees of right-to-left shunting predict migraine and stroke: data
from 420 patients.

Anzola GP, Morandi E, Casilli F, Onorato E.

ervizio di Neurologia, Ospedale S. Orsola FBF, Associazione Fatebenefratelli per 
la Ricerca (AFaR), Brescia, Italy. gpanzola@numerica.it

The authors analyzed the extent of right-to-left shunting in patients with
migraine, patients with cryptogenic stroke, and controls. Patients with both
migraine and stroke had larger shunts than did patients with migraine without
stroke (p = 0.038), patients with no migraine with stroke (p = 0.007), and
control patients (p < 0.0001). Patients with migraine have overall larger shunts 
than nonmigraineurs, particularly if they have had a stroke. Right-to-left
shunting may be causally related to migraine and to the increased stroke risk of 
migraine.

PMID: 16534123 [PubMed - indexed for MEDLINE]

1335: Expert Rev Neurother. 2006 Mar;6(3):307-12.

New insights into brain dysfunction in migraine.

Aurora SK, Bowyer SM.

Swedish Headache Center, Seattle, WA, USA. Sheena.Aurora@swedish.org

Headache is one of the most common presenting symptoms to a physician's office.
The majority of headaches are in the category known as primary headaches, where
there are no structural disturbances. Secondary headaches are uncommon and
usually occur in less than 10% of patients. The mechanisms of secondary headaches
are usually due to the underlying pathology. These are usually evident on
neuroimaging or laboratory testing. This review will focus mainly on mechanisms
of primary headache (i.e., migraine and cluster).

Publication Types: 
    Review

PMID: 16533135 [PubMed - indexed for MEDLINE]

1336: Expert Rev Neurother. 2006 Mar;6(3):297-306.

When migraine progresses: transformed or chronic migraine.

Bigal ME, Lipton RB.

Department of Neurology, Albert Einstein College of Medicine, Bronx, NY 10461,
USA. mbigal@aecom.yu.edu

Migraine may be conceptualized, not just as an episodic disorder, but as a
chronic recurrent and sometimes chronic progressive disorder. Transformed
migraine, often referred to as chronic migraine is the result of migraine
progression. This article will review the clinical features of transformed
migraine, highlighting that its phenotype varies according to stage. Early in the
process of transformation, attacks with migraine features are very common. As the
disease evolves, most attacks lack the migraine features. The risk factors for
migraine progression and the mechanisms for progression will be discussed. This
review concludes with the prospects for treating transformed migraine and
avoiding migraine progression.

Publication Types: 
    Review

PMID: 16533134 [PubMed - indexed for MEDLINE]

1337: Expert Rev Neurother. 2006 Mar;6(3):291-6.

Pediatric migraine: new diagnostic strategies and treatment options.

Pakalnis A.

Headache Clinic, Columbus Children's Hospital, Ohio State University College of
Medicine, Columbus, OH, USA. PakalnisA@pediatrics.ohio-state.edu

Migraine headaches are seen commonly by physicians caring for children and
adolescents. The prevalence in the pediatric population ranges from 3.2 to 10.6%.
With the advent of new inclusive diagnostic criteria, reproducibility of
definitive diagnosis in children and adolescents should improve. Although
advances with clinical drug trials have yielded new, approved therapies in
adults, information remains inconclusive in the pediatric population. Further
clinical studies are warranted to develop consensus on treatment paradigms for
clinicians to utilize in children and adolescents with migraine.

Publication Types: 
    Review

PMID: 16533133 [PubMed - indexed for MEDLINE]

1338: Expert Rev Neurother. 2006 Mar;6(3):283-9.

Polytherapy in the preventive and acute treatment of migraine: fundamentals for
changing the approach.

Krymchantowski AV, Bigal ME.

Headache Center of Rio, Rua Siqueira Campos 43/1002 Copacabana, Rio de Janeiro,
22031.070, Brazil. abouchkrym@globo.com

The pathophysiology of migraine is complex and involves multiple
neurophysiological pathways. Monotherapeutic approaches for migraine are the rule
but many patients discontinue their medications owing to lack of efficacy.
Polytherapy may provide a rational strategy for some of these individuals.
Herein, we review the basis of polytherapy treatment for migraine. We suggest
that refractory patients, with previous failure to single agents, may benefit
from the use of a two- or three-drug regimen combining medications that target
different neurotransmitter systems. In addition, those patients with high
recurrence rates or not presenting pain free at 2 h and/or sustained pain free at
24 h may also respond better to combination therapy suited to their individual
profile, which must include nonsteroidal anti-inflammatory agents plus a triptan 
or a gastrokinetic drug. The three-drug regimen may also be considered. Finally, 
changing the time medicine is taken (before the development of central
sensitization and allodynia cutanea) and switching the choice of formulations to 
non-oral potentially achieves a better response and can be determined
individually. Although highly speculative, these hypotheses could stimulate
further controlled studies to support changing the current paradigm of
monotherapeutic migraine treatment in some patients.

Publication Types: 
    Review

PMID: 16533132 [PubMed - indexed for MEDLINE]

1339: Saudi Med J. 2006 Mar;27(3):377-80.

Evaluation of self-medication prevalence, diagnosis and prescription in migraine 
in Kerman, Iran.

Sedighi B, Ghaderi-Sohi S, Emami S.

Department of Neurology, Shafa Hospital, Kerman Kerman, Iran.
behnaz.sedighi@gmail.com

OBJECTIVE: To investigate different diagnosis aspects, prescribed drugs and
self-medications of migraine in Iran. METHODS: We selected 210 migraineurs from
high school and university students in Kerman, Iran over a period of 6 months in 
2002 by multistage randomized screening based on the International Headache
Society criteria. We classified them into 2 groups on the basis of whether they
had consulted a physician or not. We then evaluated the physician prescriptions, 
and prevalence of self-medications. RESULTS: Only 49% of migraineurs consulted a 
physician, and only 53% were correctly diagnosed by physicians according to the
International Headache Society criteria. Our study shows that 69% of general
practitioners diagnoses were wrong. In spite of indications for prophylactic
treatment, it was not prescribed in 76% of the patients, and 50% of the general
practitioners prescribed it without any indications. Furthermore, 91% of patients
used self-medication; Acetaminophen and Codeine were the most common. CONCLUSION:
General practitioners misdiagnosis and mismanagement of the migraineurs, and easy
access to various drugs in Iran, have led to a high rate of self-medication.
Self-medication with Codeine, with regard to its side effects, such as increase
of secondary headaches and dependency is the major problem. Consequently, medical
education systems, physician reevaluating methods, and the concept of
self-medication among patients have to be revised.

PMID: 16532101 [PubMed - indexed for MEDLINE]

1340: J Neurol Sci. 2006 May 15;244(1-2):137-41. Epub 2006 Mar 13.

Assessment of MRI abnormalities of the brainstem from patients with migraine and 
multiple sclerosis.

Tortorella P, Rocca MA, Colombo B, Annovazzi P, Comi G, Filippi M.

Neuroimaging Research Unit, Scientific Institute and University Ospedale San
Raffaele, Milan, Italy.

BACKGROUND: In patients with migraine, functional changes have been described in 
the red nucleus (RN), substantia nigra (SN) and periaqueductal gray matter (PAG).
PURPOSE: To evaluate whether and at which frequency these structures are involved
by MRI-detectable structural abnormalities in migraineurs and to investigate the 
pathogenic role of these abnormalities by assessing their frequency and extent in
patients with multiple sclerosis (MS) and migraine. METHODS: On brain dual-echo
scans obtained from 58 migraineurs (40 without and 18 with aura), 37 MS patients 
with migraine without aura and 42 MS patients without migraine, the presence of
hyperintense lesions involving the brainstem structures was recorded. A test of
heterogeneity between groups was used to compare the presence of lesions among
patient groups. RESULTS: Lesions of RN, SN and PAG were found in all patient
groups, with frequency from 57.5% to 86.5%. Significant between-group differences
for all these regions were found. No difference was found between migraine
patients with and without aura. Compared with MS patients without migraine, MS
patients with migraine had more significant involvement of the SN (p=0.02) and RN
(p<0.0001). Compared with migraine patients, MS patients with migraine had more
significant involvement of the SN and PAG (p ranging from 0.009 to 0.02).
CONCLUSIONS: T2-visible lesions in the brainstem are frequent in patients with
migraine, but do not seem to be associated with the presence of aura.
Demyelinating lesions in the RN, SN and PAG might be among the factors
responsible for the presence of migraine in patients with MS.

Publication Types: 
    Comparative Study

PMID: 16530789 [PubMed - indexed for MEDLINE]

1341: Neurophysiol Clin. 2006 Jan-Feb;36(1):13-8. Epub 2006 Feb 2.

Motor and visual cortical excitability in migraineurs patients with or without
aura: transcranial magnetic stimulation.

Khedr EM, Ahmed MA, Mohamed KA.

Neuropsychiatry Department, Assiut University Hospital, Assiut, Egypt.
Emankhedr99@yahoo.com

BACKGROUND AND PURPOSE OF STUDY: Controversy surrounds measures of visual and
motor cortical excitability in migraineurs: some authors report that interictal
excitability is increased, others decreased. The aim of this work was to provide 
further evidence about motor and visual cortical excitability in migraineurs
between attacks. PATIENTS AND METHODS: Twenty-eight migraineurs patients, 18 with
aura and 10 patients without aura and 20 healthy right-handed, age and sex
matched volunteers were included in the study. Each subject underwent
transcranial magnetic stimulation and was submitted to the following:
determination of resting motor threshold (rMT), silent period (SP), MEP
input-output curves, phosphene threshold (PT). RESULTS: Patients had lower rMT,
shorter SP, and increased MEP recruitment compared with control group. There was 
an increased prevalence of phosphene (85%) as well as lower PT (63% of the
stimulator output) in migraineurs compared with control group (75%, and 72%,
respectively). There was a significant negative correlation between duration of
attacks and PT (P = 0.02). No significant differences between patients with aura 
and without aura in different parameters of cortical excitability. CONCLUSION:
Our findings confirm that the motor and visual cortexes are hyperexcitable and
this appears partly to be consequent upon a failure of inhibitory circuits.

PMID: 16530139 [PubMed - indexed for MEDLINE]

1342: Br Dent J. 2006 Mar 11;200(5):283-6; discussion 269.

Fitting acrylic occlusal splints and an experimental laminated appliance used in 
migraine prevention therapy.

Barnes MF, Geary JL, Clifford TJ, Lamey PJ.

Department of Oral Surgery Oral Medicine Oral Pathology, School of Dentistry,
Grosvenor Road, Queen's University Belfast.

OBJECTIVE: To evaluate clinical procedures and chair time required to seat and
adjust hard, heat-cured acrylic occlusal splints and an alternative laminated
appliance developed to simplify construction of migraine prevention appliances.
DESIGN AND SETTING: Single-centre study in the Oral Medicine Clinic, The Royal
Hospitals, Belfast, Northern Ireland. METHOD: Questionnaires were distributed,
January-May 2003, to operators fitting occlusal splints for 100 consecutive
patients selected for migraine prevention therapy. Half the appliances were made 
in heat-polymerised acrylic with the remainder using a novel combination of
ethylene vinyl acetate and light-curing urethane dimethacrylate. Information on
operator experience, the nature of any fitting surface and occlusal adjustments
together with an estimate of the time taken to make alterations was recorded. KEY
FINDINGS: The need for adjustment to seat appliances intraorally was
significantly less for migraine prevention appliances made using an experimental 
laminating technique. Where modifications were necessary, there was no
significant difference in the chair time required to fit either the heat-cured
hard or experimental laminated migraine prevention appliance. CONCLUSION:
Provision of migraine prevention appliances may be more time efficient if the
dental practitioner considers a laminated approach to construction.

PMID: 16528336 [PubMed - indexed for MEDLINE]

1343: Curr Neurol Neurosci Rep. 2006 Mar;6(2):106-15.

Migraine-related vertigo: diagnosis and treatment.

Eggers SD.

Department of Neurology, Mayo Clinic, 200 1st Street SW, Rochester, MN 55905,
USA. eggers.scott@mayo.edu

A comprehensive review of the neurotologic manifestations of migraine is
presented, focusing on the most recent publications regarding the epidemiology,
clinical presentation, pathophysiology, diagnosis, and management of
migraine-related vertigo (MV). A strong association exists between vertigo and
migraine, with MV being the most common cause of spontaneous (nonpositional)
episodic vertigo. Symptoms can be quite variable among patients and within
individual patients over time, creating a diagnostic challenge. MV generally
presents with attacks of spontaneous or positional vertigo lasting seconds to
days with associated migrainous symptoms. Operational diagnostic criteria have
been proposed but are not included in the most recent International Headache
Society classification of migraine. Better elucidation of the neurologic linkages
between the central vestibular pathways and migraine-related pathways and the
discovery of ion channel defects underlying some causes of familial migraine,
ataxia, and vertigo have furthered the understanding of MV pathophysiology.
Treatment of MV currently parallels that of migraine headache, as proper studies 
of optimal MV management are just beginning.

Publication Types: 
    Review

PMID: 16522263 [PubMed - indexed for MEDLINE]

1344: Curr Neurol Neurosci Rep. 2006 Mar;6(2):95-9.

Migraine headache prophylaxis: current options and advances on the horizon.

Ramadan NM.

Rosalind Franklin University of Medicine and Science, 3333 Green Bay Road, North 
Chicago, Il 60064, USA. nabih.ramadan@rosalindfranklin.edu

Migraine is increasingly recognized as a disorder of altered neuronal
excitability, in part based on genetically mediated and environmentally modified 
aberrations of ionic exchange across the brain neuronal membrane. To this end,
migraine pharmacotherapy aids in restoring the abnormally low threshold for
neuronal excitation. Indeed, modulation of neuronal excitability is a common
property of several established migraine preventive drugs such as propranolol,
valproate, amitriptyline, and topiramate. Future migraine preventive
pharmacologic therapies likely will aim at restoring the neuronal threshold for
excitation by targeting such processes as cortical spreading depression and
intracellular calcium influx. Also, strategies aimed at enhancing descending
antinociceptive inhibition will yield effective antimigraine drugs.

Publication Types: 
    Review

PMID: 16522261 [PubMed - indexed for MEDLINE]

1345: Neurosci Lett. 2006 May 29;400(1-2):86-91. Epub 2006 Mar 3.

Cerebrovascular dynamics in patients with migraine: near-infrared spectroscopy
study.

Akin A, Bilensoy D, Emir UE, Gülsoy M, Candansayar S, Bolay H.

Institute of Biomedical Engineering, Boĝaziçi University, Bebek, Istanbul 34342, 
Turkey.

Migraine is hypothesized to be a neurovascular coupling disorder where the
cerebral vascular reactivity is malfunctioning and measuring hemodynamic changes 
during migraine without causing more disturbance has always been a challenge.
Functional near infrared spectroscopy system (fNIRS) is being proposed as an
inexpensive, rapid, safe and accurate alternative to fMRI, transcranial doppler
sonography (TCD). We have developed NIROXCOPE 201, a novel device for fNIRS which
offers 16 source-detector pairs distributed on a probe that is placed on the
forehead. Measuring hemodynamic changes during migraine without causing more
disturbance has always been a challenge. Using NIROXCOPE 201, we have attempted
to investigate the cerebrovascular reactivity of migraine patients to a breath
hold task which produces a metabolic perturbation. Six normals and six migraine
patients performed four consecutive breath holding task. We calculated the peak
and latencies of the initial dip and recovery phases for [Hb], [HbO(2)], [tHb],
and [OXY] signals. [Hb], [tHb], and [OXY] ID and R amplitudes of normals are
approximately a magnitude higher than migraine patients (P<0.01), while latencies
showed no significant differences. Data suggests an altered neurovascular
coupling in frontal cortex of migraine patients interictally. The application of 
NIROXCOPE 201 to patients suffering from other primary headache disorders will
reveal diagnostic as well as therapeutic implications of the presented study.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 16516381 [PubMed - indexed for MEDLINE]

1346: Am J Med Genet B Neuropsychiatr Genet. 2006 Apr 5;141B(3):257-60.

Haplotype-based systematic association studies of ATP1A2 in migraine with aura.

Netzer C, Todt U, Heinze A, Freudenberg J, Zumbroich V, Becker T, Goebel I,
Ohlraun S, Goebel H, Kubisch C.

Institute of Human Genetics, University of Cologne, Cologne, Germany.

Mutations in ATP1A2 cause familial hemiplegic migraine (FHM) type 2, a rare
monogenic form of migraine with aura (MA). Moreover, rare ATP1A2 missense
variants are found in familial clustering of common forms of migraine in single
pedigrees. To determine whether also common ATP1A2 polymorphisms contribute to MA
pathogenesis, we performed systematic case-control association studies in 284 MA 
cases and 241 control individuals. By direct sequencing of the 23 coding exons
and adjacent intronic regions in 45 MA patients, 16 polymorphisms (12 SNPs, 3
small indels, 1 microsatellite marker) were identified. The sequencing results
were used to estimate seven common ATP1A2 haplotypes (with a frequency >5%)
covering about 97% of total haplotype diversity for this region. Subsequently,
six haplotype-tagging SNPs/polymorphisms were genotyped in 95 individuals with a 
family history of MA, in 189 individuals with sporadic MA, and in a
gender-matched control sample. A haplotype analysis was performed using the
program FAMHAP. No significant differences in the ATP1A2 haplotype distribution
could be detected between MA patients (or patient subgroups) and the control
group. In a single-marker analysis the allele and genotype frequencies of ATP1A2 
polymorphisms between cases and controls were compared. Neither the six ht-SNPs
nor a single allele of the microsatellite marker were significantly associated
with MA. In summary, we found no evidence for a common contribution of ATP1A2 to 
the pathogenesis of complex inherited MA. Copyright 2006 Wiley-Liss, Inc.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16508935 [PubMed - indexed for MEDLINE]

1347: Am J Med Genet B Neuropsychiatr Genet. 2006 Apr 5;141B(3):250-6.

The CACNA1A and ATP1A2 genes are not involved in dominantly inherited migraine
with aura.

Kirchmann M, Thomsen LL, Olesen J.

Department of Neurology, Danish Headache Center, Glostrup Hospital, University of
Copenhagen, Copenhagen, Denmark. kirchmann@dadlnet.dk

Epidemiological studies indicate that migraine with typical aura (MA) has a major
genetic component but the genes for MA have not been identified. However, the
autosomal dominantly inherited familial hemiplegic migraine (FHM) is often caused
by mutations in the CACNA1A or ATP1A2 genes. The aim of the study was to
investigate if the CACNA1A or ATP1A2 genes are involved in MA with an apparently 
autosomal dominant mode of inheritance. From a clinic population diagnosed by a
trained physician we recruited 34 extended families (comprising 174 MA patients) 
with an apparently autosomal dominant mode of inheritance of MA. We performed a
linkage analysis of 161 of 174 MA patients and 79 unaffected relatives using a
framework marker set of 44 markers for chromosome 1 and 22 markers for chromosome
19. Linkage analysis was made with a non-parametric or autosomal dominant
parametric model, either allowing for heterogeneity or not, using an affected
only analysis. We identified no linkage to CACNA1A and ATP1A2 loci on chromosome 
19 or 1, respectively. Additionally, at least two patients from each family and
92 healthy, unrelated controls were selected for a sequence analysis. We
sequenced the 48 exons of CACNA1A and the 23 exons of ATP1A2, including promoter 
and flanking intron sequences. No polymorphism was identified in the CACNA1A or
ATP1A2 genes with a strong correlation to MA. Our study shows that the CACNA1A or
ATP1A2 genes are probably not involved in MA. To identify the genes involved in
the common forms of migraine, future genetic studies should focus on MA and
migraine without aura (MO) and not FHM. Copyright 2006 Wiley-Liss, Inc.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16508934 [PubMed - indexed for MEDLINE]

1348: Pharmacotherapy. 2006 Jan;26(1):115-28.

Safety and efficacy of eletriptan in the treatment of acute migraine.

Takiya L, Piccininni LC, Kamath V.

Department of Pharmacy Practice and Pharmacy Administration, Philadelphia College
of Pharmacy, University of the Sciences in Philadelphia, 600 South 43rd Street,
Philadelphia, PA 19104, USA. l.takiya@usip.edu

Eletriptan is a new selective serotonin agonist approved for the treatment of
acute migraine headaches. To review the pharmacologic, pharmacodynamic,
pharmacokinetic, safety, and clinical efficacy data for eletriptan, we searched
the literature in PubMed/MEDLINE, EMBASE, International Pharmaceutical Abstracts,
and Science Direct databases to gather all published reports from January
1996-October 2004. All English-language reports (abstract or full trial reports) 
about the pharmacology, pharmacokinetics, clinical efficacy, and safety of
eletriptan were reviewed. Eletriptan's pharmacokinetic and pharmacodynamic
parameters translate into a favorable safety and efficacy profile. The drug is
rapidly absorbed when administered orally, has good bioavailability and central
nervous system penetration due to its lipophilicity, and has a long half-life,
which contributes to its ability to prevent recurrent headaches. Compared with
other serotonin agonists, eletriptan has a longer duration of action and greater 
lipophilicity. Eletriptan is metabolized through the cytochrome P450 3A4 system; 
therefore, it does have the potential for clinically significant drug
interactions. In clinical trials, eletriptan demonstrated efficacy superior to
that of placebo and similar or superior efficacy to that of other serotonin
agonists, with limited adverse effects. With clinical use, headache and pain-free
responses and headache recurrence rates were similar to those of other serotonin 
agonists, but the agent is superior to ergotamine tartrate-caffeine. Based on
pharmaco-economic data, eletriptan is more cost-effective than other agents in
its class. Eletriptan is a safe and cost-effective option for the treatment of
migraine headaches.

Publication Types: 
    Review

PMID: 16506353 [PubMed - indexed for MEDLINE]

1349: Thromb Res. 2007;119(2):217-22. Epub 2006 Feb 28.

Altered hemostasis in migraineurs studied with a dynamic flow system.

Tietjen GE, Al-Qasmi MM, Athanas K, Utley C, Herial NA.

Department of Neurology, Medical University of Ohio, Toledo, OH 43614, USA.
gtietjen@meduohio.edu

INTRODUCTION: Livedo reticularis (LR) refers to the violaceous netlike pattern of
skin related to arteriopathy at the dermis-subcutis border. Livedo is associated 
with migraine, and among migraineurs, LR is more common in those with prior
stroke. Other evidence of vascular perturbation in migraine comes from studies
showing elevated von Willebrand factor (vWF). The purpose of this study is to
evaluate global hemostasis in migraineurs, including the subset with LR, using a 
dynamic flow system simulating physiological conditions, and measuring vWF
activity and antigen levels. MATERIALS AND METHODS: Patients with migraine were
enrolled from the headache clinic and presence or absence of LR was noted.
Age-matched healthy, non-migraine, LR-free individuals were recruited as
controls. To evaluate hemostasis, we used the Clot Signature Analyzer (CSA)
measuring platelet hemostasis time (PHT), collagen-induced thrombus formation
(CITF), and clot time (CT). vWF activity and vWF antigen levels were also
measured. RESULTS: The mean vWF activity level (142.7 vs. 103.4, p<0.01) and
antigen level (132.1 vs. 104.5, p<0.05) were higher, and all three hemostasis
parameters shorter in the episodic migraineurs than in the controls. The subset
of migraineurs with LR had the highest vWF activity (155+/-59, p<0.05) and vWF
antigen (141+/-43, p<0.05) levels, and the shortest PHT (3.7+/-1.6, p<0.05). In
this subset there was a significant inverse correlation between vWF activity and 
PHT (r=-0.51, p=0.01). CONCLUSIONS: For migraineurs, the differences from
controls in vWF and PHT are most robust in the LR subset, with the inverse
correlation suggesting that endothelial perturbation may be causally related to
the response of the platelets.

PMID: 16504253 [PubMed - indexed for MEDLINE]

1350: BMC Med Genet. 2006 Feb 28;7:12.

No role for estrogen receptor 1 gene intron 1 Pvu II and exon 4 C325G
polymorphisms in migraine susceptibility.

Colson NJ, Lea RA, Quinlan S, Griffiths LR.

Genomics Research Centre, School of Health Science, Griffith University Gold
Coast, PMB 50, Gold Coast Mail Centre, Queensland, 9726, Australia.
n.colson@griffith.edu.au

BACKGROUND: We have previously reported an association between the estrogen
receptor 1 (ESR1) gene exon 8 G594A polymorphism and migraine susceptibility in
two independent Australian cohorts. In this paper we report results of analysis
of two further single nucleotide polymorphisms (SNPs) in the ESR1 gene in the
same study group, the T/C Pvu II SNP in intron 1 and the C325G SNP in exon 4, as 
well as results of linkage disequilibrium (LD) analysis on these markers.
METHODS: We investigated these variants by case-control association analysis in a
cohort of 240 migraineurs and 240 matched controls. The SNPs were genotyped using
specific restriction enzyme assays. Results were analysed using contingency table
methods incorporating the chi-squared statistic. LD results are presented as D'
statistics with associated P values. RESULTS: We found no evidence for
association of the Pvu II T/C polymorphism and the C325G polymorphism and
migraine susceptibility and no evidence for LD between these two SNPs and the
previously implicated exon 8 G594A marker. CONCLUSION: We have found no role for 
the polymorphisms in intron 1 and exon 4 with migraine susceptibility. To further
investigate our previously implicated exon 8 marker, we suggest the need for
studies with a high density of polymorphisms be undertaken, with particular focus
on markers in LD with the exon 8 marker.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16504171 [PubMed - indexed for MEDLINE]

1351: Pharmacotherapy. 2006 Mar;26(3):375-87.

Topiramate for migraine prevention.

Wenzel RG, Schwarz K, Padiyara RS.

Diamond Headache Clinic Inpatient Unit, Chicago, Illinois 60613, USA.
rwenz@hotmail.com

Migraine is a costly, recurrent condition that affects 28 million individuals in 
the United States yet remains underdiagnosed and undertreated. In 2004, the U.S. 
Food and Drug Administration approved topiramate for the prevention of migraine
in adults, joining three other agents with this indication: divalproex sodium,
propranolol, and timolol. We evaluated the role of topiramate in the treatment of
migraine based on published literature and our clinical experiences. A
qualitative systematic search of the literature from January 1966-December 2004
was conducted by using MEDLINE, and other pertinent literature was reviewed.
Three large, randomized, placebo-controlled trials of topiramate for migraine
prevention in individuals experiencing 3-12 attacks/month have been published, as
have several small studies and a comparator trial with propranolol. Based on the 
results of these studies, 100 mg/day is the optimum topiramate dosage in terms of
efficacy and tolerability. Using that dosage, the number of migraine
attacks/month decreased by approximately two. Several other secondary outcome
measures were also significantly reduced including the number of days/month with 
migraine and the use of acute treatment/attack. Suboptimal efficacy was shown
with 50 mg/day, whereas 200 mg/day caused considerably more tolerability issues. 
Paresthesia was dose related and the most common cause of attrition. Cognitive
dysfunction and weight loss were also commonly reported. The reduction by two
migraines/month demonstrated with topiramate in clinical trials is similar to the
published results for other preventive agents, though most of those studies were 
small, antiquated, and poorly designed. In contrast, the topiramate trials
enrolled a larger number of patients and closely adhered to the International
Headache Society research recommendations, strengthening the quality of results. 
Topiramate 100 mg/day is an effective option in adults who require migraine
prophylaxis. Although the published efficacy results of the various migraine
preventive agents are comparable, the superior study design of the topiramate
trials warrants consideration of topiramate as an agent of choice for migraine
prevention. Future studies of any preventive agent should include more refined
quality-of-life outcomes.

Publication Types: 
    Review

PMID: 16503717 [PubMed - indexed for MEDLINE]

1352: Optom Vis Sci. 2006 Feb;83(2):82-7.

The correlation between migraine headache and refractive errors.

Harle DE, Evans BJ.

The Neville Chappell Research Clinic, The Institute of Optometry, London, UK.
dharle@ioo.org.uk

PURPOSE: A literature review reveals historical references to an association
between migraine headache and refractive errors, but a lack of scientific
evidence relating to these claims. METHODS: In a masked case-controlled study, we
investigated the four aspects of refractive errors that have been implicated in
the literature as correlated with migraine: spherical refractive error,
astigmatic refractive error, anisometropia, and uncorrected ametropia. We also
compared the calculated scalar value of refractive error, aided and unaided
visual acuity, and spectacle use in migraine and control groups. We then
investigated the relationship between refractive components and key migraine
headache variables. RESULTS: Compared with the control group, the migraine group 
had higher degrees of astigmatic components of refractive error assessed both
objectively (C, p = 0.01; C(0), p = 0.01; C(45), p = 0.05) and subjectively (C, p
= 0.03; C(0), p = 0.03; C(45), p = 0.05), uncorrected astigmatic components of
refractive error (C(0), p = 0.02; C(45), p = 0.04), and anisometropia (p = 0.06).
CONCLUSIONS: Perhaps the historical literature is indeed correct that low degrees
of astigmatism and anisometropia are relevant in migraine. Our most significant
finding was of higher degrees of astigmatism in the migraine group. This study
does indicate that people who experience migraine headaches should attend their
optometrist regularly to ensure that their refractive errors are appropriately
corrected.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 16501409 [PubMed - indexed for MEDLINE]

1353: Stroke. 2006 Apr;37(4):1109-12. Epub 2006 Feb 23.

Brain stem and cerebellar hyperintense lesions in migraine.

Kruit MC, Launer LJ, Ferrari MD, van Buchem MA.

Department of Radiology, Leiden University Medical Center, PO Box 9600, The
Netherlands. m.c.kruit@lumc.nl

BACKGROUND AND PURPOSE: Migraineurs are at increased risk of cerebellar infarcts 
and supratentorial white matter lesions. The prevalence, frequency, and
distribution of infratentorial hyperintense lesions in migraine are unknown.
METHODS: Migraineurs with aura (n=161), without aura (n=134), and controls
(n=140) from a population-based sample of adults (30 to 60 years of age) were
evaluated with MRI. RESULTS: Infratentorial hyperintensities were identified in
13 of 295 (4.4%) migraineurs and in 1 of 140 (0.7%) controls (P=0.04). Twelve
cases had hyperintensities, mostly bilaterally, in the dorsal basis pontis. Those
with infratentorial hyperintensities also had supratentorial white matter lesions
more often. CONCLUSIONS: We found an increased prevalence of infratentorial
(mostly pontine) hyperintensities in migraineurs from the general population.
This extends the knowledge about vulnerable brain regions and type of lesions in 
migraine brains. A hemodynamic ischemic pathogenesis is likely, but further
research is needed.

Publication Types: 
    Research Support, N.I.H., Intramural
    Research Support, Non-U.S. Gov't

PMID: 16497982 [PubMed - indexed for MEDLINE]

1354: Pain. 2006 Jul;123(1-2):10-8. Epub 2006 Feb 21.

Comment in:
    Pain. 2006 Jul;123(1-2):1-2.

Quantitative sensory testing in children with migraine: preliminary evidence for 
enhanced sensitivity to painful stimuli especially in girls.

Zohsel K, Hohmeister J, Oelkers-Ax R, Flor H, Hermann C.

Department of Neuropsychology and Clinical Psychology at the University of
Heidelberg, Central Institute of Mental Health, Mannheim, Germany.

Recent studies showed an enhanced general sensitivity to painful stimuli in adult
migraineurs during as well as between attacks. Yet, the influence of a prolonged 
pain history and potential sex differences has not been studied. We used
quantitative sensory testing to examine 25 children with migraine between attacks
and 28 controls (age 9-15). The assessment included the measurement of heat and
mechanical pain thresholds as well as measures of perceptual sensitization in
response to repetitive (mechanical) or tonic (thermal) noxious stimulation at
both trigeminal and thenar sites. In addition, the mother was either present or
absent during the measurements. Heat pain thresholds were not significantly
different between the two groups. However, the child migraineurs showed
significantly lower mechanical pain thresholds. Children and especially girls
with migraine displayed significantly more sensitization to a tonic heat stimulus
at the trigeminal site when the mother was present. The migraineurs also showed a
trend towards higher sensitization ratings for mechanical stimuli. Overall, heat 
pain thresholds were significantly higher in the presence of the mother. In the
migraine group only, mechanical pain thresholds were significantly higher when
the mother was present. To summarize, an enhanced sensitivity to painful stimuli 
can already be observed in children suffering from migraine for an average
duration of 4.4 years. This may be the result of sensitization in nociceptive
pain pathways caused by frequent pain experiences. Girls with migraine were more 
prone to such sensitization, which may increase their risk for continuing to
suffer from migraine throughout adulthood.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 16495010 [PubMed - indexed for MEDLINE]

1355: Int J Clin Pract. 2006 Mar;60(3):295-9.

Company reference estimates for productivity loss due to migraine and
productivity gains using rizatriptan 10 mg in Germany.

Yoon MS, Katsarava Z, Liedert B, Krobot KJ, Diener HC, Limmroth V.

Department of Neurology, University Hospital Essen, Hufelandstr 55, Essen,
Germany.

The prevalence of migraine in Germany is up to 14% in the female and up to 8% in 
the male population and peaks between the age of 35 and 45. Few studies have
investigated the productivity loss and resulting costs attributable to migraine
in Germany or addressed the question whether these costs can be reduced by
optimal treatment. In recent years, 5-HT(1B/D) agonists (so-called triptans), a
generation of drugs highly specific for migraine treatment, have been introduced.
Seven 5-HT(1B/D) agonists have been approved in Germany with more than 20 dosage 
forms. We present a model that enables employers to estimate the annual cost of
migraine and the annual cost that could be saved by treatment of migraine with
rizatriptan compared with the use of non-specific antimigraine medication. A
representative German company with 10,000 employees is used for the reference
case analysis. This company is predicted to have 580 female and 284 male
employees with migraine. These employees are estimated to lose 6992 workdays or
31.8 person years of productive effort annually due to migraine, valued
approximately 1,431,719 euros. The value of work loss that could be avoided by
treating migraine with rizatriptan is estimated at 619,094 euros annually. These 
data indicate that costs arising from lost productivity can be reduced by
treating migraine headaches with a triptan.

PMID: 16494644 [PubMed - indexed for MEDLINE]

1356: Headache. 2006 Feb;46(2):322-6.

Headache disability in orofacial pain patients.

Dando WE, Branch MA, Maye JP.

Orofacial Pain Center, Naval Postgraduate Dental School, National Naval Medical
Center, Bethesda, MD 20889, USA.

OBJECTIVE: To retrospectively examine the reported history of and the disability 
caused by headaches in patients presenting for evaluation and treatment of
orofacial pain. BACKGROUND: More than 81% of patients with the chief complaint of
pain in the orofacial region concomitantly report pain in other body locations.
Among the comorbidities frequently reported with orofacial pain are a variety of 
different headaches types, including migraines, tension type headaches, and
chronic daily headaches. The extent of the disability caused by those headache
complaints in a large patient population is unknown. METHODS: The Migraine
Disability Assessment (MIDAS) is administered to all patients as a part of the
initial assessment at the Orofacial Pain Center. This investigation is
retrospectively examined the reported history of and the disability caused by
headaches in patients who presented for evaluation and treatment of orofacial
pain in the Orofacial Pain Center, National Naval Medical Center, Bethesda, MD,
between the dates of 1 September 2003 and 1 December 2004. RESULTS: In the
present study 261 (61.3%) patients reported a headache complaint and 100 (38%)
fulfilled the criteria for migraine with or without aura. MIDAS scores were
reported by 55.3% of 426 patients with the mean score of 23.68. There were no
significant differences in MIDAS scores in relation to the presence or absence of
an intracapsular disorder. Patients with masticatory and/or cervical myalgia
demonstrated significantly higher MIDAS scores when compared to patients without 
myalgia. CONCLUSIONS: These findings clearly demonstrate the necessity for
evaluation of headache and related disability in orofacial pain patients.

PMID: 16492243 [PubMed - indexed for MEDLINE]

1357: Headache. 2006 Feb;46(2):317-21.

Investigating the association between Notch3 polymorphism and migraine.

Borroni B, Brambilla C, Liberini P, Rao R, Archetti S, Venturelli E, Gipponi S,
Caimi L, Padovani A.

Neurologic Clinic, Department of Neurology, University of Brescia, Italy.

OBJECTIVE: The aim of the present study was to evaluate whether the functional
Notch3 polymorphism T6746C, which is not causative for cerebral autosomal
dominant arteriopathy with subcortical infarcts and leukoencephalopathy
(CADASIL), might be a risk factor for migraine. BACKGROUND: It has been recently 
demonstrated that migraine is characterized by subclinical brain infarctions and 
white matter lesions. Several genetic risk factors have been associated with
migraine, but no study has unraveled a possible relationship between migraine and
Notch3, which is involved in vascular damage. Mutations in Notch3 gene have been 
demonstrated to be pathogenetic for CADASIL, a small vessel disease of the brain 
characterized by migraine. METHODS: A total of 156 migraine patients and 128
nonheadache healthy volunteers entered the study. Demographic and clinical
characteristics were carefully recorded, and a neurological work-up was
performed. Moreover, each subject underwent a blood sampling for Notch3 genotype 
determination. RESULTS: Notch3 genotypes as well as allele frequencies did not
differ in migraine patients compared to controls, even adjusting for the presence
of possible confounds. No difference has been found either in migraine patients
with aura or in those without aura. CONCLUSIONS: These findings support the view 
that functional polymorphism T6746C in Notch3 gene is not involved in increasing 
the risk of migraine or migraine subtypes.

PMID: 16492242 [PubMed - indexed for MEDLINE]

1358: Headache. 2006 Feb;46(2):312-6.

Migraine in the elderly: a comparison with migraine in young adults.

Martins KM, Bordini CA, Bigal ME, Speciali JG.

School of Medicine at Ribeirão Preto, Neurology, Psychiatry and Medical
Psychology, SP, Brazil.

OBJECTIVE: In this study we compare the clinical features of migraine attacks
occurring in the elderly (60 to 70 years) and in younger migraineurs (20 to 40
years). BACKGROUND: Studies comparing the clinical features of migraine at
different ages are still lacking. These studies are important for a better
comprehension of the natural history of migraine, as well as to refine our
recognition of the disease. METHODS: We retrospectively assessed subjects seen
from 1995 to 2000 in a university-based outpatient headache clinic in Brazil. We 
reviewed 144 charts from patients 60 to 70 years (mean = 66.4). We applied a
questionnaire based on the first edition of the International Classification of
Headache Disorders (criteria for episodic migraine remained unchanged in the
second edition). Controls were migraineurs from 20 to 40 years (mean = 32.6).
RESULTS: Migraine occurred in 25% of the elderly and 29% of younger migraineurs
(NS). A lower proportion of migraine attacks in the elderly were unilateral (38% 
vs. 57%, P < .01), or with associated symptoms (nausea = 75% vs. 86%, P = .05;
vomiting = 30% vs. 54%, P < .05, photophobia and phonophobia = 83% vs. 94%, P <
.05). Other symptoms such as paleness (P = .0441), dry mouth (P = .0093), and
anorexia (P = .05) were more common in the elderly. CONCLUSION: Migraine is less 
typical in the elderly and more frequently associated with vegetative symptoms.
Therefore, the diagnosis of migraine in elderly subjects may be more challenging,
and many seniors with this primary headache can be misdiagnosed.

Publication Types: 
    Comparative Study

PMID: 16492241 [PubMed - indexed for MEDLINE]

1359: Headache. 2006 Feb;46(2):286-97.

Implications of clinical subtypes of migraine with aura.

Eriksen MK, Thomsen LL, Olesen J.

Danish Headache Center, Department of Neurology, University of Copenhagen,
Glostrup Hospital, Denmark.

OBJECTIVE: To compare the clinical characteristics of familial hemiplegic
migraine (FHM), sporadic hemiplegic migraine (SHM), and nonhemiplegic migraine
with aura (NHMA) and further, to compare subtypes of NHMA. BACKGROUND: To
discover distinct underlying genetic and pathophysiological mechanisms it is
crucial to drive clinical subdivision of migraine with aura as far as possible.
The documentation of subtypes of migraine with aura depends on the clinical
characteristics as the genetic mechanisms are unknown except for the dominantly
inherited FHM. METHODS: Patients with FHM, SHM, or familial NHMA were recruited
from specialist practice and diagnosed according to the International
Classification of Headache Disorders (ICHD) in a validated interview by a
physician. Patients with hemiplegic migraine had a physical and neurological
examination. Patients with population-based NHMA from a previous Danish study
were used for comparison. RESULTS: We recruited 147 patients with FHM, 105 with
SHM, and 362 with familial NHMA. FHM and SHM had similar aura and headache
characteristics. Patients with FHM and SHM were more likely to experience two or 
more aura symptoms (100% vs. 31%, P < .0001), they more often had prolonged aura 
symptoms, they almost always had a headache associated with the aura (93% vs.
58%, P < .0001), and they more frequently had basilar-type symptoms (69% vs. 10%,
P < .0001) than patients with population-based NHMA. Patients with familial NHMA 
were more likely to experience two or more aura symptoms than patients with
population-based NHMA (61% vs. 32%, P < .0001). Within the subtypes of NHMA,
patients with typical aura with migraine headache had an earlier age at onset (20
+/- 10 vs. 23 +/- 13 years, P= .044) and a higher co-occurrence of migraine
without aura (43% vs. 22%, P= .002) than patients with typical aura with
nonmigraine headache. CONCLUSIONS: The present study proves that distinct
subtypes of migraine with aura exist. It further underlines the phenotypic
differences between the different subtypes of migraine with aura which likely are
caused by different etiological mechanisms. In future studies FHM, SHM, and NHMA 
therefore should be analyzed as separate entities and patients with NHMA may be
stratified by ICHD-2 subtype of NHMA.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 16492238 [PubMed - indexed for MEDLINE]

1360: Headache. 2006 Feb;46(2):264-75.

Rofecoxib in the acute treatment of migraine: a randomized controlled clinical
trial.

Saper J, Dahlof C, So Y, Tfelt-Hansen P, Malbecq W, Loeys T, Barraclough E,
Klipfel M, Lines C, Visser H, Reines S, Yuen E; Rofecoxib Protocol 162 Study
Group.

Michigan Head Pain & Neurological Institute, Ann Arbor, USA.

OBJECTIVE: To investigate the efficacy, tolerability, and safety of rofecoxib and
ibuprofen for acute migraine treatment. BACKGROUND: Rofecoxib was effective and
well tolerated in a previous study of treatment of a single migraine attack. We
sought to replicate these findings for a single attack and also study the
clinical profile of rofecoxib in the acute treatment of multiple migraine
attacks. Ibuprofen was included as a reference nonselective NSAID. METHODS: Adult
migraineurs (n = 783) treated one migraine attack with either rofecoxib (25 or 50
mg), ibuprofen 400 mg, or placebo in a randomized, double-blind study. Patients
could elect to enroll in a 3-month double-blind extension phase. RESULTS: In the 
single-attack phase, headache relief at 2 hours postdose was reported by 59.4%,
62.2%, and 57.7% of patients who took rofecoxib 25 mg, rofecoxib 50 mg, and
ibuprofen 400 mg, respectively, versus 30.5% for placebo (all P < .001 vs
placebo). The active drugs were statistically superior to placebo on a variety of
additional measures. In the extension phase, the mean percentage of patients'
attacks with headache relief at 2 hours postdose was 61.8% for rofecoxib 25 mg,
65.4% for rofecoxib 50 mg, and 59.3% for ibuprofen 400 mg. The mean percentage of
patients' attacks with 24-hour sustained headache relief was greater for
rofecoxib 50 mg (52.0%) than for rofecoxib 25 mg (47.8%, P < .050) or ibuprofen
(39.0%, P < .010). In the single-attack phase, the adverse event rate was higher 
for rofecoxib 50 mg (37.8%) than placebo (27.8%, P < .050); rates were similar to
placebo for rofecoxib 25 mg (32.0%, n.s.) and ibuprofen 400 mg (28.1%, n.s.). In 
the extension phase, treatment groups had similar adverse event rates.
CONCLUSIONS: Rofecoxib 25 and 50 mg and ibuprofen 400 mg were effective and
generally well tolerated in the acute treatment of migraine.

Publication Types: 
    Comparative Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 16492236 [PubMed - indexed for MEDLINE]

1361: Headache. 2006 Feb;46(2):253-8.

Use of the ID Migraine questionnaire for migraine in TMJ and Orofacial Pain
Clinic.

Kim ST, Kim CY.

TMJ and Orofacial Pain Clinic, Department of Oral Medicine, College of Dentistry,
Yonsei University, Seoul, Korea.

OBJECTIVE: The aim of this study was to determine whether the ID Migraine
questionnaire could be applied successfully to assess the migraine patients in
TMJ and Orofacial Pain Clinic. BACKGROUND: As migraine pain represents a
substantial personal and social burden worldwide, there has been a great deal of 
effort in developing a screening instrument for migraine. METHODS: Each subject
completed a self-administered screening questionnaire consisting of nine items.
Based on the International Headache Society criteria, the clinical diagnosis of
migraine was assigned. The sensitivity and specificity of the individual items
were evaluated. An analysis of the data was performed using the SAS (Statistical 
Analysis System) V8.01. RESULTS: This study found that nausea, photophobia, and
headache-related disability had the highest individual sensitivities and
specificities, and the performance of the three-item screener was equivalent to
that reported in a previous study. Although the sensitivity of the three-item
screener in this study (0.58) was lower than in a previous study (0.81), the
specificity (0.98) was higher and the positive predictive value was 93.9%. This
suggests that the ID Migraine questionnaire is relatively efficient in this
setting. CONCLUSION: The ID Migraine questionnaire, which is a three-item
screener consisting of nausea, photophobia, and headache-related disability,
could be used as a self-administered report for detecting migraine headaches in
patients with temporomandibular disorders and orofacial pain.

PMID: 16492234 [PubMed - indexed for MEDLINE]

1362: Headache. 2006 Feb;46(2):240-52.

Validation of the revised Patient Perception of Migraine Questionnaire: measuring
satisfaction with acute migraine treatment.

Revicki DA, Kimel M, Beusterien K, Kwong JW, Varner JA, Ames MH, Mahajan S, Cady 
RK.

Center for Health Outcomes Research, MEDTAP Institute at UBC, Bethesda, MD 20814,
USA.

OBJECTIVE: To evaluate the psychometric properties of the revised Patient
Perception of Migraine Questionnaire (PPMQ-R), which measures satisfaction with
migraine treatment. BACKGROUND: The original version of the PPMQ was developed
prior to the introduction of newer migraine treatments, which may have attributes
that influence treatment satisfaction. METHODS: Literature review, patient focus 
groups, and one-on-one patient interviews guided revisions to the original PPMQ. 
The revised questionnaire was tested in 200 migraine patients visiting
neurologists and primary care clinics. At baseline, all subjects completed the
PPMQ-R, a migraine-specific quality-of-life measure, and a migraine experience
questionnaire; and 125 subjects completed assessments 24 hours after each
migraine attack and within 30 days post-baseline. Factor analysis was performed
to inform the development of a scoring algorithm, and reliability, validity, and 
responsiveness of the PPMQ-R were evaluated. RESULTS: Factor analyses confirmed
that the revised questionnaire has five domains measuring satisfaction with
efficacy, functionality, ease of use, medication cost, and bothersomeness of
medication side effects. A total score can be created by taking the average of
efficacy, functionality, and ease of use scores. The PPMQ-R scale scores and
Total score demonstrated internal consistency reliability (Cronbach's alpha: 0.80
to 0.98) and test-retest reliability (intra-class correlation coefficient: 0.79
to 0.91). Except for the Cost domain, the PPMQ-R scores discriminated among
migraine pain severity levels (all P < .05) and levels of impairment in ability
to work and perform usual activities (all P < .05). Except for the Ease of Use
and Cost domains, mean PPMQ-R scores were significantly higher among patients
with no change in treatment and whose pain improved between two consecutive
migraine attacks (all P < .01). CONCLUSION: The PPMQ-R is a reliable and valid
measure of patient satisfaction with acute migraine treatment in women with
frequent migraine attacks.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Validation Studies

PMID: 16492233 [PubMed - indexed for MEDLINE]

1363: Headache. 2006 Feb;46(2):212-22.

Comment in:
    Headache. 2006 Feb;46(2):195-6.

Sumatriptan nasal spray in adolescent migraineurs: a randomized, double-blind,
placebo-controlled, acute study.

Winner P, Rothner AD, Wooten JD, Webster C, Ames M.

Palm Beach Headache Center, West Palm Beach, FL 33407, USA.

OBJECTIVE: To compare the efficacy and tolerability of sumatriptan nasal spray
(NS) (5, 20 mg) versus placebo in the acute treatment of migraine in adolescent
subjects. BACKGROUND: Currently, no triptan is approved in the United States for 
the treatment of migraine in adolescent subjects (12 to 17 years). In a previous 
randomized, placebo-controlled study of 510 adolescent subjects, sumatriptan NS
at 5, 10, and 20 mg doses was well tolerated. However, the primary efficacy
analysis for headache relief with 20 mg at 2 hours did not demonstrate
statistical significance (P = .059). A second study was initiated to evaluate the
efficacy of sumatriptan NS in this population. METHODS: This was a randomized
(1:1:1), placebo-controlled, double-blind, parallel-group study. Overall, 738
adolescent subjects (mean age: 14 years) with > or = 6-month history of migraine 
(with or without aura) self-treated a single attack of moderate or severe
migraine. The primary endpoints were headache relief at 1 hour and sustained
relief from 1 to 24 hours. Pain-free rates, presence/absence of associated
symptoms, headache recurrence, and use of rescue medications were also assessed. 
Tolerability was based on adverse events (AEs) and vital signs. RESULTS:
Sumatriptan NS 20 mg provided greater headache relief than placebo at 30 minutes 
(42% vs. 33%, respectively; P = .046) and 2 hours (68% vs. 58%; P = .025)
postdose, but did not reach statistical significance at 1 hour (61% vs. 52%; P = 
.087) or for sustained headache relief from 1 to 24 hours (P = .061). Significant
differences (P < .05) in favor of sumatriptan NS 20 mg over placebo were observed
for several secondary efficacy endpoints including sustained relief from 2 to 24 
hours. In general, sumatriptan NS 5 mg percentages were slightly higher than
placebo but the differences did not reach statistical significance. Both doses of
sumatriptan NS were well tolerated. No AEs were serious or led to study
withdrawal. The most common event was taste disturbance (2%, placebo; 19%,
sumatriptan NS 5 mg; 25%, sumatriptan NS 20 mg). CONCLUSIONS: This study suggests
that sumatriptan may be beneficial to some adolescents and is generally well
tolerated in the acute treatment of migraine in this population.

Publication Types: 
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 16492230 [PubMed - indexed for MEDLINE]

1364: Headache. 2006 Feb;46(2):208-11.

Stroke and chest pain in young people with migraine.

Hoffmann M.

Department of Urology, University of South Florida, Tampa 33612, USA.

BACKGROUND: Cerebrovascular and cardiovascular complications in migraineurs may
be part of the migraine process and also consequent to triptan treatment. AIM: To
determine the frequency, subtypes and associations of migraine-associated stroke 
and angina in young people (18-49 years). METHODS: Patients were derived from a
tertiary referral migraine and stroke registry. Migraine-associated stroke was
classified according to the four groups described by Welch and by the TOAST
etiological stroke classification. A clinical description of angina during a
migraine attack was required for the diagnosis of cardiac migraine without
concomitant triptan or other vasoactive medications. RESULTS: Of the young
patients with stroke (349/1316; 26.5%), there were 30 (30/349; 8.6%) who had
migraine at the time of stroke when categorized by the Welch classification type 
II to IV (type II n = 5, type III n = 2, type IV n = 3). Comparison of type I (n 
= 20) versus types II-IV (n = 10) showed significant difference (P = .03).
Topographically the lesions were distributed into the partial anterior
circulation (n = 8) and posterior circulation (n = 2) (P = .04). Comparison of
anterior and posterior circulation territories of infarction indicated
significant difference (n = 26/30 and 4/30; P = .01). The stroke etiological
subtypes included cardiogenic (n = 5), atherogenic (n = 15), other (n = 5), and
unknown (n = 5), with none diagnosed with small-vessel cerebrovascular disease.
Traditional stroke mechanistic entities (cardiac and atherogenic) differed
significantly in comparison to the other and unknown categories P = .05.
Cardiovascular patients with angina during a migraine attack (n = 9/1040; 0.9%), 
included IHS subtypes; migraine without aura (n = 4), migraine with aura (n = 4),
and complicated migraine (n = 1). One patient required cardiac catheterization on
account of significant ECG changes, with documented, reversible vasospasm.
CONCLUSION: (i) Migraine-induced stroke remains controversial, with only two
probable cases of type Welch III A+B in a large registry. (ii) Cardiac migraine
may be a distinct entity requiring careful differentiation from triptan-induced
chest pain.

PMID: 16492229 [PubMed - indexed for MEDLINE]

1365: Headache. 2006 Feb;46(2):200-7.

Proinflammatory cytokines, adhesion molecules, and lymphocyte integrin expression
in the internal jugular blood of migraine patients without aura assessed ictally.

Sarchielli P, Alberti A, Baldi A, Coppola F, Rossi C, Pierguidi L, Floridi A,
Calabresi P.

Neurologic Clinic, Department of Medical Specialties and Public Health,
University of Perugia, Italy.

OBJECTIVE: The aim of the present research was to verify the levels of the
soluble adhesion molecules sL- and sE-selectins, intercellular adhesion molecule 
(sICAM)-1, and vascular cell adhesion molecule-1 in serial samples of internal
jugular venous blood taken from migraine patients without aura (MWoA) during
attacks. The expression of leukocyte function antigen (LFA)-1 and very late
activation antigen (VLA)-4 was also assessed on lymphocytes obtained from jugular
venous blood. Levels of certain proinflammatory cytokines (tumor necrosis
factor-alpha[TNF-alpha], interleukin-1beta[IL-1beta], IL-4, and IL-6) were also
determined and correlated with those of adhesion molecules. PATIENTS AND METHODS:
Seven MWoA patients were admitted in the hospital during attacks and blood
samples were taken immediately after catheter insertion, at 1, 2, and 4 hours
after attack onset, and within 2 hours after its termination. The levels of
adhesion molecules and cytokines were measured with ELISA method. The expression 
of LFA-1 and VLA-4 was assessed by flow cytometry. RESULTS: A parallel transient 
increase of sICAM-1, TNF-alpha, and IL-6 was observed in the first 2 hours after 
attack onset compared with the time of catheter insertion (P < .0001, <.001, and 
<.003, respectively). The proportion of CD4+ and CD8+ T-cells expressing high
levels of LFA-1 showed instead a progressive down-regulation with significantly
lower percentages at 2 and 4 hours after attack onset (P < .01 and <.022,
respectively). No variation in the percentage of VLA-4 expressing cells was
observed at any time of the study. CONCLUSIONS: The transient increase in sICAM-1
and TNF-alpha found in the internal jugular blood of MWoA patients assessed
ictally can be induced by sensory neuropeptides released from activated
trigeminal endings. The progressive decrease in sICAM-1 levels during attacks and
the down-regulation of LFA-1 expression by lymphocytes could antagonize their
transvascular migration, supporting the hypothesis of sterile inflammation in the
dura mater during migraine attacks.

PMID: 16492228 [PubMed - indexed for MEDLINE]

1366: Headache. 2006 Feb;46(2):197-9.

C-reactive protein may be increased in migraine patients who present with complex
clinical features.

Welch KM, Brandes AW, Salerno L, Brandes JL.

Department of Neurology, Rosalind Franklin University of Medicine and Science,
North Chicago, IL 60064, USA.

OBJECTIVES: Stroke risk is increased in migraine, the basis of which remains to
be established. C-reactive protein (CRP) is a marker of cerebrovascular disease, 
suggesting in part an inflammatory mechanism. Because attacks of migraine may
involve repeated sterile vascular inflammation, we measured CRP in migraine
patients. METHODS: Retrospective review was conducted of 60 randomly sampled
charts of patients with the diagnosis of migraine without aura (MwoA, n = 29) and
migraine with aura (MwA, n = 31), in which CRP was recorded as part of the
differential diagnostic evaluation. CRP was measured by standard commercial
laboratory methods; high sensitivity CRP (hs-CRP) values above 3mg/L were
considered abnormal. RESULTS: Elevated hs-CRP was found in 43% of all patients
(26 of 60). In MwoA, of 29 subjects, abnormal hs-CRP was recorded in 16; in 10 no
other conditions were found to explain the abnormality. In MwA, of 31 subjects,
abnormal CRP was recorded in 10; in 5 no other condition could explain the
abnormality. No associations were found between other demographic or clinical
features. CONCLUSIONS: CRP may be abnormal in MwoA and MwA patients who present
with atypical, severe, or complex clinical features that require extensive
differential diagnostic investigation.

Publication Types: 
    Comparative Study

PMID: 16492227 [PubMed - indexed for MEDLINE]

1367: J Neurol Neurosurg Psychiatry. 2006 Mar;77(3):385-7.

Headache and migraine in primary care: consultation, prescription, and referral
rates in a large population.

Latinovic R, Gulliford M, Ridsdale L.

Division of Health and Social Care Research, King's College London, 5 Lambeth
Walk, London SE11 6SP, UK.

BACKGROUND/AIMS: Headache is the most common new neurological symptom seen by
general practitioners and neurologists. This study describes headache
consultation, prescription, and referral rates in a large sample of UK general
practices. METHODS: Analysis of data from patients > or = 15 years registered at 
253 UK general practices diagnosed with headache/migraine from 1992 to 2000.
Rates were age standardised using the European standard population for reference.
RESULTS: There were 13.2 million patient years of observation. Headache
consultation rates were 6.4/100 patients/year in women and 2.5 in men. They were 
highest at 15-24 years (15.8/100 in women; 5.8/100 in men), decreasing with age. 
Antimigraine drugs were prescribed at 36.7% of consultations for women and 26.6% 
for men. Among referrals to specialists, 55% were to neurology and 30% to general
medicine. The neurology referral rate in patients with headache was 2.1/100, and 
was higher in men (2.7/100) than women (1.9/100). CONCLUSIONS: These results
provide precise age specific and age standardised estimates for headache
consulting in general practice, in addition to prescribing and referral to
specialist care. Consultation rates are highest in young women; hospital
referrals peak in middle aged men. Research is needed into reasons for referral, 
and on better ways of delivering headache services.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16484650 [PubMed - indexed for MEDLINE]

1368: Curr Sports Med Rep. 2006 Feb;5(1):29-33.

Sport and exercise-induced migraines.

Nadelson C.

Atlas Orthopaedics, Westview Hospital, Indiana University Center for Sports
Medicine, Zionsville, IN 46077, USA. cnadelso@iupui.edu

Sport and exercise-induced migraines are difficult to distinguish from benign
exertional headaches and other headache syndromes. Exertion can be the sole
cause, or may be among multiple triggers for an individual's headache. Because
approximately 10% of these headaches have an organic origin, a careful history
and physical examination is necessary. The hallmark of treatment for
exercise-induced migraines tends to be proper warm-up before exercise,
minimization of environmental risks, proper sleep hygiene, and good nutrition and
hydration; however, in many cases, the pharmacologic solutions that are applied
to other types of headaches may also be necessary. Because there is a lack of
large trial studies on the athletic headache population, more research on the
topic is needed in the future to help clarify the mechanisms, classification, and
treatments of these headaches.

Publication Types: 
    Review

PMID: 16483514 [PubMed - indexed for MEDLINE]

1369: Funct Neurol. 2005 Oct-Dec;20(4):209-11.

Cerebral blood flow changes in the different phases of migraine.

Bartolini M, Baruffaldi R, Paolino I, Silvestrini M.

Department of Neuroscience, Polytechnic University of Marche, Ancona, Italy.

The haemodynamic changes that take place in migraine are reviewed focusing on
cerebral blood flow (CBF) data measured with different techniques in patients
suffering from migraine with and without aura during the different phases of
attacks and in interictal periods. Special attention is paid to the factors
underpinning the conflicting cerebral blood flow data and to pathophysiological
implications of the CBF changes detected in migraineurs.

Publication Types: 
    Review

PMID: 16483463 [PubMed - indexed for MEDLINE]

1370: Funct Neurol. 2005 Oct-Dec;20(4):201-7.

Are CO2 laser evoked potentials a specific marker of migraine?

Valeriani M.

Headache Centre, Division of Neurology, IRCCS Bambino Gesù, Children's Hospital, 
Rome, Italy. m.valeriani@tiscali.it

Although neurophysiological studies have made a considerable contribution to
understanding of migraine pathophysiology, the diagnosis of migraine continues to
be based on clinical examination of the patient, which also includes careful
history taking and a search for neurological signs. Indeed, no instrumental
technique has ever disclosed specific features in migraineurs, able to
distinguish them from healthy subjects or from patients with non-migraine
headache. CO2 laser evoked potentials (LEPs) have been used in migraine research 
in the past three years, proving very useful for demonstrating functional
abnormalities of the central nociceptive system which might be linked to the
pathophysiological mechanisms of this disease. However, like other
neurophysiological methods, LEP recording in migraineurs has not revealed
abnormalities specific enough to allow diagnosis of migraine in individual
subjects.

Publication Types: 
    Review

PMID: 16483462 [PubMed - indexed for MEDLINE]

1371: Funct Neurol. 2005 Oct-Dec;20(4):199-200.

Intensity dependence of auditory evoked cortical potentials in migraine. Changes 
in the peri-ictal period.

Afra J.

National Institute of Neurosurgery, Budapest, Hungary. juditafra@hotmail.com

The presence of premonitory symptoms in about 20% of patients suggest that the
migraine attack is initiated long before the occurrence of the aura or headache
symptoms. Recording of evoked and event-related potentials has revealed a strong 
intensity dependence of auditory evoked potentials (IDAP) in migraine with and
without aura. We studied changes in IDAP in the peri-ictal period in 63 migraine 
patients (55 presenting migraine without aura, four migraine with aura, and four 
both types) and compared findings with interictal controls. The results of this
study indicated that cortical processing of sensory information tends to
normalize just before and during an attack. The normalization of IDAP may reflect
an increase in central serotonergic activity. The study has been published in
Cephalalgia (Afra J, Sándor PS, Schoenen J. Cephalalgia 2000;20:714-719).

PMID: 16483461 [PubMed - indexed for MEDLINE]

1372: Funct Neurol. 2005 Oct-Dec;20(4):193-7.

Slow cortical potentials in migraine. Predictive value and possible novel
therapeutic strategies to prevent an attack.

Kropp P, Gerber WD.

Institute of Medical Psychology and Medical Sociology, University of Rostock,
Germany. peter.kropp@med.uni-rostock.de

During the pain-free interval migraine patients display increased negative
amplitudes in recordings of slow cortical potentials compared to healthy
controls. This fact can be linked to diminished or absent habituation during the 
recording session. This difference in amplitude and habituation is at its maximum
the day before the migraine attack. After the attack, amplitudes and habituation 
course are comparable with those of healthy controls. This observation enables
the migraine patient to predict the next migraine attack and to become acquainted
with other symptoms which indicate an imminent attack and which can be present
one or two days before it. During this period, when the attack has begun but the 
pain has not yet developed, novel therapeutic strategies for preventing the
full-blown attack can be introduced. These "pre-emptive" strategies--which may
include intake of tranquillizers to reduce the high cortical arousal, but also
non-medical relaxation methods--constitute neither acute treatment (because there
is no acute pain) nor prophylaxis.

PMID: 16483460 [PubMed - indexed for MEDLINE]

1373: Funct Neurol. 2005 Oct-Dec;20(4):185-91.

Prodromes and predictors of migraine attack.

Rossi P, Ambrosini A, Buzzi MG.

Headache Clinic, INI Grottaferrata, Rome, Italy. paolo.rossi90@tin.it

Premonitory symptoms of migraine include a wide and heterogeneous collection of
cognitive, psychic and physical changes preceding and forewarning of an attack by
a few hours to 2-3 days. To date, premonitory symptoms have received little
attention in the literature, being treated more as a curiosity than as a primary 
feature of migraine. This paper provides an extensive critical review of this
neglected area of migraine research in the light of the recent advances in our
understanding of the pathogenetic mechanisms of migraine. Epidemiological and
clinical studies that have investigated the premonitory symptoms of migraine lack
scientific rigour, producing conflicting results, whilst genetic and
pathophysiological investigations are still in their very early stages. There is 
evidence supporting the idea that premonitory symptoms could be used as a
phenotypical marker to identify subgroups of migraineurs which could show
correlations with specific clinical expressions of the disease, genotypes, or
responses to treatments. Future studies are needed to clarify the clinical,
pathophysiological and therapeutic significance of premonitory symptoms.

Publication Types: 
    Review

PMID: 16483459 [PubMed - indexed for MEDLINE]

1374: Funct Neurol. 2005 Oct-Dec;20(4):179-83.

Prodromes and the early phase of the migraine attack: therapeutic relevance.

Buzzi MG, Cologno D, Formisano R, Rossi P.

IRCCS Santa Lucia Foundation, Rome, Italy. mg.buzzi@hsantalucia.it

A migraine attack is a multiphasic event. In some patients the initial phase of
the attack is characterized by the presence of "prodromes" or "premonitory
symptoms" which are not recognized by the patient as part of the attack.
Premonitory symptoms are defined as "symptoms preceding and forewarning of a
migraine attack by 2-48 hours, occurring before the aura in migraine with aura
and before the onset of pain in migraine without aura". Migraine premonitory
symptoms should be differentiated from aura and symptoms of premenstrual
syndrome. This differentiation, which is crucial to correct diagnosis, is based
on two principal aspects, namely, the timing of these premonitory symptoms prior 
to the headache pain and their clinical characteristics. The neurotransmitters
dopamine and serotonin are possibly involved in the development of premonitory
symptoms, as demonstrated by experimental models and by the efficacy of migraine 
aborting and preventive treatments. Accurate recording of premonitory symptoms
may contribute to efforts to design the best therapeutic approach in migraine
patients.

Publication Types: 
    Review

PMID: 16483458 [PubMed - indexed for MEDLINE]

1375: Funct Neurol. 2005 Oct-Dec;20(4):169-71.

Ictal and interictal hypoactivation of the occipital cortex in migraine with
aura. A neuroimaging and electrophysiological study.

Bramanti P, Grugno R, Vitetta A, Marino S, Di Bella P, Nappi G.

Centro Studi Neurolesi, University of Messina, Italy.

In recent studies, several authors have highlighted and studied an altered blood 
oxygenation level dependent (BOLD) signal in subjects affected by migraine with
aura, using functional magnetic resonance imaging (fMRI) during the migraine
attack or during the period between two attacks. Using fMRI, we assessed a
27-year-old man affected by migraine with aura at two different times: during the
migraine attack, and a fortnight later, in order to look for differences in
regional cerebral blood flow after visual stimulation. In addition, during the
attack-free period we carried out a series of electrophysiological examinations. 
Our results demonstrate different activation patterns of the occipital cortex
during the asymptomatic period and during the migraine attack. Furthermore, the
electrophysiological data obtained demonstrated altered activity due to the
patient's disease.

Publication Types: 
    Case Reports

PMID: 16483455 [PubMed - indexed for MEDLINE]

1376: Can J Psychiatry. 2005 Nov;50(13):832-7.

Comorbidity of major depression and migraine--a Canadian population-based study.

Molgat CV, Patten SB.

Department of Psychiatry, University of Saskatchewan, Saskatoon.
cvmolgat@yahoo.ca

OBJECTIVE: To estimate the prevalence of major depressive episodes (MDEs) in
patients with migraine and to compare the strength of association with that of
other long-term medical conditions. METHODS: This study used a large-scale
probability sample (over 130,000 sample) from the Canadian Community Health
Survey (CCHS), a cross-sectional survey conducted by Statistics Canada. The CCHS 
screened for a broad set of medical conditions. Major depression was evaluated
with the Composite International Diagnostic Interview Short Form for Major
Depression, and the diagnosis of migraine was self-reported. The annual
prevalence of major depression was calculated in the general population, in
subjects with migraine, and in those with chronic conditions other than migraine.
RESULTS: The prevalence of major depression in subjects reporting migraine was
higher than that in the general population or in subjects with other chronic
medical conditions (17.6%, compared with 7.4% and 7.8%, respectively).
CONCLUSIONS: There is a strong association between major depression and migraine.
The migraine-MDE association may account for a large fraction of the chronic
condition-MDE association. The association between migraines and MDE differs from
that of other chronic conditions, as the association persists into older age
groups.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16483117 [PubMed - indexed for MEDLINE]

1377: AANA J. 2006 Feb;74(1):61-9.

Migraine development, treatments, research advances, and anesthesia implications.

O'Sullivan J, McCabe JT.

Uniformed Services University of the Health Sciences, Bethesda, MD, USA.
josullivan@usuhs.mil

The purpose of this course is to update anesthesia providers on the phenomenology
and biological mechanisms underlying migraines. As experts in pain management who
encounter this common ailment, anesthesia providers frequently are consulted to
assist in patient care. Effective assessment and treatment of migraine will lead 
to better anesthesia management. Knowledge of preventive measures of surgical
patients with migraine history can avoid events that can elicit a headache
attack. The clinical implications of migraine disorder--and each patient's
preventive medication profile--is relevant to safe, accommodative anesthesia
nursing care. Research advances in migraine treatment may profoundly improve our 
current pain relief measures. Adequate knowledge of the development, treatments, 
and research advances concerning migraine will improve patient care.

Publication Types: 
    Review

PMID: 16483070 [PubMed - indexed for MEDLINE]

1378: Neurology. 2006 Feb 14;66(3):344-8.

Familial risk of migraine: variation by proband age at onset and headache
severity.

Stewart WF, Bigal ME, Kolodner K, Dowson A, Liberman JN, Lipton RB.

Center for Health Research and Rural Advocacy, Geisinger Health System,
Baltimore, MD, USA.

BACKGROUND: It is well established that migraine aggregates within families. Less
is known about the influence of proband characteristics (e.g., age at onset,
headache severity) on familial aggregation. OBJECTIVE: To examine the association
between the proband's migraine severity and age at migraine onset and familial
aggregation of migraine. METHODS: The authors investigated the migraine
prevalence in first-degree relatives of 532 persons with migraine and control
subjects in a population study. Familial aggregation was expressed as the risk of
migraine in family members of probands divided by risk in control family members.
RESULTS: The relative risk (RR) of migraine in first-degree relatives of migraine
probands was elevated compared with family members of controls (RR = 1.88; 95%
CI: 1.30 to 2.72). The RR was also significantly higher for relatives of probands
reporting onset of migraine before age 16 (2.50; 95% CI: 1.65 to 3.79) compared
with those with onset at age 16 or older (1.44; 95% CI: 0.93 to 2.23). Among
probands with very severe average pain scores (i.e., 9 to 10 on a 0 to 10 scale),
the RR of migraine in family members was 2.38 (95% CI: 1.56 to 3.62) compared
with 1.52 (0.99 to 2.34) for less severe pain (p < 0.05). CONCLUSION: Early onset
of migraine in the proband as well as the severity of migraines are associated
with higher levels of family aggregation.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16476932 [PubMed - indexed for MEDLINE]

1379: Eur J Med Genet. 2006 Jan-Feb;49(1):57-62. Epub 2005 Feb 12.

No mutations detected in the INSR gene in a chromosome 19p13 linked migraine
pedigree.

Curtain R, Tajouri L, Lea R, MacMillan J, Griffiths L.

Genomics Research Centre, School of Health Sciences, Griffith University, Gold
Coast, Qld, Australia.

The aim of this study was to investigate through direct sequencing the insulin
receptor (INSR) gene in DNA samples from a migraine affected family previously
showing linkage to chromosome 19p13 in an attempt to detect disease associated
mutations. Migraine is a common debilitating disorder with a significant genetic 
component. At present, the number and type of genes involved in the common forms 
of migraine are not clear. The INSR gene on chromosome 19p13.3-13.2 is a gene of 
interest since a number of single nucleotide polymorphisms (SNPs) located within 
the gene have been implicated in migraine with (MA) and without aura (MO). Six
DNA samples obtained from non-founding migraine affected members of migraine
family 1 (MF1) were used in this study. Genomic DNA was sequenced for the INSR
gene in exons 1-22 and the promoter region. In the six migraine family member
samples, previously reported SNPs were detected within two exonic DNA coding
regions of the INSR gene. These SNPs, in exons 13 and 17, do not alter the normal
INSR polypeptide sequence. In addition, intron 7 also revealed a DNA base
sequence variation. For the 5' untranslated promoter region of the gene, no
mutations or polymorphisms were detected. In conclusion, this study detected no
INSR mutations in affected members of a chromosome 19 linked migraine pedigree.
Hence, migraine linkage to this chromosomal region may involve other candidate
genes.

PMID: 16473310 [PubMed - indexed for MEDLINE]

1380: Cephalalgia. 2006 Mar;26(3):332-5.

Implication of augmented vasogenic leakage in the mechanism of persistent aura in
sporadic hemiplegic migraine.

Iizuka T, Sakai F, Suzuki K, Igarashi H, Suzuki N.

Department of Neurology, School of Medicine, Kitasato University, Kanagawa,
Japan. takahiro@med.kitasato-u.ac.jp

The aim of this study is to report a possible implication of augmented vasogenic 
leakage in the mechanism of prolonged aura in sporadic hemiplegic migraine. A
35-year-old woman with sporadic hemiplegic migraine presented with headache
followed by right arm weakness, right visual field defect, aphasia and confusion 
that persisted for 1 week. During the acute stage, focal hyperaemia was seen in
the left cerebral hemisphere corresponding to persistent aura symptoms. Augmented
vasogenic leakage was demonstrated on delayed enhanced fluid-attenuated inversion
recovery image. Magnetic resonance angiography showed dilation of the left middle
cerebral artery. During the convalescent stage, such abnormal findings were not
seen. Based on these results, we speculate that augmented vasogenic leakage from 
the leptomeningeal vessels, probably associated with activation of the
trigeminovascular system, may delay the recovery of hemiplegic migraine aura.

Publication Types: 
    Case Reports
    Research Support, Non-U.S. Gov't

PMID: 16472342 [PubMed - indexed for MEDLINE]

1381: Cephalalgia. 2006 Mar;26(3):324-8.

A novel ATP1A2 mutation in a family with FHM type II.

Pierelli F, Grieco GS, Pauri F, Pirro C, Fiermonte G, Ambrosini A, Costa A, Buzzi
MG, Valoppi M, Caltagirone C, Nappi G, Santorelli FM.

Department of Neurology and ORL, University Centre for Adaptive Disorders and
Headache (UCADH), La Sapienza University, Rome.

Familial hemiplegic migraine (FHM) is a rare subtype of migraine with aura with
an autosomal dominant pattern of inheritance. Six FHM families underwent
extensive clinical and genetic investigation. The authors identified a novel
ATP1A2 mutation (E700K) in three patients from one family. In the patients,
attacks were triggered by several factors including minor head trauma. In one
subject a 3-day coma developed after a cerebral angiography. Overall, the
phenotype of the patients closely resembles that of previously reported cases of 
FHM type II. The E700K variant might be regarded as the cause of the disease in
this family, but this was not tested functionally.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 16472340 [PubMed - indexed for MEDLINE]

1382: Cephalalgia. 2006 Mar;26(3):310-3.

The practice pattern of migraine management among neurologists in Taiwan.

Lu SR, Wang SJ, Fuh JL.

Department of Neurology, Kaohsiung Medical University Chung-Ho Memorial Hospital,
Kaohsiung, Taiwan.

To assess the prevalence of migraine and the attitudes and practice patterns of
Taiwanese neurologists regarding migraine management, we mailed the survey
questionnaire to all of the actively practicing board-certified neurologists from
the membership list of the Taiwan Neurological Association. Of the targeted 531
neurologists, 123 (23.2%) participated in this study. Thirty of the participants 
(27.6%) reported having migraine. Most neurologists (88.5%) felt that headache
was an important part of their practice. Many neurologists (65.0%) used
neuroimaging to evaluate patients with severe headache and 44.7% used
electroencephalography for headache evaluation. Many participants knew that
combination analgesic was a common cause of medication-overuse headache, but did 
not know that ergotamine, acetaminophen and triptans were possible aetiologies of
medication-overuse headache. Our study suggests that awareness of
medication-overuse headache and the indications of neuroimaging should be
stressed in Taiwan, and headache guidelines should be modified according to local
factors.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16472337 [PubMed - indexed for MEDLINE]

1383: Cephalalgia. 2006 Mar;26(3):295-309.

Cardiorespiratory regulation in migraine. Results in children and adolescents and
review of the literature.

Ebinger F, Kruse M, Just U, Rating D.

Department of Child Neurology, University Paediatric Hospital, Heidelberg,
Germany. friedrich.ebinger@med.uni-heidelberg.de

To investigate autonomic regulation in juvenile migraine we studied 70 children
and adolescents with migraine during the headache-free period and 81 healthy
controls by cardiorespiratory function tests. Heart rate variability was analysed
with time and frequency domain indices during spontaneous breathing at rest and
during metronomic breathing. Changes of heart rate and blood pressure were
studied during tilt-table test, active standing, Valsalva manoeuvre and sustained
handgrip. We found significant differences in metronomic breathing, tilt-table
test and Valsalva manoeuvre. We interpret our findings and results reported in
the literature as pointing to a restricted ability of the system to rest, which
supports therapies intending to further this ability. In autonomic tests,
hyperreactivity in juvenile migraineurs changes to hyporeactivity and passive
coping in adults. This might be explained by disturbances of raphe nuclei and the
periaqueductal grey. It corresponds to psychological findings in juvenile
migraineurs reporting hypersensitivity and repressed aggression and claiming
learned helplessness.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16472336 [PubMed - indexed for MEDLINE]

1384: Cephalalgia. 2006 Mar;26(3):277-81.

Biochemical changes in endocannabinoid system are expressed in platelets of
female but not male migraineurs.

Cupini LM, Bari M, Battista N, Argirò G, Finazzi-Agrò A, Calabresi P, Maccarrone 
M.

Centro Cefalee, Clinica Neurologica, Ospedale S. Eugenio, Roma, Italy.
lecupini@tin.it

The endogenous cannabinoid anandamide (AEA) plays important roles in modulating
pain. Head pain is an almost universal human experience, yet primary headache
disorders, such as migraine without aura (MoA) or episodic tension-type headache 
(ETTH), can represent a serious threat to well-being when frequent and disabling.
We assessed the discriminating role of endocannabinoids among patients with ETTH 
or MoA, and control subjects. We measured the activity of AEA hydrolase and AEA
transporter, and the level of cannabinoid receptors in peripheral platelets from 
MoA, ETTH and healthy controls. Sixty-nine headache patients and 36 controls were
selected. Diagnosis of headache type was made according to the International
Headache Society criteria. We observed significant sex differences concerning AEA
membrane transporter and fatty acid amide hydrolase activity in all groups. An
increase in the activity of AEA hydrolase and AEA transporter was found in female
but not male migraineurs. Cannabinoid receptors were the same in all groups. Here
we show that the endocannabinoid system in human platelets is altered in female
but not male migraneurs. Our results suggest that in migraineur women an
increased AEA degradation by platelets, and hence a reduced concentration of AEA 
in blood, might reduce the pain threshold and possibly explain the prevalence of 
migraine in women. The involvement of the endocannabinoid system in migraine is
new and broadens our knowledge of this widespread and multifactorial disease.

Publication Types: 
    Comparative Study

PMID: 16472333 [PubMed - indexed for MEDLINE]

1385: Cephalalgia. 2006 Mar;26(3):257-65.

Clinical-biochemical correlates of migraine attacks in rizatriptan responders and
non-responders.

Sarchielli P, Pini LA, Zanchin G, Alberti A, Maggioni F, Rossi C, Floridi A,
Calabresi P.

Headache Centre, Neurologic Clinic, Department of Medical and Surgical
Specialties and Public Health, University of Perugia, Perugia, Italy.
neuro.pg@tiscalinet.it

The present study was aimed at verifying the clinical characteristics of a
typical attack in 20 migraine patients, 10 responders and 10 non-responders to
rizatriptan, and at investigating any differences in the levels of neuropeptides 
of the trigeminovascular or parasympathetic systems [calcitonin gene-related
peptide (CGRP), neurokinin A (NKA) and vasoactive intestinal peptide (VIP)
measured by radioimmunoassay methods in external jugular blood] between
responders and non-responders. In all responders to rizatriptan, pain was
unilateral, severe, and pulsating, and in five of them at least one sign
suggestive of parasympathetic system activation was recorded. Five patients who
were non-responders to rizatriptan referred bilateral and non-pulsating pain,
even though severe in most of them. CGRP and NKA levels measured before
rizatriptan administration were significantly higher in responders than in
non-responders (P < 0.0001 and P < 0.002, respectively). In the five patients
with autonomic signs among rizatriptan responders, detectable VIP levels were
found at baseline. One hour after rizatriptan administration, a decrease in CGRP 
and NKA levels was evident in the external jugular venous blood of rizatriptan
responders, and this corresponded to a significant pain relief and alleviation of
accompanying symptoms. VIP levels were also significantly reduced at the same
time in the five patients with autonomic signs. After rizatriptan administration,
CGRP and NKA levels in non-responder patients showed less significant variations 
at all time points after rizatriptan administration compared with rizatriptan
responders. The present study, although carried out on a limited number of
patients, supports recent clinical evidence of increased trigeminal activation
associated with a better triptan response in migraine patients accompanied by
parasympathetic activation in a subgroup of patients with autonomic signs. In
contrast, the poor response seems to be correlated with a lesser degree of
trigeminal activation, lower variations of trigeminal neuropeptides after triptan
administration, and no evidence of parasympathetic activation at baseline.

Publication Types: 
    Comparative Study

PMID: 16472331 [PubMed - indexed for MEDLINE]

1386: Cephalalgia. 2006 Mar;26(3):246-56.

Preference for rizatriptan 10-mg wafer vs. eletriptan 40-mg tablet for acute
treatment of migraine.

Láinez MJ, Evers S, Kinge E, Allais G, Allen C, Rao NA, Massaad R, Lis K.

Department of Neurology, Hospital Clínico Universitario, University of Valencia, 
Valencia, Spain. jlaineza@meditex.es

Preference is a composite, patient-oriented endpoint incorporating efficacy,
tolerability, formulation, and convenience of medications. The objective of this 
study was to compare patient preference for rizatriptan 10-mg wafer vs.
eletriptan 40-mg tablet for acute treatment of migraine. In this multicentre,
open-label, two-period, crossover study, out-patients were randomly assigned to
treat the first of two moderate to severe migraines with rizatriptan or
eletriptan and the second with the alternate therapy. Patients completed diary
assessments at baseline and up to 24 h after taking study medication. At the last
visit, patients completed a psychometrically validated preference questionnaire. 
A total of 372 patients (mean age 38 years, 85% female) treated two migraine
attacks, and 342 patients (92%) expressed a preference for treatment.
Significantly more (P < or = 0.001) patients preferred rizatriptan 10-mg wafer
[61.1%; 95% confidence interval (CI) 55.7, 66.3] to eletriptan 40-mg tablet
(38.9%; 95% CI 33.7, 44.3). The most common reason given for preference of either
treatment was speed of headache relief. At 2 h, 80% and 69% of patients reported 
that rizatriptan and eletriptan, respectively, was convenient or very convenient 
to take (mean convenience score 1.99 vs. 2.31, respectively; P < or = 0.001).
Both triptans were well tolerated. In this head-to-head study designed to
evaluate global patient preference, significantly more patients preferred the
rizatriptan 10-mg wafer to the eletriptan 40-mg tablet for acute treatment of
migraine. The single most important reason for preference was speed of relief,
consistent with results from previous preference studies.

Publication Types: 
    Multicenter Study
    Randomized Controlled Trial

PMID: 16472330 [PubMed - indexed for MEDLINE]

1387: Cephalalgia. 2006 Mar;26(3):225-32.

Sneddon's syndrome: another migraine-stroke association?

Tietjen GE, Al-Qasmi MM, Gunda P, Herial NA.

Department of Neurology, Medical University of Ohio, Toledo, OH 43614, USA.
gtietjen@mco.edu

Sneddon's syndrome refers to the enigmatic association of ischaemic stroke and
livedo reticularis. We review the Sneddon's syndrome literature examining the
association of this condition with headache, including migraine. Case reports and
series are stratified into two groups based on headache reference. In the group
without a reference to headache, there are 208 persons, with a female to male
ratio of 3 : 1. In the headache reference group, there are 175 persons, with a
female to male ratio of 3.5 : 1. The proportion with headache in this second
group is 58% (102 individuals), with headache described as migraine in 28 (27.5%)
of the headache subjects, including six with migraine with aura. The frequency of
headache is not significantly higher in persons with positive anti-phospholipid
antibodies compared with the negative cohort (43% vs. 32%, P = 0.07). A review of
the histopathological, radiological and serological data in Sneddon's syndrome
and migraine underscores the plausibility of an association. Considered in the
context of increased risk of stroke with migraine, a higher frequency of livedo
in migraineurs with stroke, and the association of migraine and livedo
reticularis, the question of whether livedo reticularis may be a risk marker for 
stroke in migraineurs is an area for further study.

Publication Types: 
    Review

PMID: 16472327 [PubMed - indexed for MEDLINE]

1388: Scand J Prim Health Care. 2006 Mar;24(1):16-21.

Intensive community pharmacy intervention had little impact on triptan
consumption: a randomized controlled trial.

Søndergaard J, Foged A, Kragstrup J, Gaist D, Gram LF, Sindrup SH, Muckadell HU, 
Larsen BO, Herborg H, Andersen M.

Research Unit for General Practice, University of Aarhus, Aarhus, Denmark.
js@alm.au.dk

OBJECTIVE: To evaluate the impact of an intensive pharmaceutical care campaign
targeting inappropriate use of triptans. DESIGN: Randomized controlled trial.
SETTING: 22 community pharmacies in the County of Funen, Denmark. SUBJECTS: A
total of 1123 triptan users at intervention pharmacies and 1340 at control
pharmacies. INTERVENTION: Intervention pharmacy staff received information on
migraine and other types of headache, detection of inappropriate triptan use and 
other drug-related problems, and techniques for establishing a dialogue with
patients. Intervention consisted of a folder and a structured dialogue with the
pharmacy staff. The folder included questions aimed at detecting overuse and
inappropriate triptan use. MAIN OUTCOME MEASURES: Change in average triptan
consumption in doses per month measured by means of a prescription database with 
information on all purchases of reimbursed drugs at the level of the individual
patient. RESULTS: Overall, intervention had no statistically significant
short-term impact on patients' consumption of triptans either among incident
users (intervention/control ratio 1.02; 95% confidence interval 0.95 to 1.12), or
among prevalent users (1.02; 0.97 to 1.08). No effects were observed after 6 and 
9 months, apart from a possible borderline effect after 9 months among prevalent 
users with intermediate triptan consumption (0.93; 0.87 to 1.00). CONCLUSION: The
pharmaceutical care campaign did not reduce the use of triptans.

Publication Types: 
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 16464810 [PubMed - indexed for MEDLINE]

1389: Yale J Biol Med. 2005 May;78(3):147-50.

Myocardial infarction after taking zolmitriptan.

Pacheco-Coronado R, McMullan PW, Galbut BH, Galbut EJ, Snell J, Schaer GL,
Kavinsky CJ.

Rush University Medical Center, Chicago, Illinois, USA.

We report the case of a patient with mild non-obstructive coronary artery disease
who sustained an inferior wall myocardial infarction shortly after taking
zolmitriptan as abortive therapy for migraine headaches. A Medline search was
performed to review all reported cases of myocardial infarction related to
migraine therapy with zolmitriptan and related medications. Zolmitriptan may
cause myocardial infarction (MI) even in the absence of significant coronary
artery disease.

Publication Types: 
    Case Reports
    Review

PMID: 16464313 [PubMed - indexed for MEDLINE]

1390: Life Sci. 2006 Jun 13;79(3):265-71. Epub 2006 Feb 3.

Characterisation of CGRP receptors in the human isolated middle meningeal artery.

Gupta S, Mehrotra S, Avezaat CJ, Villalón CM, Saxena PR, Maassenvandenbrink A.

Department of Pharmacology, Erasmus MC, University Medical Center Rotterdam, P.O.
Box 1738, 3000 DR Rotterdam, The Netherlands.

Although the understanding of migraine pathophysiology is still incomplete, there
seems to be little doubt that dilatation of cranial blood vessels, including
meningeal arteries, is involved in the headache phase of migraine. Since
calcitonin gene-related peptide (CGRP) has been implicated in this
vasodilatation, the present study set out to compare the relaxant effects of the 
endogenous ligand h-alphaCGRP, and [ethylamide-Cys(2,7)]h-alphaCGRP
([Cys(Et)(2,7)]h-alphaCGRP), a CGRP(2) receptor agonist, on human isolated middle
meningeal artery segments, precontracted with KCl. Classical Schild plot analysis
was used to characterise the receptor population in this artery using BIBN4096BS 
and h-alphaCGRP(8-37) as antagonists. h-alphaCGRP relaxed arterial segments more 
potently than [Cys(Et)(2,7)]h-alphaCGRP (pEC(50): 8.51+/-0.16 and 7.48+/-0.24,
respectively), while the maximal responses to these agonists were not
significantly different. BIBN4096BS equipotently blocked the relaxations induced 
by both agonists with a pA(2) of approximately 10 and with a Schild plot slope
not significantly different from unity. h-alphaCGRP(8-37) also antagonised the
response to h-alphaCGRP with a pA(2) of 6.46+/-0.16 and a Schild plot slope not
different from unity. Furthermore, the results obtained from RT-PCR studies
confirmed the presence of all the essential components required for a functional 
CGRP(1) receptor in these arteries. Considering the high antagonist potency of
BIBN4096BS, coupled to the lower agonist potency of [Cys (Et)(2,7)]h-alphaCGRP,
it is reasonable to suggest a predominant role of CGRP(1) receptors in the human 
middle meningeal artery. This view is reinforced by Schild plot analysis, which
revealed a slope of unity in all experiments, giving further evidence for a
homogeneous CGRP receptor population in this vascular preparation.

Publication Types: 
    In Vitro

PMID: 16458930 [PubMed - indexed for MEDLINE]

1391: Eye. 2007 Feb;21(2):218-23. Epub 2006 Feb 3.

Assessment of spatial-contrast function and short-wavelength sensitivity deficits
in patients with migraine.

Yenice O, Onal S, Incili B, Temel A, Afşar N, Tanridağ T.

Marmara University School of Medicine, Department of Ophthalmology, Istanbul,
Turkey. yeniceozlem@yahoo.com

AIMS: To study spatial-contrast function and short-wavelength sensitivity
deficits in a migraine population with a disease duration of 30 years or less.
MATERIALS AND METHODS: In this prospective, cross-sectional study, we evaluated
28 subjects with migraine headache and 15 nonheadache healthy controls. Visual
fields were evaluated using the Humphrey Field Analyzer 750i and the 30-2, blue
and yellow threshold programme. Contrast sensitivity (CS) was measured at 1.5, 3,
6, 12, and 18 cpd spatial frequencies, using the Functional Acuity Contrast Test 
(F.A.C.T.). The results of the visual field parameters (mean defect (MD) and
pattern standard defect (PSD)) and CS were compared with 15 age-equivalent normal
subjects. RESULTS: Short-wavelength amplitude perimetry (SWAP) parameters and CS 
scores at all spatial frequencies were significantly altered in the migraine
patients when compared with the control subjects. Visual field parameters
correlated significantly with contrast sensitivity scores: positively for MD
(r=0.39, P=0.01; r=0.43, P=0.005; r=0.56, P=0.0001; r=0.45, P=0.003; r=0.48,
P=0.0001) and negatively for PSD (r=-0.45, P=0.003; r=-0.45, P=0.003; r=-0.51,
P=0.001; r=-0.53, P=0.0001; and r=-0.67, P=0.0001) at all (1.5, 3, 6,12, and 18
cpd) spatial frequencies, respectively. Migraine duration correlated negatively
with MD (r=-0.42, P=0.04) and positively with PSD (r=0.42, P=0.03). CONCLUSION:
Migraineurs had significantly altered visual field and contrast function at all
spatial frequencies to the normal population. These defects share some features
with early stages of glaucoma and may relate a possibility for a common vascular 
disease pathogenesis in these two conditions.

PMID: 16456594 [PubMed - indexed for MEDLINE]

1392: Ann Neurol. 2006 Apr;59(4):652-61.

Suppression of cortical spreading depression in migraine prophylaxis.

Ayata C, Jin H, Kudo C, Dalkara T, Moskowitz MA.

Stroke and Neurovascular Regulation Laboratory, Department of Radiology,
Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129,
USA.

OBJECTIVE: Topiramate, valproate, propranolol, amitriptyline, and methysergide
have been widely prescribed for migraine prophylaxis, but their mechanism or site
of action is uncertain. Cortical spreading depression (CSD) has been implicated
in migraine and as a headache trigger and can be evoked in experimental animals
by electrical or chemical stimulation. We hypothesized that migraine prophylactic
agents suppress CSD as a common mechanism of action. METHODS: Rats were treated
either acutely or chronically over weeks and months, with one of the above
migraine prophylactic drugs, vehicle, or D-propranolol, a clinically ineffective 
drug. The impact of treatment was determined on the frequency of evoked CSDs
after topical potassium application or on the incremental cathodal stimulation
threshold to evoke CSD. RESULTS: Chronic daily administration of migraine
prophylactic drugs dose-dependently suppressed CSD frequency by 40 to 80% and
increased the cathodal stimulation threshold, whereas acute treatment was
ineffective. Longer treatment durations produced stronger CSD suppression.
Chronic D-propranolol treatment did not differ from saline control.
INTERPRETATION: Our data suggest that CSD provides a common therapeutic target
for widely prescribed migraine prophylactic drugs. Assessing CSD threshold may
prove useful for developing new prophylactic drugs and improving upon existing
ones.

Publication Types: 
    Comparative Study
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 16450381 [PubMed - indexed for MEDLINE]

1393: J Headache Pain. 2006 Feb;7(1):27-33. Epub 2006 Jan 31.

Value of postmarketing surveillance studies in achieving a complete picture of
antimigraine agents: using almotriptan as an example.

Pascual J, Diener HC, Massiou H.

Service of Neurology, University Hospital, Salamanca 39008, Spain.
juliopascual@telefonica.net

Randomised controlled trials cannot collect all the data relevant for use in
everyday clinical practice because drug exposure is limited, endpoints are
restricted and some patient populations are excluded. Postmarketing surveillance 
(PS) studies can add important information for real-world clinical practice.
Acute migraine therapy with almotriptan 12.5 mg was evaluated in 4 PS studies, 2 
conducted in Spain, 1 in Germany and 1 in France. Almotriptan was associated with
a high rate of treatment response and was well tolerated in all 4 studies. In the
Spanish and German studies, 2-hour pain-relief, 2-hour pain-free, and sustained
painfree rates were enhanced when patients treated mild pain. Patient
satisfaction with almotriptan, assessed in the German and French studies, was
high and the majority of patients preferred almotriptan to their previous acute
migraine therapy. In conclusion, PS studies augment our knowledge of antimigraine
therapy, giving a more complete picture of how such agents work in the general
population.

Publication Types: 
    Comparative Study
    Multicenter Study

PMID: 16440139 [PubMed - indexed for MEDLINE]

1394: Ann Neurol. 2006 Feb;59(2):310-4.

Severe episodic neurological deficits and permanent mental retardation in a child
with a novel FHM2 ATP1A2 mutation.

Vanmolkot KR, Stroink H, Koenderink JB, Kors EE, van den Heuvel JJ, van den
Boogerd EH, Stam AH, Haan J, De Vries BB, Terwindt GM, Frants RR, Ferrari MD, van
den Maagdenberg AM.

Department of Human Genetics, Leiden University Medical Centre, Leiden, The
Netherlands.

OBJECTIVE: Attacks of familial hemiplegic migraine (FHM) are usually associated
with transient, completely reversible symptoms. Here, we studied the ATP1A2 FHM2 
gene in a young girl with episodes of both very severe and transient neurological
symptoms that were triggered by mild head trauma as well as permanent mental
retardation. Her family members suffered from hemiplegic and confusional migraine
attacks. METHODS: Mutation analysis of the ATP1A2 gene was performed by direct
sequencing of all exons and flanking intronic regions, using genomic DNA of the
proband. Functional consequences of the mutation were analyzed by cellular
survival assays. RESULTS: We identified a novel G615R ATP1A2 mutation in the
proband and several of her family members. Functional analysis of mutant
Na,K-ATPase in cellular survival assays showed a complete loss-of-function
effect. INTERPRETATION: Permanent mental retardation in children may be caused by
ATP1A2 mutations.

Publication Types: 
    Case Reports
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 16437583 [PubMed - indexed for MEDLINE]

1395: Neurology. 2006 Jan 24;66(2):202-5.

Embolization of pulmonary arteriovenous malformations and decrease in prevalence 
of migraine.

Post MC, Thijs V, Schonewille WJ, Budts W, Snijder RJ, Plokker HW, Westermann CJ.

Department of Cardiology, St. Antonius Hospital, Nieuwegein, The Netherlands.
m.post@antonius.net

OBJECTIVE: To determine if embolization of pulmonary arteriovenous malformations 
(PAVMs) decreases the occurrence of migraine. METHODS: All 105 patients with
hereditary hemorrhagic telangiectasia (HHT), minimum age 16 years, who underwent 
an embolization of PAVM in our hospital between June 1995 and April 2004, were
included in this study. A structured headache questionnaire was sent to all
patients and focused on two periods: 1 year before and at least 6 months after
embolization. Two independent neurologists diagnosed migraine according to the
International Headache Society criteria. RESULTS: Eighty-four patients (80%) sent
back the questionnaire (mean age 47.8 +/- 15.1 years, 51 female). Median
follow-up time was 48 months (first quartile: 23 months; third quartile: 66
months). The overall prevalence of migraine decreased from 45.2% before to 34.5% 
after embolization (p = 0.01). The prevalence of migraine with aura decreased
from 33.3% before to 19.0% after embolization (p = 0.002). The severity of
headache attacks decreased in patients who still had migraine (p = 0.15) or
migraine with aura after embolization (p = 0.11). CONCLUSION: Embolization of
pulmonary arteriovenous malformations in patients with hereditary hemorrhagic
telangiectasia seems to be related to a decrease in prevalence of migraine,
suggesting that the presence of a right-to-left shunt rather than the
localization of this shunt plays a causative role in the pathogenesis of
migraine.

PMID: 16434654 [PubMed - indexed for MEDLINE]

1396: Neuropediatrics. 2005 Dec;36(6):395-8.

Oculomotor nerve schwannoma mimicking ophthalmoplegic migraine.

Murakami T, Funatsuka M, Komine M, Hirayama Y, Suzuki H, Shishikura K, Aihara Y, 
Shibata K, Hori T, Kobayashi M, Osawa M.

Department of Pediatrics, Tokyo Women's Medical University, Tokyo, Japan.
terumi.tooyama@nifty.com

Ophthalmoplegic migraine (OM) is a rare variant of migraine characterized by
recurrent attacks of severe headache followed by oculomotor nerve palsy. The
recent revision of the International Headache Classification has reclassified OM 
from a subtype of migraine, defined as a functional headache, to the neuralgia
category. We describe a case of an 11-year-old girl with pathologically confirmed
oculomotor nerve schwannoma who had been suffering from symptoms mimicking OM.
For five years, she has been under treatment for OM, an initial diagnosis which
was corroborated by brain magnetic resonance imaging (MRI). Usually, most OM
attacks occur during one period in a lifetime and remit completely. In contrast, 
however, her attacks became more frequent and were not controlled by medication. 
After surgery, the frequency of OM attacks was reduced. From this experience, we 
hypothesize that optic nerve tumor is one condition that can mimic OM, without
apparent signs suggestive of intracranial mass. To our knowledge, this is the
first report to describe a pathologically confirmed case of oculomotor nerve
schwannoma mimicking OM.

Publication Types: 
    Case Reports

PMID: 16429381 [PubMed - indexed for MEDLINE]

1397: Lancet Neurol. 2006 Feb;5(2):148-57.

Chronic disorders with episodic manifestations: focus on epilepsy and migraine.

Haut SR, Bigal ME, Lipton RB.

Comprehensive Epilepsy Management Center, Montefiore Medical Center and the
Albert Einstein College of Medicine, Bronx, NY 10467-2490, USA. haut@aecom.yu.edu

Epilepsy and migraine are chronic neurological disorders with episodic
manifestations that are commonly treated in neurological practice and frequently 
occur together. In this review we examine similarities and contrasts between
these disorders, with focus on epidemiology and classification, temporal
coincidence, triggers, and mechanistically based therapeutic overlap. This
investigation draws attention to unique aspects of both epilepsy and migraine,
while identifying areas of crossover in which each specialty could benefit from
the experience of the other.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't
    Review

PMID: 16426991 [PubMed - indexed for MEDLINE]

1398: Cephalalgia. 2006 Feb;26(2):214-20.

The postdrome of the acute migraine attack.

Kelman L.

Headache Center of Atlanta, Atlanta, GA 30342, USA. lkelman@mindspring.com

This study was performed to document the frequency, duration and types of
symptoms of postdrome in migraine patients. Eight hundred and twenty-seven
consecutive headache clinic patients (IHS 1.1, 1.2 and 1.5.1) were evaluated at
first visit. Postdrome frequency, duration and characteristics were analysed.
Sixty-eight per cent of 827 patients reported postdrome (69.1% females; 56.8%
males, P<0.007). The average duration of the postdrome was 25.2 h. Fifty-six per 
cent had postdrome for <or=12 h, 32% for 12-24 h, 88% for <or=24 h, and 12% for
>24 h. The commonest symptoms were tiredness (71.8%), head pain (33.1%),
cognitive difficulties (11.7%), 'hangover' (10.7%), gastrointestinal symptoms
(8.4%), mood change (6.8%), and weakness (6.2%). Patients with postdrome compared
with patients without postdrome have more characteristic and more frequent
migraine features. This study demonstrated postdrome in 68% of patients,
duration<or=24 h in most patients, more often associated with a full-blown
migraine attack, more common in females, and with commonest symptoms being
tiredness and low-grade headache.

PMID: 16426278 [PubMed - indexed for MEDLINE]

1399: Cephalalgia. 2006 Feb;26(2):208-13.

Right-to-left shunt and migraine: the strength of the relationship.

Wammes-van der Heijden EA, Tijssen CC, Egberts AC.

Utrecht Institute for Pharmaceutical Sciences, Utrecht, The Netherlands.

Several studies have shown that the prevalence of a cardial right-to-left shunt
(RLS) in patients with migraine with aura is significantly higher than in
patients without migraine. To assess the strength of the possible relationship
between RLS and migraine, the literature concerning this subject was
systematically reviewed. We identified seven relevant studies. Among patients
with RLS migraine with aura was 3.5 times more prevalent than among subjects
without RLS [Mantel-Haenszel odds ratio (ORMH) 3.5; 95% confidence interval (CI) 
2.1, 5.8]. In patients with ischaemic stroke migraine was more than two times
more prevalent in patients with RLS than in patients without RLS (ORMH 2.1; 95%
CI 1.6, 2.9). Our review shows that there is a clear association between RLS and 
migraine, especially migraine with aura. The relationship between RLS and
migraine is further substantiated by the observations of disappearance and
improvement of migraine symptoms after closure of the foramen ovale. However, the
mechanism as well as the question about causality of this association has to be
further elucidated.

Publication Types: 
    Meta-Analysis
    Review

PMID: 16426277 [PubMed - indexed for MEDLINE]

1400: Cephalalgia. 2006 Feb;26(2):172-9.

The relationship between migraine and atopic disorders-the contribution of
pulmonary function tests and immunological screening.

Ozge A, Ozge C, Oztürk C, Kaleagasi H, Ozcan M, Yalçinkaya DE, Ozveren N, Yalçin 
F.

Department of Neurology, Mersin University School of Medicine, Mersin, Turkey.
aozge@mersin.edu.tr

This cross-sectional clinical study was conducted in order to explore the
relationship between atopic disorders and migraine. We evaluated 186 consecutive 
patients with migraine. Patients with a history of atopic disorders were compared
with the others during headache-free intervals, for their headache
characteristics, pulmonary test (PFT) performances and immunological screenings, 
through appropriate statistical methods. Of the patients with migraine, 77
(41.4%) reported at least one atopic disorder. PFT screening showed a general
decreased pulmonary capacity and an important correlation between a positive
history of atopic disorders and both increased eosinophil and IgE levels in
headache-free periods. It should be discussed whether screening with PFT or
immunological tests helps in early detection of progressive lung disease which
might develop in these patients.

Publication Types: 
    Controlled Clinical Trial

PMID: 16426272 [PubMed - indexed for MEDLINE]

1401: Cephalalgia. 2006 Feb;26(2):158-61.

Genetic variants of the NOTCH3 gene in migraine--a mutation analysis and
association study.

Schwaag S, Evers S, Schirmacher A, Stögbauer F, Ringelstein EB, Kuhlenbäumer G.

Department of Neurology, University of Münster, Münster, Germany.

Mutations in the NOTCH3 gene cause cerebral autosomal dominant arteriopathy with 
subcortical infarcts and leukoencephalopathy (CADASIL). Exons 3 and 4 are
mutation hotspots. Migraine is a clinical hallmark of CADASIL. The objective of
this study was to investigate whether genetic variants in exons 3 and 4 of the
NOTCH3 gene are associated with migraine. Exons 3 and 4 of the NOTCH3 were
analysed for mutations and polymorphisms by direct DNA sequencing in 97
migraineurs and the same number of control individuals. No mutations in exons 3
and 4 of the NOTCH3 gene were found in 97 patients with migraine. However,
association analysis revealed significant association of the single nucleotide
polymorphism (SNP) rs1043994 with migraine.

Publication Types: 
    Controlled Clinical Trial

PMID: 16426270 [PubMed - indexed for MEDLINE]

1402: Cephalalgia. 2006 Feb;26(2):143-9.

Comment in:
    Cephalalgia. 2007 Feb;27(2):187-8; author reply 188-9.

Induction of long-lasting changes of visual cortex excitability by five daily
sessions of repetitive transcranial magnetic stimulation (rTMS) in healthy
volunteers and migraine patients.

Fumal A, Coppola G, Bohotin V, Gérardy PY, Seidel L, Donneau AF, Vandenheede M,
Maertens de Noordhout A, Schoenen J.

Department of Neurology, University of Liège, Belgium.

We have shown that in healthy volunteers (HV) one session of 1 Hz repetitive
transcranial magnetic stimulation (rTMS) over the visual cortex induces
dishabituation of visual evoked potentials (VEPs) on average for 30 min, while in
migraineurs one session of 10 Hz rTMS replaces the abnormal VEP potentiation by a
normal habituation for 9 min. In the present study, we investigated whether
repeated rTMS sessions (1 Hz in eight HV; 10 Hz in eight migraineurs) on 5
consecutive days can modify VEPs for longer periods. In all eight HV, the 1 Hz
rTMS-induced dishabituation increased in duration over consecutive sessions and
persisted between several hours (n=4) and several weeks (n=4) after the fifth
session. In six out eight migraineurs, the normalization of VEP habituation by 10
Hz rTMS lasted longer after each daily stimulation but did not exceed several
hours after the last session, except in two patients, where it persisted for 2
days and 1 week. Daily rTMS can thus induce long-lasting changes in cortical
excitability and VEP habituation pattern. Whether this effect may be useful in
preventative migraine therapy remains to be determined.

Publication Types: 
    Controlled Clinical Trial
    Research Support, Non-U.S. Gov't

PMID: 16426268 [PubMed - indexed for MEDLINE]

1403: Cephalalgia. 2006 Feb;26(2):136-42.

Peripheral levels of BDNF and NGF in primary headaches.

Blandini F, Rinaldi L, Tassorelli C, Sances G, Motta M, Samuele A, Fancellu R,
Nappi G, Leon A.

Laboratory of Functional Neurochemistry, Neurological Institute C. Mondino,
Pavia, Italy.

Neurotrophins, such as brain-derived neurotrophic factor (BDNF) and nerve growth 
factor (NGF), have been implicated in the generation and modulation of pain. To
investigate whether alterations in neurotrophin levels can be detected in
subjects suffering from nociceptive disorders, such as primary headaches, we
determined the peripheral (platelet and plasma) levels of BDNF and NGF in
patients suffering from migraine, with or without aura, or cluster headache (CH),
in the interictal phase, and in healthy volunteers. All primary headaches
patients studied showed significantly decreased platelet levels of BDNF (migraine
vs. controls P<0.001; CH vs. controls P<0.01), while a selective reduction of
platelet NGF was observed in migraine sufferers and not in CH patients compared
with control subjects (migraine vs. controls P<0.001). These changes were not
accompanied by significant modifications of neurotrophin plasma levels. Our
findings show for the first time that changes in peripheral levels of
neurotrophines (BDNF and NGF) occur in patients suffering from different types of
primary headaches, suggesting a potential involvement of BDNF and NGF in the
pathophysiology of these disorders, and raising the possibility that differences 
in peripheral neurotrophins may help to distinguish migraine biologically from
CH.

Publication Types: 
    Controlled Clinical Trial
    Research Support, Non-U.S. Gov't

PMID: 16426267 [PubMed - indexed for MEDLINE]

1404: Cephalalgia. 2006 Feb;26(2):113-21.

Subcutaneous sumatriptan provides symptomatic relief at any pain intensity or
time during the migraine attack.

Linde M, Mellberg A, Dahlöf C.

Gothenburg Migraine Clinic, and Institute of Clinical Neuroscience, Sahlgrenska
Academy, Göteborg University, Gothenburg, Sweden. mattias.linde@neuro.gu.se

Over the years the paradigm of treating early during the migraine attack has
become well established in clinical practice. It is also recommended that the
5-HT(1B/1D) agonists be administered early during the migraine attack for
efficacy. This is because it has been proposed that most migraineurs are less
responsive to delayed treatment, owing to the development of central
sensitization of the pain transmission. The main objective of this prospective,
cross-over study at a specialist clinic was to evaluate if these recommendations 
should also apply to the subcutaneous formulation of sumatriptan. Results are
based on 20 adult International Headache Society migraineurs. Two attacks (n=40) 
were treated with 6 mg subcutaneous sumatriptan as early as possible after the
onset of migraine headache and two attacks (n=40) as late as the patients could
bear. The median intra-individual difference between the two strategies in time
from first occurrence of pain to injection was 5.7 h and the median
intra-individual difference in pain intensity at the time of injection was 29
visual analogue units. No significant differences were found in time to freedom
from pain, pain severity at 1 and 2 h, area under the curves from injection to
pain free or in headache recurrence after injection. At the end of the study,
most of the patients claimed that their medication was as effective when given
early as when given late in the course of the attack. The discrepancy between our
present findings and retrospective analyses of trials on oral triptans probably
has more to do with the less disturbed pharmacokinetics early during the migraine
attack than with central sensitization. Consequently, we recommend nonoral
formulations of triptans, which do not necessarily have to be administered early 
during the migraine attack to provide efficacy. In conclusion, it is reassuring
for migraineurs that it is worthwhile taking their medication in an appropriate
formulation even if they have not been able to do so early in the course of the
attack.

Publication Types: 
    Controlled Clinical Trial
    Research Support, Non-U.S. Gov't

PMID: 16426264 [PubMed - indexed for MEDLINE]

1405: Cephalalgia. 2006 Feb;26(2):98-106.

Infrequent or non-response to oral sumatriptan does not predict response to other
triptans--review of four trials.

Dahlöf CG.

Gothenburg Migraine Clinic, Gothenburg, Sweden. carl.dahlof@migraineclinic.se

A migraineur can claim to be an infrequent responder ('non-responder') to an oral
triptan independent of which triptan he or she is presently using. Four trials of
an alternative triptan (zolmitriptan/rizatriptan; eletriptan; naratriptan;
almotriptan) in patients with a history of infrequent response to oral
sumatriptan were compared and contrasted in terms of study design, patient
characteristics, and efficacy and tolerability of the triptan under
investigation. Unfortunately, none of the reported studies used an appropriate
parallel design, which would have had the non-responding triptan (oral
sumatriptan) in one arm and without encapsulation. While the four trials differed
in terms of study design (open-label vs. placebo-controlled), definition of
sumatriptan 'non-responder' (retrospective vs. prospective) and pain intensity at
baseline (30% severe to 70% severe), all four demonstrated that lack of response 
to sumatriptan did not predict lack of response to an alternative triptan.
Changing triptans resulted in 2-h pain-relief rates of 25-81% in patients with a 
history of poor response to sumatriptan. It can be concluded that migraine
patients who respond infrequently to sumatriptan should be switched to a
different triptan, as lack of response to one triptan does not predict likelihood
of responsiveness to another. A review of the available evidence suggests that
almotriptan may be one of the most appropriate choices for an alternative
triptan.

Publication Types: 
    Comparative Study
    Meta-Analysis
    Review

PMID: 16426262 [PubMed - indexed for MEDLINE]

1406: Cephalalgia. 2006 Feb;26(2):89-97.

Post-marketing experience with an opioid nasal spray for migraine: lessons for
the future.

Loder E.

Harvard Medical School, Boston, MA, USA. eloder@partners.org

In 1992 a nasal spray formulation of butorphanol, an opioid medication intended
for pain relief, was marketed in the USA on an unscheduled basis. Only a few
years later, amid widespread reports of abuse and dependence, primarily in
migraine patients, its manufacturer voluntarily requested the Food and Drug
Administration to reschedule the drug as a Schedule IV narcotic. The events
surrounding this episode are reviewed, and four problem areas that might have
contributed are identified: (i) inadequate review of previous experience with
other formulations of butorphanol; (ii) failure to consider the impact of disease
state and drug formulation on the risk of adverse events; (iii) the limited scope
of clinical trials prior to approval; and (iv) aggressive marketing efforts. The 
implications of these lessons for future drug development and post-marketing
surveillance in the migraine field are considered.

Publication Types: 
    Review

PMID: 16426261 [PubMed - indexed for MEDLINE]

1407: Acta Paediatr. 2005 Dec;94(12):1860-2.

Raynaud phenomena and migraine in two children: inclusion within a family of
related disorders.

Besser RE, Stern CM.

Department of Paediatrics, St. Thomas' Hospital, London, United Kingdom.

We report a case of two siblings with Raynaud phenomena and migraine, whose
symptoms were successfully treated with pizotifen. CONCLUSION: To our knowledge, 
this is the first case documenting the association between Raynaud phenomena and 
migraine in two siblings with a family history of Raynaud phenomena and ischaemic
heart disease.

Publication Types: 
    Case Reports

PMID: 16421056 [PubMed - indexed for MEDLINE]

1408: Eur J Neurol. 2006 Jan;13(1):85-8.

Adult abdominal migraine: a new syndrome or sporadic feature of migraine
headache? A case report.

d'Onofrio F, Cologno D, Buzzi MG, Petretta V, Caltagirone C, Casucci G, Bussone
G.

Azienda Ospedaliera S.G. Moscati, Avellino, Italy.

Abdominal migraine is one of the variants of migraine headache typically
occurring in children and coded as 1.3.2 in the revised edition of IHS
classification within the group 'Childhood periodic syndromes that are commonly
precursors of migraine'. The affected children frequently develop typical
migraine later in their life. We report a case of a 23 years old woman affected
by attacks of recurrent abdominal pain accompanied by migraine. Abdominal pain
attacks started in the adolescence and persisted without headache until the
patient was 21. At this time, she experienced migraine pain accompanied by
nausea, photophobia and phonophobia and associated to acute abdominal pain.
Neuroimaging investigations and laboratory testing excluded any underlying
organic disease. Complete remission of abdominal attacks was obtained during
4-month treatment period with pizotifen. Attacks fulfil IHS diagnostic criteria
for 'abdominal migraine', although of late onset. This case report suggests that 
'abdominal migraine' is a migraineous disorder to be hypothesized in adult
patients after having disclosed any organic disease. As reported in the
literature, 'adult abdominal migraine' is a sporadic migraine subtype in adult
patients and it is not to be considered as a new migraineous syndrome.

Publication Types: 
    Case Reports

PMID: 16420398 [PubMed - indexed for MEDLINE]

1409: Int Tinnitus J. 2005;11(1):81-4.

Vestibular rehabilitation for migraine-associated dizziness.

Gottshall KR, Moore RJ, Hoffer ME.

Department of Defense Spatial Orientation Center, Naval Medical Center, San
Diego, CA 92134, USA. krgottshall@nmcsd.med.navy.mil

The purpose of this study was to investigate the effects of a vestibular
rehabilitation program on patients with the diagnosis of migraine-associated
dizziness. Subjects were placed in four groups as follows: idiopathic
migraine-associated dizziness; idiopathic migraine-associated dizziness and
associated benign positional vertigo; posttraumatic migraine-associated
dizziness; and posttraumatic migraine-associated dizziness and benign positional 
vertigo. Vestibular rehabilitation therapy was administered to all patients.
Criterion measurements included the dizziness handicap inventory,
activities-specific balance confidence scale, computerized dynamic posturography 
performance, and dynamic gait index. After vestibular physical therapy, all
subjects showed significant improvement in the dizziness handicap,
activities-specific balance confidence, dynamic gait, and computerized dynamic
posturography measures. Patients with migraine-associated dizziness can benefit
from physical therapy intervention. The results of this study are important in
considering the approach to vertiginous migraine patients with and without head
injury.

PMID: 16419697 [PubMed - indexed for MEDLINE]

1410: J Child Neurol. 2005 Oct;20(10):809-13.

Serial headache drawings by children with migraine: correlation with clinical
headache status.

Stafstrom CE, Goldenholz SR, Dulli DA.

Department of Neurology, University of Wisconsin, 600 Highland Avenue, Madison,
53792, USA. stafstrom@neurology.wisc.edu

Children's artistic self-depictions of headache provide valuable insights into
their experience of pain and aid in the diagnostic differentiation of headache
types. In a previous study, we compared the clinical diagnosis (gold standard)
and artistic diagnosis of headaches in 226 children. In approximately 90% of
cases, the drawing predicted the clinical diagnosis of migraine versus
nonmigraine headache correctly. In the present study, we explored whether
headache drawings correlate with clinical improvement after treatment in children
with migraine headaches followed longitudinally. Children seen in the Pediatric
Neurology Clinic with the chief complaint of headache were asked to draw a
picture of what their headache feels like. On subsequent clinic visits, children 
with the clinical diagnosis of migraine were asked to draw another picture
depicting their current headache. The two drawings were compared to assess
whether there was improvement; this "artistic response" was then correlated with 
the child's clinical status (ie, whether the headaches were improved clinically).
One hundred eleven children (66 girls, 45 boys) participated in the study, with a
mean interval of 5.3 +/- 2.3 (standard error of the mean) months between the
first and second visits. The mean age at the first visit was 11.6 +/- 3.1 years. 
The raters agreed that serial drawings were both improved or both not improved in
99 of the 111 cases (89%; interrater reliability kappa score of 0.767).
Fifty-three children had improvements in their headaches and drawings, 3 children
had an improved drawing but no clinical headache improvement, 32 children had no 
improvement in either their drawing or clinical headaches, and 11 children had
improved headaches but no improvement in their drawing. The sensitivity of the
drawings for clinical improvement was 0.83, and the specificity was 0.91. The
predictive value of an improved headache drawing for an improved clinical
response was 0.946. There was no correlation between specific treatment modality 
and artistic response. We concluded that children's headache drawings are a
useful adjunct for the diagnosis of headache type and provide valuable insights
into their experience of pain. The present data show that headache drawings can
be used longitudinally to provide additional information about the clinical
course. The technique is simple, inexpensive, and enjoyable for children and can 
be applied in a variety of clinical settings.

Publication Types: 
    Evaluation Studies

PMID: 16417875 [PubMed - indexed for MEDLINE]

1411: Eur J Neurol. 2006 Feb;13 Suppl 1:51-4.

Botulinum toxin therapy of migraine and tension-type headache: comparing
different botulinum toxin preparations.

Schulte-Mattler WJ, Martinez-Castrillo JC.

Department of Neurology, University of Regensburg, Regensburg, Germany.
wilhelm.schulte-mattler@klinik.uni-regensburg.de

Most of the initial reports on botulinum toxin in tension-type headache (TTH) and
in migraine were positive. Unfortunately, these results were not reproduced in
well-designed, randomized controlled trials. So far, doses from 20 U (Botox) to
500 U (Dysport) have been studied in patients with chronic TTH, and doses from 16
to 200 U (Botox) in patients with migraine. Overall, there is no evidence for a
beneficial effect of botulinum toxin, although trends favoring botulinum toxin
were reported. Experience with botulinum toxin type B (Myobloc/NeuroBloc) is
limited and similar to the experience with the type A. Thus, a widespread use of 
botulinum toxin therapy in headache can currently not be recommended.

Publication Types: 
    Review

PMID: 16417598 [PubMed - indexed for MEDLINE]

1412: Am Fam Physician. 2006 Jan 1;73(1):72-8.

Erratum in:
    Am Fam Physician. 2006 Nov 15;74(10):1685.

Medications for migraine prophylaxis.

Modi S, Lowder DM.

Department of Family Medicine, Brody School of Medicine at East Carolina
University, Greenville, North Carolina 27834, USA. modis@mail.ecu.edu

Sufficient evidence and consensus exist to recommend propranolol, timolol,
amitriptyline, divalproex, sodium valproate, and topiramate as first-line agents 
for migraine prevention. There is fair evidence of effectiveness with gabapentin 
and naproxen sodium. Botulinum toxin also has demonstrated fair effectiveness,
but further studies are needed to define its role in migraine prevention. Limited
evidence is available to support the use of candesartan, lisinopril, atenolol,
metoprolol, nadolol, fluoxetine, magnesium, vitamin B2 (riboflavin), coenzyme
Q10, and hormone therapy in migraine prevention. Data and expert opinion are
mixed regarding some agents, such as verapamil and feverfew; these can be
considered in migraine prevention when other medications cannot be used. Evidence
supports the use of timed-release dihydroergotamine mesylate, but patients should
be monitored closely for adverse effects.

Publication Types: 
    Review

PMID: 16417067 [PubMed - indexed for MEDLINE]

1413: Contraception. 2006 Feb;73(2):189-94. Epub 2005 Oct 21.

Use of combined oral contraceptives among women with migraine and nonmigrainous
headaches: a systematic review.

Curtis KM, Mohllajee AP, Peterson HB.

WHO Collaborating Center in Reproductive Health, Division of Reproductive Health,
Centers for Disease Control and Prevention, Atlanta, GA 30341, USA. kmc6@cdc.gov

This systematic review examines evidence evaluating whether women with headaches 
who use combined oral contraceptives (COCs) have a greater risk of stroke than
women with headaches who do not use COCs. We searched MEDLINE for articles
published from 1966 through March 2005 relevant to headaches and COC use as risk 
factors for stroke. Of the 79 articles identified, nine met our selection
criteria (eight reports of six observational studies plus one meta-analysis). All
studies reported specifically on migraine headaches. Evidence from six
case-control studies suggested that COC users with a history of migraine were two
to four times as likely to have an ischemic stroke as nonusers with a history of 
migraine. The odds ratios for ischemic stroke ranged from 6 to almost 14 for COC 
users with migraine compared with nonusers without migraine. The three studies
that provided evidence on hemorrhagic stroke reported low or no risk associated
with migraine or with COC use.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, Non-P.H.S.
    Research Support, U.S. Gov't, P.H.S.
    Review

PMID: 16413849 [PubMed - indexed for MEDLINE]

1414: Headache. 2006 Jan;46(1):169-73.

Solitary fourth ventricular neurocysticercosis presenting as status migrainosus.

Shukla R, Paliwal VK, Jha D.

Fourth ventricular cysts in patients with neurocysticercosis are generally
solitary without accompanying parenchymal cysts and hence present with
hydrocephalic symptoms at the time of implantation. We report a patient with
status migrainosus-like presentation in whom the neurological examination was
normal and the diagnosis was made by imaging (CT and MRI scan).

Publication Types: 
    Case Reports
    Letter

PMID: 16412167 [PubMed - indexed for MEDLINE]

1415: Headache. 2006 Jan;46(1):138-49.

Zolmitriptan intranasal: a review of the pharmacokinetics and clinical efficacy.

Goadsby PJ, Yates R.

Institute of Neurology, Headache Group, London, UK.

Migraine is a common disabling neurological disorder, associated with headache,
nausea, and on occasions vomiting. Zolmitriptan is a widely available serotonin
5HT(1B/1D) receptor agonist with a long track record in clinical studies and in
the treatment of acute migraine. A nasal formulation has been developed that has 
clear evidence for local absorption, resulting in plasma drug concentrations
within 2 minutes of dosing, central nervous system penetration 3 minutes later,
and a significant efficacy benefit versus placebo 10 to 15 minutes after dosing. 
Intranasal zolmitriptan offers advantages to migraineurs, particularly those
seeking a more rapid onset of effect without wishing to self-inject, or those
with gastrointestinal upset. The comparison of pharmacokinetic and clinical data 
available from different formulations of zolmitriptan contributes both to the
understanding of its mode of action and the characteristics required of an acute 
migraine treatment if it is to meet patient needs.

Publication Types: 
    Review

PMID: 16412161 [PubMed - indexed for MEDLINE]

1416: Headache. 2006 Jan;46(1):125-37.

Symptoms of premenstrual syndrome and their association with migraine headache.

Martin VT, Wernke S, Mandell K, Ramadan N, Kao L, Bean J, Liu J, Zoma W, Rebar R.

Departmentof Internal Medicine, University of Cincinnati, Cincinnati, OH
45267-4217, USA.

OBJECTIVES: To determine the association between the severity of premenstrual
(PMS) symptoms and headache outcome measures during natural menstrual cycles and 
after medical oophorectomy. BACKGROUND: Premenstrual syndrome may occur in 64% of
those with pure menstrual migraine and 33% of those with menstrually related
migraine. Few past studies have examined the relationship between the severity of
PMS symptoms and migraine headache. METHODS: Data were obtained from a 6.5-month 
randomized-controlled trial examining the role of medical oophorectomy in the
prevention of migraine headache and later divided into two data sets for analysis
purposes. The menstrual cycle data set was composed of data from three natural
menstrual cycles obtained from 21 participants during lead-in and placebo run-in 
phases. Each menstrual cycle was subdivided into seven 3-day intervals based on
urine hormone metabolites. The medical oophorectomy data set included data from a
2-month treatment period in which a medical oophorectomy was induced by
gonadotropin-releasing hormone agonists (GnRHa) and participants were randomized 
to transdermal estradiol or a matching placebo (GnRHa/estradiol and GnRHa/placebo
groups, respectively). All participants completed a daily diary recording the
severity of PMS symptoms and headache outcome measures. The primary outcome
measures were the PMS index (mean of the daily PMS severity scores) and the
headache index (mean of the headache severity scores). Pearson correlation
coefficients were used to assess the degree of association between the outcome
measures. RESULTS: Menstrual Cycle Data Set.-The PMS index was significantly
correlated with the headache index during native menstrual cycles (correlation
coefficient of 0.47; P < .05) and during all seven intervals of the menstrual
cycle (correlation coefficients of 0.39 to 0.65; all P values < .05). Medical
Oophorectomy Data Set.-Correlation coefficients between the PMS and headache
indices were 0.58 and 0.47 for the GnRHa/estradiol (n = 9) and GnRHa/placebo
groups, respectively (P-values of <.05). CONCLUSIONS: Moderate correlations exist
within female migraineurs between the severity of PMS symptoms and headache
outcome measures throughout natural menstrual cycles as well as after medical
oophorectomy. Our data would suggest that the presence and severity of headache
might modulate PMS symptoms in female migraineurs.

Publication Types: 
    Randomized Controlled Trial
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 16412160 [PubMed - indexed for MEDLINE]

1417: Headache. 2006 Jan;46(1):115-24.

Oral sumatriptan for the acute treatment of probable migraine: first randomized, 
controlled study.

Tepper SJ, Cady R, Dodick D, Freitag FG, Hutchinson SL, Twomey C, Kuhn TA.

New England Center ofr Headache, Stamford, CT 06902, USA.

OBJECTIVE: To evaluate the efficacy and tolerability of sumatriptan tablets in
adults who meet International Headache Society (IHS) criteria for probable
migraine but who do not meet IHS criteria for migraine with or without aura.
BACKGROUND: Headaches with some but not all of the features of migraine meet
criteria for probable migraine, a form of migraine recognized by the IHS.
Probable migraine attacks are also prevalent and frequently underdiagnosed.
METHODS: This was a randomized, multicenter, double-blind, placebo-controlled,
parallel-group study. Adults (18 to 65 years) with a 1-year history of headaches 
that met 2004 IHS criteria for probable migraine without aura (same operational
definition as 1988 IHS migrainous disorder) were eligible for enrollment. All
patients were triptan- and ergot-naïve and had never been diagnosed with
migraine. Patients were randomized in a 1:1:1:1 fashion to receive sumatriptan
25, 50, or 100 mg conventional tablets or matching placebo and were instructed to
treat a single moderate or severe probable migraine attack. A post hoc analysis
was conducted to evaluate the population of patients who achieved headache relief
sustained throughout the immediate posttreatment period. Patients who reported
relief within 2 hours and subsequently lost headache relief within 4 hours were
considered nonresponders. RESULTS: At 2 hours, more patients treated with
sumatriptan achieved headache relief, the primary efficacy measure, compared with
placebo, but differences only approached statistical significance for 100 mg (P= 
.053). The 2-hour headache relief rate in the sumatriptan 25 or 50 mg groups was 
not significantly different than placebo. The time to use of rescue was
significantly shorter in the placebo group compared with the sumatriptan 100 mg
group (P= .002). The time to use of rescue in the sumatriptan 25 or 50 mg groups 
was not significantly different than placebo. More patients treated with placebo 
(22%) lost headache relief within 4 hours compared with patients treated with
sumatriptan 25 mg (17%), 50 mg (14%), or 100 mg (7%). A post hoc analysis
demonstrated that at 2 hours, headache relief sustained through 4 hours (S 0-4
hours) was achieved in 44%, 49%, and 57% of patients treated with sumatriptan 25,
50, and 100 mg, respectively, compared with 34% of patients treated with placebo 
(P < .05 for sumatriptan 50 and 100 mg vs. placebo). All doses of sumatriptan
were well tolerated and no serious adverse events were reported. CONCLUSION:
These results suggest that oral sumatriptan may be effective and is well
tolerated for the acute treatment of probable migraine without aura, however, the
difference between sumatriptan and placebo was not statistically significant for 
the a priori defined primary endpoint.

Publication Types: 
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 16412159 [PubMed - indexed for MEDLINE]

1418: Headache. 2006 Jan;46(1):101-9.

Zolmitriptan oral tablet in migraine treatment: high placebo responses in
adolescents.

Rothner AD, Wasiewski W, Winner P, Lewis D, Stankowski J.

Cleveland Clinic Foundation, Cleveland, OH, USA.

OBJECTIVE: The objective of this randomized, double-blind, placebo-controlled
study was to evaluate the efficacy and tolerability of the zolmitriptan
conventional tablet at three different doses for the treatment of a single
migraine attack in adolescents. BACKGROUND: Preliminary data from an open-label
study suggested that the zolmitriptan conventional tablet could be effective in
the treatment of acute migraine in adolescent patients. Methods: Migraine
patients aged 12 to 17 years (n = 850) were randomized to receive zolmitriptan
2.5, 5, or 10 mg, or placebo for treatment of a single migraine attack. Patients 
recorded migraine headache intensity before and after treatment using a 4-point
scale. RESULTS: There was no statistically significant improvement between
zolmitriptan 10 mg (2 x 5 mg tablet) and placebo for the primary efficacy
variable, headache response at 2 hours, nor any of the secondary variables
tested. Two-hour headache response rates were 54%, 53%, and 57% for zolmitriptan 
10, 5, and 2.5 mg, respectively, and 58% for placebo. Two-hour pain-free rates
were 25%, 19%, and 23% for zolmitriptan 10, 5, and 2.5 mg, respectively, and 20% 
for placebo. Zolmitriptan was well tolerated, with a tolerability profile similar
to the pattern seen in adults. CONCLUSION: The similar efficacy between
zolmitriptan and placebo appears to be the result of the high placebo response
rate. This is a recognized issue in pediatric migraine studies and there is an
ongoing debate on ways to address this problem. Since this study was initiated,
there has been some debate on the appropriateness of the 2-hour endpoint for
response rates in adolescent studies, given the shorter duration of headache pain
in adolescents compared with adults. Furthermore, accurate information regarding 
the timeliness of treatment and reporting of headache-related information by
adolescents is difficult.

Publication Types: 
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 16412157 [PubMed - indexed for MEDLINE]

1419: Headache. 2006 Jan;46(1):92-100.

Effects of a Website designed to improve the management of migraines.

Sciamanna CN, Nicholson RA, Lofland JH, Manocchia M, Mui S, Hartman CW.

Jefferson Medical College, Philadelphia, PA 19107, USA.

OBJECTIVE: The aim was to examine the effect of using a Web-based computer
program that provides personalized feedback to migraine patients, on the
interactions of patients and providers. Background.-Despite the widespread
availability of evidence-based migraine treatment guidelines, patients often do
not receive optimal treatment to reduce migraine pain and disability. METHODS: To
address these quality gaps in migraine care, we developed a Web-based computer
program, to be used by migraine patients before doctor visits. The feedback is
designed to prompt patients to ask questions that lead to higher quality of care.
This study was conducted to examine the effect of using the program on
migraine-specific doctor-patient communications. Patients were randomized to use 
the Website before (intervention) or after (control) a visit with their provider.
The outcome measures were the migraine-specific topics discussed during the
visit, measured by an exit survey after the visit. RESULTS: Fifty of 53 subjects 
randomized completed the postvisit measures (94%). Overall, the mean age was 42.0
years, most patients were female (86.5%), all were white, and 58.5% saw a
headache specialist during their visit. Most (75.0%) reported having headaches at
least once per week and 48.1% rated their headaches as "severe." Intervention
patients were significantly more likely to "discuss whether you had migraine
headaches or some other type of headache?" (89.3% vs 54.5%; P < .01) and to
"discuss whether or not there may be a more serious cause of your headaches?"
(50.0% vs 13.6%; P < .01). Intervention patients were more likely to report
discussing 8 of 12 migraine-related topics more frequently and a greater overall 
number of topics (5.5 vs 4.3) than control patients. This difference was not
statistically significant. CONCLUSIONS: These results suggest that the Website
may have a positive impact on migraine-specific doctor-patient communications. A 
larger study, including important quality of life and utilization outcomes, is
warranted.

Publication Types: 
    Randomized Controlled Trial
    Research Support, N.I.H., Extramural

PMID: 16412156 [PubMed - indexed for MEDLINE]

1420: Headache. 2006 Jan;46(1):64-72.

Weather and emergency room visits for migraine headaches in Ottawa, Canada.

Villeneuve PJ, Szyszkowicz M, Stieb D, Bourque DA.

Air Health Effects Division, Health Canada, Ottawa, Ontario, Canada.

BACKGROUND: Self-reported surveys have indicated that weather can trigger
migraine headaches. However, to date, we know of no previous study that has
examined the relationship between weather and emergency room (ER) visits for this
condition. OBJECTIVE: To examine associations between ER visits for migraines and
selected meteorological conditions within the 24 hours preceding the visit.
DESIGN AND METHODS: A case-crossover design was used to study 4039 visits for
migraines (ICD-9: 346) that occurred at an Ottawa hospital between 1993 and 2000.
Meteorological conditions were defined using hourly readings from a fixed-site
monitoring station. Conditional logistic regression was used to compare the
occurrence of meteorological conditions during the 24 hours leading up to the
time of the visit to control periods occurring 1 week before and after. RESULTS: 
Precipitation-related weather events (fog, snow, rain, thunder) were not
associated with migraine visits. Similarly, no associations were observed with
changes in atmospheric pressure, wind speed, and relative humidity during the 24 
hours preceding presentation. No statistically significant differences in the
frequency distribution of clusters defined by relative humidity, atmospheric
pressure, and temperature were found between case and control intervals.
Conversely, a mean wind speed in excess of 19 km per hour was associated with a
reduction in ER visits 8 to 12 hours later. CONCLUSIONS: Our findings provide
little support for the hypothesis that ER visits for migraines are related to
weather conditions occurring within the 24 hours preceding presentation. These
results should be interpreted cautiously as some comparisons are based on a small
number of cases, and ER visits for migraine may represent a highly selective
group of patients who suffer from this condition.

PMID: 16412153 [PubMed - indexed for MEDLINE]

1421: Headache. 2006 Jan;46(1):57-63.

Comment in:
    Headache. 2007 Jun;47(6):929; author reply 929-30.

Gastric stasis in migraine: more than just a paroxysmal abnormality during a
migraine attack.

Aurora SK, Kori SH, Barrodale P, McDonald SA, Haseley D.

Swedish Medical Center, Seattle, WA, USA.

OBJECTIVE: The aim of this article is to evaluate gastric motility and emptying
in the ictal and interictal period in migraine. BACKGROUND: Nausea is a
predominant symptom of migraine and the basis of it is thought to be gastric
stasis. Objective methods to establish this are however lacking. We utilized
gastric scintigraphy studies to determine gastric motility in the ictal and
interictal period of migraine. METHODS: Ten migraine subjects were compared to
equal number of age and sex matched controls. Gastric scintigraphy using a
standard meal was performed in all control subjects once and in all 10 migraine
subjects in the interictal period and nine studies were performed in the ictal
period migraine. RESULTS: The time to half emptying was delayed in migraine
ictally (78%) and interictal period (80%) using normative data at this
institution. Gastric stasis was less pronounced ictally (149.9 minutes) compared 
to interictal period (188.8 minutes). There was a significant delay compared to
nonmigrainous controls (migraine 188.8 minutes vs normal controls 111.8 minutes; 
P < .05). These data were replicated in percentage of radioactive material
remaining in the stomach at 2 hours. CONCLUSIONS: Contrary to previous belief,
this study has demonstrated that migraineurs suffer from gastric stasis both
during and outside an acute migraine attack. This may suggest that migraineurs
may have an abnormal autonomic function compared to nonmigrainous controls. The
potential role of this in pathophysiology of migraine is discussed and avenues
for further investigations are explored.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16412152 [PubMed - indexed for MEDLINE]

1422: Headache. 2006 Jan;46(1):46-56.

Comment in:
    Headache. 2007 Jan;47(1):136.

Subclinical left ventricular dysfunction in migraine attacks.

Vidalón M.

Department of Cardiology and Neurology, Promitra Center for Research and
Treatment of Stress, São Carlos Hospital, Curitiba, Brazil.

OBJECTIVE: The aim of the present study was to evaluate cardiac performance of
patients with migraine attacks during the overload produced by phenylephrine
infusion. Background.-It is known that circulatory changes occur during migraine.
However, the relationship between this finding and transient cardiac dysfunction 
is still unknown. METHODS: By means of two-dimensional direct M-mode
echocardiography, we measured fractional shortening, ejection fraction, and mean 
velocity of circumferential fibers shortening in 18 patients with migraine and in
10 normal subjects as a control group. These measures were performed in two
different periods: during attack-free intervals and during attacks. Pain
intensity of typical migraine attack was evaluated on a 0 to 10 scale. RESULTS:
Cardiac size and function were normal at rest in both groups. However, during
migraine attacks, phenylephrine infusion provoked significant decrease in
fractional shortening, EF, and mean velocity of circumferential fibers
shortening, followed by concomitant increase of headache severity. On the other
hand, during the attack-free interval and in the control group phenylephrine
infusion did not show significant changes in cardiac function parameters.
CONCLUSIONS: Our data suggest that left ventricular dysfunction during the
phenylephrine test could participate in the complex pathophysiological mechanism 
of migraine attacks.

Publication Types: 
    Clinical Trial

PMID: 16412151 [PubMed - indexed for MEDLINE]

1423: Headache. 2006 Jan;46(1):24-33.

Salivary levels of CGRP and VIP in rhinosinusitis and migraine patients.

Bellamy JL, Cady RK, Durham PL.

Department of Biology, Missouri State University, MO 65804, USA.

BACKGROUND: Secretion of calcitonin gene-related peptide (CGRP) from trigeminal
nerves and vasoactive intestinal peptide (VIP) from parasympathetic nerves is
involved in the pathophysiology of migraine and rhinosinusitis. Analysis of these
neuropeptides in human saliva samples can be used as markers of trigeminal and
parasympathetic nerve activity in patients between and during attacks as well as 
in response to specific treatments. OBJECTIVE: To compare the amount of
trigeminal sensory and parasympathetic nerve activation by measuring CGRP and VIP
levels in the saliva of subjects experiencing noninfectious allergic
rhinosinusitis, migraine with sinus symptoms, and no symptoms. METHODS: Subjects 
were enrolled in three groups. Group A: subjects without a history of migraine,
"sinus" headache, or allergic rhinosinusitis within the previous 6 months. Group 
B: subjects with chronic recurrent noninfectious rhinosinusitis and no history of
migraine or "sinus" headache. Group C: subjects with self-described "sinus"
headaches whose symptoms met International Headache Society diagnostic criteria
(1.1 or 1.2) for migraine. The total amount of CGRP and VIP present in saliva
collected under normal, pathological, and therapeutic conditions was determined
by radioimmunoassay. Neuropeptide levels were normalized to total volume and
amount of protein, and levels were correlated to onset and change in clinical
symptoms. RESULTS: Total volume, total protein, and CGRP and VIP levels did not
significantly change in saliva collected on consecutive days in the clinic and at
the subject's home, respectively. No appreciable change in baseline salivary
levels of CGRP and VIP was detected in control subjects. However, baseline
salivary levels of CGRP and VIP were significantly elevated between attacks in
allergic rhinosinusitis and migraine subjects compared to control values. For
rhinosinusitis subjects, the amount of CGRP and VIP during attacks returned to
baseline values following treatment with pseudoephedrine and relief of symptoms. 
Similarly, CGRP and VIP levels during a migraine headache were significantly
reduced within 2 hours after sumatriptan treatment and reported symptom relief.
CONCLUSION: Correlation of CGRP and VIP saliva levels observed in our study
supports physiologically coordinated regulation of trigeminal and parasympathetic
nerve activation in allergic rhinosinusitis and migraine patients between and
during attacks as well as following treatment. Furthermore, our findings
demonstrate that analysis of human saliva neuropeptides may provide a
semiquantitative index of pathological and therapeutic states and, therefore,
function as a clinical model for studying neuronal mechanisms involved in
migraine and rhinosinusitis.

PMID: 16412148 [PubMed - indexed for MEDLINE]

1424: Headache. 2006 Jan;46(1):3-23.

Ovarian hormones and migraine headache: understanding mechanisms and
pathogenesis--part I.

Martin VT, Behbehani M.

Department of Internal Medicine, University of Cincinnati College of Medicine, OH
45267-4217, USA.

Ovarian hormones have a significant effect on the central nervous system of
female migraineurs. Reproductive milestones such as menarche, pregnancy, and
menopause are associated with changes in the clinical course of migraine
headache. Migraine attacks are commonly triggered during declines in serum
estrogen levels that occur before and during the time of menstruation. Therefore,
substantial clinical evidence suggests that changes in ovarian hormones affect
migraine headache. This represents the first of two manuscripts defining the role
of ovarian hormones in the pathogenesis of migraine headache. The purpose of the 
first article will be to review the molecular and neurophysiologic effects of
estrogen and progesterone on neurotransmitter systems and pain processing
networks relevant to migraine headache. The second manuscript will focus on the
clinical studies detailing the influence of estrogen and progesterone on migraine
headache.

Publication Types: 
    Review

PMID: 16412147 [PubMed - indexed for MEDLINE]

1425: Mol Genet Metab. 2006 Jun;88(2):107-13. Epub 2006 Jan 5.

The role of vascular and hormonal genes in migraine susceptibility.

Colson NJ, Lea RA, Quinlan S, Griffiths LR.

Genomics Research Centre, School of Health Science, Griffith University, Gold
Coast, Qld 9726, Australia.

Migraine is a primary headache disorder that involves both genetic and
environmental components. Migraine is considered to be a polygenic disorder with 
a number of susceptibility genes having a minor but nonetheless significant
impact on susceptibility. Migraine candidate gene studies have concentrated
mainly on genes involved in neurotransmitter pathways, however evidence also
exists for a role for alterations in vascular and hormonal function in migraine
susceptibility. We present here a mini-review of genetic studies, investigating
the potential role of vascular and hormonal gene variants, and discuss how
vascular and hormonal dysfunction may impact on migraine susceptibility. We
propose that the potential role of vascular and hormonal genes in this disorder
warrants further investigation.

Publication Types: 
    Review

PMID: 16403664 [PubMed - indexed for MEDLINE]

1426: Eur J Clin Pharmacol. 2006 Mar;62(3):161-72. Epub 2006 Jan 10.

A meta-analysis of the placebo response in acute migraine and how this response
may be influenced by some of the characteristics of clinical trials.

Macedo A, Farré M, Baños JE.

Department of Pharmacology, Therapeutics and Toxicology, Universitat Autònoma de 
Barcelona, Bellaterra, Spain.

Migraine is the most common cause of vascular headache and a highly prevalent
illness. In the last 20 years, the discovery of new agents has increased clinical
research on migraine. In most of clinical trials that have been conducted, the
efficacy was established using a placebo as a control treatment. The objective of
the study reported here was to analyse the response rate in patients who received
a placebo as well as to determine how a number of the methodological factors may 
affect the effect of the placebo in clinical trials of acute migraine.
Computer-based information searches were conducted on the Medline database. Data 
analysis included the outcomes 'pain relief', 'pain-free', 'associated symptoms',
'recurrence', 'patients' opinion' about pain relief and 'adverse events'.
Administration route, study design and country in which the study was carried out
were the methodological factors that were analyzed. Meta-analysis was computed
using Mantel-Haenszel, and a total of 98 papers were considered in the final
analysis. After 2 h, 28.6% of the patients of the placebo group improved and 8.8%
were pain-free. The percentage of pain-free patients was the highest in the
placebo and active drug groups in which the placebo or drug had been administered
subcutaneously, in parallel design studies (vs. cross-over trials) and in studies
performed in Europe (vs. North America). Adverse events in the placebo group were
significantly higher in studies performed in North America. These data reinforce 
the need for knowing the magnitude of the placebo response in each specific
situation during the planning of clinical trials on acute migraine.

Publication Types: 
    Meta-Analysis

PMID: 16402240 [PubMed - indexed for MEDLINE]

1427: Rev Neurol Dis. 2004 Summer;1(3):155-60.

Chronic migraine: diagnosis and management strategy.

Silberstein SD.

Department of Neurology, Jefferson Medical College, Thomas Jefferson University, 
Philadelphia, PA, USA.

The case presented underscores the complexities encountered in diagnosing and
managing patients with a long-standing history of headache and some of the
difficulties in classifying patients according to the new International Headache 
Society (IHS) criteria. A 42-year-old nurse with 4 children whose headaches began
at age 24 years developed continuous headaches of varying intensity, regularly so
debilitating that she was unable to get out of bed and occasionally so disabling 
that she required an injection of meperidine from her physician. Management
strategies are presented and the revised IHS criteria are discussed.

Publication Types: 
    Case Reports
    Review

PMID: 16400273 [PubMed - indexed for MEDLINE]

1428: J Behav Med. 2006 Feb;29(1):61-7. Epub 2006 Jan 6.

The contribution of pain-related anxiety to disability from headache.

Nash JM, Williams DM, Nicholson R, Trask PC.

Centers for Behavioral and Preventive Medicine, Brown Medical School/The Miriam
Hospital, Providence, Rhode Island, USA. Justin_Nash@brown.edu

Disability associated with headache cannot be fully accounted for by pain
intensity and headache frequency. As such, a variety of cognitive and affective
factors have been identified to help explain headache-related disability beyond
that accounted for by pain levels. Pain-related anxiety, a multidimensional
construct, also has been found to contribute to disability in headache sufferers.
What is not known is whether pain-related anxiety is unique in contributing to
disability beyond the role of headache-specific cognitive factors and emotional
distress. The present study examines the influence of pain-related anxiety on
disability, after controlling for pain, cognitive (self-efficacy and locus of
control), and affective factors (emotional distress) in a sample of 96 primary
headache sufferers. Pain, headache-related control beliefs, and emotional
distress accounted for 32%, with locus of control related to health care
professionals contributing unique variance. In the full model, with the addition 
of pain-related anxiety, only pain-related anxiety was a unique predictor of
disability. These findings suggest that pain-related anxiety may have a unique
and important role in contributing to disability in headache sufferers.

PMID: 16397822 [PubMed - indexed for MEDLINE]

1429: Cephalalgia. 2006 Jan;26(1):74-80.

Cognitive function is not impaired in people with a long history of migraine: a
blinded study.

Pearson AJ, Chronicle EP, Maylor EA, Bruce LA.

Pennine Acute Hospitals NHS Trust, Manchester, UK.

Little is known about the long-term consequences of migraine for cognitive
functioning. This study compared older migraine patients with matched controls on
four measures of cognitive ability, in a blinded design. Migraine patients and
case-matched controls were recruited from the database records of a pre-existing 
study of ageing. Data were available from four tests of cognitive ability:
verbal/arithmetic problem solving, spatial problem solving, processing speed, and
vocabulary. There were no significant differences between the mean scores of
migraine and control groups on any of the four cognitive tests. In addition,
there were no significant differences between migraine and control groups in the 
effect of age on any of the four tests. A long history of migraine does not
compromise scores on the four cognitive tests used in this study. These tests are
predictive of memory and executive functioning in cognitive ageing, but it
remains possible that lower-level cognitive processes, particularly as assessed
by visual tasks, may be vulnerable to migraine.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16396669 [PubMed - indexed for MEDLINE]

1430: Cephalalgia. 2006 Jan;26(1):64-73.

Stress-induced pain and muscle activity in patients with migraine and
tension-type headache.

Leistad RB, Sand T, Westgaard RH, Nilsen KB, Stovner LJ.

Department of Neuroscience, Norwegian University of Technology and Science and
Department of Neurology and Clinical Neurophysiology, St Olavs Hospital,
Trondheim, Norway.

We recorded deep pain and surface electromyographic (EMG) responses to stress in 
22 migraineurs during headache-free periods, 18 patients with tension-type
headache (TTH), and 44 healthy controls. Sixty minutes of cognitive stress was
followed by 30 min relaxation. EMG and pain (visual analogue scale) in the
trapezius, neck (splenius), temporalis and frontalis areas were recorded. TTH
patients had higher pain responses in temporalis and frontalis (with similar
trends for trapezius and splenius) and more potentiation of pain during the test 
than controls. Migraine patients developed more pain in the splenius and
temporalis than controls. Muscle pain responses were more regional (more pain in 
the neck and trapezius compared with the temporalis and frontalis) in migraine
than in TTH patients. TTH patients had delayed pain recovery in all muscle
regions compared with controls, while migraine patients had delayed pain recovery
in a more restricted area (trapezius and temporalis). EMG responses were not
different from controls in headache patients, and EMG responses did not correlate
with pain responses. TTH patients had delayed EMG recovery in the trapezius
compared with controls and migraine patients. These results support the concept
that (probably central) sensitization of pain pathways and the motor system is
important in TTH. Less pronounced and more regional (either peripheral or
central) trigeminocervical sensitization seems to be important in migraine.
Surface-detectable muscular activation does not seem to be causal for pain during
cognitive stress either in migraine or in TTH.

Publication Types: 
    Comparative Study

PMID: 16396668 [PubMed - indexed for MEDLINE]

1431: Cephalalgia. 2006 Jan;26(1):56-63.

Forearm vascular response to nitric oxide and calcitonin gene-related peptide:
comparison between migraine patients and control subjects.

de Hoon JN, Smits P, Troost J, Struijker-Boudier HA, Van Bortel LM.

Centre for Clinical Pharmacology, University Hospital Gasthuisberg (K.U.Leuven), 
Leuven, Belgium.

The forearm vascular response to nitric oxide (NO) and calcitonin gene-related
peptide (CGRP) was investigated in 10 migraine patients and 10 matched control
subjects. Changes in forearm blood flow (FBF) during intrabrachial infusion of:
(i) serotonin (releasing endogenous NO), (ii) sodium nitroprusside (SNP,
exogenous NO-donor), and (iii) CGRP were measured using venous occlusion
plethysmography. Flow-mediated dilation (FMD) of the brachial artery, a measure
for the endogenous release of NO reactive to occlusion, was measured using
ultrasound and expressed as percentage change vs. baseline diameter. FBF ratio
(i.e. FBF in the infused over the control arm) at baseline (1.1 +/- 0.1) did not 
differ between both populations. Serotonin, SNP and CGRP induced a dose-dependent
increase (P < 0.001) in FBF ratio in controls (to 2.8 +/- 0.3, 6.7 +/- 1.4 and
6.9 +/- 1.2 at the highest dose, respectively) and migraineurs (2.5 +/- 0.4, 5.6 
+/- 0.8 and 6.5 +/- 1.3, respectively); these ratios did not differ between both 
groups. FMD was comparable in control subjects (5.8 +/- 1%) and migraine patients
(5.2 +/- 1%). Based on the forearm vascular response to NO and CGRP, migraine
patients do not display generalized changes in vascular function.

Publication Types: 
    Comparative Study
    Controlled Clinical Trial

PMID: 16396667 [PubMed - indexed for MEDLINE]

1432: Cephalalgia. 2006 Jan;26(1):43-9.

Patterns of medical diagnosis and treatment of migraine and probable migraine in 
a health plan.

Bigal ME, Kolodner KB, Lafata JE, Leotta C, Lipton RB.

Department of Neurology, Albert Einstein College of Medicine, Bronx, New York,
NY, USA.

The objectives of this study were to assess the proportion of subjects with
strict migraine (SM, migraine with and without aura), probable migraine (PM), and
all migraine (AM, SM and PM pooled together), who receive a medical diagnosis or 
a specific treatment within a health plan. Eligible participants were 18-55-year 
participants of a non-profit health maintenance organization (HMO) who had
received out-patient, emergency department, or in-patient care from a physician
within the past year. We used a validated computer-assisted telephone interview
(CATI) survey to identify SM, PM and controls (received out-patient, emergency
department, or in-patient care from a physician for any reason within the past
year, but did not have SM or PM). Medical and prescription drug claims for the
24-month period were linked to participant files. Among 8579 respondents, we
identified 1265 SM sufferers and 1252 PM sufferers, which were compared with 960 
randomly selected controls. Just 194 (15.3%) SM, 21 (1.7%) PM, and 215 (8.5%) AM 
sufferers received an in-patient or out-patient primary migraine claim in the
previous 24 months, compared with six (0.5%) controls; 240 (18.9%) SM, 39 (3.1%) 
PM, 279 (11.1%) AM sufferers, and eight controls (0.6%) received any migraine
claim. There were claims for migraine drugs (ICD-9 code for triptans or ergot
compounds) for just 140 (11.1%) SM and 34 (2.7%) PM sufferers, and migraine
analgesics (butalbital and isomethepthene compounds), for 6.3% SM and 2.2% PM
sufferers (0.7% of the controls). Migraine preventives were used for a larger
number of SM and PM sufferers (19.6% and 13.1%), but also for controls (10.5%),
indicating that they were probably used for other medical reasons. Both SM and PM
are underdiagnosed and undertreated within a health plan. Educational strategies 
should focus on physician education addressing diagnosing the full spectrum of
migraine and physician management of migraine with specific migraine therapy in
appropriate patients.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16396665 [PubMed - indexed for MEDLINE]

1433: Cephalalgia. 2006 Jan;26(1):33-42.

Effects of oestrogen on trigeminal ganglia in culture: implications for hormonal 
effects on migraine.

Puri V, Puri S, Svojanovsky SR, Mathur S, Macgregor RR, Klein RM, Welch KM,
Berman NE.

Department of Anatomy and Cell Biology, University of Kansas Medical Center,
Kansas City, KS 66160, USA.

Although migraine is more common in women than men and often linked to the
menstrual cycle, few studies have investigated the biological basis of hormonal
influences on the trigeminovascular system. In the present study we investigated 
the effect of physiological levels (10(-9) m) oestrogen on female rat trigeminal 
ganglia in vitro. Immunocytochemical analysis demonstrated the presence of
oestrogen receptor-alpha in a predominantly cytoplasmic location and in neurites.
Microarray analysis demonstrated that oestrogen treatment regulates several genes
with potential relevance to menstrual migraine. The genes that were upregulated
included synapsin-2, endothelin receptor type B, activity and
neurotransmitter-induced early gene 7 (ania-7), phosphoserine aminotransferase,
MHC-1b, and ERK-1. Down-regulated genes included IL-R1, bradykinin B2 receptor,
N-tropomodulin, CCL20, GABA transporter protein, fetal intestinal
lactase-phlorizin hydrolase, carcinoembryonic antigen-related protein, zinc
finger protein 36, epsin 1 and cysteine string protein. Protein activity assays
demonstrated that exposure of the cultured neurons to oestrogen leads to
activation of ERK, which has been linked to inflammatory pain.
Immunocytochemistry demonstrated that activated ERK was present in neurons
containing peripherin, a marker of nociceptive neurons. Several of the genes in
the present study may provide potential targets for understanding the association
of oestrogen with migraine and other hormone-related orofacial pain.

Publication Types: 
    In Vitro
    Research Support, N.I.H., Extramural

PMID: 16396664 [PubMed - indexed for MEDLINE]

1434: Cephalalgia. 2006 Jan;26(1):26-32.

Comorbid migraine is associated with a negative impact on quality of life in
patients with major depression.

Hung CI, Liu CY, Fuh JL, Juang YY, Wang SJ.

Department of Psychiatry, Chang-Gung Memorial Hospital and Chang-Gung University 
School of Medicine, Taipei, Taiwan.

This study investigated the impact of migraine on health-related quality of life 
(HRQoL) among patients with major depressive disorder (MDD). We prospectively
enrolled 151 consecutive psychiatric out-patients meeting DSM-IV criteria for
MDD. Migraine and other headache types were diagnosed based on the International 
Classification of Headache Disorders, 2nd edition (2004). The Short Form-36
(SF-36) was administered as a generic instrument of HRQoL. Among 151 patients
with MDD, migraine (N = 73, 48.3%) was very common. Comorbidity of migraine
predicted a significantly negative impact on all physical subscales and vitality 
but not on the other mental subscales of the SF-36 after controlling for
depression, age and gender. The presence of migraine should be considered as an
important physical symptom in clinic-based MDD samples. Simultaneous management
of depression and severe headaches, especially migraine, might improve HRQoL in
patients with MDD.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16396663 [PubMed - indexed for MEDLINE]

1435: Cephalalgia. 2006 Jan;26(1):14-25.

Increased expression of endothelial and neuronal nitric oxide synthase in dura
and pia mater after air stress.

Zinck T, Illum R, Jansen-Olesen I.

Department of Pharmacology, The Danish University of Pharmaceutical Sciences,
Copenhagen, Denmark.

Stress is the leading precipitating factor for migraine attacks but the
underlying mechanism is currently unknown. Nitric oxide (NO) has been implicated 
in migraine pathogenesis based on the ability of NO donors to induce migraine
attacks. In the present study, we investigated in Wistar rats the effect of air
stress on nitric oxide synthase (NOS) mRNA and protein expression in dura and pia
mater using real-time polymerase chain reaction and Western blotting,
respectively. Endothelial (e)NOS protein expression was significantly increased
in dura and pia mater after air stress. Significantly augmented neuronal (n)NOS
protein expression was detected in pia mater after air stress but not in dura
mater. Inducible NOS mRNA and protein expression levels in dura and pia mater
were unaffected by stress. The increased expression of eNOS in dura mater and
eNOS and nNOS in pia mater seen after stress could not be antagonized by
treatment with the migraine drug sumatriptan. These findings point towards the
involvement of increased NO concentrations in dura and pia mater in response to
air stress. However, the role of these findings in relation to migraine
pathophysiology remains unclear.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16396662 [PubMed - indexed for MEDLINE]

1436: Cephalalgia. 2006 Jan;26(1):7-13.

Prognostic factors, disability, and functional status among patients in a
headache specialty practice.

Coeytaux RR, Spierings EL.

University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA.

The objective of this study was to identify prognostic factors and assess
functional status over time among patients in a headache specialty practice.
Study questionnaires were mailed to 599 patients who previously presented to a
headache specialty practice. Outcome measures included headache frequency, the
Headache Impact Test (HIT) and the SF-36 Health Survey. Completed surveys were
received from 333 respondents (56%). Thirty-five respondents (11%) had HIT scores
in the 'little or no impact' range at follow-up and 191 (57%) had HIT scores in
the 'severe impact' range. A diagnosis of migraine at baseline was an independent
predictor of elevated HIT scores at follow-up, but gender, age, age at headache
onset, daily headache at baseline, and time to follow-up did not predict poor
prognosis. A subset of headache patients continue to experience marked disability
and impaired functional status, months to years after presenting for headache
specialty care. A diagnosis of migraine at the time of presentation may predict
prognosis, but additional cohort studies with careful attention to baseline
variables are needed to help identify other prognostic factors.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16396661 [PubMed - indexed for MEDLINE]

1437: Cephalalgia. 2006 Jan;26(1):1-6.

Migraine with and without aura: association with depression and anxiety disorder 
in a population-based study. The HUNT Study.

Oedegaard KJ, Neckelmann D, Mykletun A, Dahl AA, Zwart JA, Hagen K, Fasmer OB.

Department of Psychiatry, University of Bergen, Bergen, Norway.

Some data indicate that migraine with aura (MA) is more strongly associated with 
anxiety disorder and depression than migraine without aura (MoA), but the
evidence is not conclusive. In the Nord-Trøndelag Health study 1995-1997, a total
of 49 205 (75% of the participants) subjects gave valid answers to both HADS
(Hospital Anxiety and Depression Scale) and a validated headache questionnaire.
Associations between anxiety disorder/depression and MA/MoA were evaluated by
multiple logistic regression analysis. Depression (DEP) [odds ratio (OR) 1.7; 95%
confidence interval (CI) 1.2, 2.6] and depression with comorbid anxiety disorder 
(COM) (OR 1.6; 95% CI 1.2, 2.1) were more likely in women having MA than in those
with MoA. No stronger association was found for pure anxiety disorder (ANX) in MA
vs. MoA (OR 0.9; 95% CI 0.7, 1.5). Among men, we found no difference in
prevalence of depression and anxiety disorders between MA and MoA. This is a new 
finding that might have relevance for both research and clinical treatment.

PMID: 16396660 [PubMed - indexed for MEDLINE]

1438: Tex Heart Inst J. 2005;32(3):362-5.

Does patent foramen ovale promote cryptogenic stroke and migraine headache?

Tobis MJ, Azarbal B.

Adult Cardiac Catheterization Laboratory, UCLA, Center for Health Sciences, Los
Angeles, California 90095-1717, USA. jtobis@mednet.ucla.edu

Cryptogenic stroke is a diagnosis of exclusion. These are strokes that occur in
people who are usually less than 55 years old, without an identifiable cause. Our
sensitivity to these events has been heightened because of the new definitions of
a transient ischemic attack. Transient ischemic attack (TIA) is a clinical
diagnosis of a neurologic deficit without MRI abnormalities: if there is an MRI
abnormality, whether or not that person is symptomatic, it is now defined as a
stroke. With these new definitions, and the sensitivity of MRI, we are seeing
more cryptogenic strokes. It has been hypothesized that many cryptogenic strokes 
are caused by small emboli that travel from the legs to the right atrium; during 
straining (such as a Valsalva maneuver) these emboli can go across a PFO into the
left atrium and then travel to the brain, producing a stroke. The problem is that
these are very small emboli, approximately 1 to 3 mm, and we can't actually show 
these small emboli crossing from right to left. However, large emboli have been
observed by echocardiography to be trapped in the PFO. So the diagnosis of
cryptogenic stroke is a diagnosis of exclusion that is impossible to verify. What
is the scope of the problem? Of the 700,000 strokes per year in the United
States, 80% of them are ischemic, and 20% of those are defined as cryptogenic.
The prevalence of PFO among this cryptogenic stroke population is about 40% to
50%; in the general population, it's only about 20%. Current estimates are that
somewhere between 30,000 and 60,000 strokes per year in the U.S. are caused by
paradoxical embolism through a PFO. There are some other fascinating
associations: scuba divers with PFOs are more susceptible to decompression
illness. Platypnea-orthodeoxia is a condition of desaturation that occurs when
you're standing up but not when you're lying down; these patients are quite
symptomatic, with arterial saturations in the low 80s. They also frequently have 
PFOs; if you close the PFO, the arterial desaturation is alleviated. Fat emboli
during orthopedic surgery or air emboli during neurosurgery may also travel
through the venous system. If you don't have a PFO, the fat or the air is trapped
in the lungs and doesn't cause much of a problem unless it's massive; but if you 
have a PFO, then the embolus can go from right to left atrium up to the brain,
with devastating neurologic consequences.

Publication Types: 
    Review

PMID: 16392219 [PubMed - indexed for MEDLINE]

1439: J Headache Pain. 2005 Dec;6(6):455-8. Epub 2005 Nov 10.

Clinical efficacy of rizatriptan for patients with migraine: efficacy of drug
therapy for migraine accompanied by tension headache-like symptoms, focusing on
neck stiffness.

Okuma H, Kitagawa Y, Takagi S.

Department of Neurology, Tokai University Tokyo Hospital, 1-2-5 Shibuy-ku Yoyogi,
151-0053, Tokyo, Japan. ookuma@tok.u-tokai.ac.jp

According to an epidemiological study in Japan, there are as many as 22 million
patients with tension headache and 8.4 million with migraine. Furthermore,
patients suffering from both types of headache concurrently are estimated to
account for more than 50% of headache patients. We studied the efficacy of drug
therapy for migraine accompanied by tension headache-like symptoms, focusing
principally on neck stiffness. We evaluated the efficacy of rizatriptan by
comparison of findings before and after therapy in 34 migraine patients,
consisting of 16 without neck stiffness (migraine without neck factor: WONF) and 
18 with it (migraine with neck factor: WNF), who received treatment at our
neurology/internal medicine department from 1 March 2004 to 31 May 2005. In the
study, all the patients were asked to keep a record of their migraine status. The
severity of migraine was classified by physicians according to the International 
Headache Society diagnostic criteria, based on which drug efficacy was evaluated.
We selected rizatriptan for migraine treatment in our study based on Dr.
Ferrari's report. In the efficacy study of rizatriptan, in the group of 34
migraine patients, the pain relief rate (79.4%) and pain-free rate (41.2%) at two
hours after treatment were as high as those reported in the meta-analysis
performed by Ferrari et al., indicating high efficacy of rizatriptan. In the
efficacy comparison between the WONF and WNF groups, the painfree rates were
56.3% and 27.8%, and cumulative pain relief rates were 100% and 61.1%,
respectively, with better results in the WONF group. A test result was also
significantly better (p=0.0076) in the WONF group. Rizatriptan was proved
effective in treating migraine patients accompanied by tension headache-like
symptoms. Comparison of efficacy rates between patient groups with and without
tension headache-like symptoms showed that the pain relief rate in the group
without neck stiffness was higher.

Publication Types: 
    Clinical Trial

PMID: 16388340 [PubMed - indexed for MEDLINE]

1440: J Headache Pain. 2005 Dec;6(6):429-40. Epub 2005 Dec 15.

The global burden of migraine: measuring disability in headache disorders with
WHO's Classification of Functioning, Disability and Health (ICF).

Leonardi M, Steiner TJ, Scher AT, Lipton RB.

Scientific Direction, Italian National Neurological Institute Carlo Besta, Via
Celoria 11, I-20133, Milan, Italy. leonardi@istituto-besta.it

This overview of the published epidemiological evidence of migraine helps to
identify the size of the public-health problem that migraine represents. It also 
highlights the need for further epidemiological studies in many parts of the
world to gain full understanding of the scale of clinical, economic and
humanistic burdens attributable to it. This paper presents some of the work on
migraine undertaken by the World Health Organization (WHO) in the Global Burden
of Disease study conducted in 2000 and reported in the World Health Report 2001. 
Migraine was not included in the first Global Burden of Disease 1990. The paper
also discussed the measurement of disability attributable to headache disorders
using WHO ICF Classification. Using disability-adjusted life years (DALYs) as a
summary measure of population health (which adds disability to mortality), WHO
have shown that mental and neurological disorders collectively account for 30.8% 
of all years of healthy life lost to disability (YLDs) whilst migraine, one
amongst these, alone accounts for 1.4% and is in the top 20 causes of disability 
worldwide. This information is combined with the increasingly widely accepted
belief that disability and functioning are relevant parameters for monitoring the
health of nations and that there is an increasing need to measure them. WHO's
Classification of Functioning, Disability and Health (ICF) provides a model of
human functioning and disability, as well as a classification system, that allows
us to highlight and measure all dimensions of disability. ICF applied to headache
disorders allows comparability with other health conditions as well as evaluation
of the role of the environment as a cause of disability amongst people with
headache. Migraine causes a large proportion of the non-fatal disease-related
burden worldwide. Our knowledge of headache related burden is incomplete and it
is necessary to add to it epidemiological studies in many parts of the world and 
to combine this with measurements of disability using both DALYs and WHO's ICF
Classification. The work described here has been the base for the Global Campaign
against Headache disorders: "Lifting the Burden", launched in 2004 jointly by
WHO, IHS (International Headache Society), WHA (World Headache Alliance) and EHF 
(European Headache Federation).

Publication Types: 
    Review

PMID: 16388337 [PubMed - indexed for MEDLINE]

1441: Neurology. 2005 Dec 29;65(12 Suppl 4):S50-8.

Clinical trials of acute treatments for migraine including multiple attack
studies of pain, disability, and health-related quality of life.

Lipton RB, Bigal ME, Stewart WF.

Department of Neurology, Albert Einstein College of Medicine, Bronx, NY 10461,
USA. Rlipton@aecom.yu.edu.

Because migraine has features in common with episodic monophasic pain disorders
(such as postoperative or posttraumatic pain) and with chronic pain disorders
(such as osteoarthritis or painful neuropathy), it is often considered an
episodic-chronic disorder. In clinical practice, the chronic aspects of migraine 
are addressed using preventive treatment strategies, while the episodic attacks
are addressed by acute treatment strategies. Acute treatment strategies have
generally been supported by clinical trial designs that focus on single attacks, 
whereas preventive treatment strategies evaluate multiple attacks over a period
of time. Recently, long-term acute treatment clinical designs have emerged that
may inform the design of clinical trials for other episodic-chronic disorders.
After reviewing traditional acute treatment clinical trials, we focus here on
study methods designed to evaluate treatment and management strategies for
migraine over multiple attacks, including outcomes that assess the
chronic-episodic nature of migraine (such as headache recurrence and consistency 
of relief), rather than relief from single attacks. We also discuss end points
that reflect the treatment needs of patients, such as disability and
health-related quality of life. The traditional randomized controlled trial
designed to assess treatment efficacy for a single attack is insufficient to
address the broader set of issues that arise in clinical practice. We consider
clinical trials strategies designed to address the more complex clinical and
policy requirements for meeting the needs of those with migraine.

Publication Types: 
    Review

PMID: 16385104 [PubMed - indexed for MEDLINE]

1442: Neurosci Lett. 2006 Mar 27;396(2):137-42. Epub 2005 Dec 27.

Exclusion of the juvenile myoclonic epilepsy gene EFHC1 as the cause of migraine 
on chromosome 6, but association to two rare polymorphisms in MEP1A and RHAG.

Norberg A, Forsgren L, Holmberg D, Holmberg M.

Department of Medical Biosciences, Clinical and Medical Genetics, Umeå
University, 901 87 Umeå, Sweden.

Migraine is a complex, multifactorial disorder for which several loci have been
identified in the human genome. We have previously reported linkage to a 10
Mb-region on chromosome 6p12.2-p21.1 in one large Swedish pedigree involving
migraine with and without aura. To further investigate this candidate region, a
dense set of single nucleotide polymorphic (SNP) markers was used for
fine-mapping, decreasing the critical region to 8.5 Mb. Within this region, EFHC1
was recently identified as the disease gene for juvenile myoclonic epilepsy.
Migraine and epilepsy has been suggested to share disease mechanisms and
therefore EFHC1 is an excellent candidate gene for migraine in this family.
Mutation analysis of the gene revealed a disease-segregating polymorphism in the 
promoter. Association analysis of the polymorphism in a case-control material did
not support a role for this gene in migraine pathology. We therefore analyzed
five additional candidate genes in the disease-critical region, including MEP1A, 
RHAG, IL17, SLC25A27 and TNFRSF21. In two of these genes, MEP1A and RHAG, we
identified two novel polymorphisms associated with the disease haplotype. The
combination of these polymorphisms could not be found in any control individuals,
suggesting that they might be involved in genetic predisposition to migraine in
this family.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16378686 [PubMed - indexed for MEDLINE]

1443: Ann Neurol. 2006 Jan;59(1):210-3.

Comment in:
    Ann Neurol. 2006 Jun;59(6):988.

Migraine with aura is a risk factor for unprovoked seizures in children.

Ludvigsson P, Hesdorffer D, Olafsson E, Kjartansson O, Hauser WA.

Department of Pediatrics, Landspitalinn University Hospital, Reykjavik, Iceland.

OBJECTIVE: Migraine is associated with epilepsy, but the time order and nature of
the relationship are unclear. We conducted a population based case control study 
to clarify the time order to determine whether migraine is a risk factor for
epilepsy. METHODS: Migraine symptoms were evaluated in a population-based
case-control study of all incident epilepsy in Icelandic children and in matched 
controls (next two same sex births in the country). RESULTS: Migraine was
associated with a fourfold increased risk for developing epilepsy, an association
explained by migraine with aura (odds ratio, 8.1; 95% confidence interval,
2.7-24.3). Migraine without aura did not increase risk for epilepsy.
INTERPRETATION: Children with migraine with aura have a substantial increased
risk to develop subsequent epilepsy. This finding is consistent with the
hypothesis that migraine with aura and migraine without aura may be different
disorders.

Publication Types: 
    Research Support, N.I.H., Extramural

PMID: 16374824 [PubMed - indexed for MEDLINE]

1444: Coron Artery Dis. 2006 Feb;17(1):29-33.

Decreased endothelium-dependent vasodilatation in patients with migraine: a new
aspect to vascular pathophysiology of migraine.

Yetkin E, Ozisik H, Ozcan C, Aksoy Y, Turhan H.

Department of Cardiology, Inonu University School of Medicine, Malatya, Turkey.
eryetkin@ttnet.net.tr

BACKGROUND: Migraine is a common neurovascular disorder characterized by attacks 
of severe headache, autonomic and neurological symptoms. We hypothesized that
patients with migraine had abnormal endothelial function. The vascular theory of 
migraine assumes that the major pathophysiological events that initiate the
migraine attack occur in the perivascular nerves of the major cerebral vessels.
Accordingly, we aimed to measure endothelium-dependent vasodilatation in
migraineurs by means of flow-mediated dilatation, which reflects
endothelium-dependent vasodilatation capacity. MATERIALS AND METHODS: Forty-five 
patients who fulfilled the diagnostic criteria for migraine and 45 age and
sex-matched healthy participants were enrolled in the study. Flow-mediated
dilatation of the brachial artery was determined using a high-resolution B-mode
ultrasonographic system. Flow-mediated vasodilatation was expressed as the change
in post-stimulus diameter as a percentage of the baseline diameter. RESULTS: Mean
ages of the patients were 33+/-10 years in migraineurs (range: 18-52 years, 36
female, 9 male) and 33+/-9 years in non-migraineurs (range: 17-50 years, 36
female and 9 male). Flow-mediated dilatation of patients with migraine is
significantly lower than that of the controls (8.02+/-4.095% vs. 10.72+/-3.52%,
respectively, P=0.001). CONCLUSION: We have shown that migraineurs have decreased
endothelium-dependent vasodilatation capacity compared with non-migraineurs.
Migraine may be a local manifestation of systemic vascular vasomotion
abnormalities.

Publication Types: 
    Comparative Study

PMID: 16374138 [PubMed - indexed for MEDLINE]

1445: Stroke. 2006 Feb;37(2):430-4. Epub 2005 Dec 22.

Comment in:
    Stroke. 2006 Dec;37(12):2876; author reply 2877.    Stroke. 2006 Jun;37(6):1361; author reply 1362.    Stroke. 2006 Sep;37(9):2212; author reply 2213.

Shunt-associated migraine responds favorably to atrial septal repair: a
case-control study.

Anzola GP, Frisoni GB, Morandi E, Casilli F, Onorato E.

Servizio di Neurologia, Ospedale S. Orsola FBF, AFaR, Associazione
Fatebenefratelli per la Ricerca, Brescia, Italy. gpanzola@numerica.it

BACKGROUND AND PURPOSE: Transcatheter closure of patent foramen ovale (PFO) has
been reported to improve migraine in patients with cerebrovascular disorders in
noncontrolled studies. The aim of the study was to compare the course of migraine
assessed prospectively over a 12-month period in symptomatic (for cerebrovascular
disease) and asymptomatic patients undergoing PFO closure and in patients with
PFO treated medically. METHODS: Twenty-three stroke symptomatic (SS; 39+/-10
years of age; males/females [M/F] 5/18) and 27 stroke asymptomatic (SA; 40+/-12
years of age; M/F 5/22) patients with migraine underwent PFO closure.
Twenty-seven patients with migraine and PFO (controls [CTRLS]; 36+/-11 years of
age; M/F 4/23) were followed up medically. Migraine severity was assessed at
baseline with a scale that takes into account the frequency, duration, and
intensity of the attacks and the occurrence of aura (score range 0 to 10). Six
months later, the patients were given a structured diary to annotate monthly with
the same scale the characteristics of the attacks for the next 6 months. By the
end of 1 year, the migraine score was averaged for the last 6 months. RESULTS:
Baseline severity of migraine did not differ between groups (6.3 to 6.1 and 6.7
in SS, SA, and CTRLS groups, respectively). At the 1-year assessment, the overall
migraine score had significantly improved by 3.7 and 2.8 points in SS and SA,
respectively (P<0.001 on repeated-measure ANOVA), whereas it had nonsignificantly
worsened by 0.1 points in CTRLS. Multiple linear regression analysis showed that 
the improvement in SS and SA was independent of migraine type, age, and
cerebrovascular risk factors. Twenty-one of 21 patients with migraine with aura
in the CTRLS group still had aura at the end of follow-up, whereas only 3 of 14
among SA and 4 of 19 among SS continued to have migraine preceded by aura
(P<0.0001 on Fisher exact test). CONCLUSIONS: Compared with medical treatment,
closure of PFO brings about a significant overall improvement in migraine. This
seems to occur irrespective of migraine type and of previous cerebrovascular
disease. In addition to the overall improvement, in migraine with aura, the
occurrence of aura is dramatically reduced.

PMID: 16373630 [PubMed - indexed for MEDLINE]

1446: Pediatr Pulmonol. 2006 Feb;41(2):171-6.

Cough-induced hemiplegic migraine with impaired consciousness in cystic fibrosis.

Rao DS, Infeld MD, Stern RC, Chelimsky TC.

Department of Neurology, Case Western Reserve University School of Medicine and
University Hospitals of Cleveland, Cleveland, Ohio, USA.

The coughing paroxysms of patients with cystic fibrosis may occasion neurological
symptoms. Although cough syncope is well-known, and is associated with headache
and paralysis, a migrainous mechanism has not been reported. We reviewed the
medical records, autonomic testing results, and responses to treatment in two
cystic fibrosis patients with similar presentations of cough-induced impairment
of consciousness followed by headache and paralysis. A 24-year-old woman and an
unrelated 38-year-old man, both with cystic fibrosis, developed post-tussive
neurologic deficits. Both patients reported infrequent dramatic spells, always
preceded by major hemoptysis, and associated with left-sided paralysis, transient
blindness, nausea, and severe pulsating headaches. Autonomic testing demonstrated
only postural tachycardia and a near-vasodepressor episode in the woman, and
mild, generalized sympathetic dysfunction in the man. Treatment for presumptive
migraine with aura with verapamil nearly eradicated symptoms in both patients.
Discontinuation of verapamil in the woman was associated with symptom recurrence 
and a stroke, with significant persistent residual left hemiparesis. In
conclusion, cough-induced neurologic deficits were previously reported with
cystic fibrosis, without clear understanding of the mechanism of impairment of
consciousness. Based on the hemiparesis, nausea, and throbbing headache, which
repeatedly followed the events in both patients, and based on the response to
verapamil, we hypothesize a migrainous mechanism in both of our patients. The
pathophysiology that links the hemoptysis to the spells deserves further
investigation. (c) 2005 Wiley-Liss, Inc.

Publication Types: 
    Case Reports

PMID: 16372353 [PubMed - indexed for MEDLINE]

1447: Med Sci Monit. 2006 Jan;12(1):PI1-7. Epub 2005 Dec 19.

Prevention of motion sickness with rizatriptan: a double-blind,
placebo-controlled pilot study.

Marcus DA, Furman JM.

Department of Anesthesiology, Pain Evaluation and Treatment Institute, University
of Pittsburgh School of Medicine, 5750 Centre Avenue, Pittsburgh, PA 15206,
U.S.A. MarcusD@anes.upmc.edu

BACKGROUND: Serotonergic triptan medications effectively reverse pain and
associated symptoms of migraine. Vestibular symptoms, including dizziness and
vertigo, occur in about one-third of migraineurs. The most frequent and
consistent balance symptom in migraineurs is motion sickness, which is
experienced by about half of migraineurs and may be related to serotonergic
influences. This double-blind, placebo-controlled, crossover pilot study was
designed to test the hypothesis that pre-treatment with the serotonin agonist
rizatriptan would prevent motion sickness provocation in headache-free
migraineurs. MATERIAL/METHODS: Ten healthy adult migraineurs (5 migrainous
vertigo and 5 migraine without associated vestibular symptoms) with a history of 
motion sickness were tested in three sessions: a baseline vestibular battery and 
two motion sickness provocation sessions two hours following randomly ordered
blinded pre-treatment with either oral rizatriptan 10 mg or placebo. Motion
sickness was assessed using two standardized questionnaires. RESULTS: Motion
sickness scores were lower following pre-treatment with rizatriptan compared with
placebo in subjects with migrainous vertigo. Rizatriptan did not affect motion
sickness in migraineurs without vertigo. Otolith-ocular reflex sensitivity was
reduced following pretreatment with rizatriptan in both groups. CONCLUSIONS: This
is the first study in humans testing a triptan serotonin agonist as a preventive 
tool for motion sickness. Rizatriptan prevented the development of motion
sickness and severe motion sickness symptoms in patients with migrainous vertigo.
These pilot data suggest a possible role for serotonin in the development of
motion sickness symptoms in migraineurs with migrainous vertigo.

Publication Types: 
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 16369474 [PubMed - indexed for MEDLINE]

1448: Clin Ther. 2005 Nov;27(11):1785-94.

Early intervention in migraine with sumatriptan tablets 50 mg versus 100 mg: a
pooled analysis of data from six clinical trials.

Winner P, Landy S, Richardson M, Ames M.

Palm Beach Headache Center, Premiere Research Institute, 5205 Greenwood Avenue,
Ste. 200, West Palm Beach, FL 33407, USA. Pwinner777@aol.com

BACKGROUND: In clinical trials evaluating sumatriptan in the treatment of
moderate or severe migraine pain, the 50- and 100-mg doses have been comparably
effective and well tolerated. OBJECTIVE: To assess the dose-efficacy relationship
of sumatriptan tablets given early for mild pain, data from 6 randomized,
double-blind, placebo-controlled, early-intervention studies of sumatriptan
tablets 50 mg and 100 mg (5 of which have been published) were pooled for
analysis. These constitute all the studies conducted to date of sumatriptan
tablets prospectively given early for mild pain. METHODS: The primary efficacy
end point in all the studies was the proportion of patients reporting a pain-free
result (ie, mild, moderate, or severe pain reduced to none) 2 hours postdose.
Other efficacy end points included the proportion of patients who were migraine
free (ie, no pain and no associated symptoms of nausea, vomiting, photophobia, or
phonophobia) 2 hours postdose; the proportion reporting worsening of pain (ie,
moderate or severe pain) 2 hours postdose; and the proportion with a sustained
pain-free result (ie, pain free from 2-24 hours postdose with no use of a second 
dose of study medication or of rescue medication). Tolerability was assessed by
evaluating the incidence of individual adverse events. The investigators assessed
each adverse event's relationship to study medication. RESULTS: The number of
patients in the intent-to-treat population was 2297 (771 sumatriptan 50 mg, 759
sumatriptan 100 mg, 767 placebo). Patients' mean age ranged from 39.4 to 39.8
years across groups, and most patients were female (90%-92%) and white (89%-90%).
A pain-free result 2 hours post dose was reported by significantly more patients 
who took either dose of sumatriptan tablets compared with placebo and by
significantly more patients who took the 100-mg dose compared with the 50-mg dose
(50 mg, 49%; 100 mg, 58%; placebo, 24%; P < 0.001, both sumatriptan doses vs
placebo, and 100 mg vs 50 mg). A similar pattern was observed for migraine-free
results 2 hours postdose (50 mg, 42%; 100 mg, 47%; placebo, 20%; P < 0.05, both
sumatriptan doses vs placebo, and 100 mg vs 50 mg), worsening of pain 2 hours
postdose (50 mg, 26%; 100 mg, 21%; placebo, 46%; P < 0.05, both sumatriptan doses
vs placebo, and 100 mg vs 50 mg), and sustained pain-free results from 2 through 
24 hours postdose (50 mg, 30%; 100 mg, 35%; placebo, 12%; P < 0.05, both
sumatriptan doses vs placebo, and 100 mg vs 50 mg). Both doses of sumatriptan
were well tolerated, and no dose-related trends in the incidence of individual
drug-related adverse events were observed. CONCLUSIONS: In this analysis of
pooled data from 6 clinical trials, sumatriptan tablets 50 mg and 100 mg
administered early in a migraine attack while the pain was mild were well
tolerated and significantly more effective than placebo. The 100-mg dose of
sumatriptan was significantly more effective than the 50-mg dose.

Publication Types: 
    Meta-Analysis

PMID: 16368449 [PubMed - indexed for MEDLINE]

1449: Ann Neurol. 2006 Feb;59(2):372-5.

Comment in:
    Ann Neurol. 2006 Nov;60(5):621-2; author reply 622-3.

Migraine and MTHFR C677T genotype in a population-based sample.

Scher AI, Terwindt GM, Verschuren WM, Kruit MC, Blom HJ, Kowa H, Frants RR, van
den Maagdenberg AM, van Buchem M, Ferrari MD, Launer LJ.

Department of Preventive Medicine and Biometrics, Uniformed Services University, 
Bethesda, MD 20814-4799, USA. ascher@usuhs.mil

OBJECTIVE: Migraine with aura is associated with increased risk of stroke. The
MTHFR C677T genotype has been associated with increased risk of migraine in
selected clinical samples and with elevated homocysteine, a risk factor for
stroke. We assessed the association of the MTHFR C677T variant with migraine and 
the mediating effect of cardiovascular risk factors and metabolic markers of
genotype status. METHODS: We compared adult migraineurs with aura (MA; n = 187), 
without aura (MO; n = 226), and nonmigraineurs (n = 1,212) from the
population-based Genetic Epidemiology of Migraine study. RESULTS: Compared with
the wild-type genotype, the T/T genotype was associated with increased odds of MA
(odds ratio [OR], 2.05; 95% confidence interval, 1.2-3.4; p < 0.006), with a
trend of increasing numbers of T alleles (OR, 1.40; 95% confidence interval,
1.1-1.8; p < 0.007). ORs were slightly attenuated after adjusting for
homocysteine. INTERPRETATION: Risk of MA is associated with MTHFR C674T
homozygosity, independent of other cardiovascular risk factors.

Publication Types: 
    Comparative Study
    Research Support, N.I.H., Intramural
    Research Support, Non-U.S. Gov't

PMID: 16365871 [PubMed - indexed for MEDLINE]

1450: J Headache Pain. 2005 Oct;6(5):412-6. Epub 2005 Sep 21.

Clinic-based study of family history of vascular risk factors and migraine.

Yoon G, Baggaley S, Bacchetti P, Fu YH, Digre KB, Ptácek LJ.

Division of Medical Genetics, Department of Pediatrics, University of California,
San Francisco, CA 94143-2922, USA.

The objective was to evaluate the presence of a positive family history (FH) of
vascular risk factors between patients with migraine with aura (MA) and migraine 
without aura (MO), and in chronic migraine (CM) compared to other headache types.
As migraine patients are typically too young to have developed vascular events,
studying older relatives of migraine patients may be a practical means of
evaluating associations between vascular risk factors and migraine. A
cross-sectional study of a clinic-based sample of adults with migraine headache
was carried out at the University of Utah. Predictor variables comprised first or
second degree relatives with stroke, hypertension, diabetes or
hypercholesterolaemia. Outcome measures comprised diagnosis of MA, MO or CM
according to the revised International Headache Society criteria. There was no
significant difference in FH of vascular risk factors in MA compared to MO
(adjusted OR 1.04, 95% CI 0.61-1.78). CM was associated with a decreased risk of 
FH of stroke (OR=0.11, 95% CI 0.02-0.87, p=0.036). There was no significant
difference in FH of vascular risk factors in MA patients compared to MO. CM
patients were more likely to have a negative FH of stroke compared to other
headache types, suggesting that CM is likely a neuronal disease rather than a
vascular one.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16362715 [PubMed - indexed for MEDLINE]

1451: J Headache Pain. 2005 Oct;6(5):405-11. Epub 2005 Sep 21.

Treatment satisfaction with zolmitriptan nasal spray for migraine in a real life 
setting: results from phase two of the REALIZE study.

Gawel M, Aschoff J, May A, Charlesworth BR; REALIZE Study Group.

Department of Medicine (Neurology), Sunnybrook and Women's Health Sciences
Centre, Suite 515, 60 Grosvenor Street, Toronto, Ontario M5S 1B6, Canada.
marek.gawel@sw.ca

In phase one of the REALIZE study, zolmitriptan nasal spray demonstrated a
significant headache response from 10 min post-dose and total symptom relief from
30 min post-dose. The objective of phase two was to investigate patients' dosing 
patterns, satisfaction and preference following open-label treatment with the
nasal spray. Up to 3 attacks were treated. The ITT population consisted of 851
patients. The median time from onset of symptoms to treatment was 1 h 15 min
(primary endpoint). Most patients reported being satisfied or very satisfied with
zolmitriptan nasal spray (75.7%). Furthermore, the majority of patients would be 
willing to use zolmitriptan nasal spray in the future (59.8%) and preferred
zolmitriptan nasal spray over previous therapies (57.8%). Zolmitriptan nasal
spray was well tolerated. Most patients were satisfied with zolmitriptan nasal
spray, were willing to continue using it and preferred it to previous therapies.

Publication Types: 
    Clinical Trial, Phase II
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 16362714 [PubMed - indexed for MEDLINE]

1452: J Headache Pain. 2005 Oct;6(5):392-9. Epub 2005 Sep 21.

Anger and emotional distress in patients with migraine and tension-type headache.

Perozzo P, Savi L, Castelli L, Valfrè W, Lo Giudice R, Gentile S, Rainero I,
Pinessi L.

Fondazione Carlo Molo, CE.R.NE., Turin, Italy.

The objective was to evaluate the prevalence and the characteristics of anger and
emotional distress in migraine and tension- type headache patients. Two hundred
and one headache patients attending the Headache Center of the University of
Turin were selected for the study and divided into 5 groups: (1) migraine, (2)
episodic tension-type headache, (3) chronic tension-type headache, (4) migraine
associated with episodic tension-type headache and (5) migraine associated with
chronic tension-type headache. A group of 45 healthy subjects served as controls.
All the subjects completed the State-Trait Anger Expression Inventory, the Beck's
Depression Inventory and the Cognitive Behavioral Assessment. Anger control was
significantly lower in all headache patients (p<0.05) except in migraineurs.
Patients with migraine and tension-type headache showed a significantly higher
level of angry temperament and angry reaction (p<0.05). In addition, chronic
tension-type headache and migraine associated with tension-type headache patients
reported a higher level of anxiety (p<0.05), depression (p<0.001), phobias
(p<0.001) and obsessive-compulsive symptoms (p<0.01), emotional liability
(p<0.001) and psychophysiological disorders (p<0.001). Our study shows that
chronic tension-type headache and migraine associated with tension-type headache 
patients present a significant impairment of anger control and suggests a
connection between anger and the duration of headache experience.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16362712 [PubMed - indexed for MEDLINE]

1453: J Headache Pain. 2005 Oct;6(5):387-91. Epub 2005 Aug 1.

Effect of preventive treatment on health-related quality of life in episodic
migraine.

Bordini CA, Mariano da Silva H, Garbelini RP, Teixeira SO, Speciali JG.

Department of Neurology, São Paulo University, School of Medicine at Ribeirão
Preto, Av. Bandeirantes 3900, 14049-900 Ribeirão Preto, SP, Brazil.

The purpose of our study was to prospectively evaluate the impact of preventive
drug treatment on the quality of life of patients with episodic migraine (EM).
Quality of life evaluations can enhance traditional measures of therapeutic
efficacy. Thirty-five consecutive EM without aura patients attending a tertiary
care unit (Batatais Headache Clinic) entered the study. They were given a
prescription for preventive medication and completed the validated Portuguese
version of the generic instrument Short Form-36 (SF-36) questionnaire. Six months
later, patients were given another SF-36. We compared the pre-treatment and
post-treatment scores for the SF-36 and analysed the headache diaries. The mean
age of the 35 patients (32 women and 3 men) was 40.2 years (range 18-60 years).
All 35 patients completed the pretreatment and follow-up SF-36. The pre-treatment
and post-treatment mean frequency of migraine attacks was 9.16 and 2.4 crises per
month, respectively (p<0.05). After the six months of preventive treatment, six
of the eight domains evaluated by the SF-36 (role physical, bodily pain, general 
health, vitality, social function and mental health) showed statistically
significant (p<0.05) improvement. The preventive treatment of migraine leads to a
significant improvement in the quality of life of patients with EM. This
improvement was measurable by the general quality of life instrument SF-36.

Publication Types: 
    Clinical Trial

PMID: 16362711 [PubMed - indexed for MEDLINE]

1454: J Headache Pain. 2005 Oct;6(5):378-86. Epub 2005 Aug 1.

Migraine aura without headache compared to migraine with aura in patients with
affective disorders.

Oedegaard KJ, Angst J, Neckelmann D, Fasmer OB.

Department of Psychiatry, University of Bergen, Haukeland Hospital, N-5021
Bergen, Norway. keti@haukeland.no

The characteristics of psychiatric comorbidity in migraine have been studied in
migraine with aura (MA) and migraine without aura (MO). Little information is
available concerning patients with migraine aura without headache. In a study of 
201 patients with major affective disorders (DSM-IV) we have described the
clinical characteristics of patients with these three sub-types of migraine (IHS 
criteria) and compared the MA and migraine aura without headache groups. Compared
to patients having MA (n=57), the group with migraine aura without headache
(n=18) had a higher age of onset of migraine (28.5 vs. 19.2, p=0.001),
significantly lower prevalences of affective temperaments (28% vs. 56%, p=0.036),
suicide attempts (17% vs. 53%, p=0.013) and Raynaud's syndrome (0% vs. 25%,
p=0.017). These results indicate that there seem to be differences in the
clinical characteristics found in patients with migraine with aura when compared 
to those having the migraine subtype without a headache phase. This may convey
new information concerning the comorbid expression of migraine and affective
disorders or concerning the processes that differentiates the migraine types with
and without a subsequent pain attack.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 16362710 [PubMed - indexed for MEDLINE]

1455: J Headache Pain. 2005 Sep;6(4):341-2.

Preventive non-pharmacological treatment and nitric oxide in chronic migraine.

Ciancarelli I, Tozzi-Ciancarelli MG, Di Massimo C, Olivieri L, Carolei A.

Department of Neurology, Regional Headache Center Università degli Studi di
L'Aquila, Piazzale Salvatore Tommasi 1, I-67010, Coppito-L'Aquila, Italy.
i_ciancarelli@yahoo.it

In chronic migraine the central sensitisation and the changes of regional
cerebral blood flow are mediated by nitric oxide (NO) and oxygen free radicals.
Biofeedback is considered a preventive non-pharmacological treatment decreasing
migraine attacks. We investigated whether biofeedback effectiveness is related to
relaxation processes and its influence on oxidative stress. The Migraine
Disability Assessment Score (MIDAS) and serum NO stable metabolites (NO(x)) were 
evaluated in 20 patients with chronic migraine before and at the end of
biofeedback sessions. MIDAS score was lower after biofeedback than that reported 
before treatment. NO(x) serum levels were higher after biofeedback than those
measured before starting treatment. Thus, the effectiveness of biofeedback is
related to a muscular relaxation and to its influence on NO bioavailability in
patients with chronic migraine.

Publication Types: 
    Clinical Trial

PMID: 16362706 [PubMed - indexed for MEDLINE]

1456: J Headache Pain. 2005 Sep;6(4):334-7.

Preliminary results of a withdrawal and detoxification therapeutic regimen in
patients with probable chronic migraine and probable medication overuse headache.

Trucco M, Meineri P, Ruiz L; "Gruppo Neurologico Ospedaliero Interregionale per
lo Studio delle Cefalee" (Neurological Hospital Interregional Group for the Study
of Headache).

Headache Centre, Department of Neurology, Santa Corona Hospital, Via XXV Aprile
38, I-17027, Pietra Ligure (SV), Italy. marco.trucco@ospedalesantacorona.it

Chronic migraine (CM) is an invalidating condition affecting a significant
population of headache sufferers, frequently associated with medication overuse
headache (MOH). Controlled trials and guidelines for the treatment of MOH are
currently not available. We studied the efficacy of a therapeutic regimen for the
withdrawal of the overused drug and detoxification in a sample of patients
suffering from probable CM and probable MOH during admission in eight hospitals
of Piemonte-Liguria-Valle d'Aosta. Fifty patients, 42 females (84%) and 8 males
(16%), mean age at observation 50.66+/-13.08 years, affected by probable CM and
daily medication overuse following IHS diagnostic criteria were treated as
inpatients or in a day hospital. Headache index (HI) and daily drug intake (DDI) 
were used for evaluating the severity of headache and medication overuse. The
patients were treated by abrupt discontinuation of the overused drug and by a
therapeutic protocol including i.v. hydration, dexamethasone, metoclopramide and 
benzodiazepines for 7-10 days. Prophylactic medication was started immediately
after admission. Analgesics or triptans were used under medical control only in
cases of severe rebound headache. Diagnostic protocol included routine blood
tests (at admission and at discharge), dosage of B12 and folic acid. Patients
underwent follow-up controls one, three and six months after discharge. The
initial diagnosis was probable CM in almost all patients included in the study
(41 patients); in nine patients the diagnosis was not specified (coded only as
CDH). The overused medications were simple analgesics in 17 cases (34%),
combination analgesics in 19 cases (38%), triptans alone or with analgesics in 13
cases (26%) and ergotamine in 2 cases (4%). We collected data from 39 patients at
first follow-up (1 month), 32 after 3 months and 14 after 6 months. Mean HI was
0.91 at admission, 0.22 at discharge, 0.38 after 30 days, 0.46 after 3 months and
0.48 after 6 months. Mean DDI was 2.80 at admission, 0.39 at discharge, 0.41
after 1 month, 0.52 after 3 months and 0.59 after 6 months. These results are on 
average positive and tend to remain stable with time. Although preliminary and
obtained on a limited number of patients at 6-month follow-up, our results seem
to be encouraging about the use of the proposed therapeutic protocol.

Publication Types: 
    Clinical Trial

PMID: 16362704 [PubMed - indexed for MEDLINE]

1457: J Headache Pain. 2005 Sep;6(4):331-3.

Preventing chronicity of migraine.

Fanciullacci M, De Cesaris F.

Headache Center, Department of Internal Medicine, University of Florence, Viale
Pieraccini 18, I-50139, Firenze, Italy. fanciullac.marcello@tiscalinet.it

Chronic migraine and transformed migraine are conditions with a progression from 
episodic to chronic headache, a disabling stage. During attack, cutaneous
allodynia frequently occurs: it reflects sensitisation of the central neurons of 
the trigeminovascular system. Early triptan therapy (prior to the development of 
central sensitisation) may protect from the chronicisation of migraine. In
addition, early recognition of non-headache changes in neurologic function
between episodes of headache offers a sensitive indicator of headache
transformation. Attack frequency is the stronger predictor for migraine
progression: prophylactic agents could be administered to patients with a high
number of attacks. Medication overuse is the most important iatrogenic risk
factor for the acceleration of disease and it must be prevented; other important 
risk factors are female sex, obesity and stressful life events.

Publication Types: 
    Review

PMID: 16362703 [PubMed - indexed for MEDLINE]

1458: J Headache Pain. 2005 Sep;6(4):325-7.

Headache and botulinum toxin.

Porta M, Camerlingo M.

Department of Neurology, Headache Center, Policlinico San Marco, Corso Europa 7, 
Bergamo-Zingonia, Italy. prof.porta@inwind.it

The authors discuss clinical and international experience about botulinum toxins 
(BTX types A and B) in headache treatment. Data from literature suggest good
results for the treatment of tension-type headache, migraine and chronic
tension-type headache. In the present paper mechanisms of action and injection
sites will also be discussed.

Publication Types: 
    Review

PMID: 16362701 [PubMed - indexed for MEDLINE]

1459: J Headache Pain. 2005 Sep;6(4):322-4.

Weight variations in the prophylactic therapy of primary headaches: 6-month
follow-up.

Maggioni F, Ruffatti S, Dainese F, Mainardi F, Zanchin G.

Headache Centre, Department of Neurosciences, University of Padua, Via
Giustiniani 3, I-35128, Padua, Italy. ferdinando.maggioni@unipd.it

We conducted a study on 367 patients (86% female, 14% male; mean age 37+/-15
years) suffering from migraine with and without aura and chronic tension-type
headache to evaluate the incidence of weight gain, an undesirable side effect
observed during prophylactic therapy in primary headaches. Patients treated with 
amitriptyline (20 and 40 mg), pizotifen (1 mg), propranolol (80-160 mg), atenolol
(50-100 mg), verapamil (160-240 mg), valproate (600 mg) and gabapentin (900-1200 
mg) were evaluated after a period of 3 and 6 months. In particular, 89 patients
were assessed (78% female, 22% male) at 6 months, of whom 10 were in treatment
with amitriptyline 20 mg, 19 with amitriptyline 40 mg, 7 with pizotifen (1 mg),
13 with propranolol (80-160 mg), 4 with verapamil (160 mg), 10 with valproate
(600 mg), 15 with atenolol (50 mg) and 11 with gabapentin (900-1200 mg). The
control group consisted of 97 patients with migraine (79% female, 21% male; mean 
age 35+/-16 years) without indication for prophylactic therapy. Weight variations
>or=1 kg were considered. After 6 months of therapy, the percentage of patients
with weight gain was 86% with pizotifen (6/7; mean weight increase 4.4+/-2.5 kg),
60% with amitriptyline 20 mg (6/10; 3.1+/-1.6), 47% with amitriptyline 40 mg
(9/19; 5.4+/-2.7), 25% with valproate 600 mg (2/8, 3.0+/-2.8 kg), 25% with
verapamil (1/4, 2.5 kg), 20% with atenolol (3/15, 1.7+/-0.6 kg), 9% with
gabapentin (1/11, 1.5 kg) and 8% with propranolol (1/13; 6 kg). We conclude that 
propranolol, gabapentin, atenolol, verapamil and valproate affect body weight in 
a modest percentage of patients at 6 months. A greater mean weight gain at 6
months was found in patients treated with pizotifen, amitriptyline, and, in one
patient out of 13, with propranolol.

Publication Types: 
    Clinical Trial

PMID: 16362700 [PubMed - indexed for MEDLINE]

1460: J Headache Pain. 2005 Sep;6(4):319-21.

Pharmacokinetics of sumatriptan in non-respondent and in adverse drug reaction
reporting migraine patients.

Sternieri E, Pinetti D, Coccia CP, Leone S, Bertolini A, Ferrari A.

Headache Centre, Division of Toxicology and Clinical Pharmacology, University of 
Modena and Reggio Emilia, Largo del Pozzo 71, I-41100, Modena, Italy.
sternieri.emilio@unimore.it

Sumatriptan is a selective agonist of 5HT1 (1B/1D) receptors, which has proved to
be effective and safe for the acute treatment of migraine attacks. Nevertheless, 
its use by migraine sufferers is still limited and some patients consider adverse
reactions related to sumatriptan, especially chest symptoms, unacceptable even if
not serious. Moreover, in clinical trials, almost one third and one sixth of
patients, respectively, fail to experience headache relief either after oral or
after subcutaneous sumatriptan administration. Our aim was to verify whether
differences in sumatriptan pharmacokinetics could explain non-response and/or
adverse drug reactions. Sumatriptan levels were determined by HPLC with
electrochemical detection. Pharmacokinetic parameters were calculated using a
computer program (PK Solutions 2.0; non compartmental Pharmacokinetics Data
Analysis). After oral administration, sumatriptan is rapidly absorbed and
sometimes displays multiple peaks of plasma concentration. This "multiple
peaking" gives rise to considerable inter-subject variability in the time of
reaching maximum plasma concentration. Pharmacokinetic parameters of sumatriptan,
both after oral and subcutaneous administration, were similar in the three
patient groups. Blood pressure and heart rate did not show any significant
differences between groups. Pharmacokinetic parameters and bioavailability of
sumatriptan did not seem to be correlated either to the lack of efficacy or the
appearance of side effects. These results could depend on the limited number of
patients studied.

Publication Types: 
    Clinical Trial

PMID: 16362699 [PubMed - indexed for MEDLINE]

1461: J Headache Pain. 2005 Sep;6(4):315-8.

Risk-benefit and cost-benefit ratio in headache treatment.

Pini LA, Cainazzo MM, Brovia D.

Centro Cefalee, Università di Modena e Reggio Emilia, via del Pozzo 71, I-41100, 
Modena, Italy. pinila@unimore.it

The cost-benefit and the risk-benefit ratios are two of the most relevant items
in ongoing health organisation procedures. The choice of a new or an old
therapeutic treatment depends on a number of factors and the evaluation of the
cost, in terms of economics, but also in terms of quality of life and type of
facilities necessary for one treatment are crucial criteria. Therefore, we have
to consider in evaluating treatment strategies not only the activity of a drug in
reaching the main end-points, (i.e., pain free or headache relief) but also the
safety and perception of safety by patients, and the cost effectiveness,
including indirect costs compared with personal and social benefits. Because it
is reasonable that a subgroup of migraine patients may have a clinically
progressive disorder, studies should be necessary to assess strategies for
migraine treatments.

Publication Types: 
    Review

PMID: 16362698 [PubMed - indexed for MEDLINE]

1462: J Headache Pain. 2005 Sep;6(4):312-4.

Study on management of headache by general practitioners in South Italy.

Iannacchero R, Cannistrà U, La Vitola A, Peltrone F, De Caro E.

Via Salvatore Miceli 4, I-88046, Lamezia Terme (CZ), Italy.
rosarioiann@tiscali.it

The impact of migraine headaches is one of the major public health problems in
several industrialised countries, with many patients reporting frequent and
significant disability. Previous studies have assessed general practitioners'
(GPs) perceptions towards evidence-based medicine (EBM) and its influence on
health care decisions. Of 500 questionnaires distributed, responses were received
from 455 for a response rate of 91%. Respondents' awareness of technical terms
used in EBM indicated that only 27.2% of GPs agreed that clinical trials are
needed to evaluate the efficacy of treatments and this awareness was higher in
those who learned about migraine from scientific journals or continuing education
courses and who attended courses on epidemiology or EBM. Training and continuing 
educational programmes on EBM and guidelines in terms of treatments of headache
for GPs are strongly needed.

PMID: 16362697 [PubMed - indexed for MEDLINE]

1463: J Headache Pain. 2005 Sep;6(4):304-6.

Migraine disease: evolution and progression.

Buzzi MG, Cologno D, Formisano R.

Headache Centre, IRCCS Fondazione Santa Lucia, Via Ardeatina 306, I-00179, Rome, 
Italy. mg.buzzi@hsantalucia.it

Migraine is a complex pathology and it should be regarded as a disease evolving
during the lifetime along with other comorbid conditions. Migraine susceptibility
may be unmasked by exogenous substances and the occurrence of migraine attacks
may change following drugs given for therapeutical purposes. The evolution of
migraine should be followed up because childhood migrainous manifestations may
vary over the years and an earlier diagnosis may not apply later on.

Publication Types: 
    Review

PMID: 16362694 [PubMed - indexed for MEDLINE]

1464: J Headache Pain. 2005 Sep;6(4):301-3.

Migraine in the Emergency Department: a psychometric study of a migraine
"repeaters" sample.

Villani V, Bruti G, Mostardini C, Di Stani F, Scattoni L, Dugoni D, Vanacore N,
Cerbo R.

Headache Section of Pain Center Enzo Borzomati, Policlinico Umberto I, Department
of Neurological Sciences, University of Rome La Sapienza, Rome, Italy.
gianluca.bruti@uniroma1.it

To evaluate the influence of psychometric variables on the "repeater" phenomenon 
in an emergency department, 15 "repeaters" and 27 outpatient migraineurs were
recruited. All patients were submitted to the Beck Depression Inventory (BDI),
State and Trait Anxiety Inventory, Toronto Alexithymia Scale-20 (TAS-20),
Tridimensional Personality Questionnaire and Migraine DIsability Assessment Scale
(MIDAS). The "repeater" group showed higher MIDAS total scores (p=0.02) and
higher scores in TAS-20 (p=0.02) than the outpatients. A higher frequency of
alexithymic trait (p=0.02) and higher BDI scores (p=0.07) have also been observed
in the "repeater" group than the outpatients. Alexithymia and depressive mood
associated with high disability may be a specific psychosocial pattern of
"repeater" migraineurs. The psychometric evaluation of this population may be
important to explain the "repeaters" phenomenon.

PMID: 16362693 [PubMed - indexed for MEDLINE]

1465: J Headache Pain. 2005 Sep;6(4):271-3.

The prevalence of allodynia, osmophobia and red ear syndrome in the juvenile
headache: preliminary data.

Raieli V, Pandolfi E, La Vecchia M, Puma D, Calò A, Celauro A, Ragusa D.

Via Giuseppe Pagano 14, I-90129, Palermo, Italy. vinzi.raielk@inwind.it

The aim of the study was to determine the frequency of clinical allodynia,
osmophobia and red ear syndrome in a young population. Medical records of the
children admitted for headache between 1 December 2004 and 31 March 2005 were
consecutively studied. A questionnaire was used to find the prevalence of
allodynia, osmophobia and red ear syndrome. We visited 96 children with headache.
The range of age was 6-18 years. We classified migraine in 57%, other primary
headaches in 25% and secondary headaches in about 18%. The presence of
ipsilateral clinical allodynia was 14.5% in migraine, osmophobia in 20% of
migraine and red ear syndrome in about 24% of migraine cases and they were absent
in the other two headache groups. Our study shows that features like osmophobia, 
allodynia and red ear syndrome are not uncommon in migraine while they are absent
in other types of headache.

PMID: 16362684 [PubMed - indexed for MEDLINE]

1466: J Headache Pain. 2005 Sep;6(4):258-60.

Sleep quality, chronotypes and preferential timing of attacks in migraine without
aura.

Gori S, Morelli N, Maestri M, Fabbrini M, Bonanni E, Murri L.

Institute of Neurology, Department of Neurosciences, University of Pisa, Via Roma
67, I-56126, Pisa, Italy. s.gori@med.unipi.it

Clinical observations show that migraine attacks have a seasonal, menstrual and
circadian timing, suggesting a role of chronobiological mechanisms and their
alterations in the disease, but little experimental data exists about this issue.
The aim of this study was to estimate sleep quality chronotypes and the possible 
circadian timing of attacks in migraneurs. One hundred patients suffering from
migraine without aura according to the IHS criteria (2004), and 30 controls were 
enrolled. Morning and evening type subjects were more represented in migraine
patients than in controls and showed a tendency towards worse sleep quality and
higher disability. Forty-two percent of migraineurs presented more than 75% of
their attacks at night. Morning and evening types rather than intermediate and
differences between real and preferred times may represent stressors that can
worsen the disease. A preferential timing for occurrence of migraine attacks
during the night and early morning hours was documented.

PMID: 16362680 [PubMed - indexed for MEDLINE]

1467: J Headache Pain. 2005 Sep;6(4):247-9.

The temperament and character inventory in women with migraine.

Mongini F, Fassino S, Rota E, Deregibus A, Levi M, Monticone D, Abbate-Daga G.

Department of Clinical Pathophysiology, Headache and Facial Pain Unit, University
of Turin, Corso Dogliotti 14, I-10126, Turin, Italy. franco.mongini@unito.it

The purpose of this work was to investigate: (1) the differences in temperament
and character between 49 women with migraine and 49 controls using the
Temperament and Character Inventory (TCI), and (2) the extent to which these
differences were related to migraine or to the presence of comorbid depression.
The migraine patients scored significantly higher than the controls in two
temperament dimensions-Harm Avoidance (HA) and Persistence (P)-and significantly 
lower in one character dimension-Self-Directedness (SDir) (Student's t). After
multiple logistic regression, the TCI P and HA dimensions were significantly
associated with the presence of migraine. The HA dimension was also related to
the presence of depression. Our results show that in migraine the higher HA score
could be partly associated to comorbid depression while the high P dimension
seems to be solely related to the presence of migraine.

PMID: 16362677 [PubMed - indexed for MEDLINE]

1468: J Headache Pain. 2005 Sep;6(4):227-30.

Psychiatric disorders and pain location in unilateral migraineurs.

Cologno D, Buzzi MG, Carlesimo GA, Cicinelli P, Costa A, Fadda L, Formisano R,
Marconi B, Pero S, Caltagirone C.

I.R.C.C.S.-Fondazione S. Lucia, Via Ardeatina 306, Rome, Italy.
danielacologno@virgilio.it

To explore the relationship between the side of pain during attacks and
psychopathological features in strictly unilateral migraine, we recruited 35
patients affected by migraine with and/or without aura diagnosed according to the
revised ICHD-II criteria. Seventeen patients had right side-locked pain (R-SUM), 
11 had left side-locked (L-SUM) and 7 had side-shifting pain (SSM). Patients were
administered the Hamilton Anxiety Scale, the State and Trait Anxiety
Inventory-State Anxiety, the Beck Depression Inventory and the 20-item Toronto
Alexithymia Scale. Statistical analyses showed that the L-SUM group was
significantly more anxious and depressed than the other two groups of patients.
Our preliminary data suggest that strictly left unilateral migraine is associated
with more severe anxiety and depression. This finding appears to be consistent
with studies that reported a higher degree of these disorders in patients with
left cerebral hemispheric damage.

PMID: 16362671 [PubMed - indexed for MEDLINE]

1469: J Headache Pain. 2005 Sep;6(4):223-6.

Patients with headache and functional dyspepsia present meal-induced
hypersensitivity of the stomach.

Pucci E, Di Stefano M, Miceli E, Corazza GR, Sandrini G, Nappi G.

University Centre for Adaptive Disorders and Headache (UCADH), University of
Pavia, IRCCS C. Mondino, Via Mondino 2, I-27100 Pavia, Italy.
ennio.pucci@mondino.it

Headache is a frequent feature of functional gastrointestinal disorders but there
is no data on the responsible pathophysiological mechanism. The aim of this study
was to verify whether alteration of post-prandial gastric tone or sensitivity
might explain this association. Fourteen patients affected by functional
dyspepsia (7 migraine without aura) and 7 healthy volunteers (HV) underwent
gastric tone measurement in fasting condition and after the administration of a
liquid meal by barostat. Gastric volume (GV) and accommodation were calculated as
difference between mean post-prandial and mean fasting volume. Mean postprandial 
GV increase and fasting perception and discomfort threshold (DTh) were similar
among the 3 groups. DTh after meal was lower in dyspeptic headache patients than 
in HV and dyspeptic without headache patients. Patients with migraine and
functional dyspepsia may be characterised by meal-induced hypersensitivity of the
stomach.

PMID: 16362670 [PubMed - indexed for MEDLINE]

1470: J Headache Pain. 2005 Sep;6(4):220-2.

The comorbidity of migraine and hypertension. A study in a tertiary care headache
centre.

Prudenzano MP, Monetti C, Merico L, Cardinali V, Genco S, Lamberti P, Livrea P.

Headache Disorders Centre, Neurological and Psychiatric Sciences Department,
University of Bari, Piazza G. Cesare 11, I-70124, Bari, Italy.
m.p.prudenzano@neurol.uniba.it

Literature data concerning the comorbidity of migraine and hypertension are
conflicting and lacking in consistency. This study was designed to evaluate the
distribution of hypertension in a sample of migraineurs in comparison with a
group of tension type headache (TTH) patients. Hypertension prevalence was more
elevated in headache sufferers than in the general population. This finding might
be due to a Berkson's bias; in fact individuals seeking medical care often show a
high rate of association between two medical conditions which may be independent 
in the general population. The highest hypertension prevalence was found in
patients with TTH, supporting the hypothesis that this type of headache might be 
based upon vascular mechanisms.

PMID: 16362669 [PubMed - indexed for MEDLINE]

1471: J Headache Pain. 2005 Sep;6(4):216-9.

A validation study of an Italian version of the ID Migraine: preliminary results.

Brighina F, Salemi G, Fierro B, Gasparro A, Balletta G, Aloisio A, La Pegna GB,
Randisi G, Saporito V, Calagna G, Lanaia F, Morana R.

Dipartimento di Neurologia, Oftalmologia, Otorinolaringoiatria e Psichiatria,
Università di Palermo, Via G. La Loggia 1, I-90129 Palermo, Italy.
fbrighina@neuro.unipa.it

Migraine is a highly prevalent and disabling disease that is substantially
undiagnosed in primary care. Recently, the ID Migraine, a self-administered
questionnaire, was shown to be a valid and reliable screener for migraine in
primary care in the USA. To validate an Italian version of the ID Migraine, we
planned a multicentric study, evaluating at least 220 patients affected by
various form of headache. The responses to the questionnaire were compared with
the diagnosis of headache made by a headache specialist blind to the result of
the questionnaire. Sensitivity, specificity, and positive and negative predictive
values for migraine were calculated. The statistical analysis on 140 patients now
examined showed a very good performance of the ID Migraine with high sensitivity:
0.94 (95% CI: 0.89-0.95), specificity: 0.70 (95% CI: 0.54-0.86) and positive
predictive value: 0.89 (0.82-0.95). If confirmed, these results would establish
ID Migraine as a valid screening instrument for migraine in Italian headache
patients and warrant further investigation in primary care to assess the validity
of this ID screener in Italian population.

Publication Types: 
    Validation Studies

PMID: 16362668 [PubMed - indexed for MEDLINE]

1472: J Headache Pain. 2005 Sep;6(4):199-202.

Medication-overuse headache: pathophysiological insights.

Cupini LM, Calabresi P.

Ospedale Sant'Eugenio, Reparto di Neurologia, Unità Operativa Cefalee, Piazzale
dell'Umanesimo, Rome, Italy.

Medication overuse headache (MOH) is a clinically important entity and it is now 
well documented that the regular use of acute symptomatic medication by people
with migraine or tensiontype headache increases the risk of aggravation of the
primary headache. MOH is one of the most common causes of chronic migraine-like
syndrome. Because of easy availability and low expense, the greatest problem
appears to be associated with barbiturate-containing combination analgesics and
over-the-counter caffeine-containing combination analgesics. Even though triptan 
overuse headache is not encountered with great frequency, all triptans should be 
considered potential inducers of MOH. There are several different theories
regarding the aetiology of MOH, including: (i) central sensitisation from
repetitive activation of nociceptive pathways; (ii) a direct effect of the
medication on the capacity of the brain to inhibit pain; (iii) a decrease in
blood serotonin due to repetitive medication administration with alteration of
serotonin receptors; (iv) cellular adaptation in the brain; and (v) changes in
the periaqueductal grey matter. The principal approach to management of MOH is
built around cessation of overused medication. Without discontinuation of the
offending medication, improvement is almost impossible to attain. Thus, the best 
management advice is to raise awareness and strive for prevention. In this
article, we analyse also the possible mechanisms that underlie sensitisation in
MOH by comparing these mechanisms with those reported for other forms of drug
addiction.

Publication Types: 
    Review

PMID: 16362663 [PubMed - indexed for MEDLINE]

1473: J Headache Pain. 2005 Sep;6(4):195-8.

Habituation of single CO2 laser-evoked responses during interictal phase of
migraine.

de Tommaso M, Libro G, Guido M, Losito L, Lamberti P, Livrea P.

Clinica Neurologica, Policlinico, Piazza G. Cesare 11, I-70124, Bari, Italy.
m.detommaso@neurol.niba.it

A reduced habituation of averaged laser-evoked potential (LEP) amplitudes was
previously found in migraine patients. The aim of the present study was to assess
the habituation of single LEP responses and pain sensation during the interictal 
phase in migraine patients. Fourteen migraine patients were compared with ten
control subjects. The pain stimulus was laser pulses, generated by CO2 laser,
delivered to right supraorbital zone. Patients were evaluated during attack-free 
conditions. The LEP habituation was studied by measuring the changes of LEP
amplitudes across and within three consecutive repetitions of 21 non-averaged
trials. In migraine patients the N2-P2 wave amplitudes did not show a tendency
toward habituation across and, above all, within the three repetitions. Anomalous
behaviour of nociceptive cortex during the interictal phase of migraine may
predispose patients to headache occurrence and persistence.

PMID: 16362662 [PubMed - indexed for MEDLINE]

1474: J Headache Pain. 2005 Sep;6(4):188-90.

Cytotoxic T lymphocyte antigen 4 polymorphism 49 (A>G) and migraine.

Lulli P, Trabace S, Morellini M, Cicciarelli G, Coloprisco G, Piane M, de
Filippis S, Santi PG, Avramakou O, Ferlicca E, Martelletti P.

Clinical Genetics, 2nd School of Medicine, Rome University La Sapienza,
Sant'Andrea Hospital, Via di Grottarossa 1035, I-00189 Rome, Italy.
patrizia.lulli@uniroma1.it

Migraine without aura (MO) and migraine with aura (MA) are disorders involving
multiple environmental and genetic factors. The A/G polymorphism located within
exon 1 of the gene encoding the cytotoxic T lymphocyte antigen 4 (CTLA-4) is
associated with several HLA-associated multifactorial diseases. The CTLA-4 family
shows a negative control on T-cell proliferation and cytokine production
(TNF-alpha and IL-10). In the present study we investigated the contribution of
the candidate gene CTLA-4 in migraine pathophysiology. Included in the study were
96 MO and 39 MA migraine patients and 106 healthy individuals as control group.
The results showed no statistical difference of allele frequencies between
patient group and control group. These results would indicate no association
between MA and MO migraine and CTLA-4 polymorphism, excluding any possible role
of the CTLA-4 gene as a genetic factor determining susceptibility to migraine.

PMID: 16362660 [PubMed - indexed for MEDLINE]

1475: J Headache Pain. 2005 Sep;6(4):185-7.

Association between migraine and HLA-DRB1 gene polymorphisms.

Rainero I, Fasano E, Rubino E, Rivoiro C, Valfrè W, Gallone S, Savi L, Gentile S,
Lo Giudice R, De Martino P, Dall'Omo AM, Pinessi L.

Neurology III-Headache Center, Department of Neuroscience, University of Turin,
Via Cherasco 15, I-10126, Turin, Italy. irainero@molinette.piemonte.it

We examined the distribution of HLA-DRB1 alleles in a cohort of 255 Italian
migraine patients and in a control group of 325 healthy subjects. The frequency
of DRB1*12 allele was found to be significantly reduced (p=0.02) in patients with
migraine while the DRB1*16 allele was significantly increased (p=0.04) in
comparison with controls. When the patients were divided into disease subgroups
(migraine with and without aura), HLA-DRB1**16 allele was significantly increased
(p<0.05) only in migraine without aura patients. We conclude that, in Italian
patients, migraine is associated with different alleles of the HLA-DRB1 locus.
Our data suggest the presence of a genetic susceptibility factor for migraine
within the HLA region.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16362659 [PubMed - indexed for MEDLINE]

1476: J Headache Pain. 2005 Sep;6(4):182-4.

Functional serotonin 5-HTTLPR polymorphism is a risk factor for migraine with
aura.

Borroni B, Brambilla C, Liberini P, Rao R, Archetti S, Gipponi S, Volta GD,
Padovani A.

Department of Neurology, University of Brescia, Piazza Spedali Civili 1, I-25100 
Brescia, Italy. bborroni@inwind.it

In the present work, we report that the functional serotonin transporter gene
promoter (5-HTTLPR) polymorphism is involved in migraine pathogenesis. The
distribution of 5-HTTLPR genotypes was significantly different in MA patients
(S/S vs. S/L vs. L/L=32.7 vs. 42.3 vs. 25.0%), MO patients (18.5 vs. 39.1 vs.
42.4%) and CON (18.0 vs. 51.3 vs. 30.7%; chi-square test, p<0.05). In 5-HTTLPR
S/S carriers, the odds ratio for MA risk was 2.60 (95% confidence interval
[95%CI]=1.75-3.85) compared to CON, and it was 2.14 (95%CI=1.42-3.21) compared to
MO. These data provide a further insight on the complex genotype-phenotype
relationship involved in MA pathogenesis, and might eventually result in new and 
individualised prognostic and therapeutic measures.

PMID: 16362658 [PubMed - indexed for MEDLINE]

1477: J Headache Pain. 2005 Sep;6(4):179-81.

Genetic risk factors in primary paediatric versus adult headache: complexities
and problematics.

Lisi V, Garbo G, Miccichè F, Stecca A, Terrazzino S, Franzoi M, Tripoli E,
Clementi M, Leon A, Battistella PA.

Research and Innovation (R&I) Company, Padua, Italy.

Numerous candidate genes for migraine have been proposed on the basis of their
possible functional role in its pathogenesis. Genetic polymorphisms have been
evaluated in association studies, some of which have been suggested to be
susceptibility markers for adult migraine. To date, however, none of the
identified polymorphisms in adult migraine susceptibility have been investigated 
in children, raising the possibility that they may not be necessarily involved in
paediatric migraine susceptibility. This paper reviews studies of the genetic
basis of migraine and summarises our experience in genetic association studies in
primary paediatric headache susceptibility.

Publication Types: 
    Review

PMID: 16362657 [PubMed - indexed for MEDLINE]

1478: J Headache Pain. 2005 Sep;6(4):172-4.

Headaches in pregnancy.

Silberstein SD.

Jefferson Headache Center, 111 South Eleventh Street, Gibbon Building, Suite
8130, Philadelphia, PA 19107, USA. Stephen.Silberstein@jefferson.edu

Most women with migraine improve during pregnancy. Some women have their first
attack. Migraine often recurs postpartum and can begin for the first time. Drugs 
are commonly used during pregnancy despite insufficient knowledge about their
effects on the growing fetus. Most drugs are not teratogenic. Adverse effects,
such as spontaneous abortion, developmental defects and various postnatal effects
depend on the dose and route of administration and the timing of the exposure
relative to the period of foetal development. While medication use should be
limited, it is not absolutely contraindicated in pregnancy. Nonpharmacologic
treatment is the ideal solution; however, analgesics such as acetaminophen and
opioids can be used on a limited basis. Preventive therapy is a last resort.

Publication Types: 
    Lectures

PMID: 16362655 [PubMed - indexed for MEDLINE]

1479: J Headache Pain. 2005 Apr;6(2):93-6. Epub 2005 Apr 8.

Migraine with aura, bipolar depression, ACM aneurysm. A case report.

de Filippis S, Salvatori E, Bozzao A, Fantozzi LM, Martelletti P.

Regional Referral Headache Centre, Department of Medicine, Sant'Andrea Hospital, 
II School of Medical Sciences, University La Sapienza, Via di Grottarossa 1035,
I-00189 Rome, Italy. sergio.defilippis@uniroma1.it

B.D. is a 48-year-old professional woman. She has been suffering for migraine
since she was 28, but she did not have serious problems until last year, when
headache episodes became more frequent and it was necessary an admission to
emergency room. At the beginning, the events were about 6 per month, lasting from
2 to 4 days, beating and of high intensity together with nausea, vomit, photo and
phonophobia and visual area. Looking at the anamnesis, we report a psychiatric
treatment since about ten years, because of type II bipolar disorder. In spite of
the psychopharmacological treatment, as the patient came in our Regional Headache
Center, she talked about 7 events with aura (scintillating scotomas, emianopsia) 
per month, lasting 2-4 days with photo and phonophobia, nausea, crying crisis,
anxiety. Although the neurological examination was normal, the sudden aggravation
of pain symptomatology and the unresposiveness to usual painkillers, suggested a 
cerebral CT and CT-angiography. CT and CT-angiography discovered the presence of 
an aneurysm of the right middle cerebral artery (MCA) of 4 mm diameter, with
parietal irregularities. The patient was operated to reduce the hemorrhagic risk,
with a positive result. One year after the operation, the patient reports a
decrease of headache events with a frequency of 2 per month, lasting only a few
hours, which she can now solve with COXIB.

Publication Types: 
    Case Reports

PMID: 16362650 [PubMed - indexed for MEDLINE]

1480: J Headache Pain. 2005 Apr;6(2):91-2. Epub 2005 Apr 8.

A woman with daily headaches.

Pascual J, Leno C.

Service of Neurology, University Hospital Marqués de Valdecilla, Santander,
Spain. juliopascual@telefonica.net

Headache, and migraine in particular, is the main neurological reason for
consultation. We present the case of a 48-year-old woman who experienced a
transformation of her episodic migraine attacks into daily headache episodes due 
to the ingestion of biscuits containing wheat as their main ingredient. This
experience emphasises that a good clinical interview remains the most important
point in the diagnosis and management of headache.

Publication Types: 
    Case Reports
    Research Support, Non-U.S. Gov't

PMID: 16362649 [PubMed - indexed for MEDLINE]

1481: J Headache Pain. 2005 Apr;6(2):81-7. Epub 2005 Apr 8.

Managing migraine headaches experienced by patients who self-report with
menstrually related migraine: a prospective, placebo-controlled study with oral
sumatriptan.

Dowson AJ, Massiou H, Aurora SK.

The King's Headache Service, King's College Hospital, Denmark Hill, London SE5
9RS, UK. andydowson@psim-limited.com

The objective was to evaluate the efficacy and tolerability of oral sumatriptan
(100 mg) in patients who self-reported with menstrually related migraine. A
prospective, multicentre, randomised, double-blind, placebo-controlled, two-group
crossover study was carried out in 20 UK primary and secondary care surgeries. Of
115 patients with a self-reported history of menstrually related migraine that
entered the study, 93 patients completed it. Patients treated all migraine
attacks for 2 months with sumatriptan (100 mg) and for 2 months with placebo. The
primary endpoint was the proportion of patients reporting headache relief at 4
hours for the first treated attack. Only 11% of patients fulfilled the protocol
definition of menstrually related migraine. Patients reported a variable pattern 
of migraine attacks occurring inside and outside the menstrual window. For the
first attack, significantly more patients receiving sumatriptan than placebo
reported headache relief for attacks occurring inside (67% vs. 33%, p=0.007) and 
outside (79% vs. 31%, p<0.001) the menstrual period. Sumatriptan was generally
well tolerated. Oral sumatriptan (100 mg) is an effective and well tolerated
acute treatment for patients who report menstrually related migraine.

Publication Types: 
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 16362647 [PubMed - indexed for MEDLINE]

1482: J Headache Pain. 2005 Apr;6(2):71-6. Epub 2005 Apr 8.

High prevalence of patent foramen ovale in migraine with aura.

Ferrarini G, Malferrari G, Zucco R, Gaddi O, Norina M, Pini LA.

Centro Cefalee Alta Specialità, Dipartimento Area Critica, Reggio Emilia, Italy.

In this study we evaluated the presence of patent foramen ovale (PFO) in a cohort
of 25 consecutive patients suffering from migraine with aura (MA) during an
attack presenting to the emergency ward of an Italian hospital. Patients
underwent brain magnetic resonance imaging (MRI) with contrast medium, routine
coagulation tests, contrast transcranial echocolour-coded sonography (c-TCCS) and
transoesophageal echocardiography (TEE). Of the enrolled patients, 88.7% showed a
PFO according to the c-TCCS test, whereas only in 72% TEE confirmed the presence 
of PFO. This discordance could be due to the fact that c-TCCS is more sensitive
even with shunts with minimal capacity also located in the pulmonary vasculature.
After surgical treatment of the PFO, MA disappeared within two months. Also, the 
treatment with warfarin as well as with acetylsalicylic acid and flunarizine was 
able to dramatically reduce the frequency of migraine attacks. These data
indicate a higher prevalence of PFO in MA vs. normal population (OR=2.92) and
could suggest that the presence of arteriovenous (AV) shunts could represent a
trigger for MA attacks as well as for stroke, but more studies are needed to
confirm this preliminary hypothesis.

Publication Types: 
    Case Reports

PMID: 16362645 [PubMed - indexed for MEDLINE]

1483: J Headache Pain. 2005 Apr;6(2):61-70. Epub 2005 Apr 8.

CGRP and migraine: neurogenic inflammation revisited.

Geppetti P, Capone JG, Trevisani M, Nicoletti P, Zagli G, Tola MR.

Headache Center, U.O. Neurology, Department of Neuroscience, Azienda
Università-Ospedale, S. Anna, Ferrara, Italy. pierangelo.geppetti@unifi.it

For more than a century neurogenic inflammation has been proposed to have a role 
in various human diseases. The present review will cover the conceptual steps of 
the itinerary that has led to the conclusion that neurogenic inflammation is
important in migraine. Of particular relevance for the object of this article is 
the observation that tachykin-independent neurogenic inflammatory responses are
evident in rodents, but much less pronounced or absent in other mammal species,
including man, whereas neurogenic vasodilatation, most likely mediated by CGRP,
occurs in most mammalian species and also in man. Recent evidence that a CGRP
receptor antagonist was effective in the treatment of migraine attack supports
the hypothesis that neurogenic vasodilatation is a major underlying mechanism of 
migraine.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 16362644 [PubMed - indexed for MEDLINE]

1484: J Headache Pain. 2005 Feb;6(1):51-4. Epub 2005 Jan 25.

Observations of the "carry-over effect" following successful termination of
chronic migraine in the adolescent with short-term dihydroergotamine,
dexamethasone and hydroxyzine: a pilot study.

Charles JA, Jotkowitz S.

Department of Neurosciences, New Jersey Medical School, 185 S. Orange Avenue,
Newark, NJ 07103-2714, USA. BANDPAR@aol.com

Chronic migraine management almost always requires daily oral preventative
medication with potential adverse effects. Daily oral preventative therapy may
also not be effective in terminating chronic migraine. Chronic central
sensitisation caused by repetitive migraine attacks in a young person may lower
the threshold for future migraine episodes leading to an intractable and
debilitating disease course. The objective was to determine if short-term
parenteral dihydroergotamine, dexamethasone and hydroxyzine can terminate chronic
migraine and be followed by a continuous respite or conversion to a more benign
episodic form without the need for daily oral preventative medication
("carry-over effect"). We treated ten patients, seven adolescents and three
adults, with parenteral dihydroergotamine, dexamethasone and hydroxyzine given
once a week for a maximum of three weeks. No oral preventative daily medication
was administered. The setting was a private practice. Chronic migraine was
terminated in all 7 adolescents. Their post-treatment course was converted to a
more benign episodic migraine course and no adolescent required daily oral
migraine preventative therapy for significantly long carry-over post-treatment
observational periods. None of the three adult chronic migraine cases could be
terminated satisfactorily as they all required daily oral preventative therapy.
In the adolescent group only, this strategy terminated chronic migraine and
resulted in a significant carry-over effect that appeared to favourably modify
the long-term course without the need for daily pharmacological, potentially
toxic, preventive therapy. Although this is a very small study, which requires
confirmation by a larger controlled study, our data suggest a significant
carryover effect in the young migraineur by administering short-term parenteral
dihydroergotamine, dexamethasone and hydroxyzine.

Publication Types: 
    Clinical Trial

PMID: 16362192 [PubMed - indexed for MEDLINE]

1485: J Headache Pain. 2005 Feb;6(1):40-7. Epub 2005 Jan 25.

The patients' perceptions of migraine and chronic daily headache: a qualitative
study.

Peters M, Huijer Abu-Saad H, Vydelingum V, Dowson A, Murphy M.

European Institute of Health and Medical Sciences, Duke of Kent Building,
University of Surrey, Guildford, Surrey GU2 7TE, UK.

This study aimed to gain insight into the management of migraine and chronic
daily headache (CDH) from the patients' perspective. This article outlines the
patients' perceptions of migraine and chronic daily headache. Thirteen
semi-structured interviews were carried out with patients suffering from IHS
migraine. Five patients, due to their headache frequency of more than 15 headache
days per month, were classed as CDH patients. The data were transcribed verbatim 
and analysed in accordance with the grounded theory methodology. The main themes 
were: headaches, impact and headaches related to health issues. The theme
'headaches' was sub-divided into 'their pain and symptoms', 'differentiating
between their headaches' and 'perceptions of headaches as barriers and
facilitators to management'. The patients' perceptions of migraine and CDH were
sometimes conflicting and influenced the patients' management behaviours. The
qualitative methodology may help to inform doctors, other healthcare
professionals and headache researchers about the patients' perspective and
possibly develop future headache research, care and education.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16362190 [PubMed - indexed for MEDLINE]

1486: J Headache Pain. 2005 Feb;6(1):10-9. Epub 2005 Jan 25.

Feeling and seeing headaches.

Blau JN.

City of London Migraine Clinic, 22 Charterhouse Square, London EC1 6DX, UK.
blaujn@yahoo.co.uk

The aim is to deepen our understanding of headache by three approaches. First, by
trying to feel patients' total experience by eliciting their symptoms in detail, 
and from their reactions to these experiences. Second, by trying to remember
one's own experience of headache, and observing a few patients during different
headache types. Third, by attempting to see the different mechanisms of headaches
by their sites of origin and their pathophysiology. Migraine, tension-type and
cluster headache are the three headaches examined by these approaches. Migraine
seems to arise from disturbances of the brain's cortex followed by meningeal
pain--hence is intracranial in origin. Tension-type headache seems to arise from 
extracranial muscles, although the pain derives from the fascia or tendons of
those muscles; common sites are the masticatory apparatus and the neck--hence
extracranial. Cluster headache remains a mystery although vasodilatation
provokes, and vasoconstriction stops, attacks--hence vasomotor control is
therapeutically valuable. It is concluded that we need more adventurous ideas to 
deepen our understanding of these and other headaches.

Publication Types: 
    Review

PMID: 16362186 [PubMed - indexed for MEDLINE]

1487: Neuroreport. 2006 Jan 23;17(1):61-4.

Association of migraine and ESR1 G325C polymorphism.

Oterino A, Pascual J, Ruiz de Alegría C, Valle N, Castillo J, Bravo Y, González
F, Sánchez-Velasco P, Cayón A, Leyva-Cobián F, Alonso-Arranz A, Muñoz P.

Services of Neurology, Universitary Hospital Marqués de Valdecilla, Santander,
Spain. aoterino@humv.es

Migraine is a genetically complex disorder in which sexual hormones influence the
phenotype. ESR1 G594A polymorphism has been associated with migraine in
Australians. We performed a case-control study with G594A and G325C polymorphisms
to determine whether ESR1 is associated with migraine in our population. An
association between G594A and migraine could not be demonstrated here. By
contrast, we observed that the C325 allele conferred a 1.6 (95% confidence
interval=1.1-2.4) higher risk for suffering from migraine in women than the G
allele. Women carrying the C352C genotype were over 3 times more likely to suffer
from migraine than those carrying the G325G genotype. Therefore, we conclude that
ESR1 G325C polymorphism is associated with migraine in our population.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 16361951 [PubMed - indexed for MEDLINE]

1488: Epilepsia. 2005;46 Suppl 10:2-6.

Comment in:
    Epilepsia. 2006 Apr;47(4):806-8; author reply 808.

A case of "migralepsy".

Milligan TA, Bromfield E.

Department of Neurology, Brigham and Women's Hospital and Harvard Medical School,
Boston, MA 02115, USA.

Migraine and epilepsy are common neurological conditions that may share a
pathophysiologic and genetic basis. The following case is presented to illustrate
key aspects of their relationship.

Publication Types: 
    Case Reports

PMID: 16359463 [PubMed - indexed for MEDLINE]

1489: Med Hypotheses. 2006;66(3):454-60. Epub 2005 Dec 13.

Migrainous scintillating scotoma and headache is ocular in origin: A new
hypothesis.

Gupta VK.

Dubai Police Medical Services, P.O. Box 12005, Dubai, United Arab Emirates.
dr_vkgupta@yahoo.com

Brain neuronal dysfunction has been implicated in pathogenesis of migraine but
direct evidence is lacking. Scintillating scotoma of migraine is generally
believed to originate at the visual cortex. While cortical spreading depression
is a relatively late physiological alteration in migraine, its protective role in
neuronal ischaemia is increasingly being recognized. Atenolol, nadolol, or
verapamil prevent migraine but do not readily cross the blood-brain barrier or
critically influence any brain or peripheral neuronal function. Typical migraine 
headache, aura, or scintillating scotoma has not been reported following
enucleation or evisceration of the eye. In humans, pain and temperature fibres
from only the ophthalmic division of the trigeminal nerve reach the upper
cervical spinal segments. Pain in migraine attacks including occipital and nuchal
discomfort reflects selective involvement of the ophthalmic nerve. Photophobia is
largely a retinal reflex involving the ophthalmic division of the trigeminal
nerve. Key clinical features of the migrainous scintillating scotoma are
consistent with retinal origin. Spreading depression in the retina is
well-established. A subtle regional ocular sympathetic deficit prevails in
migraine patients and possibly impairs regulation of intraocular choroidal blood 
volume and intraocular pressure. Several first-line migraine prophylactic agents 
lower the intraocular pressure. The neuro-ophthalmological basis for a monocular 
origin of migrainous scintillating scotomata due to mechanical deformation of the
posterior segment of the corneo-scleral envelope consequent to choroidal venous
congestion and rise in intraocular pressure is presented. Study of distribution
and displaceability of the migrainous scintillating scotoma can settle its site
of origin. Headache of migraine possibly arises from a similar mechanical
deformation of the anterior eye segment followed by antidromic discharge in the
trigeminovascular system. Lateralizing negative deficits such as homonymous
hemianopia probably reflect vasospastic complications of migraine. A rational
explanation for the most characteristic clinical features of migraine and a new
template to elucidate the pharmacological basis of anti-migraine drugs is
offered.

PMID: 16356654 [PubMed - indexed for MEDLINE]

1490: Neurosci Lett. 2006 Jan 30;393(2-3):90-3. Epub 2005 Dec 13.

HLA-DRB1 genotyping in Italian migraine patients.

Rainero I, Dall'Omo AM, Rubino E, Valfrè W, Fasano ME, Rivoiro C, Brancatello F, 
Savi L, Gallone S, Pinessi L.

Neurology III-Headache Center, Department of Neuroscience, University of Torino, 
Via Cherasco 15, Torino 10126, Italy. irainero@molinette.piemonte.it

We examined the distribution of HLA-DRB1 alleles in a cohort 255 Italian migraine
patients and in a control group of 325 healthy subjects. 214 patients fulfilled
the ICHD-II criteria for migraine without aura and 41 patients the criteria for
migraine with aura. The frequency of DRB1*16 allele was found to be significantly
increased in migraine without aura patients (p=0.02; OR 1.97, 95% CI: 1.10-3.54) 
than in healthy controls. The frequencies of HLA-DRB1 alleles were not
significantly different between migraine with aura patients and controls. We did 
not detect any effect of DRB1 alleles on age at onset, duration of the disease,
frequency and duration of migraine attacks. Our data suggest the presence of a
genetic susceptibility factor for migraine without aura within the HLA region.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 16356649 [PubMed - indexed for MEDLINE]

1491: J Headache Pain. 2005 Jun;6(3):143-8. Epub 2005 May 13.

Intramuscular tramadol vs. diclofenac sodium for the treatment of acute migraine 
attacks in emergency department: a prospective, randomised, double-blind study.

Engindeniz Z, Demircan C, Karli N, Armagan E, Bulut M, Aydin T, Zarifoglu M.

Department of Emergency Medicine, Uludag University Medical Faculty, Acil Tip ABD
Gorukle, Bursa 16059, Turkey. zengindeniz@hotmail.com

The aim of this prospective, randomised, double-blind study was to evaluate the
efficacy of intramuscular (IM) tramadol 100 mg in emergency department treatment 
of acute migraine attack and to compare it with that of IM diclofenac sodium 75
mg. Forty patients who were admitted to our emergency department with acute
migraine attack according to the International Headache Society criteria were
included in the study. Patients were randomised to receive either tramadol 100 mg
(n=20) or diclofenac sodium 75 mg (n=20) intramuscularly. Patients rated their
pain on a four-point verbal scale (0=none, 1=mild, 2=moderate, 3=severe) at the
beginning of the trial and at 30, 60, 90 and 120 min. At each time interval,
severity of associated symptoms were also questioned and recorded. Global
evaluation of the drugs by patients and doctors were also recorded. Patients were
also asked if they would prefer the same injection in future visits. Any adverse 
events, whether related to the drug or not, were also recorded. Patients were
followed up by telephone 48 h later to check for any headache recurrence.
Two-hour pain response rate, which was the primary endpoint, was 80% for both
tramadol and diclofenac groups. There were no statistically significant
differences among groups in terms of 48-h pain response, rescue treatment,
associated symptoms' response, headache recurrence and adverse event rates.
Fifteen (75%) patients in the tramadol group and 16 (80%) patients in the
diclofenac group stated that they may prefer the same agent for future
admissions. In selected patients, tramadol 100 mg IM may be an effective and
reliable alternative treatment choice in acute migraine attacks.

Publication Types: 
    Comparative Study
    Randomized Controlled Trial

PMID: 16355295 [PubMed - indexed for MEDLINE]

1492: J Headache Pain. 2005 Jun;6(3):128-34. Epub 2005 May 13.

Demographic, clinical and comorbidity data in a large sample of 1,147 patients
with migraine in Mexico City.

Téllez-Zenteno JF, García-Ramos G, Zermeño-Pöhls F, Velazquez A; GGSM.

GGSM, Department of Neurology and Psychiatry, National Institute of Medical
Sciences and Nutrition, Salvador Zubirán, Vasco de Quiroga No. 15, Colonia
Sección XVI, Delegación Tlalpan, México, D.F. CP 14000, Mexico.
jftellez@yahoo.com

The objective was to identify the sociodemographic and clinical characteristics
of a large sample of patients with migraine in Mexico City. This cross-sectional 
study was performed in two tertiary centers in Mexico City and affiliated
hospitals. We evaluated the presence of migraine through a standardised interview
according to the criteria of the International Headache Society. We studied 1,147
patients. The mean age was 37.1+/-13.6 (6-77) years. Nine hundred and twenty one 
patients were female (80%). The age of onset of migraine was 19.4+/-10.3 (1-69)
years. Six hundred and four patients had migraine with aura (53%) and 543 without
aura (47%). The female/male ratio was 4:1. One hundred and forty-seven patients
had cardiovascular problems (13%), 72 had neurological problems (6%), 233 had
gastrointestinal problems (20%) and 323 had psychiatric problems (28%). In this
study we described the clinical characteristics of a large sample of patients
with migraine in Mexico City. Our sample has similar characteristics to other
countries.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16355293 [PubMed - indexed for MEDLINE]

1493: J Headache Pain. 2005 Jun;6(3):121-7. Epub 2005 May 13.

Nosology and treatment of primary headache in a Swiss headache clinic.

Kozak S, Gantenbein AR, Isler H, Merikangas KR, Angst J, Gamma A, Agosti R.

Headache and Pain Unit, Neurology Department, Zürich University Hospital,
Frauenklinikstrasse 26, Switzerland.

We assessed demographics, diagnoses, course, severity, impact and treatment of
primary headache outpatients from records in the Headache and Pain Clinic,
Neurological Department, Zürich University Hospital. All outpatients seen from
1996 to 1998 for migraine, tension-type headache, and both, were included.
Diagnoses, drug, physical and alternative treatments before and after referral
were listed. Descriptive statistics were used for differences between the general
population and this sample, the diagnoses, and treatments. The coexistence of
migraine and tension-type headache, and the high frequencies of headache days
would have excluded most migraine patients from typical drug trials: at best,
only one third were eligible. The socioeconomic impact of combined and difficult 
syndromes calls for comprehensive management beyond simple treatment with instant
relief drugs. The diagnostic and therapeutic practices of referring physicians
exposed a deficit of information on headache, and a need for relevant education.

PMID: 16355292 [PubMed - indexed for MEDLINE]

1494: J Headache Pain. 2005 Jun;6(3):112-20. Epub 2005 May 13.

Patients' preference for triptans and other medications as a tool for assessing
the efficacy of acute treatments for migraine.

Dowson AJ, Tepper SJ, Dahlöf C.

King's Headache Service, King's College Hospital, Denmark Hill, London SE5 9RS,
UK. andydowson@psim-limited.com

Oral triptans are effective and well tolerated acute treatments for migraine, but
clinical differences between them are small and difficult to measure in
conventional clinical trials. Patient preference assesses a global measure of
efficacy and tolerability, and may be a more sensitive means of distinguishing
between these drugs. In a series of studies, patients consistently expressed a
clear preference for triptans over their usual non-triptan acute medications,
e.g., analgesics and ergotamine. Direct comparator studies of patient preference 
with oral triptans showed that patients could distinguish between different
triptans, and between different formulations of the same triptan. Patients could 
even distinguish between the three oral doses of sumatriptan. The most frequently
provided reasons for preference were speed of response and overall effectiveness.
Patient preference is a sensitive clinical trial endpoint and physicians should
consider using it when reviewing the efficacy of acute migraine medications.

Publication Types: 
    Review

PMID: 16355291 [PubMed - indexed for MEDLINE]

1495: J Headache Pain. 2005 Jun;6(3):105-11. Epub 2005 May 13.

The pathophysiology of migraine: year 2005.

Buzzi MG, Moskowitz MA.

Headache Centre, IRCCS Santa Lucia Foundation, Via Ardeatina 306, I-00179, Rome, 
Italy. mg.buzzi@hsantalucia.it

Migraine is a complex patholophysiology in which both central and peripheral
components of the trigeminal pain pathway probably play a significant role, both 
in the symptoms and signs of the attack and in the mechanisms of action of
antimigraine compounds, such as triptans, which constitute the most important
therapy for aborting migraine pain and possess several mechanisms on 5-HT
receptor-mediated actions. The experimental neurogenic inflammation model
represents a simple procedure to obtain preliminary information on well
characterized receptortargeted drugs. The apparent paradox observed with certain 
drugs that are shown to be effective in this model but not in clinical trials
offers the opportunity to better manipulate structure-activity to obtain the best
pharmacological profile using an array of experimental models. The observation
that nitric oxide donors induce migraine-like pain in migraineours and that
nitric oxide plays a pivotal role in the control of several functions in the
central nervous system, has prompted the use of such molecules for better
understanding the pathophysiology of migraine attacks. A link between central and
peripheral components of the trigeminal pain pathway is provided by the
observation that cortical spreading depression in the rat activates
trigeminovascular afferents and induces a series of cortical meningeal and
brainstem events consistent with the development of headache. Studies in humans
support the hypothesis that cortical spreading depression underlies
migraine.aura. Therefore, tt is possible that visual, motor or sensory aura might
be responsible for the generation of the pain through the above mechanisms.

Publication Types: 
    Review

PMID: 16355290 [PubMed - indexed for MEDLINE]

1496: Neurology. 2006 Feb 28;66(4):545-50. Epub 2005 Dec 14.

Comment in:
    Neurology. 2007 Jan 16;68(3):241; author reply 241.    Neurology. 2007 Jan 16;68(3):241; author reply 241.

Obesity and migraine: a population study.

Bigal ME, Liberman JN, Lipton RB.

Department of Neurology, Albert Einstein College of Medicine, Bronx, NY, USA.
mbigal@aecom.yu.edu

OBJECTIVE: To assess the influence of body mass index (BMI) on the prevalence,
attack frequency, and clinical features of migraine. METHODS: In a
population-based telephone interview study, the authors gathered information on
headache, height, and weight. The 30,215 participants were divided into five
categories, based on BMI: 1, underweight (< 18.5), normal weight (18.5 to 24.9), 
overweight (25 to 29.9), obese (30 to 24.9), and morbidly obese (> or = 35).
Migraine prevalence and modeled headache features were assessed as a function of 
BMI, adjusting by covariates (age, sex, marital status, income, medical
treatment, depression). RESULTS: Subjects were predominantly female (65% female) 
and in middle life (mean age 38.4). BMI group was not associated with the
prevalence of migraine, but was associated with the frequency of headache
attacks. In the normal weight group, 4.4% had 10 to 15 headache days per month,
increasing to 5.8% of the overweight (odds ratio [OR] = 1.3), 13.6% of the obese 
(OR = 2.9), and 20.7% of the morbidly obese (OR = 5.7). The proportion of
subjects with severe headache pain increased with BMI, doubling in the morbidly
obese relative to the normally weighted (OR = 1.9). Similar significant
associations were demonstrated with BMI category for disability, photophobia, and
phonophobia. CONCLUSION: Though migraine prevalence is not associated with body
mass index, attack frequency, severity, and clinical features of migraine
increase with body mass index group.

Publication Types: 
    Multicenter Study
    Research Support, Non-U.S. Gov't

PMID: 16354886 [PubMed - indexed for MEDLINE]

1497: Dis Manag. 2005 Dec;8(6):382-91.

Impact of a migraine management program on improving health outcomes.

Campinha-Bacote DL, Kendle JB, Jones C, Callicoat D, Webert A, Stoukides CA, Kaul
AF.

Aetna Health Inc., Cincinnati, Ohio 45202, USA. capinahabacoted@aetna.com

The goals of this program were to evaluate the effectiveness of migraine disease 
management techniques in improving patient satisfaction with migraine care,
decreasing the frequency and severity of headaches and migraine-associated
disability, increasing the effectiveness of migraine treatment and work
productivity, improving physician diagnosis and treatment of migraine, and
ultimately determining the program's impact on healthcare resource utilization. A
prospective observational study was undertaken. This prospective Migraine
Management Program (MMP) used active patient and healthcare physician-based
disease management resources, tools, and techniques. Members were identified
using administrative and medical claims databases indicating an ICD-9 diagnosis
code (346.XX) for migraine during the previous twelve months. All identified
patients received the Migraine Therapy Assessment Questionnaire (MTAQ) to assess 
their level of migraine control for pre/post measurement. Of the 2,134 patients
responding to the initial MTAQ, 789 completed both a baseline and follow-up and
1,345 completed only a baseline questionnaire. For those patients completing
both, there was a statistically significant reduction in all identified
management issues: poor symptom control, high attack frequency,
knowledge/behavior barriers, economic burden, and dissatisfaction with treatment.
Comparing the former group to those completing only the baseline MTAQ, the latter
were significantly more likely to report problems with three migraine management 
issues; poorer symptom control, greater economic burden, and dissatisfaction with
their treatment. The use of appropriate patient and physician educational
interventions, such as Aetna's MMP incorporating disease management principles
and the MTAQ questionnaire, can have a significant impact on patient-centered
outcomes and satisfaction with their migraine treatment.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16351556 [PubMed - indexed for MEDLINE]

1498: CNS Spectr. 2005 Dec;10(12):980-3.

Magnetic resonance imaging changes in a patient with migraine attack and
transient global amnesia after cardiac catheterization.

Fernandez A, Rincon F, Mazer SP, Elkind MS.

Department of Neurology, College of Physicians and Surgeons, Columbia University,
New York, NY 10032, USA.

The presence of magnetic resonance imaging (MRI) abnormalities in patients with
transient global amnesia has been an interesting phenomenologic finding. Several 
theories surround the occurrence of this syndrome, but little is known about its 
true physiopathology. We present a case of transient global amnesia after cardiac
catheterization associated with migraine headache and MRI changes compatible with
an ischemic insult. A discussion on potential explanations for this finding is
made, as well as a review of the pertinent literature.

Publication Types: 
    Case Reports
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 16344834 [PubMed - indexed for MEDLINE]

1499: Neurology. 2005 Dec 13;65(11):1826-8.

Familial basilar migraine associated with a new mutation in the ATP1A2 gene.

Ambrosini A, D'Onofrio M, Grieco GS, Di Mambro A, Montagna G, Fortini D,
Nicoletti F, Nappi G, Sances G, Schoenen J, Buzzi MG, Santorelli FM, Pierelli F.

Headache Clinic, INM Neuromed, Pozzilli, Italy. anna.ambrosini@neuromed.it

Basilar migraine (BM), familial hemiplegic migraine (FHM), and sporadic
hemiplegic migraine (SHM) are phenotypically similar subtypes of migraine with
aura, differentiated only by motor symptoms, which are absent in BM. Mutations in
CACNA1A and ATP1A2 have been found in FHM. The authors detected a novel mutation 
in the ATP1A2 gene (R548H) in members of a family with BM, suggesting that BM and
FHM may be allelic disorders.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16344534 [PubMed - indexed for MEDLINE]

1500: Pharmacopsychiatry. 2005 Nov;38(6):327-8.

Exacerbation of migraine attacks during treatment with the selective serotonin
reuptake inhibitor sertraline. A case report.

Bickel A, Kornhuber J, Maihöfner C, Ropohl A.

Abnormal signal transmission in central serotonergic pathways is supposed to play
an important role in the pathogenesis of migraine and major depression. We report
on a patient, who was treated during an episode of depression with the selective 
serotonin reuptake inhibitor (SSRI) sertraline and developed frequent migraine
attacks under this therapeutical regime. Single migraine attacks were treated
successfully with triptanes. Although SSRIs may be beneficial for migraine
prophylaxis at long term administration, this case suggests that acute
administration of SSRIs in migraineurs may include the risk of worsening
migraine.

Publication Types: 
    Case Reports
    Letter

PMID: 16342007 [PubMed - indexed for MEDLINE]

1501: Clin Neuropharmacol. 2005 Nov-Dec;28(6):277-9.

Efficacy of topiramate and valproate in chronic migraine.

Bartolini M, Silvestrini M, Taffi R, Lanciotti C, Luconi R, Capecci M,
Provinciali L.

Department of Neuroscience, Polytechnic University of Marche, Via Conca 71, 60020
Ancona, Italy.

OBJECTIVES: The aim of this study was to compare the efficacy of sodium valproate
and topiramate in treating chronic migraine. METHODS: Forty-nine patients with
chronic migraine were randomly assigned to 1 of 2 groups of treatment: 750 mg/day
valproate or 75 mg/day topiramate. Efficacy variables were number of days with
headache over a 30-day period and changes in Migraine Disability Assessment
(MIDAS) scores at 3 months. RESULTS: At baseline the 2 groups had similar numbers
of days with headache and mean MIDAS scores. At the end of the treatment period, 
a significant reduction in 30-day headache frequency with respect to baseline (P 
< 0.00001) and a significant reduction in MIDAS scores (P < 0.00001) were
recorded in both groups. There were no significant differences in beneficial
effects between the 2 drugs. DISCUSSION: Valproate and topiramate seem to be able
to manage successfully chronic migraine without substantial differences in
efficacy and tolerability. This affords clear practical advantages-in the event
of failure of or intolerance for one treatment, the patient may be switched to
the other.

Publication Types: 
    Clinical Trial
    Comparative Study
    Randomized Controlled Trial

PMID: 16340383 [PubMed - indexed for MEDLINE]

1502: Tohoku J Exp Med. 2006 Jan;208(1):87-92.

Prevalence and clinical characteristics of migraine in university students in
Turkey.

Demirkirkan MK, Ellidokuz H, Boluk A.

Department of Neurology, Kocatepe University School of Medicine, Afyon, Turkey.

Migraine is a significant health problem due to its frequency and accompanying
morbidity, which includes disability and loss of performance. We aimed to
estimate the prevalence of migraine and assess the disability and preferences of 
treatment among university students in Afyon, a Turkish city. This is the first
cross-sectional prevalence study of migraine conducted on university students in 
Turkey. The study has been carried out in two stages. The first stage aimed to
identify the students with migraine by using a standardized International
Headache Society (IHS) questionnaire. In this questionnaire, the students were
asked about medical consultations and medicines used during attacks. The standard
questionnaire was applied to 1,029 students, and migraine was found in 128
students (12.4%). Of these headache sufferers, 104 students were using
non-prescribed drugs during headache attacks, while the remaining 24 students
were using the drugs on advice of physicians. At the second stage, we evaluated
the impact of disease on daily life in these students by the Migraine Disability 
Assessment Scale (MIDAS) questionnaire, showing that the degrees of disability
are minimal in 11 students (8.6%), mild in 30 students (23.4%), moderate in 34
students (26.6%), and severe in 53 students (41.4%). In conclusion, migraine
attacks are associated with a considerable degree of handicap in activities of
daily living. However, many university students with migraine do not consult a
physician and continue to treat their headaches with simple analgesics. Global
educational programs are required for patients to recognize the importance of
effective migraine treatment.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16340178 [PubMed - indexed for MEDLINE]

1503: J Clin Pharm Ther. 2005 Dec;30(6):521-32.

Efficacy and tolerability of frovatriptan in acute migraine treatment: systematic
review of randomized controlled trials.

Poolsup N, Leelasangaluk V, Jittangtrong J, Rithlamlert C, Ratanapantamanee N,
Khanthong M.

Department of Pharmacy, Faculty of Pharmacy, Silpakorn University, Nakhon-Pathom,
Thailand. nalinee@email.pharm.su.ac.th

OBJECTIVE: To evaluate the efficacy and tolerability of frovatriptan in acute
migraine treatment. METHODS: Systematic review and meta-analysis of randomized
controlled trials. Clinical trials of frovatriptan were systematically identified
through electronic searches and historical searches up until February 2005.
Studies were included if they were (i) double-blind, randomized, placebo
controlled trials that evaluated frovatriptan 2.5 mg in acute migraine treatment 
and (ii) reporting the efficacy data in terms of pain-free, headache response,
headache recurrence, or relief of migraine-associated symptoms. Two authors
extracted data independently. Disagreements were resolved through discussion. The
efficacy was estimated using risk ratio (RR), risk difference, and number needed 
to treat together with 95% confidence intervals. RESULTS: Five trials involving a
total of 2,866 patients were included. Frovatriptan 2.5 mg was more effective
than placebo in rendering patient pain-free (RR 3.70, 95% CI 2.59-5.29, P <
0.0001 at 2 h and 2.67, 95% CI 2.21-3.22, P < 0.0001 at 4 h post-dose). It was
also superior to placebo in reducing headache severity. The pooled RR was 1.66
(95% CI 1.48-1.88, P < 0.0001) and 1.83 (95% CI 1.66-2.00, P < 0.0001),
respectively, at 2 and 4 h after treatment. In those whose headache was relieved 
at 4 h, the risk of headache recurrence within 24 h was reduced by 26% with
frovatriptan (RR 0.74, 95% CI 0.59-0.93, P = 0.009). Frovatriptan was also
superior to placebo in improving symptoms associated with migraine. At 2 h after 
dosing, frovatriptan reduced the risk of nausea by 14% (95% CI 6-20%, P =
0.0005), photophobia 17% (95% CI 12-22%, P < 0.0001), and phonophobia 14% (95% CI
17-20%, P < 0.0001). The corresponding numbers at 4 h after dosing were 37% (95% 
CI 30-43%, P < 0.0001), 34% (95% CI 29-39%, P < 0.0001) and 30% (95% CI 23-36%, P
< 0.0001), respectively. Frovatriptan caused more adverse events than did placebo
(RR 1.31, 95% CI 1.07-1.62, P = 0.01). CONCLUSION: The available evidence
suggests that frovatriptan is more effective but may cause more adverse events
than placebo in the treatment of acute moderate to severe migraine. It is
effective in providing pain relief and reducing the risk of recurrence. However, 
its effectiveness relative to other more established agents needs to be better
defined by appropriate head to head trials.

Publication Types: 
    Review

PMID: 16336284 [PubMed - indexed for MEDLINE]

1504: Pharmacoeconomics. 2005;23(12):1283-98.

Rizatriptan: a pharmacoeconomic review of its use in the acute treatment of
migraine.

McCormack PL, Foster RH.

Adis International Limited, Auckland, New Zealand. demail@adis.co.nz

Rizatriptan (Maxalt; Maxalt-MLT; Maxalt-Melt) is an oral serotonin 5-HT(1B/1D)
receptor agonist (triptan) used in the acute treatment of migraine with or
without aura in adults. Rizatriptan 5 mg and 10 mg are effective in relieving the
symptoms of migraine and the 10 mg dose provided faster pain relief than
sumatriptan 50 mg, naratriptan 2.5 mg, ergotamine/caffeine 2 mg/200 mg and
possibly zolmitriptan 2.5 mg, while displaying similar tolerability. Two
cost-utility analyses performed from a societal perspective indicated that
rizatriptan 10 mg was dominant over ergotamine/caffeine 2 mg/200 mg, sumatriptan 
50 mg or 100 mg, naratriptan 2.5 mg, zolmitriptan 2.5 mg and analgesic-based
usual care in the acute treatment of migraine. In one analysis also performed
from the perspective of a healthcare payer, rizatriptan was still dominant over
naratriptan, sumatriptan and zolmitriptan. Rizatriptan was cost effective
compared with usual care with an incremental cost per quality-adjusted life-year 
(QALY) gained of 31,845 Can dollars (2002 values) and an incremental cost per
additional attack aborted of 49.82 Can dollars. A modelled cost-effectiveness
analysis conducted from a healthcare payer's perspective indicated that
almotriptan 12.5 mg was more cost effective than rizatriptan 10 mg as a result of
better tolerability. The incremental cost per additional successfully treated
patient (defined as being sustained pain free without adverse events) with
almotriptan was 6.94 US dollars (1999 values). In other nonmodelled
cost-effectiveness analyses, rizatriptan 10 mg, eletriptan 40 mg and almotriptan 
12.5 mg most consistently displayed the greatest cost effectiveness in different 
analyses using different clinical endpoints. A modelled analysis of the costs of 
migraine-related productivity losses in US corporations indicated that the use of
rizatriptan rather than usual care to treat migraines could result in annual cost
offsets of approximately 84-118 US dollars (2000 values) per employee in lost
productivity avoided. An intervention study in Spanish postal service workers
demonstrated that replacement of usual care with rizatriptan reduced the mean
per-patient cost of lost productivity per migraine attack from 34.47 euros
(2001/2002 values) before the intervention to 13.94 euros and 4.59 euros for the 
first and second post-intervention migraine attacks. In conclusion, rizatriptan
is one of the more clinically effective and therefore cost-effective oral
triptans available for the acute treatment of migraine. The available data from
cost-utility analyses suggest that rizatriptan is more cost effective than
ergotamine/caffeine, simple analgesics, naratriptan, zolmitriptan and
sumatriptan. The economic value of rizatriptan depends on the payer's
perspective, as the greatest savings can be expected to be achieved in terms of
reduced migraine-related loss of work productivity compared with less effective
treatments. For healthcare payers, the high acquisition cost appears to be at
least partly offset by reduced migraine-related healthcare resource use when
compared with usual care. The comparative cost effectiveness of the newer
triptans requires further elucidation from comprehensive direct comparisons.

Publication Types: 
    Meta-Analysis
    Review

PMID: 16336021 [PubMed - indexed for MEDLINE]

1505: Eur J Epidemiol. 2005;20(12):1007-14.

Secular changes in health care utilization and work absence for migraine and
tension-type headache: a population based study.

Lyngberg AC, Rasmussen BK, Jørgensen T, Jensen R.

Research Centre for Prevention and Health, Copenhagen University Hospital,
Copenhagen County, Glostrup, Denmark. acl@hsd.hosp.dk

OBJECTIVE: To assess changes in consultation rates, medication use and work
absences due to migraine and tension-type headache (TTH) in Denmark over a
12-year period. METHODS: Surveys of the general population in 1989 and 2001.
Medical doctors conducted all headache diagnostic interviews based on ICDH-I and 
II. The participation rate was 76% (740) in 1989 and 74% (711) in 2001. Headache 
status was categorized as pure migraine, pure frequent TTH (frequent episodic or 
chronic TTH), coexisting migraine and frequent TTH, and healthy subjects (no
primary headache or only infrequent TTH). RESULTS: Headache-related consultation 
rates (OR = 1.6 (1.1-2.2)), especially specialist consultations (OR = 3.6
(2.3-5.6)), increased for all headache groups. Use of prescription medication
because of headache increased moderately (OR = 2.1 (1.1-3.9)) while the use of
prophylactic medication was stable (OR = 1.1 (0.3-4.0)). Both headache-related
(OR = 1.1 (0.7-1.7)) and overall (OR = 0.9 (0.7-1.2)) absence rates were largely 
unchanged. Headache-related absence rates were higher for subjects with both
headache types (OR = 7.5 (4.3-13.1)) or with pure migraine (OR = 3.6 (2.0-6.6))
than for subjects with frequent TTH alone. Triptans users had higher migraine
headache frequency and tended to have higher absence rates than non-users.
Overall absence rates were higher for subjects with both headache types (OR = 2.3
(1.3-4.0)) or with frequent TTH (OR = 1.9 (1.4-2.7)) than for healthy subjects.
Pure migraine was not associated with higher overall absence rates (OR = 1.0
(0.6-1.6)). CONCLUSION: Despite an increase in headache consultation rates and in
use of prescription medication and triptans, no improvement in work absence rates
was observed. Consultations, medication use, and absence rates were highest for
individuals with both migraine and frequent TTH.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16331432 [PubMed - indexed for MEDLINE]

1506: Arch Pediatr Adolesc Med. 2005 Dec;159(12):1157-60.

The prognosis of childhood headache: a 20-year follow-up.

Brna P, Dooley J, Gordon K, Dewan T.

Division of Pediatric Neurology, Department of Pediatrics, Dalhousie University, 
Halifax, Nova Scotia, Canada. pbrna@hotmail.com

BACKGROUND: Headaches affect most children and rank third among illness-related
causes of school absenteeism. Although the short-term outcome for most children
appears favorable, few studies have reported long-term outcome. OBJECTIVE: To
evaluate the long-term prognosis of childhood headaches 20 years after initial
diagnosis in a cohort of Atlantic Canadian children who had headaches diagnosed
in 1983. METHODS: Ninety-five patients with headaches who consulted 1 of the
authors in 1983 were previously studied in 1993. The 77 patients contacted in
1993 were followed up in 2003. A standardized interview protocol was used.
RESULTS: Sixty (78%) of 77 patients responded (60 of the 95 of the original
cohort). At 20-year follow-up, 16 (27%) were headache free, 20 (33%) had
tension-type headaches, 10 (17%) had migraine, and 14 (23%) had migraine and
tension-type headaches. Having more than 1 headache type was more prevalent than 
at diagnosis or initial follow-up (P<.001), and headache type varied across time.
Of those with headaches at follow-up, 80% (35/44) described their headaches as
moderate or severe, although an improvement in headaches was reported by 29
(66%). Tension-type headaches were more likely than migraine to remit (P<.04).
Headache severity at diagnosis was predictive of headache outcome at 20 years.
During the month before follow-up, nonprescription medications were used by 31
(70%) of those with ongoing headaches, and prescription medications were used by 
6 (14%). However, 20 (45%) believed that nonpharmacological methods were most
effective. Medication use increased during the 10 years since last follow-up. No 
patient used selective serotonin receptor agonists (triptans). CONCLUSIONS:
Twenty years after diagnosis of pediatric headache, most patients continue to
have headache, although the headache classification often changes across time.
Most patients report moderate or severe headache and increasingly choose to care 
for their headaches pharmacologically.

Publication Types: 
    Comparative Study

PMID: 16330740 [PubMed - indexed for MEDLINE]

1507: Brain. 2006 Feb;129(Pt 2):543-50. Epub 2005 Dec 5.

Comment in:
    Brain. 2006 Jul;129(Pt 7):E52; author reply E53.

Orbitofrontal cortex involvement in chronic analgesic-overuse headache evolving
from episodic migraine.

Fumal A, Laureys S, Di Clemente L, Boly M, Bohotin V, Vandenheede M, Coppola G,
Salmon E, Kupers R, Schoenen J.

Department of Neurology, University of Liège, Liège, Belgium.
arnaud.fumal@ulg.ac.be

The way in which medication overuse transforms episodic migraine into chronic
daily headache is unknown. To search for candidate brain areas involved in this
process, we measured glucose metabolism with 18-FDG PET in 16 chronic migraineurs
with analgesic overuse before and 3 weeks after medication withdrawal and
compared the data with those of a control population (n = 68). Before withdrawal,
the bilateral thalamus, orbitofrontal cortex (OFC), anterior cingulate gyrus,
insula/ventral striatum and right inferior parietal lobule were hypometabolic,
while the cerebellar vermis was hypermetabolic. All dysmetabolic areas recovered 
to almost normal glucose uptake after withdrawal of analgesics, except the OFC
where a further metabolic decrease was found. A subanalysis showed that most of
the orbitofrontal hypometabolism was due to eight patients overusing combination 
analgesics and/or an ergotamine-caffeine preparation. Medication overuse headache
is thus associated with reversible metabolic changes in pain processing
structures like other chronic pain disorders, but also with persistent
orbitofrontal hypofunction. The latter is known to occur in drug dependence and
could predispose subgroups of migraineurs to recurrent analgesic overuse.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16330505 [PubMed - indexed for MEDLINE]

1508: Hum Mol Genet. 2006 Jan 15;15(2):251-8. Epub 2005 Dec 5.

A genome-wide linkage scan of familial benign recurrent vertigo: linkage to 22q12
with evidence of heterogeneity.

Lee H, Jen JC, Wang H, Chen Z, Mamsa H, Sabatti C, Baloh RW, Nelson SF.

Department of Human Genetics, University of California, Los Angeles, 90095, USA.

Benign recurrent vertigo (BRV) is a common disorder affecting up to 2% of the
adult population and may be etiologically related to migraine because of
similarities in the clinical spectrum of the phenotypes and a high co-morbidity
within families. Many families have multiple-affected genetically related
individuals suggesting familial transmission of the disorder with moderate to
high penetrance. While clinically similar to episodic ataxias, there are
currently no genes identified that contribute to BRV and no systematic linkage
studies performed. In an initial effort to genetically define BRV, we have
selected from our Neurology Clinic population a subset of 20 multigenerational
families with apparent autosomal dominant transmission, and performed genetic
linkage mapping using both parametric and non-parametric linkage (NPL)
approaches. The Affymetrix 10K SNP Mapping Assay was used for the genotyping.
Heterogeneity LOD (HLOD) analysis reveals the evidence of genetic heterogeneity
for BRV and evidence of linkage in a subset of the families to 22q12 (HLOD =
4.02). An additional region was identified by NPL analysis at 5p15 (LOD = 2.63). 
As migraine is observed substantially more commonly both within the BRV-affected 
individuals and the related family members, it is possible that a form of
migraine is allelic to the BRV locus at 22q12. However, testing linkage or the
chromosome 22q12 region to a broader migraine/vertigo phenotype by defining
affectation status as either migrainous headaches or BRV greatly weakened the
linkage signal, and no significant other peaks were detected. Thus, BRV and
migraine does not appear to be allelic disorders within these families. We
conclude that BRV is a heterogeneous genetic disorder, appears genetically
distinct from migraine with aura and is linked to 22q12. Additional family and
population-based linkage and association studies will be needed to determine the 
causative alleles.

Publication Types: 
    Comparative Study
    Research Support, N.I.H., Extramural

PMID: 16330481 [PubMed - indexed for MEDLINE]

1509: J Neuroimmunol. 2006 Feb;171(1-2):184-8. Epub 2005 Dec 1.

The importance of cytokines, chemokines and nitric oxide in pathophysiology of
migraine.

Fidan I, Yüksel S, Ymir T, Irkeç C, Aksakal FN.

Gazi University, Faculty of Medicine, Department of Medical Microbiology,
Beşevler/Ankara 06500, Turkey. isilfidan@yahoo.com

The certain etiology migraine is unknown. The study was aimed at determining to
the efficiency of cytokines, chemokines and nitric oxide (NO) to the
pathophysiology of migraine. The levels of cytokines, chemokines and NO in serum 
of 25 patients with migraine during attacks and attack-free periods and 25
healthy controls were investigated. The levels of cytokines and chemokines were
determined by enzyme-linked immunosorbent assay. NO concentrations were
determined by a nitrate/nitrite colorimetric assay kit. In attack groups, IL-10
levels were found higher than in attack-free groups and healthy controls
(p<0.05). IL-6 levels in migraine patients were significantly higher than in
healthy controls. The levels of RANTES were high in attacks groups. There was an 
increase NO concentrations in migraine attacks. The study's results reflect that 
the etiology of migraine is multifactorial and probably related to immunological 
changes.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 16325275 [PubMed - indexed for MEDLINE]

1510: Headache. 2005 Nov-Dec;45(10):1413-6.

Recurrent syncope, hypotension, asthma, and migraine with aura: role of
metoclopramide.

Gupta VK.

Dubai Police Medical Services, United Arab Emirates.

Migraine associated with asthma or symptomatic orthostatic hypotension is a
particularly difficult subgroup to manage. Metoclopramide is a useful
pharmacological agent for orthostatic hypotension. I present the case report of a
migraine patient with asthma and recurrent hypotensive syncope. Metoclopramide
relieved recurrent syncope as well as migraine attacks in this patient.
Metoclopramide has a striking influence on arginine vasopressin (AVP) secretion. 
AVP promotes antinociception and influences vasomotor and behavior control, which
actions possibly keep migraine in remission. Further studies are necessary to
confirm the migraine prophylactic value of metoclopramide.

Publication Types: 
    Case Reports

PMID: 16324177 [PubMed - indexed for MEDLINE]

1511: Headache. 2005 Nov-Dec;45(10):1400-6.

Naratriptan in the preventive treatment of refractory transformed migraine: a
prospective pilot study.

Sheftell FD, Rapoport AM, Tepper SJ, Bigal ME.

The New England Center for Headache, College of Medicine, Stanford, CT, USA.

OBJECTIVE: To assess the efficacy, safety, and tolerability of daily naratriptan 
in the preventive treatment of transformed migraine (TM) refractory to previous
first line therapies. BACKGROUND: Limited evidence suggests that the triptans can
be used in the preventive treatment of refractory headaches. DESIGN/METHODS: We
included subjects from 18 to 65 years old, with TM, with or without medication
overuse (Silberstein and Lipton, 1996). All participants had previously failed at
least two preventive medications. Concomitant, preventive medications were
allowed if on a stable dose. After the baseline period, all patients received
naratriptan 2.5 mg bid. The treatment phase lasted 3 months. The primary endpoint
was change in headache frequency per month. Safety assessment included monthly
ECGs, complete ophthalmologic exam, and monthly blood tests. Statistical analyses
were performed using the intent-to-treat (ITT) population. We also conducted
per-protocol (PP) analyses. RESULTS: Our ITT population consisted of 30 subjects 
(79% female, mean age of 46.5 years). Mean headache frequency per month at
baseline was 27.1 days and a significant reduction of headache frequency was
obtained in 1 month (20.4, P < .001), 2 months (18.9, P < .001), and 3 months
(19.0, P < .001). HIT scores were 64.3 at baseline, 57.4 after 1 month (P <
.001), 55.7 after 2 months (P < .01), and 60 at 3 months (P < .05). The mean
number of days using rescue medication was reduced from 17.7 at baseline, to 9.7 
at 3 months (P < .001). Our PP population consisted of 22 subjects, and 54% had
fewer than 15 headaches per month at the end of the study (converted to an
episodic pattern). No serious adverse events were reported. No significant
changes were observed in blood pressure or in heart rate. ECGs and ophthalmologic
exam were unchanged from baseline. CONCLUSIONS: (1) Daily use of naratriptan
provided good preventive efficacy in an important subset of subjects with TM
refractory to other preventive treatments. (2) The tolerability of this treatment
was excellent. (3) Over a short period of time (3 months), no serious adverse
events were reported, nor significant changes were found in the ECG or
ophthalmologic evaluation.

Publication Types: 
    Clinical Trial

PMID: 16324173 [PubMed - indexed for MEDLINE]

1512: Headache. 2005 Nov-Dec;45(10):1394-9.

Visual cortex excitability in migraine evaluated by single and paired magnetic
stimuli.

Gerwig M, Niehaus L, Kastrup O, Stude P, Diener HC.

Department of Neurology, University of Essen, Germany.

OBJECTIVE: To determine the excitability of the visual cortex by phosphene
thresholds (PT) in patients with migraine using transcranial magnetic stimulation
(TMS) with single- and paired-pulses. METHODS: Nineteen patients with migraine
with aura (MWA), 19 patients with migraine without aura (MWoA), and 22 control
subjects were included. Patients were free from preventive anti-migraine
treatment and were investigated within 3 days before or after an acute migraine
attack. In each subject, PT were assessed by single-pulse and paired-pulse TMS
with an interstimulus interval of 50 ms. RESULTS: The main effect of diagnosis
indicated that mean PT were significantly lower in migraine patients than in
control subjects (P = .001). Using single-pulse TMS, mean PT tended to be lower
in MWoA-patients (57.7 +/- 11.8%) compared with control subjects (64.4 +/- 10.5%)
(P = .064). In MWA-patients, mean PT (53.1 +/- 5.7%) were significantly lower
compared with controls (P < .001). Using TMS with paired pulses, mean PT were
significantly reduced in MWoA-patients (40.3 +/- 4.9%, P = .017) as well as in
MWA-patients (39.6 +/- 4.2%, P = .005) compared with controls (44.6 +/- 6.0%).
The main effect of stimulation type indicated that mean PT were lower determined 
with paired-pulse stimulation than with single pulses (P < .001). CONCLUSIONS: PT
are reduced in patients with migraine in the interictal state suggesting an
increased excitability of visual cortical areas. Compared with single-pulse TMS, 
paired-pulse magnetic stimulation is more efficient to elicit phosphenes. This
technique provides the opportunity to evaluate visual cortex excitability with
lower stimulus intensities and less discomfort.

Publication Types: 
    Clinical Trial

PMID: 16324172 [PubMed - indexed for MEDLINE]

1513: Headache. 2005 Nov-Dec;45(10):1388-93.

Nociceptive blink reflex and visual evoked potential habituations are correlated 
in migraine.

Di Clemente L, Coppola G, Magis D, Fumal A, De Pasqua V, Schoenen J.

Headache Research Unit, University Department of Neurology, University of Liège, 
Belgium.

BACKGROUND: Lack of habituation, as reported in migraine patients between attacks
for evoked cortical responses, was also recently found for the nociceptive blink 
reflex (nBR) mediated by brainstem neurons. It is not known if both brain stem
and cortical habituation deficits are correlated in the same patient, which would
favor a common underlying mechanism. OBJECTIVE: To search for intraindividual
correlations between habituation of pattern reversal-visual evoked potentials and
that of the nociception-specific blink reflex in migraineurs and in healthy
volunteers (HV). METHODS: We recorded 15 HV and 15 migraine without aura patients
between attacks. Habituation for visual evoked potentials was measured by
comparing the N1-P1 amplitude change (%) between the first and sixth block of 100
sequential averaged responses. Habituation for the nBR was defined as the
percentage change of the R2 response area between the 1st and 10th block of five 
averaged EMG responses, elicited by stimulating the right side every 2 minutes
for 32 minutes. We also calculated the slope of N1-P1 amplitude and R2 response
area changes from the first to the last response and the correlation with attack 
frequency. RESULTS: A significant habituation deficit in both cortical and brain 
stem evoked activity characterized on average the group of migraineurs compared
to controls. In migraine patients, but not in HV, we found a significant positive
correlation between habituation of pattern reversal-visual evoked potentials and 
that of the nociception-specific blink reflex both for the degree of habituation 
between first and last blocks of averagings (r = 0.703; P = .003) and for the
habituation slope (r = 0.751; P = .001). Moreover, nBR habituation was positively
correlated with attack frequency (r = 0.548; P = .034). CONCLUSION: The positive 
correlation between visual evoked potential and nBR habituations is consistent
with the idea that in migraine the same neurobiological dysfunction might be
responsible for the habituation deficit both in cortex and brain stem. As nBR
habituation increases with attack frequency, its interictal deficit is unlikely
to be due to trigeminal sensitization.

Publication Types: 
    Clinical Trial

PMID: 16324171 [PubMed - indexed for MEDLINE]

1514: Headache. 2005 Nov-Dec;45(10):1375-87.

Psychophysiological response patterns of migraine patients in two habituation
tests.

Huber D, Henrich G, Gündel H.

Institut und Poliklinik für Psychosomatische Medizin, Psychotherapie und Med.
Psychologie, Klinikum rechts der Isar de Technischen Universität München,
Germany.

OBJECTIVE: To investigate the habituation response pattern of patients with
migraine to a simple standard stressor and to a more complex
performance-dependent (achievement) stressor in three peripheral systems
(electrodermal, vasomotor, and cardiovascular). We hypothesized that the migraine
patients would show abnormal habituation in these peripheral systems, especially 
in response to achievement stimuli. BACKGROUND: Abnormal central habituation to
repetitive stimuli has been reported frequently in patients with migraine. But
little is known about habituation of the peripheral autonomic nervous system to
stressors in these patients. METHODS: A total of 30 female migraineurs and 30
physically and mentally healthy women matched for age and social status
participated in a simple habituation test (auditory stimuli) and an achievement
habituation test (mental arithmetic). RESULTS: Habituation was impaired in the
electrodermal (skin conductance response), vasomotor (pulse volume amplitude),
and cardiovascular (heart rate response) systems during the mental arithmetic
test (achievement stimuli) in the migraineurs as compared to the healthy
controls. With the simple stressor (auditory stimuli), however, habituation was
impaired in the vasomotor system only. Consistent with these findings were the
participants' verbal reports, which indicated significantly more subjective
tension in the migraine group than in the control group during the calculation
test. CONCLUSION: Our results suggest that the mental arithmetic (achievement)
habituation paradigm is an important tool for demonstrating reduced habituation
in several specific components of the autonomic nervous system. Further research 
is needed to target the covariance of central and autonomic nervous system
habituation phenomena in migraine.

Publication Types: 
    Clinical Trial

PMID: 16324170 [PubMed - indexed for MEDLINE]

1515: Headache. 2005 Nov-Dec;45(10):1339-44.

Validation of the classification of migraine without aura (IHS A1.1) proposed in 
ICHD-2.

Kelman L.

Headache Center of Atlanta, GA 30342, USA.

OBJECTIVE: This study attempts to validate the alternative criteria for
classification of migraine without aura (International Headache Society [IHS]
A1.1) proposed in the appendix of The International Classification of Headache
Disorders, 2nd edition. This method uses at least two of the associated symptoms 
(nausea, vomiting, photophobia, phonophobia, and osmophobia) in category D of the
IHS classification. BACKGROUND: In the appendix of The International
Classification of Headache Disorders, 2nd edition, an alternative method of
classification of migraine without aura is proposed. This method of
classification has never been validated. METHODS: A total of 1480 consecutive
headache patients in a tertiary care setting were evaluated at first visit.
Headache-associated features, such as intensity, lifetime duration, frequency per
month, duration, triggers, prodrome, percentage recurrence, and postdrome
frequency, were recorded. In addition, medication satisfaction, acute and monthly
disability, grading of headache days, sleep normality, mood, and habits were
documented. RESULTS: Of the 1480 patients, 901 were initially classified as
having migraine IHS 1.1. Using the proposed alternative method (IHS A1.1), 885
(98.2%) of these patients were reclassified as having migraine. The remaining 16 
(1.8%) patients not classified had only nausea and none of the other specified
associated symptoms. They also exhibited different characteristics from the IHS
migraine population as a whole regarding their headache and other features.
CONCLUSIONS: This classification of migraine in a headache center population
shows that the proposed use of any two of nausea, vomiting, photophobia,
phonophobia, and osmophobia in category D of the classification may be a valid
alternative method of classification. This study also demonstrates that the
standard IHS methodology includes a very small group of patients who appear to be
different from other migraine patients.

PMID: 16324166 [PubMed - indexed for MEDLINE]

1516: Headache. 2005 Nov-Dec;45(10):1328-38.

Development and validation of the Migraine Screen Questionnaire (MS-Q).

Láinez MJ, Domínguez M, Rejas J, Palacios G, Arriaza E, Garcia-Garcia M, Madrigal
M.

Hospital Clínico Universitario, Universidad de Valencia, Neurology Department,
Spain.

AIM: To develop and evaluate the clinimetric properties of a new migraine
screening questionnaire: the Migraine Screen Questionnaire (MS-Q). BACKGROUND:
Migraine is a public health problem requiring screening programs and tools to
ensure early detection. METHODS: A questionnaire was developed based on the
criteria of the International Headache Society (IHS) and a review of the
literature by a committee of experts. Stage I: The original version of the MS-Q
was distributed by mail and completed by Pfizer employees and self-administered
to neurological patients; all subjects were afterward evaluated by a neurologist 
who was blinded to the MS-Q results, to establish an independent IHS diagnosis.
Stage II: A final version of the MS-Q was administered to neurological patients
to confirm clinimetric properties. Logistic regression and receiver-operator
characteristic curve statistical methods were used and the 95% confidence
interval, sensitivity, specificity, and positive (PPV) and negative (NPV)
predictive values, were estimated. RESULTS: Of the 605 subjects recruited, 465
were evaluable (325 in stage I and 140 in stage II). Of the original 15 items, 5 
conformed the final version of the MS-Q: frequency and intensity of headache; a
duration of between 4 hours and 3 days; nausea; sensitivity to light/noise; and
disability. A cutoff point of > or = 4 points showed a sensitivity of 0.93 (95%
CI = 0.87 to 0.99), specificity of 0.81 (95% CI = 0.72 to 0.91), PPV of 0.83 (95%
CI = 0.75 to 0.91), and NPV of 0.92 (95% CI = 0.85 to 0.99). Cronbach's alpha
coefficient = 0.82. CONCLUSIONS: The MS-Q showed adequate validity and
reliability, and it could be a good screening tool for application to clinical
practice and research.

Publication Types: 
    Clinical Trial

PMID: 16324165 [PubMed - indexed for MEDLINE]

1517: Headache. 2005 Nov-Dec;45(10):1317-27.

Tramadol/acetaminophen for the treatment of acute migraine pain: findings of a
randomized, placebo-controlled trial.

Silberstein SD, Freitag FG, Rozen TD, Kudrow DB, Hewitt DJ, Jordan DM, Fisher AC,
Rosenthal NR; CAPSS-223 Investigators.

Jefferson Medical College, Philadelphia, PA, USA.

OBJECTIVE: To compare tramadol/acetaminophen (APAP) and placebo for the
management of acute migraine pain. BACKGROUND: Tramadol/APAP tablets reduced
moderate-to-moderately severe acute pain in controlled studies of other painful
conditions. METHODS: This randomized, double-blind, placebo-controlled, parallel 
group study enrolled adults with migraine pain as per International Headache
Society criteria. Subjects took tramadol/APAP (total dose, 75 mg/650 mg) or
placebo for a typical migraine with moderate-to-severe pain. Severity of pain and
migraine-related symptoms were recorded before study medication and at 0.5, 1, 2,
3, 4, 6, and 24 hours after study medication. RESULTS: Efficacy analyses included
305 subjects (154 tramadol/APAP and 151 placebo). Treatment response was higher
for tramadol/APAP than a placebo at 2 hours after dosing (55.8% vs. 33.8%, P <
.001) and at every other assessment from 30 minutes (12.3% vs. 6.6%) through 6
hours (64.9% vs. 37.7%) (all P< or = .022). Subjects in the tramadol/APAP group
were more likely than those in the placebo group to be pain-free at 2 hours
(22.1% vs. 9.3%), 6 hours (42.9% vs. 25.2%), and 24 hours (52.7% vs. 37.9%) (all 
P< or = .007). Two hours after dosing, moderate-to-severe symptoms that were less
common for tramadol/APAP than placebo included photophobia (34.6% vs. 52.2%, P=
.003) and phonophobia (34.3% vs. 44.9%, P = .008), but not migraine-related
nausea (38.5% vs. 29.4%, P= .681). Treatment-related adverse events included
nausea, dizziness, vomiting, and somnolence. CONCLUSIONS: Tramadol/APAP reduces
the severity of pain, photophobia, and phonophobia associated with migraine
headache, but does not reduce migraine-associated nausea. Tramadol/APAP might be 
an appropriate option for the management of moderate-to-severe migraine headache.

Publication Types: 
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 16324164 [PubMed - indexed for MEDLINE]

1518: Headache. 2005 Nov-Dec;45(10):1313-6.

Serum S100beta protein in children with acute recurrent headache: a potentially
useful marker for migraine.

Papandreou O, Soldatou A, Tsitsika A, Kariyannis C, Papandreou T, Zachariadi A,
Papassotiriou I, Chrousos GP.

First Department of Pediatrics, University of Athens, Goudi, Greece.

OBJECTIVE: To examine the role of glia-derived S100beta protein and to evaluate
its use as a biochemical marker in childhood acute recurrent headache. METHODS:
Twenty-five patients with acute recurrent headache (according to International
Headache Society criteria) from our department's Headache Clinic were studied.
Blood samples for measurement of serum S100beta were drawn: (1) < or = 3-hour
post pain attack from our patients and (2) from 23 healthy controls. RESULTS: Of 
the 25 patients evaluated, 15 suffered from migraine and 10 from tension-type
headache (TTH). Statistical analysis of the mean values of S100beta levels
demonstrated a significant elevation in children with migraine headache, with
values higher than those of both children with TTH and controls (P = .001).
CONCLUSIONS: Our data suggest a direct relation between childhood migraine
attacks and increased production of glial S100beta protein. Serum S100beta
determination may be a useful biochemical marker for migraine in acute recurrent 
headache in childhood.

PMID: 16324163 [PubMed - indexed for MEDLINE]

1519: Headache. 2005 Nov-Dec;45(10):1304-12.

Topiramate for migraine prevention in children: a randomized, double-blind,
placebo-controlled trial.

Winner P, Pearlman EM, Linder SL, Jordan DM, Fisher AC, Hulihan J; Topiramate
Pediatric Migraine Study Investigators.

Palm Beach Headache Center/Palm Beach Neurology, West Palm Beach, FL 33407, USA.

OBJECTIVE: To assess the efficacy and safety of topiramate for the prevention of 
pediatric migraine with or without aura in a double-blind, randomized,
placebo-controlled trial. BACKGROUND: Treatment options for pediatric migraine
are currently limited, and no migraine preventive agents are approved for use in 
children in the United States. Topiramate is an effective migraine preventive
therapy in adults, as demonstrated in several large, randomized,
placebo-controlled trials. METHODS: One hundred and sixty-two children with
migraine (age, 6 to 15 years) were randomized in a 2:1 ratio to receive
topiramate (n = 112) or placebo (n = 50). This study was designed to ensure that 
150 participants were randomized to study medication. An additional 12 qualified 
patients were randomized because they had successfully completed the screening
phase. The double-blind phase of the trial consisted of a titration period and a 
maintenance period. Topiramate was initiated at 15 mg/day and titrated over 8
weeks to 2 to 3 mg/kg per day, or maximum tolerated dose, whichever was less
(maximum allowed dose was 200 mg/day). The target dose was maintained for 12
weeks. The primary efficacy variable was the change in mean number of migraine
days per month (28 days) during the double-blind phase relative to the 4-week
prospective baseline phase for each treatment group. RESULTS: Topiramate
treatment was associated with a mean reduction over the entire double-blind phase
of 2.6 migraine days per month, compared with a mean reduction of 2.0 migraine
days per month for placebo (P = .061 topiramate vs. placebo). A significantly
greater percentage of topiramate patients (32%) experienced a > or = 75%
reduction in mean monthly migraine days compared with placebo (14%, P = .02).
Discontinuation rates due to adverse events were low: 6.5% for the topiramate
group and 4.0% for the placebo group. The adverse events that occurred most
commonly in the topiramate group at an incidence rate greater than in the placebo
group were: upper respiratory tract infection, anorexia, weight decrease,
gastroenteritis, paresthesia, and somnolence. The mean average daily dose of
topiramate during the maintenance period was 2.0 mg/kg per day. CONCLUSIONS: This
pilot study suggests that topiramate may be an effective migraine preventive
therapy in children. Topiramate was well tolerated in this population. Further
randomized studies would be required to definitively establish the efficacy of
topiramate for pediatric migraine prevention.

Publication Types: 
    Randomized Controlled Trial

PMID: 16324162 [PubMed - indexed for MEDLINE]

1520: Headache. 2005 Nov-Dec;45(10):1298-303.

Outcome of a multidisciplinary approach to pediatric migraine at 1, 2, and 5
years.

Kabbouche MA, Powers SW, Vockell AL, LeCates SL, Ellinor PL, Segers A, Manning P,
Burdine D, Hershey AD.

Division of Neurology, Cincinnati Children's Hospital Medical Center, OH, USA.

OBJECTIVE: To assess the long-term effectiveness and outcome of multidisciplinary
treatment of childhood headaches 1, 2, and 5 years after initial treatment.
BACKGROUND: Headaches are a common problem for children and adolescents and for
many patients continue into adulthood. Outcome research for pediatric migraine
headaches is limited, thus restricting knowledge of the effectiveness of
long-term management and outcome. METHODS: Headache characteristics were assessed
at the initial visit and were reevaluated 1, 2, and 5 years later in independent 
sub-groups of consecutive patients. These characteristics included headache
frequency, severity, average duration, school absences, and overall perceived
response to treatment. RESULTS: At 1 year, 96 patients were evaluated (mean age =
11.0 +/- 3.4, 59% females), 69 patients at 2 years (mean age = 10.6 +/- 3.4, 48% 
females), and 32 at 5 years (mean age = 10.5 +/- 3.9, 66% females). The headaches
were reported as better in 94% at 1 year, 85% at 2 years, and 94% at 5 years. The
initial frequency was at 13.4 +/- 10.8 headaches per month, 4.9 +/- 7.0 at 1 year
(P < .001), 4.7 +/- 7.6 at 2 years (P < .001), and 4.5 +/- 7.5 at 5 years (P <
.001). The severity decreased from 6.8 +/- 1.8 to 5.1 +/- 2.3 at 1 year (P <
.001), to 5.0 +/- 2.4 at 2 years (P < .001), and to 4.6 +/- 2.5 at 5 years (P <
.01). The school days missed per month showed a marked decrease from 4.5 +/- 9.5 
at initial visit to 1.55 +/- 2.8 at 5 years (P < .001). Patients that were only
seen at their initial visit and did not choose to return for follow-up had less
frequent and shorter duration headaches on initial visit when compared with the
rest of the sample and continued to be doing well at the 1-, 2-, and 5-year
assessments. CONCLUSIONS: Multidisciplinary treatment was found to be effective
for children and adolescents with improvement of multiple outcome variants of
pediatric migraine care, including frequency, severity, and school days missed.
Patients who did not return to follow-up evaluation were more likely to have less
frequent and shorter duration headaches at initial presentation. Regular
follow-up care is needed for those children with more severe initial headache
presentation.

PMID: 16324161 [PubMed - indexed for MEDLINE]

1521: Headache. 2005 Nov-Dec;45(10):1288-97.

Use of the ICHD-II criteria in the diagnosis of pediatric migraine.

Hershey AD, Winner P, Kabbouche MA, Gladstein J, Yonker M, Lewis D, Pearlman E,
Linder SL, Rothner AD, Powers SW.

Division of Neurology, Children's Hospital Medical Center, Cincinnati, OH
45229-3039, USA.

OBJECTIVE: To evaluate the sensitivity of the new International Classification of
Headache Disorders-2nd edition (ICHD-II) criteria in the diagnosis of childhood
migraine and to propose specific criteria for the diagnosis of childhood
migraine. BACKGROUND: In 2004, ICHD-II was adopted by the International Headache 
Society. The prior version had been criticized for its lack of sensitivity in
diagnosing childhood headaches. ICHD-II is felt to be an improvement as it
provides for some differences between pediatric and adult migraine diagnosis in
its footnotes, however, has yet to be validated. Clinically, it is the impression
of many pediatric headache specialists that children's migraines are of shorter
duration, tend to be bilateral rather than unilateral, and that children more
often report either photophobia or phonophobia, rather than both. METHODS: The
characteristics of headache in 260 patients, ages 18 and under, clinically
diagnosed with migraine at two large pediatric headache centers were compiled
using standard intake questionnaires. Inter-rater reliability in clinical
diagnosis was determined by consensus of the clinical diagnosis. These data were 
analyzed applying the International Classification of Headache Disorders-1st
edition (ICHD-I) and ICHD-II criteria for migraine to determine sensitivity of
migraine diagnosis in comparison with clinical impression. Each headache
characteristic in ICHD-II was analyzed individually to determine its effect on
sensitivity of diagnosis. RESULTS: 183/260 patients (70.4%) met ICHD-I criteria. 
161/260 patients (61.9%) met the ICHD-II criteria with a 4- to 72-hour range.
When the footnoted allowance of ICHD-II for short duration (2 hours) was
utilized, 187/260 patients (71.9%) met criteria, while this improved to 192/260
patients (73.9%) with 1-hour duration. If duration was excluded, 210/260 patients
(80.8%) met criteria. The most common reasons for patients not meeting the
standard criteria were the requirement of unilateral location, headache duration 
and number of associated symptoms. Based on these observations, modified criteria
were empirically derived and the sensitivity increased to 84.4%. Data were
reanalyzed using the criteria of focal head pain, either bilateral or unilateral,
shortened duration, and modified associated symptoms, which resulted in an
improved sensitivity in migraine diagnosis of 84.4%. CONCLUSIONS: Modification of
ICHD-II criteria to include bilateral headache, headache duration of 1 to 72
hours, and nausea and/or vomiting plus two of five other associated symptoms
(photophobia, phonophobia, difficulty thinking, lightheadedness, or fatigue), in 
addition to the usual description of moderate to severe pain of a throbbing or
pulsating nature worsening or limiting physical activity, improved sensitivity of
migraine diagnosis to 84.4%.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 16324160 [PubMed - indexed for MEDLINE]

1522: Headache. 2005 Nov-Dec;45(10):1280-7.

Evolution of migraine after a 10-year follow-up.

Nachit-Ouinekh F, Dartigues JF, Chrysostome V, Henry P, Sourgen C, El Hasnaoui A.

University Victor Segalen, INSERM U 593, Bordeaux, France.

OBJECTIVE: To assess the evolution of headaches in a workplace cohort over a
10-year period. BACKGROUND: Migraine headaches are associated with significant
handicap in everyday activities and poor quality of life. The prevalence of
migraine shows a bell-shaped age distribution with a peak during the third and
fourth decades. However, there is little longitudinal data available on the
natural history of this condition. A prospective health survey undertaken in a
large workplace cohort since 1989 provides an opportunity to assess the evolution
of migraine and other headache syndromes over a 10-year period. METHODS: A sample
of 2500 subjects who reported regular headaches was chosen at random from those
with headache identified in a cohort of 46,244 employees of the French national
power company aged between 35 and 50 years in 1989 participating in a yearly
health survey. In 1993, all subjects were sent a headache questionnaire to
complete and return. In 2003, an identical questionnaire was sent to all subjects
who had returned exploitable data in 1993. Headache diagnosis was assigned
retrospectively using the International Headache Society (IHS) criteria to
migraine (IHS categories 1.1 and 1.2), migrainous disorder (IHS category 1.7), or
other episodic headaches. RESULTS: Of 2500 subjects sampled, 2051 (82%) returned 
exploitable data for the first questionnaire in 1993. In 2003, 1250 (61%) of
these provided a second data set. In 1993, 623 (30.4%) of subjects fulfilled
diagnostic criteria for migraine. However, only 37% of these retained the
diagnosis 10 years later. In contrast, the proportion of subjects with other
forms of episodic headache rose from 23.7% to 31.6%. In 2003, 9.5% of the sample 
were headache-free. Retention or acquisition of a diagnosis of migraine was more 
common in women than in men, and age was associated with evolution to a less
severe headache syndrome. In those subjects who continued to have headaches,
frequency and severity were lower at the second assessment. CONCLUSIONS: Only a
minority of subjects diagnosed with migraine or migrainous disorder retain the
diagnosis 10 years later, with most subjects evolving to a less disabling
headache type.

Publication Types: 
    Randomized Controlled Trial

PMID: 16324159 [PubMed - indexed for MEDLINE]

1523: J Am Board Fam Pract. 2005 Nov-Dec;18(6):563-6.

Patient satisfaction with migraine management by family physicians.

Walling AD, Woolley DC, Molgaard C, Kallail KJ.

Department of Family and Community Medicine, University of Kansas School of
Medicine, 1010 N. Kansas, Wichita, KS 67214-3124, USA. awalling@kumc.edu

Over 70% of the estimated 5 million office visits per year for migraine headache 
are to family physicians. Both the number of visits and proportion of migraine
patients seeking medical care are increasing rapidly. Patient satisfaction with
migraine care by primary care physicians is reported to be low but most data are 
obtained from patients referred to subspecialists or entered in clinical trials. 
We surveyed patients who consulted family physicians in 10 Kansas practices
during 2002 to assess patient satisfaction and investigate any differences
between satisfied and unsatisfied migraine patients. Of our 447 respondents, 74% 
were "satisfied" or "very satisfied" with migraine care by family physicians.
Dissatisfied patients were significantly more likely to report moderate or severe
migraine-related disability and less likely to use triptans or to have most
medications paid by insurance. Dissatisfied patients were twice as likely to have
discontinued taking triptans than satisfied patients. Patient satisfaction with
migraine treatment in family practice is substantially higher than generally
reported. Statistically significant differences exist between satisfied and
dissatisfied patients.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16322420 [PubMed - indexed for MEDLINE]

1524: Expert Opin Pharmacother. 2005 Dec;6(15):2691-7.

Motion sickness in migraine sufferers.

Marcus DA, Furman JM, Balaban CD.

Department of Anesthesiology, University of Pittsburgh School of Medicine,
Pittsburgh, PA 15206, USA. MarcusD@anes.upmc.edu

Motion sickness commonly occurs after exposure to actual motion, such as car or
amusement park rides, or virtual motion, such as panoramic movies. Motion
sickness symptoms may be disabling, significantly limiting business, travel and
leisure activities. Motion sickness occurs in approximately 50% of migraine
sufferers. Understanding motion sickness in migraine patients may improve
understanding of the physiology of both conditions. Recent literature suggests
important relationships between the trigeminal system and vestibular nuclei that 
may have implications for both motion sickness and migraine. Studies
demonstrating an important relationship between serotonin receptors and motion
sickness susceptibility in both rodents and humans suggest possible new motion
sickness prevention therapies.

Publication Types: 
    Review

PMID: 16316307 [PubMed - indexed for MEDLINE]

1525: Cephalalgia. 2005 Dec;25(12):1168-72.

The 3p21.1-p21.3 hereditary vascular retinopathy locus increases the risk for
Raynaud's phenomenon and migraine.

Hottenga JJ, Vanmolkot KR, Kors EE, Kheradmand Kia S, de Jong PT, Haan J,
Terwindt GM, Frants RR, Ferrari MD, van den Maagdenberg AM.

Department of Human Genetics, Leiden University Medical Centre, Leiden, and
Department of Neurology, Rijnland Hospital, Leiderdorp, The Netherlands.

Previously, we described a large Dutch family with hereditary vascular
retinopathy (HVR), Raynaud's phenomenon and migraine. A locus for HVR was mapped 
on chromosome 3p21.1-p21.3, but the gene has not yet been identified. The fact
that all three disorders share a vascular aetiology prompted us to study whether 
the HVR haplotype also contributed to Raynaud's phenomenon and migraine in this
family. Whereas the parent-child transmission disequilibrium test (TDT) did not
reach significance, the sibling TDT revealed that the HVR haplotype harbours a
susceptibility factor for Raynaud's phenomenon and migraine. Identification of
the HVR gene will improve the understanding of the pathophysiology of HVR,
Raynaud's phenomenon and migraine.

Publication Types: 
    Clinical Trial, Phase I
    Research Support, Non-U.S. Gov't

PMID: 16305605 [PubMed - indexed for MEDLINE]

1526: Cephalalgia. 2005 Dec;25(12):1146-58.

Migraine and probable migraine--results of FRAMIG 3, a French nationwide survey
carried out according to the 2004 IHS classification.

Lantéri-Minet M, Valade D, Géraud G, Chautard MH, Lucas C.

Department of Evaluation and Treatment of Pain, Hospital Pasteur, Nice, France.
lanteri-minet.m@chu-nice.fr

The 2004 International Headache Society (IHS) classification of headache
disorders introduced the new category of probable migraine defined by the
existence of all but one of typical migraine criteria. FRAMIG 3, the first
nationwide population-based survey performed in France using the 2004 IHS
classification, assessed the prevalence of probable migraine and compared its
features and management with those of strict migraine. Of a representative sample
of 10,532 adult subjects interviewed, 1179 subjects (11.2%) were diagnosed as
having strict migraine and 1066 (10.1%) as having probable migraine. The
criterion most frequently missing was typical headache duration (4-72 h) and most
subjects with probable headache had shorter average headache duration. Migraine
severity and disability, although lower than those noted in subjects with strict 
migraine, were significant in subjects with probable migraine and quality of life
impairment was identical among the two groups of migraine sufferers. Strict and
probable migraine, which have similar prevalence and impact on migraine subjects,
deserve similar medical and therapeutic management.

Publication Types: 
    Clinical Trial

PMID: 16305603 [PubMed - indexed for MEDLINE]

1527: Cephalalgia. 2005 Dec;25(12):1122-32.

Assessment of migraineurs referred to a specialist headache clinic in Singapore: 
diagnosis, treatment strategies, outcomes, knowledge of migraine treatments and
satisfaction.

Soon YY, Siow HC, Tan CY.

Department of Pharmacy, Singapore General Hospital, Singapore.

This study aimed to compare (i) migraineurs' diagnosis, treatment strategies and 
satisfaction when treated by community care physicians (CCPs) and at the
specialist headache clinic; (ii) migraineurs' knowledge of migraine treatments
and outcomes at baseline and at 3 months' interval. Thirty-eight patients were
interviewed at baseline visit and 3 months after neurologist consultation, using 
a survey form which consisted of a series of self-designed questions, the MIDAS
questionnaire and the SF-36 Health Survey. More patients were informed of the
diagnosis of migraine by the neurologist than by CCPs. Compared with CCPs, the
neurologist was more likely to employ preventive therapies, prescribe triptans
and ask patients to keep a headache diary. Patients' number of days with
headaches in the last 3 months, pain intensity, MIDAS score and five out of the
eight SF-36 domain scores were significantly improved at the 3 months' interval
(P<0.05) compared with baseline at the specialist headache clinic. More patients 
recognized migraine-specific therapies and reported satisfaction with treatment
after the neurologist consultation. This is the first study detailing significant
improvements in patients' clinical outcomes, knowledge of migraine treatments and
satisfaction after consultation at a specialist headache clinic in Singapore.

Publication Types: 
    Comparative Study
    Controlled Clinical Trial

PMID: 16305601 [PubMed - indexed for MEDLINE]

1528: Cephalalgia. 2005 Dec;25(12):1117-21.

Migraine in the Andes and headache at sea level.

Appenzeller O, Minko T, Qualls C, Pozharov V, Gamboa J, Gamboa A, Wang Y.

New Mexico Health Enhancement and Marathon Clinics Research Foundation,
Albuquerque, NM, USA. ottoarun12@aol.com

In Cerro de Pasco (CP), Peru (altitude 4338 m) 24% of men have migraine with
aura. We studied 30 men. Twenty CP natives, examined in CP, were rated using a
chronic mountain sickness (CMS) score to separate controls (10) from those with
CMS (10), a maladaptation syndrome in natives to altitude which includes severe, 
recurring headache. We collected white cells in CP and, from the same men, within
1 h of arrival in Lima (150 m above sea level). Ten normal US men volunteered
white cells for comparison. After RNA extraction we assessed gene expression by
reverse transcription-polymerase chain reaction. Low ATP1A1 subunit of the ATPase
gene mRNA expression in CP was correlated with headache (P=0.002), acral
paraesthesias (P=0.004) and CMS score (P<0.001). ATP1A1 subunit expression was
increased in all Andeans in Lima (P<0.001). There were no differences between
Andean controls in Lima and US controls. Manipulation of Na+/K+ATPase could offer
relief for migraineurs at sea level.

Publication Types: 
    Controlled Clinical Trial
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 16305600 [PubMed - indexed for MEDLINE]

1529: Ophthal Plast Reconstr Surg. 2005 Nov;21(6):418-22.

Corrugator superciliaris muscle excision for tension and migraine headaches.

Bearden WH, Anderson RL.

Center for Facial Appearances, Salt Lake City, Utah, USA. whbearden@hotmail.com

PURPOSE: This study investigates the effect of corrugator superciliaris muscle
excision on patients with frequent tension or chronic migraine headaches
emanating from the glabellar or frontal regions. METHODS: We present a
prospective study of 12 patients with chronic and frequent tension and/or
migraine headaches. Patients who had already elected to undergo corrugator
excision for cosmesis (n = 64) were given questionnaires to evaluate for the
presence of chronic, recurrent migraine and/or tension headaches. Patients who
answered in the affirmative went on to answer questions such as onset, location, 
frequency, severity, and duration of their headaches. Patients were grouped by
types of headaches: tension, migraine, and combined headaches. Twelve patients
who met all criteria were entered into the study and underwent corrugator
excision in combination with blepharoplasty. Postoperative questionnaires and
interviews were administered to evaluate the response of the patients' headaches 
to corrugator excision. RESULTS: All 12 patients had less frequent headaches and 
said they would have the procedure performed again for headache. Eleven of 12
patients (92%) had less intense headaches after corrugator superciliaris
excision. Overall, 58% noted complete relief of their headaches. Follow-up ranged
from 6 to 19 months. CONCLUSIONS: Corrugator superciliaris muscle excision
provides significant relief for headaches emanating from or localizing to the
frontal and glabellar regions. Although improvement of migraine headaches has
been previously described with this technique, this is the first report, to our
knowledge, of effective surgical treatment of tension headaches by corrugator
excision.

Publication Types: 
    Comparative Study

PMID: 16304517 [PubMed - indexed for MEDLINE]

1530: Neurology. 2005 Nov 22;65(10):1556-61.

Chronic migraine is an earlier stage of transformed migraine in adults.

Bigal ME, Rapoport AM, Sheftell FD, Tepper SJ, Lipton RB.

Department of Neurology, Albert Einstein College of Medicine, Bronx, NY, USA.
mbigal@aecom.yu.edu

BACKGROUND: Chronic migraine (CM) is characterized by 15 or more migraine days
per month. Most adults with chronic daily headache (CDH) that evolved from
migraine have < 15 days of migraine/month. They are often classified as
transformed migraine (TM), a disorder not addressed in the International Headache
Society classification. OBJECTIVE: To test the hypothesis that early in the
course of migraine chronification, the frequency of migraine attacks is high and 
that as illness progresses the frequency of nonmigraine headaches increases.
METHODS: Information was collected on 402 adults with TM and was divided into two
groups. Group 1 TM had > or = 15 days of migraine/month, whereas Group 2 TM had <
15 days of migraine/month. Risk factors were modeled for number of migraine days 
per month using logistic regression. RESULTS: Of 402 subjects with TM, 121
(30.1%) were in Group 1. The proportion of Group 1 subjects decreased with age,
from 71% below age 30 to 22% age 60 or above. The correspondent proportion of
Group 2 increased from 29 to 78%. More than 15 days of migraine per month was
independently predicted by younger ages (< 40 years; p = 0.002), shorter interval
from episodic to CDH (< 5 years; p = 0.003), and shorter time since the
development of CDH (< 6 years; p < 0.0001). CONCLUSION: Chronic migraine is an
earlier stage of transformed migraine.

PMID: 16301481 [PubMed - indexed for MEDLINE]

1531: Med Hypotheses. 2006;66(3):466-72. Epub 2005 Nov 18.

Epilepsy and migraine: The dopamine hypotheses.

Chen SC.

Department of Neurology, Tri-Service General Hospital, National Defense Medical
Center, No. 325, Section 2, Cheng-Kung Road, Neihu 114, Taipei, Taiwan, ROC.
csi1@pie.com.tw

Migraine and epilepsy are both chronic recurrent disorders with paroxysmal
attacks. They also share some similar risk factors, symptoms, and preventive
medications. Dopamine has long been postulated to be involved in the
pathophysiology of migraine and epileptogenesis, by many supporting evidences.
However, the role of dopamine is still controversial till now. A lack of a
comprehensive hypothetical model may be one of the reasons. "Dopamine hypothesis"
is not a new term, but it is proposed to explain the pathophysiology and the
associated phenomena of these disorders. The hypotheses suggest that, in
migraine, there is a low dopamine tone, while there is a high state of dopamine
in generalized epilepsy. But the periodic attacks of headaches and seizures maybe
both due to a fall in dopamine activity. Dopamine therefore plays a key role in
the linkage of neuroendocrine, autonomic system and neuronal activity. Dopamine
agonist is also implied in prophylaxis and neuroprotection in both disorders.

PMID: 16298497 [PubMed - indexed for MEDLINE]

1532: Med Hypotheses. 2006;66(3):461-5. Epub 2005 Nov 18.

A chronopharmacological preventive treatment for sleep-related migraine headaches
and chronic morning headaches: Nitric oxide supersensitivity can cause
sleep-related headaches in a subset of patients.

Eli R, Fasciano JA.

roberteli@sbcglobal.net

Frequent and recurrent migraine headaches can, over time, pose the additional
risks of stroke, brain damage, heart failure and attention deficit. This is why
prevention should always be a part of the treatment. Nitric oxide
supersensitivity is the hypothesis upon which this model is based. Its role in
causing migraine headaches and chronic morning headaches can be triggered by both
normal and abnormal characteristics of the sleep cycle and more specifically by
the release of nitric oxide that occurs towards the end of the sleep cycle.
Stress and the age-related loss of sleep continuity, together with the
corresponding increase in cortisol levels, potentiate delta rebound. Delta
rebound results in deeper sleep intensity. It is associated with increased nitric
oxide production. Increased delta rebound then causes an increase in the amount
and duration of nitric oxide release at night. Migraineurs are susceptible to
migraine headaches because they are supersensitive to nitric oxide. The diurnal
pattern of the incidence of sleep-related headaches in a subset of the general
population is caused by the effect of nitric oxide supersensitivity during the
sleep cycle. The proposed treatment is for both sleep-related migraine headaches 
and chronic morning headaches. It consists of melatonin and moclobemide taken
during the night, close the end of the sleep cycle so as to achieve the maximum
concentrations. Both melatonin and moclobemide affect three important aspects of 
sleep-related headaches: nitric oxide supersensitivity, stress system dysfunction
and sleep pathology. Both melatonin and moclobemide have demonstrated
effectiveness in preventing migraine headaches. Additionally, both melatonin and 
moclobemide are compatible with most of the other therapeutic agents used to
prevent migraine headaches and with at least 1 therapeutic agent that is used to 
treat migraine headaches.

PMID: 16298494 [PubMed - indexed for MEDLINE]

1533: Pain. 2005 Dec 15;119(1-3):150-8. Epub 2005 Nov 17.

Headache in schoolchildren: association with other pain, family history and
psychosocial factors.

Laurell K, Larsson B, Eeg-Olofsson O.

Department of Neuroscience, Uppsala University, Uppsala, Sweden.
katarina.laurell@akademiska.se

Limited information exist about associations between different headache types and
other pains, family history of pain, and psychosocial factors among children from
the general population suffering from less severe headache. We interviewed 130
schoolchildren together with a parent to find out whether such factors differ
between children with mainly infrequent and moderate migraine or tension-type
headache as compared to those without primary headache. Children with headache,
especially those with migraine reported other pains and physical symptoms more
frequently than children without primary headache. Coherently, parents of
children suffering from migraine reported their children to have significantly
more somatic symptoms than parents of children without primary headache. In
addition, first-degree relatives of children with headache suffered from more
migraine, other pains, and physical symptoms compared with first-degree relatives
of children without primary headache. Children with migraine visited the school
nurse, used medication and were absent from school because of headache more often
than those with tension-type headache. Few other differences in psychosocial
factors were found between the three groups. Migraine among first-degree
relatives and the total sum of physical symptoms in children were the strongest
predictors of headache in logistic regression analysis. It is concluded that in
schoolchildren with mainly infrequent and moderate headache, pain and physical
symptoms cluster within individuals as well as their families, however,
psychological and social problems are uncommon.

Publication Types: 
    Controlled Clinical Trial
    Research Support, Non-U.S. Gov't

PMID: 16298064 [PubMed - indexed for MEDLINE]

1534: Nepal Med Coll J. 2005 Jun;7(1):36-8.

Effect of application of gyrosonic waves through brain on arthritic pain and
migrainous headache.

Ganguly AK, Banerjee S, Chowdhury R, Ray S.

University College of Medicine and Wingard Analysis, Research Division, Kolkata, 
India.

Gyrosonic waves created by placing the recorded sound waves on an oscillating
frequency device has been utilized to alleviate long-standing pain in patients
suffering from arthritis of various types and in migrainous headache. It was
interesting to observe that arthritic pain had disappeared totally or there was
about 80 to 90.0% reduction with planned installation of gyrosonic waves through 
headphone. Individuals with a long history of migrainous headache also had
complete relief after a few installations; it appears that gyrosonic waves would 
be of immense help for the treatment of pain due to aforesaid problems.

PMID: 16295719 [PubMed - indexed for MEDLINE]

1535: J Neurol Neurosurg Psychiatry. 2005 Dec;76(12):1730-2.

Lamotrigine reduces migraine aura and migraine attacks in patients with migraine 
with aura.

Lampl C, Katsarava Z, Diener HC, Limmroth V.

Department of Neurology and Psychiatry, Pain and Headache Centre, Linz General
Hospital, 4020 Linz, Austria. christian.lampl@akh.linz.at

This study examined the efficacy of lamotrigine in the prevention of migraine
aura. Fifty nine patients suffering from migraine with aura received lamotrigine 
in a controlled three year prospective open study. Treatment response was defined
as a reduction of aura frequency each month by at least 50%. Primary endpoint was
reached by three quarters of the patients. Lamotrigine significantly reduced both
frequency of migraine aura (mean, 1.5 (SD, 0.6) each month before v 0.4 (0.7)
after treatment; p < 0.001) and aura duration (mean, 27 (SD, 11) minutes before v
8 (14) after treatment; p < 0.001). Furthermore, more than three quarters of
those patients with a reduction of aura symptoms experienced a significant
reduction of frequency of migraine attacks (mean, 2.1 (SD, 1.0) each month before
v 1.2 (1.1) after treatment; p < 0.001). Lamotrigine was highly effective in
reducing migraine aura and migraine attacks. The strong correlation between
reduction of aura symptoms and migraine attacks stresses the potential role of
aura-like events and possibly cortical spreading depression as a trigger for
trigeminal vascular activation, and subsequently the development of migraine
headaches.

Publication Types: 
    Clinical Trial

PMID: 16291905 [PubMed - indexed for MEDLINE]

1536: Pain. 2005 Dec 5;118(3):319-26. Epub 2005 Nov 14.

Anxiety and depression associated with migraine: influence on migraine subjects' 
disability and quality of life, and acute migraine management.

Lantéri-Minet M, Radat F, Chautard MH, Lucas C.

Department of Evaluation and Treatment of Pain, University Teaching Hospital,
Hospital Pasteur, 06602 Nice, France. lanteri-minet.m@chu-nice.fr

Anxiety and depression are reported to be frequently associated with migraine but
how they impact on migraine-related disability, migraine subjects' quality of
life, and medical and therapeutic management of migraine attacks has not been
investigated. FRAMIG 3 is a nation-wide population-based postal survey carried
out in France according to the 2004 international classification of headache
disorders. Subjects who had had migraine attacks during the last 3 months
(subjects with 'active migraine', N = 1957) were analysed for migraine-related
disability (MIDAS score), quality of life (SF-12 questionnaire), and anxiety and 
depression (Hospital Anxiety and Depression Scale [HADS]) in comparison with
non-migraine subjects (N = 8287). Survey results indicate that 50.6% of subjects 
with active migraine were anxious and/or depressive (28.0% had anxiety alone,
3.5% depression alone, and 19.1% both anxiety and depression; P < or = 0.01
versus non-migraine subjects for anxiety alone and combined anxiety and
depression, NS for depression alone). Although, migraine-associated anxiety and
depression do not appear to influence the drugs taken by migraine subjects for
the acute treatment of migraine attacks, perceived treatment efficacy and
satisfaction with treatment are lower in subjects with anxiety alone or combined 
with depression than in subjects with neither anxiety nor depression. Anxiety and
depression should be systemically looked for and cared for in subjects consulting
for migraine.

Publication Types: 
    Controlled Clinical Trial

PMID: 16289799 [PubMed - indexed for MEDLINE]

1537: Value Health. 2005 Nov-Dec;8(6):647-55.

An economic evaluation of triptan products for migraine.

Perfetto EM, Weis KA, Mullins CD, Subedi P, Healey PJ Sr.

Epidemiology and Biostatistics, The Weinberg Group Inc., Washington, DC, USA.

OBJECTIVE: A composite outcome measure in migraine treatment assessment is useful
to clinical decision-makers and payers as it can provide a more accurate
reflection of effectiveness and allows for more complete modeling of economic
value. The objective of this study was to compare the total triptan cost to treat
100 migraine patient attacks and the cost per successfully treated patient
(CPSTP) for six marketed triptans using a composite measure of effectiveness, the
"successfully treated" migraine (defined as requiring only one triptan dose to
treat one migraine attack during a 24-h period). METHODS: This analysis was
conducted from the perspective of the payer. Clinical data were abstracted from a
rigorous, published meta-analysis. Two-hour response and pain-free response were 
used in conjunction with the recurrence rate reported in the meta-analysis to
calculate the number of doses used by treatment successes and failures. The
average wholesale price per dose was then used to calculate total triptan cost.
RESULTS: Of the nine oral triptan doses compared, eletriptan 40 mg was associated
with both the lowest total triptan cost for treating 100 migraine attacks ($1560)
and with the lowest CPSTP ($56.39). CONCLUSIONS: The relative CPSTP rankings for 
migraine therapies are dependent on the definition of treatment success and
relative pricing. The results of this study support the use of eletriptan for the
treatment of acute migraine based on the model assumptions. This study can be
used to assist in formulary considerations and offers a model that can be adapted
by health-care decision-makers.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 16283865 [PubMed - indexed for MEDLINE]

1538: J Occup Environ Med. 2005 Nov;47(11):1167-73.

The effect of early intervention with sumatriptan tablets on migraine-associated 
productivity loss.

Kwong WJ, Taylor FR, Adelman JU.

GlaxoSmithKline, University of North Carolina at Chapel Hill, Chapel Hill, North 
Carolina, USA. jkwong@mail.rx.uga.edu

OBJECTIVE: Impaired performance, which can considerably impact employee output,
occurs when employees attempt to continue work with inadequate treatment while
experiencing a migraine episode. This analysis examined productivity loss as a
result of migraine after treatment with sumatriptan tablets and patients' usual
non-triptan therapy when pain was mild (early intervention) versus when pain was 
moderate/severe. METHODS: The authors conducted a retrospective analysis of data 
on 6803 migraine days reported by 251 subjects who participated in a clinical
trial. RESULTS: Although early intervention significantly reduced productivity
loss compared with treatment when pain was moderate/severe for both sumatriptan
and non-triptan therapy, productivity loss was consistently lower for sumatriptan
than non-triptan therapy for all predose pain intensity levels. CONCLUSIONS:
These findings suggest that the pharmaco-economic benefits of early intervention 
with sumatriptan tablets, like the clinical benefits, exceed those of delayed
intervention.

PMID: 16282878 [PubMed - indexed for MEDLINE]

1539: Neurology. 2005 Nov 8;65(9):1419-22.

Can allodynic migraine patients be identified interictally using a questionnaire?

Jakubowski M, Silberstein S, Ashkenazi A, Burstein R.

Department of Anesthesia and Critical Care, Beth Israel Deaconess Medical Center,
Harvard Medical School, Boston, MA, USA.

OBJECTIVE: The gradual development of cutaneous allodynia during the course of a 
migraine attack is commonly detected by quantitative sensory testing (QST) in
migraineurs seeking secondary and tertiary medical help. In this study, the
authors developed a questionnaire that tested the recollection of the patients on
their skin sensitivity during past migraine attacks. METHODS: The authors devised
a series of questions regarding skin sensitivity during migraine and posed them
to 89 migraineurs when they were free of migraine (Visit 1). To validate their
recollections, the authors determined the patients' pain thresholds to mechanical
and thermal skin stimuli in the absence of migraine (Visit 1) and during an
attack (Visit 2), using QST. RESULTS: Whereas 75.3% of the patients testified to 
at least one type of skin hypersensitivity during migraine, 24.7% were unaware of
any abnormal skin sensitivity. The questionnaire correctly identified 84.8% of
the 66 patients classified as allodynic by QST and mislabeled the remaining 15.2%
as nonallodynic (false negatives). Among the 23 patients classified as
nonallodynic by QST, 47.8% were mislabeled as allodynic using the questionnaire
(false positives). Among the total number of 89 patients studied, the
questionnaire produced 62.9% true positives and 13.5% true negatives (= 76.4%
correct labeling) vs 12.4% false positives and 11.2% false negatives (= 23.6%
mislabeling). CONCLUSION: The reliability of the questionnaire as a diagnostic
tool of allodynia varies with the proportion of allodynic patients in a given
clinic. The major source of variability is the misconception of nonallodynic
patients that their skin is hypersensitive during migraine.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 16275830 [PubMed - indexed for MEDLINE]

1540: J Matern Fetal Neonatal Med. 2005 Sep;18(3):167-72.

Risk of preeclampsia in relation to maternal history of migraine headaches.

Adeney KL, Williams MA, Miller RS, Frederick IO, Sorensen TK, Luthy DA.

Center for Perinatal Studies, Swedish Medical Center, Seattle, Washington 98122, 
USA. kathryn7@u.washington.edu

OBJECTIVE: We examined the relationship between migraines and preeclampsia risk. 
STUDY DESIGN: Cases were 244 women with preeclampsia and controls were 470
normotensive women. Women were asked if a physician had ever told them that they 
had migraines. Odds ratios (OR) and 95% confidence intervals (CI) were
calculated. RESULTS: A history of migraines was associated with a 1.8-fold
increased risk of preeclampsia (95% CI 1.1-2.7). Women who were 30+ years old
when diagnosed with migraines had the highest risk (OR 2.8, 95% CI 0.8-9.0). The 
migraine-preeclampsia association appeared to be modified by pre-pregnancy
overweight status (p = 0.06). Overweight migrainous women, compared with lean
nonmigrainous women, had a 12-fold increased preeclampsia risk (95% CI 5.9-25.7).
CONCLUSION: Our findings are consistent with reports from six of eight previous
studies on the topic. Nevertheless, prospective cohort studies are needed to
further evaluate the extent to which migraines and/or its treatments are
associated with preeclampsia risk.

Publication Types: 
    Research Support, N.I.H., Extramural

PMID: 16272039 [PubMed - indexed for MEDLINE]

1541: CNS Drugs. 2005;19(11):951-72.

The use of triptans in the management of menstrual migraine.

Mannix LK, Files JA.

Headache Associates, West Chester, OH 45069, USA. LKMannixMD@aol.com

Many women experience headaches, including migraine, in association with their
menstrual cycles. Although definitions vary, menstrual migraine generally refers 
to migraine without aura that occurs within several days prior to and several
days after the onset of menses.Although menstrual migraine has been reported to
be more difficult to treat than other types of migraines, there is no evidence
from controlled clinical trials to support this assertion. Thus, the
pharmacological treatment of menstrual migraine should be similar to that of
other types of migraines, except with respect to the use of hormonal
manipulations to treat menstrual migraine.Serotonin 5-HT(1B/1D) receptor agonists
(triptans) are effective for the acute treatment of both menstrual and
non-menstrual migraines. When used as acute therapy, a triptan should be
administered early, when the headache is still mild in severity. Ideally, an
acute therapy will provide rapid and complete pain relief with no disability.
Some patients may require preventive therapy for menstrual migraine based on
suboptimal response to an adequate trial of acute therapy. Patient diaries that
record headache onset, relationship to the menstrual cycle and treatment response
through three complete cycles will allow accurate prediction of the onset of
menstrual migraine; this information is also needed to make decisions about
timing of intermittent preventive therapy. The goals of intermittent preventive
therapy are to reduce the frequency, duration and intensity of menstrual migraine
attacks.Clinical studies show that triptans are effective when used as either
acute therapy or as intermittent preventive therapy for menstrual migraine.
Sumatriptan and zolmitriptan have been evaluated in prospective, randomised,
controlled trials for acute treatment. Retrospective analyses and open-label
studies also support the use of other triptans as acute therapy. In addition,
sumatriptan, frovatriptan, naratriptan and zolmitriptan have been evaluated as
intermittent preventive therapy in prospective studies. Thus, data from clinical 
studies indicate that triptans are effective for the treatment of menstrual
migraine.

Publication Types: 
    Review

PMID: 16268666 [PubMed - indexed for MEDLINE]

1542: Ann Pharmacother. 2005 Dec;39(12):2081-5. Epub 2005 Nov 1.

Role of botulinum toxin type A in the prophylactic treatment of migraine
headaches.

Chilson CN, Brown SJ.

Skaggs School of Pharmacy, University of Montana, Missoula, USA.
crystinichole@gmail.com

OBJECTIVE: To evaluate the role of botulinum toxin type A in the prophylaxis of
migraine headaches. DATA SOURCES: MEDLINE (1966-July 2005), Iowa Drug Information
Service (1966-July 2005), and International Pharmaceutical Abstracts (1970-July
2005) searches were performed. Key search terms included botulinum and migraine. 
DATA SYNTHESIS: Patients who received botulinum toxin type A injections for
treatment of hyperfunctional facial lines also experienced relief of migraine
symptoms, leading to further investigation. Four clinical trials and 2
retrospective chart reviews evaluating the use of botulinum toxin type A
injections for the prophylactic treatment of migraines are discussed. Limitations
of these trials include problems with blinding, use of different injection sites,
and inconsistent dosing. CONCLUSIONS: The results of 3 double-blind,
placebo-controlled trials, 2 retrospective chart reviews, and an open-label study
indicate that botulinum toxin type A may be a safe and efficacious prophylactic
treatment for migraine headaches.

Publication Types: 
    Meta-Analysis

PMID: 16264063 [PubMed - indexed for MEDLINE]

1543: J Fam Plann Reprod Health Care. 2002 Jan;28(1):27-31.

Prevention of migraine in the pill-free interval of combined oral contraceptives:
a double-blind, placebo-controlled pilot study using natural oestrogen
supplements.

Macgregor EA, Hackshaw A.

The City of London Migraine Clinic, London, UK.

CONTEXT: Migraine in the pill-free interval of combined oral contraceptives is
reported by many women, but there is little published information on possible
mechanisms and treatments. OBJECTIVE: To determine whether the use of natural
oestrogen patches affected the occurrence and severity of migraine during the
pill-free interval. DESIGN: A double-blind, placebo-controlled, randomised,
crossover study. SETTING: The City of London Migraine Clinic. PARTICIPANTS:
Fourteen women with migraine during the pill-free interval. INTERVENTIONS: 50
microg oestradiol patches (Evorel) used during the pill-free interval for two
cycles versus placebo for two cycles (total four cycles). MAIN OUTCOME MEASURES: 
Number of pill-free intervals (zero, one or two) during which migraine occurred; 
number of days of migraine; severity of migraine; number of days of migraine
accompanied by nausea, vomiting and/or photophobia. RESULTS: Complete data were
available for 12 women and for two cycles for one woman. Use of 50 microg
oestrogen patches during the pill-free interval showed a trend towards reducing
the frequency and severity of migraine. DISCUSSION: These results were not as
good as expected. However, we had originally aimed for 20 eligible women to
participate in the trial, but only 14 were recruited and only 12 completed the
study with full data for analysis. CONCLUSION: The results of this pilot study
suggest that use of 50 microg oestrogen patches during the pill-free interval may
reduce the frequency and severity of migraine at that time. This study should be 
repeated with larger numbers of women and a higher dose of oestrogen.

Publication Types: 
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 16259812 [PubMed - indexed for MEDLINE]

1544: J Comp Neurol. 2005 Dec 5;493(1):9-14.

Unitary hypothesis for multiple triggers of the pain and strain of migraine.

Burstein R, Jakubowski M.

Department of Anesthesia and Critical Care, Beth Israel Deaconess Medical Center,
Boston, Massachusetts 02115, USA. rburstei@caregroup.harvard.edu

Migraine headache is triggered by and associated with a variety of hormonal,
emotional, nutritional, and physiological changes. The perception of migraine
headache is formed when nociceptive signals originating in the meninges are
conveyed to the somatosensory cortex through the trigeminal ganglion, medullary
dorsal horn, and thalamus. Is there a common descending pathway accounting for
the activation of meningeal nociceptors by different migraine triggers? We
propose that different migraine triggers activate a wide variety of brain areas
that impinge on parasympathetic neurons innervating the meninges. According to
this hypothesis, migraine triggers such as perfume, stress, or awakening activate
multiple hypothalamic, limbic, and cortical areas, all of which contain neurons
that project to the preganglionic parasympathetic neurons in the superior
salivatory nucleus (SSN). The SSN, in turn, activates postganglionic
parasympathetic neurons in the sphenopalatine ganglion, resulting in vasodilation
and local release of inflammatory molecules that activate meningeal nociceptors. 
Are there ascending pathways through which the trigeminovascular system can
induce the wide variety of migraine symptoms? We propose that trigeminovascular
projections from the medullary dorsal horn to selective areas in the midbrain,
hypothalamus, amygdala, and basal forebrain are functionally positioned to
produce migraine symptoms such as irritability, loss of appetite, fatigue,
depression, or the quest for solitude. Bidirectional trafficking by which the
trigeminovascular system can activate the same brain areas that have triggered
its own activity in the first place provides an attractive network of perpetual
feedback that drives a migraine attack for many hours and even days. (c) 2005
Wiley-Liss, Inc.

Publication Types: 
    Research Support, N.I.H., Extramural
    Review

PMID: 16258903 [PubMed - indexed for MEDLINE]

1545: Vision Res. 2006 Jan;46(1-2):141-8. Epub 2005 Oct 27.

Processing of global form and motion in migraineurs.

Ditchfield JA, McKendrick AM, Badcock DR.

School of Psychology, University of Western Australia, 35 Stirling Hwy, Crawley, 
WA 6009, Australia.

Previous studies have identified anomalies of cortical visual processing in
migraineurs that appear to extend beyond V1. Migraineurs respond differently than
controls to transcranial magnetic stimulation of V5, and can demonstrate
impairments of global motion processing. This study was designed to assess the
integrity of intermediate stages of both motion and form processing in people
with migraine. We measured the ability to integrate local orientation information
into a global form percept, and to integrate local motion information into a
global motion percept. Control subjects performed significantly better than
migraineurs on both tasks, suggesting a diffuse visual cortical processing
anomaly in migraine.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16257032 [PubMed - indexed for MEDLINE]

1546: Clin Neurophysiol. 2005 Dec;116(12):2775-82. Epub 2005 Oct 25.

Comment in:
    Clin Neurophysiol. 2005 Dec;116(12):2717-8.

The measure of randomness by leave-one-out prediction error in the analysis of
EEG after laser painful stimulation in healthy subjects and migraine patients.

de Tommaso M, Marinazzo D, Stramaglia S.

TIRES-Center of Innovative Technologies for Signal Detection and Processing,
University of Bari, Italy. m.detommaso@neurol.uniba.it

OBJECTIVE: We aimed to perform a quantitative analysis of event-related
modulation of EEG activity, resulting from a not-warned and a warned paradigm of 
painful laser stimulation, in migraine patients and controls, by the use of a
novel analysis, based upon a parametric approach to measure predictability of
short and noisy time series. METHODS: Ten migraine patients were evaluated during
the not-symptomatic phase and compared to seven age and sex matched controls. The
dorsum of the right hand and the right supraorbital zone were stimulated by a
painful CO(2) laser, in presence or in absence of a visual warning stimulus. An
analysis time of 1s after the stimulus was submitted to a time-frequency analysis
by a complex Morlet wavelet and to a cross-correlation analysis, in order to
detect the development of EEG changes and the most activated cortical regions. A 
parametric approach to measure predictability of short and noisy time series was 
applied, where time series were modeled by leave-one-out (LOO) error. RESULTS:
The averaged laser-evoked potentials features were similar between the two groups
in the alerted and not alerted condition. A strong reset of the beta rhythms
after the painful stimuli was seen for three groups of electrodes along the
midline in patients and controls: the predictability of the series induced by the
laser stimulus changed very differently in controls and patients. The separation 
was more evident after the warning signal, leading to a separation with P-values 
of 0.0046 for both the hand and the face. DISCUSSION: As painful stimulus causes 
organization of the local activity in cortex, EEG series become more predictable 
after stimulation. This phenomenon was less evident in migraine, as a sign of an 
inadequate cortical reactivity to pain. SIGNIFICANCE: The LOO method enabled to
show in migraine subtle changes in the cortical response to pain.

PMID: 16253556 [PubMed - indexed for MEDLINE]

1547: Acta Neurol Taiwan. 2005 Sep;14(3):120-5.

Homozygous deletion genotype of angiotensin converting enzyme confers protection 
against migraine in man.

Lin JJ, Wang PJ, Chen CH, Yueh KC, Lin SZ, Harn HJ.

Department of Neurology, Chushang Show-Chwan Hospital, No. 75, Sec. 2, Chi-Shang 
Road, Chushang Jenn, Nantou, Taiwan. jjlinn@tcts.seed.net.tw

Studies have shown that migraine may have a major genetic component. Meanwhile,
angiotensin converting enzyme (ACE) gene has been implicated as a genetic factor 
associated with migraine. We designed a case-control study to investigate the
association between ACE and migraine in 240 migraine patients and 200 healthy
controls, matched by age and sex. There was no significant difference in allelic 
frequency (I and D) and genotype polymorphism (DD, DI and II) of the ACE gene in 
migraine patients and controls. Analysis of the difference in ACE polymorphism
stratified by gender revealed that male migraine patients with the homozygote DD 
genotype (ACE-DD) were significantly fewer than that of male controls (OR =
0.331, p = 0.045). There was no existence of a difference among the frequency and
duration of headache in each subgroup of migraine patients stratified by ACE
genotype. Our findings indicate that ACE-DD may have a slight protective effect
against migraine in male patients.

PMID: 16252613 [PubMed - indexed for MEDLINE]

1548: Eur J Drug Metab Pharmacokinet. 2005 Jul-Sep;30(3):151-64.

Metabolism and excretion of the antiepileptic/antimigraine drug, Topiramate in
animals and humans.

Caldwell GW, Wu WN, Masucci JA, McKown LA, Gauthier D, Jones WJ, Leo GC,
Maryanoff BE.

Johnson & Johnson Pharmaceutical Research and Development, Spring House, PA
19477, USA.

The metabolism and excretion of
2,3:4,5-bis-O-(1-methylethylidene)-beta-D-fructopyranose sulfamate (TOPAMAX,
topiramate, TPM) have been investigated in animals and humans. Radiolabeled [14C]
TPM was orally administered to mice, rats, rabbits, dogs and humans. Plasma,
urine and fecal samples were collected and analyzed. TPM and a total of 12
metabolites were isolated and identified in these samples. Metabolites were
formed by hydroxylation at the 7- or 8-methyl of an isopropylidene of TPM
followed by rearrangement, hydroxylation at the 10-methyl of the other
isopropylidene, hydrolysis at the 2,3-O-isopropylidene, hydrolysis at the
4,5-O-isopropylidene, cleavage at the sulfamate group, glucuronide conjugation
and sulfate conjugation. A large percentage of unchanged TPM was recovered in
animal and human urine. The most dominant metabolite of TPM in mice, male rats,
rabbits and dogs appeared to be formed by the hydrolysis of the
2,3-O-isopropylidene group.

PMID: 16250251 [PubMed - indexed for MEDLINE]

1549: Mol Interv. 2005 Oct;5(5):304-11.

Neurogenic inflammation and migraine: implications for the therapeutics.

Peroutka SJ.

Synergia Pharma, Inc., 601 Gateway Boulevard, Suite 350, South San Francisco, CA 
94080, USA. DrPeroutka@aol.com

Significant recent advances in molecular pharmacology have elucidated the
molecular pathways involved in neurogenic inflammation (NI). The release of
tachykinins and endothelin-3 (ET-3) from trigeminal neurons induces dural
vascular permeability and vasodilatation via activation of tachykinin receptor 1 
(Tacr1) and endothelin receptor type B (Ednrb) on endothelial cells. Endothelial 
cell receptor stimulation results in cellular contraction, leading to plasma
protein extravasation (PPE), which is the most recognized physiological hallmark 
of NI, and nitric oxide-induced vasodilatation. By contrast, the release of
calcitonin gene-related peptide (CGRP) from trigeminal neurons--also a key
physiological component of NI--does not affect vascular permeability but does
induce neurogenic vasodilatation (NV) via the direct, (i.e.,
endothelium-independent) relaxation of vascular smooth muscle. The molecular
pharmacology of NI is discussed within the context of migraine research and
assesses the putative role of the two key physiological components of NI (i.e.,
PPE and NV) in migraine pathophysiology. The data indicate that the PPE component
of NI plays no significant role in migraine but that NV is likely to be involved 
in migraine pathophysiology.

Publication Types: 
    Review

PMID: 16249526 [PubMed - indexed for MEDLINE]

1550: Eur J Pain. 2005 Dec;9(6):661-71. Epub 2005 Jan 19.

Are migraineurs hypersensitive? A test of the stimulus processing disorder
hypothesis.

Kröner-Herwig B, Ruhmland M, Zintel W, Siniatchkin M.

Department of Clinical Psychology and Psychotherapy, University of Goettingen,
Gosslerstreet 14, 37073 Goettingen, Germany. bkroene@uni-goettingen.de

The concept of hypersensitivity in migraineurs was advanced mainly on the basis
of studies on information processing in which increased amplitudes and reduced
habituation in cortical evoked and event related potentials were found in
migraine sufferers. The present investigation examined whether migraineurs
exhibit hypersensitivity within three different experimental paradigms and
various non electrocortical response parameters. Samples of 24 migraine, 19
tension-type headache sufferers, and 24 normal controls were compared regarding
their subjective estimation of intensity and discomfort due to visual and
acoustical stimuli. Subjects also participated in an experiment using the
eyeblink startle response paradigm. In a last experimental task the Stroop test
was applied. The trait variables emotionality, arousal, and extraversion were
also measured. None of the experimental tasks revealed the predicted
hypersensitivity of migraineurs in relation to the control samples. The series of
experiments was conducted a second time with half of the participants in order to
replicate the findings. The conclusions remained the same. The results of earlier
studies on cortical processing can not be interpreted as demonstrating general
hypersensitivity in the sense of a dispositional trait in migraine afflicted
individuals irrespective of the involved response system.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 16246819 [PubMed - indexed for MEDLINE]

1551: Ann Neurol. 2005 Nov;58(5):698-705.

Calcitonin gene-related peptide does not excite or sensitize meningeal
nociceptors: implications for the pathophysiology of migraine.

Levy D, Burstein R, Strassman AM.

Department of Anesthesia, Critical Care and Pain Medicine, Beth Israel Deaconess 
Medical Center, Harvard Medical School, Boston, MA 02115, USA.
dlevy1@bidmc.harvard.edu

Migraine is among the most common types of pain, but its mechanisms are poorly
understood. A growing body of evidence points to a critical role of calcitonin
gene-related peptide (CGRP) in the pathophysiology of migraine headache. During
migraine, CGRP is thought to be released from peripheral endings of perivascular 
meningeal nociceptors primary and to promote vasodilatation. A current hypothesis
suggests that peripheral CGRP and its related meningeal vasodilatation results in
activation and sensitization, leading to the generation of migraine headache.
However, direct evidence supporting this idea is lacking. Here, using
electrophysiological, extracellular, single-unit recording combined with
laser-Doppler flowmetry measurements of dural blood flow (DBF), we examined
whether CGRP and meningeal vasodilatation promote activation or sensitization of 
meningeal nociceptors. Changes in (DBF), ongoing discharge, and responsiveness to
mechanical stimulation of the dura were studied after either topical
administration or intravenous infusion of rat alpha-CGRP in anesthetized rats.
Both topical and systemic administration of CGRP caused a significant increase in
dural blood flow; however, neither method of CGRP administration resulted in
activation or sensitization of meningeal nociceptors. The results of this study
suggest that CGRP effects in the meninges, including meningeal vasodilatation,
are not sufficient to activate or sensitize meningeal nociceptors.

Publication Types: 
    Comparative Study
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 16240341 [PubMed - indexed for MEDLINE]

1552: Curr Med Res Opin. 2005 Oct;21(10):1603-10.

Efficacy of almotriptan 12.5 mg in achieving migraine-related composite
endpoints: a double-blind, randomized, placebo-controlled study in patients
controlled study in patients with previous poor response to sumatriptan 50 mg.

Diener HC.

Department Of Neurology, University of Essen, D-45145 Essen, Germany.
h.diener@uni-essen.de

BACKGROUND: Triptans are not identical and migraine sufferers respond differently
to different triptans. Few studies have evaluated the efficacy of switching
triptans in migraine patients who have shown poor response to another agent.
OBJECTIVE: To investigate the efficacy and tolerability of almotriptan 12.5 mg in
patients who did not achieve 2-h pain relief with sumatriptan 50 mg. METHODS:
This double-blind, placebo-controlled study recruited patients with IHS-defined
migraine and at least 2 previous unsatisfactory responses to sumatriptan. Those
who did not achieve pain relief (moderate or severe pain decreasing to mild or no
pain) 2 h after taking oral sumatriptan 50 mg on an open-label basis for the
treatment of their first migraine attack during this trial (Attack 1) were
randomized to receive either oral almotriptan 12.5 mg or placebo for the
treatment of their next migraine attack (Attack 2). RESULTS: Of 302 patients
receiving sumatriptan 50 mg for the treatment of their first migraine attack, 221
(73%) did not achieve 2-h pain relief and were randomized to almotriptan 12.5 mg 
or placebo for the treatment of Attack 2. The majority (70%) of randomized
patients treating their headache in Attack 2 reported severe pain at baseline
characterizing this as a difficult-to-treat population. In the intent-to-treat
population (n = 198), significantly more patients in the almotriptan group
compared with the placebo group achieved 2-h complete relief (free from pain and 
migraine-associated symptoms) at 2 h (17.1% vs. 4.4%; p < 0.05) and sustained
pain free (20.9% vs. 9.0%; p < 0.05). Adverse events of mild-to-moderate
intensity occurred in 7.1% of patients in the almotriptan group compared to 5.1% 
in the placebo group (not statistically different). CONCLUSION: Almotriptan is
more effective than placebo and similarly well-tolerated for the acute treatment 
of migraine in patients who responded poorly to oral sumatriptan.

Publication Types: 
    Clinical Trial
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 16238900 [PubMed - indexed for MEDLINE]

1553: Chest. 2005 Oct;128(4):2485-9.

A pulmonary right-to-left shunt in patients with hereditary hemorrhagic
telangiectasia is associated with an increased prevalence of migraine.

Post MC, Letteboer TG, Mager JJ, Plokker TH, Kelder JC, Westermann CJ.

Department of Cardiology, St. Antonius Hospital., 3435 CM Nieuwegein,
Netherlands.

INTRODUCTION: Hereditary hemorrhagic telangiectasia (HHT) is a rare
autosomal-dominant vascular dysplasia with a high prevalence of pulmonary
arteriovenous malformation (PAVM). Recent studies report an increased prevalence 
of migraine in patients with a cardiac right-to-left shunt. The aim of our study 
was to evaluate whether there is also an increased prevalence of migraine in
patients with a pulmonary right-to-left shunt (PAVM). METHODS: All patients with 
HHT referred to our hospital till April 2004 with or without PAVM and with or
without migraine were included in the study. RESULTS: In total, 538 HHT patients 
(41.6% men; mean age +/- SD, 39.3 +/- 18.6 years) could be included. PAVM was
present in 208 patients (38.7%; mean age, 39.3 +/- 17.6 years). Significantly
more women were present in the PAVM subgroup compared to the non-PAVM subgroup,
65.4% vs 53.9% (p = 0.009). Migraine occurred in 88 patients with HHT, a
prevalence of 16.4%. The prevalence of migraine in women with HHT was
significantly higher compared to men, 19.4% vs 12.1%, respectively (p = 0.03) The
prevalence of migraine in patients with PAVM was 21.2%, which was significantly
higher then in patients without PAVM, 13.3% (p = 0.02). The occurrence of PAVM in
the patients with migraine is significantly higher than in those without
migraine, 50.0% vs 36.4%, respectively (p = 0.02). CONCLUSION: This study showed 
a higher prevalence of PAVM in patients with migraine and HHT. The right-to-left 
shunt due to the PAVM might play a causal role in the pathogenesis of migraine in
patients with HHT. This needs to be determined in further studies.

PMID: 16236913 [PubMed - indexed for MEDLINE]

1554: Int J Clin Pract. 2005 Nov;59(11):1356-65.

Focus on trial endpoints of clinical relevance and the use of almotriptan for the
acute treatment of migraine.

Sandrini G, Dahlöf CG, Mathew N, Nappi G.

Department of Neurological Rehabilitation, University Centre for Adaptive
Disorders and Headache, Pavia, Italy.

Almotriptan is a 5-HT(1B/1D) receptor agonist, or triptan, indicated for the
acute treatment of migraine. It has been shown to be effective and well tolerated
for the treatment of acute migraine in approximately 5000 patients enrolled in
short-term placebo- and active-controlled trials and long-term open-label trials.
A recent meta-analysis reported that almotriptan has the highest sustained
pain-free (SPF) rate and lowest adverse-event (AE) rate of all oral triptans.
Sustained pain free is a composite endpoint of pain freedom at 2 h, no recurrence
of moderate-to-severe headache and no use of rescue medication from 2 to 24 h
after dosing. Patient surveys have indicated that migraine sufferers consider
complete pain relief, no recurrence, rapid onset and no side-effects to be the
most important attributes of their acute treatment. Composite endpoints such as
SPF and SPF with no AEs (SNAE) contain the attributes that migraine sufferers
express as being the most important elements of an acute migraine therapy, and
their use in future clinical trials should aid in the selection of agents that
can offer patients the highest likelihood of consistent treatment success.

Publication Types: 
    Review

PMID: 16236092 [PubMed - indexed for MEDLINE]

1555: Neurogenetics. 2005 Dec;6(4):217-24. Epub 2005 Oct 19.

Familial risks for migraine and other headaches among siblings based on
hospitalizations in Sweden.

Hemminki K, Li X, Johansson SE, Sundquist K, Sundquist J.

Division of Molecular Genetic Epidemiology, German Cancer Research Center (DKFZ),
Im Neuenheimer Feld 580, 69120 Heidelberg, Germany. k.hemminki@dkfz.de

Migraine and other headaches are common disabling conditions, reducing the
quality of life in the affected individuals. The unambiguous definition of
familial risk for subtypes of migraine and other headaches will advance the
search for the heritable causes of these conditions and their underlying
mechanisms. We aim at defining familial risks for siblings to be hospitalized
because of migraine or other headaches. An ad hoc migraine database was
constructed by linking the Multigeneration Register on 0- to 69-year-old siblings
to the Hospital Discharge Register for data on migraines of all hospitalized
patients in Sweden from years 1987 to 2001. Standardized incidence ratios (SIRs) 
were calculated for affected sibling pairs by comparison with those whose
siblings had no migraine. Among a total of 14,123 hospitalized patients, 205
affected siblings were identified, with a familial SIR of 2.84. SIRs for migraine
with and without aura were 3.08 and 2.67, respectively. The highest familial risk
of 3.71 was noted for unspecified migraine. The risk tended to be higher for
concordant (both siblings sharing the migraine subtype, ranging from 4.0 to 6.0) 
than discordant subtypes, but even many discordant SIRs were significant. The SIR
for spouse correlation was 1.14 for husbands and 1.22 for wives, far from being
significant. All subtypes of hospitalized migraines and other headaches show an
increased familial risk, at least in specific age groups. The different subtypes 
appear to share susceptibility, which may imply common disease mechanisms.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't

PMID: 16235063 [PubMed - indexed for MEDLINE]

1556: Cephalalgia. 2005 Nov;25(11):1048-53.

Comparison of the effects of amitriptyline and flunarizine on weight gain and
serum leptin, C peptide and insulin levels when used as migraine preventive
treatment.

Berilgen MS, Bulut S, Gonen M, Tekatas A, Dag E, Mungen B.

Firat University School of Medicine, Department of Neurology, Elazig, Turkey.
msberilgen@firat.edu.tr

The tricyclic antidepressant amitriptyline (AMT) and the calcium channel blocker 
flunarizine are frequently used in the preventive treatment of migraine, but the 
side-effect of prominent weight gain that frequently emerges during preventive
treatment of migraine with these agents often leads to the discontinuation of
therapy. In this study, we aimed to investigate the possible relationship between
the weight gain associated with the use of these agents and serum levels of
leptin, C-peptide and insulin in patient with migraine. Forty-nine migraine
patients with a body mass index (BMI) < 25 and without any endocrinological,
immunological or chronic diseases were randomly divided into two groups,
receiving AMT or flunarizine. There was a statistically significant increase in
serum levels of leptin, C-peptide, insulin and measures of BMI in both groups
when measured at the 12th week of therapy compared to their respective basal
levels. To our knowledge this is the first study investigating the effects of AMT
and flunarizine on serum leptin levels in preventive use of migraine treatment. A
result from this study indicates that AMT and flunarizine may cause leptin
resistance possibly by different mechanisms and thereby result in increase in
serum leptin levels and BMI.

Publication Types: 
    Comparative Study
    Randomized Controlled Trial

PMID: 16232156 [PubMed - indexed for MEDLINE]

1557: Cephalalgia. 2005 Nov;25(11):1042-7.

Critical analysis of the international classification of headache disorders
diagnostic criteria (ICHD I-1988) and (ICHD II-2004), for migraine in children
and adolescents.

Lima MM, Padula NA, Santos LC, Oliveira LD, Agapejev S, Padovani C.

Headache Outpatient Ward for Children and Adolescents, General Hospital Medical
School, State University (UNESP), Botucatu, Brazil. marcialimabtu@yahoo.com.br

The present study analyzed the (ICHD I-1988) and (ICHD II-2004) diagnostic
criteria in children and adolescents. Our population consisted of 496 patients of
the Headache Outpatient Ward for Children and Adolescents retrospectively studied
from 1992 to 2002. Individuals were classified according to three diagnostic
groups: Intuitive Clinical Diagnosis (Gold Standard), ICHD I-1988 and ICHD
II-2004. They were statistically compared using the variables: Sensitivity (S),
Specificity (Sp), Positive Predictive Value (PPV), Negative Predictive Value
(NPV). When ICHD I-1988 was used, the sensitivity of migraine without and with
aura was 21% and 27%, respectively, whereas in ICHD II-2004 it changed to 53% and
71% without affecting specificity. As a conclusion, the current classification
criteria (ICHD II-2004) showed greater sensitivity and high specificity for
migraine than ICHD I-1988, although it improved migraine diagnosis in children
and adolescents, the sensitivity remains poor.

Publication Types: 
    Comparative Study

PMID: 16232155 [PubMed - indexed for MEDLINE]

1558: Cephalalgia. 2005 Nov;25(11):1031-41.

Efficacy and safety of 6.25 mg t.i.d. feverfew CO2-extract (MIG-99) in migraine
prevention--a randomized, double-blind, multicentre, placebo-controlled study.

Diener HC, Pfaffenrath V, Schnitker J, Friede M, Henneicke-von Zepelin HH.

Neurologische Universitätsklinik, Essen, Germany. h.diener@uni-essen.de

The efficacy and tolerability of a CO(2)-extract of feverfew (MIG-99, 6.25 mg
t.i.d.) for migraine prevention were investigated in a randomized, double-blind, 
placebo-controlled, multicentre, parallel-group study. Patients (N = 170
intention-to-treat; MIG-99, N = 89; placebo, N = 81) suffering from migraine
according to International Headache Society criteria were treated for 16 weeks
after a 4-week baseline period. The primary endpoint was the average number of
migraine attacks per 28 days during the treatment months 2 and 3 compared with
baseline. Safety parameters included adverse events, laboratory parameters, vital
signs and physical examination. The migraine frequency decreased from 4.76 by 1.9
attacks per month in the MIG-99 group and by 1.3 attacks in the placebo group (P 
= 0.0456). Logistic regression of responder rates showed an odds ratio of 3.4 in 
favour of MIG-99 (P = 0.0049). Adverse events possibly related to study
medication were 9/107 (8.4%) with MIG-99 and 11/108 (10.2%) with placebo (P =
0.654). MIG-99 is effective and shows a favourable benefit-risk ratio.

Publication Types: 
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 16232154 [PubMed - indexed for MEDLINE]

1559: Curr Psychiatry Rep. 2005 Oct;7(5):371-5.

Neuropsychiatric aspects of migraine.

Peterlin BL, Ward TN.

Darthmouth-Hitchcock Medical Center, One Medical Center Drive, Lebanon, NH 03756,
USA.

Migraine is a common chronic disorder that presents with recurrent attacks of
headache and associated symptoms. Various somatic and psychiatric conditions have
been reported as comorbid conditions with migraine. Among the psychiatric
disorders that have been reported as comorbid with migraine are major depression,
anxiety, panic disorder, and bipolar disorder. Recent studies discussing the
comorbidity of headache and psychiatric disorders are reviewed here.

Publication Types: 
    Review

PMID: 16216157 [PubMed - indexed for MEDLINE]

1560: Otolaryngol Head Neck Surg. 2005 Oct;133(4):489-96.

Sinus headache, migraine, and the otolaryngologist.

Mehle ME, Schreiber CP.

Northeastern Ohio Universities College of Medicine, Cleveland, OH 44070, USA.
dr.m.mehle@att.net

"Sinus headache" is a common complaint in the otolaryngology office. Recent
literature has shown that the majority of patients with this complaint satisfy
the diagnostic criteria for migraine. This review article presents an overview of
the sinus headache literature, with emphasis on the incidence, identification,
and treatment of migraine headache for the otolaryngologist.

Publication Types: 
    Review

PMID: 16213917 [PubMed - indexed for MEDLINE]

1561: Pain. 2005 Nov;118(1-2):137-44. Epub 2005 Oct 4.

Comment in:
    Pain. 2005 Nov;118(1-2):1-2.

Multilevel somatosensory system disinhibition in children with migraine.

Valeriani M, Rinalduzzi S, Vigevano F.

Headache Center, Divisione di Neurologia, Ospedale Pediatrico Bambino Gesù,
IRCCS, Piazza Sant'Onofrio 4, 00165 Rome, Italy. m.valeriani@tiscali.it

Although migraine is characterised by an abnormal cortical excitability level,
whether the central nervous system is hyper- or hypo-excitable in migraine still 
remains an unsolved problem. The aim of our study was to compare the
somatosensory evoked potential (SEP) recovery cycle, a marker of the
somatosensory system's excitability, in a group of 15 children suffering from
migraine without aura (MO) (mean age 11.7+/-1.6 years, five males, 10 females)
and 10 control age-matched subjects (CS) (mean age 10.9+/-2.1 years, six males,
four females). We calculated the SEP's latency and amplitude modifications after 
paired electrical stimuli at 5, 20 and 40 ms interstimulus intervals (ISIs),
comparing it with a single stimulus condition assumed as the baseline. In MO
patients, the amplitudes of the cervical N13 and of the cortical N20, P24 and N30
responses at 20 and 40 ms ISIs showed a higher recovery than in CS (two-way
ANOVA, P<0.05). Since, the SEP recovery cycle depends on the inhibitory
interneuron function, our findings suggest that a somatosensory system
disinhibition takes place in migraine. This is a generalized phenomenon, not
limited to the cerebral cortex, but concerning also the cervical grey matter. The
SEP recovery cycle reflects the intracellular concentration of Na(+), therefore, 
the shortened recovery cycle in our MO patients suggests a high level of
intracellular Na(+) and a consequent depolarized resting membrane potential,
possibly due to an impaired Na(+) -K(+) ATPase function in migraine.

Publication Types: 
    Comparative Study

PMID: 16213092 [PubMed - indexed for MEDLINE]

1562: J Pain. 2005 Oct;6(10):700-3.

Cervicogenic headache in patients with presumed migraine: missed diagnosis or
misdiagnosis?

Yi X, Cook AJ, Hamill-Ruth RJ, Rowlingson JC.

Division of Pain Medicine, Department of Anesthesiology, University of Virginia
Health System, Charlottesville, Virginia, USA. yix@wustl.edu

The differential diagnosis of headache is often challenging, with significant
clinical and socioeconomic consequences of incomplete or inaccurate diagnosis.
Overlapping symptoms contribute to the diagnostic challenge. Four female
patients, ages 26 to 69 with standing diagnoses of migraine, were evaluated and
treated for complaints of chronic, severe headaches. All had obtained limited
relief from migraine therapies. On physical examination, all had occipital nerve 
tenderness or positive Tinel sign over the occipital nerve. All responded well to
occipital nerve blocks with local anesthetic, achieving complete or substantial
pain relief lasting up to 2 months. We conclude that accurate diagnosis of
occipital neuralgia or cervicogenic headache as contributing factors can lead to 
substantial headache relief through occipital nerve blocks in patients with
coexisting or misdiagnosed migraine. PERSPECTIVE: The pathophysiology of many
types of chronic headaches is not well understood. Mixed mechanisms such as
neurovascular, neuropathic, myofascial, and cervicogenic may all contribute. Our 
four patients with chronic headaches responded well to occipital nerve blocks.
The neuroanatomical relationship between the trigeminocervical nucleus and
occipital nerve may serve as the basis of efficacy for these blocks.

Publication Types: 
    Case Reports

PMID: 16202963 [PubMed - indexed for MEDLINE]

1563: Pain. 2005 Nov;118(1-2):155-63. Epub 2005 Oct 3.

A human experimental capsaicin model for trigeminal sensitization.
Gender-specific differences.

Gazerani P, Andersen OK, Arendt-Nielsen L.

Laboratory for Experimental Pain Research, Center for Sensory-Motor Interaction
SMI, Department of Health Science and Technology, Aalborg University, Fredrik
Bajers Vej 7D-3, DK-9220, Aalborg, Denmark.

Migraine is much more common in women (18%) than in men (6%). Menstrual migraine 
in female migraineurs also varies from 7 to 19%. The main goals of the present
study were (1) to investigate gender specific differences in an experimental
capsaicin model of trigeminal sensitization (a proposed mechanism of migraine)
and (2) to explore the influence of menstrual cycle phases. Twenty-eight healthy 
female and male volunteers were studied. Capsaicin (100 microg/0.1 ml) was
injected intradermally to the forehead. Pain intensity and distribution together 
with the visual flare and allodynic area (central sensitization) were assessed
for females (during their menstrual and luteal phases) and for males. Pain area
significantly changed across the menstrual cycle with 19.2+/-2.0 cm x min at
menstrual and 16.4+/-0.9 cm x min at luteal phase (P<0.001). The area was
significantly larger in both phases for females compared to males (14.2+/-1.3 cm 
x min, P<0.0001). Flare area at menstrual phase (69.2+/-4.2 cm(2)) was
significantly (P<0.0001) larger than luteal phase (58.6+/-2.1 cm(2)). Females, in
both phases, showed larger flare area compared to males (44.9+/-3.6 cm(2),
P<0.0001). Area of brush-evoked allodynia was also larger at the menstrual phase 
compared to the luteal phase (P<0.0001) and males (P<0.0001). A significant
difference was found in the capsaicin-evoked pain distribution with a greater
response in menstrual phase compared to the luteal phase (P<0.01) and men
(P<0.0001). Capsaicin induced trigeminal sensitization and evoked gender specific
sensory and vaso-motor responses, with menstruating females generally showing the
strongest manifestations. The model may be further applied to explore mechanisms 
of human trigeminal sensitization.

Publication Types: 
    Comparative Study

PMID: 16202522 [PubMed - indexed for MEDLINE]

1564: J Hum Genet. 2005;50(12):607-10. Epub 2005 Oct 1.

A genetic analysis of serotonergic biosynthetic and metabolic enzymes in migraine
using a DNA pooling approach.

Johnson MP, Griffiths LR.

Genomics Research Centre, School of Medical Science, Griffith University, PMB 50 
GCMC, 9726 Gold Coast, QLD, Australia.

Migraine is a common debilitating primary headache disorder with significant
mental, physical and social health implications. The brain neurotransmitter
5-hydroxytryptamine (5-HT; serotonin) is involved in nociceptive pathways and has
been implicated in the pathophysiology of migraine. With few genetic studies
investigating biosynthetic and metabolic enzymes governing the rate of 5-HT
activity and their relationship to migraine, it was the objective of this study
to assess genetic variants within the human tryptophan hydroxylase (TPH), amino
acid decarboxylase (AADC) and monoamine oxidase A (MAOA) genes in migraine
susceptibility. This objective was undertaken using a high-throughput DNA pooling
experimental design, which proved to be a very accurate, sensitive and specific
method of estimating allele frequencies for single nucleotide polymorphism,
insertion deletion and variable number tandem repeat loci. Application of DNA
pooling to a wide array of genetic loci provides greater scope in the assessment 
of population-based genetic association study designs. Despite the application of
this high-throughput genotyping method, negative results from the two-stage DNA
pooling design used to screen loci within the TPH, AADC and MAOA genes did not
support their role in migraine susceptibility.

Publication Types: 
    Evaluation Studies
    Research Support, Non-U.S. Gov't

PMID: 16200390 [PubMed - indexed for MEDLINE]

1565: Pediatrics. 2005 Oct;116(4):e555-8.

Relationship between significant perinatal events and migraine severity.

Maneyapanda SB, Venkatasubramanian A.

Department of Ecology and Evolutionary Biology, Princeton University, Princeton, 
New Jersey, USA.

OBJECTIVE: Nociceptive neuronal circuits are formed during embryonic and
postnatal times, so insult during these periods may result in long-term
alterations to pain circuitry via synaptic plasticity. One possible long-term
result of plasticity is central hyperexcitability, which is suspected to be
involved in chronic headache. This study aimed to establish whether there is an
association between early pain experiences and the experience of migraines in
later childhood. METHODS: In a retrospective study, we examined the charts of 280
pediatric migraineurs at the Division of Pediatric Neurology at Robert Wood
Johnson Medical School and documented their perinatal history and migraine
characteristics. RESULTS: Analysis revealed that there was a significant
relationship between patients who had been in the NICU at birth and the type of
pain medication prescribed when compared with patients who had not been in the
NICU (chi2 test, chi2(2) = 23.304; N = 30250). Findings also suggested that
pediatric migraine patients who had been in the NICU at birth had a significantly
earlier age of onset of their migraines (chi2 +/- SD = 7.83 +/- 3.23; N = 30)
when compared with patients who did not remain in the NICU (chi2 +/- SD = 9.68
+/- 3.57; N = 250; Kolmogorov-Smirnov Test, chi2 = 10.699). CONCLUSION: On the
basis of these findings, we speculate that pain experience as a neonate, through 
neuronal plasticity and resulting central hyperexcitability, can alter the later 
experience of pain. However, this observational study cannot validate these
links. Other potential explanations that work either synergistically or alone
include other forms of stimulation and greater parental vigilance that may occur 
when neonates spend time in the NICU. This study would prompt additional
development of a larger prospective study to establish a link between early pain 
experience and subsequent pain syndromes and also future investigation into the
treatment of pain in neonates as a preventive measure for avoiding long-lasting
neuronal alterations.

PMID: 16199683 [PubMed - indexed for MEDLINE]

1566: Pediatr Neurol. 2005 Oct;33(4):283-4.

Bordetella pertussis as a trigger of migraine without aura.

Eidlitz-Markus T, Zeharia A.

Day Hospitalization Unit, Schneider Children's Medical Center of Israel, Petah
Tiqva, Israel.

This report describes a 10-year-old child in whom the clinical and serologic
appearance of pertussis coincided with new-onset migraine without aura. The
child's mother, who had a history of migraine, also complained of exacerbation of
symptoms and was found to be positive for Bordetella pertussis. The migraine
improved in both mother and child concomitant with the clinical improvement of
symptoms of the pertussis infection. The possible molecular basis of pertussis as
a trigger for migraine is discussed.

Publication Types: 
    Case Reports

PMID: 16194729 [PubMed - indexed for MEDLINE]

1567: Neuropathology. 2005 Sep;25(3):228-34.

Autopsy case of acute encephalopathy linked to familial hemiplegic migraine with 
cerebellar atrophy and mental retardation.

Takahashi T, Arai N, Shimamura M, Suzuki Y, Yamashita S, Iwamoto H, Inayama Y,
Kameda Y, Kuroiwa Y.

Department of Neurology, Yokohama City Kowan Hospital, Kanagawa, Japan.
takahashitatsuya@jcom.home.ne.jp

A 19-year-old female patient, who had exhibited esotropia, mild cerebellar
ataxia, mild mental retardation, and cerebellar atrophy on magnetic resonance
images at the age of 15, developed signs of acute encephalopathy, and thereafter 
died of disseminated intravascular coagulation on the day of her admission. Both 
her mother and sister suffered from attacks of hemiplegic migraine, mild mental
retardation, and cerebellar ataxia. Neuropathological examinations revealed acute
changes in the widespread cerebral cortex, chronic degenerative changes in the
anterior lobe of the cerebellar vermis, axonal spheroids in the Goll's nucleus,
pseudo-calcinosis in the globus pallidus, and glial bundles in the cranial
nerves. The most fascinating features were changes of Purkinje cells, such as
cactuses (asteroid bodies, dendritic expansions), somatic sprouts, and torpedoes.
These changes may be characteristic of familial hemiplegic migraine with
cerebellar atrophy, as well as the other metabolic diseases, such as Menkes'
kinky hair disease, infantile (Tay-Sachs type) amaurotic idiocy, organic mercury 
intoxication, and mitochondrial encephalopathy, of which cases often exhibit such
pathological changes of Purkinje cells. Therefore, familial hemiplegic migraine
may share some metabolic abnormalities with the diseases mentioned above.

Publication Types: 
    Case Reports

PMID: 16193840 [PubMed - indexed for MEDLINE]

1568: Neurol Sci. 2005 Oct;26(4):203-7.

A comparative analysis of personality profile and muscle tenderness between
chronic migraine and chronic tension-type headache.

Mongini F, Rota E, Deregibus A, Mura F, Francia Germani A, Mongini T.

Department of Clinical Pathophysiology, Headache and Facial Pain Unit, University
of Turin, Corso Dogliotti 14, I-10126 Turin, Italy. franco.mongini@unito.it

This study was aimed at comparing the personality profile, the psychiatric
comorbidity (depression and anxiety) and the tenderness of the pericranial and
cervical muscles in women with chronic migraine (CM) and chronic tension-type
headache (CTTH). Forty-one CM and 34 CTTH women were enrolled. A clinical
evaluation (according to SCID-I) and a psychometric assessment (MMPI-2, STAI-1
and STAI-2) were performed. After palpation, a Pericranial muscle Tenderness
Score (PTS) and a Cervical Muscle Tenderness Score (CTS) were calculated. No
significant difference was detected in MMPI-2, STAI-1, STAI-2, PTS and CTS scores
between the two groups. Anxiety and depression were present in 80% of CM and in
63% of CTTH women. We did not find any significant difference either in the
personality profile or in the muscle tenderness between CM and CTTH patients.
This similarity points to a role of these factors, in association with
psychiatric comorbidity, in the chronicisation of headache.

Publication Types: 
    Comparative Study

PMID: 16193246 [PubMed - indexed for MEDLINE]

1569: Cell Mol Biol (Noisy-le-grand). 2005 Sep 5;51(3):285-92.

A population genomics overview of the neuronal nitric oxide synthase (nNOS) gene 
and its relationship to migraine susceptibility.

Johnson MP, Lea RA, Colson NJ, Macmillan JC, Griffiths LR.

Genomics Research Centre, School of Health Science, Griffith University, PMB 50
GCMC, Gold Coast 9726, Australia.

The ubiquitous chemical messenger molecule nitric oxide (NO) has been implicated 
in a diverse range of biological activities including neurotransmission, smooth
muscle motility and mediation of nociception. Endogenous synthesis of NO by the
neuronal isoform of the nitric oxide synthase gene family has an essential role
within the central and peripheral nervous systems in addition to the autonomic
innervation of cerebral blood vessels. To investigate the potential role of NO
and more specifically the neuronal nitric oxide synthase (nNOS) gene in migraine 
susceptibility, we investigated two microsatellite repeat variants residing
within the 5' and 3' regions of the nNOS gene. Population genomic evaluation of
the two nNOS repeat variants indicated significant linkage disequilibrium between
the two loci. Z-DNA conformational sequence structures within the 5' region of
the nNOS gene have the potential to enhance or repress gene promoter activity. We
suggest that genetic analysis of this 5' repeat variant is the more functional
variant expressing gene wide information that could affect endogenous NO
synthesis and potentially result in diseased states. However, no association with
migraine (with or without aura) was seen in our extensive case-control cohort (n 
= 579 affected with matched controls), when both the 5' and 3' genetic variants
were investigated.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16191396 [PubMed - indexed for MEDLINE]

1570: Eur J Neurol. 2005 Oct;12(10):774-81.

Efficacy of oral naratriptan in the treatment of menstrually related migraine.

Massiou H, Jamin C, Hinzelin G, Bidaut-Mazel C; The French Naramig Collaborative 
Study Group.

Service de Neurologie, Hôpital Lariboisière, Paris, France.
helene.massiou@lrb.ap-hop-paris.fr

The aim of this study was to investigate the efficacy of orally administered 2.5 
mg naratriptan in the treatment of menstrually related migraine (MRM). A high
percentage of women suffering from migraine report increased frequency of attacks
in association with menstruation that may be more severe, of longer duration and 
more difficult to treat than at other times. This was a phase IIIb, randomized,
double-blind, placebo-controlled clinical trial. Subjects were given either 2.5
mg naratriptan or placebo to treat a single MRM episode, defined as starting
between days -2 and +4 relative to the start of menstruation. The primary
efficacy measure was the percentage of subjects who were free of pain 4 h after
treatment, the absence of pain at 30 min, 1 and 2 h being secondary efficacy
measures. Other secondary measures were the absence of associated symptoms,
sustained headache relief 24 h after a single dose of the study medication,
recourse to a second dose of study medication or escape medication, pain
intensity 4-24 h after first treatment, the ability to carry out work or daily
activities, and patient satisfaction. Adverse events were also monitored. A total
of 275 women were enrolled in the trial and 229 (115 naratriptan group, 114
placebo group) provided data on the effects of the study medication on MRM. A
higher percentage of subjects in the naratriptan group (58%) reported complete
pain relief 4 h after medication than in the placebo group (30%) (P<0.001).
Significant differences between the naratriptan and placebo groups and in favor
of naratriptan were also found for: total pain relief at 2 h (P=0.004), sustained
pain-free response within 4-24 h (P<0.001), absence of all associated symptoms at
2 and 4 h (P=0.004), ability to work and carry out daily activities at 2 h
(P=0.036), and patient overall satisfaction (P<0.001). Three adverse events were 
recorded that might potentially be attributable to naratriptan. Naratriptan given
orally at a dose of 2.5 mg is effective in the acute treatment of MRM as early as
2 h after treatment.

Publication Types: 
    Clinical Trial, Phase III
    Comparative Study
    Multicenter Study
    Randomized Controlled Trial

PMID: 16190915 [PubMed - indexed for MEDLINE]

1571: Headache. 2005 Oct;45(9):1263-7.

Migraine, celiac disease, and cerebral calcifications: a new case.

D'Amico D, Rigamonti A, Spina L, Bianchi-Marzoli S, Vecchi M, Bussone G.

Headace Center, National Institute, Milan, Italy.

Celiac disease is sometimes associated with neurological complications. Only one 
case of celiac disease associated with migraine and cerebral calcifications has
been reported. We present a patient with migraine (with and without aura) in whom
neuroimaging revealed cerebral calcifications in the occipital and parietal
regions bilaterally. Visual examination showed bilateral double scotoma, and
further investigations revealed celiac disease. Migraine may on occasion be a
sentinel symptom of mild celiac disease.

Publication Types: 
    Case Reports

PMID: 16178961 [PubMed - indexed for MEDLINE]

1572: Headache. 2005 Oct;45(9):1250-4.

Removing barriers to appropriate migraine treatment: formulary limitations and
triptan package size.

Silberstein SD, Dodick D, Kesslick J.

Jefferson Headache Center, Philadelphia, PA 19107, USA.

The main goals in the pharmacologic management of migraine headache are to avert 
or relieve debilitating pain, prevent escalating acute medication use, and
improve day-to-day functioning. This review will examine the evidence supporting 
the early use of acute medication, usually when pain is mild, to enhance patient 
outcomes. We will also discuss imposed quantity limits as a practical impediment 
to the implementation of this strategy in the managed care setting, and will
identify strategies for overcoming this barrier to effective care. Quantity
limits imposed on triptan therapy by health plans can hinder the optimal acute
treatment of migraine. A standard triptan quantity limit sufficient to permit
early migraine treatment and a movement by manufacturers to provide blister packs
consistent with a standard quantity limit should reduce patients costs, permit
brand mobility when appropriate, and bolster long-term cost effectiveness by
removing an important impediment to the use of triptans when they are most
effective, early in the migraine attack when pain is often still mild.

Publication Types: 
    Review

PMID: 16178957 [PubMed - indexed for MEDLINE]

1573: Headache. 2005 Oct;45(9):1244-9.

Familial hemiplegic migraine presenting as recurrent encephalopathy in a Native
Indian family.

Spacey SD, Vanmolkot KR, Murphy C, van den Maagdenberg AM, Hsiung RG.

Division of Neurology, Department of Medicine, University of British Columbia,
Vancouver, British Columbia, Canada.

BACKGROUND: Familial hemiplegic migraine (FHM) is an autosomal dominant disorder,
which can result from mutations in the CACNA1A (FHM1) and ATP1A2 (FHM2) genes.
Typically, FHM presents with an aura of hemiplegia accompanied by a
moderate-to-severe headache. FHM can be associated with other neurological
findings including coma and seizures. METHODS: We describe the clinical and
genetic features of a two-generation, seven-member Native Indian family with
recurrent encephalopathy and FHM. RESULTS: Two of the three affected family
members presented initially with encephalopathy, the third family member
presented with classic episodes of migraine and hemiparesis. The CACNA1A gene
locus was excluded in this family by haplotype analysis and no mutations were
identified in the coding region of the ATP1A2 gene by direct sequencing.
CONCLUSIONS: This emphasizes the genetic and clinical heterogeneity in familial
hemiplagic migraine FHM and highlights the need to consider the diagnosis of FHM 
in cases of recurrent encephalopathy.

Publication Types: 
    Case Reports

PMID: 16178956 [PubMed - indexed for MEDLINE]

1574: Headache. 2005 Oct;45(9):1224-8.

Increased plasma transforming growth factor-beta1 in migraine.

Ishizaki K, Takeshima T, Fukuhara Y, Araki H, Nakaso K, Kusumi M, Nakashima K.

Department of Neurology, Institute of Neurological Sciences, Faculty of Medicine,
Tottori University, Yonago, Japan.

BACKGROUND AND OBJECTIVES: Migraine is characterized by the peripheral and
central sensitization of pain perceptive neural systems, and neurogenic
inflammation is a key step in the development of migraine headache. We focused on
transforming growth factor-beta1 (TGF-beta1), which is a multifunctional
proinflammatory cytokine. To address the possibility of TGF-beta1 involvement in 
migraine, we investigated the plasma level of TGF-beta1 in patients with migraine
headache during headache-free periods. Subjects and METHODS: Sixty-eight subjects
with migraine participated: 23 with migraine with aura (MWA) and 45 without aura 
(MWoA). We recruited 58 healthy subjects without headache as controls. In
addition, we examined 12 subjects with episodic tension-type headache. Platelet
poor plasma (PPP) was obtained from subjects during headache free-periods.
TGF-beta1 levels in PPP were determined by enzyme-linked immunosorbent assay.
RESULTS: The TGF-beta1 level in PPP was 2.62*+/- 0.23 (mean +/- SE) ng/mL in
migraine, 2.08 +/- 0.20 ng/mL in tension-type headache, and 1.80 +/- 0.09 ng/mL
in controls (P= .007, ANOVA; *P < .01, post hoc tests vs. the controls).
CONCLUSION: TGF-beta1 in PPP was significantly increased in patients with
migraine during headache-free periods. TGF-beta1 may play some role in the
development of migraine headache.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 16178953 [PubMed - indexed for MEDLINE]

1575: Headache. 2005 Oct;45(9):1208-18.

Changes in cortical processing of pain in chronic migraine.

de Tommaso M, Losito L, Difruscolo O, Libro G, Guido M, Livrea P.

Department of Neurologic and Psychiatric Sciences, University of Bari, Bari,
Italy.

OBJECTIVE: The aim of this study was to perform a topographic and dipolar
analysis of nociceptive-evoked responses obtained by laser stimulus under basal
conditions in a cohort of chronic migraine (CM) patients, compared with migraine 
without aura (MWA) patients and noncraniofacial pain controls. BACKGROUND: An
increased activation of cortical areas devoted to the emotional and attentive
components of pain was previously found during the course of the migraine attack;
it was more pronounced in patients reporting higher frequency of migraine.
METHODS: Twenty-six outpatients were enrolled in the study; 16 fulfilled the
criteria of CM, and 10 were affected by MWA. Fifteen noncraniofacial pain
subjects were also selected. The pain stimulus was a CO2 laser pulses. The
right-supraorbital zone was stimulated. Source localization analysis was
performed on the most prominent laser-evoked potentials (LEPs) peak (P2) for each
data set. The anatomical locations of the P2 sources were projected onto a
standard normalized 3D MRI model. RESULTS: The CM group differed significantly
from both MWA patients and controls for the x coordinate and from controls for
the z coordinates. The P2 dipole localized in the rostral cingulate cortex in CM 
patients, lying in a more posterior location within the anterior cingulate cortex
(ACC) in both controls and MWA patients. The x coordinate of the P2 dipole,
expressing the postero-anterior location, was significantly correlated with
frequency of headache. CONCLUSIONS: CM seems to be characterized by a distinctive
pattern of cortical elaboration of pain, with a prevalent activation of the
rostral portion of the ACC: our results suggest that this may be a predisposing
factor to migraine chronicity.

Publication Types: 
    Comparative Study

PMID: 16178951 [PubMed - indexed for MEDLINE]

1576: Headache. 2005 Oct;45(9):1202-7.

Assessing cortical excitability in migraine: reliability of magnetic suppression 
of perceptual accuracy technique over time.

Custers A, Mulleners WM, Chronicle EP.

Department of Neurology, Atrium Medical Center, Heerlen, The Netherlands.

OBJECTIVES: To examine test-retest reliability of magnetic suppression of
perceptual accuracy (MSPA) prior to its use as a marker of cortical excitability 
in a trial of migraine prophylactic agents. BACKGROUND: MSPA is a relatively
novel avenue of research in headache, providing an opportunity to study cortical 
responsiveness objectively and noninvasively. However, little is known about the 
reliability of magnetic stimulation protocols such as MSPA in longitudinal
research designs. METHODS: We tested 10 healthy headache-free volunteers who had 
no family history of migraine. In 54 trials, they were briefly presented
different three-letter combinations, flashed on a computer screen for 24 ms
(target). After a brief interval, each target was followed by a single magnetic
pulse through a 90-mm circular coil centered 7 cm above inion in the midline. The
interval between target and magnetic pulse was systematically varied. Volunteers 
were requested to report as many letters as they had possibly identified. After 2
weeks, all volunteers were retested using identical methods. RESULTS: MSPA
performance is expressed as a profile of response accuracy (ie, percentage of
correctly identified letters) across target-pulse intervals. Profiles were
characteristic of normal headache-free subjects at the first test. Analysis of
variance revealed no significant difference in profiles between test and retest
(F= 2.05; P= .136): the retest profiles are almost coincidental with the test
profiles. CONCLUSIONS: MSPA is a safe and objective measure of cortical
excitability, which is reliable over time. MSPA, therefore, shows excellent
promise as a biological marker of cortical response in trials of migraine
prophylactics.

Publication Types: 
    Clinical Trial
    Research Support, Non-U.S. Gov't

PMID: 16178950 [PubMed - indexed for MEDLINE]

1577: Headache. 2005 Oct;45(9):1190-201.

Defining the relationship between ovarian hormones and migraine headache.

Martin VT, Wernke S, Mandell K, Ramadan N, Kao L, Bean J, Liu J, Zoma W, Rebar R.

Department of Internal Medicine, University of Cincinnati, Cincinnati, OH
45267-4217, USA.

OBJECTIVE: (1) To determine whether the attack characteristics of migraine differ
between different intervals of the menstrual cycle; (2) To ascertain whether the 
"rate of change,""magnitude of change," or "total burden" of urinary hormone
metabolites correlates with headaches outcome measures during different intervals
of the menstrual cycle. BACKGROUND: The mechanisms through which migraines are
influenced by ovarian hormones remain unclear. No previous studies until now have
identified "hormonally defined" time intervals within the female menstrual cycle 
and compared headache outcome measures among these intervals in female
migraineurs. METHOD: Daily headache diary data were obtained from 21 female
migraineurs during three native menstrual cycles. Daily urine samples were
collected and later assayed for estrogen and progesterone metabolites. Seven
3-day time intervals were identified within each menstrual cycle based on urine
hormone measurements. Primary (headache index) and secondary (disability index,
headache severity, and headache frequency) outcome measures were compared between
intervals using the mixed model approach. "Rates of change,""magnitude of
change," and the "total burden" of ovarian hormones were estimated from urine
hormone metabolites and correlated with headache outcome measures. RESULTS: The
headache index was significantly different across different intervals of the
menstrual cycle (P values <.001) and was higher during menstrual intervals (first
6 days of the menstrual cycle) than during mid-cycle and mid-luteal intervals (P 
< .002). Similarly, secondary outcome measures were highest during the menstrual 
intervals. "Higher burdens" of urinary progesterone metabolites were positively
correlated with headache outcome measures during the luteal intervals of the
menstrual cycle. "Rates of change" and the "magnitude of change" of urinary
hormone metabolites did not correlate with headache outcome measures.
CONCLUSIONS: Migraine headache is more severe, disabling, and frequent during the
menstrual intervals of the female reproductive cycle than during mid-luteal or
mid-cycle intervals. Progesterone metabolites may play a role in modulating
migraine headaches during luteal intervals of the menstrual cycle.

Publication Types: 
    Comparative Study
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 16178949 [PubMed - indexed for MEDLINE]

1578: Headache. 2005 Oct;45(9):1181-9.

Hormones, menstrual distress, and migraine across the phases of the menstrual
cycle.

Kibler JL, Rhudy JL, Penzien DB, Rains JC, Meeks GR, Bennett W, Dollar KM.

Center for Psychological Studies, Nova Southeastern University, Ft. Lauderdale,
FL 33314, USA.

OBJECTIVE: The primary objectives of the present study were to (1) contrast
reproductive hormone levels and ratings of menstrual distress of female
migraineurs with those of a control group in each menstrual cycle phase, (2)
examine correlations between hormone levels and migraine frequency, severity, and
migraine-related disability, and (3) examine correlations between menstrual
distress and migraine frequency, severity, and migraine-related disability. A
secondary objective was to evaluate the validity of a migraine disability measure
modified to reflect 7-day recall. BACKGROUND: Further controlled, prospective
study is needed regarding the temporal relationships between reproductive
hormones at each stage of the menstrual cycle and fluctuations in migraine
activity across the cycle. METHODS: Twenty-three women (17 with migraine, 6
control participants) completed laboratory hormone assays and measures of
menstrual distress and disability at each phase of one menstrual cycle, and
monitored their headache activity daily during the same cycle. Results.-The
migraine group evidenced lower premenstrual luteinizing hormone and more
menstrual distress symptoms at each phase of the menstrual cycle. Hormones were
associated with migraine activity and disability within cycle phases, and across 
phases in a time-lagged manner. Menstrual distress was associated with ovulatory 
phase migraine activity and with migraine-related disability across the menstrual
cycle. A retrospective 7-day migraine disability measure appeared to be a
consistently valid index. CONCLUSIONS: Both reproductive hormones and menstrually
related distress appear to predict migraine activity and disability. These
associations were evident not only for perimenstrual migraine, but also for
migraine at each phase of the menstrual cycle.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 16178948 [PubMed - indexed for MEDLINE]

1579: Headache. 2005 Oct;45(9):1171-80.

Patterns and predictors of prescription medication use in the management of
headache: findings from the 2000 Medical Expenditure Panel Survey.

Devine JW, Farley JF, Hadsall RS.

Social and Administrative Graduate Program, College of Pharmacy, University of
Minnesota, MN 55455, USA.

OBJECTIVE: The primary objectives were to examine national trends of prescription
medication use for headache and explore patterns of variation in the use of these
medications across social and demographic levels. BACKGROUND: Despite widespread 
use of prescription medication for management of headache, little is known about 
utilization patterns or patient characteristics associated with receiving this
type of treatment. METHODS: This study conducted a secondary analysis of data
obtained during the 2000 Medical Expenditure Panel Survey, a representative
survey of the U.S. noninstitutionalized population. Weighted descriptive
statistics and logistic regression models were used to evaluate patterns and
rates of overall prescription medication use in patients reporting headache as a 
household condition. RESULTS: An estimated 9.7 million people 18 years or older
reported suffering from headache in 2000. Of these, 46% reported using at least
one medication for the treatment of headache. Migraine-specific abortive
medication (ie, selective serotonin receptor agonists and ergotamine derivatives)
was the most frequently reported medication class, used by 36% of participants.
Opiate analgesics and butalbital-containing products also experienced extensive
prescribing reported by 22% and 17% of survey respondents, respectively. After
adjustment for covariates, wide variation in the use of prescription medication
was observed across sociodemographic characteristics including age, ethnicity,
and insurance status. CONCLUSION: The observed variation in prescription
medication use by drug class and sociodemographic characteristics suggests
strategies are needed for improving current prescribing patterns in this patient 
population.

PMID: 16178947 [PubMed - indexed for MEDLINE]

1580: Headache. 2005 Oct;45(9):1151-62.

Valdecoxib for treatment of a single, acute, moderate to severe migraine
headache.

Kudrow D, Thomas HM, Ruoff G, Ishkanian G, Sands G, Le VH, Brown MT.

California Medical Clinic for Headache, Santa Monica, CA, USA.

OBJECTIVE: To evaluate the analgesic efficacy and safety of a single 20- or 40-mg
dose of valdecoxib compared with placebo in treatment of a single, acute,
moderate or severe migraine headache, with or without aura. BACKGROUND:
Valdecoxib, an oral COX-2 specific inhibitor, is indicated for relief of the
signs and symptoms of rheumatoid arthritis and osteoarthritis and treatment of
primary dysmenorrhea. This study assessed the optimal dose of valdecoxib for
treatment of a single, acute, moderate to severe migraine headache. METHODS: This
was a double-blind, randomized, placebo- and active-controlled, multicenter,
single-dose (primary end point) and multiple-dose (secondary end point), 56-day
study of valdecoxib in the treatment of a single, acute, moderate or severe
migraine headache, with or without aura. Migraine headaches were diagnosed
according to International Headache Society (IHS) criteria. The primary efficacy 
end point was headache response (defined as reduction of headache pain intensity 
from moderate or severe to mild or none) at 2 hours postdose. Patients assessed
their headache pain intensity and presence or absence of migraine-associated
nausea, vomiting, phonophobia, and photophobia at intervals from 0 to 24 hours
postdose. Sumatriptan 50 mg (encapsulated, in standard method, to maintain
blinding) was included as a positive control for assay sensitivity. No
statistical comparisons were performed between active treatment arms (valdecoxib 
20 mg, valdecoxib 40 mg, and sumatriptan 50 mg). Adverse events and safety
parameters were monitored throughout the study. RESULTS: In the intent-to-treat
population of 570 patients (135 valdecoxib 20 mg, 151 valdecoxib 40 mg, 143
sumatriptan, and 141 placebo), no significant differences in baseline
demographics among treatment groups were observed. The headache response rate
with valdecoxib 40 mg and sumatriptan 50 mg was significantly greater than that
with placebo at all time points from 2 to 24 hours postdose. With valdecoxib 20
mg, headache response rate was significantly greater than placebo from 2 to 4
hours. Significantly fewer patients treated with valdecoxib 40 mg, compared with 
placebo, experienced nausea, vomiting, and phonophobia at 2 hours postdose.
CONCLUSIONS: A single 40-mg dose of valdecoxib is effective and well tolerated in
treatment of migraine headache pain and associated symptoms.

Publication Types: 
    Comparative Study
    Multicenter Study
    Randomized Controlled Trial

PMID: 16178945 [PubMed - indexed for MEDLINE]

1581: Headache. 2005 Oct;45(9):1140-50.

Comment in:
    Nat Clin Pract Neurol. 2006 Apr;2(4):182-3.

Rizatriptan 10-mg wafer versus usual nontriptan therapy for migraine: analysis of
return to function and patient preference.

Pascual J, García-Moncó C, Roig C, Yusta Izquierdo A, López-Gil A; eMAX Study
Group.

Neurology Service, University Hospital Marqués de Valdecilla (UC), Santander,
Spain.

BACKGROUND: More than half of patients with migraine suffer moderate to severe
functional disability during migraine attacks. OBJECTIVE: To compare effects on
functional disability at 2 hours after treating a migraine with rizatriptan 10-mg
wafer versus usual nontriptan therapy for triptan-naïve patients with migraine.
DESIGN: Open-label, prospective, two-attack study conducted at 111 neurology
clinics. METHODS: Adult patients with migraine treated two migraine attacks, the 
first with their usual nontriptan therapy (nonsteroidal anti-inflammatory drugs, 
57%; analgesics, 27%; or ergot derivatives, 16%) and the second with rizatriptan 
10-mg wafer. Patients recorded pain intensity and functional disability at the
start, and functional disability at 2 hours, as well as the time of return to
normal function. RESULTS: A total of 1353 patients, 76% of them female, completed
the study and were considered evaluable. During first and second migraine
attacks, 55% and 63% of patients, respectively, reported severe disability or
requiring bed rest. At 2 hours after treatment, the likelihood of experiencing
any disability was more than five times greater after usual nontriptan therapy
than after rizatriptan (odds ratio, 5.68; 95% confidence interval (CI), 4.66 to
6.94; P < .001). Rizatriptan was twice as likely to return patients to normal
function than usual nontriptan therapy after adjusting for confounding factors
(adjusted hazard ratio, 2.08; 95% CI, 1.92 to 2.25; P < .001). Assessed over all 
time points up to 6 hours, the speed of return to normal function was 52% faster 
after rizatriptan therapy (P < .001). Significantly more patients preferred
rizatriptan than usual nontriptan therapy (78.8% vs. 21.2%; P < .001). The most
common reasons cited for preference for rizatriptan were faster relief of
headache pain and faster return to normal function. CONCLUSIONS: Patients in this
study were more likely to experience a return to normal function at 2 hours after
receiving rizatriptan than after their usual nontriptan therapy for migraine. The
results of this study, using patient-oriented, clinically relevant endpoints such
as functional disability and preference, will help to guide practitioners in
making recommendations for acute migraine treatment.

Publication Types: 
    Clinical Trial
    Comparative Study
    Multicenter Study
    Research Support, Non-U.S. Gov't

PMID: 16178944 [PubMed - indexed for MEDLINE]

1582: Headache. 2005 Oct;45(9):1124-39.

A self-administered behavioral intervention using tailored messages for migraine.

Nicholson R, Nash J, Andrasik F.

St.Louis University School of Medicine, Community and Family Medicine, St. Louis,
MO 63104, USA.

OBJECTIVE: The objective of this study was to evaluate the effectiveness of a
Self-Administered Behavioral Intervention using Tailored messages (SEABIT) for
migraine. The primary measures were headache days, headache-related disability,
behavioral/emotional factors, and headache-related beliefs. BACKGROUND:
Behavioral and cognitive-behavioral interventions for migraine treatment are well
established and possess "Grade-A" evidence based on the U.S. Headache Consortium 
evidence-based guidelines. To increase the accessibility of behavioral
interventions in primary and other settings, treatment can be delivered in
self-administered formats. Incorporating tailored health communication strategies
(via tailored messages) into a self-administered format can help maintain a level
of personalization without requiring regular visits to a behavioral specialist.
Tailored messages are created using individual-level assessment data to educate
and motivate the patient to develop behavioral skills and strategies for migraine
prevention and management. METHODS: Twenty-five individuals (95% female, 90%
Caucasian, mean headache years = 21.0) began and 84% (21/25) completed all phases
of the 8-week SEABIT developed for migraine prevention (preceded by a 1-month
baseline phase and followed by a 1-month postintervention phase). RESULTS:
Overall, 62% (13/21) reported at least a 50% reduction in headache frequency, and
mean headache frequency for the group was also significantly reduced from
baseline to postintervention (16.9 vs. 10.7, P < .001; eta2= .61).
Headache-related disability, behavioral/emotional factors, and
headache-management self-efficacy also showed significant improvement.
CONCLUSION: The findings suggest that the SEABIT for migraine prevention is an
effective behavioral intervention that potentially could be accessed and
distributed in a variety of settings including primary care.

Publication Types: 
    Clinical Trial

PMID: 16178943 [PubMed - indexed for MEDLINE]

1583: Headache. 2005 Oct;45(9):1102-12.

The predictive value of abbreviated migraine diagnostic criteria.

Martin VT, Penzien DB, Houle TT, Andrew ME, Lofland KR.

Division of General Medicine, University of Cincinnati College of Medicine, OH
45267-0535, USA.

OBJECTIVE: To determine the operating characteristics and predictive value of
abbreviated criteria for the diagnosis of migraine headache. BACKGROUND: The
International Headache Society (IHS) diagnostic criteria for migraine have been
adopted in limited fashion in clinical practice. Primary care physicians in
particular deal with innumerable conditions and diagnostic algorithms. Unless the
IHS criteria are simplified the recognition of migraine headache in primary care 
settings will not be apt to improve. METHODS: This study was a retrospective
analysis of four discrete research databases: headache clinic patients (N = 390),
private practice neurology patients (N = 290), college students (N = 99), and
community-based patients (N = 784). Physicians and psychologists expert in the
diagnostic criteria for migraine headache syndromes conducted a standardized
diagnostic interview in all patients (N = 1524). Each was later assigned an IHS
headache diagnosis by a previously validated computer-based algorithm. The
sensitivity, specificity, positive and negative predictive values, and accuracy
were calculated for single- and multiple-variable models of migraine predictors. 
Optimal models were defined as those with positive likelihood ratios (+LRs) of
>4.5 and negative likelihood ratios (-LRs) of <0.25 for the combined population. 
RESULTS: The only optimal single-variable model was nausea, which had an overall 
+LR of 4.8 and -LR of 0.23. None of the two-variable models met criteria for an
optimal model. The best of the optimal three-variable models were
nausea/photophobia/pulsating (+LR 6.7, -LR 0.23) and nausea/photophobia/worsening
with physical activity (+LR 5.9, -LR 0.21). These three models maintained
positive predictive values >0.80 in all 4 patient populations and negative
predictive values >0.70 in the majority of populations. CONCLUSION: The
single-variable model of nausea and the three-variable models of
nausea/photophobia/worse with exertion and nausea/phonophobia/pulsating can
effectively predict migraine in diverse clinical settings. These models however, 
should only be applied after a careful exclusion of secondary headache disorders.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16178941 [PubMed - indexed for MEDLINE]

1584: Ann Neurol. 2005 Oct;58(4):561-8.

No increase of calcitonin gene-related peptide in jugular blood during migraine.

Tvedskov JF, Lipka K, Ashina M, Iversen HK, Schifter S, Olesen J.

Danish Headache Center, University of Copenhagen and Department of Neurology,
Glostrup University Hospital, Glostrup, Copenhagen, Denmark. tvedskov@dadlnet.dk

Increased calcitonin gene-related peptide (CGRP) in external jugular venous blood
during migraine attack is one of the most cited findings in the headache
literature. The finding has not been convincingly reproduced and is based on
comparison with historic control subjects. The validity of this finding is
important for the understanding of migraine. We therefore investigated the issue 
using an intrapatient comparison design and two different CGRP assays. We sampled
blood from the external jugular and cubital vein during, as well as outside of,
an attack of migraine without aura. We succeeded in 17 patients, whereas only
cubital fossa blood could be sampled in an additional 4 patients. CGRP was
measured with the same assay as most previous studies (assay I) and furthermore
with a more sensitive and validated assay (assay II). For assay I, mean CGRP
concentration in external jugular venous blood during attack was 17.18 pmol/L
compared with 15.88 pmol/L outside of attack. Mean difference was 1.81 pmol/L
(95% confidence interval [CI]: -2.88, 6.41; p = 0.44). In peripheral blood during
attack, CGRP was 16.86 pmol/L compared with 17.57 pmol/L outside of attack. Mean 
difference was -0.79 pmol/L (95% CI: -4.64, 3.06; p = 0.69). For assay II,
external jugular venous blood concentration of CGRP during attack was 32.59
pmol/L compared with 30.59 pmol/L outside of attack; mean difference was 2.00
pmol/L (standard error, 2.39; 95% CI: -3.07, 7.07; p = 0.416). In peripheral
blood during attack, CGRP was 33.37 pmol/L compared with 31.84 pmol/L outside of 
attack; mean difference was 1.53 pmol/L (standard error, 1.90; 95% CI: -2.46,
5.51; p = 0.431). Thus, no difference between CGRP level in external jugular or
cubital fossa blood during and outside of attack was found. No difference was
found between external jugular and peripheral venous blood. Thus, previous
findings of increased CGRP level in external jugular or cubital fossa venous
blood could not be confirmed. Our finding strongly suggests that CGRP is not
increased in jugular venous blood during migraine without aura. CGRP cannot be
used as a biomarker to validate human or animal models of migraine.

Publication Types: 
    Comparative Study
    Validation Studies

PMID: 16178016 [PubMed - indexed for MEDLINE]

1585: Value Health. 2005 Sep-Oct;8(5):591-600.

Functional Assessment in Migraine (FAIM) questionnaire: development of an
instrument based upon the WHO's International Classification of Functioning,
Disability, and Health.

Pathak DS, Chisolm DJ, Weis KA.

Florida International University, Miami, FL, USA.

OBJECTIVE: The goal of this project was to develop a migraine functional
measurement instrument, derived from the World Health Organization International 
Classification of Impairments, Disabilities, and Handicaps version 2
classification system, which focuses on functional outcomes, and is both reliable
and valid. METHODS: The Functional Assessment in Migraine (FAIM) questionnaire
was developed using a multistep approach to ensure the brevity, relevance,
reliability, and validity of items. A test set of 71 Mental Functioning and 50
Activity and Participation items was generated and administered to migraineurs in
the United States and Germany. A subset of 22 Mental Functioning and 28 Activity 
and Participation items that rated highly on frequency-weighted importance and
showed strong psychometric properties was piloted to determine a final item set
and to test reliability and validity. RESULTS: The final version of the FAIM
included nine Mental Functioning items measuring the dimensions of
Attention/Thought (5 items) and Perception (4 items), and a list of 28 Activity
and Participation items from which respondents chose the five items most relevant
to their lifestyle. Construct validity analysis of FAIM dimensions found
significant positive correlations with self-reported symptom severity, moderately
significant positive correlations with dimensions of the Migraine-Specific
Quality of Life questionnaire and no significant correlation with Short Form
Health Survey (SF-12) component scores. CONCLUSION: The FAIM offers physicians a 
brief and valid method of measuring the impact of migraine on mental functioning 
and activity and participation as defined by the WHO International Classification
of Functioning, Disability, and Health. Additional testing is underway to assess 
its responsiveness to change.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Validation Studies

PMID: 16176497 [PubMed - indexed for MEDLINE]

1586: Graefes Arch Clin Exp Ophthalmol. 2006 May;244(5):589-95. Epub 2005 Sep 21.

Comment in:
    Graefes Arch Clin Exp Ophthalmol. 2006 Oct;244(10):1377-8; author reply 1379-80.

Short-wavelength automated perimetry in patients with migraine.

Yenice O, Temel A, Incili B, Tuncer N.

Department of Ophthalmology, Marmara University School of Medicine, Istanbul,
Turkey. yeniceozlem@yahoo.com

BACKGROUND: The aim was to investigate short-wavelength sensitivity deficits in
patients with migraine. METHODS: Fifteen migraine and 18 age-matched healthy
volunteers with normal ophthalmologic examination participated in this study.
Migraine characteristics were graded by the Migraine Disability Assessment
Questionnaire (MIDAS). All participants underwent SWAP (short wavelength
amplitude perimetry) testing using a Humphrey field analyzer; there was a 30-2
presentation pattern. RESULTS: Short wavelength amplitude perimetry parameters
for mean deviation (MD; p<0.0001) and pattern standard deviation (PSD; p<0.0001) 
were significantly worse in the migraine group. In the migraine group 53.3%. of
eyes had glaucoma hemi-field tests (GHT) outside normal limits and 10 of these
had early glaucomatous visual field loss. Statistically significant correlations 
were found between frequency of migraine attacks and MD (p=0.02; r=0.56) and PSD 
(p=0.03; r=0.41) and also between the MIDAS score and MD (p=0.03; r=0.49) and PSD
(p=0.04; r=0.51). In all migraine cases with early glaucomatous visual field
defect a corresponding site of the head was predominantly involved in headache
(p=0.03). CONCLUSION: Some patients with severe migraine have earlier defects on 
SWAP suggesting a common vascular insult of glaucoma and migraine, and all
migraine cases with high MIDAS scores should be further evaluated for early
glaucomatous visual field defects using SWAP.

PMID: 16175372 [PubMed - indexed for MEDLINE]

1587: BMC Med Genet. 2005 Sep 14;6:32.

Association analysis of a highly polymorphic CAG Repeat in the human potassium
channel gene KCNN3 and migraine susceptibility.

Curtain R, Sundholm J, Lea R, Ovcaric M, MacMillan J, Griffiths L.

Genomics Research Centre, School of Health Science, Griffith University, Gold
Coast, Queensland, Australia. r.curtain@griffith.edu.au

BACKGROUND: Migraine is a polygenic multifactorial disease, possessing
environmental and genetic causative factors with multiple involved genes.
Mutations in various ion channel genes are responsible for a number of
neurological disorders. KCNN3 is a neuronal small conductance calcium-activated
potassium channel gene that contains two polyglutamine tracts, encoded by
polymorphic CAG repeats in the gene. This gene plays a critical role in
determining the firing pattern of neurons and acts to regulate intracellular
calcium channels. METHODS: The present association study tested whether length
variations in the second (more 3') polymorphic CAG repeat in exon 1 of the KCNN3 
gene, are involved in susceptibility to migraine with and without aura (MA and
MO). In total 423 DNA samples from unrelated individuals, of which 202 consisted 
of migraine patients and 221 non-migraine controls, were genotyped and analysed
using a fluorescence labelled primer set on an ABI310 Genetic Analyzer. Allele
frequencies were calculated from observed genotype counts for the KCNN3
polymorphism. Analysis was performed using standard contingency table analysis,
incorporating the chi-squared test of independence and CLUMP analysis. RESULTS:
Overall, there was no convincing evidence that KCNN3 CAG lengths differ between
Caucasian migraineurs and controls, with no significant difference in the allelic
length distribution of CAG repeats between the population groups (P = 0.090).
Also the MA and MO subtypes did not differ significantly between control allelic 
distributions (P > 0.05). The prevalence of the long CAG repeat (>19 repeats) did
not reach statistical significance in migraineurs (P = 0.15), nor was there a
significant difference between the MA and MO subgroups observed compared to
controls (P = 0.46 and P = 0.09, respectively), or between MA vs MO (P = 0.40).
CONCLUSION: This association study provides no evidence that length variations of
the second polyglutamine array in the N-terminus of the KCNN3 channel exert an
effect in the pathogenesis of migraine.

PMID: 16162291 [PubMed - indexed for MEDLINE]

1588: Cephalalgia. 2005 Oct;25(10):817-21.

A single-fibre EMG study of neuromuscular transmission in migraine patients.

Domitrz I, Kostera-Pruszczyk A, Kwieciñski H.

Department of Neurology, Medical University, 1a Banacha Street, 02-097 Warsaw,
Poland. domitrz@amwaw.edu.pl

It is known that mutations of CACNA1A, which encodes a neuronal P/Q Ca(2+)
channel, are present in patients with familial hemiplegic migraine, and possibly 
in other types of migraine as well. This calcium channel is also involved in
neuromuscular transmission. To assess if the single-fibre EMG (SFEMG) method can 
demonstrate a neuromuscular transmission deficit in migraine, a group of 26
patients with different types of migraine and 20 healthy control subjects were
studied. The migraine patients were divided into three groups: 8 patients with
migraine without aura (MoA), 12 with migraine with aura excluding visual aura
(MA) and 6 with visual aura (VA). A SFEMG of the voluntarily activated extensor
digitorum communis muscle was performed. The SFEMG results were normal in the
healthy controls and the MoA group (migraine without aura). Slight neuromuscular 
transmission disturbances were present in 6/12 (50%) of patients with MA and in
1/6 (17%) of patients with VA. We suggest that abnormal neuromuscular
transmission detectable by SFEMG may reflect a genetically determined dysfunction
of the P/Q Ca(2+) channels in a subgroup of migraineurs with aura.

Publication Types: 
    Clinical Trial
    Controlled Clinical Trial

PMID: 16162259 [PubMed - indexed for MEDLINE]

1589: Cephalalgia. 2005 Oct;25(10):811-6.

Seasonal variation in migraine.

Alstadhaug KB, Salvesen R, Bekkelund SI.

Department of Neurology, Nordlandssykehuset 8092, Bodø, Norway.
karl.bjornar.alstadhaug@nordlandssykehuset.no

Our group has previously shown that migraineurs, as opposed to individuals with
other headaches, are more likely to have headache during the bright arctic summer
than during the polar night season. We set out to investigate the impact of
seasonal light exposure in migraine with and without aura. We performed a
questionnaire-based study of 169 female volunteer migraineurs in an arctic area
where light conditions during summer and winter seasons are extreme. We included 
98 patients with migraine with aura (MA) and 71 with migraine without aura (MoA).
One hundred and seven patients (63%) reported seasonal variation in migraine
attack frequency. Close to half (47%) of patients with aura, but only 17% of
patients without aura, reported more frequent attacks during the light season (P 
< 0.001). Patients with MA reported interictal light hypersensitivity and light
exposure as an attack precipitating factor significantly more often than
individuals with MoA. They also reported significantly more frequent use of
sunglasses to prevent attacks. We found no significant differences between MA and
MoA as regards sleep disturbances, use of oral contraceptives, impact of headache
or circadian variations. Seasonal periodicity of migraine in an arctic population
with more frequent attacks during the light season is a convincing phenomenon in 
MA but not in MoA. The amount of light exposure seems to be pivotal to this
variation.

Publication Types: 
    Clinical Trial
    Controlled Clinical Trial

PMID: 16162258 [PubMed - indexed for MEDLINE]

1590: Cephalalgia. 2005 Oct;25(10):801-10.

The Visual Aura Rating Scale (VARS) for migraine aura diagnosis.

Eriksen MK, Thomsen LL, Olesen J.

Danish Headache Center, University of Copenhagen, and Department of Neurology,
Glostrup Hospital, Nordre Ringvej 57, DK-2600 Glostrup, Denmark.
kirchmann@dadlnet.dk

To supplement the traditional ICHD-2 diagnosis for migraine with aura (MA) we
developed a diagnostic scale for migraine aura that quantifies the importance of 
the cardinal characteristics of MA. Since more than 99% of MA patients have
visual aura, we developed for simplicity a Visual Aura Rating Scale (VARS). In
total 427 patients with MA (ICHD-2) or nonaura visual disturbances were diagnosed
in a validated semistructured interview by a trained physician. The patients were
separated into a derivation sample and a validation sample. By regression
analysis we identified the visual aura characteristics associated with MA in the 
derivation sample. Based on the identified characteristics we developed VARS and 
derived a predictive VARS score which was tested in the validation sample. The
VARS score is the weighted sum of the presence of five visual symptom
characteristics: duration 5-60 min (3 points), develops gradually > or = 5 min (2
points), scotoma (2 points), zig-zag lines (2 points), and unilateral (1 point). 
The maximum score is 10 points. A VARS score of 5 or more diagnosed MA with a
sensitivity of 96% (95% CI 92-99%) and a specificity of 98%(95% CI 95-100%) in
the derivation sample, and a sensitivity of 91% (95% CI 86-95%) and a specificity
of 96% (95% CI 91-100%) in the validation sample. VARS adds evidence based
weights to a number of clearly specified characteristics; it is easy to learn,
apply and teach and may therefore be a valuable addition to traditional ICHD-2
diagnosis.

Publication Types: 
    Clinical Trial
    Research Support, Non-U.S. Gov't
    Validation Studies

PMID: 16162257 [PubMed - indexed for MEDLINE]

1591: Cephalalgia. 2005 Oct;25(10):788-94.

Altered motion perception in migraineurs: evidence for interictal cortical
hyperexcitability.

Antal A, Temme J, Nitsche MA, Varga ET, Lang N, Paulus W.

Department of Clinical Neurophysiology, Georg-August University of Göttingen,
Robert Koch Strasse 40, 37075 Göttingen, Germany. aantal@gwdg.de

Much research on visual functions in migraine has pinpointed the existence of
abnormal visual processing between attacks. However, it is not clear if this is
due to cortical hyper- or hypoexcitability. We aimed to clarify this issue by
comparing motion perception thresholds of subjects with migraine with (MA) or
without aura (MoA) and control subjects. Two types of dot kinetograms were used: 
in the first experiment coherently moving dots were presented in an incoherent
environment, while in the second only coherent motion was seen. Subjects with
migraine displayed significantly impaired motion perception compared with
controls when they had to detect the direction of the coherently moving dots in
an incoherent environment, while they were slightly better in a direction
discrimination task, where only coherent motion was presented. This pattern of
results is comparable to those achieved by an external excitability enhancement
of V5 induced in healthy human subjects in a former study of our group. According
to this, a cortical excitability enhancement can result in an impaired focusing
on a given signal against a noisy background, but improves perception of
non-ambiguous stimuli. Thus we conclude that migraineurs display enhanced visual 
cortical excitability between attacks in V5.

Publication Types: 
    Clinical Trial
    Controlled Clinical Trial
    Research Support, Non-U.S. Gov't

PMID: 16162255 [PubMed - indexed for MEDLINE]

1592: Cephalalgia. 2005 Oct;25(10):776-87.

Comment in:
    Cephalalgia. 2006 Dec;26(12):1487; author reply 1487-90.    Cephalalgia. 2006 Oct;26(10):1260-1.

The fixed combination of acetylsalicylic acid, paracetamol and caffeine is more
effective than single substances and dual combination for the treatment of
headache: a multicentre, randomized, double-blind, single-dose,
placebo-controlled parallel group study.

Diener HC, Pfaffenrath V, Pageler L, Peil H, Aicher B.

Department of Neurology, University of Essen, Essen, Germany.

We investigated efficacy, safety, and tolerability of two tablets of the fixed
combination of 250 mg acetylsalicylic acid (ASA) + 200 mg paracetamol + 50 mg
caffeine (Thomapyrin) in comparison with two tablets of 250 mg ASA + 200 mg
paracetamol, two tablets of 500 mg ASA, two tablets of 500 mg paracetamol, two
tablets of 50 mg caffeine, and placebo in patients who were used to treating
their episodic tension-type headache or migraine attacks with non-prescription
analgesics. For the primary endpoint "time to 50% pain relief" in the
intention-to-treat dataset (n = 1743 patients), the fixed combination of ASA,
paracetamol and caffeine was statistically significantly superior to the
combination without caffeine (P = 0.0181), the mono-substances ASA (P = 0.0398), 
paracetamol (P = 0.0016), caffeine (P < 0.0001) and placebo (P < 0.0001). All
active treatments except caffeine differed significantly (P < 0.0001) from
placebo. The superior efficacy of the triple combination could also be shown for 
all secondary endpoints such as time until reduction of pain intensity to 10 mm, 
weighted sum of pain intensity difference (%SPIDweighted), extent of impairment
of daily activities, global assessment of efficacy. All treatments were well
tolerated. The incidence of adverse events observed was low.

Publication Types: 
    Clinical Trial
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 16162254 [PubMed - indexed for MEDLINE]

1593: Expert Rev Neurother. 2005 Sep;5(5):653-61.

Migraine: new treatment options from molecular biology.

Stam AH, Haan J, Frants RR, Ferrari MD, van den Maagdenberg AM.

Department of Neurology, Leiden University Medical Centre, Leiden, 2300 RC
Leiden, The Netherlands. a.h.stam@lumc.nl

Migraine is a common, disabling, multifactorial, episodic neurovascular disorder 
of largely unknown etiology. The disease is typically characterized by recurrent 
attacks of headaches and associated autonomic and neurologic symptoms. Current
acute and prophylactic treatment options are far from optimal and in many cases, 
empirically chosen. Clearly, improved treatment is desperately needed. New drug
targets may emerge from molecular research as the unravelling of the molecular
basis of migraine should improve our understanding of the disease, notably why
patients experience attacks so frequently. The first two migraine genes
discovered in families with hemiplegic migraine encode ion transporters,
emphasising that dysfunction of ion transport may be an important factor in
migraine. Therefore, ion transporters can be considered as novel targets for the 
development of future antimigraine drugs. Molecular biologic research will
increasingly become important in understanding the pathophysiology of migraine
and in identifying potential molecular targets for novel treatments.

Publication Types: 
    Review

PMID: 16162089 [PubMed - indexed for MEDLINE]

1594: Expert Rev Neurother. 2005 Sep;5(5):635-42.

Psychiatric disorders and muscle tenderness in episodic and chronic migraine.

Mongini F, Deregibus A, Rota E.

Department of Clinical Pathophysiology, Headache and Facial Pain Unit, University
of Turin, 14 Corso Dogliotti, I-10126 Torino, Italy. franco.mongini@unito.it

This review first reports on the data concerning the relationship between
migraine and personality traits and psychiatric disorders. The relationship
between migraine and tenderness of the pericranial and cervical muscles is then
discussed. In one study, a psychologic assessment was performed in 56 women with 
migraine, and the Minnesota Multiphase Personality Inventory (MMPI) and State
Trait Anxiety Inventory were administered at baseline (T0) and after 6-7 years
(T2). Frequency, severity and duration of migraine were recorded at T0, after
treatment (T1) and at T2, and their relationship to the prevalence of depression,
MMPI and State Trait Anxiety Inventory data were examined. Pain parameters
improved in all patients in T0-1, but were higher at T2 in patients with
depression at T0. The patients whose migraine improved at T2 had significantly
lower MMPI and State Trait Anxiety Inventory scores at T0 and T2. Moreover, the
prevalence of depression of the patients whose migraine improved at T2 was 37.5% 
at T0 and decreased to 12.5% at T2. The authors subsequently studied the function
of the frontal lobe in 23 female patients previously treated for chronic migraine
and 23 controls by applying three neuropsychologic tests (gambling task, tower of
hanoi-3 and object alternation test). The patient group performed significantly
worse on the tower of hanoi-3 and the object alternation test. In order to assess
the extent to which muscle tenderness may relate to psychiatric disorders in
patients with migraine and tension-type headache, diagnosed according
International Headache Society criteria [2004], a psychologic assessment was
performed and palpation tenderness scores calculated for the pericranial and
cervical muscles in 459 patients. In total, 125 patients had frequent episodic
migraine, 97 had chronic migraine, 82 had frequent episodic tension-type headache
and chronic tension-type headache was present in 83. In a further 72 patients,
both episodic migraine and episodic tension-type headache were present. The main 
finding was a positive relationship between muscle tenderness and psychiatric
disorders in patients with episodic migraine alone or associated with episodic
tension-type headache.

Publication Types: 
    Review

PMID: 16162087 [PubMed - indexed for MEDLINE]

1595: Expert Rev Neurother. 2005 Sep;5(5):597-603.

Rizatriptan in migraine.

Krymchantowski AV, Bigal ME.

Instituto de Neurologia Deolindo Couto, Av das Americas 1155/1608 Barra Rio de
Janeiro, Brazil. abouchkrym@globo.com

The prevalence of migraine is high, affecting a significant proportion of the
adult population during their most productive years of life and promoting
impairment of their normal daily activities. Although guidelines for the acute
treatment of migraine are available, outcome parameters are sometimes still below
the expectations of both patients and physicians. Triptans represented an advance
in clinical practice and have become the most well-studied class of medication
for migraine. These agents present class I evidence for efficacy. However, they
differ with regard to several of their clinical parameters, including onset of
relief and consistency of response. Rizatriptan is a selective agonist of the
5-hydroxytryptophan(1B/1D )receptors, with proven superiority over placebo,
ergotamine and selected oral triptans, demonstrating a good profile of safety and
tolerability.

Publication Types: 
    Comparative Study
    Evaluation Studies
    Review

PMID: 16162083 [PubMed - indexed for MEDLINE]

1596: J Med Chem. 2005 Sep 22;48(19):5921-31.

Development of human calcitonin gene-related peptide (CGRP) receptor antagonists.
1. Potent and selective small molecule CGRP antagonists.
1-[N2-[3,5-dibromo-N-[[4-(3,4-dihydro-2(1H)-oxoquinazolin-3-yl)-1-piperidinyl]car
bonyl]-D-tyrosyl]-l-lysyl]-4-(4-pyridinyl)piperazine: the first CGRP antagonist
for clinical trials in acute migraine.

Rudolf K, Eberlein W, Engel W, Pieper H, Entzeroth M, Hallermayer G, Doods H.

Boehringer Ingelheim Pharma GmbH & Co. KG, Research Division, Birkendorfer
Strasse 65, 88397 Biberach/RISS, Germany.
klaus.rudolf@bc.boehringer-ingelheim.com

Although the triptans have greatly improved the acute treatment of migraine
headache, there are yet many shortcomings. Therefore, new strategies for the
treatment of migraine are needed which offer advantages over current therapy,
e.g. triptans. Our novel approach was based on the hypothesis that the release of
calcitonin gene-related peptide (CGRP) could play a causative role in migraine
headache. Thus we initiated a program aimed at the design and synthesis of small 
molecule CGRP receptor antagonists. High throughput screening led to the
identification of (R)-Tyr-(S)-Lys dipeptide-like compounds that showed weak but
unequivocal binding to the human CGRP receptor. Lead optimization afforded highly
potent CGRP antagonists, the prototype being compound 19 (BIBN4096). This
compound exhibiting a favorable biological profile was selected for initial
clinical trials. A proof of concept study indicated that intravenous application 
of 19 was effective in the treatment of acute migraine headache. This finding
strongly supports our initial working hypothesis that CGRP plays an important
role in the pathophysiology of migraine.

Publication Types: 
    In Vitro

PMID: 16161996 [PubMed - indexed for MEDLINE]

1597: Percept Mot Skills. 2005 Jun;100(3 Pt 2):1137-42.

Handedness, eyedness, and crossed hand-eye dominance in male and female patients 
with migraine with and without aura: a pilot study.

Aygül R, Dane S, Ulvi H.

Ataturk University.

The possible relationships of migraine to left-handedness and left-eyedness, as
well as sex and aura-related differences, were examined. 146 migraine patients (M
age=32.1 yr., SD=9.5) and 141 controls (M age=30.0 yr., SD=9.3) participated.
Hand preference was assessed by the modified version of the Edinburgh Handedness 
Inventory. Ocular dominance was measured by means of the near-far alignment test.
Migraine diagnoses were made on the basis of criteria provided from the
International Headache Society. In the overall sample and in women,
left-handedness and left-eyedness were not significantly correlated with
migraine. In men, the incidence of left-handedness and left-eyedness were
significantly higher in patients than in controls. The presence of aura in
patients with migraine was significantly associated with the incidence of
left-eyedness and crossed hand-eye dominance, but not handedness, for the total
sample and women. These results suggest that there may be a tendency towards
anomalous dominance, especially left-eyedness, in migraine patients particularly 
those with aura.

PMID: 16158700 [PubMed - indexed for MEDLINE]

1598: Curr Pain Headache Rep. 2005 Oct;9(5):363-7.

Management of migraine in children and adolescents in the emergency department
and inpatient setting.

Kabbouche MA, Linder SL.

Division of Neurology, Cincinnati Children's Hospital Medical Center, Headache
Center, MLC #2015, Cincinnati, OH 45229-3039, USA. marielle.kabbouche@cchmc.org

Migraine is a chronic disorder that can be debilitating, especially when the
attacks are severe and frequent. Children and adolescents are significantly
affected. The prevalence of migraine in this age group is higher than predicted
due to more recognition of the disease in this population throughout the past
century. Severe chronic migraine can cause failure in academic work and may lead 
to depression. Multiple medications are used to break an acute attack. Most
approaches are based on outpatient treatments and include the use of
over-the-counter medications and triptans and narcotics. This manuscript reviews 
most of the available therapies for acute treatment of primary headache that did 
not respond to outpatient management.

Publication Types: 
    Review

PMID: 16157067 [PubMed - indexed for MEDLINE]

1599: Curr Pain Headache Rep. 2005 Oct;9(5):345-50.

How do we diagnose migraine and childhood periodic syndromes?

Winner P.

Palm Beach Headache Center, Premiere Research Institute, Palm Beach Neurology,
Nova Southeastern University, West Palm Beach, FL 33407, USA. PWinner777@aol.com

Migraine remains substantially underdiagnosed and undertreated in the pediatric
population. The incidence and prevalence of migraine in the pediatric population 
is not fully appreciated. The recently revised International Headache Society
(IHS) criteria, The International Classification of Headache Disorders, is a step
in the right direction to improving our diagnostic accuracy. These criteria are
the basis for scientific studies and serve as the foundation for future research 
and clinical care. In this article, the diagnostic issues related to migraine and
childhood periodic syndromes in the IHS 2004 revisions are reviewed.

Publication Types: 
    Review

PMID: 16157064 [PubMed - indexed for MEDLINE]

1600: Neurol Res. 2005 Sep;27(6):647-52.

Analysis of chromosome 1 microsatellite markers and the FHM2-ATP1A2 gene
mutations in migraine pedigrees.

Curtain RP, Lea RA, Tajouri L, Haupt LM, Ovcaric M, MacMillan J, Griffiths LR.

Genomics Research Centre, School of Medical Science, Griffith University, Gold
Coast, Queensland, Australia.

OBJECTIVES: The aims of the study were: (i) to extend our linkage analysis of
chromosome 1q microsatellite markers in predominantly migraine with aura
pedigrees and (ii) to test the novel FHM-2 ATP1A2 gene for involvement in these
migraine affected pedigrees and a previous pedigree (MF14) showing evidence of
linkage of markers to C1q31.METHODS: A chromosome 1 scan (31 markers) was
performed in 21 multiplex pedigrees affected predominantly with migraine with
aura (MA). The known FHM-2 ATP1A2 gene mutations were tested, by sequencing, for 
the involvement in MA and migraine without aura (MO) in these pedigrees.
Sequencing was performed in the coding areas of the ATP1A2 gene through three MA 
individuals from MF14.RESULTS: Evidence for linkage was obtained at C1q23 to
markers spanning the ATP1A2 gene. However, testing of the known ATP1A2 gene
mutations (for FHM) in common migraine probands of pedigrees showing excess
allele sharing was negative. Sequencing of the entire coding areas of the gene
through all the three MA affected from MF14 was also negative for
mutations.DISCUSSION: Microsatellite markers on chromosome 1q23 show evidence of 
excess allele sharing in MA and some MO pedigrees, suggesting linkage to the
common forms of migraine and the presence of a susceptibility gene in this
region. The FHM-2 (ATP1A2 gene) does not seem to be involved in the common types 
of migraine. Despite certain clinical characteristics, the genetic correlation
between FHM and familial typical migraine remains unclear. Several candidate
genes lie within the C1q23 and C1q31 cytogenetic regions; therefore, further
studies are needed.

Publication Types: 
    Comparative Study

PMID: 16157018 [PubMed - indexed for MEDLINE]

1601: Pain. 2005 Oct;117(3):396-400.

Evaluation of the efficacy of intravenous acetaminophen in the treatment of acute
migraine attacks: a double-blind, placebo-controlled parallel group multicenter
study.

Leinisch E, Evers S, Kaempfe N, Kraemer C, Sostak P, Jürgens T, Straube A, May A.

Department of Neurology, University of Regensburg, Regensburg, Germany.

The efficacy of intravenous acetaminophen (1000mg) in the treatment of acute
migraine attacks as an alternative to parenteral application of lysine
acetylsalicylate or triptans was investigated, using a multi-center, randomized, 
double-blind, placebo controlled study design. Migraine diagnosis was made
according to the International Headache Society Classification. Sixty patients
were included in three headache outpatient centers (Neurology Departments of the 
Universities of Regensburg, Münster and München). In the acute migraine attack
patients were treated intravenously with either 1000mg paracetamol
(acetaminophen) or placebo. The primary end point was pain-free after 2h.
Secondary efficacy criteria were pain-free after 24h or pain relief after 2hours 
and after 24hours. With regard to the efficacy criteria, 37% of patients reported
pain relief or painfree after two hours, 12 patients after treatment with
acetaminophen and 10 patients after treatment with placebo. Out of these, 3
patients in the acetaminophen and 4 patients in the placebo group were painfree. 
After 24hours 86% of the patients reported pain relief: 24 treated with
acetaminophen and 27 treated with placebo. The results indicate, that 1000mg
intravenous acetaminophen is not superior to placebo in treating severe acute
migraine attacks.

Publication Types: 
    Comparative Study
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 16153780 [PubMed - indexed for MEDLINE]

1602: Complement Ther Med. 2005 Sep;13(3):165-74.

Biofeedback assisted diaphragmatic breathing and systematic relaxation versus
propranolol in long term prophylaxis of migraine.

Kaushik R, Kaushik RM, Mahajan SK, Rajesh V.

Department of Medicine, Himalayan Institute of Medical Sciences, Swami Rama
Nagar, Dehradun 248140, Uttaranchal, India. rmkaushik1@rediffmail.com

OBJECTIVES: To evaluate utility of biofeedback assisted diaphragmatic breathing
and systematic relaxation in migraine and to compare their efficacy with
propranolol in long term prophylaxis of migraine. METHODS: 192 migraine patients 
were randomly distributed into two groups. Propranolol group received propranolol
80 mg/day while biofeedback group received electromyogram (EMG) and temperature
biofeedback assisted diaphragmatic breathing and systematic relaxation training
accompanied by home practice for 6 months. RESULTS: Significant clinical response
was seen with biofeedback in 66.66% and with propranolol in 64.58% of patients.
Frequency, severity, duration of attacks and number of vomiting episodes were
significantly reduced in both the groups at 6 months but inter-group differences 
were statistically insignificant. During 1 year post-treatment period,
significantly lesser resurgence of migraine was seen in biofeedback group as
whole (9.37%) and in biofeedback responders in biofeedback group (9.37%) in
comparison to resurgence of migraine in propranolol group as whole (38.54%) and
in propranolol responders in propranolol group (53.22%) respectively.
CONCLUSIONS: Biofeedback assisted diaphragmatic breathing and systematic
relaxation were very useful in migraine and had significantly better long-term
prophylactic effect than propranolol in migraine.

Publication Types: 
    Clinical Trial
    Comparative Study
    Randomized Controlled Trial

PMID: 16150370 [PubMed - indexed for MEDLINE]

1603: Neurology. 2005 Nov 8;65(9):1415-8. Epub 2005 Sep 7.

Prevalence and size of directly detected patent foramen ovale in migraine with
aura.

Schwerzmann M, Nedeltchev K, Lagger F, Mattle HP, Windecker S, Meier B, Seiler C.

Department of Cardiology, University Hospital, Inselspital, CH-3010 Bern,
Switzerland.

BACKGROUND: Transcranial contrast Doppler studies have shown an increased
prevalence of right-to-left shunts in patients with migraine with aura compared
with controls. The anatomy and size of these right-to-left shunts have never been
directly assessed. METHODS: In a cross-sectional case-control study, the authors 
performed transesophageal contrast echocardiography in 93 consecutive patients
with migraine with aura and 93 healthy controls. RESULTS: A patent foramen ovale 
was present in 44 (47% [95% CI 37 to 58%]) patients with migraine with aura and
16 (17% [95% CI 10 to 26%]) control subjects (OR 4.56 [95% CI 1.97 to 10.57]; p <
0.001). A small shunt was equally prevalent in migraineurs (10% [95% CI 5 to
18%]) and controls (10% [95% CI 5 to 18%]), but a moderate-sized or large shunt
was found more often in the migraine group (38% [95% CI 28 to 48%] vs 8% [95% CI 
2 to 13%] in controls; p < 0.001). The presence of more than a small shunt
increased the odds of having migraine with aura 7.78-fold (95% CI 2.53 to 29.30; 
p < 0.001). Besides patent foramen ovale prevalence and shunt size, no other
echocardiographic differences were found between the study groups. Headache and
baseline characteristics did not differ in migraine patients with and without
shunt. CONCLUSIONS: Nearly half of all patients with migraine with aura have a
right-to-left shunt due to a patent foramen ovale. Shunt size is larger in
migraineurs than controls. The clinical presentation of migraine is identical in 
patients with and without a patent foramen ovale.

PMID: 16148260 [PubMed - indexed for MEDLINE]

1604: Acta Neurol Scand. 2005 Oct;112(4):259-64.

Hypertension in headache patients? A clinical study.

Pietrini U, De Luca M, De Santis G.

Headache Center, Department of Internal Medicine, University of Florence,
Florence, Italy. u.pietrini@libero.it

OBJECTIVES: The aim of the present study was to assess the prevalence of
hypertension in patients with headache, coming to the observation of an Headache 
Center. MATERIALS AND METHODS: A total of 1486 consecutive outpatients were
examined, and blood pressure was determined in all patients. RESULTS: Migraine
without aura (MO) was the most common diagnosis, followed by migraine associated 
with tension-type headache, migraine with aura (MA), episodic tension-type
headache (ETTH), chronic tension-type headache (CTTH), cluster headache (CH), and
medication-overuse headache (MOH). Hypertension was present in 28% of the
patients, and it was particularly common in MOH (60.6%), CTTH (55.3%), CH (35%), 
ETTH (31.4%), less common in MO (23%) and MA (16.9%). In all headache groups, the
prevalence of hypertension was higher than in the general population, within all 
age groups. After adjustment for age and gender, hypertension was found to be
more common in tension-type, and especially in CTTH, than in migraine. These
findings could be affected by 'Berkson's bias': and should not be extrapolated to
the general population, but apply only to the subpopulation of patients who come 
to the observation of an Headache Center, and who may have more disabling
symptoms. CONCLUSION: Hypertension could be one of the factors leading to
exacerbation of the frequency and severity of attacks, both in migraine and
tension-type headache. Hypertension has important therapeutic implications and
should be actively sought in headache patients, and more thoroughly investigated,
with ad-hoc surveys in the general population.

PMID: 16146497 [PubMed - indexed for MEDLINE]

1605: CNS Drugs. 2005;19(9):769-84.

Fixed drug combinations for the acute treatment of migraine : place in therapy.

Loder E.

Harvard Medical School, Pain and Headache Management Programs, Spaulding
Rehabilitation Hospital, Boston, Massachusetts 02114, USA.

Fixed drug combinations (FDCs) combine standardised doses of two or more drugs in
a single tablet, injection, nasal spray or suppository. FDCs may improve
treatment compliance, efficacy or tolerability through a variety of mechanisms.
At present, FDCs are commonly used in migraine treatment, and more are in
development. This systematic review identified 43 prospective trials of FDCs in
use for the acute treatment of migraine. Quantitative combination and analysis of
the data were not possible, but results of the review support the following
qualitative conclusions. First, many FDCs in use for the acute treatment of
migraine are older drugs. In these cases, clinical trial evidence that the FDC is
efficacious or has important advantages over its treatment components is lacking.
The benefits assumed for some common FDC ingredients such as caffeine and
metoclopramide are not clearly confirmed in these trials. Secondly, the use of
barbiturate-containing FDCs for the acute treatment of migraine is not evidence
based, and these drugs are frequently implicated in the development of dependence
or medication-induced headache syndromes. Thirdly, studied opioid-containing FDCs
are generally superior to placebo, but evidence regarding the safety and
tolerability of their repeated use in the treatment of migraine is lacking;
clinical experience dictates caution in the use of these agents. Fourthly,
ergotamine-containing FDCs are generally superior to placebo, but perform poorly 
in comparison with single-agent selective serotonin 5-HT(1B/1D) receptor agonists
('triptans'), NSAIDs or even isometheptene or opioid comparators, and are less
well tolerated. Fifthly, the most consistent and impressive evidence of benefit
is for NSAID-containing FDCs. These invariably outperform placebo and are
equivalent or superior to active comparators. Finally, with renewed interest in
the use of FDCs for the acute treatment of migraine, high-quality evidence of a
benefit for such treatments is emerging. An FDC containing a triptan and NSAID
seems most likely to provide efficacy and tolerability benefits in the acute
treatment of migraine. Such an FDC is in development but not yet approved for
use.

Publication Types: 
    Review

PMID: 16142992 [PubMed - indexed for MEDLINE]

1606: Rev Neurol (Paris). 2005 Jul;161(6-7):685-6.

Non pharmaceutical treatments for migraine.

Göbel H.

Kiel Neurological Pain Centre, Kiel, Germany. hg@schmerzklinik.de

The target of non-drug treatment of migraine is to reduce attack frequency and
intensity. To reach this goal, the general relationship between the patient and
the physician, i.e. the drug consumer and prescriber, has to be changed
fundamentally. To understand migraine attacks the patient must learn to
distinguish between the cause of migraine, a special readiness of the brain to
react, and the triggers of a headache attack. Today, we have access to effective 
methods that prevent inherited migraine from coming to an effect, or to
effectively arrest an attack if it has nevertheless broken out. There are three
available strategies: prevention by avoiding trigger factors, prevention via
reduction of attack readiness and treatment of the acute effects of the migraine 
attack.

Publication Types: 
    Review

PMID: 16141959 [PubMed - indexed for MEDLINE]

1607: Rev Neurol (Paris). 2005 Jul;161(6-7):679-80.

The treatment of acute migraine.

Olesen J.

Department of Neurology N39, University of Copenhagen, Glostrup Hospital,
Glostrup, Denmark.

A patient with migraine needs acute treatment as early as possible when the
attack occurs. The most frequently used drugs are non-steroidal anti-inflammatory
drugs and triptans. Ergotamine is less and less used. A new perspective has
developed since the demonstration of the efficacy of a CGRP antagonist. Using the
whole armamentarium, a satisfactory treatment for acute migraine attacks can
almost always be found, but several visits may be needed before acute treatment
for the individual patient is optimal.

Publication Types: 
    Review

PMID: 16141957 [PubMed - indexed for MEDLINE]

1608: Rev Neurol (Paris). 2005 Jul;161(6-7):677-8.

Female sex hormones and migraine.

MacGregor EA.

The City of London Migraine Clinic, London.
anne.macgregor@bartsandthelondon.nhs.uk

During the reproductive years migraine is three times more common in women than
in men. Although it is often assumed that this female preponderance is associated
with the additional trigger of fluctuating sex hormones of the menstrual cycle,
few studies have been undertaken to confirm or refute this. There is increasing
evidence confirming an association between estrogen 'withdrawal' and attacks of
migraine without aura, as well as evidence for an association between high
estrogen states and attacks of migraine with aura.

Publication Types: 
    Review

PMID: 16141956 [PubMed - indexed for MEDLINE]

1609: Rev Neurol (Paris). 2005 Jul;161(6-7):671-4.

The persistent foramen ovale and migraine.

Wilmshurst PT.

The Royal Shrewsbury Hospital, Shrewsbury, United-Kingdom.
peter.wilmshurst@rsh.nhs.uk

There is association between migraine, particularly migraine with aura, and large
persistent foramen ovale (PFO) and other right-to-left shunts. Migraine is often 
improved by closure of a PFO in patients who have a large shunt. Inheritance of
migraine is linked to the inheritance of large atrial shunts in some families.
The data indicate that in some patients PFOs play a causal role in migraine with 
aura. These observations may also improve understanding of the etiology of
migraine in patients who do not have a shunt.

Publication Types: 
    Review

PMID: 16141954 [PubMed - indexed for MEDLINE]

1610: Rev Neurol (Paris). 2005 Jul;161(6-7):661-5.

MRI findings in migraine.

Kruit MC, Launer LJ, van Buchem MA, Terwindt GM, Ferrari MD.

Department of Radiology, Leiden University Medical Center, Leiden, the
Netherlands. m.c.kruit@lumc.nl

INTRODUCTION: For long time, migraine has been considered to be an episodic,
multifactorial, neurovascular disorder, without long-term consequences to the
brain, although an association between migraine and clinical stroke and white
matter hyperintense lesions has been suggested in numerous studies. Due to
various methodological problems no definite conclusion could be drawn from these 
studies. STATE OF THE ART: Recently, data from a population-based cross-sectional
MRI study were published, establishing migraine to be a true and independent risk
factor for white matter lesions (in female migraine patients) and subclinical
posterior circulation territory infarcts. PERSPECTIVES: The methodology and
results of previous investigations of a relationship between migraine and
clinical ischemic stroke, silent infarction and white matter lesions are
reviewed, and integrated in the results from the new population-based MRI study. 
CONCLUSION: Brain infarction occurs far more frequently than expected in migraine
patients, most pronounced in migraine with aura (8 percent have subclinical
cerebellar infarcts), although most infarcts remain clinically silent. Female
migraine patients are at increased risk of deep white matter lesions, independent
of the effects of cardiovascular risk factors. The influence of migraine severity
(attack frequency) on the risk of both types of lesions suggests a causal
relationship between migraine severity and lesion load. Future studies are needed
to assess whether these (probably) ischemic lesions have relevant (long-term)
functional correlates.

Publication Types: 
    Review

PMID: 16141952 [PubMed - indexed for MEDLINE]

1611: Rev Neurol (Paris). 2005 Jul;161(6-7):658-60.

Effects of sensitization of trigeminovascular neurons to triptan therapy during
migraine.

Burstein R, Levy D, Jakubowski M.

Department of Anesthesia and Critical Care, Beth Israel Deaconess Medical Center,
Harvard Medical School, Boston, USA. rburstei@caregroup.harvard.edu

Migraine is a neurological disorder which leads to recurring, unilateral,
throbbing headache, associated with variable incidence of aura (i.e., visual,
sensory and motor function disturbances), nausea and vomiting, photophobia and
phonophobia, fatigue, and enhanced irritability. We have recently shown that
migraine headache is also associated with high incidence of ipsilateral cutaneous
allodynia, particularly in periorbital and temporal skin areas. Patients who
experience cutaneous allodynia during migraine feel that their skin hurts in
response to otherwise innocuous activities such as combing, shaving, taking a
shower, or wearing glasses or earrings. Here, we present evidence to support the 
view that the development of throbbing in the initial phase of migraine is
mediated by sensitization of peripheral trigeminovascular neurons that innervate 
the meninges, and that the development and maintenance of cutaneous allodynia
later in the attack is propelled by sensitization of central trigeminovascular
neurons which receive converging sensory input from the meninges as well as from 
the scalp and facial skin. We also present evidence that the development of
cutaneous allodynia during migraine is detrimental to termination of acute
migraine attacks using triptans (5HT1B/1D receptor agonist).

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.
    Review

PMID: 16141951 [PubMed - indexed for MEDLINE]

1612: Rev Neurol (Paris). 2005 Jul;161(6-7):655-7.

The emerging importance of cortical spreading depression in migraine headache.

Bolay H, Moskowitz MA.

Department of Neurology, Gazi University Hospitals, Ankara, Turkey.

Migraine is a disabling neurovascular disorder with a complex pathophysiology.
Functional imaging and magneto encephalographic studies strongly suggest that
Cortical Spreading Depression (CSD) constitutes the biological basis for the
neurologic aura that precedes headache in one fourth of migrainers. It is likely 
that the aura is the generator of the headache since experimentally, CSD triggers
the activation of the trigeminovascular system, possibly through matrix
metalloproteases activation which is associated with an increase in vascular
permeability. These data may have therapeutic implications: strategies to block
trigeminal activation or its downstream consequences are central to treat the
acute headache whereas strategies to block events lying upstream of trigeminal
activation would be crucial in prophylaxis.

Publication Types: 
    Review

PMID: 16141950 [PubMed - indexed for MEDLINE]

1613: Curr Neurol Neurosci Rep. 2005 Sep;5(5):376-81.

Visual disturbances and migraine.

Maxner CE, Moeller JJ.

Room 3819, Halifax Infirmary, Queen Elizabeth II Health Sciences Centre, 1796
Summer Street, Halifax, Nova Scotia B3H 3A7, Canada. cmaxner@dal.ca

There is a close relationship between headache and the visual system. Visual
symptoms are prominent features of clinical syndromes such as migraine, cluster
headache, and the trigeminal autonomic cephalgias. There are also strong links
between headache and the visual system on the basis of genetics, molecular
biology, neurophysiology, and neuroimaging. Studies of these links are leading to
the development of novel therapies for a variety of headache syndromes. This
review is designed to summarize the most recent literature on headache and the
visual system. A particular emphasis is placed on publications of interest to
clinicians.

Publication Types: 
    Review

PMID: 16131420 [PubMed - indexed for MEDLINE]

1614: Med Sci Monit. 2005 Sep;11(9):PI65-9. Epub 2005 Aug 26.

Gelstat Migraine (sublingually administered feverfew and ginger compound) for
acute treatment of migraine when administered during the mild pain phase.

Cady RK, Schreiber CP, Beach ME, Hart CC.

Clinvest, Inc., Springfield and Headache Care Center, Springfield, Missouri, USA.
rcady@primarycarenet.org

BACKGROUND: Treatment of migraine headaches is often delayed due to assessing the
potential severity of an evolving headache or anticipating unwanted consequences 
from prescription medication. Studies have demonstrated improved pain-free
response when prescription treatments are taken during the mild headache phase of
a migraine. This study was designed to evaluate the efficacy of an OTC product,
GelStat Migraine, when taken in the early, mild pain phase of migraine.
MATERIAL/METHODS: An open-label study enrolling 30 subjects, male and female,
with a one-year history of migraine meeting IHS diagnostic criteria with or
without aura, 2-8 migraines per month and < or = 15 headache days per month.
Inclusion required having migraines that consistently started at mild and
worsened to moderate or severe, if untreated, in at least 75% of attacks.
Subjects also had to be able to distinguish migraine from non-migraine headaches 
and reliably identify migraine early in the course of an attack. One headache was
treated in the mild pain phase with GelStat Migraine, a combination of feverfew
and ginger. RESULTS: 29 evaluable subjects completed the study, all treating at
mild pain. Two hours after treatment, 48% were pain-free with 34% reporting a
headache of only mild severity. 29% reported a recurrence within 24 hours. Side
effects were minimal and not serious. 59% of subjects were satisfied with Gelstat
Migraine therapy and 41% preferred GelStat Migraine or felt it was equal to their
pre-study medication. CONCLUSIONS: GelStat Migraine is effective as a first line 
abortive treatment for migraine when initiated early during the mild headache
phase.

Publication Types: 
    Clinical Trial
    Research Support, Non-U.S. Gov't

PMID: 16127373 [PubMed - indexed for MEDLINE]

1615: Invest Ophthalmol Vis Sci. 2005 Sep;46(9):3221-6.

Evidence for association of endothelial nitric oxide synthase gene in subjects
with glaucoma and a history of migraine.

Logan JF, Chakravarthy U, Hughes AE, Patterson CC, Jackson JA, Rankin SJ.

Department of Ophthalmology, The Royal Group of Hospitals, Belfast, N. Ireland,
United Kingdom. joanne.logan1@btopenworld.com

PURPOSE: There is evidence to suggest that vasospasm and vascular dysregulation
play a role in the etiology of glaucoma. This effect may be particularly relevant
in patients with glaucoma who have a history of migraine or vasospastic
tendencies. This study was conducted to investigate the role of genes with
products that regulate blood flow to ocular tissues. The candidate genes were the
two isoforms of nitric oxide synthase (NOS), NOS3 and -2A, and endothelin (ET)-l.
The frequency of the T786C mutation in NOS3 was also examined. METHODS: DNA was
obtained from 58 patients with primary open-angle glaucoma (POAG), 76 with normal
tension glaucoma (NTG), and 38 control subjects. Polymerase chain reactions (PCR)
were used to compare the frequency of the alleles between the subjects with
glaucoma and the control subjects and the subjects with glaucoma with vasospasm
or migraine. The PCR product was sequenced to identify the frequency of the T786C
mutation. RESULTS: The distribution of the NOS3 repeat alleles in subjects with
glaucoma and control subjects just failed to reach statistical significance (P = 
0.06). The distribution in subjects with NTG or POAG did not differ
significantly. A significant difference was found (P < 0.001) in the distribution
of allele frequencies of the NOS3 marker in subjects who had glaucoma with
migraine versus control subjects. There were no differences in the distribution
of the NOS2A or ET-1 markers between the subjects with glaucoma and the control
subjects. CONCLUSIONS: This study provides evidence of an association between the
NOS3 gene and subjects with glaucoma who have a history of migraine. Unlike in
other studies, no evidence was found of an association between ET-1 and glaucoma.

PMID: 16123422 [PubMed - indexed for MEDLINE]

1616: Hum Reprod. 2005 Dec;20(12):3423-8. Epub 2005 Aug 25.

Estradiol supplementation modulates neuroendocrine response to
M-chlorophenylpiperazine in menstrual status migrainosus triggered by oral
contraception-free interval.

Nappi RE, Sances G, Brundu B, De Taddei S, Sommacal A, Ghiotto N, Polatti F,
Nappi G.

Research Centre for Reproductive Medicine, University of Pavia, Italy.
renappi@tin.it

BACKGROUND: Migraine triggered by oral contraception (OC)-free interval is very
common and may be extremely severe, long-lasting and poorly responsive to
analgesics (status migrainosus). The serotoninergic (5-HT) system is crucially
involved in pain threshold and it is sensitive to estradiol (E2). Therefore, we
aimed to assess neuroendocrine correlates of OC status migrainosus in response to
the direct central 5-HT agonist meta-chlorophenylpiperazine (m-CPP) and to test
the effect of transdermal E2 supplementation of the OC-free interval. METHODS:
Clinical investigative protocol, single-blinded placebo-controlled treatment.
Oral m-CPP (0.5 mg/kg body weight) challenge test was performed in 10 patients
with status migrainosus occurring within 48 h of the discontinuation of a
monophasic pill (30 microg of ethinyl estradiol and 150 microg of desogestrel)
and in six healthy women assuming the same OC as controls. In a consecutive
menstrual cycle, patients with OC status migrainosus underwent to the same test
after they were blindly treated with 2.0 g of percutaneous E2 gel or placebo
daily during the pill-free interval. Plasma prolactin and cortisol levels and
clinical characteristics of migraine attacks were evaluated. RESULTS: Women with 
OC-status migrainosus showed a derangement of prolactin release (F = 4.8; P <
0.01) and a lack of cortisol response (F = 5.8; P < 0.001) after m-CPP in
comparison with controls. Transdermal E2 during the pill-free interval
significantly restored prolactin (F = 2.8; P < 0.01) and cortisol responses (F = 
18.9; P < 0.001) against placebo and positively affected the duration (P <
0.001), the number of hours in which pain intensity prohibits daily activity (P <
0.001), the episodes of vomiting (P < 0.001) and the consumption of analgesics (P
< 0.001). CONCLUSIONS: Status migrainosus triggered by OC-free interval is
associated with impaired prolactin and cortisol responses following m-CPP
challenge. Transdermal E2 supplementation is able to restore neuroendocrine
response to this specific 5-HT agent, exerting a positive clinical effect on the 
course of menstrually related migraine.

Publication Types: 
    Clinical Trial
    Research Support, Non-U.S. Gov't

PMID: 16123089 [PubMed - indexed for MEDLINE]

1617: Nat Rev Drug Discov. 2005 Sep;4(9):741-50.

Can we develop neurally acting drugs for the treatment of migraine?

Goadsby PJ.

Headache Group, Institute of Neurology, and The National Hospital for Neurology
and Neurosurgery, Queen Square, London WC1N 3BG, UK. peterg@ion.ucl.ac.uk

Serotonin (5-HT)(1B/1D) receptor agonists, which are also known as triptans,
represent the most important advance in migraine therapeutics in the four
millennia that the condition has been recognized. The vasoconstrictive activity
of triptans produced a small clinical penalty in terms of coronary
vasoconstriction but also raised an enormous intellectual question: to what
extent is migraine a vascular problem? Functional neuroimaging and
neurophysiological studies have consistently developed the theme of migraine as a
brain disorder and, therefore, demanded that the search for neurally acting
antimigraine drugs should be undertaken. The prospect of non-vasoconstrictor
acute migraine therapies, potential targets for which are discussed here, offers 
a real opportunity to patients and provides a therapeutic rationale that places
migraine firmly in the brain as a neurological problem, where it undoubtedly
belongs.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 16121129 [PubMed - indexed for MEDLINE]

1618: Epileptic Disord. 2005 Sep;7 Suppl 1:S27-33.

Erratum in:
    Epileptic Disord. 2008 Jun;10(2):191.

Epilepsy and common comorbidities: improving the outpatient epilepsy encounter.

Gilliam FG, Mendiratta A, Pack AM, Bazil CW.

Department of Neurology, Neurological Institute, Columbia University, New York,
NY 10032, USA. fgilliam@neuro.columbia.edu

Epilepsy is a chronic disorder that has been associated with other specific
health problems. Evidence from recent clinical and basic investigations indicates
that aspects of cerebral dysfunction associated with a lowered seizure threshold 
may also predispose toward other disorders such as depression, cognitive
impairment, sleep disorders, and migraine. Similarly, certain types of brain
injury may also increase the risk of adverse antiepileptic drug (AED) effects.
For example, a history of febrile seizures is associated with a three fold
increase in the occurrence of negative psychiatric effects of two newer AEDs.
Poor fitness and obesity are also reported at higher rates in epilepsy. Some
comorbid conditions in epilepsy, such a depression and anxiety, may have a
greater influence on subjective health status than does seizure rate. Management 
strategies employed in the outpatient clinic to maximize overall health outcomes 
should include screening and treatment for the commonly coexistent conditions in 
persons with epilepsy.

Publication Types: 
    Research Support, N.I.H., Extramural
    Review

PMID: 16120491 [PubMed - indexed for MEDLINE]

1619: Eur J Paediatr Neurol. 2005;9(5):333-8. Epub 2005 Aug 24.

Sodium Valproate versus Propranolol in paediatric migraine prophylaxis.

Ashrafi MR, Shabanian R, Zamani GR, Mahfelati F.

Department of Pediatric Neurology, Tehran University of Medical Sciences,
Children's Medical Center, 62 Gharib Street, 14194 Tehran, Iran.

In a randomized clinical trial the effect of Sodium Valproate in pediatric
migraine prophylaxis was compared with that of Propranolol. One hundred and
twenty patients with common migraine (migraine without aura) aged from 3 to 15
years who met the defined criteria enrolled into the study. Randomly the patients
were divided in two groups of A and B, treating with sodium Valproate and
Propranolol, respectively. Three phases of baseline period (phase I), titration
and adjustment period (phases II) and fixed -dose treatment period (phase III)
have been designed. A total of 57 patients in group A, and 58 patients in group B
completed all phases of the trial. Seventy two percent of patients in group A and
69% of patients in group B have responded to Sodium Valproate and Propranolol,
respectively, as a reduction of more than 50% in headache frequency per month.
Further more both drugs have shown efficacy in reducing the severity and duration
of headache and also better response to rescue medications (p value <0.01). There
was no significant difference in all previously mentioned therapeutic effects
between two groups (p value <0.05).

Publication Types: 
    Multicenter Study
    Randomized Controlled Trial

PMID: 16120482 [PubMed - indexed for MEDLINE]

1620: Neurology. 2005 Aug 23;65(4):620-2.

Summary for patients in:
    Neurology. 2005 Aug 23;65(4):E9-10.

Effect of tryptophan depletion on symptoms of motion sickness in migraineurs.

Drummond PD.

School of Psychology, Murdoch University, Perth 6150, Western Australia.
p.drummond@murdoch.edu.au

Seven hours after 39 migraineurs and 37 controls consumed an amino acid drink
that contained or omitted l-tryptophan (thereby reducing brain serotonin
synthesis), motion sickness was provoked by the visual illusion of movement.
Tryptophan depletion boosted dizziness, nausea, and the illusion of movement in
controls to levels that approached those of migraineurs. Thus, reduced brain
serotonin activity may promote vestibuloocular disturbances during motion
sickness and attacks of migraine.

Publication Types: 
    Comparative Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 16116130 [PubMed - indexed for MEDLINE]

1621: Neurology. 2005 Aug 23;65(4):580-5.

Prognosis of migraine and tension-type headache: a population-based follow-up
study.

Lyngberg AC, Rasmussen BK, Jørgensen T, Jensen R.

Research Centre for Prevention and Health, Glostrup University Hospital, Nordre
Ringvej 57, Building 84/85, DK-2600 Glostrup, Denmark.
anchly01@glostruphosp.kbhamt.dk

OBJECTIVE: To determine the prognosis of migraine and tension-type headache and
to identify prognostic factors. METHODS: Of 740 persons (aged 25 to 64 years)
examined in a 1989 Danish cross-sectional headache study, 673 were eligible for
follow-up in 2001. All interviews at baseline and at follow-up were conducted by 
medical doctors and based on the 1988 IHS-criteria. RESULTS: A total of 549
persons (81.6%) participated in the follow-up study. Of 64 migraineurs at
baseline, 42% had experienced remission, 38% had low migraine frequency, and 20% 
had more than 14 migraine days per year (poor outcome) at follow-up. Poor outcome
was associated with high migraine frequency at baseline and age at onset younger 
than 20 years. Among 146 subjects with frequent episodic tension-type headache
and 15 with chronic tension-type headache at baseline, 45% experienced infrequent
or no tension-type headache (remission), 39% had frequent episodic tension-type
headache, and 16% experienced chronic tension-type headache (poor outcome) at
follow-up. Poor outcome was associated with baseline chronic tension-type
headache, coexisting migraine, not being married, and sleeping problems.
CONCLUSIONS: The prognosis of migraine, frequent episodic tension-type headache, 
and chronic tension-type headache was favorable.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16116119 [PubMed - indexed for MEDLINE]

1622: Neurology. 2005 Aug 23;65(4):E9-10.

Original report in:
    Neurology. 2005 Aug 23;65(4):620-2.

Both migraine and motion sickness may be due to low brain levels of serotonin.

Brey RL.

Scientists believe that low levels of a brain chemical called serotonin may make 
people susceptible to developing migraine headaches. Many people with migraine
also have a problem with motion sickness, but it is not clear why this might be. 
We know that many drugs to treat motion sickness increase brain levels of
serotonin, an important brain chemical. It is possible that low brain levels of
serotonin may also be responsible for motion sickness. In this issue of
Neurology, Drummond reports on a study that evaluated whether low brain levels of
serotonin trigger motion sickness in people with and without migraine. More
information about migraine can be found on the next page.

Publication Types: 
    Patient Education Handout

PMID: 16116103 [PubMed - indexed for MEDLINE]

1623: Aust Fam Physician. 2005 Aug;34(8):647-51.

Migraine and tension headache--a complementary and alternative medicine approach.

Woolhouse M.

michellewoolhouse@hotmail.com

BACKGROUND: Migraine and tension headache are common--affecting up to 10% and 40%
of the Australian population respectively--and result in significant reduction in
social activities and work capacity for sufferers. OBJECTIVE: This article
considers the evidence for the use of a range of complementary therapies and
treatment in the prevention and management of both migraine and tension headache.
DISCUSSION: Migraine and tension headache can have many precipitating factors.
Considering dietary and environmental factors complements a migraine/headache
consultation. There is evidence for the role of mind-body approaches, nutritional
supplements such as riboflavin and magnesium, and acupuncture in the treatment of
headache. By using a holistic approach we may be able to tailor a treatment
program that is both effective and safe.

Publication Types: 
    Review

PMID: 16113701 [PubMed - indexed for MEDLINE]

1624: Aust Fam Physician. 2005 Aug;34(8):627-32.

Migraine--diagnosis and treatment.

Joubert J.

Epworth and Royal Melbourne Hospitals, Victoria, Australia.

BACKGROUND: Migraine is a genetically determined recurrent pain syndrome
accompanied by neurological and gastrointestinal features, involving interaction 
of external triggers and internal pathophysiology and the cause of considerable
disability to sufferers. OBJECTIVE: This article discusses the pathophysiology
and diagnosis of migraine and outlines a patient centred approach to
management.DISCUSSION: Establishing the correct diagnosis is essential for
success. Discussing a structured approach ("a puff, a gust, and a gale") in the
recognition of a developing migraine attack can assist patients in appropriate
self management. A "stepped care" approach to management of acute migraine
involves initial nonpharmacological methods followed by antiemetics and simple
analgesics or nonsteroidal anti-inflammatory medications. Moderate episodes are
treated with antiemetics and migraine specific medications. More severe migraines
often require parenteral medications and sometimes intravenous fluids.
Prophylaxis involves adoption of a chronic disease model, identifying and
avoiding triggers and causative factors for migraine, nonpharmacological methods 
such as dietary modification and biofeedback, and for some patients,
pharmacological prophylaxis.

Publication Types: 
    Review

PMID: 16113698 [PubMed - indexed for MEDLINE]

1625: Hum Mutat. 2005 Oct;26(4):315-21.

Rare missense variants in ATP1A2 in families with clustering of common forms of
migraine.

Todt U, Dichgans M, Jurkat-Rott K, Heinze A, Zifarelli G, Koenderink JB, Goebel
I, Zumbroich V, Stiller A, Ramirez A, Friedrich T, Göbel H, Kubisch C.

Institut für Humangenetik, Universitätsklinikum Bonn, Bonn, Germany.

Migraine is a recurrent neurovascular disease. Its two most common forms-migraine
without aura (MO) and migraine with aura (MA)-both show familial clustering and a
complex pattern of inheritance. Familial hemiplegic migraine (FHM) is a rare
monogenic subform caused by mutations in the calcium channel gene CACNA1A or the 
Na(+)/K(+)-ATPase gene ATP1A2. An involvement of FHM genes in the pathogenesis of
common forms of migraine is not proven. We therefore systematically screened
ATP1A2 in families with several members affected by MA and/or MO. We identified
two novel missense alterations [c.520G>A (p.E174 K) and c.1544G>A (p.C515Y)] in
two out of 45 families, which were not found in 520 control chromosomes.
Functional studies of these variants in Xenopus oocytes by two-electrode voltage 
clamp measurements and radiochemical determination of ATPase activity showed that
C515Y leads to a complete loss of function comparable with the effect of
FHM-mutations whereas for E174 K no functional alteration could be found in the
in vitro assays. In conclusion we propose that rare variants in ATP1A2 are
involved in the susceptibility to common forms of migraine, because of 1) the
absence of alterations in controls, 2) the particular pattern of segregation in
both families, 3) the high conservation of mutated residues in
Na(+)/K(+)-ATPases, 4) the functional effect of C515Y, and 5) the involvement of 
ATP1A2 in a monogenic form of migraine. (c) 2005 Wiley-Liss, Inc.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 16110494 [PubMed - indexed for MEDLINE]

1626: Lancet Neurol. 2005 Sep;4(9):533-42.

Relation between migraine and stroke.

Bousser MG, Welch KM.

Hôpital Lariboisière, Service de Neurologie, Paris, France.
mg.bousser@lrb.aphp.fr

A complex bidirectional relation between migraine, mostly migraine with aura
(MA), and ischaemic stroke is known. A cerebral infarction can occur during a MA,
and MA is a risk factor for ischaemic stroke, particularly in young women.
Conversely, cerebral ischaemia can induce MA. Both ischaemic stroke and MA might 
be consequences of many underlying vascular disorders. Despite the relation
between migraine and stroke, migraine as a primary headache disorder is mostly
benign.

Publication Types: 
    Review

PMID: 16109360 [PubMed - indexed for MEDLINE]

1627: Int J Psychophysiol. 2005 Sep;57(3):203-10. Epub 2005 Apr 14.

Visually evoked phase synchronization changes of alpha rhythm in migraine:
correlations with clinical features.

de Tommaso M, Marinazzo D, Guido M, Libro G, Stramaglia S, Nitti L, Lattanzi G,
Angelini L, Pellicoro M.

TIRES: Center of Innovative Technologies for Signal Detection and Processing,
Bari, Italy. m.detommaso@neurol.uniba.it

OBJECTIVE: This study aimed to compute phase synchronization of the alpha band
from a multichannel electroencephalogram (EEG) recorded under repetitive flash
stimulation from migraine patients without aura. This allowed examination of
ongoing EEG activity during visual stimulation in the pain-free phase of
migraine. METHODS: Flash stimuli at frequencies of 3, 6, 9, 12, 15, 18, 21, 24,
and 27 Hz were delivered to 15 migraine patients without aura and 15 controls,
with the EEG recorded from 18 scalp electrodes, referred to the linked earlobes. 
The EEG signals were filtered in the alpha (7.5-13 Hz) band. For all stimulus
frequencies that we evaluated, the phase synchronization index was based on the
Hilbert transformation. RESULTS: Phase synchronization separated the patients and
controls for the 9, 24 and 27 Hz stimulus frequencies; hyper phase
synchronization was observed in patients, whereas healthy subjects were
characterized by a reduced phase synchronization. These differences were found in
all regions of the scalp. CONCLUSIONS: During migraine, the brain synchronizes to
the idling rhythm of the visual areas under certain photic stimulations; in
normal subjects however, brain regions involved in the processing of sensory
information demonstrate desynchronized activity. Hypersynchronization of the
alpha rhythm may suggest a state of cortical hypoexcitability during the
interictal phase of migraine. SIGNIFICANCE: The employment of non-linear EEG
analysis may identify subtle functional changes in the migraine brain.

Publication Types: 
    Comparative Study

PMID: 16109290 [PubMed - indexed for MEDLINE]

1628: Headache. 2005 Sep;45(8):1083-7.

Tinnitus in migraine: an allodynic symptom secondary to abnormal cortical
functioning?

Volcy M, Sheftell FD, Tepper SJ, Rapoport AM, Bigal ME.

The New England Center for Headache, Stanford, Connecticut 06902, USA.

Tinnitus is not a common auditory symptom in migraine. Recent research suggests
that central sensitization (CS) develops in most migraneurs during the course of 
a migraine attack. Herein we describe 3 patients with primary headache disorders 
and tinnitus as their chief complaint, in whom the tinnitus intensity
consistently increased during headache attacks. In headache patients, tinnitus
may be related to spontaneous and aberrant neural activity at any level along the
auditory axis, with abnormal reorganization processes in the auditory cortex
following hearing receptor damage. We hypothesize that the tinnitus intensity
increase could be an allodynic symptom related to CS, or alternatively could be
associated with cortical hyperexcitability.

Publication Types: 
    Case Reports
    Research Support, Non-U.S. Gov't

PMID: 16109127 [PubMed - indexed for MEDLINE]

1629: Headache. 2005 Sep;45(8):1061-8.

Enhanced trigemino-cervical-spinal reflex recovery cycle in pain-free
migraineurs.

Serrao M, Perrotta A, Bartolo M, Fiermonte G, Pauri F, Rossi P, Parisi L,
Pierelli F.

Department of Neurology and Otolaryngology, University of Rome, Italy.

OBJECTIVE: To evaluate trigemino-cervical-spinal reflexes (TCSRs) in a group of
migraine patients during the pain-free period. BACKGROUND: TCRSs are part of a
complex nocifensive response involving the cervical and the upper limb muscles,
and are modulated by supraspinal inhibitory pathways; it may, thus, be possible
to use TCRSs to explore the trigeminal system in migraineurs. METHODS: A total of
43 migraine patients without aura (MWoA, 32 patients) or with typical aura (MWA, 
11 patients) and 30 age- and sex-matched healthy subjects took part in the study.
TCRSs were obtained by stimulating the supraorbital nerve and recorded from the
semispinalis capitis muscle and the biceps brachii. The latency (L, msec), area
(A, mVms) and recovery cycle of the reflexes were recorded. The effects of
heterotopic painful stimulation on the neurophysiological parameters were studied
by a validated cold pressor test (CPT). RESULTS: No significant changes were
found between either migraine patients and controls or MWoA and MWA patients in
the mean values in the L and A of TCRSs (t-test, P > .05). The recovery curve of 
the trigemino-cervical reflexes (TCRs) was significantly faster in migraine
patients than in controls, while no differences were found in the
trigemino-spinal reflexes (TSRs) (t-test, P < .01). Activation of the diffuse
inhibitory controls through the CPT induced a significant reduction in the TCRs
and TSRs area in both migraine patients and controls (paired t-test, P < .01),
though the extent of this reduction did not differ significantly between
migraineurs and controls (t-test, P > .05). COMMENTS: Our data suggest that the
pain-free period in migraine patients is characterized by a hyperexcitability of 
the trigeminal pathways and of their anatomical and functional connections with
the upper cervical cord neurons, and that this abnormal hyperexcitability does
not appear to be due to a lack of a supraspinal inhibitory modulation.

Publication Types: 
    Comparative Study

PMID: 16109121 [PubMed - indexed for MEDLINE]

1630: Headache. 2005 Sep;45(8):1056-60.

Serotonin transporter gene polymorphism and migraine in the Korean population.

Kim WK, Kim HS, Kim WJ, Lee KY, Park H, Kim CH, Kim SJ, Choi YC.

Department of Neurology, Hallym University, Kangdong Sacred Heart Hospital, Seoul
Korea.

OBJECTIVE: To evaluate the association between a serotonin (5-HT) transporter
gene polymorphism and migraines in Koreans. BACKGROUND: The 5-HT metabolism is
believed to play an important part in the pathophysiology of migraines, and a
polymorphism of the serotonin transporter (5-HTT) promoter region might influence
5-HTT expression and serotonin uptake. METHODS: This study compared 52 patients
with migraine and 170 healthy control subjects in order to determine the
association between a polymorphism of the 5-HTT gene-linked polymorphic region
(5-HTTLPR) and migraine. Using PCR techniques, the products of the 484-base pair 
(bp) fragments were denoted as being short alleles (s) and those of 528 bp as
being long (l). RESULTS: The genotype distribution of the healthy controls was
s/s (56.5%), s/l (38.2%), and l/l (5.3%) and that of the patients with migraine
was 65.4%, 30.8%, and 3.8%, respectively. No significant differences were noted
in the genotype and allele frequencies of 5-HTTLPR between the patients with
migraine and the control subjects. CONCLUSIONS: A 5-HTTLPR polymorphism does not 
appear to be involved in the genetic predisposition to migraines.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 16109120 [PubMed - indexed for MEDLINE]

1631: Headache. 2005 Sep;45(8):1048-55.

Burden of illness and satisfaction with care among patients with headache seen in
a primary care setting.

Harpole LH, Samsa GP, Matchar DB, Silberstein SD, Blumenfeld A, Jurgelski AE.

Duke University Medical Center, Department of Medicine, Durham, NC 27705, USA.

OBJECTIVE: To assess the current level of headache burden and the headache
management needs at three diverse clinical sites. BACKGROUND: Headache is a
common disabling disorder that is costly for the patient and a management
challenge for physicians. The determination of whether and how to intervene to
improve headache management depends on both the burden of disease and the
characteristics of patients that would likely be targeted. METHODS: Patients from
three healthcare organizations were identified by administrative records as
having either migraine or tension-type headache and then mailed a survey that
addressed demographics, headache type, headache-related disability, depression
and anxiety, satisfaction with care, general health, worry about headache,
problems with headache management, and healthcare utilization. Comparisons were
made across sites and between patients with more and less severe headache-related
impairments. RESULTS: Of the 789 patients contacted, 385 (50%) returned a survey.
While the socio-demographic characteristics of the patients were diverse,
headache-related characteristics were similar. These patients have significant
problems with headache management, disability, pain, worry, and dissatisfaction
with care. Patients who described higher headache-related impairment experienced 
significantly greater problems in these areas, perceived themselves to be in
worse general health, and had significantly greater use of medical services than 
those with lower headache severity. CONCLUSIONS: Despite various elements of
heterogeneity, we observed across the sites a consistent need for improvement in 
headache management. Future efforts should be directed at developing and
evaluating methods for effectively improving headache management.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16109119 [PubMed - indexed for MEDLINE]

1632: Headache. 2005 Sep;45(8):1038-47.

Migraine pain location: a tertiary care study of 1283 migraineurs.

Kelman L.

Headache Center of Atlanta, GA 30342, USA.

OBJECTIVES: This study of headache location in migraine was performed (1) to
document the location of pain in a large group of migraine patients and (2) to
assess the impact of different types of migraine, gender, aura, and headache
features on the location of the headache. BACKGROUND: The literature documenting 
the location of the pain of acute attack of migraine is sparse. METHODS: A total 
of 1283 migraine patients (ICHD, 2004, 1.1, 1.2, 1.5.1, and 1.6) were evaluated
at the 1st visit. Headache location and character were graded on a scale of 0 to 
3 with 0 being none and 3 the most. Triggers were graded on a frequency scale of 
0 to 3; 0 = none; 1 = less than 1/3 of time; 2 = between 1/3 and 2/3 of time; 3 =
greater than 2/3 of time. Other headache features and medication responsiveness, 
were also recorded. Patients were stratified by migraine type and headache
frequency. Combined and isolated locations, and the impact of age, gender,
headache frequency, migraine types, and aura were addressed. Unremitting headache
was excluded. RESULTS: Migraine patients reported that the highest location
frequencies were in the eyes (67.1%), temporal (58.0%), and frontal (55.9%). The 
lowest were diffusely (17.5%) and vertex (24.1%). The intermediate were in the
occipital (39.8%) and neck areas (39.7%). Other migraine types were remarkably
similar. Hemi-cranial location was present in 66.6% of patients, 71.2% in
episodic migraine and 61.4% in chronic migraine, 67.2% in females and 63.2% in
males, 59.7% in migraine without aura and 68.9% in migraine with aura 100% of the
time. Headaches were reported on the right side in 27.3%, left side 24.3%, both
sides 23.7%, either side 15.0%, and in the middle of the head in 4.6% of cases.
Significant differences in headache location were seen only within migraine and
not other migraine types. Headache location was not correlated with lifetime
duration of migraine, prodrome, response to triptan, intensity, time to peak of
headache, recurrence frequency, and time to recurrence. CONCLUSIONS: This study
provides a detailed documentation of headache location in a large cohort of
patients. The commonest locations are the orbital, frontal, and temporal areas
and least common sites being diffuse and the vertex. A single location is
infrequent. Hemi-cranial location is present in two thirds of subjects and a
quarter each are on the left side, right side, and both sides. The locations of
the headache are very similar in different migraine types, but there are some
differences. Under age 21 and older patients tended to show some differences in
location and side. Location differences are seen with gender, headache frequency,
and aura. Location shows many correlations with triggers and headache features.

PMID: 16109118 [PubMed - indexed for MEDLINE]

1633: Headache. 2005 Sep;45(8):1031-7.

Effect of divalproex on metabolic parameters is dose related in migraine
prophylaxis.

Green MW, Giordano S, Jiang P, Jafari M, Smith TB.

Department of Neurology, Columbia University College of Physicians and Surgeons, 
New York, NY 10022, USA.

OBJECTIVE: To examine the metabolic effects of three divalproex dosing regimens
in patients with migraine. BACKGROUND: Epidemiological and clinical studies have 
demonstrated a strong association between serum lipid levels and the development 
of coronary artery disease. Thus, it is important to understand the impact of
chronically administered medications on serum lipids. Metabolic properties of
divalproex, an approved and commonly used treatment for migraine prophylaxis,
have not been systematically studied in patients with migraine. METHODS: Adult
patients with migraine were randomized to receive one of three daily doses of
divalproex (500 mg [n = 45], 1000 mg [n = 43], or 1500 mg [n = 44]) or placebo (n
= 44) for 12 weeks. Post hoc analyses were performed to determine the effects of 
divalproex on total cholesterol, glucose, weight, and body mass index (BMI).
RESULTS: The treatment groups were similar at baseline based on demographic and
clinical characteristics and the use of concomitant medications. Divalproex
resulted in a dose-related mean decrease from baseline in total cholesterol: -5.7
mg/dL or 3% reduction with 500 mg/day; -8.4 mg/dL or 4% reduction with 1000
mg/day; and -12.8 mg/dL or 7% reduction with 1500 mg/day (P < .05 for 1500 mg/day
vs. placebo). There were no differences between any divalproex dose group and
placebo for mean change from baseline in glucose, weight, or BMI. CONCLUSIONS:
Divalproex results in a dose-dependent reduction in serum cholesterol within the 
first 3 months of therapy, with no significant change in serum glucose or BMI.

Publication Types: 
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 16109117 [PubMed - indexed for MEDLINE]

1634: Headache. 2005 Sep;45(8):1023-30.

Topiramate improves health-related quality of life when used to prevent migraine.

Diamond M, Dahlöf C, Papadopoulos G, Neto W, Wu SC.

Diamond Headache Clinic, Chicago, IL 60614, USA.

OBJECTIVE: To assess changes in health-related quality of life (HRQoL) measures
among patients receiving topiramate (TPM) 100 mg/d in two divided doses for
migraine prevention in three randomized, double-blind, placebo-controlled,
26-week trials with similar protocols and study populations. BACKGROUND: Migraine
substantially impairs HRQoL and work productivity before, during, and after
attacks. Approximately 50% of patients with migraine could be recommended for
preventive therapies, yet only 3% to 5% of patients receive them. TPM is an
effective and generally well-tolerated migraine prophylactic (preventive) therapy
for adults, as demonstrated in several randomized, double-blind,
placebo-controlled trials. The most common adverse events in double-blind,
placebo-controlled studies of TPM in migraine prevention are paresthesia,
fatigue, anorexia, nausea, taste alteration, and diarrhea. DESIGN AND METHODS:
The Migraine-Specific Questionnaire (MSQ, version 2.1) was used to assess the
effect of TPM 100 mg/d on the functionality and HRQoL of randomized
intent-to-treat (ITT) and study-completer populations pooled from three
randomized, double-blind, placebo-controlled trials. MSQ scores (0 to 100, higher
score indicates better functioning) were assessed for the following three
domains: role restriction (examines the degree to which performance of daily
activities is limited by migraine), role prevention (examines the degree to which
performance of daily activities is interrupted by migraine), and emotional
function (examines feelings of frustration and helplessness due to migraine).
Between-group differences from baseline in mean MSQ domain scores for TPM 100
mg/d and placebo were compared using a mixed-effects model with piecewise linear 
regression. Effect sizes were calculated to estimate the magnitude of change in
HRQoL that can be associated with TPM therapy. RESULTS: TPM 100 mg/d
significantly improved all three MSQ domains compared with placebo for both the
ITT (TPM, n = 372; placebo, n = 362) and study-completer (TPM, n = 220; placebo, 
n = 216) populations (P < .001 for all three domains, both populations). Effect
sizes for TPM 100 mg/d varied from 0.40 to 0.78, indicating that the changes in
MSQ scores for TPM 100 mg/d were moderate and may be clinically significant.
CONCLUSION: TPM 100 mg/d has been shown to be effective in the prevention of
migraine headache in adults. As the MSQ results from the three randomized,
placebo-controlled trials indicate, HRQoL is significantly improved for up to 6
months following initiation of treatment.

Publication Types: 
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 16109116 [PubMed - indexed for MEDLINE]

1635: Headache. 2005 Sep;45(8):1012-22.

Cost-effectiveness of topiramate in migraine prevention: results from a
pharmacoeconomic model of topiramate treatment.

Brown JS, Papadopoulos G, Neumann PJ, Friedman M, Miller JD, Menzin J.

Boston Health Economics, Inc., Waltham, MA 02451, USA.

OBJECTIVE: Patients whose migraines are frequent, cause disruptions of daily
routines, or are unresponsive to acute treatment are primary candidates for
preventive migraine therapy. This cost-effectiveness model assesses the clinical 
and economic impact of topiramate (TPM) therapy versus no preventive treatment
for migraine headache in the United States. BACKGROUND: Despite significant
progress in treatment options, the economic burden of migraine to patients,
employers, health systems, and society is substantial. Treatment strategies for
migraine are directed toward managing acute episodes. However, preventive therapy
should be used for patients with frequent migraine attacks (>2 per month) or
those experiencing attacks that disrupt daily routines. METHODS: Data for the
model were obtained from the published literature and pooled results of two
randomized, double-blinded, placebo-controlled trials of TPM in migraine
prevention. Model inputs included baseline migraine frequency (the base case
assumed 6 per month, consistent with the average rate in the TPM trials),
treatment discontinuation (including discontinuation due to adverse events),
treatment response (ie, > or = 75%, 50% to 75%, and <50% reduction in migraine
frequency), cost of preventive therapy (TPM plus physician visits for medication 
titration), cost of acute treatment per attack (including pharmacy and medical
service costs), hours of disability per attack, hourly wage, and quality-of-life 
(utility) weights. Model outcomes included the number of migraines averted,
disability hours, total cost of acute and preventive treatment, and lost wages.
Results were expressed as cost per migraine averted and cost per quality-adjusted
life years (QALY). All costs were stated as 2002 U.S. dollars. We also conducted 
sensitivity analyses to assess the robustness of model findings with respect to
variation in key parameters. RESULTS: We estimated that the use of TPM would
prevent 1.85 migraines per patient and almost 5 hours of disability per month
versus no preventive treatment. Resulting savings in cost of acute treatment
(dollar 27) and work loss (dollar 51) offset 68% of the expected monthly cost of 
TPM (dollar 113). The incremental cost per migraine averted was dollar 19, while 
the incremental cost per QALY was estimated to be dollar 10,888 (dollar 26,191
when indirect costs were excluded from the analysis). Model results were
sensitive to baseline migraine rate and gain in health utility from migraine
prevention. CONCLUSIONS: Economic savings associated with reduced migraine
frequency offset approximately two thirds of the cost of preventive TPM therapy. 
The cost-effectiveness of TPM depends on utility gains associated with a reduced 
frequency of migraine headaches, which is the subject of ongoing research.
However, results from our model suggest that the use of TPM in prevention of
migraine may offer reasonable value for money relative to many well-accepted
medical interventions.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 16109115 [PubMed - indexed for MEDLINE]

1636: Headache. 2005 Sep;45(8):1004-11.

Efficacy of the 5-HT1A agonist, buspirone hydrochloride, in migraineurs with
anxiety: a randomized, prospective, parallel group, double-blind,
placebo-controlled study.

Lee ST, Park JH, Kim M.

Department of Neurology, Seoul National University Hospital, Youngon-Dong,
Chongno-gu, South Korea.

OBJECTIVE: To examine the efficacy of buspirone, a 5-HT1A agonist, for migraine
combined with anxiety disorder. BACKGROUND: Modulation of the 5-hydroxytryptamine
(5-HT) system is used for the neuropharmacology of migraine treatment; however,
the involvement of the 5-HT1A system in migraine is not fully understood.
METHODS: Seventy-four outpatients aged 20 to 70 years (mean, 46.4; SD, 12.8) were
analyzed. All subjects were diagnosed to have migraine according to the
International Headache Society criteria and anxiety disorder according to DSM-IV.
Subjects were randomly assigned to treatment with either buspirone (10 mg/day) or
placebo for 6 weeks. Efficacy variables included changes in headache frequency,
headache intensity, Hamilton Anxiety Rating Scale (HAM-A), Headache Self-Efficacy
Scale (HMSE), and Headache Disability Inventory (HDI). The correlation between
the headache improvement and the anxiolytic effect was analyzed. RESULTS:
Headache frequency showed a 43.3% reduction in the buspirone-treated group, but
by only 10.3% in the placebo group. HAM-A and HDI were also significantly more
lowered in buspirone-treated patients than in placebo-treated patients. However, 
headache intensity and HMSE score were unchanged. Correlation analysis of the
relation between headache frequency reduction and HAM-A improvement, revealed no 
significant association. CONCLUSIONS: In this study, buspirone showed a
prophylactic effect in migraine with anxiety disorder, which was not secondary to
its anxiolytic effect. This suggests that the agonistic action for 5-HT1A can be 
directly effective in migraine prophylaxis. However, more long-term study is
warranted before concluding the efficacy.

Publication Types: 
    Comparative Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 16109114 [PubMed - indexed for MEDLINE]

1637: Headache. 2005 Sep;45(8):992-8.

Pain thresholds in daily transformed migraine versus episodic migraine headache
patients.

Kitaj MB, Klink M.

Kitaj Headache Center, LLC, Southbury, CT 06488, USA.

OBJECTIVE: The objective of this study was to test whether pain thresholds of
patients with episodic migraine (EM) are significantly different from transformed
migraine (TM) patients as measured by Quantitative Sensory Testing (QST) and
Semmes-Weinstein Monofilaments (SW). BACKGROUND: Although there are many
theories, none have undeniably proven why many TM patients are refractory to
triptans and other gold standard medications. The hypothesis was that baseline
pain thresholds of TM patients are lower than EM patients. METHODS: Episodic (n =
40) and Transformed (n = 41) migraineurs with and without aura were examined with
QST and SW over eight locations (bilateral ophthalmic, maxillary, C4/posterior
neck, and forearm). All patients completed two visits, baseline and severe
migraine. RESULTS: TM patients have lower pain thresholds, than EM patients, as
measured on QST and SW testing. A total of 81 out of 129 patients completed both 
parts of the study at baseline and severe migraine. There were significant
differences (P < .05) between EM and TM groups at baseline on maxillary, neck (EM
= 45.91 degrees C and TM = 42.94 degrees C), and arm. CONCLUSIONS: TM patients,
clinically known to report skin hypersensitivity during migraine, were found to
have lower pain thresholds than EM patients, both with severe migraine, and at
baseline, measured by QST and SW mechanical testing. As with Burstein's work in
EM patients with lowered pain thresholds during their acute migraine, central
sensitization may be the explanation for non-responsiveness to triptans in a high
proportion of TM patients. The difference in pain threshold at the neck location 
was such a strikingly frequent difference between EM and TM patients, that this
indicates the need for future research to clarify the directional relationship
and the relative importance of muscular versus peripheral versus central
hypersensitivity in the determination of allodynia.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 16109112 [PubMed - indexed for MEDLINE]

1638: Headache. 2005 Sep;45(8):983-91.

Sumatriptan and naproxen sodium for the acute treatment of migraine.

Smith TR, Sunshine A, Stark SR, Littlefield DE, Spruill SE, Alexander WJ.

Mercy Health Research/Ryan Headache Center, Chesterfield, MO 63017, USA.

OBJECTIVE: To evaluate the efficacy and tolerability of treatment with a
combination of sumatriptan 50 mg (encapsulated) and naproxen sodium 500 mg
administered concurrently in the acute treatment of migraine. BACKGROUND: The
pathogenesis of migraine involves multiple peripheral and central neural
mechanisms that individually have been successful targets for acute (abortive)
and preventive treatment. This suggests that multi-mechanism therapy, which acts 
on multiple target sites, may confer improved efficacy and symptom relief for
patients with migraine. DESIGN AND METHODS: This was a multicenter, randomized,
double-blind, double-dummy, placebo-controlled, four-arm study. Participants (n =
972) treated a single moderate or severe migraine attack with placebo, naproxen
sodium 500 mg, sumatriptan 50 mg, or a combination of sumatriptan 50 mg and
naproxen sodium 500 mg. In the latter two treatment arms, the sumatriptan tablets
were encapsulated in order to achieve blinding of the study. RESULTS: In the
sumatriptan plus naproxen sodium group, 46% of subjects achieved 24-hour pain
relief response (primary endpoint), which was significantly more effective than
sumatriptan alone (29%), naproxen sodium alone (25%), or placebo (17%) (P <
.001). Two-hour headache response also significantly favored the sumatriptan 50
mg plus naproxen sodium 500 mg therapy (65%) versus sumatriptan (49%), naproxen
sodium (46%), or placebo (27%) (P < .001). A similar pattern of between-group
differences was observed for 2-hour pain-free response and sustained pain-free
response (P < .001). The incidence of headache recurrence up to 24 hours after
treatment was lowest in the sumatriptan plus naproxen sodium group (29%) versus
sumatriptan alone (41%; P = .048), versus naproxen sodium alone (47%; P= .0035), 
and versus placebo (38%; P= .08). The incidences of the associated symptoms of
migraine were significantly lower at 2 hours following sumatriptan 50 mg plus
naproxen sodium 500 mg treatment versus placebo (P < .001). The frequencies and
types of adverse events reported did not differ between treatment groups, with
dizziness and somnolence being the most common. CONCLUSIONS: This is among the
first prospective studies to demonstrate that multi-mechanism acute therapy for
migraine, combining a triptan and an analgesic, is well tolerated and offers
improved clinical benefits over monotherapy with these selected standard
antimigraine treatments. Specifically, sumatriptan 50 mg (encapsulated) and
naproxen sodium 500 mg resulted in significantly superior pain relief as compared
to monotherapy with either sumatriptan 50 mg (encapsulated) or naproxen sodium
500 mg for the acute treatment of migraine. Because encapsulation of the
sumatriptan for blinding purposes may have altered its pharmacokinetic profile
and thereby decreased the efficacy responses, additional studies are warranted
that do not involve encapsulation of the active treatments and assess the true
onset of action of multi-mechanism therapy in migraine. This study did show that 
the combination of sumatriptan and naproxen sodium was well tolerated and that
there was no significant increase in the incidence of adverse events compared to 
monotherapy.

Publication Types: 
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 16109111 [PubMed - indexed for MEDLINE]

1639: Headache. 2005 Sep;45(8):973-82.

Comment in:
    Headache. 2006 Feb;46(2):340; author reply 341.    Headache. 2006 Feb;46(2):341; author reply 341-3.    Headache. 2007 Apr;47(4):623; author reply 623-5.

Acetaminophen, aspirin, and caffeine versus sumatriptan succinate in the early
treatment of migraine: results from the ASSET trial.

Goldstein J, Silberstein SD, Saper JR, Elkind AH, Smith TR, Gallagher RM,
Battikha JP, Hoffman H, Baggish J.

San Francisco Headache Clinic, San Francisco Clinical Research Center, CA 94109, 
USA.

OBJECTIVE: To address the need for a rigorous, direct comparison of prescription 
and over-the-counter (OTC) migraine drugs and to expand the database on early
treatment of migraine. BACKGROUND: Most people who experience migraine use OTC
medications to treat their symptoms, but no head-to-head clinical trials
comparing these agents with prescription migraine therapies have been published. 
In addition, even though most migraineurs treat early in the attack, few studies 
have been conducted to reflect this treatment pattern. METHODS: We compared a
combination of nonprescription migraine medication (acetaminophen 500 mg, aspirin
500 mg, and caffeine 130 mg) with a prescription migraine product (50 mg
sumatriptan) in a randomized, controlled clinical trial in which subjects treated
at the first sign of a migraine attack. Subjects who reported vomiting during
more than 20% of migraine episodes or who required bedrest during more than 50%
of migraine episodes were excluded from the study. Of the 188 subjects
randomized, 171 took study medication and were included in the analysis.
CONCLUSION: The combination of acetaminophen, aspirin, and caffeine was
significantly more effective (P > .05) than sumatriptan in the early treatment of
migraine, as shown by superiority in summed pain intensity difference, pain
relief, pain intensity difference, response, sustained response, relief of
associated symptoms, use of rescue medication, disability relief, and global
assessments of effectiveness. An additional, larger clinical trial is needed to
confirm these results.

Publication Types: 
    Comparative Study
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 16109110 [PubMed - indexed for MEDLINE]

1640: Cephalalgia. 2005 Sep;25(9):735-42.

Eletriptan in the early treatment of acute migraine: influence of pain intensity 
and time of dosing.

Brandes JL, Kudrow D, Cady R, Tiseo PJ, Sun W, Sikes CR.

Nashville Neuroscience Group, Nashville, TN 37203, USA.
jbrandes@nashvilleneuroscience.com

This double-blind, placebo-controlled study was designed to evaluate the efficacy
and tolerability of early treatment of a single migraine attack, when headache
pain was mild, with two doses (20 mg and 40 mg) of eletriptan. Patients (N = 613;
female 79%; mean age 39 years) meeting International Headache Society criteria
for migraine were encouraged, but not required, to utilize early treatment, thus 
providing an opportunity to assess the relative contribution to efficacy of pain 
severity and timing of dose. For the total patient sample (mild-to-severe
headaches), 2-h pain-free rates were significantly higher than placebo (22%) on
both eletriptan 20 mg (35%; P < 0.01) and eletriptan 40 mg (47%; P < 0.0001). For
the cohort of patients who treated their headache when the pain intensity was
mild, the 2-h pain-free rate on eletriptan 40 mg was 68% compared with 25% on
placebo (P < 0.0001). Pain intensity at the time of taking eletriptan appeared to
influence outcome more than the timing of the dose relative to headache onset.
Eletriptan was well-tolerated, with adverse event rates similar to placebo when
mild headaches were treated.

Publication Types: 
    Clinical Trial
    Comparative Study
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 16109056 [PubMed - indexed for MEDLINE]

1641: Cephalalgia. 2005 Sep;25(9):726-34.

Eletriptan treatment of migraine in patients switching from
barbiturate-containing analgesics: results from a multiple-attack study.

Martin VT, Loder E, Taylor K, Almas M, Hilliard B.

Division of General Internal Medicine, University of Cincinnati, Cincinnati, OH
452674217, USA. martindoc@pol.net

The aim of this study was to examine efficacy and tolerability of eletriptan in
patients switched from barbiturate-containing combinations (Fiorinal), Fioricet. 
Migraineurs (n = 160) meeting IHS criteria, with unsatisfactory response in the
past year to butalbital-containing combinations, treated up to 16 attacks over 3 
months with eletriptan 40 mg. Assessments included headache response and
pain-free rates and functional impairment at baseline and 2 h postdose, and
global ratings of treatment satisfaction at 24 h. At 2 h postdose, average
headache response and pain-free rates were 71% (95% CI, 69-74%) and 37% (95% CI, 
35-40%), respectively; 68.5% of patients (95% CI, 65-72%) reported functional
response. Within-patient analysis found no efficacy diminution over time (no
tolerance). Average headache recurrence rate was 20% (95% CI, 18-23%). Eletriptan
was well-tolerated; 6 (3.7%) patients discontinued due to adverse events. There
were no serious treatment-related adverse events. We conclude that in poor
responders to butalbital-caffeine combinations, switching to eletriptan 40 mg was
well-tolerated and efficacious.

Publication Types: 
    Clinical Trial
    Multicenter Study
    Research Support, Non-U.S. Gov't

PMID: 16109055 [PubMed - indexed for MEDLINE]

1642: Cephalalgia. 2005 Sep;25(9):715-25.

Therapeutic benefit of eletriptan compared to sumatriptan for the acute relief of
migraine pain--results of a model-based meta-analysis that accounts for
encapsulation.

Mandema JW, Cox E, Alderman J.

Pharsight Corporation, Mountain View, CA, USA. jmandema@wequantify.com

A novel model-based meta-analysis was used to quantify the dose-response
relationship of sumatriptan and eletriptan for the proportion of patients that
achieve migraine pain relief up to 4 h after treatment. The proportion of
patients that became pain free was also evaluated. This analysis includes some
unique features, allowing comparison of sumatriptan and eletriptan doses that
have not been directly compared in a head to head study and also permitting
comparison between the two drugs at multiple time points up to 4 h after
treatment. Because the analysis allows comparison of response to blinded
sumatriptan with that to marketed sumatriptan and contains timepoints as early as
0.5 h, it is especially suited to detection of possible effects of encapsulation 
on sumatriptan's therapeutic effectiveness and thus was employed to assess this
also. Data from 19 randomized placebo controlled clinical trials were jointly
analysed using a random-effects logistic regression model. The results of this
analysis show a significant clinical benefit of eletriptan 40 mg compared to
sumatriptan 100 mg at any point in time up to 4 h after treatment. The benefit of
eletriptan 40 mg is greatest around 1.5-2 h after treatment with an absolute
difference at 2 h of 9.1% (7.4-11.5%) more patients achieving pain relief and
7.3% (5.8-8.6%) more patient achieving pain free when compared to sumatriptan 100
mg. An absolute benefit of more than 5% of patients is maintained from 45 min up 
to 4 h after treatment for pain relief and from 1.5 h up to 4 h for pain free.
Eletriptan 20 mg was superior to sumatriptan 50 mg and similar to sumatriptan 100
mg for pain relief while it was similar to sumatriptan 50 mg for pain free. The
benefit of eletriptan 20 mg when compared to sumatriptan 50 mg is greatest around
1.5-2 h after treatment with an absolute difference at 2 h of 5.0% (2.9-8.1%)
more patients achieving pain relief. An absolute benefit of more than 3% of
patients was maintained from 1 h up to 3 h after treatment. No significant
difference was found between eletriptan 20 mg and sumatriptan 50 mg for the
fraction of patients that became pain free. No significant effect of
encapsulation of sumatriptan was found on the time course of response up to 4 h
after treatment when compared to commercial sumatriptan.

Publication Types: 
    Comparative Study
    Meta-Analysis
    Research Support, Non-U.S. Gov't

PMID: 16109054 [PubMed - indexed for MEDLINE]

1643: Heart. 2005 Sep;91(9):1173-5.

Clopidogrel reduces migraine with aura after transcatheter closure of persistent 
foramen ovale and atrial septal defects.

Wilmshurst PT, Nightingale S, Walsh KP, Morrison WL.

Royal Shrewsbury Hospital, Shrewsbury SY3 8XQ, UK. peter.wilmshurst@rsh.nhs.uk

OBJECTIVE: To report the clinical events leading to alteration of an
anticoagulation regimen for patients undergoing transcatheter closure of an
atrial shunt and how this affected migraine symptoms after the closure procedure.
METHOD: Audit of a change of anticoagulant regimen. RESULTS: In the first few
weeks after a closure procedure migraine frequency and severity increased despite
treatment with aspirin for six months in 71 patients. Severe attacks of migraine 
with aura, including status migrainosus, in the first few weeks after
transcatheter closure were terminated by addition of clopidogrel to aspirin
treatment. Therefore, the anticoagulant regimen was changed with addition of
clopidogrel for the first month after the closure procedure (90 procedures in 89 
patients). Fewer patients had migraine with aura in the first month after
transcatheter closure when taking the combination of clopidogrel and aspirin
compared with aspirin alone (11 of 90 (12.2%) v 30 of 71 (42.3%), p < 0.001).
Episodes of migraine with aura were more severe and more frequent in patients
taking aspirin alone. CONCLUSION: The combination of clopidogrel for four weeks
and aspirin for six months is superior to aspirin alone for six months for
preventing migraine with aura after transcatheter closure of an atrial shunt.
This beneficial effect of a powerful inhibitor of platelet aggregation suggests
that platelets may have a role in pathogenesis of migraine. This may be because
of an effect on serotonin stores. Whether clopidogrel has a role in treatment of 
migraine in other clinical situations requires investigation.

PMID: 16103551 [PubMed - indexed for MEDLINE]

1644: Arq Neuropsiquiatr. 2005 Jun;63(2A):217-20.

Depression in chronic migraine: severity and clinical features.

Mercante JP, Peres MF, Guendler V, Zukerman E, Bernik MA.

Psicóloga, pesquisadora do Instituto de Ensino e Pesquisa do Hospital Israelita
Albert Einstein, São Paulo SP, Brasil. julianeperes@terra.com.br

INTRODUCTION: Chronic migraine (CM) is a common medical condition affecting 2.4% 
of the general population. Depression is one of the most frequent comorbid
disorders in CM. METHOD: Seventy patients diagnosed with chronic migraine were
studied. All patients evaluated filled out the Beck Depression Inventory (BDI).
Depression severity was divided into none or minimal depression, mild, moderate, 
and severe. RESULTS: BDI ranged from 4 to 55, mean 21 +/- 10.7. Moderate or
severe depression, were present in 58.7% of the patients. Some degree of
depression appeared in 85.8% of patients. The BDI scores correlated with pain
intensity (p = 0.02). Severe depression was more frequent in patients with
comorbid fibromyalgia and in patients reporting fatigue. CONCLUSION: The BDI is
an easy tool to access depression in CM patients. Suicide risk assessment is
needed in CM patients. Patients with fibromyalgia and fatigue are at even higher 
risk for severe depression.

PMID: 16100965 [PubMed - indexed for MEDLINE]

1645: Magnes Res. 2005 Jun;18(2):109-22.

Headache due to photosensitive magnesium depletion.

Durlach J, Pagès N, Bac P, Bara M, Guiet-Bara A.

SDRM, SDRM, Université Pierre et Marie Curie, Paris VI, 75252 Paris Cedex 05,
France. jean.durlach@wanadoo.fr

Clinical and paraclinical data (visual stress tests, electroencephalographic and 
cerebrovascular photic driving, visual evoked potentials) demonstrate that the
concept of photosensitive headache is fully justified. The interictal hallmark of
photosensitive cephalalgic patients is potentiation (or sensitization) instead of
habituation. The aetiopathogenic mechanisms of photosensitive headache associate 
hypofunction of the biological clock and magnesium depletion. The new concept of 
headache due to photosensitive magnesium depletion seems justified. It appears
logical to add the treatments of magnesium depletion and of photosensitivity to
classical treatment of headache. Prophylactic magnesium treatment relies on
atoxic nutritional magnesium supplementation in case of primary magnesium
deficiency. Pharmacological doses of parenteral magnesium may be used but may
induce toxicity. Therefore it is necessary to know the therapeutic index of
magnesium compound used: the larger its value, the greater the safety margin.
Treatment of photosensitivity uses various types of <<darkness therapies>>:
darkness therapy through physiologic, psychotherapic, physiotherapic,
pharmacologic stimulating techniques and substitutive darkness therapy through
palliative treatment. Melatonin is only a partial substitutive treatment of
photosensitivity. A new model of photosensitive magnesium depletion with
potentiation should be a useful tool for discriminating the most efficient gent.

Publication Types: 
    Review

PMID: 16100849 [PubMed - indexed for MEDLINE]

1646: Stroke. 2005 Sep;36(9):1886-90. Epub 2005 Aug 11.

The linear behavior of the system middle cerebral artery flow velocity and blood 
pressure in patients with migraine: lack of autonomic control?

Müller M, Marziniak M.

Department of Neurology, Kantonsspital Lucerne, CH-6000, Lucerne 16, Switzerland.
martin.mueller@ksl.ch

BACKGROUND AND PURPOSE: Migraine is considered a disorder of the autonomic
nervous system. We used the frequency analysis of dynamic cerebral autoregulation
to assess whether blood flow regulation disturbances can be found at the
frequencies at which sympathetic and parasympathetic activity is present.
METHODS: We measured simultaneously mean arterial blood pressure (BP) and the
mean blood velocity (V) in the middle cerebral artery using transcranial Doppler 
ultrasound in 33 healthy controls (mean age+/-SD; 36+/-13 years) and in 22
patients with migraine (mean age; 39+/-7 years). Apart from assessing spectral
power density for BP and V, we calculated the transfer function parameters gain, 
phase, and coherence at the frequency range between 0.0 and 0.25 Hz. RESULTS:
Compared with the controls, the spectral power density of BP and V exhibited a
maximum magnitude of 10(26) in the migraine patients, whereas the maximum
magnitude of BP and V in the controls was 10(-3). Coherence showed no difference 
between patients and controls. Gain between BP and V increased in the controls
>0.01 Hz but was approximately 0 or negative in the migraine patients over the
whole frequency range (P<0.01). The usually observed phase lead of V against BP
was absent in the migraine patients in whom BP leaded V over nearly the whole
frequency range (P<0.01). CONCLUSIONS: In terms of phase and gain, dynamic
cerebral autoregulation is completely different in migraine patients compared
with healthy subjects. Insofar, this can be interpreted as a lack of sympathetic 
and parasympathetic control of cerebral blood flow.

PMID: 16100026 [PubMed - indexed for MEDLINE]

1647: Vascul Pharmacol. 2005 Sep;43(3):176-87.

Migraine: current concepts and emerging therapies.

Arulmozhi DK, Veeranjaneyulu A, Bodhankar SL.

New Chemical Entity Research, Lupin Research Park, Village Nande, Taluk Mulshi,
Pune 411 042, Maharashtra, India. adk_bits@yahoo.com

Migraine is a recurrent incapacitating neurovascular disorder characterized by
attacks of debilitating pain associated with photophobia, phonophobia, nausea and
vomiting. Migraine affects a substantial fraction of world population and is a
major cause of disability in the work place. Though the pathophysiology of
migraine is still unclear three major theories proposed with regard to the
mechanisms of migraine are vascular (due to cerebral vasodilatation),
neurological (abnormal neurological firing which causes the spreading depression 
and migraine) and neurogenic dural inflammation (release of inflammatory
neuropeptides). The modern understanding of the pathogenesis of migraine is based
on the concept that it is a neurovascular disorder. The drugs used in the
treatment of migraine either abolish the acute migraine headache or aim its
prevention. The last decade has witnessed the advent of Sumatriptan and the
'triptan' class of 5-HT1B/1D receptor agonists which have well established
efficacy in treating migraine. Currently prophylactic treatments for migraine
include calcium channel blockers, 5-HT2 receptor antagonists, beta adrenoceptor
blockers and gamma-amino butyric acid (GABA) agonists. Unfortunately, many of
these treatments are non specific and not always effective. Despite such
progress, in view of the complexity of the etiology of migraine, it still remains
undiagnosed and available therapies are underused. In this article, the diverse
pieces of evidence that have linked the different theories of migraine with its
pathophysiology are reviewed. Furthermore, the present therapeutic targets and
futuristic approaches for the acute and prophylactic treatment of migraine, with 
a special emphasis to calcitonin gene-related peptide, are critically evaluated.

Publication Types: 
    Review

PMID: 16099727 [PubMed - indexed for MEDLINE]

1648: CNS Drugs. 2005;19(8):683-92.

The risk of stroke in patients with migraine and implications for migraine
management.

Tietjen GE.

Department of Neurology, Medical College of Ohio, Toledo, Ohio 43614-5811, USA.
gtietjen@mco.edu

Assessing the risk of stroke in persons with migraine is complicated by the
intricate relationship between these two conditions. Both migraine and stroke are
common and co-morbidity may, in some cases, be coincidental. Given the overlap of
clinical symptoms in stroke and migraine, each condition may also mimic the
other. Numerous studies have, however, shown that migraine is an independent risk
factor for stroke both during, and remote from, the migraine attack. Women of
childbearing age and those with aura are at greatest risk of migraine-related
stroke. Additional risk of stroke in migraineurs occurs in those using oral
contraceptive pills and who smoke cigarettes. Elevated blood pressure, an
important stroke risk factor, is less common in migraineurs. Acquired
antiphospholipid antibodies, not clearly a cause of migraine per se, may raise
the risk of infarction in migraineurs. Hereditary conditions, including CADASIL
(cerebral autosomal dominant arteriopathy with sub-cortical infarcts and
leukoencephalopathy), MELAS (mitochondrial myopathy, encephalopathy, lactacidosis
and stroke) and hereditary haemorrhagic telangiectasia, appear to predispose to
both migraine and stroke. Purported mechanisms for migraine-associated stroke
include involvement of the vasculature (including vasospasm, arterial dissection 
and small vessel arteriopathy), hypercoagulability (elevated von Willebrand
Factor, platelet activation) and elevated risk of cardioembolism (patent foramen 
ovale, atrial septal aneurysm). Triptans and ergotamines, used to treat acute
migraine attacks, appear to be safe in low-risk populations. These medications
should be avoided in persons with haemiplegic migraine, basilar migraine,
vascular risk factor and prior cerebral or cardiac ischaemia.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 16097850 [PubMed - indexed for MEDLINE]

1649: Pharmacoeconomics. 2005;23(8):837-50.

An economic evaluation of rizatriptan in the treatment of migraine.

Thompson M, Gawel M, Desjardins B, Ferko N, Grima D.

Innovus Research Inc., Burlington, Ontario, Canada.

BACKGROUND: Migraine is a common, chronic, neurovascular disorder, generally
characterised by attacks of severe headache and autonomic nervous system
dysfunction. Triptans are selective serotonin 5-HT(1B/1D) receptor agonists that 
represent effective therapeutic options for moderate-to-severe migraine attacks
but with higher acquisition costs relative to usual care therapies. OBJECTIVE:
The objective of this study was to examine the cost effectiveness of rizatriptan 
treatment compared with 'Usual Care' or other triptans available in Canada for
patients with moderate-to-severe migraine for whom other therapies (e.g. NSAIDs, 
simple analgesics) are insufficient or contraindicated. METHODS: A
decision-analysis model was created to estimate migraine treatment costs over a
24-hour period in patients with a diagnosis of moderate-to-severe migraine as
defined by the International Headache Society criteria. Costs and clinical
outcomes were observed over a 24-hour period from therapy initiation. Efficacy
measures consisted of 'pain-free response at 2 hours' and 'sustained pain free
for 2-24 hours'. Oral rizatriptan 10 mg was compared with other oral triptans
(i.e. sumatriptan 50 or 100 mg), naratriptan 2.5 mg and zolmitriptan 2.5 mg,
based on a meta-analysis and compared with 'Usual Care' based on a naturalistic
study of people who experience migraine and who were similar to the target
population. 'Usual Care' was defined as an aggregate of medications prescribed
for the Canadian population for the indication of migraine, weighted by the
relative frequency of use of prescriptions over a 1-year period. Analyses were
conducted from the Ontario (Canada) Ministry of Health and Long-Term Care (MOH<C)
perspective and the broader societal perspective. Results are presented as the
cost per migraine attack aborted (i.e. pain free at 2 hours), as well as the cost
per QALY. Several one-way sensitivity analyses were conducted to test the
robustness of the model. All costs are expressed in 2002 $Can. RESULTS: Cost
estimates are similar to previously published Canadian studies. Rizatriptan
compared with 'Usual Care' produced an incremental cost per attack aborted of
$Can49.82 and a cost per QALY gained of $Can31 845 from the MOH<C perspective.
When a societal perspective was considered (which included time loss from paid
and unpaid work activities), rizatriptan dominates 'Usual Care': that is, it is
cost saving and more effective. All other triptans are also dominated by
rizatriptan as they offer higher costs and lower efficacy. CONCLUSIONS: This
study shows that rizatriptan treatment for patients who experience
moderate-to-severe migraines may represent a cost-effective strategy for
improving care of migraine patients in Canada.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16097844 [PubMed - indexed for MEDLINE]

1650: Am J Manag Care. 2005 Jun;11(2 Suppl):S68-71.

Migraine in the managed care environment.

Owens GM.

Medical Management and Policy, Independence Blue Cross, Philadelphia,
Pennsylvania, USA.

Migraine headache remains a major clinical problem in the managed care
environment, incurring a heavy toll in terms of treatment costs, patient
disability, and patient quality of life. Abortive treatment with triptans has
become the standard of care in patients with acute episodic migraine. However,
there is no such consensus about the optimal approach to prophylaxis in patients 
with frequent or intractable migraine. The agents currently approved in this role
are not always effective and may cause systemic side effects. One potential
alternative to currently approved treatments may be botulinum toxin. When
injected into carefully pinpointed pericranial locations at 3-month intervals,
botulinum toxin may offer effective prophylaxis with minimal side effects.
However, the evidence available to date has been inconsistent, with benefit seen 
in some reports but not in others. Consequently, managed care policymakers have
been cautious about approval of coverage for this treatment. Specific criteria
for the use of botulinum toxin vary among different plans. At present, many plans
do not approve coverage for this agent for the treatment of migraine; other plans
do allow coverage as needed for patients in whom conventional approaches have
been ineffective or intolerable, but not as a first-line approach to prophylaxis.

Publication Types: 
    Review

PMID: 16095270 [PubMed - indexed for MEDLINE]

1651: Am J Manag Care. 2005 Jun;11(2 Suppl):S62-7.

The cost of migraine and its treatment.

Goldberg LD.

Goldberg, MD & Associates, Battle Ground, Washington, USA.

Migraine headache incurs estimated annual costs totaling as much as 17 billion
dollars in the United States. Most of the direct costs are for outpatient
services: medications, office or clinic visits, emergency department visits,
laboratory and diagnostic services, and management of treatment side effects.
Indirect costs from lost productivity in the workplace add substantially to the
total. The triptan class of drugs, used for abortive treatment, account for the
greatest portion of medication costs. Because these agents are expensive, optimal
use is critical. Research suggests that a stratified care strategy, with initial 
therapy based on the patient's score on the Migraine Disability Assessment Scale,
is both clinically advantageous and more cost-effective than stepped-care
strategies. Also, the triptans are not interchangeable, and costs as well as
clinical outcomes may vary with different agents in this class. Migraine
prophylaxis is aimed at preventing frequent attacks and the development of a
long-term condition that often incurs heavy costs for abortive treatment,
diagnostic services, and medical care. Agents approved for migraine prophylaxis
include the antiepileptics divalproex and topiramate and the beta blockers
propranolol and timolol. As with abortive therapy, costs vary widely among these 
prophylactic agents. A novel approach to migraine prophylaxis is injection of
botulinum toxin. A cost-analysis model is presented to show the impact of
utilizing botulinum toxin in a large managed care system.

Publication Types: 
    Review

PMID: 16095269 [PubMed - indexed for MEDLINE]

1652: Am J Manag Care. 2005 Jun;11(2 Suppl):S55-61.

Clinical approaches to migraine prophylaxis.

Blumenfeld A.

The Headache Center of Southern California, Scripps Memorial Hospital-Encintas,
USA.

Chronic migraine is a recognized complication of episodic migraine. A high
frequency of attacks and frequent use of abortive medications are important risk 
factors associated with conversion to a chronic condition. Prophylaxis is
therefore recommended for patients with frequent episodic migraine. The agents
approved for migraine prophylaxis are the anti-epileptic agents divalproex and
topiramate, and the beta-adrenergic antagonists propranolol and timolol. However,
a wide range of other systemic agents and local injections of botulinum toxin
have also been used in migraine prophylaxis. The anticipated benefits must be
weighed against the adverse effects associated with each agent in determining the
optimal preventive regimen for individual patients.

Publication Types: 
    Review

PMID: 16095268 [PubMed - indexed for MEDLINE]

1653: Intern Med. 2005 Jul;44(7):743-6.

Comment in:
    Intern Med. 2005 Jul;44(7):690-1.

A patient of migraine-like headache with amnesia, pleocytosis and transient
hypoperfusion of cerebral blood flow.

Tada Y, Negoro K, Abe M, Ogasawara J, Kawai M, Morimatsu M.

Department of Neurology and Clinical Neuroscience, Yamaguchi University, Ube,
Yamaguchi.

Pseudomigraine with pleocytosis (PMP) is an uncommon disease in Japan. The
diagnostic criteria include at least one episode of transient neurological
deficit accompanied or followed by migraine-like severe headache, cerebrospinal
fluid (CSF) lymphocytosis, and normal neuroimaging. Both the etiology and the
pathophysiology of PMP is not yet well defined. We report a 40-year-old man with 
a PMP-like syndrome. He came to our clinic because of severe throbbing headache
and amnesia, and the examination showed CSF lymphocytosis of 23/mm3, a transient 
decrease of cerebral blood flow in the left thalamus. All the symptoms were
completely resolved within 2 months.

Publication Types: 
    Case Reports
    Review

PMID: 16093598 [PubMed - indexed for MEDLINE]

1654: J Pediatr Psychol. 2005 Dec;30(8):698-707. Epub 2005 Aug 10.

Relationships between family and parent characteristics and functional abilities 
in children with recurrent pain syndromes: an investigation of moderating effects
on the pathway from pain to disability.

Logan DE, Scharff L.

Pain Treatment Service, Children's Hospital Boston, 333 Longwood Avenue, Boston, 
MA 02115, USA. deirdre.logan@childrens.harvard.edu

OBJECTIVE: To identify family characteristics associated with children's ability 
to function with recurrent pain. METHODS: Seventy-eight children ages 7-17 years 
with recurrent pain syndromes [migraine headache or recurrent abdominal pain
(RAP)] were recruited from clinic settings. Children completed pain diaries and
the Functional Disability Inventory (FDI). Mothers and fathers completed
self-report measures of psychological distress, and mothers reported on family
environment. RESULTS: Controlling for the influence of pain intensity, family
environment and parental distress jointly predicted children's ability to
function with pain. Among children with migraine, family environment moderated
the relationship between pain and functional disability; in this group, greater
pain associated with more functional disability in children from disruptive
family environments, but not in children from more adaptive family environments. 
CONCLUSIONS: For some pediatric recurrent pain sufferers, family characteristics 
associate with the extent of pain-related disability and may help identify
children likely to experience more impaired functioning in response to recurrent 
pain.

Publication Types: 
    Research Support, U.S. Gov't, P.H.S.

PMID: 16093517 [PubMed - indexed for MEDLINE]

1655: Hum Mutat. 2005 Sep;26(3):281.

ATP1A2 mutations in 11 families with familial hemiplegic migraine.

Riant F, De Fusco M, Aridon P, Ducros A, Ploton C, Marchelli F, Maciazek J,
Bousser MG, Casari G, Tournier-Lasserve E.

Laboratoire de Génétique Moléculaire, Hôpital Lariboisière AP-HP, Paris, France.

Familial hemiplegic migraine (FHM) is an autosomal dominant form of migraine with
aura. The disease is caused by mutations of at least three genes among which two 
have been identified, CACNA1A and ATP1A2. Very few mutations have been identified
so far in ATP1A2. We screened the coding sequence of ATP1A2 in 26 unrelated FHM
probands in whom CACNA1A screening was negative. A total of eight different
mutations were identified in 11 of the probands (41%), including six missense
mutations, one small deletion leading to a frameshift, and one in frame deletion.
All were novel mutations. Two mutations were recurrent, in three and two
families, respectively. Genotyping of 94 relatives of these 11 probands
identified 47 mutation carriers, among whom 36 were clinically affected.
Sequencing of all 23 exons in an ethnically matched panel detected only one
exonic coding polymorphism.

PMID: 16088919 [PubMed - indexed for MEDLINE]

1656: Arch Neurol. 2005 Aug;62(8):1270-5.

Comment in:
    Arch Neurol. 2006 Sep;63(9):1347.

A positron emission tomographic study in spontaneous migraine.

Afridi SK, Giffin NJ, Kaube H, Friston KJ, Ward NS, Frackowiak RS, Goadsby PJ.

Headache Group, Institute of Neurology and The National Hospital for Neurology
and Neurosurgery, London, England.

BACKGROUND: Functional brain imaging in acute migraine has proved challenging
because of the logistic problems associated with an episodic condition. Since the
seminal observation of brainstem activation in migraine, there has been only a
single case substantiating this finding. OBJECTIVE: To test the hypothesis that
brainstem activation could be detected in migraine and to refine the anatomic
localization with higher-resolution positron emission tomography than previously 
used. DESIGN: Using positron emission tomography with radioactive water
(H(2)15O), we studied acute migraine attacks occurring spontaneously. Five
patients underwent imaging in ictal and interictal states, and the differences
were analyzed by means of statistical parametric mapping. SETTING: Tertiary
referral center. PATIENTS: Six volunteers with episodic migraine were recruited
from advertisements in migraine newsletters. One patient was excluded because of 
use of preventive medication. MAIN OUTCOME MEASURE: Brainstem activation during
migraine state vs interictal state. RESULTS: Two patients had a typical
migrainous aura before the onset of the headache. All of the attacks studied
fulfilled standard diagnostic criteria for migraine. Comparing the migraine scans
with interictal scans, there was significant activation in the dorsal pons,
lateralized to the left (small volume correction, P = .003). Activation was also 
seen in the right anterior cingulate, posterior cingulate, cerebellum, thalamus, 
insula, prefrontal cortex, and temporal lobes. There was an area of deactivation 
in the migraine phase also located in the pons, lateralized to the right.
CONCLUSIONS: Our findings provide clear evidence of dorsal pontine activation in 
migraine and reinforce the view that migraine is a subcortical disorder
modulating afferent neural traffic.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16087768 [PubMed - indexed for MEDLINE]

1657: Pediatr Neurol. 2005 Aug;33(2):94-7.

Migraine and recurrent epistaxis in children.

Jarjour IT, Jarjour LK.

Department of Neurology, Allegheny General Hospital, Drexel University College of
Medicine, Pittsburgh, Pennsylvania 1512, USA.

Recurrent epistaxis is a common pediatric problem with uncertain etiology in most
cases. We observed frequent complaints, or history of epistaxis in children with 
migraine. The aim of this study was to determine whether there is an association 
between epistaxis and migraine in children. A detailed questionnaire was used to 
conduct a study of 45 consecutive patients, ages 6-11 years, with migraine,
diagnosed according to the 1997 proposed pediatric revisions to the International
Headache Society criteria; the patients were evaluated in our Pediatric Neurology
Clinic. Control subjects consisted of 64 children without recurrent headaches,
matched as a group for age and sex, and drawn as a convenient sample from two
general pediatric practices and an elementary school. Sixteen (36%) of 45
patients with migraine had epistaxis as compared with 7 (11%) of 64 control
subjects (odds ratio = 4.5; 95% confidence interval 1.6-12.1; P = 0.002).
Epistaxis began an average of 3 years before migraine with similar
characteristics to idiopathic epistaxis in habitual nose-bleeders, such as onset 
in early childhood, high incidence in sleep, and family history of epistaxis.
This study demonstrates a significant association between migraine and recurrent 
epistaxis in children. Recurrent epistaxis increased the odds of migraine more
than fourfold. Moreover, these data raise the question of whether epistaxis may
represent a precursor to childhood migraine. The two disorders may share a common
pathogenesis, and a prospective, longitudinal study is required to define further
the relationship between them.

PMID: 16087052 [PubMed - indexed for MEDLINE]

1658: Curr Med Res Opin. 2005 Aug;21(8):1297-305.

The impact of migraine on psychological well-being of young women and their
communication with physicians about migraine: a multinational study.

Dueland AN, Leira R, Cabelli ST.

Sandvika Neurologic Service, Sandvika, Norway.

OBJECTIVE: To describe the impact of migraine on psychological well-being of
young women and to evaluate their communication with physicians about migraine.
RESEARCH DESIGN AND METHODS: This cross-sectional telephone survey was conducted 
in Israel and eight European countries (Finland, Germany, Greece, Italy, Norway, 
Spain, Sweden, and The Netherlands). Random-digit dialing was used to identify
eligible study participants: women 18-35 years of age with migraine, who used
medication to treat their migraine, and who were employed or full-time students. 
RESULTS: Of 1810 participants, 42% self-reported having a physician diagnosis of 
migraine. Eighty-six per cent believed that their life would be better if they
did not suffer from migraines; and 58% of participants felt frustrated, 46% felt 
angry, and 44% felt depressed because of their migraines. Negative feelings
related to migraine varied substantially from country to country. For example,
feelings of frustration caused by migraine ranged from 32% in Italy to 84% in
Finland; feelings of anxiety ranged from 21% in Norway to 57% in Italy; and
feelings of confusion ranged from 13% in Greece to 61% in Italy. Overall, 81% of 
participants had visited a physician in the past year but only 50% of them had
discussed their severe headaches or migraines with their physician within the
year. While 68% of those who had visited a physician stated that they were
comfortable speaking with their physician about migraine, 71% reported being the 
one who initiated the conversation about severe headaches or migraines. Of all
participants, 39% did not feel that their physician understood how much severe
headaches or migraines interfered with their life. CONCLUSIONS: Migraines and
severe headaches impose a substantial burden on the psychological well-being of
young women with migraine in Europe and Israel. In general, communication between
these women and their physicians about migraine is incomplete.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16083540 [PubMed - indexed for MEDLINE]

1659: Curr Med Res Opin. 2005;21 Suppl 3:S18-24.

Part IV: effects of zolmitriptan orally disintegrating tablet on migraine
symptoms and ability to perform normal activities: a post-marketing surveillance 
study in Germany.

Diener HC, Gendolla A.

Department of Neurology, University Essen, Germany. h.diener@uni-essen.de

Zolmitriptan has been developed in an orally disintegrating tablet (ODT)
formulation that rapidly dissolves on the tongue and can be taken quickly,
conveniently and discreetly without fluid intake. In this 3-month,
non-comparative, observational, post-marketing surveillance (PMS) study, 5,570
physicians prescribed the zolmitriptan 2.5 mg ODT for 16,261 patients with
migraine. Of the 14,543 patients who were evaluable for efficacy analysis, 94%
had reduced headache intensity within 2 hours of taking zolmitriptan 2.5 mg ODT
for the first attack. Improvements were reported within 30 minutes in 35% of
patients and within 15 minutes in 7% of patients. Non-headache migraine symptoms 
and normal daily activities improved for the majority of patients within 2 hours 
of taking zolmitriptan ODT. Ninety-one percent of patients required only a single
dose of zolmitriptan 2.5 mg ODT to treat each attack. Ninety-two percent of
patients considered zolmitriptan ODT as having very good or good efficacy and 96%
said that tolerability was very good or good. This study also demonstrated that
94% of patients would be willing to continue to use zolmitriptan ODT in the
future and 81% of patients considered that being able to take the ODT without
water was important or very import ant. In summary, zolmitriptan ODT has
demonstrated high efficacy and excellent tolerability. In addition, patients
found zolmitriptan ODT to be convenient and easy to use, and were willing to
continue using the product. Following placebo-controlled studies, these PMS
results provide insight into the use of zolmitriptan ODT in a setting more
representative of real life than randomised clinical trials, further
demonstrating that it provides a reliable and convenient alternative to
conventional tablets.

PMID: 16083520 [PubMed - indexed for MEDLINE]

1660: Curr Med Res Opin. 2005;21 Suppl 3:S13-7.

Part III: the convenience of, and patient preference for, zolmitriptan orally
disintegrating tablet.

Dowson AJ, Almqvist P.

The King's Headache Services, King's College Hospital, London, UK.
AndyDowson@psim-limited.com

As part of an optimal strategy for the management of migraine, the individual
needs and preferences of patients need to be considered when of patients need to 
be considered when prescribing treatments. Zolmitriptan has been available as a
conventional oral tablet for more than seven years, and is established as a
highly effective, well-tolerated compound for the acute treatment of migraine. A 
bioequivalent, orally disintegrating tablet (ODT) of zolmitriptan, which
dissolves on the tongue without the need for additional fluid intake, has been
developed. In a study designed to compare patient preference for zolmitriptan ODT
and conventional oral sumatriptan tablets, > 60% of the 186 patients questioned
had an overall preference for zolmitriptan ODT, with > 80% of patients reporting 
that this was the more convenient and less disruptive therapy to take.
Approximately 90% of patients agreed that, unlike a conventional tablet,
zolmitriptan ODT can be taken wherever and whenever a migraine occurs. When
patient preference for zolmitriptan ODT and the ODT formulation of rizatriptan
was compared in 171 migraineurs, 70% had an overall preference for zolmitriptan
ODT to be superior to rizatriptan ODT with respect to taste and aftertaste, as
well as packaging. In summary, not only is zolmitriptan ODT a convenient tablets,
such as the sumatriptan oral tablet, but patients generally consider it to be a
more attractive option for the acute treatment of migraine than the orally
disintegrating version of rizatriptan.

Publication Types: 
    Review

PMID: 16083519 [PubMed - indexed for MEDLINE]

1661: Curr Med Res Opin. 2005;21 Suppl 3:S8-12.

Part II: clinical efficacy and tolerability of zolmitriptan orally disintegrating
tablet in the acute treatment of migraine.

Loder EW, Dowson AJ, Spierings EL.

Spaulding Rehabilitation Hospital, Harvard Medical School, Boston, MA 02114, USA.
eloder@partners.org

Controlled clinical trials and extensive clinical use of conventional oral
tablets of zolmitriptan, a selective agonist of serotonin1B/1D receptors, have
proven the compound to be fast-acting, highly effective, and well-tolerated in
the acute treatment of migraine. An orally disintegrating tablet (ODT) of
zolmitriptan that dissolves on the tongue without the need for fluid intake has
been developed in order to provide an acceptable, convenient alternative for
patients who prefer not to, or cannot, take conventional tablets. A fast onset of
effective, sustained pain relief was predicted for zolmitriptan ODT on the basis 
of its bioequivalence with the conventional tablet, which has been confirmed in
three randomised, double-blind, placebo-controlled trials of zolmitriptan ODT in 
the acute treatment of migraine. Compared with placebo, significantly higher
proportions of patients treated with zolmitriptan ODT responded to treatment
(reduction of moderate or severe headache to mild or no pain) as early as 30
minutes after dosing. Headache response was maintained at 24 hours in
significantly higher proportions of patients receiving zolmitriptan ODT compared 
with placebo. Zolmitriptan ODT also resulted in significantly greater pain-free
rates than placebo as early as 1 hour after dosing. Zolmitriptan ODT relieved
patients of other migraine-associated symptoms, including nausea, photophobia and
phonophobia, and enabled >50% of patients to resume normal daily activities 2
hours after dosing. Adverse events observed with zolmitriptan ODT were similar to
those associated with the serotonin1B/1D agonists as a class, and were generally 
transient and of mild or moderate intensity.

PMID: 16083518 [PubMed - indexed for MEDLINE]

1662: Curr Med Res Opin. 2005;21 Suppl 3:S3-7.

Part I: what do patients really need and want from migraine treatment?

Gendolla A.

Department of Neurology, University Essen, Germany. astrid.gendolla@uni-essen.de

Migraine is characterised by recurrent episodes of head pain, often accompanied
by other symptoms, such as nausea and vomiting. In addition to migraine impairing
a patient's ability to function normally during an attack, fear of the next
attack can detract from quality of life between attacks. Of those migraineurs who
consult a physician for headache, the minority are prescribed migraine-specific
triptans and many are dissatisfied with current therapy. Clinical trials have
shown that triptans are capable of providing rapid and effective relief of
headache pain, which is what patients primarily desire from acute migraine
therapies. Patients generally prefer to administer acute migraine therapies
orally, but conventional tablets do not suit all patients and situations. Some
patients dislike swallowing tablets, nausea can make swallowing difficult and can
be exacerbated by fluid intake, and attacks can easily strike when fluids are not
readily available, especially as many young migraineurs lead busy, active lives. 
Patients need a treatment that enables any migraine attack to be treated promptly
and effectively in any given situation. Tablets that dissolve rapidly on the
tongue without a requirement for extra fluid intake are a popular alternative to 
conventional tablets, allowing discreet, convenient and early treatment of
migraine anywhere and anytime it strikes. Several triptans are currently on the
market in conventional tablet form, but some are available in other formulations,
such as orally disintegrating tablets or nasal sprays, making it possible to
prescribe rapidly effective migraine treatments in formulations that suit
individual patient preferences, lifestyles and attack characteristics.

Publication Types: 
    Editorial

PMID: 16083517 [PubMed - indexed for MEDLINE]

1663: Am J Hum Genet. 2005 Sep;77(3):500-12. Epub 2005 Jul 28.

Genomewide significant linkage to migrainous headache on chromosome 5q21.

Nyholt DR, Morley KI, Ferreira MA, Medland SE, Boomsma DI, Heath AC, Merikangas
KR, Montgomery GW, Martin NG.

Queensland Institute of Medical Research, Brisbane, Australia. daleN@qimr.edu.au

Familial typical migraine is a common, complex disorder that shows strong
familial aggregation. Using latent-class analysis (LCA), we identified subgroups 
of people with migraine/severe headache in a community sample of 12,245
Australian twins (60% female), drawn from two cohorts of individuals aged 23-90
years who completed an interview based on International Headache Society
criteria. We report results from genomewide linkage analyses involving 756 twin
families containing a total of 790 independent sib pairs (130 affected
concordant, 324 discordant, and 336 unaffected concordant for LCA-derived
migraine). Quantitative-trait linkage analysis produced evidence of significant
linkage on chromosome 5q21 and suggestive linkage on chromosomes 8, 10, and 13.
In addition, we replicated previously reported typical-migraine susceptibility
loci on chromosomes 6p12.2-p21.1 and 1q21-q23, the latter being within 3 cM of
the rare autosomal dominant familial hemiplegic migraine gene (ATP1A2), a finding
which potentially implicates ATP1A2 in familial typical migraine for the first
time. Linkage analyses of individual migraine symptoms for our six most
interesting chromosomes provide tantalizing hints of the phenotypic and genetic
complexity of migraine. Specifically, the chromosome 1 locus is most associated
with phonophobia; the chromosome 5 peak is predominantly associated with
pulsating headache; the chromosome 6 locus is associated with
activity-prohibiting headache and photophobia; the chromosome 8 locus is
associated with nausea/vomiting and moderate/severe headache; the chromosome 10
peak is most associated with phonophobia and photophobia; and the chromosome 13
peak is completely due to association with photophobia. These results will prove 
to be invaluable in the design and analysis of future linkage and linkage
disequilibrium studies of migraine.

Publication Types: 
    Comparative Study
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 16080125 [PubMed - indexed for MEDLINE]

1664: Pediatrics. 2005 Aug;116(2):e295-302.

Symptomatic treatment of migraine in children: a systematic review of medication 
trials.

Damen L, Bruijn JK, Verhagen AP, Berger MY, Passchier J, Koes BW.

Department of General Practice, Erasmus Medical Centre, PO Box 1738, 3000 DR,
Rotterdam, The Netherlands.

OBJECTIVE: Treatment of pediatric migraine includes an individually tailored
regimen of both nonpharmacologic and pharmacologic measures. The mainstay of
symptomatic treatment in children with migraine is intermittent oral or
suppository analgesics, but there is no coherent body of evidence on symptomatic 
treatment of childhood migraine available. The objective of this review is to
describe and assess the evidence from randomized and clinical controlled trials
concerning the efficacy and tolerability of symptomatic treatment of migraine in 
children. DESIGN: Systematic review according to the standards of the Cochrane
Collaboration. METHODS: Databases were searched from inception to June 2004.
Additional reference checking was performed. Two authors independently selected
randomized and controlled trials evaluating the effects of symptomatic treatment 
in children (<18 years old) with migraine, using headache (HA) clinical
improvement as an outcome measure. Two authors assessed trial quality
independently by using the Delphi list, and data were extracted from the original
reports by using standardized forms. Quantitative and qualitative analysis was
conducted according to type of intervention. RESULTS: A total of 10 trials were
included in this review, of which 6 studies were considered to be of high
quality. The number of included participants in each trial ranged from 14 to 653,
with a total of 1575 patients included in this review. Mean dropout rate was
19.8% (range: 0-39.1%), and the mean age of participants was 11.7 +/- 2.2 years
(range: 4-18 years). All studies used HA diaries to assess outcomes. In most
studies, a measure of clinical improvement was calculated by using these diaries.
Improvement often was regarded as being clinically relevant when the patients' HA
declined by > or =50%. Regarding oral analgesic treatment, the effectiveness of
acetaminophen, ibuprofen, and nimesulide were evaluated. When compared with
placebo, acetaminophen (relative risk [RR]: 1.5; 95% confidence interval [CI]:
1.0-2.1) and ibuprofen (pooled RR: 1.5; 95% CI: 1.2-1.9) significantly reduced
HAs. We conclude that there is moderate evidence that both acetaminophen and
ibuprofen are more effective in reduction of symptoms 1 and 2 hours after intake 
than placebo with minor adverse effects. No clear differences in effect were
found between acetaminophen and ibuprofen or nimesulide. Regarding the
nonanalgesic interventions, nasal-spray sumatriptan, oral sumatriptan, oral
rizatriptan, oral dihydroergotamine, intravenous prochlorperazine, and ketorolac 
were evaluated. When compared with placebo, nasal-spray sumatriptan (pooled RR:
1.4; 95% CI: 1.2-1.7) seemed to significantly reduce HAs. We conclude that there 
is moderate evidence that nasal-spray sumatriptan is more effective in reduction 
of symptoms than placebo but with significantly more adverse events. No
differences in effect were found between oral triptans and placebo. All
medications were well tolerated, but significantly more adverse events were
reported for nasal-spray sumatriptan compared with placebo. We also conclude that
there is moderate evidence that intravenous prochlorperazine is more effective
than intravenous ketorolac in the reduction of symptoms 1 hour after intake. No
differences in effect were found between oral dihydroergotamine and placebo.
CONCLUSIONS: Acetaminophen, ibuprofen, and nasal-spray sumatriptan are all
effective symptomatic pharmacologic treatments for episodes of migraine in
children. The new frontier for symptomatic treatment is likely to be the
development of triptan agents for use in children. Most treatments have only been
evaluated in 1 or 2 studies, which limits the generalizability of the findings.
We strongly recommend performing a large, high-quality randomized, controlled
trial evaluating different symptomatic medications compared with each other or to
placebo treatment. Favorable high-quality studies should be performed and
reported according to the CONSORT statement. Clinical improvement of HA should be
used as the primary outcome measure, but quality of life, days missed at school, 
and satisfaction of child or parents should also be used as an outcome measure in
future studies.

Publication Types: 
    Meta-Analysis
    Research Support, Non-U.S. Gov't
    Review

PMID: 16061583 [PubMed - indexed for MEDLINE]

1665: Neuroscientist. 2005 Aug;11(4):373-86.

Migraine: new molecular mechanisms.

Pietrobon D.

Department of Biomedical Sciences, University of Padova, Padova, Italy.
daniela.pietrobon@unipd.it

Migraine is an episodic headache disorder affecting more than 10% of the general 
population. Migraine arises from a primary brain dysfunction that leads to
activation and sensitization of the trigeminovascular system. A major
incompletely understood issue in the neurobiology of migraine concerns the
molecular and cellular mechanisms that underlie the primary brain dysfunction and
lead to activation and sensitization of the trigeminovascular system, thus
generating and maintaining migraine pain. Here the author reviews recent
discoveries that have advanced our understanding of these mechanisms toward a
unifying pathophysiological hypothesis, in which cortical spreading depression
(CSD), the phenomenon underlying migraine aura, assumes a key role. In
particular, the author discusses the main recent findings in the genetics and
neurobiology of familial hemiplegic migraine and the insights they provide into
the molecular and cellular mechanisms that may lead to the increased
susceptibility of CSD in migraineurs.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 16061523 [PubMed - indexed for MEDLINE]

1666: Lancet. 2005 Jul 30-Aug 5;366(9483):371-7.

Comment in:
    Lancet. 2005 Jul 30-Aug 5;366(9483):345-6.

Mutation in the neuronal voltage-gated sodium channel SCN1A in familial
hemiplegic migraine.

Dichgans M, Freilinger T, Eckstein G, Babini E, Lorenz-Depiereux B, Biskup S,
Ferrari MD, Herzog J, van den Maagdenberg AM, Pusch M, Strom TM.

Department of Neurology, Klinikum Grosshadern, Ludwig-Maximilians-Universität,
81377 München, Germany. martin.dichgans@med.uni-muenchen.de

BACKGROUND: Familial hemiplegic migraine is an autosomal dominant severe subtype 
of migraine with aura characterised by some degree of hemiparesis during the
attacks. So far, mutations in two genes regulating ion translocation-CACNA1A and 
ATP1A2-have been identified in pedigrees with this disease. METHODS: To identify 
additional genes for familial hemiplegic migraine, we did a genome-wide linkage
analysis of two disease pedigrees without mutations in CACNA1A and ATP1A2. Ion
channel genes in the candidate interval were analysed for mutations, and the
functional consequences of the recorded sequence alteration were determined.
FINDINGS: We identified a novel locus for familial hemiplegic migraine on
chromosome 2q24. Sequencing of candidate genes in this region revealed a
heterozygous missense mutation (Gln1489Lys) in the neuronal voltage-gated sodium 
channel gene SCN1A, mutations of which have been associated with epilepsy. This
same mutation was present in three families with familial hemiplegic migraine. It
results in a charge-altering aminoacid exchange in the so-called hinged-lid
domain of the protein, which is critical for fast inactivation of the channel.
Whole-cell recordings in transiently transfected tsA201 cells expressing the
highly homologous SCN5A sodium channel showed that the mutation induces a
two-fold to four-fold accelerated recovery from fast inactivation without
altering any of the other channel parameters investigated. INTERPRETATION:
Dysfunction of the neuronal sodium channel SCN1A can cause familial hemiplegic
migraine. Our findings have implications for the understanding of migraine aura. 
Moreover, our study reinforces the molecular links between migraine and epilepsy,
two common paroxysmal disorders.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16054936 [PubMed - indexed for MEDLINE]

1667: Turk J Pediatr. 2005 Apr-Jun;47(2):150-2.

Evaluation of visual evoked potentials in children with headache.

Akin R, Unay B, Sarici SU, Ulaş U, Gökçay E.

Department of Pediatrics, Gülhane Military Medical Academy, Ankara, Turkey.

Headache is a common problem in childhood. Visual evoked potential (VEP) P100
latencies were recorded in children with headache. Sixty-four patients, aged 10.7
+/- 1.2 years, met the criteria of the International Headache Society for the
diagnosis of migraine. Fifty-eight patients, aged 10.2 +/- 1.3 years, with
tension headache and 56 healthy subjects, aged 10.3 +/- 1.3 years, as the control
group were also studied. Patients with migraine had slightly longer P100
latencies than the other two groups. We conclude that VEP latency recording is a 
valuable test in the diagnosis of migraine, and can be safely used in children.

PMID: 16052855 [PubMed - indexed for MEDLINE]

1668: Br J Sports Med. 2005 Aug;39(8):552-4.

Open label study of intranasal sumatriptan (Imigran) for footballer's headache.

McCrory P, Heywood J, Ugoni A.

Centre for Health, Exercise and Sports Medicine, University of Melbourne,
Melbourne, Victoria 3010, Australia. paulmccr@bigpond.net.au

OBJECTIVE: To study the efficacy and practicality of treating headache in
professional footballers with intranasal sumatriptan. METHODS: An open label drug
trial was performed in elite Australian footballers using intranasal sumatriptan 
(20 mg) treatment for acute headache. The main outcome measures were treatment
response at 30 minutes, two hours, and 24 hours using two criteria: (a) initial
severity moderate or severe to nil or mild; (b) stricter criteria of initial
severity moderate to severe to subsequent nil headache. RESULTS: Thirty eight
attacks were analysed. The two hour response showed that 86% of attacks of
migraine with aura and all of the attacks of migraine without aura responded to
treatment with sumatriptan nasal spray. Complete relief of headache at two hours 
was reported by 71% of players with migraine with aura and 90% of those without
aura. Recurrence rates were generally low, with 0% of migraine headaches and 25% 
non-migraine attacks recurring at 24 hours. Minor side effects were reported in
28 attacks. CONCLUSIONS: This pilot open label trial suggests that sumatriptan
nasal spray may be a valuable, effective, and convenient treatment of headache in
professional sport. There are potential risks of this drug that need to be
considered.

PMID: 16046342 [PubMed - indexed for MEDLINE]

1669: J Am Acad Nurse Pract. 2005 Aug;17(8):309-17.

Optimizing the diagnosis and treatment of migraine.

Sheftell FD, Cady RK, Borchert LD, Spalding W, Hart CC.

New England Center for Headache, Stamford, CT 06902, USA. ninotores1@aol.com

PURPOSE: To describe and discuss short headache questionnaires, which can
simplify and improve the diagnosis of migraine. DATA SOURCES: Review of the
worldwide scientific literature on short diagnostic questionnaires for migraine. 
CONCLUSIONS: A new three-question Headache Screen addressing disability due to
recurring headaches, headache duration, and changes in headache characteristics
and/or pattern over the previous 6 months displayed high sensitivity when used to
survey >3000 migraineurs, correctly identifying 77% of migraineurs diagnosed by
International Headache Society (IHS) criteria, clinical impression, or the
presence of recurring, disabling headaches. IMPLICATIONS FOR PRACTICE: The
underdiagnosis and undertreatment of migraine are problems that may be attributed
to many causes involving both patients and medical providers. These include
stringent diagnostic criteria established by the IHS, which fail to easily
classify many common migraine presentations, the lack of clear outcome measures
of successful management of migraine, and failure to recognize the iatrogenic
role of prescription and nonprescription medications as an etiologic factor in
chronic daily headache. The recent development of reliable, clinically useful,
short headache questionnaires that are focused on headache impact facilitates the
understanding and diagnosis of migraine for both patients and healthcare
professionals. As a diagnostic tool, the Headache Screen has the potential to
expand appropriate medication use, leading to improved functional status and
quality of life for migraineurs.

Publication Types: 
    Review

PMID: 16045591 [PubMed - indexed for MEDLINE]

1670: Clin Neurophysiol. 2005 Sep;116(9):2220-7.

Evaluating the effects of spatial frequency on migraines by using
pattern-reversal visual evoked potentials.

Shibata K, Yamane K, Iwata M, Ohkawa S.

Department of Medicine, Tokyo Women's Medical University, School of Medicine,
Daini Hospital, 2-1-10 Nishiogu, Arakawa-ku, Tokyo 116-8567, Japan.
kshbtgm@dnh.twmu.ac.jp

OBJECTIVE: To clarify the effects of contrast and spatial frequency in patients
with migraine by means of pattern-reversal visual evoked potentials (PVEPs).
METHODS: PVEPs were obtained from 14 patients who had migraine without aura (MO),
11 patients who had migraine with aura (MA), and 25 age-matched, healthy controls
(CO). PVEPs were binocularly recorded with a reversal rate of 1Hz (2 reversal/s) 
at 3 spatial frequencies (0.5, 1.0 and 4.0 cpd) at high (98%), medium (83%) and
low (29%) contrast. N75, P100 and N135 latency and the amplitudes of P50-N75,
N75-P100 and P100-N135 were analyzed. RESULTS: Increased amplitude of PVEPs in
patients with migraines were revealed at 3 different spatial frequencies in all
components. The MO and the MA showed increased amplitudes mostly in high
contrasts (98%). These findings were detected more at a high spatial frequency
(4.0 cpd) than at a low spatial frequency (0.5 cpd). Increased amplitude with
prolonged latency of N135 were found both in MO and MA at 4.0 cpd. CONCLUSIONS:
We conclude that pattern stimuli of high contrasts may be particularly effective 
in uncovering abnormal cortical reactivity which may be modified in the primary
and secondary visual cortex in the interictal state of migraine. SIGNIFICANCE:
These findings indicate that there is abnormal visual cortex processing in
patients with migraine.

Publication Types: 
    Clinical Trial

PMID: 16043404 [PubMed - indexed for MEDLINE]

1671: Proc Natl Acad Sci U S A. 2005 Aug 2;102(31):11106-11. Epub 2005 Jul 21.

Alterations in the alpha2 isoform of Na,K-ATPase associated with familial
hemiplegic migraine type 2.

Segall L, Mezzetti A, Scanzano R, Gargus JJ, Purisima E, Blostein R.

Departments of Biochemistry and Medicine, McGill University and Montreal General 
Hospital Research Institute, Montreal, Quebec, Canada H3G 1A4.

A number of missense mutations in the Na,K-ATPase alpha2 catalytic subunit have
been identified in familial hemiplegic migraine with aura. Two alleles (L764P and
W887R) showed loss-of-function, whereas a third (T345A) is fully functional but
with altered Na,K-ATPase kinetics. This study describes two additional mutants,
R689Q and M731T, originally identified by Vanmolkot et al. [Vanmolkot, K. R., et 
al. (2003) Ann. Neurol. 54, 360-366], which we show here to also be functional
and kinetically altered. Both mutants have reduced catalytic turnover and
increased apparent affinity for extracellular K(+). For both R689Q and M731T,
sensitivity to vanadate inhibition is decreased, suggesting that the steady-state
E(1) <==> E(2) poise of the enzyme is shifted toward E(1). Whereas the K'(ATP) is
not affected by the R689Q replacement, the M731T mutant has an increase in
apparent affinity for ATP. Analysis of the structural changes effected by T345A, 
R689Q, and M731T mutations, based on homologous replacements in the known crystal
structure of the sarcoplasmic reticulum Ca-ATPase, provides insights into the
molecular bases for the kinetic alterations. It is suggested that the disease
phenotype is the consequence of lowered molecular activity of the alpha2 pump
isoform due to either decreased K(+) affinity (T345A) or catalytic turnover
(R689Q and M731T), thus causing a delay in extracellular K(+) clearance and/or
altered localized Ca(2+) handling/signaling secondary to reduced activity in
colocalized Na(+)/Ca(2+) exchange.

Publication Types: 
    In Vitro
    Research Support, Non-U.S. Gov't

PMID: 16037212 [PubMed - indexed for MEDLINE]

1672: Cochrane Database Syst Rev. 2005 Jul 20;(3):CD002919.

Selective serotonin re-uptake inhibitors (SSRIs) for preventing migraine and
tension-type headaches.

Moja PL, Cusi C, Sterzi RR, Canepari C.

Centro Cochrane Italiano, Istituto Mario Negri, Via Eritrea, 62, Milano, Italy,
20157. moja@marionegri.it

BACKGROUND: Headache is a common medical problem. In view of recent discoveries
about the role of serotonin in pain mechanisms, selective serotonin re-uptake
inhibitors (SSRIs) have been evaluated for the prevention of migraine and
tension-type headaches (TTH). OBJECTIVES: To evaluate the efficacy and
tolerability of SSRIs for preventing migraine and TTH. SEARCH STRATEGY: We
searched MEDLINE (1966-2004), EMBASE (1994-2003), the Cochrane Central Register
of Controlled Trials (Issue 4, 2003), and reference lists of retrieved articles. 
Headache Quarterly was hand searched from 1990 to 2003. SELECTION CRITERIA: We
included randomised controlled trials comparing SSRIs with any type of control
intervention in patients of either sex, over 18 years of age, with migraine or
TTH. DATA COLLECTION AND ANALYSIS: Two authors independently extracted data
(headache frequency, index, severity, and duration; use of symptomatic/analgesic 
medication; days off work; quality of life; mood improvement; cost-effectiveness;
and adverse events) and assessed the methodological quality of trials. MAIN
RESULTS: Thirteen studies utilizing five SSRIs met the inclusion criteria (636
participants). Most of the included studies had methodological and/or reporting
shortcomings; follow up rarely extended beyond 3 months.After 2 months SSRIs did 
not significantly lower headache index scores in patients with migraine when
compared to placebo (SMD -0.14; 95% CI -0.57 to 0.30). Patients with chronic TTH 
treated with an SSRI had a significantly higher analgesic intake of 5 more doses 
per month when compared to patients treated with a tricyclic antidepressant (WMD 
4.98; 95% CI 1.12 to 8.84). Tricyclics also significantly reduced headache
duration by 1.26 hours per day (WMD 1.26; 95% CI 0.06 to 2.45) and marginally
reduced headache indexes (SMD 0.42; 95% CI 0.00 to 0.85) when compared to SSRIs
in patients with chronic TTH. When the data on adverse events were considered
without regard to headache diagnostic subgroups, there were no significant
differences between SSRIs and placebo for withdrawals due to adverse events (Peto
OR 1.02; 95% CI 0.31 to 3.34). For minor adverse events, SSRIs were generally
more tolerable than tricyclics (OR 0.34; 95% CI 0.13 to 0.92). However, there
were no differences in the number of patients withdrawing due to any reason in
the SSRI and tricyclic groups (OR 1.01; 95% CI 0.56 to 1.80). AUTHORS'
CONCLUSIONS: Over 2 months of treatment, SSRIs are no more efficacious than
placebo in patients with migraine. In patients with chronic TTH, SSRIs are less
efficacious than tricyclic antidepressants. In comparison with SSRIs, the burden 
of adverse events in patients receiving tricyclics was greater. These results are
based on short-term trials and may not generalise to longer-term treatment.

Publication Types: 
    Meta-Analysis
    Review

PMID: 16034880 [PubMed - indexed for MEDLINE]

1673: Am J Phys Med Rehabil. 2005 Aug;84(8):644-7.

Migraines linked to interferon-beta treatment of multiple sclerosis.

Khromov A, Segal M, Nissinoff J, Fast A.

Department of Physical Medicine and Rehabilitation, Weiler Hospital, Albert
Einstein College of Medicine, Bronx, New York, USA.

Migraine headache is now emerging as a previously under-recognized side effect of
interferon-beta, the most commonly used therapy for relapsing multiple sclerosis 
(MS). We describe an MS patient who developed migraine headaches, which followed 
a specific pattern coincident with interferon-beta administration. The frequency 
and severity of these migraines escalated and seemed to culminate in an MS
exacerbation. Since initiation of migraine prophylaxis with daily amitriptyline, 
our patient reported a significant decrease in the frequency and severity of her 
migraines on interferon. It has been postulated that migraine headaches may
trigger MS relapse. If so, migraine prophylaxis in MS patients, especially those 
treated with interferon-beta, is of paramount importance. Migraine headaches can 
be a significant source of disability. Identifying and treating migraines in MS
patients serves to enhance their function and reduce disability.

Publication Types: 
    Case Reports

PMID: 16034235 [PubMed - indexed for MEDLINE]

1674: Int J Clin Pract. 2005 Aug;59(8):961-8.

Comment in:
    Int J Clin Pract. 2006 Mar;60(3):367-8; author reply 368-9.

Topiramate 100 mg/day in migraine prevention: a pooled analysis of double-blind
randomised controlled trials.

Bussone G, Diener HC, Pfeil J, Schwalen S.

C. Besta Neurological Institute, Milan, Italy.

Topiramate has been shown to be effective as a preventive treatment for migraine 
in three large placebo-controlled, dose-ranging trials. Because the protocols
were similar in design using the same primary and secondary endpoints, data from 
these studies were pooled to evaluate the consistency of efficacy, efficacy by
gender and tolerability of topiramate 100 mg/day (n = 386) versus placebo (n =
372). Topiramate was superior to placebo as measured by the reduction in mean
monthly migraine frequency, monthly migraine days and monthly migraine duration. 
The responder rates, defined as at least 50% reduction for the respective
parameters, were significantly in favour of topiramate (p < 0.001), for example
46.3% of patients on topiramate achieved at least 50% reduction in monthly
migraine period frequency compared with 22.8% on placebo (p < 0.001). Use of
medication to treat the acute migraine attack was significantly reduced by
topiramate compared with placebo (p < 0.001). The therapeutic effect was
consistent throughout the different studies and independent of gender. The most
common adverse effect was paraesthesia, mostly of mild-to-moderate severity. The 
findings confirm that, at a dose of 100 mg/day, topiramate is an effective and
well-tolerated drug for migraine prevention.

Publication Types: 
    Meta-Analysis

PMID: 16033621 [PubMed - indexed for MEDLINE]

1675: Cephalalgia. 2005 Aug;25(8):612-21.

Parthenolide is the component of tanacetum parthenium that inhibits
nitroglycerin-induced Fos activation: studies in an animal model of migraine.

Tassorelli C, Greco R, Morazzoni P, Riva A, Sandrini G, Nappi G.

Laboratory of Pathophysiology of Integrative Autonomic Systems, IRCCS
Neurological Institute C. Mondino Foundation and University Centre for the Study 
of Adaptive Disorder and Headache, Pavia, Italy. cristina.tassorelli@mondino.it

Tanacetum parthenium (TP) is a member of the Asteracee family long used
empirically as a herbal remedy for migraine. So far, however, clinical trials
have failed to prove consistently the effectiveness of TP extracts in preventing 
migraine attacks, probably as a consequence of the uncertainty as regards the
active principle. In this study, the biological effects of different TP extracts 
and purified parthenolide were tested in an animal model of migraine based on the
quantification of neuronal activation induced by nitroglycerin. The extract
enriched in parthenolide significantly reduced nitroglycerin-induced Fos
expression in the nucleus trigeminalis caudalis. Purified parthenolide inhibited 
nitroglycerin-induced neuronal activation in additional brain nuclei and,
significantly, the activity of nuclear factor-kappaB. These findings strongly
suggest that parthenolide is the component responsible for the biological
activity of TP as regards its antimigraine effect and provide important
information for future controlled clinical trials.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16033387 [PubMed - indexed for MEDLINE]

1676: Cephalalgia. 2005 Aug;25(8):593-7.

Insulin sensitivity is impaired in patients with migraine.

Rainero I, Limone P, Ferrero M, Valfrè W, Pelissetto C, Rubino E, Gentile S, Lo
Giudice R, Pinessi L.

Neurology III-Headache Centre, Department of Neuroscience, University of Turin,
Italy. irainero@molinette.piemonte.it

Several studies have shown the presence of a comorbidity between migraine and
vascular diseases, like hypertension and stroke. The mechanisms of this
comorbidity are unknown. Impaired insulin sensitivity has recently emerged as a
risk factor for hypertension and stroke. We evaluated insulin sensitivity in 30
young, nonobese, nondiabetic, normotensive migraine patients and in 15 healthy
controls. During the OGTT, glucose plasma concentrations were significantly
higher in migraineurs than in controls. Insulin sensitivity, as measured by
ISI-stumvoll and OGIS-180 indexes, was significantly altered in migraine. Our
data show that insulin sensitivity is impaired in migraine and suggest a role for
insulin resistance in the comorbidity between migraine and vascular diseases.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 16033384 [PubMed - indexed for MEDLINE]

1677: Cephalalgia. 2005 Aug;25(8):575-80.

History of migraine and the risk of spontaneous cervical artery dissection.

Pezzini A, Granella F, Grassi M, Bertolino C, Del Zotto E, Immovilli P, Bazzoli
E, Padovani A, Zanferrari C.

Clinica Neurologica, Università degli Studi di Brescia, Brescia, Italy.
ale_pezzini@hotmail.com

The pathophysiology of spontaneous cervical artery dissection (sCAD) is largely
unknown. An association with migraine has been suggested, but not definitively
proven. In the setting of a hospital-based prospective case-control study we
assessed personal and family history of migraine in 72 patients with sCAD, 72
patients with cerebral infarct unrelated to a CAD (non-CAD) and 72 control
subjects. Personal history of migraine was significantly associated to sCAD
compared to non-CAD (59.7% vs. 30.6%; OR 3.14; 95% CI 1.41-7.01) and controls
(18.1%; OR 7.41; 95% CI 3.11-17.64). As opposed to migraine with aura, migraine
without aura was significantly more frequent among sCAD than among non-CAD (56.9%
vs. 25.0%; OR 3.91; 95% CI 1.71-8.90) and controls (12.5%; OR 9.84; 95% CI
3.85-25.16). Similar results were observed when the frequencies of family history
of migraine were compared. These findings are consistent with the hypothesis that
migraine may represent a predisposing condition for sCAD.

PMID: 16033382 [PubMed - indexed for MEDLINE]

1678: Cephalalgia. 2005 Aug;25(8):567-74.

Coupling between visual evoked cerebral blood flow velocity responses and visual 
evoked potentials in migraneurs.

Zaletel M, Strucl M, Bajrović FF, Pogacnik T.

Department of Neurology, University Medical Centre Ljubljana, Ljubljana,
Slovenia. marjan.zaletel@kclj.si

Neurovascular coupling may be altered in migraneurs. Therefore, visual evoked
potentials (VEP) and visually evoked cerebral blood flow velocity responses
(VEFR) were simultaneously recorded in 30 healthy controls and 30 migraneurs
interictally using a checkerboard stimulus with visual contrasts of 1%, 10% and
100%. The VEFR were measured in the posterior cerebral artery using transcranial 
Doppler and VEP were recorded from occipital leads. We found an increase in VEFR 
and VEP in both the healthy and migraneur groups (P < 0.01). VEFR were
significantly higher in migraneurs (P < 0.01), while VEP did not significantly
differ between the groups (P > 0.05). Regression showed a significant association
between VEP and VEFR in both healthy controls (r = 0.66, P < 0.01) and migraneurs
(r = 0.63, P < 0.01). The regression coefficient of migraneurs (b = 0.88, SE =
0.08) was significantly higher than that of healthy controls (b = 0.55, SE =
0.07) (P = 0.04). We conclude that neurovascular coupling is increased in
migraneurs interictally.

PMID: 16033381 [PubMed - indexed for MEDLINE]

1679: Cephalalgia. 2005 Aug;25(8):561-6.

Migraine--new perspectives from chaos theory.

Kernick D.

St Thomas Health Centre, Exeter, UK. su1838@eclipse.co.uk

Converging from a number of disciplines, non-linear systems theory and in
particular chaos theory offer new descriptive and prescriptive insights into
physiological systems. This paper briefly reviews an approach to physiological
systems from these perspectives and outlines how these concepts can be applied to
the study of migraine. It suggests a wide range of potential applications
including new approaches to classification, treatment and pathophysiological
mechanisms. A hypothesis is developed that suggests that dysfunctional
consequences can result from a mismatch between the complexity of the environment
and the system that is seeking to regulate it and that the migraine phenomenon is
caused by an incongruity between the complexity of mid brain sensory integration 
and cortical control networks. Chaos theory offers a new approach to the study of
migraine that complements existing frameworks but may more accurately reflect
underlying physiological mechanisms.

Publication Types: 
    Review

PMID: 16033380 [PubMed - indexed for MEDLINE]

1680: Curr Med Chem. 2005;12(15):1801-9.

Drug targets in stress-related disorders.

Covelli V, Passeri ME, Leogrande D, Jirillo E, Amati L.

Division of Neurology, Polyclinic Hospital, Bari Italy.

Nervous and immune systems mutually cooperate via release of mediators of both
neurological and immunological derivation. Adrenocorticotropin hormone (ACTH) is 
a product of the hypothalamus-pituitary adrenal axis (HPAA) which stimulates
secretion of corticosteroids from adrenals. In turn, corticosteroids modulate the
immune response in virtue of their anti-inflammatory activity. On the other hand,
catecholamines, products of the sympathetic nervous system (SNS), regulate immune
function by acting on specific beta-adrenergic receptors. Conversely, cytokines
released by monocytes/macrophages and lymphocytes, upon antigenic stimulation,
are able to cross the blood-brain-barrier, thus modulating nervous functions
(e.g., thermoregulation, sleep, and appetite). However, cytokines are locally
produced in the brain, especially in the hypothalamus, thus contributing to the
development of anorexic, pyrogenic, somnogenic and behavioural effects. Besides
pathogens and/or their products, the so-called stressors are able to activate
both HPAA and SNS, thus influencing immune responses. In this respect, many
studies conducted in medical students taking exams have evidenced an array of
stress-induced immune alterations. Phobic disorders and migraine without aura
(MWA) represent examples of stress-related disorders in which phagocytic immune
deficits, endotoxemia and exaggerated levels of proinflammatory cytokines [Tumor 
Necrosis Factor-alpha (TNF- alpha), and interleukin- 1 beta] have been detected. 
Quite interestingly, administration of a thymic hormone could ameliorate clinical
symptoms in phobic patients. In MWA patients, a beta-blocker, propranolol, could 
mitigate migraine, whose cessation coincided with a drop of TNF-alpha serum
concentration. In phobic disorders and in MWA, benzodiazepines are very often
administered and, in this respect, some of them, such as diazepam, inhibit immune
functions, while others, e.g., alprazolam, enhance immune responses. Alprazolam
could improve clinical symptoms in MWA patients. Chronic Fatigue Syndrome (CFS)
is a disorder whose etiology and pathogenesis are still unknown. In this syndrome
both abnormalities of nervous and immune systems have been reported. Despite many
immune parameters evaluated in CFS no specific biomarkers of disease have been
found. Our own data are in agreement with current literature in that we found
decreased levels of serum (IFN)-gamma in these patients, thus indicating a
predominance of T helper (h)1 response in CFS. Also leptin, a hormone which
regulates food intake, fluctuates within normal ranges in CFS individuals. Quite 
interestingly, in depressed patients, used as controls, leptinaemia was more
elevated than in CFS. Finally, in a series of recent therapeutic trials several
immunomodulating agents have been used, such as staphypan Berna, lactic acid
bacteria, kuibitang and intravenous immunoglobulin. In conclusion, it seems that 
major drug targets in stress-related disorders are immune cells in terms of
inhibition of proinflammatory cytokines and modulation of Th responses. In
particular, according to recent evidences, antidepressants seem to exert
beneficial effects in experimental autoimmune neuritis in rats by decreasing IFN-
beta release or augmenting NK activity in depressed patients.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 16029148 [PubMed - indexed for MEDLINE]

1681: J Pharmacol Exp Ther. 2005 Nov;315(2):849-57. Epub 2005 Jul 18.

Donitriptan decreases jugular venous oxygen saturation in rats in the absence of 
cranial vasoconstriction: an overlooked mechanism of antimigraine action?

Létienne R, Blanchet JC, Sole E, John GW, Le Grand B.

Centre de Recherche Pierre Fabre, Castres, France.
robert.letienne@pierre-fabre.com

The aim of the present study was to determine whether donitriptan and sumatriptan
decreased jugular venous oxygen saturation and increased carbon dioxide partial
pressure in venous blood. However, previous studies conducted with these
compounds cannot discriminate whether the decrease of venous oxygen saturation is
dependent of cranial vasoconstrictor. In the present study, vehicle (n = 10),
donitriptan (2.5, 10, and 40 microg/kg; n = 8) or sumatriptan (630 microg/kg; n =
8) were infused into the carotid artery in the anesthetized rat. Regional blood
flows were evaluated in the presence of donitriptan (10 microg/kg; n = 6) or
vehicle (n = 6). Jugular venous oxygen saturation was significantly decreased by 
donitriptan (from 10 microg/kg) with maximal changes of -32.9 +/- 8.0%. Jugular
carbon dioxide partial pressure was increased by donitriptan, reaching maximal
changes of 17.7 +/- 4.6% (P < 0.05 versus vehicle). Similarly, sumatriptan
significantly decreased venous oxygen saturation and increased jugular carbon
dioxide partial pressure. These changes induced by donitriptan are abolished by
the 5-hydroxytryptamine (5-HT)(1B/1D) receptor antagonist GR 127935
(N-[4-methoxy-3-(4-methyl-1-piperazinyl)phenyl]-2-[-methyl-4(5-methyl-1,2,4)-oxad
iazol-3-yl]-(1,1 biphenyl)-4-carboxamide dihydrochloride). In addition,
donitriptan was devoid of significant effects on systemic arterial pressure,
heart rate, or regional blood flows, including systemic arterial-jugular venous
anastomotic, systemic, or cranial. The results demonstrate that donitriptan
increases cerebral oxygen consumption by 5-HT(1B/1D) receptor activation in the
absence of cranial vasoconstriction.

PMID: 16027226 [PubMed - indexed for MEDLINE]

1682: Man Ther. 2006 May;11(2):118-29. Epub 2005 Jul 18.

Clinical tests of musculoskeletal dysfunction in the diagnosis of cervicogenic
headache.

Zito G, Jull G, Story I.

School of Physiotherapy, The University of Melbourne, Vic. 3010, Australia.
g.zito@unimelb.edu.au

Persistent intermittent headache is a common disorder and is often accompanied by
neck aching or stiffness, which could infer a cervical contribution to headache. 
However, the incidence of cervicogenic headache is estimated to be 14-18% of all 
chronic headaches, highlighting the need for clear criterion of cervical
musculoskeletal impairment to identify cervicogenic headache sufferers who may
benefit from treatments such as manual therapy. This study examined the presence 
of cervical musculoskeletal impairment in 77 subjects, 27 with cervicogenic
headache, 25 with migraine with aura and 25 control subjects. Assessments
included a photographic measure of posture, range of movement, cervical manual
examination, pressure pain thresholds, muscle length, performance in the
cranio-cervical flexion test and cervical kinaesthetic sense. The results
indicated that when compared to the migraine with aura and control groups who
scored similarly in the tests, the cervicogenic headache group had less range of 
cervical flexion/extension (P=0.048) and significantly higher incidences of
painful upper cervical joint dysfunction assessed by manual examination (all
P<0.05) and muscle tightness (P<0.05). Sternocleidomastoid normalized EMG values 
were higher in the latter three stages of the cranio-cervical flexion test
although they failed to reach significance. There were no between group
differences for other measures. A discriminant analysis revealed that manual
examination could discriminate the cervicogenic headache group from the other
subjects (migraine with aura and control subjects combined) with an 80%
sensitivity.

Publication Types: 
    Controlled Clinical Trial

PMID: 16027027 [PubMed - indexed for MEDLINE]

1683: J Neurol Neurosurg Psychiatry. 2005 Aug;76(8):1158-60.

Occipital activation in glyceryl trinitrate induced migraine with visual aura.

Afridi S, Kaube H, Goadsby PJ.

Headache Group, Institute of Neurology, Queen Square, London, WC1, UK,

A case of migraine is presented with visual aura triggered on two separate
occasions by glyceryl trinitrate (GTN). Positron emission tomography was carried 
out during the second triggering session. Activation in the primary visual area
of the occipital cortex was demonstrated during the aura. This is the first
published case of migraine aura triggered reproducibly by GTN.

Publication Types: 
    Case Reports

PMID: 16024898 [PubMed - indexed for MEDLINE]

1684: J Affect Disord. 2005 Sep;88(1):109-16.

Mitochondrial inheritance in depression, dysmotility and migraine?

Burnett BB, Gardner A, Boles RG.

Division of Medical Genetics and the Saban Research Institute, Childrens Hospital
Los Angeles, CA 90027, USA.

BACKGROUND: Several studies have reported a high degree of association of the
common conditions of depression, bowel dysmotility and migraine. Mitochondrial
dysfunction and mitochondrial DNA (mtDNA) sequence variants have been linked
individually to each of these three conditions, providing a plausible hypothesis 
for the reported association. If this hypothesis is correct, the matrilineal
relatives (who all share essentially the same mtDNA sequence) of patients with
mitochondrial disease secondary to inherited mtDNA mutations would be expected to
have an elevated prevalence of each of these three conditions. METHODS: Families 
were recruited by an advertisement posted on the United Mitochondrial Disease
Foundation website and invited to participate in an on-line questionnaire if at
least one member was diagnosed with mitochondrial disease by a physician. Based
upon the reported family histories, families were assigned by the investigators
to either the probable maternal inheritance (PMI) group (55 families) or the
probable non-maternal inheritance (PnMI) group (111 families). RESULTS: Bowel
disorders, migraine and depression were reported at very high prevalence in the
PMI mothers (60%, 54% and 51%, respectively), but were present at significantly
lower prevalence rates among the PnMI mothers (16%, 26% and 12%; P<0.0001 for
each) and the fathers of both groups (range 9-16%; P < 2 x 10(-6) for each).
Similar data was obtained comparing the prevalence rates among maternal and
paternal grandmothers, aunts and uncles. LIMITATIONS: Our data was obtained from 
families ascertained by the presence of a severely affected individual, and may
not be applicable to families lacking this proband. CONCLUSIONS: Depression,
bowel dysmotility and migraine are common manifestations in individuals with
mtDNA sequence-related mitochondrial dysfunction, which supports our hypothesis
that mitochondrial dysfunction is a major common factor underlying the
association of these three conditions.

PMID: 16019080 [PubMed - indexed for MEDLINE]

1685: Cleve Clin J Med. 2005 Jun;72(6):529-34.

Erratum in:
    Cleve Clin J Med. 2005 Aug;72(8):640.

Migraine aura without headache: benign, but a diagnosis of exclusion.

Kunkel RS.

Headache Center, Department of Neurology, The Cleveland Clinic Foundation, OH
44195, USA. kunkelr@ccf.org

Migraine aura without headache should be considered as a diagnosis in anyone who 
has recurrent episodes of transient symptoms, especially those that are visual or
neurological or involve vertigo. Visual and neurological symptoms due to migraine
are not unusual and most commonly occur in older persons with a history of
migraine headaches. Migraine aura without headache should be diagnosed only when 
transient ischemic attack and seizure disorders have been excluded.

Publication Types: 
    Review

PMID: 16018294 [PubMed - indexed for MEDLINE]

1686: Pediatr Ann. 2005 Jun;34(6):486-8, 490-2, 494-7.

The migraine variants.

Lewis DW, Pearlman E.

Children's Hospital of the King's Daughters, Eastern Virginia Medical School,
Norfolk, VA, USA. dlewis@chkd.com

The migraine variants are unique to pediatrics and are a fascinating and
challenging group of disorders characterized by the onset of focal neurological
signs and symptoms such as hemiparesis, altered consciousness nystagmus, or
ophthalmoparesis followed by headache. Because all of the diagnoses discussed
represent diagnoses of exclusion, only after a careful medical history, a
physical examination, and appropriate neurodiagnostic studies can they be
entertained comfortably. Often, these ominous neurological signs initially lead
the clinician in the direction of epileptic, cerebrovascular, traumatic, or
metabolic disorders, and only after thorough neurodiagnostic testing does the
diagnosis become apparent. Some of these entities occur in infants and young
children in which the medical history is limited.

Publication Types: 
    Review

PMID: 16018231 [PubMed - indexed for MEDLINE]

1687: Pediatr Ann. 2005 Jun;34(6):448-60.

The treatment of pediatric migraine.

Lewis DW, Yonker M, Winner P, Sowell M.

Children's Hospital of the King's Daughters, Eastern Virginia Medical School,
Norfolk, VA, USA. dlewis@chkd.com

The management of pediatric migraine requires a balance of biobehavioral measures
coupled with agents for acute treatment and, if needed, daily preventive
medicines. A recent American Academy of Neurology practice parameter has
critically reviewed the limited data regarding the efficacy and safety of
medicines for the acute and preventive therapy of pediatric migraine. The first
step is to establish the headache frequency and degree to which the migraines
impact upon lifestyle and performance. The next step is to institute
nonpharmacologic measures such as regulation of sleep (improved sleep hygiene),
moderation of caffeine, regular exercise, and identification of provocative
influences (eg, stress, foods, social pressures). A wide variety of therapeutic
options exist for patients whose migraine headaches occur with sufficient
frequency and severity to produce functional impairment. The most rigorously
studied agents for the acute treatment of migraine are ibuprofen, acetaminophen, 
and sumatriptan nasal spray, all of which have shown safety and efficacy in
controlled trials. Daily preventive drug therapies are warranted in about 20% to 
30% of young migraine sufferers. The particular drug selected for the individual 
patient requires an appreciation of comorbidities such as affective or anxiety
disorders, co-existent medical conditions such as asthma or diabetes, and
acceptability of potential toxicities such as weight gain, sedation, or tremor.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 16018227 [PubMed - indexed for MEDLINE]

1688: Clin Pediatr (Phila). 2005 Jul-Aug;44(6):505-8.

Relationship between cyclic vomiting syndrome and migraine.

Stickler GB.

Department of Pediatric and Adolescent Medicine, Mayo Clinic, Rochester, MN
55905, USA.

The strength of the association between cyclic vomiting syndrome (CVS) and
migraine was explored by studying the prevalence of migraine in patients with CVS
and their relatives versus geographic normal controls. A questionnaire was sent
to patients with CVS or their parents and to individuals of the same gender and
age living within 1 mile of the home of patients with CVS. Patients with CVS,
their mothers, and their grandmothers had a prevalence of migraine almost twice
as frequent as that in controls. In a large number of patients, CVS is
migraine-related.

PMID: 16015397 [PubMed - indexed for MEDLINE]

1689: Endoscopy. 2005 Jul;37(7):622-5.

Increased prevalence of migraine in patients with uninvestigated dyspepsia
referred for open-access upper gastrointestinal endoscopy.

Meucci G, Radaelli F, Prada A, Bortoli A, Crotta S, Cerrato C, Minoli G.

Valduce Hospital, Como, Italy. gastro@valduce.it

BACKGROUND AND STUDY AIMS: The association between gastrointestinal symptoms and 
headache is frequently unrecognized. The aim of the present study was to
determine the prevalence of migraine in dyspeptic outpatients referred for upper 
gastrointestinal endoscopy. PATIENTS AND METHODS: Patients aged 18 - 55 years
undergoing upper gastrointestinal endoscopy for dyspeptic symptoms in three
endoscopic units were recruited consecutively. All of the patients were given a
validated questionnaire on headache symptoms in order to determine the prevalence
of migraine. Patients were divided into four groups (ulcer-like dyspepsia,
reflux-like dyspepsia, dysmotility-like dyspepsia, only nausea and/or vomiting). 
Age-matched blood donors were given the same questionnaires and served as
controls. RESULTS: A total of 378 patients (mean age 40 +/- 11, 52 % men) and 310
controls (mean age 39 +/- 11, 56 % men) were enrolled. No differences were
observed between the two groups in the prevalence of migraine (15 % vs. 11 %; P =
0.12). A higher prevalence of migraine was found among women in both groups (P < 
0.006). In patients with reflux-like and ulcer-like dyspepsia, the prevalence of 
migraine did not differ from that in the control individuals (8 % and 7 %,
respectively), whereas a higher prevalence of migraine was noted in patients with
dysmotility-like dyspepsia (23 %; P < 0.02 vs. controls, those with ulcer-like
dyspepsia and those with reflux-like dyspepsia) and in patients with nausea
and/or vomiting alone (53 %; P < 0.002 vs. all other groups). The multivariate
analysis confirmed that the symptom pattern and sex were the only variables
independently associated with migraine. CONCLUSIONS: A diagnosis of migraine
should be considered in young patients referred for upper gastrointestinal
endoscopy due to nausea and/or vomiting or for dysmotility-like dyspepsia.

PMID: 16010605 [PubMed - indexed for MEDLINE]

1690: Brain. 2005 Sep;128(Pt 9):2068-77. Epub 2005 Jul 8.

Comment in:
    Brain. 2006 Jan;129(Pt 1):E39.

Infarcts in the posterior circulation territory in migraine. The population-based
MRI CAMERA study.

Kruit MC, Launer LJ, Ferrari MD, van Buchem MA.

Department of Radiology, Leiden University Medical Centre, 2300 RC Leiden, The
Netherlands. m.c.kruit@lumc.nl

In a previous study, migraine cases from the general population were found to be 
at significantly increased risk of silent infarct-like lesions in the posterior
circulation (PC) territory of the brain, notably in the cerebellum. In this study
we describe the clinical and neuroimaging characteristics of migraine cases with 
and without aura and controls with PC lesions. In total, 39 PC infarct-like
lesions represented the majority (65%) of all 60 identified brain infarct-like
lesions in the study sample (n = 435 subjects with and without migraine). Most
lesions (n = 33) were located in the cerebellum, often multiple, and were round
or oval-shaped, with a mean size of 7 mm. The majority (88%) of infratentorial
infarct-like lesions had a vascular border zone location in the cerebellum.
Prevalence of these border zone lesions differed between controls (0.7%), cases
with migraine without aura (2.2%) and cases with migraine with aura (7.5%).
Besides higher age, cardiovascular risk factors were not more prevalent in cases 
with migraine with PC lesions. Presence of these lesions was not associated with 
supratentorial brain changes, such as white matter lesions. The combination of
vascular distribution, deep border zone location, shape, size and imaging
characteristics on MRI makes it likely that the lesions have an infarct origin.
Previous investigators attributed cases of similar 'very small' cerebellar
infarcts in non-migraine patients to a number of different infarct mechanisms.
The relevance and likelihood of the aetiological options are placed in the
context of known migraine pathophysiology. In addition, the specific involvement 
of the cerebellum in migraine is discussed. The results suggest that a
combination of (possibly migraine attack-related) hypoperfusion and embolism is
the likeliest mechanism for PC infarction in migraine, and not atherosclerosis or
small-vessel disease.

Publication Types: 
    Multicenter Study
    Research Support, Non-U.S. Gov't

PMID: 16006538 [PubMed - indexed for MEDLINE]

1691: Curr Pain Headache Rep. 2005 Aug;9(4):289-93.

Migraine and white matter hyperintensities.

Porter A, Gladstone JP, Dodick DW.

University of Toronto, Division of Neurology, 1333 Sheppard Avenue East, Suite
122, M2J 1V1, Toronto, Ontario, Canada.

Patients with migraine are at increased risk for white matter hyperintensities
detected on magnetic resonance imaging. The presence of nonspecific white matter 
hyperintensities may cause uncertainty for physicians and anxiety for patients.
The pathophysiology and long-term consequences of these lesions are unknown.
Occasionally, white matter lesions in a migraineur may indicate an underlying
disease such as cerebral autosomal dominant arteriopathy with subcortical
infarcts and leukoencephalopathy (CADASIL), mitochondrial encephalopathy with
lactic acidosis and stroke-like episodes (MELAS), or central nervous system
vasculitis. The ability to distinguish between nonspecific and disease-specific
patterns of white matter hyperintensities in migraine sufferers is important for 
the practicing clinician.

Publication Types: 
    Review

PMID: 16004847 [PubMed - indexed for MEDLINE]

1692: Curr Pain Headache Rep. 2005 Aug;9(4):268-71.

Retinal migraine.

Grosberg BM, Solomon S, Lipton RB.

Department of Neurology, Albert Einstein College of Medicine and The Montefiore
Headache Unit, Montefiore Medical Center, Bronx, NY 10467, USA.
bgrosber@montefiore.org

Retinal migraine is a primary headache disorder, clinically manifested by attacks
of transient monocular visual loss associated with migraine headache. Although
isolated reports suggest that retinal migraine is rare, it likely is
under-recognized. Retinal migraine usually is reported in women of childbearing
age who have a history of migraine with aura. It typically is characterized by
negative monocular visual phenomena lasting less than 1 hour. More than half of
reported cases with recurrent transient monocular visual loss subsequently
experienced permanent monocular visual loss. Although the International Headache 
Society diagnostic criteria for retinal migraine require reversible visual loss, 
our findings suggest that irreversible visual loss is part of the retinal
migraine spectrum, likely representing an ocular form of migrainous infarction.

Publication Types: 
    Review

PMID: 16004843 [PubMed - indexed for MEDLINE]

1693: Sleep Med. 2005 Nov;6(6):537-42. Epub 2005 Jul 5.

Reevaluating spells initially identified as cataplexy.

Krahn LE.

Mayo Clinic in Scottsdale AZ, Mayo Clinic College of Medicine, 13400 East Shea
Boulevard, Scottsdale, AZ 85234, USA. krahn.lois@mayo.edu

BACKGROUND AND PURPOSE: Cataplexy, transient episodes of bilateral muscle
weakness with areflexia provoked by emotions, is a state highly specific to
narcolepsy. Cataplexy is diagnosed based on clinical interview. Two screening
tools have been developed recently but their usefulness has been limited because 
of length or current lack of psychometric data. Used effectively even these
screening tests require the interpreting physician to have an understanding of
the typical features of cataplexy. Most physicians encounter patients with
cataplexy fairly infrequently, making it difficult to gain proficiency in
detecting cataplexy based on clinical interview alone. Relatively little
attention has been given to the differential diagnosis of cataplexy, which
increases the likelihood of unnecessary sleep testing or false positive
diagnosis. PATIENTS AND METHODS: This case series describes six cases where
cataplexy was initially diagnosed. In all cases the weakness spells were
eventually not attributed to cataplexy. The presentation and characteristics of
these cases will be presented as a means to discuss the differential diagnosis of
cataplexy. RESULTS: These cases represent a diverse set of medical disorders
including bradycardia, migraine, delayed sleep phase syndrome, conversion
disorder, malingering and a chronic psychotic disorder. CONCLUSIONS: A more
in-depth understanding of the classic features of cataplexy should improve
recognition of this fascinating state. Improved cataplexy recognition will
enhance the appropriate usage of sleep tests and eventually increase the
timeliness and accuracy of the diagnosis of narcolepsy with cataplexy.

Publication Types: 
    Case Reports
    Research Support, N.I.H., Extramural

PMID: 15994123 [PubMed - indexed for MEDLINE]

1694: J Laryngol Otol. 2005 Jun;119(6):455-60.

Co-morbidity of migraine and Ménière's disease -- is allergy the link?

Sen P, Georgalas C, Papesch M.

Department of Otolaryngology and Head and Neck Surgery, Whipps Cross University
Hospital, London, UK. senswathi@aol.com

This study determined the prevalence of migraine and allergy in patients with
Ménière's disease (MD) compared with age- and sex-matched controls. We tested the
hypothesis that if migraine and MD is linked by allergy, then allergy should be
more prevalent in patients with MD and migraine compared with MD patients without
migraine. A web-based questionnaire was used to recruit patients with MD (n =
108) while the control group consisted of patients attending the ENT clinic for
other problems (n = 100).The prevalence of migraine and allergy was significantly
higher in patients with MD compared with age- and sex-matched controls (p > or = 
0.005). In addition, the prevalence of allergy was significantly higher in
patients who had both MD and migraine (30/42) than MD alone (26/66,p = 0.002).
However, there was no link with any specific allergy types. This study suggests
that migraine and MD may be linked by an immunological determinant.

PMID: 15992471 [PubMed - indexed for MEDLINE]

1695: Can Fam Physician. 2005 Jun;51:838-43.

Pharmacologic treatment of migraine. Comparison of guidelines.

Schuurmans A, van Weel C.

Dutch Institute for Effective Use of Medicine in Utrecht, The Netherlands.

OBJECTIVE: To compare guidelines (not the primary studies) for pharmacologic
treatment of migraine as to methods of guideline development; recommendations,
particularly on triptans; and quality of supporting evidence (with emphasis on
comparative studies of triptans versus ergot alkaloids and nonsteroidal
anti-inflammatory drugs [NSAIDs]). DATA SOURCES: We searched MEDLINE via PubMed
for guidelines on migraine management published since 1990 in any language; in
addition, we browsed the Internet for information. STUDY SELECTION: We found nine
clinical guidelines on migraine; one guideline, not supported by references, was 
excluded. SYNTHESIS: Preference for triptans is not well founded and is largely
based on comparisons with placebo. Too few studies compared new drugs with
established ones (NSAIDs or dihydroergotamine). Guidelines that propose a
hierarchy for selection of drugs are opinion-based rather than evidence-based.
CONCLUSION: The current lack of evidence from comparative studies seriously
limits development of evidence-based clinical practice guidelines for
pharmacologic treatment of migraine.

Publication Types: 
    Comparative Study
    Review

PMID: 15986940 [PubMed - indexed for MEDLINE]

1696: Neurology. 2005 Jun 28;64(12):2145-7.

Opening of the blood-brain barrier preceding cortical edema in a severe attack of
FHM type II.

Dreier JP, Jurkat-Rott K, Petzold GC, Tomkins O, Klingebiel R, Kopp UA,
Lehmann-Horn F, Friedman A, Dichgans M.

Department of Neurology, Charité University Medicine, 10117 Berlin, Germany.
jens.dreier@charite.de

The authors report a patient with familial hemiplegic migraine type II who
developed a long-lasting attack including fever, right-sided hemiplegia, aphasia,
and coma. Quantitative analysis of early gadolinium-enhanced MRI revealed a mild 
but significant left-hemispheric blood-brain barrier (BBB) opening limited to the
cortex and preceding cortical edema. The findings suggest that the delayed
cortical edema was vasogenic in the severe migraine aura variant of this ATP1A2
mutation carrier.

Publication Types: 
    Case Reports
    Research Support, Non-U.S. Gov't

PMID: 15985592 [PubMed - indexed for MEDLINE]

1697: Headache. 2005 Jul-Aug;45(7):953-6.

Migraine with aura related to closure of atrial septal defects.

Riederer F, Kaya M, Christina P, Harald G, Peter W.

A 27-year-old woman had a history of migraine with aura (MWA) since aged 13 years
with mostly two attacks per year. After transcutaneous closure of a secundum
atrial septal defect (ASD) she suffered from almost daily recurring migraine
attacks with prolonged aura symptoms. Exacerbation and new appearance of migraine
attacks with aura after transcutaneous closure of ASD have been described
previously.

Publication Types: 
    Case Reports
    Letter

PMID: 15985118 [PubMed - indexed for MEDLINE]

1698: Headache. 2005 Jul-Aug;45(7):936-8.

A high incidence of migraine with aura among morbidly obese women.

Horev A, Wirguin I, Lantsberg L, Ifergane G.

The Department of Neurology, Soroka Medical Center, Beer-Sheva, Israel.

INTRODUCTION: Nearly two-thirds of adults in the United States and an increasing 
percentage of the population worldwide are overweight or obese. The relationship 
of obesity to headache has received inadequate attention. We evaluated the
incidence of headache in a sample of morbidly obese women. METHODS: Morbidly
obese women, attending the surgical preoperative clinic of Soroka University
Medical Center for preoperative assessment for laparoscopic gastric banding were 
evaluated using a structured interview and their medical charts were reviewed.
RESULTS: During a 2-month period, 27 morbidly obese women were interviewed, with 
a mean BMI of 41.07. Ten patients suffered from migraine with aura, three from
migraine without aura, and four from tension headache. CONCLUSION: The unusually 
high incidence of migraine with aura can be attributed to extraovarian production
of estrogen and estradiol in the adipose tissue. Further study is indicated to
explore the therapeutic role of weight loss in headache care.

PMID: 15985113 [PubMed - indexed for MEDLINE]

1699: Headache. 2005 Jul-Aug;45(7):932-5.

Predictors of a negative response to topiramate therapy in patients with chronic 
migraine.

Rothrock JF, Parada VA, Drinkard R, Zweifler RM, Key KF.

The University of South Alabama, Mobile, AL 36693, USA.

OBJECTIVE: To identify variables predictive of a negative response to
prophylactic therapy with topiramate in patients with chronic migraine.
BACKGROUND: While certain of the newer antiepileptic drugs (AEDs) have emerged as
promising or definitely effective therapies for migraine prevention, we continue 
to lack biologic or clinical variables predictive of treatment response to these 
or other widely used prophylactic therapies. METHODS: A consecutive series of 170
patients with IHS-defined migraine who were experiencing 15 or more days of
headache per month were treated with topiramate according to a uniform dosing
protocol. Variables examined for their potential value in predicting treatment
response included age, gender, prior experience with prophylactic therapy, prior 
experience with divalproex sodium specifically, headache frequency and, if
present, duration of chronic daily headache (CDH). A positive treatment response 
was defined as a 50% or greater reduction in headache days during the second
treatment month relative to the patient's pretopiramate baseline. Only patients
who completed the treatment phase and achieved the 50 mg BID target dose were
analyzed (efficacy analysis). Each variable prospectively selected was evaluated 
in regards to treatment outcome via a paired t-test, and a multiple regression
analysis of all variables subsequently was performed. RESULTS: A total of 116
patients completed at least 60 days of treatment and consequently were available 
for analysis. In the efficacy analysis, 45 (38.8%) of the 116 responded
positively to topiramate. Neither age nor gender influenced treatment response.
Those patients with CDH of more than 6 months duration, patients who previously
had tried and failed more than three prophylactic agents and patients who
previously had failed to respond to divalproex sodium were more likely to be
nonresponders, but after multiple regression analysis the only statistically
significant predictor of a negative treatment response was CDH of more than 6
months duration (P<.001). CONCLUSIONS: Patients with chronic migraine who are
treated with topiramate may respond positively at a rate approaching that
reported from placebo-controlled trials involving topiramate or other AEDs
administered to less severely afflicted migraineurs. Our analysis suggests that
patients with chronic migraine least likely to respond to topiramate would be
those with extensive and negative previous experience with prophylactic therapy, 
previous failure to respond to divalproex sodium, CDH, and, most notably, CDH of 
more than 6 months duration.

Publication Types: 
    Clinical Trial

PMID: 15985112 [PubMed - indexed for MEDLINE]

1700: Headache. 2005 Jul-Aug;45(7):926-31.

Plasma cytokine levels in migraineurs and controls.

Perini F, D'Andrea G, Galloni E, Pignatelli F, Billo G, Alba S, Bussone G, Toso
V.

The Centri Cefalee e Malattie Cerebrovascolri, Ospedale S. Bortolo Ulss 6
Vicenza, Italy.

BACKGROUND: The vasoactive peptide, calcitonin gene-related peptide (CGRP), is
released from primary afferent neurons in the trigemino-vascular circulation
during migraine headache. CGRP at physiological concentrations and possibly via
stimulation of its selective receptors on T-cells, triggers the secretion of
cytokines. Cytokines play an important role in several physiological and
pathological settings such as immunology, inflammation, and pain. OBJECTIVE: To
investigate plasma levels of pro- and anti-inflammatory cytokines in migraineurs 
and healthy controls. METHODS: We studied 25 migraine patients, during and
outside attacks, and 18 healthy control subjects measuring plasma levels of IL-6,
IL-10, tumor necrosis factor alpha (TNFalpha), IL-4, IL-1 beta, and IL-2 using
ELISA. RESULTS: Circulating levels of IL-10, TNFalpha, and IL-1 beta during
attacks were significantly higher in comparison to their levels outside attacks
(P=.0003, P=.03, and P=.05, respectively). IL-10 and TNF serum levels were higher
in patients studied soon after headache onset and lower over time (P=.004 and
P=.05). CONCLUSION: Our results suggest that TNFalpha, IL-1 beta, and IL-10 may
be involved in the pathogenesis of migraine attacks.

Publication Types: 
    Comparative Study

PMID: 15985111 [PubMed - indexed for MEDLINE]

1701: Headache. 2005 Jul-Aug;45(7):920-5.

Comment in:
    Headache. 2006 Mar;46(3):532-3.

Time-series data and the "migraine generator".

Fox AW.

EBD Group, Carlsbad, CA 92009, USA.

OBJECTIVE: To examine circadian and menstrual patterns of migraine frequency in
order to identify properties of the putative migraine generator. METHODS:
Analysis of circadian and menstrual migraine attack frequency distributions,
using between-interval differences as estimates, at each time point, of the
derivative of the equation that would, theoretically, model the observed
oscillating functions. RESULTS: Circadian and menstrual analyses exhibit many
similarities that are consistent with a single migraine generator in the final
common pathway for expression of the phenotype. These analyses are inconsistent
with a role for cortisol or ACTH to be activators of the putative migraine
generator, could be consistent with visual stimulation as a deactivator of the
generator, and may also be consistent with a low threshold concentration of
estradiol and/or progestagens as inactivators of the migraine generator.
CONCLUSIONS: Analysis of time-series data using differentials uncovers some
previously unidentified chronobiological properties of migraine, helps select
amongst various candidate provocative factors, and suggests some properties of a 
putative migraine generator.

Publication Types: 
    Comparative Study

PMID: 15985110 [PubMed - indexed for MEDLINE]

1702: Headache. 2005 Jul-Aug;45(7):911-9.

Headache in Behçet's syndrome.

Saip S, Siva A, Altintas A, Kiyat A, Seyahi E, Hamuryudan V, Yazici H.

the Department of Neurology, Cerrahpasa Medical Faculty, Istanbul University,
Istanbul, Turkey.

OBJECTIVE: To study the frequencies and characteristics of different headache
types seen in patients with Behçet's syndrome (BS) in a large cohort of patients.
BACKGROUND: Patients with BS may present with different neurological problems,
related either directly or indirectly to the disease, with headache being the
most common neurological symptom seen in this syndrome, as well as independent
from neurologic involvement. METHOD: This study was carried out at the
multidisciplinary Behçet outpatient clinic of the Behçet's Syndrome Research
Center. Every fifth admitted patient who had fulfilled the International Study
Group for Behçet's Disease classification criteria was recruited for this study. 
Each patient was interviewed by one of the examining neurologists through a
semistructured questionnaire. In case of the presence of more than one headache
type, the best defined one was diagnosed and evaluated. All patients received a
complete neurological and physical examination. A chi(2) test was used to
evaluate the differences between frequencies. One sample t-test was used to
compare means. The prevalence rates of primary headaches were compared with
results of the Turkish Headache Epidemiology study by using goodness-of-fit test.
RESULTS: Two hundred and twenty-eight patients were studied. Headache was
reported in 66.2% (151/228) of the study cohort. Primary headaches were seen in
38.6% of the patient population, which corresponds to 58% of BS patients with any
type of headache. Tension-type headache (TTHA) and migraine were seen in 23.6%
and 14.9% of the whole study cohort, respectively. In 5.2% of the study cohort,
the headache was associated with neurological involvement and in 3.9% to uveal
inflammation. A predominantly frontal, bilateral paroxysmal throbbing pain of
moderate severity was reported in 18.4% of the study cohort who did not fulfill
the criteria of the International Headache Society (IHS) for any of the primary
headaches. It was commonly associated with exacerbations of the mucocutaneous
symptoms of the syndrome. The neurological examination was normal in all of these
patients. This type of headache was categorized as the nonstructural headache of 
Behçet. CONCLUSION: Headache is the most common neurological symptom seen in BS, 
both in patients with and without neurological involvement. The results of our
study reveal that headache is seen in a majority of patients with neurological
involvement due to BS and in a minority with uveal inflammation. The prevalence
of migraine and TTHA are close to the population in general, but a nonstructural 
migrainous headache, which is commonly associated with exacerbations with some of
the systemic symptoms of the syndrome, is noteworthy in patients with BS. This
form of headache is not specific for this disorder, but may be explained by a
vascular headache triggered by the immunomediated disease activity in susceptible
individuals.

PMID: 15985109 [PubMed - indexed for MEDLINE]

1703: Headache. 2005 Jul-Aug;45(7):904-10.

Headache and sleep: examination of sleep patterns and complaints in a large
clinical sample of migraineurs.

Kelman L, Rains JC.

The Headache Center of Atlanta, GA 30342, USA.

OBJECTIVES: This study characterized sleep parameters and complaints in a large
clinical sample of migraineurs and examined sleep complaints in relation to
headache frequency and severity. BACKGROUND: The relationship between headache
and sleep has been documented at least anecdotally in medical literature for well
over a century and clinical texts allude to the importance of sleep as a headache
precipitant. A small number of empirical studies have emerged, but the precise
nature and magnitude of the headache/sleep association and underlying mechanisms 
remain poorly understood. METHODS: In this investigation, 1283 migraineurs were
drawn from 1480 consecutive headache sufferers presenting for evaluation to a
tertiary headache clinic. Patients underwent a physical examination and
structured interview assessing a variety of sleep, headache, and demographic
variables. Migraine was diagnosed according the IHS criteria (1.1 to 1.6
diagnostic codes). Migraineurs were 84% female, with a mean age of 37.4 years.
Groups were formed based on patient's average nocturnal sleep patterns, including
short, normal, and long sleep groups, and were compared on headache variables.
RESULTS: Sleep complaints were common and associated with headache in a sizeable 
proportion of patients. Over half of migraineurs reported difficulty initiating
and maintaining sleep at least occasionally. Many in this sample reported
chronically shortened sleep patterns similar to that observed in persons with
insomnia, with 38% of patients sleeping on average 6 hours per night. Migraines
were triggered by sleep disturbance in 50% of patients. "Awakening headaches" or 
headaches awakening them from sleep were reported by 71% of patients.
Interestingly, sleep was also a common palliative agent for headache; 85% of
migraineurs indicated that they chose to sleep or rest because of headache and
75% were forced to sleep or rest because of headache. Patients with chronic
migraine reported shorter nightly sleep times than those with episodic migraine, 
and were more likely to exhibit trouble falling asleep, staying asleep, sleep
triggering headache, and choosing to sleep because of headache. Short sleepers
(ie, average sleep period 6 hours) exhibited significantly more frequent and more
severe headaches than individuals who slept longer and were more likely to
exhibit morning headaches on awakening. CONCLUSIONS: These data support earlier
research and anecdotal observations of a substantial sleep/migraine relationship,
and implicate sleep disturbance in specific headache patterns and severity. The
short sleep group, who routinely slept 6 hours per night, exhibited the more
severe headache patterns and more sleep-related headache. Sleep complaints
occurred with greater frequency among chronic than episodic migraineurs. Future
research may identify possible mediating factors such as primary sleep and mood
disorders. Prospective studies are needed to determine if normalizing sleep times
in the short sleeps would impact headache threshold.

PMID: 15985108 [PubMed - indexed for MEDLINE]

1704: Headache. 2005 Jul-Aug;45(7):899-903.

Efficacy and tolerability of intravenous valproic acid in acute adolescent
migraine.

Reiter PD, Nickisch J, Merritt G.

The Department of Pharmacy, The Children's Hospital, Denver, CO 80218, USA.

OBJECTIVE: To describe the efficacy and tolerability of rapid intravenous
valproic acid (VPA) infusions in children with severe migraine headache.
BACKGROUND: Intravenous VPA is an emerging treatment option for acute migraine
headache. Adult data suggests both efficacy and tolerability of rapid VPA
infusions as abortive therapy, but little data exist in children. METHODS: We
conducted a retrospective chart review of all children who received intravenous
VPA at The Children's Hospital Headache Clinic during an 18--month study period. 
Baseline intensity of headache pain, time at which maximum relief was attained,
pain reduction following therapy, dose and duration of VPA infusion(s), patient's
pulse, blood pressure, respiratory rate, and pulse oximetry were collected.
Adverse events were also recorded. RESULTS: Thirty-one children (age=15+/- 2
years; 81% female) requiring 58 clinic visits and 71 VPA infusions were included.
Most visits (n=45; 78%) resulted in only one dose of VPA (976+/- 85 mg infused
over 12+/- 4 minutes) for desired pain relief. Percent pain reduction in those
children was 39.8%, with time to maximum relief of 63+/- 31 minutes. Some
children required a second dose of 500 mg (n=13 visits; 22%), that was infused
over 14+/- 6 minutes and produced a 57% reduction in pain intensity from
baseline. VPA infusions were well tolerated. Adverse events described included
cold sensation (1), dizziness (3), nausea (1), possible absence seizure (1),
paraesthesia (2), and tachycardia (2). CONCLUSIONS: Rapid infusion of intravenous
VPA is generally well tolerated and may play a role in the management of children
with acute migraine headache. Prospective, controlled trials to further
investigate this treatment in children are warranted.

PMID: 15985107 [PubMed - indexed for MEDLINE]

1705: Headache. 2005 Jul-Aug;45(7):883-90.

Effects on productivity and quality of life of rizatriptan for acute migraine: a 
workplace study.

Láinez MJ, López A, Pascual AM.

Hospital Clinico Universitario de Valencia, Department of Neurology, Valencia,
Spain.

OBJECTIVE: To evaluate the impact of treatment with rizatriptan 10 mg on jobs and
quality of life of patients with migraine. METHODS: Prospective, open-label study
at 27 work sites of 20 companies representing diverse labor sectors in Spain.
Eligible patients according International Headache Society (IHS) criteria were
recruited for the study by on-site physicians and instructed to treat moderate or
severe migraine attacks with one tablet of rizatriptan 10 mg. They were asked to 
complete the study questionnaires (ML-96, SF-36) at baseline, and then 3 months
later. RESULTS: A total of 259 patients (83 men and 176 women) of a mean age of
39 (range 18 to 61 years) completed the study. Only 7% had taken triptans before 
for treatment of their migraine attacks. After 3 months of rizatriptan therapy,
the use of medical services was significantly lower and all tested domains of
quality of life had improved (P<.001). Absenteeism and days worked during
migraine attacks also fell significantly during 3 months of rizatriptan therapy
as compared with the 3 months before the study (P<.001). The improvement in
productivity was reflected in the significant decreases in lost workday
equivalents (decrease from 3.32 to 1.21 days; P<.001) and also in the total
number of workdays lost (decrease from 5.16 to 1.82 days; P<.001). Two-thirds of 
patients described the efficacy of oral rizatriptan as excellent or very good
(62%), and 89% preferred it over their usual medications for acute treatment of
migraine attacks. CONCLUSION: For this employed population of patients with
migraine, treatment with rizatriptan significantly improved parameters measuring 
direct medical costs, work and productivity, and health-related quality of life. 
In accordance with these findings, direct and indirect costs related to migraine 
could be substantially reduced by gathering detailed information about the nature
of headache, eliminating triggering factors, and instituting effective treatment 
of migraine attacks.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 15985105 [PubMed - indexed for MEDLINE]

1706: Headache. 2005 Jul-Aug;45(7):874-82.

Almotriptan in migraine patients who respond poorly to oral sumatriptan: a
double-blind, randomized trial.

Diener HC, Gendolla A, Gebert I, Beneke M.

Department of Neurology, University Essen and Bayer Healthcare, Essen, Germany.

OBJECTIVE: To investigate the efficacy and tolerability of almotriptan 12.5 mg in
migraine patients who respond poorly to sumatriptan 50 mg. BACKGROUND: Poor
response to sumatriptan therapy for acute migraine attacks has been documented in
the literature, but few controlled trials have investigated the efficacy of an
alternative triptan in this subgroup of patients. METHODS: Patients with an
International Headache Society diagnosis of migraine who self-described as
experiencing at least two unsatisfactory responses to sumatriptan treated their
first migraine attack with open-label sumatriptan 50 mg. Patients who did not
achieve 2-hour pain relief (improvement of headache from moderate/severe to
mild/no headache) were then randomized to treat their second attack with
almotriptan 12.5 mg or placebo under double-blind conditions. RESULTS: In the
first attack, 221 of 302 participants (73%) did not achieve 2-hour pain relief
with sumatriptan and were randomized to treatment of their second attack with
almotriptan 12.5 mg or placebo. Of the 198 sumatriptan nonresponders who treated 
their second attack (99 almotriptan; 99 placebo), 70% had severe headache pain at
baseline. Two-hour pain-relief rates were significantly higher with almotriptan
compared to placebo (47.5% vs 23.2%; P<.001). A significant treatment effect for 
almotriptan was also seen in pain-free rates at 2 hours (33.3% vs 14.1%; P<.005) 
and sustained freedom from pain (20.9% vs 9.0%; P<.05). In the second attack,
7.1% of patients in the almotriptan group experienced adverse events compared to 
5.1% in the placebo group (P=.77). CONCLUSIONS: Almotriptan 12.5 mg is an
effective and well-tolerated alternative for patients who respond poorly to
sumatriptan 50 mg. A poor response to one triptan does not predict a poor
response to other agents in that class.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 15985104 [PubMed - indexed for MEDLINE]

1707: Headache. 2005 Jul-Aug;45(7):850-61.

Terminating migraine with allodynia and ongoing central sensitization using
parenteral administration of COX1/COX2 inhibitors.

Jakubowski M, Levy D, Goor-Aryeh I, Collins B, Bajwa Z, Burstein R.

Department of Anesthesia, Beth Israel Deaconess Medical Center, Harvard Medical
School, Boston, MA 02115, USA.

OBJECTIVE: To determine whether delayed infusion of COX1/COX2 inhibitors
(ketorolac, indomethacin) will stop migraine in allodynic patients, and suppress 
ongoing sensitization in central trigeminovascular neurons in the rat.
BACKGROUND: The majority of migraineurs seeking secondary or tertiary medical
care develop cutaneous allodynia during the course of migraine, a sensory
abnormality mediated by sensitization of central trigeminovascular neurons in the
spinal trigeminal nucleus. Triptan therapy can render allodynic migraineurs pain 
free within a narrow window of time (20 to 120 minutes) that opens with the onset
of pain and closes with the establishment of central sensitization. Can drugs
that tackle ongoing central sensitization render allodynic migraineurs pain free 
after the window for triptan therapy has expired? METHODS: Patients exhibiting
migraine with allodynia were divided in two groups (n=14, each): group 1 received
delayed sumatriptan injection (6 mg) 4 hours after onset of attack--which failed 
to render them pain free-and ketorolac infusion (two 15-mg boluses) 2 hours
later; group 2 received delayed ketorolac monotherapy 4 hours after onset of
attack. Pain intensity (visual analog scale) and skin sensitivity (quantitative
sensory testing) were measured when the patients were migraine free (baseline); 4
hours after onset of migraine (just before treatment); 2 hours after sumatriptan;
1 hour after ketorolac. In the rat, we tested whether infusion of ketorolac (0.4 
mg/kg) or indomethacin (1 mg/kg) will block ongoing sensitization in peripheral
and central trigeminovascular neurons. The induction of sensitization (using
topical application of inflammatory soup on the dura) and its suppression by
COX1/COX2 inhibitors were assessed by monitoring changes in spontaneous activity 
and responses to mechanical and thermal stimuli. RESULTS: Patients had normal
skin sensitivity in the absence of migraine, and presented cutaneous allodynia 4 
hours after onset of migraine. In group 1, all patients continued to exhibit
allodynia 2 hours after sumatriptan treatment, and none of them became pain free.
However, 71% and 64% of the patients in groups 1 and 2, respectively, were
rendered free of pain and allodynia within 60 minutes of ketorolac infusion.
Nonresponders from both groups, in contrast to the responders, had had a history 
of opioid treatment. In the rat, infusion of COX1/COX2 inhibitors blocked
sensitization in meningeal nociceptors and suppressed ongoing sensitization in
spinal trigeminovascular neurons. This inhibitory action was reflected by
normalization of neuronal firing rate and attenuation of neuronal responsiveness 
to mechanical stimulation of the dura, as well as mechanical and thermal
stimulation of the skin. CONCLUSIONS: The termination of migraine with ongoing
allodynia using COX1/COX2 inhibitors is achieved through the suppression of
central sensitization. Although parenteral administration of COX1/COX2 inhibitors
is impractical as routine migraine therapy, it should be the rescue therapy of
choice for patients seeking emergency care for migraine. These patients should
never be treated with opioids, particularly if they had no prior opioid exposure.

Publication Types: 
    Clinical Trial
    Controlled Clinical Trial
    Research Support, N.I.H., Extramural
    Research Support, U.S. Gov't, P.H.S.

PMID: 15985101 [PubMed - indexed for MEDLINE]

1708: CNS Drugs. 2005;19(7):635-42.

Cost-effectiveness analysis of rizatriptan and sumatriptan versus Cafergot in the
acute treatment of migraine.

Zhang L, Hay JW.

Department of Pharmaceutical Economics and Policy, University of Southern
California, Los Angeles, California 90089, USA.

BACKGROUND: Both ergotamine and selective serotonin 5-HT(1B/1D) receptor agonists
('triptans') are currently used in the treatment of moderate to severe migraine. 
Ergotamine is a traditional therapy with a lower drug acquisition cost compared
with triptans. It has been shown that triptans are more efficacious than
ergotamine, but the higher acquisition costs and shorter duration of action are
disadvantages of triptans compared with ergotamine. OBJECTIVE: The purpose of
this study was to provide a comparison of the cost-effectiveness of rizatriptan
10 mg and sumatriptan 50 mg tablets with that of a fixed-dose combination of
ergotamine tartrate plus caffeine (Cafergot) in the treatment of an acute
migraine attack. The cost-effectiveness of rizatriptan in comparison with
sumatriptan was also assessed. METHODS: Three separate decision tree models were 
developed (model 1: rizatriptan vs Cafergot; model 2: sumatriptan vs Cafergot;
model 3: rizatriptan vs sumatriptan). The time horizon was 1 year.
Cost-effectiveness analysis was conducted from the societal perspective using
cost and effectiveness estimates from the literature. All costs were converted to
US dollars (2003). The cost-effectiveness ratio was expressed as incremental cost
per quality-adjusted life-year (QALY) gained. RESULTS: Base case evaluation
showed that both rizatriptan and sumatriptan dominated Cafergot. The net annual
saving associated with use of rizatriptan was US dollars 622.98 per patient, with
an incremental QALY of 0.001. Use of sumatriptan resulted in a saving of US
dollars 620.90 and an increase in QALY. The cost-effective ratios were not
sensitive to changes in key variables such as efficacy, utility, drug costs,
hospitalisation cost and patient preference over alternative therapies. The study
further showed that rizatriptan is more cost effective than sumatriptan, as
evidenced by its lower cost and greater effectiveness. Sensitivity analysis
showed that the cost-effectiveness ratios were sensitive to moderate changes in
drug efficacy. CONCLUSION: Rizatriptan and sumatriptan were less costly and more 
effective than Cafergot in the treatment of an acute migraine attack. Rizatriptan
was somewhat less costly and more effective than sumatriptan. Additional
quality-of-life studies are needed to confirm the benefits of using triptans in
the management of migraine.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 15984898 [PubMed - indexed for MEDLINE]

1709: J Clin Neurosci. 2005 Jun;12(5):534-7.

Migraine and risk of subarachnoid haemorrhage: a population-based case-control
study.

Carter KN, Anderson N, Jamrozik K, Hankey G, Anderson CS; Australasian
Co-operative Research on Subarachnoid Haemorrhage Study (ACROSS) Group.

The George Institute for International Health, University of Sydney, Sydney,
Australia. kcarter@thegeorgeinstitute.org

OBJECTIVE: Evidence exists for an association between migraine and ischaemic
stroke, but there is uncertainty about whether migraine is a risk factor for
subarachnoid haemorrhage (SAH). METHODS: A multi-centre, population-based,
case-control study using cases of first-ever SAH during 1995-98 and matched
controls in four study centres in Australia and New Zealand. Self- or
proxy-reported history, frequency and characteristics of headaches, classified
according to 1988 International Headache Society diagnostic criteria. RESULTS:
206 of 432 (48%) cases and 236 of 473 (50%) controls had a history of headaches. 
The frequency and characteristics of headaches were similar between the two
groups. No association was found in logistic regression analyses for history or
frequency of headaches, or migraine headaches. CONCLUSIONS: No evidence was found
for an association between recurrent headaches and SAH. Such information is
important for counselling patients and families about the significance of past
and ongoing headaches in relation to this illness.

Publication Types: 
    Multicenter Study
    Research Support, Non-U.S. Gov't

PMID: 15978814 [PubMed - indexed for MEDLINE]

1710: Clin Neurophysiol. 2005 Jun;116(6):1280-5. Epub 2005 Mar 28.

Decreased vasoreactivity to right cerebral hemisphere pressure in migraine
without aura: a near-infrared spectroscopy study.

Shinoura N, Yamada R.

Departments of Neurosurgery, Komagome Metropolitan Hospital, 3-18-22
Hon-Komagome, Bunkyo-ku, Tokyo 113-8677, Japan. shinoura@cick.jp

OBJECTIVE: Several studies have reported changes in cerebrovascular reactivity
during the interictal period of migraine. To characterize mechanisms of migraine,
we compared changes in total haemoglobin (THbl) and regional oxygen saturation
(rSO(2)) of the right and left frontal lobes in response to intracranial pressure
changes during the interictal period of migraine. METHODS: Twelve right-handed
migraineurs without aura and twelve age- and sex-matched healthy volunteers were 
asked to perform a head-down maneuver to increase intracranial venous pressure.
Initial THbl was designated as 1.0, and all subsequent THbl measurements, which
was proportional to the change in cerebral blood flow, were expressed as a value 
relative to this baseline. RESULTS: The head-down maneuver resulted in a
significantly smaller increase in right-sided THbl in migraineurs when compared
to volunteers (migraineurs, -0.1+/-0.04; volunteers, 30+/-13; P=0.027), but there
was no significant difference in left-sided THbl when comparing migraineurs and
volunteers. Further, the head-down maneuver produced a significantly smaller
increase in right-sided THbl than in left-sided THbl in migraineurs (right side, 
-0.1+/-0.04; left side, 0.35+/-0.08; P<0.0001), but produced a significantly
greater increase in right-sided THbl than in left-sided THbl in volunteers (right
side, 30+/-13; left side, 0.44+/-0.13; P=0.030). The head-down maneuver resulted 
in a smaller decrease in right-sided rSO(2) in migraineurs when compared to
volunteers (migraineurs, -4.1+/-2.2%; volunteers, -16+/-9.1%), but produced a
significantly greater decrease in left-sided rSO(2) in migraineurs when compared 
to volunteers (migraineurs, -1.3+/-1.1%; volunteers, 2.8+/-0.63%; P=0.0037).
CONCLUSIONS: These data indicate that pressure-related vasoreactivity is
suppressed in the right hemisphere of migraineurs during the interictal period.
SIGNIFICANCE: The suppression of vasoreactivity in the right hemisphere might be 
related to the pathogenesis of migraine.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 15978490 [PubMed - indexed for MEDLINE]

1711: Clin Neurophysiol. 2005 Jun;116(6):1254-64. Epub 2005 Apr 2.

Lack of habituation of nociceptive evoked responses and pain sensitivity during
migraine attack.

de Tommaso M, Lo Sito L, Di Fruscolo O, Sardaro M, Pia Prudenzano M, Lamberti P, 
Livrea P.

Neurologic and Psychiatric Sciences Department, Bari University, Clinica
Neurologica, Policlinico, Piazza Giulio Cesare 11, 70124 Bari.
m.detommaso@neurol.uniba

OBJECTIVE: The aim of the present study was to investigate the habituation of
subjective pain sensation to CO(2) laser stimulus, in relation to the amplitude
modifications of the cortical evoked responses (LEPs), during both the migraine
attack and the not symptomatic phase. METHODS: Fourteen migraine patients were
selected and compared with 10 healthy controls. Eight patients were evaluated
during both the pain-free and the attack phases. Three following series of 20
averaged LEPs were recorded, stimulating the hands and the supraorbital zones:
during the attack, two consecutive series of 20 averaged LEPs were carried out.
The subjective sensation was requested for each laser stimulus, using a 0-10
points Verbal Rating Scale (VRS). RESULTS: In normal subjects the N2-P2 waves
amplitude showed habituation across the three repetitions, which correlated with 
the habituation of the subjective rating of the stimulus. During the not
symptomatic phase, patients showed a lack of habituation of the N2-P2 amplitude
when the hand and the face was stimulated, with a pattern of increase of the pain
rating across the three repetitions; in addition there was a lack of correlation 
between the LEPs amplitude and the subjective sensation. During the attack, the
LEPs amplitude and the pain rating were increased when the face was stimulated,
but they did not habituate across the two repetitions, likely the pain-free
condition. The percent LEPs amplitude variation across the three repetitions
correlated with the main indices of migraine severity, mainly when the
supraorbital zone was stimulated. CONCLUSIONS: The abnormal cortical excitability
in migraine could condition an anomalous behavior of nociceptive cortex during
the interictal phase of migraine: it persists during the acute phase, and
correlates with the frequency and duration of migraine. SIGNIFICANCE: The reduced
habituation of the nociceptive cortex may concur with the onset and evolution of 
headache.

Publication Types: 
    Comparative Study

PMID: 15978487 [PubMed - indexed for MEDLINE]

1712: Pediatr Cardiol. 2005 May-Jun;26(3):231-3.

Migraine: traditional or "innovative" treatment? A preliminary case-control
study.

Morandi E, Anzola GP, Casilli F, Onorato E.

Neurology Clinic, Spedali Civili, Brescia, Italy.

The aim of this preliminary case-control study was to compare, in patients with
migraine and PFO, transcatheter closure of PFO vs. medical treatments. Twelve
patients were treated with antimigraine drugs and twelve underwent percutaneous
transcatheter closure. All patients were followed-up for 12 months. Our
preliminary results seem to confirm that, compared to medical treatment, PFO
closure is by far more effective in reducing both frequency, duration and
intensity of migraine attacks. Furthermore, the occurrence of prodromal aura is
almost abolished.

Publication Types: 
    Controlled Clinical Trial

PMID: 15977084 [PubMed - indexed for MEDLINE]

1713: Neuromolecular Med. 2004;6(2-3):105-16.

Functional effects of Na+,K+-ATPase gene mutations linked to familial hemiplegic 
migraine.

Capendeguy O, Horisberger JD.

Department of Pharmacology and Toxicology, Université de Lausanne, Rue du Bugnon 
27, CH-1005 Lausanne, Switzerland.

Familial hemiplegic migraine type 2, an autosomal dominant form of migraine with 
aura, has been associated with four distinct mutations in the alpha2-subunit of
the Na+,K+-ATPase. We have introduced these mutations in the alpha2-subunit of
the human Na+,K+-ATPase and the corresponding mutations in the Bufo marinus
alpha1-subunit and studied these mutants by expression in Xenopus oocyte.
Metabolic labeling studies showed that the mutants were synthesized and
associated with the beta-subunit, except for the alpha2HW887R mutant, which was
poorly synthesized, and the alpha1BW890R, which was partially retained in the
endoplasmic reticulum. [3H]ouabain binding showed the presence of the
alpha2HR689Q and alpha2HM731T at the membrane, whereas the alpha2HL764P and
alpha2HW887R could not be detected. Functional studies with the mutants of the B.
marinus Na+,K+-ATPase showed a reduced or abolished electrogenic activity and a
low K+ affinity for the alpha1BW890R mutant. Through different mechanisms, all
these mutations result in a strong decrease of the functional expression of the
Na+,K+-pump. The decreased activity in alpha2 isoform of the Na+,K+-pump
expressed in astrocytes seems an essential component of hemiplegic migraine
pathogenesis and may be responsible for the cortical spreading depression, which 
is one of the first events in migraine attacks.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 15970628 [PubMed - indexed for MEDLINE]

1714: J Interv Cardiol. 2005 Jun;18(3):181-3.

Intense migraines secondary to percutaneous closure of atrial septal defects.

Sharifi M, Dehghani M, Mehdipour M, Al-Bustami O, Emrani F, Burks J.

Section of Cardiology, Department of Medicine, Texas Tech University Health
Sciences, Center, Odessa, Texas, USA. seyedmohsensharifi@yahoo.com

In this study we evaluated the development of migraine after percutaneous closure
of atrial septal defect. An abrupt and excruciating form of migraine developed
shortly after shunt closure in 5 of 13 consecutive patients undergoing this
procedure. A dramatic relief of pain was achieved almost instantaneously after
administration of 300 mg of clopidogrel.

Publication Types: 
    Comparative Study

PMID: 15966922 [PubMed - indexed for MEDLINE]

1715: Acta Otolaryngol. 2005 Mar;125(3):276-9.

Comment in:
    Acta Otolaryngol. 2005 Nov;125(11):1247-8.

Migraine-associated vertigo.

Brantberg K, Trees N, Baloh RW.

Department of Audiology, Karolinska Hospital, Stockholm, Sweden.

CONCLUSIONS: It is probably not wise to demand a temporal relationship between
migraine symptoms and vertigo for the definition of migrainous vertigo. When
recurrent vertigo attacks begin at an early age in a patient with normal hearing 
and migraine, there are few diagnoses other than migraine that need to be
considered. OBJECTIVE: The clinical association between migraine and vestibular
symptoms, such as dizziness, motion intolerance and spontaneous attacks of
vertigo, is well documented. Recently, investigators have attempted to develop
diagnostic criteria for this association. We hypothesized that there are multiple
migraine-associated vestibular syndromes and studied a more homogenous subset of 
them (benign recurrent vertigo). MATERIAL AND METHODS: A structured interview was
conducted over the telephone with 40 patients who presented to our neurotology
clinic with benign recurrent vertigo and met the International Headache Society
criteria for migraine. The structured interview was also conducted with 40
relatives of the patients who reported the same symptoms. RESULTS: A marked
female predominance was found. Most of the patients had vertigo attacks lasting
minutes or hours and most were completely free of dizziness between attacks.
Imbalance and nausea typically accompanied the vertigo. However, in half of the
cases, vertigo occurred without an association with headache.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 15966697 [PubMed - indexed for MEDLINE]

1716: Int J Clin Pract. 2005 Jul;59(7):760-3.

Pain-relieving factors in migraine and tension-type headache.

Bag B, Karabulut N.

Department of Psychiatry Nursing, College of Nursing, Atatürk University,
Erzurum, Turkey. beyhanbag@yahoo.com

We performed the present study to compare patients with migraine and tension-type
headache (TTH) in their behaviour during the attacks and the manoeuvres to
relieve the pain. One hundred thirty consecutive patients with either migraine (n
= 75) or TTH (n = 55) were questioned (including the use of a checklist)
concerning their usual behaviour during the attacks and non-pharmacological
manoeuvres performed to relieve the pain. The results of the two types of
headache were compared. Patients with migraine tended to perform more manoeuvres 
than patients with TTH (mean: 4.3 vs. 3.6). These manoeuvres included pressing
and applying cold stimuli to the painful site, trying to sleep, changing posture,
sitting or reclining in bed (using more pillows than usual to lay down),
isolating themselves, using symptomatic medication, inducing vomiting, changing
diet and becoming immobile during the attacks. The only measure predominantly
reported by patients with TTH was scalp massage. Migraineurs, compared to
patients with TTH, changing eating habits, pressed the pain site; there were no
significant differences between the two groups. The behaviour of patients during 
headache attacks varies with the diagnosis. Measures that do not always result in
pain relief are performed in order to prevent its worsening or to improve
associated symptoms. These behavioural differences may be because of the
different pathogenesis of the attacks or of various styles of dealing with the
pain. They can also aid the differential diagnosis between headaches in doubtful 
cases.

PMID: 15963200 [PubMed - indexed for MEDLINE]

1717: CNS Drugs. 2005;19(6):465-81.

Migraine during pregnancy: options for therapy.

Fox AW, Diamond ML, Spierings EL.

EBD Group, Carlsbad, California 92009, USA. awfox@ebdgroup.com

Migraine is common during pregnancy, but fortunately this combination of
conditions obviously exists for only a finite period. The greatest frequency of
migraine attacks occurs during the first trimester. Accurate diagnosis is a sine 
qua non in this setting as in any headache patient. It is in the first trimester 
that the fetus is at greatest risk from abortifacient and teratogenic drugs, and 
when very early pregnancy may be undiagnosed. Ergot alkaloids (including
methysergide) should be avoided during pregnancy because of their teratogenicity,
and most other drug classes should be used only when unavoidable. The use of
prophylactic agents during pregnancy should be the exception, not the rule, and
preferably only during the second and third trimesters; propranolol is probably
safest in this situation. De novo headache during pregnancy usually requires
expert review of the patient. Treatment tactics for uncomplicated migraine in
pregnancy depend on the concurrent clinical situation. Paracetamol
(acetaminophen) is the mainstay for the patient whose typical attacks continue
into the first trimester. If paracetamol is insufficient, then partial agonist
opioids may be used if typical migraine attacks persist in the second and third
trimesters (which is uncommon). 'Chronic migraine' in pregnancy, i.e. >or=15
headache days per month, is rare, and is the greatest therapeutic challenge.
Co-morbidities such as depression or epilepsy require specialised approaches. The
complexities associated with these tactics are discussed in this article, and it 
is emphasised that none has the specific approval of regulatory authorities.
Heightened pharmacovigilance will better inform the future pregnant migraineur.
However, this type of information is less likely to be available for novel
classes of neuropharmacological agents than for existing ones.

Publication Types: 
    Review

PMID: 15962998 [PubMed - indexed for MEDLINE]

1718: Brain Res Brain Res Rev. 2005 Jul;49(1):65-76.

The role of mast cells in migraine pathophysiology.

Theoharides TC, Donelan J, Kandere-Grzybowska K, Konstantinidou A.

Department of Pharmacology and Experimental Therapeutics, Tufts University School
of Medicine and Tufts-New England Medical Center, 136 Harrison Avenue, Boston, MA
02111, USA. theoharis.theoharides@tufts.edu

Mast cells are critical players in allergic reactions, but they have also been
shown to be important in immunity and recently also in inflammatory diseases,
especially asthma. Migraines are episodic, typically unilateral, throbbing
headaches that occur more frequently in patients with allergy and asthma implying
involvement of meningeal and/or brain mast cells. These mast cells are located
perivascularly, in close association with neurons especially in the dura, where
they can be activated following trigeminal nerve, as well as cervical or
sphenopalatine ganglion stimulation. Neuropeptides such as calcitonin
gene-related peptide (CGRP), hemokinin A, neurotensin (NT), pituitary adenylate
cyclase activating peptide (PACAP), and substance P (SP) activate mast cells
leading to secretion of vasoactive, pro-inflammatory, and neurosensitizing
mediators, thereby contributing to migraine pathogenesis. Brain mast cells can
also secrete pro-inflammatory and vasodilatory molecules such as interleukin-6
(IL-6) and vascular endothelial growth factor (VEGF), selectively in response to 
corticotropin-releasing hormone (CRH), a mediator of stress which is known to
precipitate or exacerbate migraines. A better understanding of brain mast cell
activation in migraines would be useful and could lead to several points of
prophylactic intervention.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.
    Review

PMID: 15960987 [PubMed - indexed for MEDLINE]

1719: Eur J Neurol. 2005 Jul;12(7):557-63.

Multiple attack study on the available triptans in Italy versus placebo.

Vollono C, Capuano A, Mei D, Ferraro D, Pierguidi L, Evangelista M, Di Trapani G.

Headache Center, Università Cattolica del Sacro Cuore, Rome, Italy.

The aim of the study is to evaluate the efficacy and tolerability of the five
triptans that are commercially available in Italy (zolmitriptan 2.5 mg,
rizatriptan 10 mg, sumatriptan 100 mg, almotriptan 12.5 mg and eletriptan 40 mg).
The study was conducted in single-blind versus placebo and its duration was 18
months. At the Headache Centre of the 'Agostino Gemelli' Hospital in Rome we
selected 42 patients, suffering from headache with and without aura
(International Headache Society Committee on Headache Classification, 1988
Cephalalgia 8:1-96), whose headache frequency ranged between 1- and 4-monthly
crises. For a total of 25 crises, for every five consecutive crises, a different 
triptan was taken. The end-points of the study were as follows: response at 2 h, 
'pain free' at 2 h and 'sustained pain free' (at 24 h). The intra-patient
consistency and the tolerability were also evaluated. Thirty patients completed
the study and the statistical analysis was only applied to these patients. No
substantial difference in terms of the efficacy of the triptans was noted; all
triptans were well tolerated. These results suggest the possibility of testing
different triptans in the same patient in order to identify the ideal drug for
every patient.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial

PMID: 15958097 [PubMed - indexed for MEDLINE]

1720: Cephalalgia. 2005 Jul;25(7):542-4.

Migraine headache in patients with Sydenham's chorea.

Teixeira AL Jr, Meira FC, Maia DP, Cunningham MC, Cardoso F.

Movement Disorders Clinic, Hospital das Clínicas, Universidade Federal de Minas
Gerais, Belo Horizonte, Brazil.

We compared the frequency of migraine among Sydenham's chorea (SC) patients,
rheumatic fever (RF) patients without neurological symptoms and matched controls.
Migraine was more frequent in SC patients (12/55, 21.8%) than in controls (9/110,
8.1%) and as common as in the RF group (10/55, 18.2%). Our data are in agreement 
with previous studies reporting higher frequency of migraine in other basal
ganglia disorders, such as essential tremor and Tourette's syndrome.

Publication Types: 
    Clinical Trial
    Controlled Clinical Trial
    Research Support, Non-U.S. Gov't

PMID: 15955042 [PubMed - indexed for MEDLINE]

1721: Cephalalgia. 2005 Jul;25(7):536-41.

Platelet activation and platelet-leucocyte interaction in patients with migraine.
Subtype differences and influence of triptans.

Zeller JA, Lindner V, Frahm K, Baron R, Deuschl G.

Department of Neurology, Christian-Albrechts-University Kiel, Kiel, Germany.
j.zeller@neurologie.uni-kiel.de

As migraine is the result of an inflammatory mechanism with serotonergic
signalling, leucocyte function, platelet function and intercellular communication
between those cells is likely to be connected to the final pathway of the
disease. We examined P-selectin expression on platelets (platelet activation) and
leucocyte-platelet aggregate formation in 72 migraine patients during their
attack-free interval and controls using a flow cytometric assay. Patients
suffering from migraine without aura had a significantly increased platelet
activation and leucocyte-platelet aggregation compared with the control group,
unlike the migraine patients with aura. Patients who had taken a triptan within 3
days prior to the investigation showed platelet activation values similar to the 
control group. The variations in platelet activation patterns of migraine
subgroups could indicate different pathomechanisms. Even outside an attack,
migraine patients, particularly those without aura, show an increased level of
platelet activation which seems to be down-regulated by triptans. This mechanism 
may account for the triptan-induced increases in headache frequency. The
involvement of proinflammatory platelet-leucocyte cross-talk suggests a possible 
therapeutic strategy using anti-inflammatory drugs.

Publication Types: 
    Clinical Trial
    Controlled Clinical Trial

PMID: 15955041 [PubMed - indexed for MEDLINE]

1722: Cephalalgia. 2005 Jul;25(7):528-35.

The impact of migraine on epilepsy: a prospective prognosis study.

Velioğlu SK, Boz C, Ozmenoğlu M.

Neurology Department, Medical Faculty, Karadeniz Technical University (KTU),
Trabzon, Turkey. sveli@meds.ktu.edu.tr

The effect of migraine on the prognosis of epilepsy has not been reported. The
aim of this prospective 5-10-year follow-up study was to examine some outcome
measures and the cumulative probability of being seizure-free in epilepsy
patients with migraine, and to compare their results with those of epilepsy
patients without migraine. Fifty-nine patients (40 women; mean age 25 years) were
diagnosed with both epilepsy and migraine (EM group). The control group consisted
of 56 patients with epilepsy but without migraine (E group). Both groups were
recruited and followed up over similar periods. We compared the outcome variables
in the EM group with those in the E group. Kaplan-Meier methods were used to
assess the seizure-free curves. The EM group had a significantly lower cumulative
probability of being seizure-free over 10 years compared with the E group. The
other epilepsy outcome measures at follow-up differed significantly between the
groups, with the EM group having a longer duration of epilepsy, a lower early
treatment response, and a higher incidence of intractable epilepsy and achieving 
remission with polytherapy, and more seizure control and medication problems for 
at least the last 2 years of follow-up. Comorbid migraine had a negative effect
on the prognosis of epilepsy.

Publication Types: 
    Clinical Trial
    Controlled Clinical Trial

PMID: 15955040 [PubMed - indexed for MEDLINE]

1723: Cephalalgia. 2005 Jul;25(7):519-22.

Psychiatric comorbidity in the evolution from migraine to medication overuse
headache.

Radat F, Creac'h C, Swendsen JD, Lafittau M, Irachabal S, Dousset V, Henry P.

Chronic Pain Treatment Unit, Centre Hospitalo-universitaire, Bordeaux, France.
francoise.radat@chu-bordeaux.fr

We set out to study the role of psychiatric comorbidity in the evolution of
migraine to medication overuse headache (MOH) by a comparative study of 41
migraineurs (MIG) and 41 patients suffering from MOH deriving from migraine.
There was an excess risk of suffering from mood disorders [odds ratio (OR) = 4.5,
95% confidence interval (CI) 1.5, 13.5], anxiety (OR = 5, 95% CI 1.2, 10.7) and
disorders associated with the use of psychoactive substances other than
analgesics (OR = 7.6, 95% CI 2.2, 26.0) in MOH compared with MIG. Retrospective
study of the order of occurrence of disorders showed that in the MOH group,
psychiatric disorders occurred significantly more often before the transformation
from migraine into MOH than after. There was no crossed-family transmission
between MOH and psychiatric disorders, except for substance-related disorders.
MOH patients have a greater risk of suffering from anxiety and depression, and
these disorders may be a risk factor for the evolution of migraine into MOH.
Moreover, MOH patients have a greater risk of suffering from substance-related
disorders than MIG sufferers. This could be due to the fact that MOH is part of
the spectrum of addictive disorders.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 15955038 [PubMed - indexed for MEDLINE]

1724: Cephalalgia. 2005 Jul;25(7):507-18.

MR-spectroscopic imaging during visual stimulation in subgroups of migraine with 
aura.

Sándor PS, Dydak U, Schoenen J, Kollias SS, Hess K, Boesiger P, Agosti RM.

Neurology Department, University Hospital, Zurich, Switzerland.

Migraine pathophysiology possibly involves deficient mitochondrial energy reserve
and diminished cortical habituation. Using functional magnetic resonance
spectroscopic imaging (fMRSI), we studied cortical lactate changes during
prolonged visual stimulation to search for different pathophysiological
mechanisms in clinically distinct subgroups of migraine with aura. Eleven healthy
volunteers (HV) and 10 migraine patients were investigated interictally: five
with visual aura (MA) and five with visual symptoms and at least one of the
following: paraesthesia, paresis or dysphasia (MAplus). Using MRSI (Philips, 1.5 
T) (1)H-spectra were repeatedly obtained from a 25 mm-thick slice covering visual
and non-visual cortex, with the first and fifth measurements in darkness and the 
second to fourth with 8-Hz checkerboard stimulation. In MAplus lactate increased 
only during stimulation, only in visual cortex; in MA resting lactate was high in
visual cortex, without further increase during stimulation. This is compatible
with an abnormal metabolic strain during stimulation in MAplus, possibly due to
dishabituation, and a predominant mitochondrial dysfunction in MA.

Publication Types: 
    Clinical Trial
    Controlled Clinical Trial
    Research Support, Non-U.S. Gov't

PMID: 15955037 [PubMed - indexed for MEDLINE]

1725: Cephalalgia. 2005 Jul;25(7):493-506.

Prevalence, pattern and predictors of use of complementary and alternative
medicine (CAM) in migraine patients attending a headache clinic in Italy.

Rossi P, Di Lorenzo G, Malpezzi MG, Faroni J, Cesarino F, Di Lorenzo C, Nappi G.

Headache Clinic, INI Grottaferrata, University Centre for Adaptive Disorders and 
Headache, IRCCS C. Mondino Institute of Neurology and University of Pavia, Pavia,
Italy. paolo.rossi90@tin.it

The use of complementary and alternative medicine (CAM) in migraine is a growing 
phenomenon about which little is known. This study was undertaken to evaluate the
rates, pattern and presence of predictors of CAM use in a clinical population of 
patients with different migraine subtypes. Four hundred and eighty-one
migraineurs attending a headache clinic were asked to undergo a
physician-administered structured interview designed to gather information on CAM
use. Past use of CAM therapies was reported by 31.4% of the patients surveyed,
with 17.1% having used CAM in the previous year. CAM therapies were perceived as 
beneficial by 39.5% of the patients who had used them. A significantly higher
proportion of transformed migraine patients reported CAM treatments as
ineffective compared with patients suffering from episodic migraine (73.1% vs.
50.7%, P < 0.001). The most common source of a recommendation of CAM was a friend
or relative (52.7%). In most cases, migraineurs' recourse to CAM treatments was
specifically for their headache (89.3%). Approximately 61% of CAM users had not
informed their medical doctors of their CAM use. The most common reason for
deciding to try a CAM therapy was that it offered a 'potential improvement of
headache' (47.7%). The greatest users of CAM treatments were: patients with a
diagnosis of transformed migraine; those who had consulted a high number of
specialists and reported a higher lifetime number of conventional medical visits;
those with a comorbid psychiatric disorder; those with a high income; and those
whose headache had been either misdiagnosed or not diagnosed at all. Our findings
suggest that headache clinic migraine patients, in their need of and quest for
care, seek and explore both conventional and CAM approaches. Physicians should be
made aware of this patient-driven change in the medical climate in order to
prevent misuse of healthcare resources and to be better equipped to meet
patients' needs.

Publication Types: 
    Clinical Trial

PMID: 15955036 [PubMed - indexed for MEDLINE]

1726: Cephalalgia. 2005 Jul;25(7):482-7.

Migraine days decline with duration of illness in adolescents with transformed
migraine.

Bigal ME, Sheftell FD, Tepper SJ, Rapoport AM, Lipton RB.

Department of Neurology, Albert Einstein College of Medicine, New York, NY, USA. 
mbigal@aecom.yu.edu

The aim of this study was to assess the proportion of subjects with transformed
migraine (TM) who have 15 or more migraine days per month as a function of
duration of chronic daily headache (CDH) in an adolescent sample. CDH is a
syndrome characterized by 15 or more headache days per month. In specialty care, 
TM is the most common type of CDH. Most adults who meet criteria for TM do not
meet the International Headache Society (IHS) criteria for chronic migraine (CM).
TM criteria require 15 or more headache days per month (not necessarily
migraine), with a current or past history of migraine. CM requires 15 or more
migraine days per month. As TM develops, attack frequency increases and the
number of migraine features diminishes. If this observation is correct,
individuals who meet criteria for TM but not CM may be at a later stage in the
evolution of the disease, compared with those who meet criteria for CM. We
reviewed charts of 267 adolescents (13-17 years) seen in a headache centre, to
identify 117 with TM. We divide subjects with TM into those with recent onset
(</=1 year) vs. longer duration (>1 year) and examined the number of migraine
days per month and demographic features. We modelled predictors of CM (>15
migraine days per month) using logistic regression. Of 117 adolescents with TM,
55 (47%) had recent-onset (<1 year) and 62 (53%) had long-duration TM. Those with
recent-onset TM were much more likely also to meet criteria for CM (74.5% vs.
25.8%, P < 0.001). This was verified in the TM with medication overuse subgroup
(recent onset 66.7%, vs. long duration 37%, P = 0.01) and in the TM without
medication overuse subgroup (62.2% vs. 19.2%, P = 0.001). Modelling the
dichotomous outcome of CM (>15 days of migraine/month) in logistic regression, CM
was predicted by recent onset of CDH, recent onset of migraine (<36 months), and 
younger ages (</=15 years), but not gender or use of migraine preventive drugs or
medication overuse. Among adolescents with TM, CM is more likely in individuals
who are young, whose episodic headache began recently, and with CDH of recent
onset. These findings suggest that early in the process of transformation,
migraine is more frequent, and that as CDH evolves, fewer typical attacks of IHS 
migraine occur.

Publication Types: 
    Clinical Trial
    Controlled Clinical Trial

PMID: 15955034 [PubMed - indexed for MEDLINE]

1727: Brain Res Mol Brain Res. 2005 Sep 13;139(1):163-8.

Thymidylate synthase promoter tandem repeat and MTHFD1 R653Q polymorphisms
modulate the risk for migraine conferred by the MTHFR T677 allele.

Oterino A, Valle N, Pascual J, Bravo Y, Muñoz P, Castillo J, Ruiz-Alegría C,
Sánchez-Velasco P, Leyva-Cobián F, Cid C.

Services of Neurology, University Hospital Marqués de Valdecilla (UC),
Santander-39008, Spain. aoterino@humv.es

There is growing evidence that folate metabolism is involved in migraine
pathophysiology, mainly in migraine with aura. Even though folate metabolism is
regulated by a number of enzymes, only two functional polymorphisms have been
tested in association studies with migraine. Here, we have explored the possible 
role in migraine of other folate-metabolizing enzymes which are in close
interdependency with 5',10'-methylenetetrahydrofolate reductase analyzing
functional polymorphisms of these enzymes in a case-control study. Individually, 
thymidylate synthase (TS), methenyltetrahydrofolate cyclohydrolase
formyltetrahydrofolate synthase (MTHFD1), or methionine synthase (MS)
polymorphisms did not modify the general risk for suffering migraine.
Nevertheless, we observed a strong interaction between TS and MTHFR mutated
genotypes, which increased over 8-fold the risk for experiencing aura among
migraineurs; MTHFD1 and MTHFR mutated genotypes also increased together the risk 
for migraine in general (OR = 3.08; 95% CI = 1.3-7.4). We conclude that the
pathogenetic role of the MTHFR T677 allele in migraine is modulated by functional
polymorphisms of TS and MTHFD1.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 15953655 [PubMed - indexed for MEDLINE]

1728: Headache. 2005 Jun;45(6):757-9.

Water deprivation: a new migraine precipitant.

Blau JN.

The City of London Migraine Clinic, 22 Charterhouse Square, London EC1M 6DX, UK.

Fifty migraineurs were asked if insufficient fluid intake could provoke their
migraine attacks. Twenty replied "yes," 7 were doubtfully positive, and 23 said
"no." In addition 14 of 45 migraineurs at a meeting of the British Migraine
association (UK) also recognized fluid deprivation as one of their migraine
triggers. Thus a total of 34 of 95 migraineurs knew that dehydration could
provoke their attacks, a precipitant not recognized by the medical profession.
This indicates that we can add fluid deprivation to our list of migraine
precipitants. It would be interesting to know the extent to which it applies in
other climates. Further research is needed into the mechanism of this
precipitant.

PMID: 15953311 [PubMed - indexed for MEDLINE]

1729: Headache. 2005 Jun;45(6):692-704.

Relaxation treatment of adolescent headache sufferers: results from a
school-based replication series.

Larsson B, Carlsson J, Fichtel A, Melin L.

Department of Child and Adolescent Psychiatry, NTNU, Kolstergata 46/48, N-7489
Trondheim, Norway.

BACKGROUND: In recent reviews of psychological and drug treatment, relaxation
training approaches have been found to be efficacious for children and
adolescents suffering from recurrent tension-type headache (TTH), while
biofeedback procedures provide effective help for migraine headache sufferers,
primarily treated in tertiary clinics. OBJECTIVE: In a school-based replication
series, the effectiveness and efficiency of relaxation training provided within
school settings were examined, in addition to the effects on various headache
features and the maintenance of treatment gains at a 6 to 10-month follow-up.
METHODS: Over a 20-year period, 288 adolescents aged 10 to 18 years participated 
in seven randomized, controlled trials conducted within regular school health
service settings. Subjects were included if they had suffered from frequent
migraine or TTHs, or from both headache types for at least 1 year. Various
formats of standardized relaxation training procedures were contrasted to
different attention-control (ATCO) approaches or self-monitoring (SM) of
headaches in prospective diary recordings. RESULTS: The results showed that a
therapist-administered relaxation approach was superior to self-help or
school-nurse administered relaxation training approaches, ATCO conditions or SM
of headaches. Students with TTHs responded positively to any form of relaxation
training, whereas those with frequent migraine responded well only to
therapist-administered relaxation. However, school-nurse administered procedures 
were found to be the most efficient form of relaxation treatment, in particular
for adolescents suffering from TTHs. Total headache activity, the number of
headache days and peak headache intensity were significantly reduced after
relaxation treatment, in addition to medication usage. Treatment gains were well 
maintained at the 6 to 10-month follow-up. CONCLUSION: Therapist-assisted
relaxation training is an effective treatment for adolescents suffering from
frequent TTHs or migraine. However, such treatment administered by school-nurses 
administered within school health care settings is an efficient treatment
approach for adolescents suffering from the most common form of primary headache,
ie, TTHs.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial

PMID: 15953302 [PubMed - indexed for MEDLINE]

1730: Headache. 2005 Jun;45(6):670-7.

The association of brainstem lesions with migraine-like headache: an imaging
study of multiple sclerosis.

Gee JR, Chang J, Dublin AB, Vijayan N.

Headache and Neurology Clinic, University of California-Davis, Davis, CA, USA.

OBJECTIVE: To determine if the prevalence of migraine-like headache in patients
with multiple sclerosis (MS) is associated with plaques in the brainstem or in
other locations. BACKGROUND: There is increasing evidence to suggest that
periaqueductal gray matter (PAG) plays a role in the pathophysiology of migraine 
headache. There are a few clinical case studies and some experimental evidence in
support of this observation. METHODS: The study population of patients with
demyelinating disease was identified by accessing the Department of Radiology
magnetic resonance imaging (MRI) database accumulated between the years of
December 1992 and June 2002. A total of 4369 MRI scan reports were available for 
review from that time period. Out of this, 1533 studies were reported to have
possible demyelinating lesions. Medical records of these patients were reviewed
to confirm the diagnosis of MS and also to document the headache complaints, if
any. Two hundred and seventy-seven patients were identified with definite MS. A
questionnaire was mailed to these patients to obtain additional details regarding
MS and headache. The questionnaire response rate was 61% (169 of 277). This data 
were added to the information previously obtained from the medical records. The
MRI films of each patient were examined, documenting location of the plaque,
rather than the actual number. MRI and clinical data were kept separate until the
final analysis. The International Headache Society criteria were used to classify
headache types. RESULTS: There were 207 female and 70 male patients available for
analysis. Sixty-six percent (182 of 277) of patients were diagnosed with
remitting-relapsing MS, 17% (47 of 277) with primary progressive MS, and 17% (48 
of 277) with secondary progressive MS. Overall, 55.6% (154 of 277) of patients
had a complaint of headache. Of these patients, 61.7% (95 of 154) met criteria
for migraine-like headache, 25.3% (39 of 154) met criteria for tension-type
headache, and 13% (20 of 154) had features of migraine and tension-type headache.
MS patients with a plaque within the midbrain/periaqueductal gray matter areas
had a four-fold increase in migraine-like headaches (odds ratio 3.91, 95%
confidence interval 2.01 to 7.32; P < .0001), a 2.5-fold increase in tension-type
headaches (odds ratio 2.58, 95% confidence interval 1.13 to 5.85; P= .02), and a 
2.7-fold increase in combination of migraine and tension-type headaches (odds
ratio 2.77, 95% confidence interval 0.98 to 7.82; P= .05) when compared to MS
patients without a midbrain/periaqueductal gray matter lesion. Although not
statistically significant, MS patients with three or more lesion locations were
found to be approximately two times more likely to have migraine-like headaches
compared to MS patients with 0 to 2 locations (3 to 5: odds ratio 2.47, 95%
confidence interval 0.90 to 6.84; 6 to 8 locations: 1.82, 0.64 to 5.17; > or =9
locations: 2.41, 0.63 to 9.13). A linear trend was also observed between numbers 
of lesion locations and migraine-like headaches (P= .02). CONCLUSION: The results
of this study indicate that the presence of a midbrain plaque in patients with MS
is associated with an increased likelihood of headache with migraine
characteristics. (Headache 2005;45:670-677).

PMID: 15953299 [PubMed - indexed for MEDLINE]

1731: Headache. 2005 Jun;45(6):653-6.

Triggers of motion sickness in migraine sufferers.

Drummond PD.

School of Psychology, Murdoch University, 6150 WA, Western Australia.

OBJECTIVE: To determine whether susceptibility to motion sickness provoked by
unexpected movement is associated with susceptibility to visually induced motion 
sickness in migraine sufferers. BACKGROUND: Migraine sufferers are unusually
susceptible to motion sickness, but the mechanism of this susceptibility is not
well understood. Possibilities include vestibular dysfunction secondary to
vasomotor disturbances during migraine attacks, hyperexcitability of brainstem
circuits that produce symptoms of motion sickness and migraine, and heightened
susceptibility to visual illusions of movement. METHOD: A motion sickness
susceptibility questionnaire that listed common triggers of motion sickness was
filled out by 42 migraine sufferers and 39 headache-free controls of similar age 
and sex distribution to migraine sufferers. RESULTS: A greater proportion of
migraine sufferers than controls reported that traveling in cars and buses,
reading in the car, using playground equipment, watching wide-screen movies and
movement simulators, induced motion sickness. However, visually induced motion
sickness appeared to be independent of motion sickness to most movement-related
stimuli in migraine sufferers. CONCLUSIONS: The lack of association between
susceptibility to movement-induced and visually induced motion sickness implies
that more than one mechanism increases susceptibility to motion sickness in
migraine sufferers.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 15953297 [PubMed - indexed for MEDLINE]

1732: Headache. 2005 Jun;45(6):624-31.

Consistent efficacy, tolerability, and high levels of satisfaction with
almotriptan 12.5 mg when used to treat multiple migraine attacks in routine
clinical practice.

Diener HC.

Department of Neurology, University of Essen, Hufelandstrasse 55, D-45145 Essen, 
Germany.

OBJECTIVE: To assess the efficacy, tolerability, and patient satisfaction with
almotriptan 12.5 mg across multiple migraine attacks in routine clinical
settings. BACKGROUND: The efficacy and tolerability of almotriptan have been
well-documented in clinical trials. Less information is available about patient
acceptance of therapy under normal prescribing conditions in routine practice.
METHODS: This was a prospective, open-label surveillance study conducted on 899
adults with documented attacks fulfilling the IHS criteria for migraine in
medical practices of 307 neurologists and primary care physicians across Germany 
from June 2001 to April 2002. Patients were eligible for inclusion in the study
if they were being treated for the first time with almotriptan. Main outcome
measures were pain relief, pain free, consistency, tolerability, and satisfaction
with almotriptan 12.5 mg when used to treat multiple migraine attacks. RESULTS: A
total of 899 patients with migraine treated 1 (18.4%), 2 (25.9%), or 3 (55.6%)
migraine attacks with almotriptan for a total of 2131 attacks. Pain relief at 2
hours was achieved in 84.5% of attacks; pain free was achieved in 41.4%.
Consistency of almotriptan 12.5 mg (at least 2 out of 3 attacks successfully
treated) was 87.3%. Most patients (88.5%) indicated that they were "satisfied" or
"very satisfied" with their treatment with almotriptan and 80.3% of patients
expressed that almotriptan 12.5 mg therapy was better than their prior therapy.
Physicians' global assessment of the efficacy of almotriptan 12.5 mg was judged
to be "good" and "very good" in 87.6% of the patients, and tolerability was
considered to be "good" and "very good" in 96.3% of patients. More than 92% of
physicians indicated that they would continue to prescribe almotriptan for their 
patients. CONCLUSION: The high levels of efficacy, consistency, and tolerability 
of almotriptan 12.5 mg observed in this postmarketing surveillance study are not 
only consistent with the findings of controlled clinical trials but also resulted
in high rates of patient and physician satisfaction with almotriptan and patient 
preference for almotriptan over prior acute treatments, including other triptans.

PMID: 15953293 [PubMed - indexed for MEDLINE]

1733: Headache. 2005 May;45(5):590-6.

Comorbidity of psychiatric and behavioral disorders in pediatric migraine.

Pakalnis A, Gibson J, Colvin A.

Department of Pediatrics, The Ohio State University, College of Medicine,
Columbus, OH 43205, and Department of Psychology, Columbus Children's Hospital,
OH, USA.

OBJECTIVE: To determine whether behavioral and psychiatric disorders occur more
frequently in school-age children with migraine headache. To also elucidate
treatment response related to comorbid psychiatric or behavioral diagnosis.
BACKGROUND: Recurrent migraine headaches are common in school-age children.
Concurrent behavioral or psychiatric diagnoses could significantly impact
headache frequency, severity, and response to treatment. METHODS: Healthy
children from 6 to 17 years of age presenting to our headache clinic with
migraine headache according to International Headache Society (IHS) criteria were
identified. Parents/guardians were asked to complete the Child Symptom Inventory,
4th edition (CSI-4) after written informed consent. Children with positive rating
scales underwent psychological interviews for confirmatory diagnosis. Results
were compared to controls. Headache patients were assigned our usual treatment
paradigm. Response regarding headache frequency was assessed at 3 months.
RESULTS: A total of 47 patients were diagnosed with migraine headaches. The mean 
age was 10.55 years. Thirty controls were identified. After completing the CSI-4 
and confirmatory psychological interview, 14 of 47 headache patients fulfilled
Diagnostic and Statistical Manual (DSM-4) criteria for a psychiatric or
behavioral disorder. Oppositional defiant disorder (ODD) was significantly
represented among children with migraine compared to the control group of
children. Headache patients improved significantly post-treatment regarding their
headache frequencies regardless of comorbid psychiatric or behavioral disorder.
No significant differences were noted between boys and girls regarding diagnoses 
or treatment outcome. CONCLUSION: ODD was a significant comorbidity in our
headache population. Although families complained of significant behavioral
symptomatology in their children, most of these symptoms did not qualify their
children for a psychiatric diagnosis and may be related to the stressors of
headache on social/school disruption.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 15953278 [PubMed - indexed for MEDLINE]

1734: Headache. 2005 May;45(5):571-81.

Patients' management of migraine and chronic daily headache: a study of the
members of the Migraine Action Association (United Kingdom).

Peters M, Abu-Saad HH, Robbins I, Vydelingum V, Dowson A, Murphy M.

University of Surrey, European Institute of Health and Medical Sciences,
Guildford, Surrey, United Kingdom

BACKGROUND: Many strategies are available to treat and prevent migraine and
chronic daily headache (CDH). Broadly these strategies can be divided into four
groups, including (i) health care consultations, (ii) medication and alternative 
remedies, (iii) general (acute and prophylactic) strategies, and (iv) social
support. OBJECTIVE: This study aimed to compare headache management between
migraine (MO), migraine with aura (MA), and those with CDH over the last 12
months. DESIGN: A postal questionnaire was sent to 887 members of the Migraine
Action Association (MAA). The response rate was 60.5% (n=537), and 438
questionnaires were included in the analysis. Migraine (n=117) and MA (n=239)
patients were classed according to the International Headache Society (IHS). CDH 
(n=82) was diagnosed when respondents had 15 or more headache days per month.
Descriptive tests, analysis of variances (ANOVAs), chi2, and Kruskal-Wallis tests
were used for statistical analysis (P<.05). RESULTS: The three groups did not
differ in age, gender, ethnicity, level of education, and employment status.
Significant differences in management strategies between the groups were found in
the number of respondents who had consulted headache specialists (P=.002) and
neurologists (P=.004), the number and types of acute medications (eg, triptans,
P=.002), the use of antidepressants (P=.004), and some acute and prophylactic
avoidance techniques. Although, no significant differences between the groups
were found in the use of other health professionals (eg, GP), alternative health 
professionals, general acute management, and the use of social support, they all 
actively used these strategies. CONCLUSIONS: The respondents of this study were
active users of management strategies that are based on a combination of health
care consultations, medication and alternative remedies, general management, and 
social support. In comparison to previous findings, the respondents in this study
frequently reported higher use of management strategies (such as the use of
triptans), which may be related to this group of patients being better informed
about headache management than those with headache within the general population.
Thus, the findings may not be representative for the general population, but they
give an indication of the influence and importance of headache-related education 
carried out by patient organizations such as the MAA.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 15953276 [PubMed - indexed for MEDLINE]

1735: Headache. 2005 May;45(5):561-70.

Depressive symptoms and insecure attachment as predictors of disability in a
clinical population of patients with episodic and chronic migraine.

Rossi P, Di Lorenzo G, Malpezzi MG, Di Lorenzo C, Cesarino F, Faroni J,
Siracusano A, Troisi A.

Headache Clinic, INI Grottaferrata, and Department of Neuroscience, University of
Rome Tor Vergata, Italy.

OBJECTIVES: To define predictors of migraine-related disability in patients with 
episodic and chronic migraine referred to a specialty migraine clinic, focusing
on depressive symptoms and insecure attachment style that, because of their
association with responses to pain and physical illness, might be predictive of
greater migraine-related disability. BACKGROUND: The Migraine Disability
Assessment questionnaire (MIDAS) has proved to be a reliable and easy-to-use
instrument to assess migraine-related disability. As clinicians are increasingly 
using MIDAS in their diagnostic and treatment decisions for patient care, an
understanding of the factors influencing migraine-related disability is essential
for a rationale use of such an instrument. METHODS: Two-hundred patients
suffering from episodic migraine without aura (EM), and chronic migraine (CM)
with and without medication overuse, and referred to a specialty headache clinic 
were evaluated using the MIDAS, the Beck Depression Inventory (BDI), and the
Attachment Style Questionnaire (ASQ). Diagnosis of episodic and chronic migraine 
was operationally defined according to the International Headache Society (IHS)
and Silberstein-Lipton criteria. RESULTS: Multiple regression analysis showed
that, in the total sample, disability was higher in those patients with CM, more 
severe depressive symptoms, an insecure style of attachment (as reflected by a
lower score on the ASQ confidence scale), and experiencing more severe headache
pain intensity. In the subgroup of patients with episodic migraine, an insecure
style of attachment emerged as the most significant predictor of disability
(other significant predictors were female sex and number of headache days per
month). In contrast, in the subgroup of patients with CM, the only significant
predictor of the total MIDAS score was a greater severity of depressive symptoms.
CONCLUSIONS: Our findings demonstrate the relevance of attachment style, an
enduring psychological trait not evaluated in previous studies, in influencing
the disability level in patients with migraine and confirm the role of comorbid
depressive symptoms in modulating the impact of migraine on every day
functioning.

PMID: 15953275 [PubMed - indexed for MEDLINE]

1736: Headache. 2005 May;45(5):553-60.

Disability pattern in chronic migraine with medication overuse: a comparison with
migraine without aura.

D'Amico D, Grazzi L, Usai S, Rigamonti A, Curone M, Bussone G.

National Neurological Institute C. Besta, Milan, Italy.

OBJECTIVES: To assess headache-related disability in chronic migraine with
medication overuse (CMO), as defined by Silberstein and Lipton (1996, 2001) in
comparison to that caused by migraine without aura, investigating similarities
and differences in disability patterns in these two conditions. BACKGROUND: It is
well known that migraine has a marked impact on daily activities. Less
information is available on the functional consequences of chronic migraine.
METHODS: This was a prospective study on 247 patients with CMO and 264 with
migraine without aura. All completed the validated Italian version of the
Migraine Disability Assessment questionnaire (MIDAS). The MIDAS total score and
scores of each question (investigating total or partial inability to perform
different daily activities) were evaluated, and compared in the two groups using 
the Mann-Whitney rank sum test. We also evaluated the number of missed days
(question 1) and days with significantly reduced effectiveness at work (question 
2) and in nonwork activities (questions 3, 4, and 5), using descriptive
statistics. RESULTS: MIDAS total score in the CMO group was rather high (mean
84.1, median 70) and significantly higher than in the migraine group (mean 23.4, 
median 19). CMO patients also reported higher scores than migraine patients in
MIDAS questions investigating disability in different domains, the differences
being highly significant for questions 3, 4, and 5. In both CMO and migraine the 
number of days with total or significant disability in nonwork activities was
higher than the number of days with total or significant disability in work
activities, and days spent at work with significantly reduced effectiveness were 
more than work days missed. CONCLUSIONS: Our findings show that CMO has a
profound effect on patients' daily functioning. They suggest that differences
between CMO and migraine are mainly quantitative, while the two groups are
similar in terms of disability pattern. These results are consistent with the
fact that CMO may be an evolution of episodic migraine, characterized by increase
in headache frequency and more evident disability in performing different daily
duties.

Publication Types: 
    Comparative Study

PMID: 15953274 [PubMed - indexed for MEDLINE]

1737: Headache. 2005 May;45(5):546-52.

Cortical inhibition is reduced in chronic and episodic migraine and demonstrates 
a spectrum of illness.

Aurora SK, Barrodale P, Chronicle EP, Mulleners WM.

Swedish Headache Center, Seattle, WA 98104, and University of Hawaii at Manoa,
Department of Psychology, Honolulu, USA.

BACKGROUND: The pathophysiological relationship between episodic migraine and
chronic migraine is not fully understood. We aimed to examine transcranial
magnetic stimulation (TMS) indices of cortical excitability in patients with
episodic migraine (EM) and probable chronic migraine (PCM), and matched controls.
METHODS: Cortical excitability was assessed at baseline with two well-established
methods: phosphene thresholds (PT) and magnetic suppression of perceptual
accuracy (MSPA) profiles. Five EM patients, five PCM patients, and five normal
controls participated in the main study. In addition, two patients were
reassessed after 30 days of treatment with topiramate. RESULTS: Both PT and MPSA 
measures were consistent in indicating a continuum of excitability across the
three groups: PCM patients had the highest excitability, followed by EM, then
controls. In the two treated patients MPSA profiles appeared to normalize at a
100 mg dosage. CONCLUSIONS: Patients with PCM appear to be characterized by very 
high cortical excitability. This may contribute to their greatly increased attack
frequency. TMS-based methods will be important for future research examining the 
evolution of chronic migraine from episodic migraine over time.

Publication Types: 
    Comparative Study

PMID: 15953273 [PubMed - indexed for MEDLINE]

1738: Headache. 2005 May;45(5):538-45.

Treating early versus treating mild: timing of migraine prescription medications 
among patients with diagnosed migraine.

Foley KA, Cady R, Martin V, Adelman J, Diamond M, Bell CF, Dayno JM, Hu XH.

Outcomes Research and Management, Merck & Co., Inc., West Point, PA 19486, USA.

INTRODUCTION: Although research suggests that early treatment of migraine
headache when the pain is mild results in better outcomes for patients, many
patients delay taking their acute-migraine medication until their headaches are
moderate or severe. Understanding when and why patients use their migraine
medications is an important first step to improve migraine management. METHODS: A
prospective observational study, conducted at a major national retail pharmacy
chain with stores across the United States between April 2001 and November 2002, 
enrolled men and women between 18 and 55 years of age with a physician diagnosis 
of migraine with or without aura. Baseline data on 690 patients included patient 
demographics, migraine history, medication use, tendency to avoid or delay
treatment of a migraine attack, and reasons for delaying treatment. Reasons for
delaying treatment were assessed via a checklist of nine potential reasons. In
the follow-up survey completed after treatment of the next migraine attack,
patients reported the timing of medication use in relation to pain onset and the 
severity of the migraine headache at the time they took the medication. RESULTS: 
Despite the severity of their typical migraine attacks, approximately 49% of the 
respondents answered, "yes" to the question, "Do you often avoid or delay taking 
your migraine medications when you start to experience a migraine attack?" The
two most common rationales for avoiding or delaying treatment were "wanting to
wait and see if it is really a migraine attack" (69%) followed by "only want to
take medications if it is a severe attack" (46%). In the follow-up survey,
regardless of medication used, about 85% of patients did not treat their next
migraine attack until the headache pain was moderate or severe, although 74%
treated within 1 hour of pain onset. CONCLUSION: These results suggest that
patients with migraine often delay their treatment until they have identified
their attack as a migraine. In addition, while many patients treated their
follow-up headache early, they did not treat when the pain was mild. This
suggests that there is an opportunity for physicians to educate their migraine
patients on how to differentiate migraine from other headache types and about
when and how to use their acute-migraine medication.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 15953272 [PubMed - indexed for MEDLINE]

1739: Headache. 2005 May;45(5):459-65.

Methodological issues in systematic reviews of headache trials: adapting
historical diagnostic classifications and outcome measures to present-day
standards.

McCrory DC, Gray RN, Tfelt-Hansen P, Steiner TJ, Taylor FR.

Duke University Medical Center, Center for Clinical Health Policy Research
Durham, NC, USA.

Recent efforts to make headache diagnostic classification and clinical trial
methodology more consistent provide valuable advice to trialists generating new
evidence on effectiveness of treatments for headache; however, interpreting older
trials that do not conform to new standards remains problematic. Systematic
reviewers seeking to utilize historical data can adapt currently recommended
diagnostic classification and clinical trial methodological approaches to
interpret all available data relative to current standards. In evaluating study
populations, systematic reviewers can: (i) use available data to attempt to map
study populations to diagnoses in the new International Classification of
Headache Disorders; and (ii) stratify analyses based on the extent to which study
populations are precisely specified. In evaluating outcome measures, systematic
reviewers can: (i) summarize prevention studies using headache frequency,
incorporating headache index in a stratified analysis if headache frequency is
not available; (ii) summarize acute treatment studies using pain-free response as
reported in directly measured headache improvement or headache severity outcomes;
and (iii) avoid analysis of recurrence or relapse data not conforming to the
sustained pain-free response definition.

PMID: 15953262 [PubMed - indexed for MEDLINE]

1740: Expert Opin Pharmacother. 2005 Jun;6(6):1019-24.

Intranasal zolmitriptan.

Gawel M, Worthington I.

Sunnybrook & Women's College Health Sciences Centre, Toronto, Ontario, Canada.
marek.gawel@sw.ca

Intranasal zolmitriptan has recently been launched in the US and Canada and is a 
novel formulation of the antimigraine drug zolmitriptan. This drug has been used 
extensively in its oral formulation. The intranasal formulation offers a more
rapid onset of action. Pharmacokinetic studies have demonstrated that it is
absorbed rapidly into the systemic circulation and traces can be seen in the
brain within 5 min. The onset of efficacy in the Real Life Intranasal
Zolmitriptan Exposure (REALIZE) study was measurable at 10 min and at 15 min in
the US 22 study, which demonstrates rapid absorption and effect at the
5-HT(1B/1D) receptors. This article reviews the initial studies of intranasal
zolmitriptan; three of the most recent studies will be examined in detail.

Publication Types: 
    Review

PMID: 15952929 [PubMed - indexed for MEDLINE]

1741: Funct Neurol. 2005 Jan-Mar;20(1):29-32.

Migraine with and without aura: electrophysiological and functional neuroimaging 
evidence.

Bramanti P, Grugno R, Vitetta A, Di Bella P, Muscarà N, Nappi G.

Centro Studi Neurolesi", University of Messina, Italy.

The neuropathological processes believed to underlie migraine with and without
aura are still widely debated in the literature. In order to arrive at a more
detailed and comprehensive picture of the altered processes present in
migraineurs, electrophysiological data obtained through transcranial magnetic
stimulation (TMS) and electroencephalography (EEG) were combined with
haemodynamic data obtained through functional magnetic resonance imaging (fMRI). 
Ten subjects affected by migraine (with or without aura) underwent TMS and EEG
investigation prior to a visual stimulation task, studied in fMRI. Our
preliminary results showed a reduced cortical silent period especially in
subjects affected by migraine with aura. The fMRI BOLD response was found to be
weaker in occipital areas proportionally to the frequency and severity of
migraine attacks. The data obtained from our study seem to support the theory of 
cortical spreading depression recently observed in human subjects. Moreover, the 
electrophysiological data were also correlated to migraine attack frequency, thus
pointing to elevated cortical excitability between attacks. Better understanding 
of the neuropathological processes that trigger migraine attacks will help in the
selection of more adequate prophylactic therapies. The results of this
preliminary study need to be confirmed in a a large sample of subjects.

PMID: 15948565 [PubMed - indexed for MEDLINE]

1742: Expert Rev Neurother. 2005 May;5(3):371-7.

Craniomandibular muscles, intraoral orthoses and migraine.

Shevel E.

The Headache Clinic, Suite 256, P Bag X2600, Houghton, 2014, South Africa.
drshevel@headclin.com

Intraoral splints are effective in migraine prevention. In this review, changes
in the quality of life of migraineurs treated with a palatal nonoccluding splint 
were measured. Using the Migraine Specific Quality of Life Instrument (Version
2.1), it was found that the palatal nonoccluding splint significantly improved
the quality of life of migraineurs. The role of the craniomandibular muscles in
the pathophysiology of migraine is also discussed.

Publication Types: 
    Review

PMID: 15938670 [PubMed - indexed for MEDLINE]

1743: Expert Rev Neurother. 2005 May;5(3):363-70.

Neuropsychology of migraine: present status and future directions.

O'Bryant SE, Marcus DA, Rains JC, Penzien DB.

Mental Health Service Line (COS6), New Orleans VA Medical Center, 1601 Perdido
St., New Orleans, LA 70112-1262, USA. s_o_bryant@hotmail.com

Migraine is recognized as a primarily neural condition. Changes in neural
physiology have been consistently identified in migraineurs. Numerous studies are
available that evaluate physical and functional differences between migraineurs
and headache-free controls. The most prominent neuroimaging findings reported in 
migraine sufferers have been white matter changes. However, physical changes on
neuroimaging have not been clearly correlated with functional impairment in
migraineurs. The current literature addressing the neuropsychologic consequences 
of migraine has been far from conclusive, and reports of cognitive testing in
adult migraineurs and controls has yielded inconsistent results. Neuropsychologic
testing suggests that there may be some subtle but possibly significant changes
in cognition that occur both during and between migraine episodes. A finding
emerging with some consistency is that migraine patients with aura experience
more neuropsychologic deficits than migraine patients without aura. The few
studies that assess nonmigraine headache suggest that physical changes may not be
unique to migraine, although neuropsychologic changes do appear to be limited to 
migraineurs. An examination of the unmet needs and priorities for future research
addressing this important topic is provided.

Publication Types: 
    Review

PMID: 15938669 [PubMed - indexed for MEDLINE]

1744: Expert Rev Neurother. 2005 May;5(3):343-53.

Migraine treatment throughout the lifecycle.

Landy SH, Lobo BL.

University of Tennessee College of Medicine, Department of Neurology, 8000
Centerview Parkway, Suite 101, Memphis, TN, USA. wesleyhead@aol.com

The treatment of migraine headache is often suboptimal despite significant
advances in our understanding of the pathophysiology and treatment of migraine.
Children, adolescents, women and the elderly are particularly at risk of
receiving inadequate or inappropriate therapy. In this review, the reader is
brought up-to-date with changes to the International Headache Society diagnostic 
criteria for migraine. The pathophysiology of migraine is also reviewed, with a
special emphasis on the evolving concept of central sensitization and cutaneous
allodynia since this concept has led to a paradigm shift in the way migraines are
managed. A review of the evidence supporting the benefits of early treatment
before pain becomes moderate-to-severe is provided. Recommendations for acute and
prophylactic treatments throughout the lifecycle are made in light of clinical
practice guidelines and more recent evidence. Lastly, the current optimal
treatment of migraine is provided and the potential role of calcitonin
gene-related peptide antagonists in the future is discussed.

Publication Types: 
    Review

PMID: 15938667 [PubMed - indexed for MEDLINE]

1745: Expert Rev Neurother. 2005 May;5(3):333-41.

Evidence-based medicine in migraine prevention.

Yoon MS, Savidou I, Diener HC, Limmroth V.

University Hospital Essen, Department of Neurology, Hufelandstrasse 55, 45122
Essen, Germany.

Migraine headache is a chronic, painful, disabling and potentially progressive,
condition primarily occurring in early and middle adulthood. For many patients,
daily activities are impaired by the sudden and unpredictable occurrence of
migraine attacks. In recent years, significant progress has been made in the
field of migraine treatment. For the acute treatment of migraine attacks,
5-hydroxytryptophan(1B/D) agonists (so called triptans), were the most innovative
development, successfully aborting attacks in less than 1 h. The search for
innovative drugs usable for migraine prevention, however, was less successful,
mainly due to the lack of reliable and predictive animal models. Recently,
neuromodulators such as valproic acid and topiramate, initially developed as
anticonvulsants, have been shown in large clinical trials to be effective in the 
prevention of migraine. As for the acute treatment of migraine attacks more than 
10 years ago, large clinical trial programs are now setting new standards for
evidence-based medicine in migraine prevention. This review summarizes the
current options in migraine prevention with special emphasis on clinical trial
design and new developments such as topiramate.

Publication Types: 
    Review

PMID: 15938666 [PubMed - indexed for MEDLINE]

1746: Neurotoxicology. 2005 Oct;26(5):795-800. Epub 2005 Jun 3.

Activation of the transcription factor NF-kappaB in the nucleus trigeminalis
caudalis in an animal model of migraine.

Greco R, Tassorelli C, Cappelletti D, Sandrini G, Nappi G.

Laboratory of Pathophysiology of Integrative Autonomic Systems, IRCCS
Neurological Institute C. Mondino Foundation and University Centre for the Study 
of Adaptive Disorder and Headache (UCADH), Via Palestro 3, 27100 Pavia, Italy.

The infusion of nitroglycerin (NTG) induces an inflammatory state in perivascular
meningeal tissues of rat via the activation, inter alia, of nuclear factor kappa 
B (NF-kappaB). This phenomenon has been related to the mechanisms involved in the
pathophysiology of migraine, a common neurovascular disorder. In the present
study, we sought to elucidate whether NF-kappaB activation might have a role in
the determinism of migraine attacks also at the neuronal level. Therefore, we
investigated the transcriptional activity of NF-kappaB in the brainstem of rats
systemically injected with NTG and killed 4h later. Activation of NF-kappaB in
brain areas was detected by means of both the immunohistochemical technique and
the Western blot analysis. A significant increase of nuclear immunostaining of
p65, an indicator of NF-kappaB activation, was detected in lamina I and II of
nucleus trigeminalis caudalis in rats injected with NTG when compared with the
control group. Western blot analysis confirmed the activation of the NF-kappaB
pathway showing an increase in the optical density of p65 in nuclear extracts of 
lower brainstem of rats injected with the nitric oxide (NO) donor. The present
study contributes to expand on our understanding of the complex mechanisms by
which NTG may trigger migraine-like headaches in migraineurs. Furthermore, these 
findings pave the way to new bio-molecular and pharmacological avenues for the
development of innovative migraine therapies.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 15936821 [PubMed - indexed for MEDLINE]

1747: Expert Opin Pharmacother. 2005 Apr;6(4):625-30.

Eletriptan review.

Färkkilä M, Kallela M.

Department of Neurology, University Hospital Haartmaninkatu 4, 00290 Helsinki,
Finland. markus.farkkila@hus.fi

Eletriptan is a selective, high affinity serotonin 5-HT(1B/1D)-receptor agonist
which is rapidly absorbed and has a long half-life in plasma. Eletriptan has been
shown to be effective and well tolerated in randomised, double-blind,
placebo-controlled acute migraine trials and long-term open-label trials.
Eletriptan maintains a consistency of response across three attacks and patients 
continue to respond to eletriptan for at least up to 1 year. Eletriptan has been 
compared with sumatriptan, zolmitriptan, naratriptan and ergotamine/caffeine in
placebo-controlled, randomised, head-to-head trials, and has shown better
efficacy with similar adverse events. In a large triptan meta-analysis, including
53 trials and > 24,000 patients, eletriptan 80 mg showed better efficacy, similar
consistency but lower tolerability compared with sumatriptan 100 mg. Eletriptan
has also shown efficacy in difficult-to-treat patients who were dissatisfied with
their previous treatment with sumatriptan, rizatriptan, nonsteroidal
anti-inflammatory drugs or Excedrin.

Publication Types: 
    Review

PMID: 15934888 [PubMed - indexed for MEDLINE]

1748: J Manag Care Pharm. 2005 Jun;11(5):394-402.

Comment in:
    J Manag Care Pharm. 2005 Jun;11(5):419-21.

Triptans for migraine therapy: a comparison based on number needed to treat and
doses needed to treat.

Mullins CD, Weis KA, Perfetto EM, Subedi PR, Healey PJ.

University of Maryland School of Pharmacy, 515 W. Lombard St., 2nd Fl.,
Baltimore, MD 21201, USA. dmullins@rx.umaryland.edu

OBJECTIVE: Managed care and other decision makers need sound comparative
information to support the formulary selection process and reimbursement
decisions for the treatment of migraine. The objective of this study was to
compare currently marketed triptan therapies using number-needed-to-treat (NNT)
and doses-needed-to-treat (DNT) measures. DNT was further used to derive triptan 
treatment cost to achieve 100 successfully treated patients such that the
cost-effectiveness of each treatment regime could be compared from the payer
perspective. METHODS: Using published meta-analysis data to categorize patients
as treatment success or failure, an NNT and a DNT were derived for each triptan. 
Treatment success was defined as achieving a 2-hour pain response, sustained
through 24 hours postdose. Costs were derived by multiplying DNT by the average
wholesale price (AWP) minus 15% for each triptan. RESULTS: Eletriptan 40 mg had
the lowest NNT, with 361 patients needing to be treated in order to have 100
patients achieve clinical benefit; rizatriptan 5 mg had the highest NNT (597
patients). Eletriptan 40 mg required 388 doses to successfully treat 100
patients.the lowest number of doses of the triptans considered; rizatriptan 5 mg 
required the highest number (662 doses). Eletriptan 40 mg had the lowest total
triptan cost of USD 5,630 to successfully treat 100 patients. The highest total
triptan cost of treatment was USD 11,136 for naratriptan 2.5 mg. CONCLUSIONS:
Eletriptan 40 mg provides the best value in terms of the lowest DNT, assuming an 
approximately equal AWP discount for each triptan. Eletriptan 40 mg also was
found to have the lowest total triptan cost to successfully treat 100 patients.
Future research should further explore the utility of DNT in managed care
decision making.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 15934798 [PubMed - indexed for MEDLINE]

1749: Acta Neurol Scand. 2005 Jul;112(1):19-23.

Retinal nerve fiber layer thickness is unaffected in migraine patients.

Tan FU, Akarsu C, Güllü R.

Department of Neurology, Faculty of Medicine, Kirikkale University, Kirikkale,
Turkey. fundauysaltan@yahoo.com

OBJECTIVES: To search for possible structural effects of migraine on the retina. 
MATERIALS AND METHODS: The study group included 39 consecutive migraine patients,
15 with visual aura and 24 without aura, and 25 healthy subjects as the control
group. Scanning laser polarimetry was used to measure and compare retinal nerve
fiber layer (RNFL) thickness between migraine and control groups. RESULTS: The
mean age of the patients and the control group were 35.64 +/- 8.3 and 35.96 +/-
9.14 years, respectively (P = 0.92) and the mean duration of migraine in patients
with aura and without aura as 4.4 +/- 2.9 and 5.3 +/- 4.3 years, respectively (P 
= 0.68). Parameters related to RNFL thickness were found to be similar (P >
0.001) in migraine and control subjects. After examining the whole patient group 
migraine patients with and without aura were compared to each other and the
control group individually for RNFL thickness parameters. Briefly no statistical 
difference was found for any of the test parameters between migraine patients
with aura, without aura and controls (P > 0.001). CONCLUSION: Retinal nerve fiber
layer thickness was found to be unaffected in migraine patients. Copyright
Blackwell Munksgaard 2005.

Publication Types: 
    Comparative Study

PMID: 15932351 [PubMed - indexed for MEDLINE]

1750: J Am Osteopath Assoc. 2005 Apr;105(4 Suppl 2):9S-15S.

Advances in migraine treatment.

Nissan GR, Diamond ML.

Diamond Headache Clinic, 467 W Deming Pl, Suite 500, Chicago, IL 60614-2970, USA.
gnissan@diamondheadache.com

Migraine is a common, incapacitating disorder that is underdiagnosed in clinical 
practice. Early and correct diagnosis of migraine is essential and can lead to
significant improvements in a patient's quality of life. In the clinical practice
setting, a screening tool can be used that can help differentiate migraine from
other headache disorders. New research into the development of central
sensitization and cutaneous allodynia in chronic migraine sufferers has led to an
early treatment approach with triptans and other agents for acute migraine
episodes. This approach results in greater 2-hour headache pain-free results. The
use of botulinum toxin type A in the prophylaxis of migraine and mixed-headache
types offers an alternative treatment in patients who may not have responded to
other currently available migraine prophylactic agents.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 15928348 [PubMed - indexed for MEDLINE]

1751: J Am Osteopath Assoc. 2005 Apr;105(4 Suppl 2):2S-8S.

Comment in:
    J Am Osteopath Assoc. 2006 Sep;106(9):528-9; discussion 529.

Pediatric migraine: recognition and treatment.

Hershey AD, Winner PK.

Division of Neurology, Cincinnati Children's Hospital Medical Center, MLC #2015, 
3333 Burnet Ave, Cincinnati, OH 45229-3039, USA. Andrew.hershey@cchmc.org

The diagnosis of migraine headache in childhood rests on criteria similar to
those used in migraine in adults. It is important, however, to appreciate several
fundamental differences. These differences include the duration of attack, which 
is often far shorter than in an adult, and the location of the attack, which may 
be bilateral in many children. The treatment of children and adolescents with
migraines includes treatment modalities for acute attacks, preventive medications
when the attacks are frequent, and biobehavioral modes of therapy to address
long-term management of the disorder. The controlled clinical trials of
medications in pediatric migraine have suffered from high placebo response rates 
that may be related to the sites conducting the study (ie, headache specialist vs
clinical research organizations). The medications have proved to be safe in the
pediatric age group. Treatment modalities for acute migraine include
over-the-counter nonsteroidal anti-inflammatory drugs (NSAIDs), as well as the
oral triptans such as sumatriptan succinate, rizatriptan benzoate, and
zolmitriptan and the nasal spray formulations of sumatriptan and zolmitriptan.
Subcutaneous sumatriptan and parenteral dihydroergotamine have also been used
limitedly. Preventive treatment for patients with frequent or disabling migraines
(or both) includes the antidepressants amitriptyline hydrochloride and
nortriptyline hydrochloride, the anticonvulsants divalproex sodium and
topiramate, and the antihistaminic agent cyprohepatine hydrochloride.
Biobehavioral approaches aimed at addressing the fundamental lifestyle issues and
nonpharmacologic approaches to management are fundamental to long-term success.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 15928347 [PubMed - indexed for MEDLINE]

1752: Neurosci Lett. 2005 Aug 12-19;384(1-2):150-5.

Capsaicin failed in suppressing cortical processing of CO2 laser pain in migraine
patients.

de Tommaso M, Losito L, Difruscolo O, Sardaro M, Libro G, Guido M, Lamberti P,
Livrea P.

Neuroscience Department, University of Bari, Bari, Italy.
m.detommaso@neurol.uniba.it

The aim of this study was to compare the properties of the nociceptive system in 
eight migraine without aura patients in the pain-free phase with 10 healthy
controls, by evaluating the topography and the source of the CO2 laser-evoked
potentials (LEPs) obtained by the right supraorbital skin, during and after
capsaicin topical application. In healthy subjects the acute cutaneous pain
induced by capsaicin reduced the amplitude of the vertex LEPs and induced a
posterior shifting of the P2 wave dipolar source within the anterior cingulate
cortex. These functional changes seemed significantly reduced in migraine
patients, for a disturbed pattern of pain modulation at the cortical level, which
may subtend the onset and persistence of migraine.

Publication Types: 
    Clinical Trial
    Comparative Study

PMID: 15927376 [PubMed - indexed for MEDLINE]

1753: J Neurosurg. 2005 May;102(5):850-5.

Comment in:
    J Neurosurg. 2005 Nov;103(5):934-5; author reply 935.

Posttraumatic migraine characteristics in athletes following sports-related
concussion.

Mihalik JP, Stump JE, Collins MW, Lovell MR, Field M, Maroon JC.

Department of Sports Medicine and Nutrition, School of Health and Rehabilitation 
Sciences, University of Pittsburgh Medical Center, Pennsylvania 15203, USA.

OBJECT: The object of this study was to compare symptom status and neurocognitive
functioning in athletes with no headache (non-HA group), athletes complaining of 
headache (HA group), and athletes with characteristics of posttraumatic migraine 
(PTM group). METHODS: Neurocognitive tests were undertaken by 261 high-school and
collegiate athletes with a mean age of 16.36 +/- 2.6 years. Athletes were
separated into three groups: the PTM group (74 athletes with a mean age of 16.39 
+/- 3.06 years), the HA group (124 athletes with a mean age of 16.44 +/- 2.51
years), and the non-HA group (63 patients with a mean age of 16.14 +/- 2.18
years). Neurocognitive summary scores (outcome measures) for verbal and visual
memory, visual motor speed, reaction time, and total symptom scores were
collected using ImPACT, a computer software program designed to assess
sports-related concussion. Significant differences existed among the three groups
for all outcome measures. The PTM group demonstrated significantly greater
neurocognitive deficits when compared with the HA and non-HA groups. The PTM
group also exhibited the greatest amount of departure from baseline scores.
CONCLUSIONS: The differences among these groups can be used as a basis to argue
that PTM characteristics triggered by sports-related concussion are related to
increased neurocognitive dysfunction following mild traumatic brain injury. Thus,
athletes suffering a concussion accompanied by PTM should be examined in a
setting that includes symptom status and neurocognitive testing to address their 
recovery more fully. Given the increased impairments observed in the PTM group,
in this population clinicians should exercise increased caution in decisions
about treatment and when the athlete should be allowed to return to play.

Publication Types: 
    Comparative Study

PMID: 15926709 [PubMed - indexed for MEDLINE]

1754: Neurol Sci. 2005 May;26 Suppl 2:s162-6.

Naratriptan in the short-term prophylaxis of pure menstrual migraine.

Moschiano F, Allais G, Grazzi L, Usai S, Benedetto C, D'Amico D, Roncolato M,
Bussone G.

L. Mandic Hospital, Merate LC, Italy.

Menstrual migraines are particularly difficult-totreat. Few studies on the use of
triptans in short-term prophylaxis of menstrually related migraine have been
recently conducted, but evidences of triptans' efficacy in the specific case of
pure menstrual migraine (PMM) are lacking.The aim of this study is to explore the
efficacy and tolerability of naratriptan as short-term prophylaxis of pure
menstrual migraine (PMM) attacks. A multi-centre, open, non comparative, pilot
six-month study was conducted in women, aged 18 years or older, with regular
menstrual cycles and with a history of migraine without aura exclusively
associated to the perimenstrual period. After an observation period of three
months, patients took for three consecutive menstrual cycles oral naratriptan 1
mg twice daily, starting two days before the expected onset of menstruation and
continuing for six days. Ninety-eight women with a history of PMM were screened
for study participation, and 61 entered the study. Fifty-nine comprised the
intent-to-treat population. The mean number of PMM attacks decreased from
3.5+/-1.4 in the 3-month observation period to 1.6+/-1.3 in the 3-month treatment
with naratriptan. The pecentage of responders (subjects who recorded a
decrease-equal or more than 50%-in the mean number of attacks) was 61.4%. A
tendency towards a decrease in headache severity and in the presence of
associated symptoms was observed during treatment. At least one adverse event
during the treatment period was reported by 19 patients (31.1%). No serious
adverse events occurred. Naratriptan may be an effective and safe treatment
option in the short-prophylaxis of PMM.

Publication Types: 
    Clinical Trial
    Comparative Study
    Multicenter Study
    Research Support, Non-U.S. Gov't

PMID: 15926020 [PubMed - indexed for MEDLINE]

1755: Neurol Sci. 2005 May;26 Suppl 2:s158-61.

Ear acupuncture in the control of migraine pain: selecting the right acupoints by
the "needle-contact test".

Romoli M, Allais G, Airola G, Benedetto C.

F.I.S.A.-Italian Federation of Acupuncture Societies, Prato, Italy.

There is increasing evidence that somatic acupuncture can be helpful in migraine 
treatment, but substantial data on ear acupuncture (EAP) are still lacking. EAP
can be useful both in the diagnosis and in the treatment of many medical
conditions. As regards the control of migrainous pain, we present a case report
in which a procedure called the "needle-contact test" is described in detail.
During a migraine attack, the patient undergoes an accurate search for tender
points of the outer ear by means of a specific pressure algometer. Once the most 
sensitive point has been identified, an acupuncture needle is placed in contact
with it for about 10 s, without skin penetration. The expected effect is a quick 
and evident reduction of acute pain. If no appreciable variation in pain
intensity occurs within the following 60 s, a second or third attempt is made on 
other previously identified tender points, until the point at which the patient
notices a clear remission of pain is found. In this positive case, the same
testing needle can be immediately used for therapy, completely penetrating the
skin, and then extracted after about 30 min. Alternatively, a temporary needle
can be implanted and left in situ for a variable period of time (1-15 days). This
innovative technique allows the identification, with maximum accuracy, of the
most effective ear acupoints on migraine pain during acute attacks.

Publication Types: 
    Case Reports

PMID: 15926019 [PubMed - indexed for MEDLINE]

1756: Neurol Sci. 2005 May;26 Suppl 2:s140-2.

Migraine: barriers for care.

Sheftell FD, Tepper SJ, Bigal ME.

The New England Center for Headache, 778 Long Ridge Road, Stamford, CT, USA.
ninotores1@aol.com

Migraine headaches affect 12% of the adult population in occidental countries and
cause a significant economic loss due to decreased workplace productivity.
However only a minority of migraine sufferers worldwide ever receive a correct
diagnosis or appropriate treatment. Several barriers for adequate care contribute
to this situation. In this article we discuss some strategies to bypass these
barriers, summarised herein as: (1) identifying migraine sufferers in need of
care; (2) improving medical recognition; (3) supporting the differential
diagnosis; (4) improving medical confidence; (5) improving medical treatment; and
(6) assessing treatment outcomes.

Publication Types: 
    Review

PMID: 15926013 [PubMed - indexed for MEDLINE]

1757: Neurol Sci. 2005 May;26 Suppl 2:s130-3.

Topiramate in migraine prophylaxis.

D'Amico D, Grazzi L, Usai S, Moschiano F, Bussone G.

U.O. Cefalee e Malattie Cerebrovascolari, C. Besta National Neurological
Institute, Via Celoria 11, I-20133, Milan, Italy. damicodo@tiscali.it

This paper reviews results of placebo-controlled trials on topiramate (TPM)
prophylaxis in migraine patients, and discusses issues regarding the use of this 
medication in clinical practice. Data from well conducted double-blind controlled
trials and from a comparative trial show that TPM is effective against migraine, 
confirming the experience of physicians in various countries. Lack of major
contraindications, high responder rate, good tolerability at the target dose (100
mg/day) following slow titration, and lack of weight gain make TPM one of the
most effective and well accepted drugs for migraine prophylaxis.

Publication Types: 
    Review

PMID: 15926010 [PubMed - indexed for MEDLINE]

1758: Neurol Sci. 2005 May;26 Suppl 2:s125-9.

Advanced strategies of short-term prophylaxis in menstrual migraine: state of the
art and prospects.

Allais G, Bussone G, De Lorenzo C, Mana O, Benedetto C.

Woman's Headache Center, Department of Gynecology and Obstetrics, University of
Turin, Via Ventimiglia 3, I-10126, Turin, Italy. gb.allais@tiscali.it

Patients suffering from menstrual migraine (MM) may be ideal candidates for an
intermittent prophylaxis, usually termed short-term or mini-prophylaxis. It
covers the whole period of vulnerability, e. g., the perimenstrual period,
starting some days before the expected onset of MM attack. Theoretically MM
attacks are an optimal target for drugs specifically developed for acute head
pain. Unfortunately, due to their particular tendency to be longer, more intense 
and less responsive to analgesics, symptomatic approaches alone are not often
able to completely control pain and its correlates. Many drugs have been proposed
for short-term prophylaxis of MM. In this paper we analyse only non-steroidal
anti-inflammatory drugs, coxibs and triptans (especially those with longer
half-life, naratriptan and frovatriptan). Moreover, MM can be prevented by a
variety of hormonal manipulations, including oral contraceptives, which may be
administered with an extended-dosing strategy; oestrogen replacement therapy;
antioestrogen agents (danazol, tamoxifen); gonadotropin-releasing hormone
agonists followed by oestrogen add-back therapy. Finally, the use of some
products, such as magnesium and phytoestrogens, that probably meet the
requirements of those patients that appreciate a more "natural" approach, is
discussed.

PMID: 15926009 [PubMed - indexed for MEDLINE]

1759: Neurol Sci. 2005 May;26 Suppl 2:s121-4.

Menstrual migraine: clinical considerations in light of revised diagnostic
criteria.

Loder E.

Faculty of Medicine, Harvard Medical School, 125 Nashua Street, Boston, MA 02114,
USA. eloder@partners.org

Menstrual migraine is not formally recognised by the International Headache
Society Diagnostic Classification, but "candidate criteria" for its diagnosis
have been published. Attacks of migraine occurring in a consistent relationship
with menstruation can be classified as "pure" menstrual migraine if they occur at
no other time of the month, and as "menstrually related" if other attacks occur
throughout the month. It remains controversial whether such attacks are longer,
more severe or more difficult to treat than other attacks, but this form of
migraine does lend itself to pre-emptive treatment because its timing and trigger
can be anticipated. This paper reviews evidence for specific acute and
pre-emptive treatment strategies, including the use of hormonal supplementation, 
scheduled triptans and nonsteroidal anti-inflammatory drugs.

Publication Types: 
    Review

PMID: 15926008 [PubMed - indexed for MEDLINE]

1760: Neurol Sci. 2005 May;26 Suppl 2:s111-20.

Migraine preventive therapy: current and emerging treatment options.

Rapoport AM, Bigal ME.

The New England Center for Headache, 778 Long Ridge Road, Stamford, CT
06902-1251, USA. alanrapaport@nech.net

In this paper we review new treatment options for migraine prevention. We start
with an overview about migraine and then briefly discuss current indications for 
migraine prevention and new and emerging preventive medications.

Publication Types: 
    Review

PMID: 15926007 [PubMed - indexed for MEDLINE]

1761: Neurol Sci. 2005 May;26 Suppl 2:s108-10.

Early triptan intervention in migraine: an overview.

Moschiano F, D'Amico D, Allais G, Rigamonti A, Melzi P, Schieroni F, Bussone G.

L. Mandic Hospital, Merate, Italy.

Although triptans are highly effective for the acute treatment of migraine,
sustained pain-free rates--considered the optimal end-point--are in the range of 
18%-27% for all triptans in clinical trials. A recently proposed strategy for
treating migraine attacks is that triptans should be given early, when the pain
is mild, rather than moderate or severe. Studies with different triptans have
shown that early intervention can result in higher pain-free rates, together with
reductions in rescue medication use and recurrence rates. However these studies
suffer from methodological pitfalls: most were retrospective analyses of trials
not designed to evaluate the benefit of early intervention; the definition of
"early" differed from study to study; and placebo effects were not correctly
evaluated. Furthermore, the disadvantages of this strategy in clinical practice, 
particularly the risk of medication overuse, have not been evaluated. We propose 
that only patients with particularly severe migraines and in whom attacks are
always characterised by rapid progression of pain and other symptoms, should be
advised to take a triptan as early as possible.

Publication Types: 
    Review

PMID: 15926006 [PubMed - indexed for MEDLINE]

1762: Neurol Sci. 2005 May;26 Suppl 2:s104-7.

Migraine with aura from pathophysiology to treatment: therapeutic strategies.

D'Andrea G, Allais G, Grazzi L, Fumagalli L.

Headache and Cerebrovascular Center, Villa Margherita Neurological Clinic,
Arcugnano VI, Italy. giovinavi@libero.it

Migraine with aura (MwA) sufferers, at times, need specific treatments. This is
the case when the auras are frequent, prolonged and cause anxiety and distress.
Abnormal release of glutamate, that may trigger auras, and abnormal platelet
behaviour, that constitute a possible predisposing factor to MwA, may be possible
targets for MwA specific prophylactic therapy. Here we present results obtained
by using lamotrigine, an agent known to inhibit glutamate release, and
picotamide, an antiplatelet drug. Both drugs significantly reduced, in two open
label trials, the frequency and the duration of auras. In comparison with
lamotrigine, the therapy with picotamide may offer some advantages, such as the
use of the therapeutical dose from the first day of treatment (lamotrigine needs 
one month to reach such a dose) and the possibility to prevent cerebral ischaemic
events and migraine stroke, a rare but severe complication of MwA attacks.

Publication Types: 
    Review

PMID: 15926005 [PubMed - indexed for MEDLINE]

1763: J Clin Neurosci. 2005 May;12(4):383-8.

The pathogenesis of migraine - 17th to early 20th century understandings.

Eadie MJ.

Department of Medicine, University of Queensland, Royal Brisbane Hospital,
Brisbane, Australia. m.eadie@mailbox.uq.edu.au

The modern understanding of the pathogenesis of migraine, based on the concept
that it is a neurovascular disorder, is often thought to have emerged from the
work of Harold Wolff in the period 1932-1962. However, over the preceding 300
years, from William Harvey onwards, various hypotheses of the pathogenesis of
migraine had been proposed, a few bearing reasonably strong resemblances to
Wolff's ideas, though based on less adequate evidence. Many of these earlier
hypotheses regarded migraine either primarily as a vascular (e.g., Willis,
Wepfer, Latham) or as a neural disorder (e.g., Harvey, Lieving and his 'nerve
storms'). There were also variations around these two major themes and in the
19th Century a number of neurovascular type hypotheses emerged assigning a major 
role in migraine pathogenesis to the autonomic nervous system. In addition,
during the three centuries there were a number of other hypotheses based on
different postulated pathogenic mechanisms, some quite ingenious, which had
relatively brief vogues. No hypothesis has yet proved capable of explaining all
the features of migraine satisfactorily.

Publication Types: 
    Historical Article

PMID: 15925767 [PubMed - indexed for MEDLINE]

1764: Clin Ther. 2005 Apr;27(4):407-17.

Two replicate randomized, double-blind, placebo-controlled trials of the time to 
onset of pain relief in the acute treatment of migraine with a
fast-disintegrating/rapid-release formulation of sumatriptan tablets.

Sheftell FD, Dahlöf CG, Brandes JL, Agosti R, Jones MW, Barrett PS.

New England Center for Headache, Stamford, Connecticut 06902-1227, USA.
ninotores1@aol.com

BACKGROUND: The gastric stasis that commonly accompanies migraine headache may
impair absorption of conventional oral tablets in the stomach. A
fast-disintegrating/rapid-release formulation of sumatriptan has been developed
to enhance tablet disintegration and drug dispersion and potentially improve
absorption. OBJECTIVE: Two studies were conducted comparing the time to onset of 
relief from moderate or severe migraine pain with the
fast-disintegrating/rapid-release formulation of sumatriptan tablets 50 and 100
mg and placebo. METHODS: These were 2 identically designed randomized,
double-blind, parallel-group studies. Sumatriptan 50 or 100 mg or placebo was
taken on an outpatient basis to treat a single moderate or severe migraine
attack. Using a personal digital assistant, patients recorded the time of dosing 
and the time at which pain severity reached none or mild (ie, pain relief) or
none (ie, pain free) in real time so that the time to onset of relief could be
measured as a continuous variable. Onset of relief was defined as the earliest
time point at which a statistically significant difference in pain relief
compared with placebo was achieved and maintained through 2 hours after dosing.
Before dosing and at pre-determined time points after dosing, patients also
provided an assessment of migraine pain as none, mild, moderate, or severe. At a 
clinic visit within 1 week after treatment of the migraine attack, patients were 
queried about adverse events. For each adverse event, investigators recorded
whether study medication was considered the cause. Data analyses were undertaken 
for each study individually and, in post hoc analyses of the primary and key
secondary end points, on pooled data from both studies. RESULTS: The 2 studies
comprised 2696 patients: 902 received sumatriptan 50 mg, 902 received sumatriptan
100 mg, and 892 received placebo. Patients' mean age ranged from 40.2 to 40.8
years across treatment groups, and most patients were female (83%-87%) and white 
(92%-93%). In the analysis of pooled data, sumatriptan tablets provided
significantly more effective pain relief compared with placebo as early as 20
minutes after dosing with the 100-mg dose and as early as 30 minutes after dosing
with the 50-mg dose (P < or = 0.05). Similar results were observed for the
individual studies: in study 1, sumatriptan tablets were significantly more
effective than placebo at 25 minutes with the 100-mg dose and at 50 minutes with 
the 50-mg dose; in study 2, sumatriptan tablets were significantly more effective
than placebo at 17 minutes for the 100-mg dose and at 30 minutes for the 50-mg
dose (P < or = 0.05). In the pooled data, the cumulative percentages of patients 
with pain relief by 2 hours after dosing were 72% for the 100-mg dose and 67% for
the 50-mg dose, compared with 42% for placebo (P < or = 0.001, both sumatriptan
doses vs placebo). The cumulative percentages of patients with a pain-free
response by 2 hours were 47% for the 100-mg dose, 40% for the 50-mg dose, and 15%
for placebo (P < or = 0.001, both sumatriptan doses vs placebo). In the
individual studies, significantly more patients receiving either sumatriptan dose
were migraine free 2 hours after dosing and had sustained pain relief and a
sustained pain-free response over 24 hours compared with placebo (P < or = 0.001,
both sumatriptan doses vs placebo). The only drug-related adverse events reported
in >2% of patients in any treatment group in either study were nausea (both
studies: 3% sumatriptan 100 mg, 2% sumatriptan 50 mg, 1% placebo) and paresthesia
(study 1: <1% sumatriptan 100 mg, <1% sumatriptan 50 mg, 0% placebo; study 2: 3% 
sumatriptan 100 mg, 1% sumatriptan 50 mg, <1% placebo). CONCLUSIONS: In these
studies, sumatriptan tablets in a fast-disintegrating/rapid-release formulation
were effective for the acute treatment of moderate to severe migraine pain, were 
generally well tolerated, and achieved an onset of pain relief as early as 20
minutes for 100 mg and as early as 30 minutes for 50 mg.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 15922814 [PubMed - indexed for MEDLINE]

1765: Eur J Epidemiol. 2005;20(3):243-9.

Has the prevalence of migraine and tension-type headache changed over a 12-year
period? A Danish population survey.

Lyngberg AC, Rasmussen BK, Jørgensen T, Jensen R.

Research Centre for Prevention and Health, Glostrup University Hospital,
Glostrup, Denmark. anchly01@glostruphosp.kbhamt.dk

OBJECTIVE: The present study aims to compare the prevalence of primary headaches 
in Denmark in two periods as only few replicate studies have re-evaluated the
prevalence of primary headaches. STUDY DESIGN AND SETTING: The 2001 study is a
replicate of a cross-sectional survey of primary headaches in 1989, and compares 
297 subjects aged 25-36 years from the general population, with the 294
comparable subjects invited in 1989. Medical doctors diagnosed all headaches
using IHS-classification. RESULTS: The participation rate was 75% in 1989 and 70%
in 2001. The prevalence of migraine did not change significantly (11-15%), while 
the prevalence of tension-type headache (79-87%), especially of frequent
tension-type headache (29-37%) increased significantly. The prevalence of chronic
tension-type headache (2-5%) tended to increase. The proportion of the
migraineurs with migraine 14 days or more per year increased (12-38%). Female
gender was a risk factor for both primary headaches. The majority of migraineurs 
(92-94%) also reported coexistent tension-type headache. CONCLUSION: The
prevalence of tension-type headache but not of migraine increased. The increase
in migraine and tension-type headache frequency suggests a higher individual and 
societal impact of primary headaches now, than 12 years ago.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 15921042 [PubMed - indexed for MEDLINE]

1766: Eur Neurol. 2005;53 Suppl 1:41-8. Epub 2005 May 3.

Almotriptan in migraine patients who respond poorly to oral sumatriptan: a
double-blind, randomized trial.

Diener HC, Gendolla A, Gebert I, Beneke M.

Department of Neurology, University Essen, Germany. h.diener@uni-essen.de

OBJECTIVE: To investigate the efficacy and tolerability of almotriptan 12.5 mg in
migraine patients who respond poorly to sumatriptan 50 mg. BACKGROUND: Poor
response to sumatriptan therapy for acute migraine attacks has been documented in
the literature, but few controlled trials have investigated the efficacy of an
alternative triptan in this subgroup of patients. METHODS: Patients with an
International Headache Society diagnosis of migraine who self-described as
experiencing at least two unsatisfactory responses to sumatriptan treated their
first migraine attack with open-label sumatriptan 50 mg. Patients who did not
achieve 2-hour pain relief (improvement of headache from moderate/severe to
mild/no headache) were then randomized to treat their second attack with
almotriptan 12.5 mg or placebo under double-blind conditions. Results: In the
first attack, 221 of 302 participants (73%) did not achieve 2-hour pain relief
with sumatriptan and were randomized to treatment of their second attack with
almotriptan 12.5 mg or placebo. Of the 198 sumatriptan nonresponders who treated 
their second attack (99 almotriptan; 99 placebo), 70% had severe headache pain at
baseline. Two-hour pain-relief rates were significantly higher with almotriptan
compared to placebo (47.5 vs. 23.2%; p < 0.001). A significant treatment effect
for almotriptan was also seen in pain-free rates at 2 h (33.3 vs. 14.1%; p <
0.005) and sustained freedom from pain (20.9 vs. 9.0%; p < 0.05). In the second
attack, 7.1% of patients in the almotriptan group experienced adverse events
compared to 5.1% in the placebo group (p = 0.77). CONCLUSIONS: Almotriptan 12.5
mg is an effective and well-tolerated alternative for patients who respond poorly
to sumatriptan 50 mg. A poor response to one triptan does not predict a poor
response to other agents in that class.

Publication Types: 
    Clinical Trial
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 15920337 [PubMed - indexed for MEDLINE]

1767: Eur Neurol. 2005;53 Suppl 1:34-40. Epub 2005 May 3.

Efficacy and tolerability of almotriptan in postmarketing surveillance studies.

Pascual J.

Service of Neurology, University Hospital Marques de Valdecilla, Santander,
Spain. juliopascual@telefonica.net

While randomized, double-blind, placebo-controlled trials are considered the gold
standard of clinical evidence, they are limited by patient numbers, duration of
patient exposure, and restricted patient populations. Data from controlled trials
may not be generalizable to all individuals likely to take the drug under
investigation. Postmarketing surveillance studies are designed to measure
efficacy and safety in larger and more diverse populations, allowing them to
detect less common and delayed adverse events. However, postmarketing
surveillance studies are limited by their lack of randomization, open-label
design that can result in patient and physician bias, incomplete follow-up, less 
than rigorous outcome measurement, and lack of a contemporaneous control group.
With regard to acute treatment of migraine, clinical trials using per protocol
primary endpoints do not reflect the more favorable experience with triptans in
general practice. Postmarketing surveillance studies have been performed to
determine whether the high levels of efficacy and tolerability of almotriptan
reported in controlled clinical trials can been reproduced in routine practice.
An observational study conducted in Spain with 2,074 migraine sufferers (4,183
attacks) reported a 2-hour pain-relief rate of 86.9%, a 2-hour pain-free rate of 
51.5%, and a sustained pain-free rate of 46.0%; 1.1% of patients reported adverse
reactions. A German postmarketing study in 899 patients (2,131 attacks) with
acute migraine treated with almotriptan 12.5 mg reported 2-hour pain relief in
84.5% of attacks and 2-hour pain free in 41.4%; 1.1% of patients reported adverse
reactions. The consistency of response (at least two out of three attacks
successfully treated) with almotriptan 12.5 mg was 87.3%. Regarding satisfaction,
88.5% of patients were satisfied or very satisfied and 80.3% of patients stated
that almotriptan was better compared to their prior therapy; 92% of physicians
indicated that they would continue treating their patients' migraines with
almotriptan. The results of these studies demonstrate that the high levels of
efficacy and tolerability seen with almotriptan in controlled clinical trials are
achieved in real-world clinical settings. In conclusion, a combination of
controlled clinical trials, postmarketing surveillance studies, and physician's
experience in the general population can give us a better understanding of the
efficacy and tolerability of acute migraine agents. Copyright 2005 S. Karger AG, 
Basel.

Publication Types: 
    Review

PMID: 15920336 [PubMed - indexed for MEDLINE]

1768: Eur Neurol. 2005;53 Suppl 1:29-33. Epub 2005 May 3.

Efficacy and tolerability of almotriptan in controlled clinical trials.

Mathew NT.

Department of Neurology, University of Texas Houston Medical School, Houston, TX 
77004, USA. ntmathew@houstonheadacheclinic.com

Seven triptans are now available for the acute treatment of migraine. While all
of these agents have been shown to be safe and more or less well tolerated, they 
differ in ways that are clinically relevant to individual patients. Almotriptan
has been investigated in approximately 3,500 patients enrolled in short-term
clinical trials and 1,500 patients enrolled in long-term open-label trials. In a 
meta-analysis of placebo-controlled almotriptan trials (n = 2,294), treatment
with almotriptan 12.5 mg results in a 2-hour pain-relief rate of 63.7% and a
2-hour pain-free rate of 36.4%. Almotriptan is associated with a rapid onset of
action, with 30-min pain-relief and pain-free rates significantly better than
placebo (p < 0.05). Direct comparator studies show the efficacy of almotriptan
12.5 mg to be comparable to that of sumatriptan but almotriptan is associated
with superior tolerability. Trials assessing the efficacy of almotriptan over
multiple attacks show that this agent is associated with a consistent and
persistent response, not differing from the first to the last attack, an
important property for a medication used to treat a chronic condition such as
migraine. Early intervention with almotriptan enhances the activity of this
agent. Treatment of mild pain with almotriptan has resulted in 2-hour pain-free
rates of 84 and 77% and a sustained pain-free rate of 67%. Early treatment
(within 1 h) of moderate to severe headaches with almotriptan also improves
outcomes. In conclusion, clinical trials and post hoc analyses of such trials
have shown almotriptan to be effective and well tolerated for the acute treatment
of migraine. Its placebo-like tolerability makes it a good choice for early
intervention, a strategy associated with better patient outcomes. Copyright 2005 
S. Karger AG, Basel.

Publication Types: 
    Review

PMID: 15920335 [PubMed - indexed for MEDLINE]

1769: Eur Neurol. 2005;53 Suppl 1:22-8. Epub 2005 May 3.

Defining response in migraine: which endpoints are important?

Edmeads J.

Sunnybrook and Women's College Health Sciences Centre, Toronto, Canada.
John.Edmeads@sw.ca

The primary endpoint traditionally measured in clinical trials of triptans for
acute migraine therapy has been 2-hour pain relief, a decrease in pain intensity 
from moderate/severe to mild/none. Although harder to achieve, endpoints such as 
2-hour pain free and the composite measure sustained pain free are now preferred 
as they better reflect what patients desire from medication, namely rapid onset
of action, and complete and lasting relief of pain. A comprehensive meta-analysis
has shown that oral triptans differ in their ability to achieve these endpoints, 
with almotriptan 12.5 mg, eletriptan 80 mg and rizatriptan 10 mg providing the
highest likelihood of success. Although all triptans have simple and consistent
pharmacokinetic features, they also have specific differences that may play a
part in their differing clinical attributes. Incorporating tolerability to
generate a more stringent endpoint, sustained pain free with no adverse events
(SNAE), may provide an even better representation of patients' expectations.
Comparison of SNAE rates using data from the meta-analysis of oral triptans
indicates that almotriptan 12.5 mg has the best balance of high efficacy and good
tolerability. Copyright 2005 S. Karger AG, Basel.

Publication Types: 
    Comparative Study
    Review

PMID: 15920334 [PubMed - indexed for MEDLINE]

1770: Eur Neurol. 2005;53 Suppl 1:17-21. Epub 2005 May 3.

Should we advise patients to treat migraine attacks early: methodologic issues.

Ferrari MD.

Department of Neurology, Leiden University Medical Centre, Leiden, The
Netherlands. M.D.Ferrari@lumc.nl

In clinical trials of triptans in acute migraine, patients have traditionally
been required to take their medication only when their pain reached moderate or
severe intensity. This methodology better ensured that migraine attacks rather
than nonmigraine headaches were treated, minimized the placebo response and
simplified comparison of improvement as all patients start from the same baseline
pain level. In clinical practice, patients do not take medication in this way,
and there is some theoretical evidence that early treatment might be beneficial. 
There are increasing numbers of reports claiming advantages of 'early' treatment,
when the pain is mild, over 'late' treatment, when pain is moderate or severe,
but these studies raise significant methodologic issues. Treating 'early' may
equate with treating 'mild' in slowly progressing attacks only but this may not
always be the case in rapidly progressing attacks; these two types of migraine
attacks should be distinguished carefully and investigated separately. Trials
should be placebo-controlled, blinded, assess the therapeutic gain versus placebo
rather than the absolute rates, and use the sustained pain-free endpoint. Early
treatment may also increase the risk of medication overuse headaches. At present,
there is no scientific support to advise patient to treat early. Patients should 
be advised to take their medication as soon as they are sure they are developing 
a migraine headache, but not during the aura phase. Copyright 2005 S. Karger AG, 
Basel.

Publication Types: 
    Review

PMID: 15920333 [PubMed - indexed for MEDLINE]

1771: Eur Neurol. 2005;53 Suppl 1:10-6. Epub 2005 May 3.

Migraine, allodynia, sensitisation and all of that ...

Goadsby PJ.

Headache Group, Institute of Neurology and The National Hospital for Neurology
and Neurosurgery, London, UK. peterg@ion.ucl.ac.uk

Migraine is the most common form of disabling primary headache. One common and
often troublesome feature of the disorder is an abnormal sensory state where
normally innocuous stimuli are felt as painful: allodynia. This occurs in about
two-thirds of patients and manifests as common complaints, such as pain when
touching the hair. The neurophysiological correlate of allodynia is
sensitisation, an increased afferent barrage for an unchanged peripheral
stimulus. Sensitisation may be peripheral, central or disinhibitory. The
potential mechanisms of each of these and their possible manipulation by
treatments of the acute attack are considered. Copyright 2005 S. Karger AG,
Basel.

Publication Types: 
    Review

PMID: 15920332 [PubMed - indexed for MEDLINE]

1772: Eur Neurol. 2005;53 Suppl 1:3-9. Epub 2005 May 3.

What do patients want from their acute migraine therapy?

Lantéri-Minet M.

Department of Evaluation and Treatment of Pain, Hôpital Pasteur, CHU de Nice,
Nice, France. lanteri-minet.m@chu-nice.fr

A minority of migraine sufferers are diagnosed and treated and medical
consultation rates are low even among those aware of their condition. Despite
guidelines recommending the use of triptans, there are high rates of usage of
nonspecific treatments, mainly simple analgesics, coupled with low prevalence of 
triptan use. Consequently, many individuals with migraine are not receiving the
kind of treatment that would meet their expectations and leave them satisfied.
For patients, the most important attributes of acute migraine treatment are
complete freedom from pain, rapid onset of action, no recurrence and absence of
side effects. More widespread use of triptans would have the potential to improve
outcomes and increase patient satisfaction, leading to a better migraine-related 
quality of life. In choosing among triptans, physicians need to match individual 
patients' needs and wants with the attributes of the particular triptans, taking 
into account a medication's complete profile of efficacy, consistency and
tolerability, and using information from meta-analyses and modelling to ensure
evidenced-based, patient-oriented decision-making.

Publication Types: 
    Review

PMID: 15920331 [PubMed - indexed for MEDLINE]

1773: Med Hypotheses. 2005;65(3):542-5.

A chronic dysfunctional stress response can cause stroke by stimulating platelet 
activation, migraine, and hypertension.

Eggers AE.

Institution SUNY-Downstate Medical Center, Box 1213, Department of Neurology, 450
Clarkson Avenue, Brooklyn, NY 11203, USA. eggersa@aol.com

A hypothesis is presented on the mechanism of acute intracranial occlusion. The
hypothesis is that a chronic dysfunctional response to stress can include
migraine, hypertension and systemic platelet activation (a hypercoagulable
state). Stress is defined as the perception of excessive threats or demands.
Migraine, hypertension, and platelet activation constitute a physiological triad 
that exists as a distinct entity and can undergo sudden provoked or unprovoked
worsening, causing acute stroke. The hypertension and headache may not be
apparent in every stroke, much as headache is absent in acephalgic migraine. In
support of this idea, a literature review is undertaken which leads to the
conclusion that the labile rise in blood pressure and headache often seen with
acute stroke are unlikely to be caused by the stroke. Systemic platelet
activation has been documented in both migraine and stroke and is the missing
piece of the puzzle. Migraine (or non-specific headache) and hypertension are
markers of co-existing platelet activation, the hypercoagulable state which
causes stroke. Migraine, and, putatively, hypertension and platelet activation,
are driven by overactive pacemaker cells in the dorsal raphe nucleus of the
midbrain, the nucleus which mediates one arm of the physiologic response to
stress. A therapeutic prediction is made that drugs such as ethosuximide, which
block the low voltage-activated T-type calcium channel, which is one of the ion
channels implicated in the generation of pacemaker currents in the dorsal raphe
nucleus, would be useful in stroke prevention.

PMID: 15913902 [PubMed - indexed for MEDLINE]

1774: J Insur Med. 2000;32(2):112-3.

Magnetic resonance angiogram and imaging.

Goodwin L.

Transamerica Reinsurance, 401 N Tryon St, Suite 900, Charlotte, NC 28202, USA.

Reports from specialized medical tests may often reveal findings that are
ambiguous. In this article, the significance of punctate signal changes and
ischemia revealed by magnetic resonance scanning are discussed.

Publication Types: 
    Case Reports

PMID: 15912911 [PubMed - indexed for MEDLINE]

1775: Contemp Clin Trials. 2005 Jun;26(3):349-64. Epub 2005 Mar 28.

A group sequential adaptive treatment assignment design for proof of concept and 
dose selection in headache trials.

Hall DB, Meier U, Diener HC.

Department of Biometrics and Data Management, Boehringer Ingelheim
Pharmaceuticals, P.O. Box 368, Ridgefield, CT 06877, USA.
dhall@rdg.boehringer-ingelheim.com

The trial objective was to test whether a new mechanism of action would
effectively treat migraine headaches and to select a dose range for further
investigation. The motivation for a group sequential, adaptive,
placebo-controlled trial design was (1) limited information about where across
the range of seven doses to focus attention, (2) a need to limit sample size for 
a complicated inpatient treatment and (3) a desire to reduce exposure of patients
to ineffective treatment. A design based on group sequential and up and down
designs was developed and operational characteristics were explored by trial
simulation. The primary outcome was headache response at 2 h after treatment.
Groups of four treated and two placebo patients were assigned to one dose.
Adaptive dose selection was based on response rates of 60% seen with other
migraine treatments. If more than 60% of treated patients responded, then the
next dose was the next lower dose; otherwise, the dose was increased. A stopping 
rule of at least five groups at the target dose and at least four groups at that 
dose with more than 60% response was developed to ensure that a selected dose
would be statistically significantly (p=0.05) superior to placebo. Simulations
indicated good characteristics in terms of control of type 1 error, sufficient
power, modest expected sample size and modest bias in estimation. The trial
design is attractive for phase 2 clinical trials when response is acute and
simple, ideally binary, placebo comparator is required, and patient accrual is
relatively slow allowing for the collection and processing of results as a basis 
for the adaptive assignment of patients to dose groups. The acute migraine trial 
based on this design was successful in both proof of concept and dose range
selection.

PMID: 15911469 [PubMed - indexed for MEDLINE]

1776: Brain Res. 2005 May 31;1045(1-2):1-11.

Patterns of fos expression in the rostral medulla and caudal pons evoked by
noxious craniovascular stimulation and periaqueductal gray stimulation in the
cat.

Knight YE, Classey JD, Lasalandra MP, Akerman S, Kowacs F, Hoskin KL, Goadsby PJ.

Headache Group, Institute of Neurology, Queen Square, London WC1N 3BG, UK.

Functional imaging studies and clinical evidence suggest that structures in the
brainstem contribute to migraine pathophysiology with a strong association
between the brainstem areas, such as periaqueductal gray (PAG), and the headache 
phase of migraine. Stimulation of the superior sagittal sinus (SSS) in humans
evokes head pain. Second-order neurons in the trigeminal nucleus that are
activated by SSS stimulation can be inhibited by PAG stimulation. The present
study was undertaken to identify pontine and medullary structures that respond to
noxious stimulation of the superior sagittal sinus or to ventrolateral PAG
stimulation. The distribution of neurons expressing the protein product (fos) of 
the c-fos immediate early gene were examined in the rostral medulla and caudal
pons of the cat after (i) sham, (ii) stimulation of the superior sagittal sinus, 
(iii) stimulation of the superior sagittal sinus with PAG stimulation, or (iv)
stimulation of the PAG alone. The structures examined for fos were the trigeminal
nucleus, infratrigeminal nucleus, reticular nuclei, nucleus raphe magnus, pontine
blink premotor area, and superior salivatory nucleus. Compared with all other
interventions, fos expression was significantly greater in the trigeminal nucleus
and superior salivatory nucleus after SSS stimulation. After PAG with SSS
stimulation, on the side ipsilateral to the site of PAG stimulation, fos was
significantly greater in the nucleus raphe magnus. These structures are likely to
be involved in the neurobiology of migraine.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 15910757 [PubMed - indexed for MEDLINE]

1777: Cephalalgia. 2005 Jun;25(6):452-6.

Validity and reliability of Turkish translation of Migraine Disability Assessment
(MIDAS) questionnaire in patients with migraine.

Gedikoglu U, Coskun O, Inan LE, Ucler S, Tunc T, Emre U.

Ministry of Health, Ankara Research Hospital, Department of Neurology, Ankara,
Turkey.

The Migraine Disability Assessment (MIDAS) questionnaire is a brief,
self-administered questionnaire which is designed to quantify headache-related
disability in a 3-month period. We have tested a Turkish version of the MIDAS
questionnaire in 60 migraine patients. Sixty of the clinically diagnosed migraine
headache sufferers were enrolled in a 90-day diary study and completed the MIDAS 
questionnaire in the first, 21st and the last day of the 90-day study. The scores
taken from the diary and the scores of the MIDAS taken at different times were
evaluated by the correlation tests of both Pearson and Spearman for each question
and total scores. Cronbach's scores taken from the diary and taken from the test 
of the MIDAS which was applied at different times were evaluated. Pearson's
correlation on the responses in the initial MIDAS questions was between 0.44
(reduced productivity in household chores) and 0.78 (missed work or school days).
The correlation of the Spearman was similar to the Pearson values. As a result,
we found that the overall score of the MIDAS has a good reliability and its
internal consistency is also good (Cronbach's alpha 0.87). These findings support
the use of the MIDAS questionnaire as a clinical and research tool on Turkish
patients.

Publication Types: 
    Validation Studies

PMID: 15910570 [PubMed - indexed for MEDLINE]

1778: Cephalalgia. 2005 Jun;25(6):444-51.

Comparison of pre-headache phases and trigger factors of migraine and episodic
tension-type headache: do they share similar clinical pathophysiology?

Karli N, Zarifoglu M, Calisir N, Akgoz S.

Department of Neurology, School of Medicine, University of Uludag, 16059 Bursa,
Turkey. nkarli@yahoo.com

Trigger factors, signs and symptoms of the preheadache phases of episodic
tension-type headache (ETTH), typical aura with non-migraine headache (TANMH),
migraine with (MA) and without aura (MwA) may show similar features. Our
objective was to investigate the preheadache phases and trigger factors of these 
headache types. Questionnaires including trigger factors, signs and symptoms of
preheadache phases were answered by all headache patients. A total of 96
patients, 31 ETTH, nine TANMH, 23 MA and 33 MwA patients were included in this
study. Analysis of seven groups consisting of 18 individual trigger factors
showed that only two groups and five individual trigger factors were
significantly different between groups. Hunger and odour were significantly more 
common in MA, MwA and TANMH patients. Foods were a significant precipitant factor
for headache in MA patients. Head and neck movements were important trigger
factors in ETTH. In prodrome phase only one out of three groups differed
significantly between headache types. Migraine and TANMH patients reported
significantly more general signs and symptoms. Analysis of aura signs and
symptoms showed that only two out of six groups were significantly more frequent 
in MA and TANMH patients. Visual aura symptoms were more frequent in MA and TANMH
groups, where sensorial auras were reported to be the most frequent in the MA
group. Our results showed that different type of headaches share common prodrome 
and aura signs and symptoms as well as the same trigger factors. We suggest that 
similar trigger factors may trigger similar mechanisms and may cause common
preheadache signs and symptoms in all headache types.

Publication Types: 
    Comparative Study

PMID: 15910569 [PubMed - indexed for MEDLINE]

1779: Cephalalgia. 2005 Jun;25(6):439-43.

Surgical treatment of patients with refractory migraine headaches and intranasal 
contact points.

Behin F, Behin B, Bigal ME, Lipton RB.

Mount Sinai Medical Center, New York, NY, USA. fbehin@yahoo.com

Contact point headaches have been attributed to intranasal contact between
opposing mucosal surfaces, resulting in referred pain in the distribution of the 
trigeminal nerve. In subjects with primary headaches, contact points may be
associated with treatment refractoriness. We aimed to assess the benefits of
surgical correction in patients with refractory migraine or transformed migraine,
and radiographic evidence of contact points in the sinonasal area. We reviewed
charts of patients who underwent endoscopic sinus surgery and septoplasty for
contact point in the same surgical facility, from October 1998 through August
2003. Subjects eligible for surgery had: (i) refractory migraine (failed to
standard pharmacological headache treatments) or refractory transformed migraine;
(ii) contact points demonstrated by computed tomography scan; (iii) reported
significant headache improvement after topical anaesthesia to the contact area.
Headache characteristics were assessed preoperatively and at follow-up (6-62
months after surgery) using a standardized questionnaire. A total of 21 subjects 
(72.5% women) were assessed. Mean headache frequency was reduced from 17.7 to 7.7
headache days per month (P = 0.003). Mean headache severity was reduced from 7.8 
to 3.6 on a 0-10 scale (P = 0.0001). Headache-related disability was reduced from
5.6 (10-point scale) to 1.8 (P < 0.0001). A total of 16 subjects (76.2%) had
their headache scores improved by 50% or more; nine (42.9%) were pain free at the
last follow-up. A total of 18 (95.8%) had at least a 25% reduction in their
headache scores. Two patients (9.5%) had increase in their headache score by less
than 25%. For selected patients with refractory headaches, demonstrable contact
points, and positive response after topical anaesthesia, surgical approach toward
the triggering factor may be useful. Prospective studies are necessary to confirm
our results.

PMID: 15910568 [PubMed - indexed for MEDLINE]

1780: Cephalalgia. 2005 Jun;25(6):433-8.

Rising prevalence of migraine in Taiwanese adolescents aged 13-15 years.

Wang SJ, Fuh JL, Juang KD, Lu SR.

The Neurological Institute, Taipei Veterans General Hospital, Taipei 112, Taiwan.
sjwang@vghtpe.gov.tw

Whether the prevalence of migraine is increasing is controversial. We conducted
annual surveys in 1999-2001 to investigate migraine prevalence among a nationwide
sample of 13 426 adolescents aged 13-15 years. Participants from five junior high
schools around different regions of Taiwan completed self-administered
questionnaires. The diagnosis of migraine was based on the classification
criteria proposed by the International Headache Society, 1988. Data for 23 433
person-years were collected and analysed for trends in prevalence and incidence. 
The 1-year prevalence of migraine increased 42% during 1999-2001 (from 5.2 to
7.4%, P < 0.001). This increasing trend was demonstrated in both sexes, all ages,
and all but one studied regions of Taiwan. Of note was the biggest increment of
prevalence (79%) among 7th graders (students aged 13 years) through these 3
years. Annual incidence rates did not differ between 1999 and 2000 and 2000 and
2001 (6.1% vs. 5.7%; P = 0.4). One-year persistence rates of migraine diagnosis, 
surrogates of migraine duration, did not differ between 1999 and 2000 and 2000
and 2001 (34.2% vs. 41.2%; P = 0.1). Our study found that the prevalence of
migraine was increasing in our sampled adolescents, which results from an
increment starting at age 13 or younger. The prevalence of migraine in Asians
might be increasing, although previous studies showed lower prevalence in this
region. Children or adolescents may be more vulnerable to the environmental or
societal change.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 15910567 [PubMed - indexed for MEDLINE]

1781: Cephalalgia. 2005 Jun;25(6):412-23.

Comment in:
    Cephalalgia. 2005 Jun;25(6):401-2.

Colour vision in migraine: selective deficits for S-cone discriminations.

Shepherd AJ.

School of Psychology, Birkbeck College, London WC1E 7HX, UK.
a.shepherd@psychology.bbk.ac.uk

Three studies are reported that explore colour perception in migraine. In each,
sensitivity for colours detected selectively by the S-cones and the L- and
M-cones was assessed separately. The first study assessed the discrimination of
small colour differences using the Farnsworth-Munsell 100-hue test. The second
assessed threshold detection for purple, yellow, red and green targets on five
equiluminant background colours. The third examined supra-threshold colour
scaling using two colour series, purple-yellow and red-green. Each study
indicated that differences in colour perception between migraine and control
groups were restricted to colours detected by the S-cones, there were no
differences in performance for colours detected by the L- and M-cones. The
results are discussed in terms of possible pathologies in the early visual
pathways.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 15910565 [PubMed - indexed for MEDLINE]

1782: Curr Pain Headache Rep. 2005 Jun;9(3):213-20.

Migraine genetics: an update.

Haan J, Kors EE, Vanmolkot KR, van den Maagdenberg AM, Frants RR, Ferrari MD.

Department of Neurology, Leiden University Medical Centre, P.O. Box 9600, 2300 RC
Leiden, The Netherlands. E-mail: J.Haan@rijnland.nl

A growing interest in genetic research in migraine has resulted in the
identification of several chromosomal regions that are involved in migraine.
However, the identification of mutations in the genes for familial hemiplegic
migraine (FHM) forms the only true molecular genetic knowledge of migraine thus
far. The increased number of mutations in the FHM1 (CACNA1A) and the FHM2
(ATP1A2) genes allow studying the relationship between genetic findings in both
genes and the clinical features in patients. A wide spectrum of symptoms is seen 
in patients. Additional cerebellar ataxia and (childhood) epilepsy can occur in
FHM1 and FHM2. Functional studies show a dysfunction in ion transport as the key 
factor in the pathophysiology of (familial hemiplegic) migraine that predict an
increased susceptibility to cortical spreading depression--the underlying
mechanism of migraine aura.

Publication Types: 
    Review

PMID: 15907261 [PubMed - indexed for MEDLINE]

1783: Curr Pain Headache Rep. 2005 Jun;9(3):206-12.

Non-oral formulations of triptans and their use in acute migraine.

Dahlöf CG.

Gothenburg Migraine Clinic, c/o Läkarhuset, Södra vägen 27, S-411 35 Gothenburg, 
Sweden. carl.dahlof@migraineclinic.se

The introduction of triptans (5-HT (1B/1D) agonists) into clinical practice has
expanded the therapeutic options for doctors treating migraine sufferers. The
triptans are available in several different formulations such as conventional
oral tablets, orally disintegrating wafers, subcutaneous injections, nasal
sprays, and suppositories, which provide an excellent opportunity to tailor
therapy to individual patients' needs. Although the oral formulations are the
most popular with patients, they are not the most appropriate route of
administration for drug delivery during the migraine attack. Due to
gastrointestinal dysmotility, the intestinal absorption of any triptan
administered orally may be impaired and treatment effects become inconsistent.
For this reason, triptans preferably should be prescribed in a non-oral
formulation (injection, nasal spray, or suppository). Parenteral administration
of a triptan is more likely to provide relief of symptoms, even when it is used
later in the course of the migraine attack.

Publication Types: 
    Review

PMID: 15907260 [PubMed - indexed for MEDLINE]

1784: Curr Pain Headache Rep. 2005 Jun;9(3):202-5.

Nonpharmacologic treatment of migraine.

Sándor PS, Afra J.

Headache and Pain Unit, Neurology Department, Frauenklinikstr 26, 8091 Zürich,
Switzerland. peter.sandor@gmx.info

Nonpharmacologic treatment of migraine is often used by patients and can provide 
interesting options for physicians. Knowledge about the evidence and its absence 
is important. Avoidance of trigger factors can help, if individualized.
Behavioral approaches, such as relaxation techniques, biofeedback, and
cognitive-behavioral therapy, require far more specialist time or technical
devices, but are supported by some evidence, which is mostly old. The same is
true for hypnosis. A new approach in migraine prevention is aerobic exercise,
which is associated with positive side effects. Whether it will take a strong
role, similar to the treatment of depression, remains to be seen. There is no
convincing evidence for the efficacy of spinal manipulation. Hyperbaric oxygen
may be an effective, but rarely practical prophylactic measure. The evidence
pertaining to the efficacy of acupuncture is controversial because of
methodologic difficulties, but an ongoing large German study may provide valuable
evidence in the near future. Nutritional supplements acting on mitochondrial
metabolism, such as magnesium, riboflavin, and coenzyme Q10, were shown to be
effective in small, randomized, controlled trials. More studies on the different 
therapeutic interventions are needed, using modern diagnostic standards and
state-of-the-art trial methodology.

Publication Types: 
    Review

PMID: 15907259 [PubMed - indexed for MEDLINE]

1785: Curr Pain Headache Rep. 2005 Jun;9(3):197-201.

Childhood periodic syndromes and migraine.

Winner P.

Palm Beach Headache Center, Premiere Research Institute at Palm Beach Neurology, 
Nova Southeastern University, 4631 North Congress Avenue, Suite 200, West Palm
Beach, FL 33407, USA. eneuro@aol.com

Headache in the pediatric population remains substantially underdiagnosed and
undertreated. The recently revised International Headache Society (IHS) criteria,
The International Classification of Headache Disorders, is a step in the right
direction to improve our diagnostic accuracy. In this article, the diagnostic
issues related to childhood periodic syndromes and migraine in the IHS 2004
revisions are reviewed.

Publication Types: 
    Review

PMID: 15907258 [PubMed - indexed for MEDLINE]

1786: Curr Pain Headache Rep. 2005 Jun;9(3):191-6.

Migraine and the neck: new insights from basic data.

Bartsch T.

Department of Neurology, University of Kiel, Schittenhelmstr. 10, 24105 Kiel,
Germany. t.bartsch@neurologie.uni-kiel.de

The clinical presentation of pain in patients with migraine showing spread and
referral of pain throughout the trigeminal and cervical innervation territories
accompanied by hyperalgesia and allodynia indicates a dynamic trigemino-cervical 
interaction. The physiologic mechanisms may be convergence of trigemino-cervical 
afferents and central sensitization of trigemino-cervical neurons leading to
dynamic neuroplastic changes during migraine. This review highlights the clinical
phenotype and mechanisms of how nociceptive input from neck structures of the
upper cervical spine are integrated into the trigemino-cervical system. The
nociceptive input into the spinal cord also is subject to a modulation by
segmental mechanisms in the spinal cord and by inhibitory projections from brain 
stem structures such as the periaqueductal gray. The functional relevance of
these basic mechanisms is discussed with reference to recent studies using
neurostimulation of afferent nerves aiming at pain modulation in patients with
migraine.

Publication Types: 
    Review

PMID: 15907257 [PubMed - indexed for MEDLINE]

1787: Clin Rheumatol. 2005 Nov;24(6):595-601. Epub 2005 May 18.

Fibromyalgia and headache: an epidemiological study supporting migraine as part
of the fibromyalgia syndrome.

Marcus DA, Bernstein C, Rudy TE.

Department of Anesthesiology, University of Pittsburgh Medical Center, PA, USA.

Fibromyalgia is defined by widespread body pain, tenderness to palpation of
tender point areas, and constitutional symptoms. The literature reports headache 
in about half of fibromyalgia patients. The current epidemiological study was
designed to determine the prevalence and characteristics of headache in
fibromyalgia patients. Treatment-seeking fibromyalgia patients were evaluated
with measures for fibromyalgia, chronic headache, quality of life, and
psychological distress. Multivariate analysis of variance (MANOVA) and t-tests
were used to identify significant differences, as appropriate. A total of 100
fibromyalgia patients were screened (24 fibromyalgia without headache and 76
fibromyalgia with headache). International Headache Society diagnoses included:
migraine alone (n = 15 with aura, n = 17 without aura), tension-type alone (n =
18), combined migraine and tension-type (n = 16), post-traumatic (n = 4), and
probable analgesic overuse headache (n = 6). Fibromyalgia tender point scores and
counts and most measures of pain severity, sleep disruption, or psychological
distress were not significantly different between fibromyalgia patients with and 
without headache. As expected, the fibromyalgia patients with headache scored
higher on the Headache Impact Test (HIT-6) (62.1 +/- 0.9 vs 48.3 +/- 1.6, p <
0.001). HIT-6 scores were >60 in 80% of fibromyalgia plus headache patients,
representing severe impact from headache, and 56-58 in 4%, representing
substantial impact. In summary, chronic headache was endorsed by 76% of
treatment-seeking fibromyalgia patients, with 84% reporting substantial or severe
impact from their headaches. Migraine was diagnosed in 63% of fibromyalgia plus
headache patients, with probable analgesic overuse headache in only 8%. General
measures of pain, pain-related disability, sleep quality, and psychological
distress were similar in fibromyalgia patients with and without headache.
Therefore, fibromyalgia patients with headache do not appear to represent a
significantly different subgroup compared to fibromyalgia patients without
headache. The high prevalence and significant impact associated with chronic
headache in fibromyalgia patients, however, warrants inclusion of a headache
assessment as part of the routine evaluation of fibromyalgia patients.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 15902517 [PubMed - indexed for MEDLINE]

1788: Am J Epidemiol. 2005 Jun 1;161(11):1066-73.

Incidence of primary headache: a Danish epidemiologic follow-up study.

Lyngberg AC, Rasmussen BK, Jørgensen T, Jensen R.

Research Centre for Prevention and Health, Glostrup University Hospital,
Glostrup, Denmark. anchly01@glostruphosp.kbhamt.dk

The incidence of migraine in a general population has been assessed in few
longitudinal studies, and the incidence of tension-type headache has never been
assessed. The authors aimed to assess the incidence of migraine and tension-type 
headache in Denmark by conducting a 12-year follow-up study of a general
population (1989-2001). The design and methods of follow-up replicated the
baseline study exactly, including use of the International Headache Society's
diagnostic criteria and administration of headache diagnostic interviews by a
physician. Of 740 persons aged 25-64 years examined in 1989, 673 were eligible in
2001 and 549 (81.6%) participated. The incidence of migraine was 8.1 per 1,000
person-years (male:female ratio, 1:6), and the incidence of frequent tension-type
headache was 14.2 per 1,000 person-years (male:female ratio, 1:3). Both rates
decreased with age. The incidence of migraine was higher than that previously
calculated from cross-sectional studies. Risk factors for migraine were familial 
disposition, no vocational education, a high work load, and frequent tension-type
headache. For tension-type headache, risk factors were poor self-rated health,
inability to relax after work, and sleeping few hours per night. The gender
difference for tension-type headache differed from that for migraine, and no
association with educational level was observed.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 15901627 [PubMed - indexed for MEDLINE]

1789: Patient Educ Couns. 2006 May;61(2):307-11.

The preliminary effectiveness of migraine lay trainers in a home-based
behavioural management training.

Mérelle SY, Sorbi MJ, Passchier J.

Erasmus University Medical Centre, Department of Medical Psychology and
Psychotherapy, P.O. Box 1738, 3000 DR Rotterdam, The Netherlands.
s.merelle@erasmusmc.nl

OBJECTIVES: This pilot study examined the effectiveness and trainer skills of the
first migraine lay trainers (MLTs). METHODS: In a stepwise training program eight
MLTs participated in a behavioural management training (BMT) aimed at the
prevention of migraine attacks by proactive relaxation and trigger management.
After successful reduction of their migraine attacks, three MLTs provided BMT
under supervision at home to one fellow patient and subsequently to a small
group. RESULTS: Migraine frequency was significantly reduced in five out of eight
patients trained by MLTs (mean 48%) and medication use decreased substantially in
four patients (mean 47%). Qualities of MLTs concerned their motivational
assistance, knowledge of premonitory symptoms and exchange of disease specific
problems. Pitfalls were that migraine symptoms hampered an active guidance of the
sessions and providing tailored feedback was difficult. CONCLUSION: The first
MLTs were successful in training fellow patients in behavioural prevention of
migraine attacks. PRACTICE IMPLICATIONS: Continuous supervision of MLTs health
and trainer skills is recommended but is likely to have implications for
cost-effectiveness.

Publication Types: 
    Evaluation Studies
    Research Support, Non-U.S. Gov't

PMID: 15896944 [PubMed - indexed for MEDLINE]

1790: Brain Res Mol Brain Res. 2005 May 20;136(1-2):112-7. Epub 2005 Feb 19.

Genetic variants of angiotensin converting enzyme and methylenetetrahydrofolate
reductase may act in combination to increase migraine susceptibility.

Lea RA, Ovcaric M, Sundholm J, Solyom L, Macmillan J, Griffiths LR.

Genomic Research Centre, School of Health Science, Griffith University, Parklands
Drive, Southport, QLD 4217, Australia.

Migraine, with and without aura (MA and MO), is a prevalent and complex
neurovascular disorder that is likely to be influenced by multiple genes some of 
which may be capable of causing vascular changes leading to disease onset. This
study was conducted to determine whether the ACE I/D gene variant is involved in 
migraine risk and whether this variant might act in combination with the
previously implicated MTHFR C677T genetic variant in 270 migraine cases and 270
matched controls. Statistical analysis of the ACE I/D variant indicated no
significant difference in allele or genotype frequencies (P > 0.05). However,
grouping of genotypes showed a modest, yet significant, over-representation of
the DD/ID genotype in the migraine group (88%) compared to controls (81%) (OR of 
1.64, 95% CI: 1.00-2.69, P = 0.048). Multivariate analysis, including genotype
data for the MTHFR C677T, provided evidence that the MTHFR (TT) and ACE (ID/DD)
genotypes act in combination to increase migraine susceptibility (OR = 2.18, 95% 
CI: 1.15-4.16, P = 0.018). This effect was greatest for the MA subtype where the 
genotype combination corresponded to an OR of 2.89 (95% CI:1.47-5.72, P = 0.002).
In Caucasians, the ACE D allele confers a weak independent risk to migraine
susceptibility and also appears to act in combination with the C677T variant in
the MTHFR gene to confer a stronger influence on the disease.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 15893594 [PubMed - indexed for MEDLINE]

1791: Med Hypotheses. 2005;65(1):114-22.

Migraine prophylactic drugs work via ion channels.

Cohen GL.

Department of Neurology, Marshfield Clinic, Marshfield, WI, USA.
cohen.gary@marshfieldclinic.org

In recent decades, the concept of a vascular origin of migraine has been replaced
by theories based on a neuronal pathophysiology. These theories all involve rapid
changes in the functioning of the brain, particularly the brain stem, and the
trigeminal nerves. While such paroxysmal changes in function could be the result 
of altered synaptic transmission, or other physiological changes, they could also
be due to changes in the function of voltage-regulated sodium and calcium ion
channels. Support for this view of migraine as a channelopathy comes from an
examination of the likely mechanism of action of migraine prophylactic drugs. It 
is the present hypothesis that most of the widely used drugs for migraine
prevention work by inhibiting the function of one or both of these ion channels. 
A review of the laboratory research done on most of the commonly used migraine
prophylactic drugs, divided into five classes, reveals that they all may work on 
sodium channels, calcium channels, or both. If this is the common mechanism of
action of migraine prophylactics, it should lead toward the development of more
effective prophylactic drugs.

PMID: 15893128 [PubMed - indexed for MEDLINE]

1792: Curr Opin Neurol. 2005 Jun;18(3):305-10.

Comorbidity of migraine.

Scher AI, Bigal ME, Lipton RB.

Department of Preventive Medicine and Biometrics, Uniformed Services University
of the Health Sciences, Bethesda, Maryland 20814, USA. ascher@usuhs.mil

PURPOSE OF REVIEW: Comorbidity refers to the greater than coincidental
association of separate conditions in the same individuals. Historically, a
number of conditions have been noted to be comorbid with migraine, notably
psychiatric disorders (anxiety, depression, panic disorder), epilepsy, asthma,
and some congenital heart defects. Migraine sufferers have increased medical
costs overall compared with others of the same sex and age, even after
considering the cost of specific migraine treatment. Thus, estimates of the
burden of migraine often include the costs of conditions comorbid with it. RECENT
FINDINGS: Conditions may be comorbid through a variety of mechanisms. Comorbidity
may be an artifact of diagnostic uncertainty when symptom profiles overlap or
when diagnosis is not based on objective markers. Comorbidity may arise due to
unidirectional causality, such as migraine resulting in blood pressure changes
due to headache-specific treatment. Finally, conditions may be comorbid because
of shared genetic or other factors that increase the risk of both conditions. In 
such cases, understanding these shared risk factors may lead to greater
understanding of the fundamental mechanisms of migraine. SUMMARY: In this
article, we will review recent developments related to migraine comorbidity. We
will emphasize findings related to the comorbidity of migraine with clinical and 
sub-clinical vascular brain lesions, congenital heart defects, coronary heart
disease, psychiatric illness, and other pain conditions.

Publication Types: 
    Review

PMID: 15891417 [PubMed - indexed for MEDLINE]

1793: Curr Opin Neurol. 2005 Jun;18(3):299-304.

Patent foramen ovale: paradoxical connection to migraine and stroke.

Diener HC, Weimar C, Katsarava Z.

Department of Neurology, University of Duisburg-Essen, Germany.
h.diener@uni-essen.de

PURPOSE OF REVIEW: In this article we aim to elucidate the relationship between
patent foramen ovale, cryptogenic stroke and migraine. RECENT FINDINGS: Small
observational and case-control studies indicate that patients with cryptogenic
stroke have a higher incidence of patent foramen ovale. Prospective trials could 
not show a higher stroke recurrence risk with isolated patent foramen ovale. The 
combination of patent foramen ovale and atrial septal aneurysm might carry a
higher recurrence risk. Secondary prevention with acetylsalicylic acid is as
effective as oral anticoagulation, but carries a lower bleeding risk. Whether
patent foramen ovale closure prevents recurrent strokes is under investigation.
Case-control studies and retrospective analyses indicate comorbidity between
patent foramen ovale and migraine, in particular migraine with aura. Recent
retrospective studies indicate a reduction in migraine frequency after patent
foramen ovale closure (intended for stroke prevention). These studies, however,
have major methodological limitations. Therefore patent foramen ovale closure
cannot be recommended for the prevention of migraine with aura. SUMMARY: At
present routine percutaneous closure of isolated patent foramen ovale cannot be
recommended for patients with cryptogenic stroke. Patent foramen ovale closure
should not be used for the prevention of migraine.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 15891416 [PubMed - indexed for MEDLINE]

1794: Curr Opin Neurol. 2005 Jun;18(3):289-92.

Preventive treatment of headaches.

Silberstein SD.

Thomas Jefferson University Hospital, Philadelphia, PA 19107, USA.
Stephen.Silberstein@jefferson.edu

PURPOSE OF REVIEW: To review recent advances in preventive headache treatment.
RECENT FINDINGS: Migraine may be a progressive disorder. Aggressive treatment may
stop progression. Propranolol, the beta-blocker, and the anticonvulsant
topiramate are effective for migraine prevention. Feverfew, montelukast and
acupuncture have not proven effective. SUMMARY: New drugs and other treatment
strategies expand the spectrum of preventive migraine treatments.

Publication Types: 
    Review

PMID: 15891414 [PubMed - indexed for MEDLINE]

1795: Appl Psychophysiol Biofeedback. 2005 Mar;30(1):53-63.

The effect of the definition of menstrually-related headache on the response to
biofeedback treatment.

Blanchard EB, Kim M.

Center for Stress and Anxiety Disorders, University at Albany 1400 Washington
Avenue, Albany, NY 12222, USA. ceblanchard@earthlink.net

Twelve women with either pure migraine headache (HA) or a combination of migraine
and tension-type HA monitored HA activity over two menstrual cycles while noting 
onset of menstruation and onset of ovulation. They then received 12 sessions of
thermal biofeedback (TBF) with adjunctive autogenic training. Six women with only
tension-type HA participated in similar monitoring before receiving 9 sessions of
progressive relaxation training. Results for those with vascular HA showed a
significant reduction in HA activity and a reduction in medication taken for HAs.
Those with tension-type HA did not respond significantly to the relaxation
training. Depending upon how one defined menstrually-related HAs among those with
vascular HA, there either was, or was not, a differential effect of TBF on
menstrual-cycle-related HA.

Publication Types: 
    Clinical Trial
    Research Support, N.I.H., Extramural
    Research Support, U.S. Gov't, P.H.S.
    Review

PMID: 15889585 [PubMed - indexed for MEDLINE]

1796: Clin Neurol Neurosurg. 2005 Jun;107(4):301-5.

Magnetic resonance angiography of the circle of Willis in migraine patients.

Paemeleire K, Proot P, De Keyzer K, Achten E, Crevits L.

Department of Neurology, Ghent University Hospital, De Pintelaan 185, B-9000
Ghent, Belgium. koenpaemeleire@yahoo.com

We analysed records of 244 consecutive adult outpatients who presented at our
neurological polyclinic between 1996 and 2001 with migraine and who underwent a
MRA of the circle of Willis. In 80 cases, a definitive migraine diagnosis
according to the International Headache Society criteria (1988) could be
retrieved from the patient records. Of these, 63 patients had migraine without
aura and 17 patients had migraine with aura. Two MRA procedures were abrupted
because of claustrophobia and another two MRA studies were unreliable because of 
movement artefacts. In only one patient of the remaining 240, an aneurysm was
suspected with MRA. However, a conventional angiography did not confirm any
cerebrovascular abnormality. All other exams were considered normal. This
retrospective study argues against a systematic screening of migraine patients
with MRA.

PMID: 15885388 [PubMed - indexed for MEDLINE]

1797: Neurology. 2005 May 10;64(9):1573-7.

Comment in:
    Neurology. 2005 May 10;64(9):1496-7.

Headache, cerebrovascular symptoms, and stroke: the Atherosclerosis Risk in
Communities Study.

Stang PE, Carson AP, Rose KM, Mo J, Ephross SA, Shahar E, Szklo M.

Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel
Hill, NC 27514, USA.

OBJECTIVE: To evaluate the occurrence of stroke/TIA symptoms and ischemic stroke 
events among those with a lifetime history of migraine or other headaches with
some migraine features in a biracial cohort of older adults. METHODS:
Participants were 12,750 African-American and white men and women from the
Atherosclerosis Risk in Communities Study (1993 to 1995). The participants were
queried about their lifetime headache history and characterized using modified
International Headache Society diagnostic criteria. Stroke/TIA symptoms were
classified using a computerized diagnostic algorithm, and ischemic stroke events 
were identified and validated using medical records. Multivariate logistic
regression was used to assess the relationship between headache types and
stroke/TIA symptoms and ischemic stroke events. RESULTS: Migraine with aura was
strongly associated with stroke symptoms (odds ratio [OR] 5.46, 95% CI: 3.64 to
8.18), TIA symptoms (OR 4.28, 95% CI: 3.02 to 6.08), and verified ischemic stroke
events (OR 2.81, 95% CI: 1.60 to 4.92). Similarly, other headaches with aura were
significantly associated with stroke symptoms (OR 3.68, 95% CI: 2.26 to 5.99) and
TIA symptoms (OR 4.53, 95% CI: 3.08 to 6.67). In contrast, the associations for
migraine without aura and other headaches without aura were not as consistent or 
robust. CONCLUSIONS: Migraines and other headaches, particularly those
accompanied by aura, were associated with an increased occurrence of stroke/TIA
symptoms and ischemic stroke events.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 15883318 [PubMed - indexed for MEDLINE]

1798: Prescrire Int. 2005 Apr;14(76):45-7.

Nasal sumatriptan: new dosage. For adolescents with migraine: too little benefit.

[No authors listed]

(1) The reference first-line drug therapy for migraine attacks in adolescents is 
a non specific analgesic such as paracetamol or a nonsteroidal antiinflammatory
drug like ibuprofen. Two specific analgesics are authorised for use in this
setting in France, namely ergotamine and dihydroergotamine. (2) Nasal sumatriptan
is the first triptan to be licensed for this age group in France. (3) Evaluation 
data includes three flawed placebo-controlled trials. (4) Effects were modest at 
best. Only one of the three trials showed that sumatriptan was more likely than
placebo to give complete pain relief within two hours. The three trials fail to
show that sumatriptan is effective against symptoms such as nausea and vomiting, 
photophobia and phonophobia. (5) The principal known adverse effects of
sumatriptan are chest tightness, flushing, and increased blood pressure. (6) In
the only trial report containing relevant information, unpleasant taste was the
only adverse effect more commonly associated with sumatriptan than with placebo. 
(7) Postmarketing follow-up revealed a number of serious adverse effects,
including stroke, myocardial infarction and loss of vision. (8) The packs
containing 6 or 12 spray vials carry a risk of overuse and self-induced headache.
(9) In practice, sumatriptan must not be used to treat migraine attacks in
adolescents.

PMID: 15875337 [PubMed - indexed for MEDLINE]

1799: JAMA. 2005 May 4;293(17):2118-25.

Acupuncture for patients with migraine: a randomized controlled trial.

Linde K, Streng A, Jürgens S, Hoppe A, Brinkhaus B, Witt C, Wagenpfeil S,
Pfaffenrath V, Hammes MG, Weidenhammer W, Willich SN, Melchart D.

Centre for Complementary Medicine Research, Department of Internal Medicine II,
Technische Universität München, Munich, Germany. Klaus.Linde@lrz.tu-muenchen.de

CONTEXT: Acupuncture is widely used to prevent migraine attacks, but the
available evidence of its benefit is scarce. OBJECTIVE: To investigate the
effectiveness of acupuncture compared with sham acupuncture and with no
acupuncture in patients with migraine. DESIGN, SETTING, AND PATIENTS:
Three-group, randomized, controlled trial (April 2002-January 2003) involving 302
patients (88% women), mean (SD) age of 43 (11) years, with migraine headaches,
based on International Headache Society criteria. Patients were treated at 18
outpatient centers in Germany. INTERVENTIONS: Acupuncture, sham acupuncture, or
waiting list control. Acupuncture and sham acupuncture were administered by
specialized physicians and consisted of 12 sessions per patient over 8 weeks.
Patients completed headache diaries from 4 weeks before to 12 weeks after
randomization and from week 21 to 24 after randomization. MAIN OUTCOME MEASURES: 
Difference in headache days of moderate or severe intensity between the 4 weeks
before and weeks 9 to 12 after randomization. RESULTS: Between baseline and weeks
9 to 12, the mean (SD) number of days with headache of moderate or severe
intensity decreased by 2.2 (2.7) days from a baseline of 5.2 (2.5) days in the
acupuncture group compared with a decrease to 2.2 (2.7) days from a baseline of
5.0 (2.4) days in the sham acupuncture group, and by 0.8 (2.0) days from a
baseline if 5.4 (3.0) days in the waiting list group. No difference was detected 
between the acupuncture and the sham acupuncture groups (0.0 days, 95% confidence
interval, -0.7 to 0.7 days; P = .96) while there was a difference between the
acupuncture group compared with the waiting list group (1.4 days; 95% confidence 
interval; 0.8-2.1 days; P<.001). The proportion of responders (reduction in
headache days by at least 50%) was 51% in the acupuncture group, 53% in the sham 
acupuncture group, and 15% in the waiting list group. CONCLUSION: Acupuncture was
no more effective than sham acupuncture in reducing migraine headaches although
both interventions were more effective than a waiting list control.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 15870415 [PubMed - indexed for MEDLINE]

1800: CNS Drug Rev. 2005 Spring;11(1):69-76.

Clinical data on the CGRP antagonist BIBN4096BS for treatment of migraine
attacks.

Edvinsson L.

Department of Internal Medicine, University Hospital, S-221 85 Lund, Sweden.
lars.edvinsson@med.lu.se

Basal studies have shown that calcitonin gene-related peptide (CGRP) is a major
sensory neuronal messenger in the trigeminovascular system, the pathway conveying
intracranial pain. In migraine and cluster headache attacks, CGRP is released in 
parallel with the pain and successful treatment of the attacks abort both the
associated pain and the CGRP release. The search for a potent small molecule CGRP
antagonist has been successful and such an agent has been tested in preclinical
and clinical studies. The aim of the present study was to examine current
knowledge on the clinical pharmacology of systemic BIBN4096BS, which has been
shown in man to abort acute migraine attacks as well or better than oral
sumatriptan. BIBN4096BS is a specific and potent CGRP receptor antagonist in
humans. In safety and tolerability studies the substance is well tolerated with
no or only mild side effects. In acute migraine attacks the overall response was 
66% with the drug and 27% with placebo. A difference as compared to placebo was
seen at 30 min; the response was still rising at 4 h suggesting a long duration
of action. At 24 h the pain-free rate was better than that with triptans,
suggesting a lower grade of rebound and perhaps even a prophylactic possibility.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 15867953 [PubMed - indexed for MEDLINE]

1801: J Psychosom Res. 2005 Mar;58(3):253-8.

Do others really know us better? Predicting migraine activity from self- and
other-ratings of negative emotion.

Lumley MA, Huffman JL, Rapport LJ, Aurora SK, Norris LL, Ketterer MW.

Department of Psychology, Wayne State University, 71 West Warren Avenue, Detroit,
MI 48202, USA. mlumley@sun.science.wayne.edu

OBJECTIVE: The validity of self-reported negative emotion to predict health
status is limited by response biases, introspection limitations, and
methodological confounds. The reports of significant others about the patients'
negative emotion may circumvent these limitations. This study sought to compare
the validity of self- versus other-reported negative emotion as a correlate of
migraine headache activity. METHODS: On 89 patients with migraine headache (74
women and 15 men), we correlated self-ratings and significant-other-ratings of
patients' negative emotion with patients' report of migraine frequency and
severity, which were assessed both cross-sectionally and prospectively, 3 months 
later. RESULTS: Other-reported negative emotion correlated with migraine activity
better than did self-reported negative emotion, both cross-sectionally and
prospectively. Patterns were different for women and men, however. Among women,
other-reported negative emotion was positively associated with migraine activity.
Among men, other-reported negative emotion was inversely associated with migraine
frequency and severity. CONCLUSION: The results suggest that it may be valuable
to obtain significant-other-ratings when assessing negative emotion in patients
and that the genders may differ in how others' ratings are related to the
patients' health.

PMID: 15865949 [PubMed - indexed for MEDLINE]

1802: Eur J Pain. 2005 Jun;9(3):285-91.

Psychiatric comorbidity in medication overuse headache patients with pre-existing
headache type of episodic tension-type headache.

Atasoy HT, Atasoy N, Unal AE, Emre U, Sumer M.

Neurology Department, Faculty of Medicine, Zonguldak Karaelmas University,
Turkey. htrlatasoy@hotmail.com

BACKGROUND: Medication overuse headache (MOH) mostly evolves from migraine and
episodic tension-type headache (ETTH). Chronic tension-type headache (CTTH) is
another headache type that evolves over time from ETTH. It is well known that
psychiatric comorbidity is high in MOH patients. AIM: To investigate the
frequency of psychiatric comorbidity, and the intensity of depression and anxiety
in MOH patients evolving from ETTH and to compare results with CTTH patients and 
MOH patients evolving from migraine. METHODS: Twenty-eight CTTH (Group C) and 89 
MOH patients were included into the study. MOH patients were divided into two
groups according to their pre-existing headache types: MOH patients with
pre-existing ETTH (Group E, n = 31), and with pre-existing migraine (Group M, n =
58). All patients were interviewed with a psychiatrist and SCID-CV and SCID-II
were applied. Beck Anxiety Inventory and Beck Depression Inventory scales were
also performed. RESULTS: Eleven patients (39.3%) in Group C, 21 patients (67.7%) 
in Group E, and 31 patients (53.7%) in Group M were diagnosed to have comorbid
psychiatric disorders. The psychiatric comorbidity was found significantly higher
in Group E than Group C. In Group E, mood disorders were found significantly
higher, but the difference between the two groups with regard to anxiety
disorders was insignificant. Mean depression scores were significantly higher in 
Group E than Group C. The mostly diagnosed type was obsessive-compulsive
personality disorder in all the three groups, and was statistically significant
in Group M than Group C. CONCLUSION: Psychiatric comorbidity in MOH patients with
pre-existing ETTH is common as in those with pre-existing migraine headache and
MOH with regard to developing psychiatric disorders should be interpreted as a
risk factor in chronic daily headache patients.

Publication Types: 
    Comparative Study

PMID: 15862478 [PubMed - indexed for MEDLINE]

1803: Plast Reconstr Surg. 2005 May;115(6):1752-8; discussion 1759-60.

The lesser and third occipital nerves and migraine headaches.

Dash KS, Janis JE, Guyuron B.

Akron Summa Health, Akron, Ohio, USA.

BACKGROUND: Reports of a correlation between relief of migraine headaches and
resection of corrugator muscles or injection of botulinum A toxin have renewed
interest in finding the cause of migraine headaches and identifying the trigger
sites. Four trigger sites have been described. One of these is along the course
of the greater occipital nerve. Recent anatomical studies of this nerve have
defined its location with respect to external landmarks, leading to new studies
with gratifying results. There is a subset of patients who undergo
chemodenervation or surgical release of the greater occipital nerve and note
improvement or elimination of the symptoms along the greater occipital nerve
course but who experience an emergence of migraine headache symptoms laterally.
The authors propose the lesser occipital nerve as the source of pain in those who
experience headaches laterally and involvement of the third occipital nerve in
those who notice residual symptoms in the midportion of the occipital region.
METHODS: To test this hypothesis anatomically, 20 cadaver heads were dissected to
trace the course of the lesser occipital nerve and third occipital nerve and
define the location of these nerves with respect to external landmarks. The
midline and a line drawn between the inferiormost points of the external auditory
canals were used to obtain standardized measurements of these nerves. RESULTS:
The location of emergence of the lesser occipital nerve was determined to be an
area centered 65.4 +/- 11.6 mm from midline and 53.3 +/- 15.6 mm below the line
between the external auditory canals. The third occipital nerve was found 13.2
+/- 5.3 mm from midline and 62.0 +/- 20.0 mm down from the line between the two
external auditory canals. CONCLUSIONS: This information can be used to conduct
clinical trials of chemodenervation of these nerves in an attempt to eliminate
migraine symptoms in the subset of patients who continue to experience residual
symptoms after surgical release of the greater occipital nerve.

PMID: 15861086 [PubMed - indexed for MEDLINE]

1804: Int J Clin Pract. 2005 May;59(5):515-21.

Examination of anxiety, hostility and psychiatric disorders in patients with
migraine and tension-type headache.

Bag B, Hacihasanoglu R, Tufekci FG.

Department of Psychiatry Nursing, College of Nursing, Atatürk University,
Erzurum, Turkey. beyhanbag@yahoo.com

The role of psychological factors related to headache has long been a focus of
investigation. The aim of this study was to evaluate anxiety, depression,
hostility and psychological symptoms in patients with migraine and tension-type
headache (TTH) and to compare the results with healthy controls. Seventy-five
subjects with migraine and 55 subjects with TTH (according to the criteria of the
International Headache Society classification) and a control group including 73
healthy subjects were studied. The Buss-Durkee Hostility Inventory, Brief Symptom
Inventory, State-trait Anxiety Inventory, Trait form were administered to the
subjects. Compared with healthy controls, the patients with headache had
significantly higher scores on measures of anxiety, depression and hostility and 
lower scores on psychological symptoms. The present results indicate the need to 
distinguish the unique dimensions of anxiety, depression and hostility that
should be assessed in the population with headaches.

PMID: 15857345 [PubMed - indexed for MEDLINE]

1805: Int J Clin Pract. 2005 Mar;59(3):281-6.

Use of a structured migraine diary improves patient and physician communication
about migraine disability and treatment outcomes.

Baos V, Ester F, Castellanos A, Nocea G, Caloto MT, Gerth WC; I-Max Study Group.

Centro de Salud Collado Villalba, Madrid, Spain.

Migraine is frequently undertreated, perhaps because impaired communication
between patients and physicians underestimate the disability associated with
migraine attacks. The purpose of this study was to evaluate the benefits of a
structured migraine diary used during a prospective open-label study of
triptan-naive patients in Spain for recording information on response to therapy 
for a pre-study migraine attack and three consecutive migraine attacks, the first
and third treated with rizatriptan 10-mg wafer and the second with usual
non-triptan therapy. Of 97 patients (83% women; mean age, 39 years) who completed
the study, all reported moderate to severe pain, and two-thirds reported severe
to total impairment during migraine attacks. At study end, 72% of patients
reported that the migraine diary helped communication with their doctor about
migraine, and 70% were more or much more satisfied than before the study with
level of overall medical care provided by their doctor. Patients who reported the
diary to be useful also reported higher overall satisfaction with medical care (p
< 0.001). Most of the 22 physicians (91%) reported that the diary enabled them to
better communicate with their patients about migraine, and all reported that it
enabled them to assess differences in pain intensity and disability across
patients. We conclude that a structured migraine diary can be a valuable aid for 
improving communication between physicians and patients regarding migraine
disability and treatment outcomes.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 15857323 [PubMed - indexed for MEDLINE]

1806: Ophthalmic Physiol Opt. 2005 May;25(3):240-5.

The pupillary light reflex in migraine.

Harle DE, Wolffsohn JS, Evans BJ.

The Neville Chappell Research Clinic, The Institute of Optometry, London.
dharle@ioo.org.uk

The literature suggests that there may be pupil size and response abnormalities
in migraine headache sufferers. We used an infra-red pupillometer to measure
dynamic pupil responses to light in 20 migraine sufferers (during non-headache
periods) and 16 non-migraine age and gender matched controls. There was a
significant increase in the absolute inter-ocular difference of the latency of
the pupil light response in the migraine group compared with the controls (0.062 
s vs 0.025 s, p = 0.014). There was also a significant correlation between
anisocoria and lateralisation of headache such that migraine sufferers with a
habitual head pain side have more anisocoria (r = 0.59, p < 0.01), but this was
not related to headache laterality. The pupil changes were not correlated with
the interval since the last migraine headache, the severity of migraine headache 
or the number of migraine headaches per annum. We conclude that subtle
sympathetic and parasympathetic pupil abnormalities persist in the inter-ictal
phase of migraine.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 15854071 [PubMed - indexed for MEDLINE]

1807: Ophthalmic Physiol Opt. 2005 May;25(3):233-9.

Comment in:
    Ophthalmic Physiol Opt. 2006 Mar;26(2):217-8; author reply 219-20.

Frequency doubling technology perimetry and standard automated perimetry in
migraine.

Harle DE, Evans BJ.

The Neville Chappell Research Clinic, The Institute of Optometry, Newington
Causeway, London. dharle@ioo.org.uk

The literature suggests that visual field defects may be more common in people
who experience migraine. The Humphrey frequency doubling (FDT) visual field
instrument selectively examines the magnocellular visual pathway, but has not
previously been used to investigate visual function in migraine. In a masked
controlled study we compared Humphrey FDT and Humphrey Swedish Interactive
Threshold Algorithm fields of 25 migraine sufferers with 25 age- and
gender-matched controls. Although both mean deviation and pattern standard
deviation were a little worse in the migraine group, these differences did not
reach statistical significance. There were no inter-eye visual field differences 
in the migraine group compared with controls. Comparing the mean of all the
contrast thresholds in each hemisphere, there were no more inter-hemifield visual
field differences in the migraine group compared with controls. There was no
significant difference between the migraine and control groups in intra-ocular
pressures. The visual field parameters were not correlated with the interval
since the last migraine headache, the severity of migraine headache, the duration
of migraine headache or the number of migraine headaches per annum. In our data, 
there was no evidence of visual field deficits, a magnocellular deficit, or
indications of glaucomatous pathology.

Publication Types: 
    Comparative Study
    Evaluation Studies
    Research Support, Non-U.S. Gov't

PMID: 15854070 [PubMed - indexed for MEDLINE]

1808: Expert Rev Neurother. 2004 Jan;4(1):33-41.

Zolmitriptan (Zomig).

Rapoport AM, Bigal ME, Tepper SJ, Sheftell FD.

College of Physicians and Surgeons, Columbia University, New York, NY, USA.
alanrapoport@nech.net

New triptans are being released in rapid succession with each addition
demonstrating some specific pharmacokinetic properties, which may be translated
into clinical advantages. Zolmitriptan (Zomig) offers a range of alternatives to 
migraine sufferers. The conventional tablet is consistently effective across a
wide range of migraine subtypes. The orally disintegrating tablet offers an
effective option for those migraineurs who are nauseated or need to take their
medication earlier in the course of their migraine. Since it can be taken without
fluid, the orally disintegrating tablet may be consistently used early in the
migraine attack when the pain is still mild. The nasal spray aggregates all the
benefits of the oral formulations and has a faster onset of action. The 5-mg dose
of all three forms of zolmitriptan offers additional benefits over the 2.5-mg
dose at early time points. The physician can now choose the optimum route of
delivery of zolmitriptan to stop the headache, increase the likelihood of
reducing disability and restore the patient to complete functionality.

Publication Types: 
    Review

PMID: 15853613 [PubMed - indexed for MEDLINE]

1809: Expert Rev Neurother. 2004 Jan;4(1):27-31.

Botulinum toxin type A (Botox) in the treatment of migraine and other headaches.

Troost BT.

Department of Neurology, Wake Forest University School of Medicine, Medical
Center Boulevard, Winston-Salem, NC 27157, USA. todd@toddtroost.com

Botulinum toxin type A (Botox) is increasingly used in the management of migraine
and tension-type headaches. The results from small placebo-controlled trials and 
extensive open-label experience has suggested a significant role for this
neurotoxin in the management of refractory headache. Several large
placebo-controlled trials of episodic and chronic migraine are currently
underway.

Publication Types: 
    Review

PMID: 15853612 [PubMed - indexed for MEDLINE]

1810: Expert Rev Neurother. 2004 Mar;4(2):199-209.

Sumatriptan: a decade of use and experience in the treatment of migraine.

Sheftell FD, Bigal ME, Tepper SJ, Rapoport AM.

The New England Center for Headache, PC 778 Long Ridge Road, Stamford, CT 06902
1251, USA. Ninotores1@aol.com

The migraine-specific triptans have revolutionized the treatment of migraine and 
are usually the drugs of choice to treat a migraine attack in progress.
Sumatriptan (Imitrex) has been available for the longest time within the class,
is most flexible in form and has been given successfully to the most number of
patients. It is useful for the full range of attacks experienced by a migraine
suffer. The aim of this review is to provide an overview of the first 10 years of
the use of sumatriptan.

Publication Types: 
    Review

PMID: 15853561 [PubMed - indexed for MEDLINE]

1811: Expert Rev Neurother. 2004 May;4(3):403-13.

Behavioral treatment of migraine: current status and future directions.

Andrasik F.

Institute for Human and Machine Cognition, University of West Florida, 40 South
Alcaniz Street, Pensacola, FL 32502, USA. 4440fandrasik@ihmc.us

The empirical support for three behavioral treatments (relaxation, biofeedback
and cognitive therapy) for managing migraine headaches in children and adults is 
reviewed. Meta-analyses and evidence-based reports show that these approaches are
of considerable value, they appear to work equally well when applied
individually, in groups or in limited contact formats. Meta-analyses comparing
behavioral and prophylactic medication show equivalent results. However, outcomes
are optimized when these treatments are combined. Researchers are currently
seeking to identify factors predictive of response to behavioral approaches.
Patients experiencing medication-overuse, refractory, cluster or post-traumatic
forms of headache or comorbid conditions present special challenges that can
require intensive, comprehensive and multidisciplinary approaches to treatment.
Behavioral treatments have met with mixed success for menstrual migraine in the
few studies that have been conducted. This review concludes by highlighting
directions for future research efforts such as importing treatments to settings
where headache patients most often seek care and developing algorithms for
optimizing combinations of behavioral and pharmacological treatments to enhance
effectiveness, reduce costs, minimize dosing requirements and improve adherence
to needed medications. Other research efforts include developing treatments that 
target the underlying pathophysiology more directly, gaining a greater
understanding of mediators and moderators of behavioral treatments, exploiting
e-technology for assessment and treatment, and assessing outcome in multiple
ways--such as quality of life.

Publication Types: 
    Review

PMID: 15853538 [PubMed - indexed for MEDLINE]

1812: Expert Rev Neurother. 2004 May;4(3):391-430.

Future pharmacologic targets for acute and preventive treatments of migraine.

Buchanan TM, Ramadan NM, Aurora S.

Rosalind Franklin University of Medicine and Science, 3333 Green Bay Road, North 
Chicago, IL 60064, USA. thomasbuchanan@finchcms.edu

Advances in investigative research (e.g., functional magnetic resonance imaging) 
have made it possible to study putative migraine processes and better understand 
the pathophysiology of the disorder. Consequently, the apparent opposing vascular
and neuronal theories of migraine are now reconciled into a neurovascular
hypothesis that pieces together migrainous events and allows us to better target 
such events in the hope of providing safe and effective therapies. Parallel
discoveries in the fields of pharmacology, physiology, genetics and other
biomedical disciplines will lead to the development of optimal migraine
therapeutics. Such discoveries have already yielded some major enhancement in
acute migraine treatment with the development of sumatriptan (Imitrex,
GlaxoSmithKline) and other triptans and the trajectory is likely to be
exponential. Novel targets, such as calcitonin gene-related peptide antagonists
and inhibitors of excitatory glutamatergic receptors, are leading the pack but
many other promising targets are in development. The post-sumatriptan decades
will witness treatment strategies that will improve the therapeutic index of
acute therapies and others which will effectively and safely prevent migraine
attacks.

Publication Types: 
    Review

PMID: 15853537 [PubMed - indexed for MEDLINE]

1813: Expert Rev Neurother. 2004 May;4(3):383-90.

Diagnosis and pathophysiology of migraine.

Ward TN, Levin M.

Dartmouth Hitchcock Medical Center, Lebanon, NH 03756, USA.
Thomas.N.Ward@hitchcock.org

Over the past 10 years there has been an explosion of knowledge about headache,
particularly migraine. Fueled by new, highly effective therapeutic agents, vast
resources have been invested in improving diagnostic accuracy and attempting to
understand the mechanisms by which this symptom is generated. Public awareness
has increased as has that of the medical community. Tools are now available to
help diagnose particular types of headache and measure/monitor disability.
Numerous pathophysiologic changes have been studied which may in turn increase
the therapeutic armamentarium. With approximately 10% of the public suffering
from migraine and with most of these cases remaining undiagnosed, it is likely
that this segment of the healthcare market will continue to expand in the future.

Publication Types: 
    Review

PMID: 15853536 [PubMed - indexed for MEDLINE]

1814: Expert Rev Neurother. 2004 May;4(3):339-48.

Oral almotriptan: practical uses in the acute treatment of migraine.

Dowson AJ.

The King's Headache Service, King's College Hospital, Denmark Hill, London, SE5
9RS, UK. drandydowson@dowsona.fsnet.co.uk

Almotriptan (Almogran, Lundbeck; Almirall Prodesfarma; Axert, Ortho-McNeil) is a 
novel 5-HT(1B/1D) receptor agonist (triptan) that is widely available on
prescription for the acute treatment of migraine. Almotriptan has pharmacodynamic
and pharmacokinetic profiles that make it suitable for use in this indication. It
is a potent agonist at 5-HT(1B), (1D) and (1F) receptors, while having a low
affinity for other 5-HT receptors. It is also a potent inhibitor of neurogenic
inflammation. Almotriptan has a high oral bioavailability, is absorbed rapidly,
has a relatively short plasma half-life and its route of elimination presents few
potential problems. Placebo-controlled dose-finding studies have demonstrated
that almotriptan tablets are effective and well-tolerated in the acute treatment 
of migraine, with a 12.5 mg dose providing the best balance between efficacy and 
tolerability. Large placebo-controlled studies show that the efficacy of oral
almotriptan is comparable with that of the other oral triptans. In direct
comparator-controlled studies, almotriptan was as effective as sumatriptan 50 and
100 mg but had a superior tolerability profile. Furthermore, the efficacy and
tolerability of almotriptan is sustained in the long term following open-label
administration. Meta-analyses and post hoc analyses of clinical data confirm
these findings. In conclusion, almotriptan 12.5 mg is a good therapeutic choice
for the symptomatic treatment of acute migraine attacks.

Publication Types: 
    Comparative Study
    Review

PMID: 15853532 [PubMed - indexed for MEDLINE]

1815: Expert Rev Neurother. 2005 Jan;5(1):55-61.

Rofecoxib in migraine.

Krymchantowski AV, Bigal ME.

abouchkrym@globo.com

Migraine is a highly prevalent primary headache. The disability of migraine
attacks results in considerable economic and social losses. The acute treatment
of migraine aims to rapidly and consistently alleviate the head pain and
associated symptoms, therefore reducing the headache-related disability, ideally 
without side effects and recurrence of the attack within 24 h. Although several
drug options and different formulations are available, the choice of a specific
medication should depend on an individual patients characteristics. Among the
available drugs, nonsteroidal anti-inflammatory drugs still represent effective
options and a new class of nonsteroidal anti-inflammatory drugs known as
selective cyclooxygenase-2 inhibitors may represent an even better-tolerated
therapy with regard to gastrointestinal side effects. This article aims to
discuss the role of rofecoxib in the acute treatment of migraine. Although this
drug was recently withdrawn from the market, it provides a good model to
understand the role of the cyclooxygenase-2 inhibitors in migraine therapy
overall. The pharmacologic profile and therapeutic use in the acute treatment of 
migraine of rofecoxib is reviewed. In addition, the limitations of a
monotherapeutic orally administered approach and possible ways of raising the
efficacy of rofecoxib and other acute migraine treatments are reviewed.

Publication Types: 
    Comparative Study
    Evaluation Studies
    Review

PMID: 15853474 [PubMed - indexed for MEDLINE]

1816: Expert Rev Neurother. 2005 Jan;5(1):43-53.

Eletriptan in migraine.

Diener HC.

Department of Neurology, University of Essen, Hufelandstr. 55, D45122 Essen,
Germany. h.diener@uni-essen.de

Migraine is a highly prevalent, chronic and disabling illness in which the gap
between practice guideline recommendations and actual clinical practice remains
wide. Eletriptan, similar to other triptans, is a potent 5-HT(1B/1D) receptor
agonist with a high selectivity for cranial versus coronary artery constriction
and favorable pharmacokinetic profile. An extensive program of double-blind,
placebo-controlled, head-to-head comparator trials has demonstrated the superior 
efficacy of eletriptan compared with the combination of ergotamine and caffeine, 
and selected oral triptans for the acute treatment of migraine. Eletriptans
tolerability profile makes it a good choice as a first-line treatment of
migraine. An early treatment study suggests that treatment of mild headache is
associated with unusually high sustained pain-free rates and a tolerability
profile that is equivalent to placebo.

Publication Types: 
    Comparative Study
    Evaluation Studies
    Review

PMID: 15853473 [PubMed - indexed for MEDLINE]

1817: J Assoc Physicians India. 2005 Feb;53:111-5.

Clinical profile of migraineurs in a referral centre in India.

Panda S, Tripathi M.

Department of Neurology, All India Institute of Medical Sciences, Delhi, India.

BACKGROUND: Migraine is one of the commonest of headache disorders presenting to 
neurologists the world over. Though the precise etiopathogenesis of migraine is
still not completely understood, there are various studies speculating on the
role of different genetic loci and various patterns of inheritance. OBJECTIVE:
The present study was conducted to characterize the migraineurs presenting to a
referral hospital in India and understand their possible modes of inheritance by 
clinical evaluation of family pedigree. METHODS: A questionnaire based,
prospective study including consecutive patients was conducted in the department 
of Neurology at a tertiary referral center in India. All patients fulfilling the 
diagnostic criteria for migraine were enrolled and their characteristics noted.
Other family members of those with a positive history of headache were also
interviewed. RESULTS: A total of 198 migraineurs were interviewed from March 2001
to July 2002. The proportion of female migraineurs was higher, comprising 72% of 
the study group, with an average age of onset of symptoms of 23.3 years. The
characteristics of migraine noted revealed certain rare factors aggravating
headache. A positive family history of headache was observed in 24.7% of probands
with a possible maternal inheritance on clinical grounds in 29 of 41 families
(70.7%). CONCLUSIONS: This is an observational study from an Indian centre on the
clinical characteristics of migraineurs in India. It revealed that migraineurs
presented a relatively low frequency of family history of headache. Though a
definite pattern of inheritance can't be commented on, majority with a positive
family history of headache had a trend to possible maternal inheritance.

PMID: 15847028 [PubMed - indexed for MEDLINE]

1818: Biochim Biophys Acta. 2005 May 15;1669(1):61-8. Epub 2005 Jan 26.

Na,K-ATPase mutations in familial hemiplegic migraine lead to functional
inactivation.

Koenderink JB, Zifarelli G, Qiu LY, Schwarz W, De Pont JJ, Bamberg E, Friedrich
T.

Department of Biochemistry, Radboud University Nijmegen Medical Centre, P.O. Box 
9101, 6500HB Nijmegen, The Netherlands.

The Na,K-ATPase is an ion-translocating transmembrane protein that actively
maintains the electrochemical gradients for Na+ and K+ across the plasma
membrane. The functional protein is a heterodimer comprising a catalytic
alpha-subunit (four isoforms) and an ancillary beta-subunit (three isoforms).
Mutations in the alpha2-subunit have recently been implicated in familial
hemiplegic migraine type 2, but almost no thorough studies of the functional
consequences of these mutations have been provided. We investigated the
functional properties of the mutations L764P and W887R in the human Na,K-ATPase
alpha2-subunit upon heterologous expression in Xenopus oocytes. No
Na,K-ATPase-specific pump currents could be detected in cells expressing these
mutants. The binding of radiolabelled [3H]ouabain to intact cells suggested that 
this could be due to a lack of plasma membrane expression. However, plasma
membrane isolation showed that the mutated pumps are well expressed at the plasma
membrane. 86Rb+-flux and ATPase activity measurements demonstrated that the
mutants are inactive. Therefore, the primary disease-causing mechanism is
loss-of-function of the Na,K-ATPase alpha2-isoform.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 15843000 [PubMed - indexed for MEDLINE]

1819: Am J Med. 2005 Mar;118 Suppl 1:36S-44S.

Evaluating the safety and tolerability profile of acute treatments for migraine.

Martin VT, Goldstein JA.

Division of General Internal Medicine, University of Cincinnati, 2624 Clifton
Avenue, Cincinnati, Ohio 45221, USA. martindoc@pol.net

Among the medications that have been used as acute treatments for migraine are
nonspecific agents, including nonsteroidal anti-inflammatory drugs (NSAIDs),
analgesics (either single or combination), and narcotics, as well as
migraine-specific medications, including ergot alkaloids and triptans
(5-hydroxytryptamine 1B/1D agonists). All of these drugs have side effects that
vary in type and severity. Side effects of nonspecific medications, including
gastrointestinal (GI) and renal effects with NSAIDs and cognitive effects and the
potential for abuse with narcotics and butalbital-containing medications, have
been documented over time, as these medications have been used for various
indications. Side effects of the migraine-specific medications include GI and
vascular symptoms with the ergots; for the triptans, they include chest and
neurologic symptoms. Although adverse events are reported fairly frequently in
patients receiving triptans, they are usually mild, and few patients discontinue 
therapy because of them. The most serious adverse events are cardiovascular.
Because of potential vasoconstrictor effects--mild and transient increases in
blood pressure and mild and transient effects on coronary artery tone--triptans
as a class are contraindicated in patients with established or clinically
suspected cardiovascular disease, specifically ischemic heart disease and
uncontrolled hypertension. Other adverse events, including the potential for
drug-drug interactions, are less common. Therefore, consideration should be given
to the tolerability and safety of medications before their use as abortive
medications for the treatment of migraine headache.

Publication Types: 
    Review

PMID: 15841886 [PubMed - indexed for MEDLINE]

1820: Am J Med. 2005 Mar;118 Suppl 1:28S-35S.

Evaluating the triptans.

Mathew NT, Loder EW.

Houston Headache Clinic, and Department of Neurology, University of Texas Medical
School, Houston, Texas 77004, USA. ntmathew@houstonheadacheclinic.com

The debilitating effect of migraine has fueled the search for more specific
agents to treat its characteristic and associated symptoms. Second-generation
oral triptans have shown an improved efficacy profile in comparison with the
pioneer sumatriptan and with the over-the-counter medications and prescription
analgesics that have been staples of migraine treatment. Although all triptans
exert effects through the 5-hydroxytryptamine 1B/1D receptors, each triptan has
distinctive pharmacokinetic properties that determine its efficacy and
tolerability profile. Empirical findings based on clinical trials have led to
associations between triptan pharmacology and efficacy. With the expanded
treatment choices, the onus is on healthcare providers (especially primary care
physicians, who see the majority of patients with migraine) to determine which
treatment has an efficacy profile that best suits the individual patient's needs.
Patients prefer pharmacotherapy with a rapid onset of action that facilitates
complete pain relief and no recurrence. Data from published comparator trials,
based on commonly used efficacy end points and pharmacokinetic properties
underlying patient-preferred outcomes, are reviewed in this article.

Publication Types: 
    Review

PMID: 15841885 [PubMed - indexed for MEDLINE]

1821: Am J Med. 2005 Mar;118 Suppl 1:18S-27S.

Initiating and optimizing acute therapy for migraine: the role of
patient-centered stratified care.

Diamond M, Cady R.

Diamond Headache Clinic, 467 Deming Place, Suite 500, Chicago, Illinois 60614,
USA. drmerle@aol.com

Migraine is a chronic, intermittently disabling condition that affects physical, 
mental, and social aspects of health-related quality of life. Because patients
seeking assistance with migraine most often present to primary care providers,
these healthcare professionals play critical roles in the diagnosis and treatment
process. A comprehensive migraine management plan involves a partnership between 
the patient and healthcare professional where treatment goals and strategies are 
established. Elements of such a plan should include preventive strategies to
reduce the frequency and effects of future attacks as well as the use of acute
treatments to address the immediate need for relief during an attack. Approaches 
to prevention include education, lifestyle modification, and, often, appropriate 
medication. Many medications have been used for acute treatment. Nonspecific
agents include nonsteroidal anti-inflammatory drugs (NSAIDs), single or
combination analgesics (sometimes including antiemetics or caffeine), and
narcotics. Migraine-specific medications include ergot alkaloids and triptans
(5-hydroxytryptamine(1B/1D) agonists). Various professional organizations have
created guidelines to help providers in choosing appropriate management
interventions. Clinical approaches to the patient with migraine include step
care, whereby all patients begin on a simple or nonspecific treatment, stepping
up to the next level of therapy if treatment is unsuccessful; or stratified care,
whereby first-line therapy is tailored to the severity of the patient's pattern
of headache. Studies have demonstrated that for more disabled headache patients, 
the stratified-care approach results in more robust headache response with less
disability and greater cost-effectiveness than step care. Patient satisfaction
studies demonstrate that the use of migraine-specific abortive medications
(triptans) is associated with a higher satisfaction rate than over-the-counter
preparations, NSAIDs, and analgesic combinations. Patients who initially reported
satisfaction with the latter medications also reported a preference for triptan
therapy. Healthcare professionals can assist patients, not only by choosing the
most appropriate medication but also by assessing whether the level of benefit
the patient is currently receiving could be improved.

Publication Types: 
    Review

PMID: 15841884 [PubMed - indexed for MEDLINE]

1822: Am J Med. 2005 Mar;118 Suppl 1:11S-17S.

Identifying migraine in primary care settings.

Sadovsky R, Dodick DW.

Department of Family Practice, SUNY Downstate Medical Center, Brooklyn, New York 
11203, USA. Richard.Sadovsky@downstate.edu

Migraine disorders are largely unrecognized and untreated, despite the heavy
burden they impose on individuals and society. Studies have shown that the
symptom severity and disability associated with undiagnosed migraine are as
burdensome as those associated with diagnosed migraine. Of those persons with
migraine identified in population-based surveys, many were previously unaware
that they had migraine. Furthermore, coexisting headache types and comorbid
conditions contribute to misdiagnosis among those who consult a physician for
headache. Patients who do seek medical attention for headaches usually visit
their primary care providers. The purpose of this review is to highlight the
distinguishing characteristics of migraine compared with other headache
disorders, based on the new International Classification of Headache Disorders.
To aid in diagnosis, simple screening tools, such as ID Migraine (Pfizer Inc.,
New York, NY), are recommended. The clinical interview and headache diary aid in 
refining the diagnosis or suggesting the need for further evaluation. Improved
recognition of migraine in primary care will increase the rate of successful
treatment with effective migraine-specific therapies. This will result in
improved functionality and decreased pain, and may help prevent disease
progression.

Publication Types: 
    Review

PMID: 15841883 [PubMed - indexed for MEDLINE]

1823: Am J Med. 2005 Mar;118 Suppl 1:3S-10S.

The epidemiology of migraine.

Lipton RB, Bigal ME.

Department of Neurology, Albert Einstein College of Medicine, 1300 Morris Park
Avenue, Bronx, New York 10461, USA. Rlipton@aecom.yu.edu

This article provides a review of the epidemiology and risk factors for migraine 
in population studies, as well as patterns for healthcare use. The burden and
costs of migraine, as well as risk factors for disease progression, are also
discussed. Although migraine is a remarkably common cause of temporary
disability, many persons with migraine, even those with disabling headache, have 
never consulted a physician for the problem. Prevalence is highest in women, in
persons between the ages of 25 and 55 years, and, at least in the United States, 
in individuals from lower income households. However, prevalence is high in
groups other than these high-risk groups. In a subgroup of patients, migraine may
be a progressive disorder.

Publication Types: 
    Review

PMID: 15841882 [PubMed - indexed for MEDLINE]

1824: Cephalalgia. 2005 May;25(5):378-90.

Chronic migraine and medication-overuse headache through the ages.

Boes CJ, Capobianco DJ.

Department of Neurology, Mayo Clinic College of Medicine, Rochester, MN 55905,
USA. boes.christopher@mayo.edu

We set out to review early descriptions of chronic migraine and
medication-overuse headache. The International Headache Society (IHS) recently
gave criteria for chronic migraine and medication-overuse headache. Chronic
migraine was absent from the 1988 IHS criteria. Peters and Horton described
ergotamine-overuse headache in 1951. In the 1980s it was more fully appreciated
that overuse of other acute headache medications could increase headache
frequency. We reviewed published English-language papers and book chapters.
Willis (1672), Oppenheim (1900), Collier (1922), Balyeat (1933), and von Storch
(1937) all described chronic migraine. Lennox (1934), O'Sullivan (1936),
Silfverskiold (1947), Graham (1955), Friedman (1955), and Lippman (1955) wrote
about ergotamine-overuse headache. Graham (1955), Friedman (1955), Lippman
(1955), and Horton and Peters (1963) outlined withdrawal protocols. Chronic
migraine has been mentioned in the literature for centuries, while
medication-overuse headache has been written about for decades. Graham, Friedman,
and Lippman deserve credit for separately reporting the first ergotamine
withdrawal programmes.

Publication Types: 
    Historical Article
    Portraits

PMID: 15839853 [PubMed - indexed for MEDLINE]

1825: Cephalalgia. 2005 May;25(5):359-68.

Effects of symptomatic treatments on cutaneous hyperalgesia and laser evoked
potentials during migraine attack.

de Tommaso M, Losito L, Libro G, Guido M, Di Fruscolo O, Sardaro M, Sciruicchio
V, Lamberti P, Livrea P.

Laboratory of Clinical Neurophysiology and Pain, Department of Neurologic and
Psychiatric Sciences, University of Bari, Policlinico, Piazza Giulio Cesare, Bari
Italy. m.detommaso@neurol.uniba.it

Previously an amplitude enhancement of laser evoked potentials (LEPs) was
detected during migraine attack: we further examined pain threshold to CO2 laser 
stimuli and LEPs during attacks, evaluating the effect of almotriptan,
lysine-acetylsalicylate and placebo treatment on cutaneous hyperalgesia to
thermal stimuli delivered by CO2 laser and on LEP components. Eighteen patients
suffering from migraine without aura were analysed. They were divided into three 
groups of six patients each, randomly assigned to lysine acetyl-salicylate,
almotriptan or placebo treatments. The supraorbital zones and the dorsum of the
hand were stimulated on both the symptomatic and not symptomatic side in all
patients. The LEPs were recorded by 25 scalp electrodes. During attacks, the P2
wave was significantly enhanced; the amplitude of the P2 component obtained by
the stimulation of the supraorbital zone during the attack on the side of the
headache was significantly correlated with the intensity of pain and the
frequency of headache. Both almotriptan and lysine acetyl-salicylate
significantly reduced the P2 amplitude but they showed no effects on hyperalgesia
to laser stimulation; headache relief following therapy was correlated with the
reduction of the P2 amplitude. The cortical elaboration of laser-induced
experimental pain seemed increased during migraine attack, and the severity of
headache was mainly related to the increase of the later LEPs components
expressing the attentive and emotive compounds of suffering. Reversion of this
process appeared to be primarily responsible for the efficacy of drugs in
treating migraine, though both almotriptan and lysine-acetil salicilate seemed to
have no effect in reducing sensitization at second and third order nociceptive
neurons.

Publication Types: 
    Clinical Trial
    Comparative Study
    Randomized Controlled Trial

PMID: 15839851 [PubMed - indexed for MEDLINE]

1826: Cephalalgia. 2005 May;25(5):353-8.

Platelet membrane fluidity and peroxynitrite levels in migraine patients during
headache-free periods.

Taffi R, Vignini A, Lanciotti C, Luconi R, Nanetti L, Mazzanti L, Provinciali L, 
Silvestrini M, Bartolini M.

Department of Neuroscience, Universita Politecnica delle Marche, Ancona, Italy.

Previous investigations have suggested that changes in platelet activity may play
a key role in the pathophysiology of migraine via mechanisms involving the nitric
oxide (NO) pathway. Changes in platelet response and nitrite levels have recently
been demonstrated during migraine attacks, while there is considerable
uncertainty about NO activity in headache-free periods. A reactive oxidant
produced from NO and superoxide anion at the site of inflammation, peroxynitrite 
(ONOO-) has effects including changes in membrane activity and fluidity. The aim 
of the present study was to determine ONOO- levels in the platelets of patients
suffering from migraine during the headache-free period. Nitric oxide synthase
(eNOS and iNOS) expression in platelets and the effects of ONOO- on membrane
Na+/K+-ATPase activity and membrane fluidity were also evaluated. Subjects were
57 patients suffering from migraine without aura and 35 controls. Blood samples
were collected in the headache-free period. Platelet ONOO- levels were determined
using dichlorofluorescein acetate with steady-state fluorescence. Platelets were 
then probed for induction of eNOS and iNOS expression by western immunoblotting. 
Membrane Na+/K+-ATPase activity and fluidity were determined with the fluorescent
probes TMA-DPH and DPH. In the presence of extracellular l-arginine(100
micromol/l), ONOO- production was significantly greater in patients' platelets
than in those of controls (P < 0.001). Western immunoblotting of platelet
proteins evidenced higher iNOS expression in patients than in controls. In
addition, platelet membrane Na+/K+-ATPase activity and membrane fluidity
evaluated by TMA-DPH were significantly lower in patients (P < 0.001). In
conclusion, migraine patients show intercritic changes in platelet membrane
fluidity and activity that may be related to the oxidative stress caused by
increased ONOO- levels.

Publication Types: 
    Comparative Study

PMID: 15839850 [PubMed - indexed for MEDLINE]

1827: Cephalalgia. 2005 May;25(5):339-43.

Critical flicker frequency in migraine. A controlled study in patients without
prophylactic therapy.

Kowacs PA, Piovesan EJ, Werneck LC, Fameli H, Zani AC, da Silva HP.

Headache Unit, Neurology Division, Internal Medicine Department, Hospital de
Clínicas da Universidade Federal do Paraná, Curitiba, Brazil. cefaleia@hc.ufpr.br

The critical flicker frequencies (CFF) of individuals with migraine with and
without aura were determined and compared to those of normal controls. Twenty-six
migraine patients, 12 with aura and 14 without aura and 30 healthy controls were 
included. Migraineurs were tested during a migraine-free period, through both the
continuous flicker method (CFM) and the forced choice method (FCM). Migraineurs
presented a mean flickering fusion threshold lower than healthy controls with the
CFM (40.45 vs. 44.33, respectively; P = 0.019) and with the FCM (34.16 Hz vs.
38.5 Hz, respectively, P = 0.019). Both groups of migraineurs had significantly
lower thresholds as compared to controls, migraineurs with aura presenting the
lowest thresholds for the fusion of flickering (P = 0.008 and P = 0.0001 with the
CFM and the FCM, respectively). Results confirmed and extended previous
observations of abnormal flicker fusion thresholds in migraineurs. We hypothesize
that this finding might be related to a shorter cortical stimulation silent
period.

Publication Types: 
    Clinical Trial
    Comparative Study
    Randomized Controlled Trial

PMID: 15839848 [PubMed - indexed for MEDLINE]

1828: Cephalalgia. 2005 May;25(5):333-8.

Evolution of migraine diagnoses in adolescents: a 3-year annual survey.

Wang SJ, Fuh JL, Juang KD, Lu SR, Hsu LC, Chen WT, Pwu RF.

The Neurological Institute, Taipei Veterans General Hospital, Taipei, Taiwan.
sjwang@vghtpe.gov.tw

We conducted a 3-year annual questionnaire survey of the International Headache
Society (IHS) migraine diagnoses among 2414 adolescents aged 13. For those with
migraine without aura (IHS 1.1) at the baseline survey (n = 89), 28% and 24%
retained the IHS 1.1 diagnosis at the 2nd and 3rd surveys. Only 0.5% of
adolescents had a persistent IHS 1.1 diagnosis for 3 years. Of those with IHS 1.1
or migrainous disorder (IHS 1.7) (n = 449), 43% and 48% retained the IHS 1.1 or
IHS 1.7 diagnosis at the 2nd and 3rd surveys. Conversion between IHS 1.1 and IHS 
1.7 was common. About 5.6% of the adolescents suffered from IHS 1.1 or IHS 1.7
for all 3 years. Independent predictors for persistent IHS 1.1 or IHS 1.7
diagnosis included frequent headache (>5 days/month) (relative risk (RR) = 1.8)
and pulsatile headache (RR = 1.5). The diagnosis of IHS 1.1 in adolescents was
quite unstable. Conversion between IHS 1.1 and IHS 1.7 was an important cause.
Factoring IHS 1.7 into the spectrum of migraine diagnoses during epidemiological 
surveys provides a realistic impression of the disease burden in this age group.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 15839847 [PubMed - indexed for MEDLINE]

1829: Cephalalgia. 2005 May;25(5):323-32.

Diffusion- and perfusion-weighted MR imaging in persistent migrainous visual
disturbances.

Jäger HR, Giffin NJ, Goadsby PJ.

Headache Group, Institute of Neurology, the National Hospital for Neurology and
Neurosurgery, London, UK.

Pathological changes on diffusion-weighted MR scans had been described in
hemiplegic migraine and perfusion changes had been demonstrated in typical
migraine aura with radio-isotope studies and, more recently, MR perfusion
imaging. However, there is relatively little knowledge of the pathophysiology of 
long-lasting migraine aura and its possibly variant phenotype, visual snow. Our
aim was to investigate with advanced MR techniques whether patients with
long-lasting visual disturbance showed regional alterations in cerebral water
diffusion and perfusion. We have studied four patients using MR perfusion and MR 
diffusion imaging. Two patients had typical visual aura and two had a primary
persistent visual disturbance (visual snow phenomenon). All patients had normal
conventional structural MR imaging. MR diffusion-weighted images were acquired
with a b-value of up to 1000 s/mm2. From the diffusion weighted images we
generated maps of apparent diffusion coefficient (ADC), which were inspected
visually and used for ADC measurements of predefined regions of interest, which
included the visual, frontal, insular and temporal cortices. MR perfusion imaging
was performed using a bolus tracking technique with dynamic
susceptibility-weighted images. Colour coded maps of relative cerebral blood
volume, mean transit time and bolus arrival time were generated, as well as
time-signal intensity curves over the anterior, middle and posterior cerebral
artery territories. The maps of the ADC and above perfusion parameters appeared
symmetrical in all patients with no evidence of decreased water diffusion or
cerebral perfusion in the occipital regions, or elsewhere. There was no
statistically significant difference between the ADC measurements of the primary 
visual cortices and other cortical regions. Our findings suggest that regional
changes in cerebral water diffusion and perfusion do not play an important part
in the pathophysiology of persistent migraine aura or primary persistent visual
disturbance.

Publication Types: 
    Case Reports
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 15839846 [PubMed - indexed for MEDLINE]

1830: Pain. 2005 May;115(1-2):21-8.

Anti-migraine action of triptans is preceded by transient aggravation of headache
caused by activation of meningeal nociceptors.

Burstein R, Jakubowski M, Levy D.

Department of Anesthesia and Critical Care, Beth Israel Deaconess Medical Center,
Harvard Institutes of Medicine, Room 830, 77 Avenue Louis Pasteur, Boston, MA
02115, USA. rburstei@bidmc.harvard.edu

Consistent with previous accounts, some of the patients visiting our pain clinic 
during the course of a migraine attack have indicated-without solicitation-that
sumatriptan injection initially intensified their headache before they were able 
to appreciate any pain relief. In this study, those patients who came forward
complaining about pain exacerbation were asked to rate their headache intensity
every 5 min. Within 5-15 min of sumatriptan injection, 17 of the 31 patients
studied (55%) reported that their migraine pain intensified for 10-15 min before 
they started to notice any pain relief. Similar pattern of pain exacerbation was 
also observed in migraine attacks treated with oral formulation of almotriptan,
eletriptan, rizatriptan, and zolmitriptan. To investigate the possible mechanism 
underlying this transient exacerbation of pain, we examined whether intravenous
administration of sumatriptan can alter the response properties of C- and
Adelta-meningeal nociceptors in the rat. Five to twenty minutes after intravenous
administration of 300 microg/kg sumatriptan, 8/10 C-units and 2/8 Adelta-units
increased their firing rate, and 6/10 C-units and 7/8 Adelta-units developed
mechanical hyper-responsiveness to dural indentation. The minimal effective dose 
for activation and sensitization of meningeal nociceptors by sumatriptan was 3
microg/kg, suggesting that relatively low levels of triptans entering the
circulation shortly after their administration can alter the physiological
properties of meningeal nociceptors and produce a transient exacerbation of
headache.

Publication Types: 
    Clinical Trial
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 15836966 [PubMed - indexed for MEDLINE]

1831: Headache. 2005 Mar;45(3):249-50.

Migraine accompanied by hemifacial spasm: a case report.

Husid MS.

Walton Headache Center, Augusta, GA 30901-1037, USA

A 36-year-old woman has had repeated episodes of concurrent hemifacial spasm and 
migraine for 8 years. Her history is summarized and possible pathophysiologic
links are discussed.

Publication Types: 
    Case Reports

PMID: 15836603 [PubMed - indexed for MEDLINE]

1832: Headache. 2005 Mar;45(3):245-6.

Recurrence of migraine with aura due to tacrolimus therapy in a liver transplant 
recipient successfully treated with sirolimus substitution.

Toth CC, Burak K, Becker W.

University of Calgary, Neurosciences, Calgary, Alberta, Canada.

We report the case of a female liver transplant recipient who developed a
recurrence of severe migraine with aura while on tacrolimus therapy with
subsequent remission of headache following discontinuation of tacrolimus and
substitution with sirolimus therapy. Headaches in transplant-recipient patients
have become a new area of interest for headache specialists. In particular,
immunosuppressant medications such as cyclosporine, tacrolimus, sirolimus, and
OKT3 have been associated with development of headache syndromes in the
transplant patient, exacerbation of previous headaches syndromes, and development
of encephalopathies including headache as a clinical feature.

Publication Types: 
    Case Reports

PMID: 15836601 [PubMed - indexed for MEDLINE]

1833: Headache. 2005 Mar;45(3):224-31.

Headache and combination estrogen-progestin oral contraceptives: integrating
evidence, guidelines, and clinical practice.

Loder EW, Buse DC, Golub JR.

Spaulding Rehabilitation Hospital, Headache and Pain Program, Boston, MA, USA.

Primary headache disorders such as migraine affect almost a third of women during
their childbearing years, when decisions about contraception must be made.
Headache is also a commonly reported adverse event in clinical trials of oral
contraceptives (OCs). Health care practitioners will frequently be called upon to
give advice about the use of OCs to women with headache. This article applies
current evidence, guidelines, and recommendations about headache and OC use to
treatment decisions in four clinical scenarios: initiating OC use in a woman who 
has migraine without aura, continuing OC use in a woman who experiences worsening
of migraine and the development of aura after initiating OCs, initiating OC use
in a woman with tension-type headache (TTH) and a family history of migraine, and
use of an extended duration OC regimen to minimize migraine triggered by estrogen
withdrawal. The authors' recommendations regarding OC use in various primary
headache disorders are summarized.

Publication Types: 
    Case Reports

PMID: 15836597 [PubMed - indexed for MEDLINE]

1834: Headache. 2005 Mar;45(3):215-9.

Headaches in women undergoing in vitro fertilization and embryo-transfer
treatment.

Amir BY, Yaacov B, Guy B, Gad P, Itzhak W, Gal I.

Headache Clinic, Neurology Department, Soroka Medical Center, Faculty of Health
Sciences, Ben-Gurion University of the Negev, Berr-Sheva, Israel.

BACKGROUND: In vitro fertilization and embryo transfer has become a common
therapeutic modality in modern fertility medicines. Treatment protocols are
associated with exaggerated hormonal fluctuations in order to promote multiple
follicular development and support of embryo survival. Estrogen is considered to 
be closely linked to migraine, and its extreme serum level fluctuations have been
considered to trigger migrainous headaches. OBJECTIVE: To assess the prevalence, 
nature, and timing of headache attacks during the course of in vitro
fertilization and embryo-transfer treatments. METHODS: We retrospectively
evaluated the prevalence and the characteristics of headache among 98 women
undergoing in vitro fertilization and embryo transfer therapy using a structured 
telephone interview. RESULTS: Out of the 98 evaluated patients 25 were migraine
sufferers. Headache attacks during the in vitro fertilization and embryo transfer
protocol were reported by 28.6% (n = 28) of the women and were significantly more
prevalent among the migraineurs. The attacks were of debilitating severity in 82%
(n = 23) of patients who reported headaches during treatment. Headache occurred
most frequently following gonadotropin-releasing hormone (GnRH) analog induced
hypothalamic-pituitary-ovarian axis downregulation, typically associated with
very low 17-beta-estradiol (17-beta-E2) serum level. CONCLUSIONS: In vitro
fertilization and embryo-transfer treatment might be associated with various
degrees of headache. This is mostly observed in patients with migraine headache
background and specifically during the downregulation stage of treatment, when
very low levels of 17-beta-E2 are observed. (Headache 2005;45:215-219).

PMID: 15836595 [PubMed - indexed for MEDLINE]

1835: Headache. 2005 Mar;45(3):196-203.

Comment in:
    Headache. 2005 Sep;45(8):1090-1; author reply 1091.

Migraine prevention in children and adolescents: results of an open study with a 
special butterbur root extract.

Pothmann R, Danesch U.

Klinikum Heidberg, Zentrum für Kinderschmerztherapie, Hamburg, Germany.

OBJECTIVE: To explore the role of a special butterbur root extract for migraine
prevention in children and adolescents with severe migraines. BACKGROUND: Two
randomized and placebo-controlled trials with a total of 289 migraine patients
have demonstrated the efficacy and safety of a special butterbur root extract in 
the reduction of migraine attacks in adults. We studied whether butterbur had the
potential as an efficient and well-tolerated migraine preventive in children and 
adolescents. DESIGN/METHODS: 108 children and adolescents between the ages of 6
and 17 were included in a multicenter prospective open-label study. Participants 
suffered from migraines diagnosed according to IHS classifications for at least 1
year. Patients were treated with 50 to 150 mg of the butterbur root extract
depending on age for a period of 4 months. Treatment progression was recorded in 
migraine journals especially designed for children and adolescents. RESULTS: 77% 
of all patients reported a reduction in the frequency of migraine attacks of at
least 50%. Attack frequency was reduced by 63%. 91% of patients felt
substantially or at least slightly improved after 4 months of treatment. About
90% of each, doctors and patients, reported well-being or even improved
well-being. Undesired effects (7.4%) included mostly eructation. No serious
adverse events occurred and no adverse event caused a premature termination.
CONCLUSIONS: The results and low rate of adverse events in this open prospective 
migraine prevention study in children and adolescents are similar to the results 
of two multicenter placebo-controlled butterbur studies in adults. Butterbur root
extract shows a potential as an effective and well-tolerated migraine prophylaxis
also for children and teenagers.

Publication Types: 
    Clinical Trial
    Comparative Study
    Multicenter Study

PMID: 15836592 [PubMed - indexed for MEDLINE]

1836: Headache. 2005 Apr;45(4):385-6.

Acetazolamide efficacy and tolerability in migraine with aura: a pilot study.

De Simone R, Marano E, Di Stasio E, Bonuso S, Fiorillo C, Bonavita V.

Headache Center, Department of Neurological Sciences, University Federico II of
Naples, Italy.

The study was an open uncontrolled pilot trial to test the efficacy and the
tolerability of acetazolamide in a group of 22 outpatients suffering from
migraine with aura (MA) with at least one aura episode in the last 2 months.

Publication Types: 
    Clinical Trial

PMID: 15836579 [PubMed - indexed for MEDLINE]

1837: Headache. 2005 Apr;45(4):378-80.

Successful treatment of status migrainosus after electroconvulsive therapy with
dihydroergotamine.

Stead M, Josephs KA.

Department of Neurology, Mayo Clinic, Rochester, MN 55905, USA.

We describe a case of status migrainosus precipitated by electroconvulsive
therapy (ECT) that was refractory to treatment with triptan medications but which
resolved with dihydroergotamine (DHE). We briefly review some of the receptor
pharmacology possibly related to this observation.

Publication Types: 
    Case Reports

PMID: 15836577 [PubMed - indexed for MEDLINE]

1838: Headache. 2005 Apr;45(4):358-71.

Neuroleptics in headache.

Siow HC, Young WB, Silberstein SD.

National Neuroscience Institute, Neurology, Singapore.

OBJECTIVES: To review the mechanism of action of neuroleptics, the evidence for
their efficacy, and their clinical use in headache treatment. BACKGROUND:
Neuroleptics and antiemetics have long been used for headache treatment; however,
they have not been widely utilized because of general unfamiliarity with them and
concerns about their adverse events. With the recent advent of the atypical
neuroleptics and their improved adverse event profile, our armamentarium for
headache treatment has expanded. In this review, we explore the mechanism of
action of these classes of drugs, their adverse events, and the evidence for
their efficacy. We also detail our experience with the different drugs and how we
use them as both acute and preventive headache therapy. DESIGN: A review of
published literature was obtained through a MEDLINE search on the use of
neuroleptics in headache therapy. CONCLUSION: Neuroleptics have widespread
evidence supporting their use in headache treatment and present an important part
of the armaterium against headache.

Publication Types: 
    Review

PMID: 15836574 [PubMed - indexed for MEDLINE]

1839: Headache. 2005 Apr;45(4):355-7.

Botox therapy for refractory chronic migraine.

Conway S, Delplanche C, Crowder J, Rothrock J.

University of South Alabama Headache Center, Mobile, AL 36693, USA.

Chronic migraine is unfortunately both common and often resistant to treatment
even with prophylactic medications known to be effective in populations with
episodic migraine. We undertook an open-label study to evaluate the safety and
utility of botulinum toxin type A injection therapy for patients with chronic
migraine who previously had failed to respond to at least three prophylactic
medications.

Publication Types: 
    Clinical Trial
    Research Support, Non-U.S. Gov't

PMID: 15836573 [PubMed - indexed for MEDLINE]

1840: Headache. 2005 Apr;45(4):350-4.

The effects of greater occipital nerve block and trigger point injection on brush
allodynia and pain in migraine.

Ashkenazi A, Young WB.

Department of Neurology, Jefferson Headache Center, Thomas Jefferson University
Hospital, Philadelphia, PA 19107, USA.

OBJECTIVE: To evaluate the effect of GONB, with or without trigger point
injection (TPI), on dynamic mechanical (brush) allodynia (BA) and on head pain in
migraine. Background.-Patients with migraine often have cutaneous allodynia that 
is related to sensitization of central pain neurons. Greater occipital nerve
block (GONB) is an effective treatment for migraine headache; however, its effect
on cutaneous allodynia in migraine is unknown. METHODS: We studied patients with 
migraine and BA who were treated with GONB with or without TPI. Demographic data,
migraine history, and headache features were documented. Allodynia was evaluated 
using a structured questionnaire and by applying a 4 x 4-inch gauze pad to skin
areas in the trigeminal and cervical dermatomes. Degree of allodynia (the
allodynia score) was measured on a 100-mm visual analog scale (VAS) before
treatment and 10 and 20 minutes thereafter. Headache levels were assessed using
an 11-point verbal scale. Allodynia scores, as well as headache levels, before
and after treatment were compared. RESULTS: Nineteen patients were studied. Mean 
age was 43.6+/-11.8 years. Twenty minutes after treatment, headache was reduced
in 17 patients (89.5%) and did not change in 2 (10.5%). The average headache
level was 6.53 before treatment and 3.47, 20 minutes after it. The average
allodynia score decreased after 20 minutes in all patients. Average allodynia
score per site was reduced by 18.69 mm and 13.74 mm in the trigeminal and
cervical areas, respectively. There was a positive correlation between allodynia 
index, obtained through the questionnaire, and allodynia score, obtained by
examination. CONCLUSION: GONB, with or without TPI, reduced both head pain and
brush allodynia in this migraine patient group.

Publication Types: 
    Clinical Trial
    Comparative Study

PMID: 15836572 [PubMed - indexed for MEDLINE]

1841: Headache. 2005 Apr;45(4):346-9.

Pilot study evaluating preference for 3-mg versus 6-mg subcutaneous sumatriptan.

Landy SH, McGinnis JE, McDonald SA.

Wesley Headache and Neurology Clinic, Memphis, TN 38018, USA.

BACKGROUND: Subcutaneous sumatriptan (6 mg) is undeniably an excellent treatment 
of migraine. However, some patients have avoided using 6 mg sumatriptan because
of unpleasant or unwanted side effects. OBJECTIVE: To evaluate the efficacy of
subcutaneous sumatriptan (3 mg) during a moderate or severe migraine attack.
METHODS: Thirty subcutaneous sumatriptan-naive patients with a history of
migraine with and without aura treated their next two moderate or severe
migraines with either 3-mg or 6-mg sumatriptan injection. The primary endpoint
was whether patients preferred the low-dose (3 mg) or the high-dose (6 mg)
subcutaneous sumatriptan. Other objectives included percentage of patients pain
free at 15 and 30 minutes, 1 and 2 hours; a pain-free response lasting between 2 
and 24 hours, patient satisfaction, and acceptability of formulation. A new
combination endpoint (efficacy and lack of significant side effects) was also
evaluated. RESULTS: Eighty percent of patients preferred 3-mg over 6-mg
subcutaneous sumatriptan. At 1 hour postdose 57% of patients were pain free with 
3 mg and 53% with 6 mg. At 2 hours postdose 87% were pain free with 3 mg and 80% 
with 6 mg. A sustained pain-free response was obtained by 70 to 80% of patients. 
When combining a pain-free response at 2 hours and a sustained pain-free response
at 24 hours with no significant side effects, more patients met the endpoint with
3 mg (63 to 67%) than with 6 mg (33 to 50%). CONCLUSIONS: Combining efficacy and 
tolerability endpoints may be clinically meaningful and reflective of real-world 
expectations. In some patients, a lower dose of sumatriptan injection may be
beneficial.

Publication Types: 
    Clinical Trial
    Comparative Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 15836571 [PubMed - indexed for MEDLINE]

1842: Headache. 2005 Apr;45(4):332-6.

Vestibulo-ocular reflex abnormalities in patients with migraine.

Helm MR.

California Headache & Balance Center, Fresno, CA 93720, USA.

OBJECTIVE: To investigate the high-frequency vestibulo-ocular reflex (VOR) in
patients with migraine, with and without dizziness and aura. BACKGROUND: Migraine
is a common cause of dizziness. Although many vestibular testing abnormalities
have been documented in migraine patients, high-frequency VOR abnormalities have 
not been reported. METHODS: Thirty-nine consecutive patients with migraine were
studied with the vestibular autorotation test (VAT). The patients were
subclassified as having migraine headache only, migraine with visual aura,
migraine with dizziness, or migraine with visual aura and dizziness. RESULTS:
Only a high vertical phase in the 4 to 5 Hz range was correlated with migraine
(correlation coefficients: .356, P=.03). Further analysis revealed that an
abnormal 4 to 5 Hz vertical phase result also was positively correlated with
migraine with aura and dizziness (correlation coefficients: .392). CONCLUSION:
The results suggest that patients with migraine may have an abnormal vertical VOR
at higher head movement frequencies. Migraine patients with visual aura and
dizziness are even more likely to have this abnormality.

Publication Types: 
    Comparative Study

PMID: 15836569 [PubMed - indexed for MEDLINE]

1843: Headache. 2005 Apr;45(4):325-31.

Trigeminal stimulation elicits a peripheral vestibular imbalance in migraine
patients.

Marano E, Marcelli V, Di Stasio E, Bonuso S, Vacca G, Manganelli F, Marciano E,
Perretti A.

Federico II University of Naples, Neurological Sciences, Italy.

OBJECTIVE: The study explored the hypothesis that spontaneous nystagmus (Ny) in
migraine patients can be triggered or modulated by painful trigeminal
stimulation, providing evidence of a functional connection between vestibular and
trigeminal systems. BACKGROUND: Vertigo attacks are reported by subjects with
migraine or a familiar history of migraine, also independently of headache
episodes. Idiopathic vertigo is three times more frequent in migraine patients
than in controls. Vestibular investigations in migraine patients have
consistently demonstrated spontaneous Ny both of central and peripheral origin.
DESIGN: In the first phase of the study 10 outpatients experiencing migraine
without aura (MO) and 10 healthy volunteers were submitted to the registration of
spontaneous primary-position Ny in the dark by Ulmer's
video-ocular-nystagmographic equipment. Two electrodes for electrical stimulation
were applied on the supraorbital point of one side of the head and the intensity 
of stimulation corresponding to pain threshold was calculated. Spontaneous ocular
movements were recorded for 5 minutes at baseline and after a sequence of five
electric pulses (square waves of .5 Hz frequency and 50 micros duration, at pain 
threshold intensity). Nystagmographic responses were expressed as latency after
stimulation, direction of the quick phase, and duration. The second phase of the 
study explored, with the same procedure, the effects on Ny of supraorbital versus
median nerve stimulation in other 10 MO patients. Responses to stimulation were
considered the appearance of de novo Ny after stimulation in subjects without
baseline Ny, or the change of the frequency (at last a 50% variation) or of the
direction of Ny after stimulation in subjects with baseline Ny. The latency and
the duration of responses to stimulation were also calculated. RESULTS: In the
first series supraorbital painful electric stimulation was able to modify or to
evoke Ny in 8 of 10 migraineurs and in none of 10 volunteers (Fisher's exact
test, P<.01). Both the baseline and the induced Ny were second degree, stationary
persistent, with a linear slow phase and were suppressed by visual fixation. In
the second series, supraorbital nerve stimulation was able to induce or modify Ny
in all of 10 patients but only in 1 patient Ny was induced by median nerve
stimulation. Characters of Ny were the same as previously described. Statistical 
comparison of the responses at the two sites of stimulation was significant
(Fisher's exact test, P<.01). In those 7 patients who presented de novo Ny after 
stimulation it was possible to calculate Ny latency and duration. The mean
latency was 25 s (SD: 16, range: 14 to 60). The mean duration was 120 s (SD: 94, 
range: 20 to 290). CONCLUSION: The main result of our study is that in migraine
patients painful trigeminal stimulation elicits de novo, or modifies pre-existing
spontaneous Ny, generally increasing it. The finding was obtained after
trigeminal stimulation, but not after median nerve stimulation. We suggest that
painful trigeminal stimulation can induce an imbalance of the vestibular system
in migraine patients and possibly explain their predisposition to vertigo. Our
data require confirmation by other studies.

PMID: 15836568 [PubMed - indexed for MEDLINE]

1844: Headache. 2005 Apr;45(4):308-14.

Duration of migraine is a predictor for response to botulinum toxin type A.

Eross EJ, Gladstone JP, Lewis S, Rogers R, Dodick DW.

Mayo Clinic College of Medicine, Mayo Clinic Scottsdale, AZ 85259, USA.

OBJECTIVE: To identify the clinical characteristics and/or injection parameters
that predict a favorable response to botulinum toxin type A in patients with
episodic and chronic migraine. BACKGROUND: There is emerging scientific and
clinical evidence to support the utility of botulinum toxin type A (BoNT-A) in
the prophylaxis of episodic and chronic migraine headache. However, the patient
characteristics and injection strategies that predict a favorable treatment
response are unknown. METHODS: We conducted a prospective, open-label study on 74
patients from our clinic receiving BoNT-A for episodic or chronic migraine. For
all patients, migraine-related disability (Migraine Disability Assesment
[MIDAS]), headache frequency, and average headache intensity were obtained at
baseline and at 3 months post-BoNT-A. Information regarding demographic
characteristics and injection parameters was also collected. RESULTS: Sixty-one
patients met the study criteria and were available for 3-month follow-up. At the 
3-month follow-up visit, the mean MIDAS scores of the 61 qualified study patients
had decreased from 102 at baseline to 49 (52% decrease, P<.001). The mean number 
of headache days was reduced from 60 to 39 (P<.001), and the mean headache
intensity decreased from 7.6 at baseline to 5.9 (P<.001). Frequency of migraine
attacks, presence of analgesic overuse, total BoNT-A dose, and presence of
underlying muscle tenderness were not predictive of treatment response. Age and
duration of migraine were the only clinical factors significantly predictive of
treatment response. Age likely was a predictor only as a consequence of duration 
of illness as subjects with migraine duration greater than 30 years were
significantly less likely to respond to treatment with BoNT-A. CONCLUSION: BoNT-A
may be effective in decreasing headache frequency, headache intensity, and
headache-related disability in episodic and chronic migraine patients. Duration
of illness emerged as a predictor of treatment response. Randomized controlled
studies should evaluate headache-related disability as a primary endpoint in
patients with episodic and chronic headache.

Publication Types: 
    Clinical Trial

PMID: 15836566 [PubMed - indexed for MEDLINE]

1845: Headache. 2005 Apr;45(4):283-92.

Comment in:
    Evid Based Nurs. 2005 Oct;8(4):107.

Aspirin is efficacious for the treatment of acute migraine.

Lipton RB, Goldstein J, Baggish JS, Yataco AR, Sorrentino JV, Quiring JN.

Department of Neurology, Albert Einstein College of Medicine, Bronx, NY 10467,
USA.

BACKGROUND: More than 50% of migraine sufferers rely on over-the-counter
medications for the treatment of migraine. Along with other over-the-counter
products, aspirin is considered by the US Headache Consortium to be an option for
first-line migraine treatment. This study assessed the efficacy and tolerability 
of aspirin versus placebo for the acute treatment of a single acute attack of
migraine. METHODS: This prospective, randomized, double-blind, parallel-group,
placebo-controlled study evaluated the efficacy of a single, 1000-mg dose of
aspirin for the treatment of acute moderate to severe migraine, with or without
aura. Subjects recorded all study evaluations in a diary at baseline and at .5,
1, 2, 3, 4, 5, 6, and 24 hours after treatment. Pain was rated on a 4-point
ordinal scale from no pain to severe pain. The primary efficacy end point was
headache response at 2 hours. Secondary efficacy parameters included reduction of
nausea, photophobia and phonophobia, pain intensity difference, and headache
recurrence at 24 hours. RESULTS: Of 485 subjects enrolled, 409 took study
medication and 401 treated a confirmed migraine attack (201 with aspirin and 200 
with placebo). Baseline demographic and migraine characteristics were not
significantly different between groups. The 2-hour headache response rate was 52%
with aspirin versus 34% with placebo (P<.001). Aspirin was significantly more
effective than placebo for pain reduction beginning 1 hour after dosing (P<.001) 
and continuing throughout the 6-hour evaluation period. Significantly (P<.05),
more subjects were pain free from the 1-hour evaluation through the 6-hour
evaluation. Of the aspirin-treated subjects, 20% were pain free at 2 hours versus
only 6% of placebo-treated subjects. At 24 hours, the headache recurrence rate
was 21.8% for aspirin (23 of 105 subjects) and 27.7% for placebo (19 of 68
subjects). Only 34% of aspirin-treated subjects needed rescue medication at 24
hours compared with 52% of placebo-treated subjects (P<.001). Aspirin was well
tolerated, and adverse events were not significantly different between groups.
CONCLUSIONS: This study demonstrates that aspirin is safe and effective for
treatment of acute migraine in appropriately selected patients.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 15836564 [PubMed - indexed for MEDLINE]

1846: Headache. 2005 Apr;45(4):274-82.

Disability associated with headaches occurring inside and outside the menstrual
period in those with migraine: a general practice study.

Dowson AJ, Kilminster SG, Salt R, Clark M, Bundy MJ.

King's Headache Service, King's College Hospital, London, UK.

OBJECTIVES: This study investigated the disability of females who have migraine
and other headache attacks occurring during and outside the menstrual period.
METHODS: One thousand four hundred and thirty-four of 3470 female patients
(41.3%) aged 14 to 50 years registered at a UK general practice completed two
questionnaires. The first questionnaire assessed the prevalence of headache,
depression, and bodily pain in the total population. The second questionnaire
assessed the disability of all headaches over a 2-month period (to capture a
complete menstrual cycle) for patients reporting migraine who were still
menstruating. Disability was assessed as the time lost and time spent at less
than 50% productivity in normal activities due to headache, and analyzed as rank 
sums using the Mann-Whitney U-test. RESULTS: The first part of the study showed
that the prevalence of headache (66.1%), depression (55.4%), and bodily pain
(40.6%) were high in this population of women. Thirty migraine patients who were 
still menstruating reported 89 migraine and 114 nonmigraine headache episodes in 
the second part of the study. For migraine, the rank order of time at less than
50% productivity was greater for attacks taking place inside the menstrual period
than for those occurring outside the menstrual period. The comparison was
significant for time at less than 50% productivity (P=.01). For nonmigraine
headaches, the rank order of time lost was greater for attacks taking place
outside the menstrual period than for those occurring inside the menstrual
period. The comparison was not significant for time lost (P= .06). CONCLUSIONS:
For those with migraine, migraine attacks that took place during the menstrual
period tended to be slightly more disabling than those taking place outside the
menstrual period, but the opposite was true for nonmigraine headache.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 15836563 [PubMed - indexed for MEDLINE]

1847: Pharmacoeconomics. 2005;23(3):259-74.

Oral serotonin receptor agonists: a review of their cost effectiveness in
migraine.

Lofland JH, Nash DB.

Department of Health Policy and Clinical Outcomes, Thomas Jefferson University,
Philadelphia, Pennsylvania 19107, USA. jennifer.lofland@jefferson.edu

Migraine headache is a highly prevalent chronic, episodic condition. The direct
and indirect costs of migraine headache have a tremendous economic impact in the 
US. Research has shown that serotonin (5HT(1B/D)) receptor agonists reduce
healthcare costs, improve health-related QOL (HR-QOL), decrease migraine
disability and keep patients effective in the workplace. The purpose of this
manuscript is to examine the cost effectiveness of oral 5HT(1B/D) receptor
agonists for the treatment of migraine headache. In general, 5HT(1B/D) receptor
agonists are associated with increases in direct healthcare costs; however, they 
are also associated with reductions in the indirect costs associated with
migraine headache. Therefore, it appears that the relatively high acquisition
cost of these medications is offset and, as a class, these medications appear to 
be cost effective and demonstrate net benefits from the societal perspective.
Based on meta-analyses in which data on eletriptan were not available, it appears
that within the class, almotriptan and rizatriptan are the most cost effective.
In a prospective study comparing eletriptan with sumatriptan, it appears that the
former may be more cost effective than the latter. Additional investigations are 
needed to further explore the application of the friction-cost approach and QALYs
to cost-effectiveness analyses of this class of medication.

Publication Types: 
    Meta-Analysis
    Research Support, N.I.H., Extramural
    Research Support, U.S. Gov't, P.H.S.
    Review

PMID: 15836007 [PubMed - indexed for MEDLINE]

1848: Headache. 2005 Apr;45 Suppl 1:S66-73.

Practical use of topiramate for migraine prevention.

Brandes JL.

Nashville Neuroscience Group and Department of Neurology, Vanderbilt University
Medical School, TN 37203, USA.

When treating patients with migraine, clinicians should consider prescribing
appropriate combinations of acute and preventive therapies. An effective
migraine-preventive therapy should be prescribed to patients with frequent (> or 
= 2 migraines per month) or severe migraine. Topiramate has been shown to be an
effective and generally well-tolerated migraine prophylaxis (preventive) therapy 
in adults, as demonstrated in several large, controlled trials. The most common
adverse events in these trials were paresthesia, fatigue, anorexia, nausea, taste
alteration, and diarrhea. Most adverse events were mild to moderate and transient
in nature. Although patients should take migraine-preventive medications for
approximately 2 to 3 months before evaluating effect, topiramate has shown
efficacy as early as the first month of treatment. This article describes
"real-world" approaches to using topiramate as a migraine-preventive therapy.
Topiramate has received regulatory approval for the prophylaxis of migraine
headache in adults in the United States and many other countries. The practical
issues discussed in this article will enable clinicians to maximize the
effectiveness while minimizing the side effects associated with this preventive
agent.

Publication Types: 
    Review

PMID: 15833092 [PubMed - indexed for MEDLINE]

1849: Headache. 2005 Apr;45 Suppl 1:S57-65.

Topiramate in migraine prevention.

Silberstein SD.

Jefferson Headache Center, Thomas Jefferson University Hospital, Philadelphia, PA
19107, USA.

The efficacy of topiramate in migraine prevention (prophylaxis) was established
in two multicenter, randomized, double-blind, placebo-controlled, pivotal trials.
Topiramate has received regulatory approval for use in adults for migraine
prophylaxis (prevention) in the US and numerous other countries, including
France, Ireland, Switzerland, Brazil, Taiwan, Spain, and Australia. Treatment
with 100 or 200 mg per day of topiramate was associated with significant
reductions in the frequency of migraine headaches, number of migraine days, and
use of acute medications. No increase in efficacy was observed between 100 and
200 mg per day of topiramate. Based on efficacy and tolerability, 100 mg per day 
of topiramate should be the initial target dose for most patients. The most
common adverse events were paresthesia, fatigue, decreased appetite, nausea,
diarrhea, weight decrease, and taste perversion. Topiramate is a first-line
migraine preventive drug and should especially be considered as a preferred
treatment for all patients who are concerned about gaining weight, who are
currently overweight, or who have coexisting epilepsy.

Publication Types: 
    Review

PMID: 15833091 [PubMed - indexed for MEDLINE]

1850: Headache. 2005 Apr;45 Suppl 1:S48-56.

Molecular pharmacology of topiramate: managing seizures and preventing migraine.

White HS.

Anticonvulsant Drug Development Program, Department of Pharmacology and
Toxicology, University of Utah, Salt Lake City 84112, USA.

Topiramate is a neuromodulatory compound with stabilizing properties that was
initially introduced for the management of partial seizures. Topiramate has been 
demonstrated to modify several receptor-gated and voltage-sensitive ion channels,
including voltage-activated Na+ and Ca2+ channels and non-NMDA receptors. These
receptors have been implicated in the pathophysiology of both epilepsy and
migraine. The pharmacological mechanisms of action for topiramate that may
explain its antiepileptic and migraine preventive activities will be discussed in
this review. In addition, the potential relationship between the molecular
activities of topiramate and its efficacy in epilepsy and migraine prevention
will be emphasized.

Publication Types: 
    Review

PMID: 15833090 [PubMed - indexed for MEDLINE]

1851: Headache. 2005 Apr;45 Suppl 1:S33-47.

General principles of migraine management: the changing role of prevention.

Loder E, Biondi D.

Headache Program, Spaulding Rehabilitation Hospital, Harvard Medical School,
Boston, MA 02114, USA.

The role of preventive treatment in the management of migraine must be
reassessed. Many patients who would benefit from preventive therapy do not
receive it, and many might benefit from earlier and more aggressive use of
preventive therapy. Physicians who treat migraine have long recognized that a
subset of patients with episodic migraine evolve to chronic forms of the disorder
that are difficult to treat and have a poor outcome. This article reviews the
evidence for current and emerging prophylactic migraine treatment and raises the 
possibility that timely use of prophylactic treatment might modify or prevent the
transformation to chronic migraine and the extreme disability that characterizes 
a small but significant subset of the migraine population. Along with aggressive 
treatment of the acute pain and other symptoms of migraine, prevention of
progression to severe forms of this disorder will increasingly be a focus and
goal of the treatment.

Publication Types: 
    Review

PMID: 15833089 [PubMed - indexed for MEDLINE]

1852: Headache. 2005 Apr;45 Suppl 1:S3-S13.

Migraine: epidemiology, impact, and risk factors for progression.

Lipton RB, Bigal ME.

Department of Neurology, Albert Einstein College of Medicine and Montefiore
Headache Unit, Bronx, NY 10461, USA.

Migraine is a chronic and sometimes progressive disorder characterized by
recurrent episodes of headache and associated symptoms. This article reviews the 
epidemiology of and the risk factors for migraine described in population
studies, and discusses the burden of disease and the socioeconomic costs of
migraine. In the years prior to puberty, migraine is more common among boys than 
girls. By the onset of puberty, migraine is more prevalent in girls, and by the
late teens, females are about twice as likely to suffer from migraine as males.
The prevalence of migraine peaks in both sexes during the most productive years
of adulthood (age 25 to 55 years) and, in the United States, the prevalence is
higher in individuals of lower socioeconomic status. Direct costs of migraine
include the cost of migraine medications and health care expenses. Indirect costs
associated with migraine include reduced productivity due to absenteeism and
reduced performance while at work. Recent evidence suggests that a subgroup of
migraine patients may have a clinically progressive disorder. Future
epidemiologic studies should focus on identifying patients who are at higher risk
for progression and on assessing the impact of intervention strategies on disease
progression.

Publication Types: 
    Review

PMID: 15833088 [PubMed - indexed for MEDLINE]

1853: Headache. 2005 Apr;45 Suppl 1:S25-32.

Brain hyperexcitability: the basis for antiepileptic drugs in migraine
prevention.

Welch KM.

Rosalind Franklin University of Medicine and Science, Department of Neurology,
The Chicago Medical School, North Chicago, IL 60064, USA.

Abnormal brain excitability may provide the susceptibility for triggering
migraine attacks. Antiepileptic drugs may diminish neuronal excitability and
consequently reduce the frequency of migraine. Because migraine aura is
predominantly visual, hyperexcitability of the occipital cortex has been the
focus of investigations. Functional magnetic resonance imaging of the brain and
magnetoencephalography provide the most consistent evidence for the role of brain
hyperexcitability in migraine and confirm that triggering an abnormal electric
and metabolic event consistent with the cortical spreading depression (CSD) of
Leao is anatomically and functionally linked with migraine aura symptoms. Future 
drug discovery should focus on the interface between the excitable cell and the
earliest events of CSD.

Publication Types: 
    Review

PMID: 15833087 [PubMed - indexed for MEDLINE]

1854: Headache. 2005 Apr;45 Suppl 1:S14-24.

Migraine pathophysiology.

Goadsby PJ.

Institute of Neurology, The National Hospital for Neurology and Neurosurgery,
London, UK.

A combination of basic science and human physiology, particularly functional
neuroimaging, has radically altered our understanding of migraine with a focus on
brain mechanisms for this common and disabling disorder. Genetic studies have
begun to provide plausible targets for the basic molecular defect in terms of ion
channels, albeit thus far in the rare condition of familial hemiplegic migraine
(FHM). Migraine pathophysiology involves the trigeminovascular system and central
nervous system modulation of the pain-producing structures of the cranium. The
degree to which head pain results from the activation of the nociceptors of
pain-producing intracranial structures, or to the facilitation or lack of
inhibition of afferent signals, is not clear at this time. An understanding of
the pain mechanism is likely to provide insights into the mechanisms underlying
the more generalized sensory dysfunction that is so typical of migraine.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 15833086 [PubMed - indexed for MEDLINE]

1855: J Child Neurol. 2005 Mar;20(3):251-3.

Comment in:
    J Child Neurol. 2007 Jan;22(1):123-4.

Topiramate in the prophylactic treatment of migraine in children.

Campistol J, Campos J, Casas C, Herranz JL.

Neuropediatric Department, Hospital Universitario Sant Joan de Déu, Paseo San
Juan de Dios, Barcelona, Spain. campistol@hsjdbcn.org

We present a prospective case series of 24 children diagnosed with migraine
refractory to prophylactics and treated for 4 months with topiramate as the only 
prophylactic drug. At the final visit, the mean topiramate dose was 3.5 +/- 1.7
mg/kg/day. Nearly all patients (87.5%) reported a shorter duration of attacks,
and the average pain intensity was rated as mild by 14 patients (58.3%). Eight
(33.3%) patients had adverse events, none of which were serious. In our sample of
pediatric patients, topiramate was effective for the prophylactic treatment of
migraine in children. It was well tolerated at the doses used for titration and
maintenance. Controlled trials are needed to verify the efficacy of topiramate
for migraine in children.

Publication Types: 
    Clinical Trial
    Multicenter Study

PMID: 15832623 [PubMed - indexed for MEDLINE]

1856: Neurogenetics. 2005 May;6(2):67-72. Epub 2005 Apr 14.

A genome-wide scan provides evidence for loci influencing a severe heritable form
of common migraine.

Lea RA, Nyholt DR, Curtain RP, Ovcaric M, Sciascia R, Bellis C, Macmillan J,
Quinlan S, Gibson RA, McCarthy LC, Riley JH, Smithies YJ, Kinrade S, Griffiths
LR.

Genomics Research Centre, School of Health Science, Griffith University,
Queensland, Australia.

Migraine is a prevalent neurovascular disease with a significant genetic
component. Linkage studies have so far identified migraine susceptibility loci on
chromosomes 1, 4, 6, 11, 14, 19 and X. We performed a genome-wide scan of 92
Australian pedigrees phenotyped for migraine with and without aura and for a more
heritable form of "severe" migraine. Multipoint non-parametric linkage analysis
revealed suggestive linkage on chromosome 18p11 for the severe migraine phenotype
(LOD*=2.32, P=0.0006) and chromosome 3q (LOD*=2.28, P=0.0006). Excess allele
sharing was also observed at multiple different chromosomal regions, some of
which overlap with, or are directly adjacent to, previously implicated migraine
susceptibility regions. We have provided evidence for two loci involved in severe
migraine susceptibility and conclude that dissection of the "migraine" phenotype 
may be helpful for identifying susceptibility genes that influence the more
heritable clinical (symptom) profiles in affected pedigrees. Also, we concluded
that the genetic aetiology of the common (International Headache Society) forms
of the disease is probably comprised of a number of low to moderate effect
susceptibility genes, perhaps acting synergistically, and this effect is not
easily detected by traditional single-locus linkage analyses of large samples of 
affected pedigrees.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 15830246 [PubMed - indexed for MEDLINE]

1857: J Cereb Blood Flow Metab. 2005 Sep;25(9):1225-35.

Noradrenergic agonists and antagonists influence migration of cortical spreading 
depression in rat-a possible mechanism of migraine prophylaxis and prevention of 
postischemic neuronal damage.

Richter F, Mikulik O, Ebersberger A, Schaible HG.

Institute of Physiology-Neurophysiology, Friedrich Schiller University Jena,
Jena, Germany. FRIC@mti.uni-jena.de

Cortical spreading depression (CSD) is thought to be a neuronal mechanism that
expands the penumbra zone after focal brain ischemia and that causes migraine
aura. Both adrenergic agonists and antagonists significantly influence the size
of the penumbra zone and decline the frequency of migraine. To study whether
these compounds act by influencing CSD, we applied different drugs topically to
an area of the exposed cortex of anesthetized adult rats and observed the
migration of CSD-related DC potential deflections across the treated area. The
adrenergic agonist norepinephrine (1 mmol/L) and the alpha(2)-agonist clonidine
(0.56 mmol/L) blocked reversibly the migration of CSD. The beta-blocker
propranolol (250 micromol/L to 1 mmol/L) dose-dependently diminished migration
velocity or even blocked migration of CSD. The CSD blockade by the
alpha(2)-antagonist yohimbine (1.75 mmol/L) was because of its action on
inhibitory 5-HT(1A) receptors. None of the substances in the concentrations used 
had influence on regional cerebral blood flow or on systemic arterial blood
pressure. The data suggest that the interference of these compounds with CSD may 
contribute to their beneficial therapeutic effect. The effect of beta-receptor
antagonists in human migraine needs further exploration, since these drugs also
work in migraine without aura.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 15829916 [PubMed - indexed for MEDLINE]

1858: Ann N Y Acad Sci. 2005 Apr;1039:517-20.

Use of topiramate (topamax) in a subgroup of migraine-vertigo patients with
auditory symptoms.

Carmona S, Settecase N.

Instituto de Neurociencias de Buenos Aires (INEBA), Buenos Aires, Argentina.
scarmona@arnet.com.ar

Five-three percent of the patients who suffer from migraine present severe
incapacity and need rest in bed. If we add to this the incapacity produced by
vertigo, then the quality of life of these patients is seriously affected.
Migraine/Vertigo (MV) should be another criterion in the selection of preventive 
treatment even when other criteria are not fulfilled. Auditory symptoms may
accompany MV. We treated 10 patients with Topiramate in an open trial, twice a
day, with an average dose of 100 mg/day. The treatment period for these patients 
ranges between 6 and 16 months, with a mean of 9. As of today, all patients
present no crisis. Regarding auditory symptoms, all the patients referred that
they were stabilized. The effect began quickly, from the first month in most
patients as it has been reported in other studies.

Publication Types: 
    Clinical Trial

PMID: 15827012 [PubMed - indexed for MEDLINE]

1859: Can J Ophthalmol. 2005 Feb;40(1):51-7.

Effect of the menstrual cycle on standard achromatic and blue-on-yellow visual
field analysis of women with migraine.

Yucel I, Akar ME, Dora B, Akar Y, Taskin O, Ozer HO.

Department of Ophthalmology, Akdeniz University School of Medicine, Antalya,
Turkey.

BACKGROUND: It has been postulated that migraine and glaucoma may have common
vascular causative factors. Significant sex-based differences in the incidence of
many important ocular conditions raise the possibility that estrogens may have
direct effects on the eye. We performed a study to determine the effect of the
menstrual cycle on standard achromatic automated perimetry (SAP) and
short-wavelength automated perimetry (SWAP) (blue-on-yellow perimetry) of women
with migraine. METHODS: Both eyes of 73 normally menstruating women (31 subjects 
with migraine and 42 healthy control subjects) were included in the study.
Subjects underwent a complete ocular examination including SAP and SWAP in both
the follicular phase (12th to 13th day of the cycle) and the luteal phase (1 to 2
days before the onset of bleeding) of two consecutive menstrual cycles.We
performed visual field analysis using the Humphrey Field Analyzer II with the
full-threshold central 30-2 program. Mean sensitivity was calculated for the
superior temporal, inferior temporal, superior nasal and inferior nasal regions
separately. RESULTS: Thirteen subjects were lost to follow-up (5 in the migraine 
group and 8 in the control group), leaving 26 subjects and 34 subjects
respectively. There was no significant difference in mean age between the two
groups (33.9 years [standard deviation (SD) 3.4 years] vs. 35.1 years [SD 3.3
years]). The mean duration of migraine was 7.6 (SD 3.1) years (range 3-14 years).
In both groups, serum estradiol levels were significantly lower (p = 0.001) and
serum progesterone levels were significantly higher (p < 0.001) in the luteal
phase than in the follicular phase. In the control group, the mean sensitivity
values with SWAP were significantly lower in the luteal phase than in the
follicular phase (p = 0.04). A similar decrease was observed for the subjects
with migraine with both SAP and SWAP (p = 0.01). There was no difference in
regional mean sensitivity between the two phases with either perimetric test in
the control group. For the subjects with migraine, there was no difference in
regional mean sensitivity between the two phases with SAP. However, with SWAP,
the mean sensitivity for the nasal visual field locations was significantly lower
in the luteal phase than in the follicular phase (p = 0.01). INTERPRETATION: Our 
study provides further evidence of an effect of sex hormones on the visual field 
of women with migraine. In addition to assessment of intraocular pressure,
menstrual cycle phases should be considered in women with migraine at risk for
glaucomatous optic neuropathy.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 15825530 [PubMed - indexed for MEDLINE]

1860: J Med Assoc Thai. 2004 Dec;87(12):1466-70.

Flunarizine for prophylactic treatment of childhood migraine.

Visudtibhan A, Lusawat A, Chiemchanya S, Visudhiphan P.

Department of Pediatrics, Faculty of Medicine, Ramathibodi Hospital, Mahidol
University, Bangkok 10400, Thailand. raavs@mahidol.ac.th

OBJECTIVE: To determine the effectiveness of flunarizine for migraine prophylaxis
in children. PATIENTS AND METHOD: Children aged between 7 and 15 years who had
the indication for prophylactic treatment of migraine were recruited into a
prospective study at the Department of Pediatrics, Ramathibodi Hospital, from
January 1st to December 31st 1999. After verbal consent was obtained, flunarizine
was administered either at 5-mg daily in those who had never received it or at
10-mg daily in those who previously took this drug within one year Serial
evaluation for the severity of migraine including duration, intensity, and
frequency of headache attacks was performed every 2 weeks for 6 months. RESULTS: 
Twenty-one children (10 boys, 11 girls) with a mean age of 11.3+/-2.48 years
(range 7-15 years) were enrolled in the study. There were ten children who had
migraine with aura. Initially, 5-mg daily and 10-mg daily of flunarizine were
administered in 19 and 2 patients respectively. The dosage was increased to 10-mg
daily after two weeks in 5 patients because of the unresponsiveness to the
initial dose. Improvement was observed in 14 patients (66%) including 13 of 14
patients who received 5-mg daily and 1 of 7 patients who received 10 mg daily.
Five patients (23%) had no recurrent attack. Nine patients (42%) had more than
50%-reduction of frequency of migraine and 3 of these had either shorter duration
or less intensity of the attack. Clinical improvement was observed between 2 and 
4 weeks after initiation of treatment. There was no adverse effect observed
CONCLUSION: This is a preliminary result demonstrating that flunarizine is one of
the effective drugs for migraine prophylaxis in children.

PMID: 15822542 [PubMed - indexed for MEDLINE]

1861: Dis Manag Advis. 2005 Feb;11(2):19-21, 13.

Higher profile for migraine management spurs boom in DM offerings.

[No authors listed]

With more employers taking an interest in DM, the economic case has been
broadened to include such factors as absenteeism and worker productivity. This
trend has prompted many organizations to take a new look at managing migraines.
Surveys suggest these debilitating headaches arc responsible for millions in lost
productivity, and yet there are several effective treatment strategies. Further, 
developers believe even modest migraine DM programs can deliver an ROI.

PMID: 15822369 [PubMed - indexed for MEDLINE]

1862: CNS Drugs. 2005;19(4):335-43; discussion 345-6.

Intranasal sumatriptan: in adolescents with migraine.

Curran MP, Evans HC, Wagstaff AJ.

Adis International Limited, Auckland, New Zealand. demail@adis.co.nz

Sumatriptan, a serotonin 5-HT(1B/1D) agonist, constricts cranial blood vessels
and inhibits neuroinflammatory processes. A single dose of sumatriptan 10 mg
(approved European dosage) was significantly more effective than placebo in
achieving headache relief at 1 hour post-dose in a well designed study. Headache 
relief occurred in significantly more adolescents administered a single dose of
intranasal sumatriptan 20 mg (at 1 and 2 hours) and 5 mg (at 2 hours) than
placebo (pooled data from two studies). Sustained headache relief (1-24 and 2-24 
hours) occurred in significantly more recipients of a single dose of intranasal
sumatriptan 20mg and 5mg than placebo (pooled data from two studies). Intranasal 
sumatriptan was generally well tolerated in adolescent migraineurs (in
single-episode studies or long term in multiple-episode studies). Taste
disturbance occurred more often with intranasal sumatriptan than with placebo
[Chart: see text].

Publication Types: 
    Review

PMID: 15813647 [PubMed - indexed for MEDLINE]

1863: Brain Res Bull. 2005 Apr 30;65(4):297-300.

Rizatriptan does not change cerebral blood flow velocity during migraine attacks.

Gori S, Morelli N, Bellini G, Bonanni E, Manca L, Orlandi G, Iudice A, Murri L.

University Centre for Adaptive Disorders and Headache (UCADH), Section of Pisa I 
Institute of Neurology, Department of Neurosciences, University of Pisa, Via Roma
67, 56126 Pisa, Italy. s.gori@med.unipi.it

Rizatriptan represents a major advance in the treatment of migraine attack:
inhibition of peripheral trigeminal nerve and constriction of intracranial
extracerebral blood vessels have been proposed as its main antimigraine
mechanisms of action. Although many studies may suggest that rizatriptan causes
highly selective vasoconstriction within intracranial extracerebral vessels
(i.e., meningeal arteries), no literature data are available to date on possible 
cerebral hemodynamic changes in humans after treatment with rizatriptan. The aim 
of this study was to evaluate the effect of rizatriptan on cerebral blood flow
velocity performing transcranial Doppler during spontaneous attacks of migraine
without aura. Fourteen patients suffering from migraine without aura were
monitored to evaluate mean flow velocity changes on both middle cerebral arteries
during migraine attack 30 min before and 120 min after oral administration of
rizatriptan 10mg. Monitoring was repeated for 30 min during the pain-free period.
All patients turned out to be drug responders and no significant mean flow
velocity changes were observed between the pain-free period and pre-treatment
phase; besides no significant difference in mean flow velocity value have been
detected between the periods after the drug administration during the attack
versus both pre-treatment period and pain-free phase. These findings indicate
that the antimigraine action of rizatriptan is not associated with clear
intracranial cerebral hemodynamic changes and may support its cerebrovascular
safety.

Publication Types: 
    Clinical Trial
    Comparative Study

PMID: 15811594 [PubMed - indexed for MEDLINE]

1864: Clin Ther. 2005 Feb;27(2):154-65.

Topiramate monotherapy in epilepsy and migraine prevention.

Silberstein SD, Ben-Menachem E, Shank RP, Wiegand F.

Thomas Jefferson University, Thomas Jefferson University Hospital, Philadelphia, 
Pennsylvania 19107, USA. stephen.silberstein@jefferson.edu

OBJECTIVES: The purposes of this review were to assess the efficacy of topiramate
as monotherapy for epilepsy and migraine prevention, describe how it should be
used, and give clinical advice on how to manage the practical aspects of dosing, 
titration, and possible adverse events in these 2 indications. METHODS: We
searched the PubMed and BIOSIS databases using the key words topiramate,
epilepsy, and migraine from the year 1987 onward, and subsequently focused the
search on larger controlled trial studies of topiramate as monotherapy. RESULTS: 
Studies have evaluated the use of topiramate as monotherapy in the treatment of
partial-onset and generalized seizures and in the prevention of migraine. In a
randomized study, 75% of epilepsy patients treated with 400 mg/d topiramate
remained seizure free at 1 year. Patients in the same study treated with a lower 
dose of topiramate (50 mg/d) also experienced notable seizure reductions, with
59% of patients free of seizures at 1 year. A comparison trial of topiramate (100
or 200 mg/d), valproate, and carbamazepine found that topiramate was associated
with a similar time to first posttreatment seizure as the other 2 agents (P =
NS). Trials of topiramate monotherapy in migraine prevention found that 100 mg/d 
was associated with a > or =50% reduction in monthly migraine frequency in 49% to
54% of patients. The migraine prevention trials typically used a starting dose of
25 mg/d, with weekly increases of 25 mg and an initial monotherapy target dose of
100 mg/d. The most common adverse events associated with topiramate are
paresthesia, weight loss, and other centrally mediated symptoms, many of which
may be ameliorated by proper titration and dosing and by good communication
between physician and patient. CONCLUSIONS: Data from controlled trials suggest
that 100 mg/d topiramate as monotherapy is effective in the treatment of
partial-onset and generalized seizures and in the prevention of migraine.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 15811478 [PubMed - indexed for MEDLINE]

1865: Curr Med Res Opin. 2005 Mar;21(3):413-24.

How treatment priorities influence triptan preferences in clinical practice:
perspectives of migraine sufferers, neurologists, and primary care physicians.

Lipton RB, Cutrer FM, Goadsby PJ, Ferrari MD, Dodick DW, McCrory D, Liberman JN, 
Williams P.

Department of Neurology, Albert Einstein College of Medicine, Bronx, NY 10461,
USA. rlipton@aecom.yu.edu

BACKGROUND: In treating migraine sufferers, physicians can choose from among
seven triptans with different attributes. OBJECTIVE: To develop a system for
selecting an oral triptan based on treatment priorities of migraine sufferers,
neurologists, and primary care physicians (PCPs) in the United States, and
evidence-based performance of triptans in clinical trials. METHODS: The TRIPSTAR 
project combines data on the treatment preferences of migraineurs and physicians 
with results from a meta-analysis of individual triptans, which evaluated their
effectiveness on various clinical endpoints. Telephone interviews with migraine
sufferers, neurol ogists, and PCPs were conducted to elicit individual views on
the relative importance of a prespecified set of acute treatment outcomes. Four
hundred and fifteen migraine sufferers, both triptan-experienced and
triptan-naive, were interviewed. Also, 200 board-certified neurologists and 200
PCPs provided information on migraine patients from their clinical practice. A
multiattribute decision model for selecting an oral triptan was constructed using
attribute importance weights collected at telephone interview and the
meta-analysis data, which were drawn from 53 clinical trials of 6 oral triptans. 
RESULTS: Efficacy attributes were rated significantly more important than
tolerability or consistency in selecting an oral triptan, according to migraine
sufferers and physicians. Freedom from cardiovascular adverse events was the most
important tolerability attribute, according to migraine sufferers and physicians 
alike. Pain free at 1 h was the most important lower-level efficacy attribute for
migraine sufferers, while sustained pain free was most important for physicians. 
When weighted treatment attributes were combined with meta-analysis data in a
multi-attribute decision model, almotriptan 12.5 mg, eletriptan 80 mg, and
rizatriptan 10 mg were significantly closer to the hypothetical ideal triptan
than was suma triptan 100 mg. Triptans selected by the model were generally
closer to the patient-specific ideal triptan than were the triptans prescribed by
physicians. CONCLUSIONS: Almotriptan, eletriptan, and rizatriptan were the three 
triptans closest to the ideal, from the perspectives of migraine sufferers, PCPs,
and neurologists alike. The TRIPSTAR model may be a potentially useful
decision-support tool to help physicians select the triptan most likely to
produce a successful outcome in migraine sufferers.

Publication Types: 
    Multicenter Study
    Research Support, Non-U.S. Gov't

PMID: 15811210 [PubMed - indexed for MEDLINE]

1866: Curr Med Res Opin. 2005 Mar;21(3):381-9.

Pain-free rates with zolmitriptan 2.5 mg ODT in the acute treatment of migraine: 
results of a large double-blind placebo- controlled trial.

Loder E, Freitag FG, Adelman J, Pearlmand S, Abu-Shakra S.

Spaulding Rehabilitation Hospital, Harvard Medical School, Boston, MA, USA.
eloder@partners.org

CONTEXT: Zolmitriptan 2.5 mg orally disintegrating tablets (ODT) allow patients
to take the medication without fluids, which is convenient and avoids the risk of
fluid-induced exacerbation of nausea/vomiting. OBJECTIVE: To evaluate the
efficacy and tolerability of zolmitriptan 2.5 mg ODT taken as soon as possible
after onset of a migraine. DESIGN: Multicenter, double-blind, parallel-group,
placebo-controlled two-attack trial. SETTING: Outpatient headache clinics in the 
US. PATIENTS: 608 patients were randomized; 566 patients treated at least 1
migraine and were included in the tolerability assessment (565 patients were
included in the intent-to-treat population). INTERVENTION: Patients were
randomized to either zolmitriptan 2.5 mg ODT or placebo. Patients treated up to 2
migraine attacks as soon as possible after the start of their migraine pain. MAIN
OUTCOME MEASURE: Pain-free rates at 2 h. RESULTS: Zolmitriptan 2.5 mg ODT (n =
281) demonstrated a significant pain-free rate vs. placebo (n = 284) at 2 h (40% 
vs. 20%, p < 0.001), 1.5 h (25% vs. 15%, p < 0.001), and 1 h (13% vs. 8%, p =
0.004). Sustained pain-free rate was significantly higher than placebo (31% vs.
15%; p < 0.001). Return to normal activities favored zolmitriptan 2.5 mg ODT at 1
h (p = 0.004), 1.5 h (p < 0.001), and 2 h (p < 0.001). Adverse events associated 
with zolmitriptan 2.5 mg ODT were those commonly reported with the use of
triptans. CONCLUSIONS: Zolmitriptan 2.5 mg ODT, taken as early as possible after 
onset of a migraine attack, is effective in the treatment of migraine, producing 
a significantly higher pain-free rate than placebo 2 h post-dose, and also at the
earlier time points of 1 h and 1.5 h post-dose.

Publication Types: 
    Clinical Trial
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 15811207 [PubMed - indexed for MEDLINE]

1867: Curr Med Res Opin. 2005 Mar;21(3):375-9.

Clinical and economic issues associated with switching between triptans in
clinical practice.

Dowson AJ, Fuat A, Gruffydd-Jones K.

King's Headache Service, King's College Hospital, London, UK.
drandydowson@dowsona.fsnet.co.uk

Seven oral triptans are now generally available for the acute treatment of
migraine, and physicians may sometimes feel under pressure to switch patients
from one triptan to another for nonclinical reasons. This commentary article
provides advice on what information should be taken into account by the physician
before they consider switching one triptan for another. We review recommendations
on switching triptans from international guidelines for migraine management and
relate these to data from a recently published study on the economic implications
of switching triptans in the UK. Controlled clinical studies reveal that most of 
the oral triptans have broadly similar efficacy profiles. Switching triptans can 
therefore only be recommended if the patient experiences problems such as lack of
efficacy or intolerable side effects following repeated use of the initial
triptan. The retrospective database study revealed that most patients who had
their triptan switched were subsequently switched again during a 15 month review 
period, most usually back to their original triptan. Overall, switching a
patient's triptan led to increased costs (analysed as costs of medication and the
GP consultation) to the healthcare provider. These data indicate that patients
should only be switched from one triptan for another for clinical reasons and not
for perceived economic reasons, i.e. cost of the medication.

Publication Types: 
    Editorial
    Research Support, Non-U.S. Gov't

PMID: 15811206 [PubMed - indexed for MEDLINE]

1868: Curr Eye Res. 2005 Mar;30(3):163-9.

The effect of the menstrual cycle on the optic nerve head analysis of migrainous 
women.

Yucel I, Akar M, Durukan A, Akar Y, Taskin O, Dora B, Yilmaz N.

Department of Ophthalmology, Akdeniz University School of Medicine, Antalya,
Turkey.

PURPOSE: To determine the effect of the menstrual cycle on the optic nerve head
topographic analysis of normally menstruating migrainous women. MATERIAL AND
METHODS: Randomly selected one eye of 44 migrainous and 49 healthy control women 
with regular menstrual cycles were included in the study. All subjects underwent 
complete ocular examination. Optic nervehead topographic analysis were performed 
using a confocal scanning laser ophthalmoscope, HRT II (Heidelberg Retinal
Tomograph II, software version 1.6;Heidelberg Engineering, Heidelberg, Germany). 
They were repeated for two times during the menstrual cycle: in follicular phase 
(7th to 10th day of the cycle) and in the luteal phase (days 3 to 4 before the
menstrual bleeding). Serum estradiol, progesterone, and luteinizing hormone
measurements were repeated at each menstrual phase. Results: The mean age of
migrainous and control subjects were 31.5 + 5.1 years and 33.4 +/- 3.7 years,
respectively (P > 0.05). Their mean disc areas were 2.26 +/- 0.46 mm(2) and 1.95 
+/- 0.39 mm(2), respectively(P < 0.05). Control subjects did not demonstrate any 
difference in the disc topography (P > 0.05). The parameter rim volume decreased,
while the parameters cup volume and cup shape measure increased significantly in 
the luteal phase of the migrainous women (all P values <0.05). Mean intraocular
pressure of the migrainous women decreased significantly in luteal phase (P <
0.05). CONCLUSION: Significant differences exist in the optic rim and cup
parameters during the menstrual cycle of the migrainous women. Further clinical
trials on ocular blood flow changes during the menstrual cycle of the migrainous 
women may highlight the role of sex steroids in the optic nerve head of the
migrainous women.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 15804741 [PubMed - indexed for MEDLINE]

1869: Tohoku J Exp Med. 2005 May;206(1):51-9.

Prevalence and characteristics of migraine in women of reproductive age in
Istanbul, Turkey: a population based survey.

Börü UT, Koçer A, Lüleci A, Sur H, Tutkan H, Atli H.

Neurology Department, Dr. Lutfi Kirdar Kartal Research and Education Hospital,
Istanbul, Turkey.

Migraine is more common in female and onset of migraine is most commonly seen in 
the second and third decades of life. In this study, we aimed to estimate the
prevalence and characteristics of migraine among women of ages between 15 to 45
years in Turkey. This is the first study to target this age group. The women were
interviewed on a door-to-door basis, from early morning to late evening. Once
responded positively to headache, an in-depth interview was performed questioning
for migraine features. Diagnosis was made from a questionnaire by eight
neurologists. One thousand eight hundred thirty five (1,835) out of 96,000 women 
living in Maltepe which is a town of Istanbul participated in this study. The
prevalence of migraine in females aged 15-45 (reproductive ages) was 15.8% (95%
CI, 0.142-0.176). This study showed that migraine onset occurred at a mean age of
22.7, 33% having family history, and with migraine with and without aura having
near equal frequencies. The prevalence of migraine in women of reproductive ages 
in Istanbul as found in our study is lower than that reported in United States
and Europe countries, but higher than that in Middle and Far Eastern countries.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 15802875 [PubMed - indexed for MEDLINE]

1870: Ann Emerg Med. 2005 Apr;45(4):393-401.

Parenteral dihydroergotamine for acute migraine headache: a systematic review of 
the literature.

Colman I, Brown MD, Innes GD, Grafstein E, Roberts TE, Rowe BH.

Department of Psychiatry, University of Cambridge, Cambridge, United Kingdom.

STUDY OBJECTIVE: Many therapies are used in the treatment of acute migraine
headache, with little agreement on effectiveness. This systematic review is
designed to determine the effectiveness of parenteral dihydroergotamine in
reducing pain, nausea, and relapse for episodes of acute migraine in adults.
METHODS: Randomized controlled trials were identified using MEDLINE, EMBASE,
other computerized databases, hand searching, bibliographies, and contacts with
industry and authors. Studies in which dihydroergotamine (alone or in combination
with an antiemetic) was compared with placebo or any other common migraine
therapy were considered. Relevance, inclusion, and study quality were assessed
independently by 2 reviewers. RESULTS: From 281 potentially relevant abstracts,
11 studies met the inclusion criteria. Solitary dihydroergotamine use was
compared to sumatriptan and phenothiazines in 3 studies; results failed to
demonstrate a significant benefit of dihydroergotamine over these therapies. In 8
combination treatment studies, heterogeneity in study methodology prevented
statistical pooling. However, dihydroergotamine administered with an antiemetic
was as effective as or more effective than meperidine, valproate, or ketorolac
across all pain, nausea, and relapse outcomes reported in all studies.
CONCLUSION: This evidence suggests that dihydroergotamine is not as effective as 
sumatriptan or phenothiazines as a single agent for treatment of acute migraine
headache; however, when administered with an antiemetic, dihydroergotamine
appears to be as effective as opiates, ketorolac, or valproate. Given its
nonnarcotic properties, parenteral dihydroergotamine combined with an antiemetic 
should be considered as effective initial therapy in clinical practice.

Publication Types: 
    Review

PMID: 15795718 [PubMed - indexed for MEDLINE]

1871: J Biol Chem. 2005 Jun 24;280(25):24064-71. Epub 2005 Mar 28.

Gating deficiency in a familial hemiplegic migraine type 1 mutant P/Q-type
calcium channel.

Barrett CF, Cao YQ, Tsien RW.

Department of Molecular and Cellular Physiology, Stanford University School of
Medicine, Stanford, California 94305, USA.

Familial hemiplegic migraine type 1 (FHM1) arises from missense mutations in the 
gene encoding alpha1A, the pore-forming subunit of P/Q-type calcium channels. The
nature of the channel disorder is fundamental to the disease, yet is not well
understood. We studied how the most prevalent FHM1 mutation, a threonine to
methionine substitution at position 666 (TM), affects both ionic current and
gating current associated with channel activation, a previously unexplored
feature of P/Q channels. Whole-cell currents were measured in HEK293 cells
expressing channels containing either wild-type (WT) or TM alpha1A. Calcium
currents were significantly smaller in cells expressing TM channels, consistent
with previous reports. In contrast, surface expression of TM channels, measured
by immunostaining against an extracellular epitope, was not decreased, and
Western blots demonstrated that TM alpha1A subunits were expressed as full-length
proteins. WT and TM gating currents were isolated by replacing Ca2+ with the
nonpermeant cation La3+. The gating currents generated by the mutant channels
were one-third that of WT, a deficiency sufficient to account for the observed
attenuation in calcium current; the remaining gating current was no different in 
kinetics or voltage dependence. Thus, the decreased calcium influx seen with TM
channels can be attributed to a reduced number of channels available to undergo
the voltage-dependent conformational changes needed for channel opening, not to
fewer channel proteins expressed on the cell surface. This identification of an
intrinsic defect in FHM1 mutant channels helps explain their impact on
neurotransmission when they occupy type-specific slots for P/Q channels at
central nerve terminals.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, U.S. Gov't, P.H.S.

PMID: 15795222 [PubMed - indexed for MEDLINE]

1872: Neurology. 2005 Mar 22;64(6):1020-6.

Migraine, headache, and the risk of stroke in women: a prospective study.

Kurth T, Slomke MA, Kase CS, Cook NR, Lee IM, Gaziano JM, Diener HC, Buring JE.

Division of Preventive Medicine, Department of Medicine, Brigham and Women's
Hospital, Harvard Medical School, 900 Commonwealth Ave. E., Boston, MA
02215-1204, USA. tkurth@rics.bwh.harvard.edu

BACKGROUND: Migraine and headache in general have been associated with subsequent
risk of stroke, primarily in retrospective case-control studies. Prospective data
evaluating the association between specific headache forms and stroke are sparse.
METHODS: A prospective cohort study was conducted among 39,754 US health
professionals age 45 and older participating in the Women's Health Study with an 
average follow-up of 9 years. Incident stroke was self-reported and confirmed by 
medical record review. RESULTS: A total of 385 strokes (309 ischemic, 72
hemorrhagic, and 4 undefined) occurred. Compared with nonmigraineurs,
participants who reported migraine overall or migraine without aura had no
increased risk of any stroke type. Participants who reported migraine with aura
had increased adjusted hazards ratios (HRs) of 1.53 (95% CI 1.02 to 2.31) for
total stroke and 1.71 (95% CI 1.11 to 2.66) for ischemic stroke but no increased 
risk for hemorrhagic stroke. Participants with migraine with aura who were <55
years old had a greater increase in risk of total (HR 1.75; 95% CI 1.02 to 3.00) 
and ischemic (HR 2.25; 95% CI 1.30 to 3.91) stroke. Compared with participants
without headache, headache in general and nonmigraine headache were not
associated with total, ischemic, or hemorrhagic stroke. CONCLUSIONS: In these
prospective data, migraine was not associated with total, ischemic, or
hemorrhagic stroke. In subgroup analyses, we found increased risks of total and
ischemic stroke for migraineurs with aura. The absolute risk increase was,
however, low, with 3.8 additional cases per year per 10,000 women.

Publication Types: 
    Research Support, N.I.H., Extramural
    Research Support, U.S. Gov't, P.H.S.

PMID: 15781820 [PubMed - indexed for MEDLINE]

1873: J Pharmacol Exp Ther. 2005 Jul;314(1):162-9. Epub 2005 Mar 18.

The role of dopamine in a model of trigeminovascular nociception.

Akerman S, Goadsby PJ.

Institute of Neurology, Queen Square, London, WC1N 3BG UK.

Migraine is a common, disabling problem with three phases: premonitory, main
headache attack, and postdrome. The headache phase is thought to involve
activation of trigeminal neurons, whereas the premonitory and postdrome phases
may involve dopaminergic mechanisms. In animal studies, dopamine has been found
to cause vasodilation of cranial arteries at very low doses. Using intravital
microscopy, we examined the effect of dopamine receptor agonists on dural blood
vessel caliber and the effect of dopamine and specific dopamine receptor
antagonists on trigeminovascular neurogenic dural vasodilation. Dopamine
hydrochloride caused a significant vasoconstriction (P < 0.05) and increase in
arterial blood pressure (P < 0.05) that was reversed by a alpha2-adrenoceptor
antagonist, yohimbine, rather than specific dopamine receptor antagonists. The D1
receptor agonist caused a vasoconstriction (P < 0.05) and a blood pressure
increase (P < 0.05), which was reversed by yohimbine and therefore
alpha2-adrenoceptor-mediated. None of the specific dopamine receptor antagonists 
were able to attenuate neurogenic dural vasodilation. Dopamine hydrochloride
infusion (P < 0.05) and a D1 receptor agonist were able to attenuate the
vasodilation (P < 0.05), with maximal dilation returning after cessation of the
dopamine agonist infusion. This response may be due to the vasoconstrictor
effects of the alpha2-adrenoceptor and an action at the D1 receptor. In the
intravital model of trigeminal activation, it seems that dopamine receptors do
not play a major role and may not present an acute treatment option. Our data do 
not exclude a role for dopamine receptor modulators in short- or long-term
prevention.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 15778266 [PubMed - indexed for MEDLINE]

1874: Cephalalgia. 2005 Apr;25(4):280-9.

Maturation of early visual processing investigated by a pattern-reversal
habituation paradigm is altered in migraine.

Oelkers-Ax R, Parzer P, Resch F, Weisbrod M.

Department of Child and Adolescent Psychiatry, University of Heidelberg, D-69115 
Heidelberg, Germany. rieke_oelkers@med.uni-heidelberg.de

Evidence for a disturbed maturation of information processing in migraine came
recently from evoked and event-related potential studies during childhood. In
adult migraineurs, deficient habituation is proposed as principal interictal
abnormality and was found inter alia for Visual Evoked Potentials (VEPs). This
study investigated response and habituation to pattern-reversal VEPs and its
maturation in 102 children with primary headache (migraine with and without aura,
tension-type headache) and 79 healthy controls from 6 to 18 years. A reduction of
N180 latency from pre- to postpubertal age reflects maturation and was clearly
present in controls but lessened in migraineurs. N180 latency was prolonged in
migraineurs without aura from 12 years onwards. Habituation did not differ
between groups. In conclusion, diminished N180 latency reduction with age in
migraineurs gives further evidence that maturation of visual information
processing is altered in migraine. Deficient habituation to pattern-reversal VEPs
could not be confirmed during childhood migraine.

Publication Types: 
    Clinical Trial
    Controlled Clinical Trial
    Research Support, Non-U.S. Gov't

PMID: 15773825 [PubMed - indexed for MEDLINE]

1875: Cephalalgia. 2005 Apr;25(4):267-79.

FRAMIG 2000: medical and therapeutic management of migraine in France.

Lucas C, Chaffaut C, Artaz MA, Lantéri-Minet M.

Neurological Clinic, Hospital Salengro, 59037 Lille, France. clucas@chru-lille.fr

FRAMIG 2000 is a population-based survey of medical and therapeutic management of
migraine in France. A total of 312 migraine sufferers were first identified from 
a representative sample of 4689 adult subjects using a validated questionnaire
based on the IHS migraine diagnostic criteria and administered by telephone.
Subjects were then interviewed using a branching questionnaire and a
computer-assisted interview technique. Although 80% were self-aware of their
migrainous state, 82% of migraine sufferers had no medical follow-up for
migraine. The proportion of migraine sufferers who did not consult decreased
slightly with increasing migraine-related disability (from 87% for subjects in
MIDAS grade I to 68% for those in MIDAS grade IV). Migraine sufferers declared to
effectively control only four attacks out of 10 after the first intake of the
usual treatment. Only 6% of subjects in the survey received a prophylactic
treatment for migraine whereas 22% were in MIDAS grade III or IV. These data show
that the burden of migraine does not result from a deficit in diagnosis but
instead from a deficit in patient information on the proper use of current
effective treatments of migraine.

Publication Types: 
    Clinical Trial

PMID: 15773824 [PubMed - indexed for MEDLINE]

1876: Cephalalgia. 2005 Apr;25(4):261-6.

Plasma nociceptin levels are reduced in migraine without aura.

Ertsey C, Hantos M, Bozsik G, Tekes K.

Department of Neurology, Semmelweis University, H-1083 Budapest, Hungary.
csaba@neur.sote.hu

It was demonstrated that both nociceptin, a novel opioid neuropeptide, and its
receptor are present in trigeminovascular neurons. In an animal model nociceptin 
dose-dependently inhibited neurogenic dural vasodilatation. These results suggest
that nociceptin may be involved in neurovascular headaches such as migraine. To
test this hypothesis, we studied circulating nociceptin levels in 18 patients
suffering from migraine without aura and in 24 controls. Headache-free
migraineurs had significantly lower nociceptin levels than controls (5.79 +/-
1.82 vs. 9.74 +/- 2.43 pg/ml, P < 0.0001, Student's t-tests). Nociceptin levels
were further reduced in six patients studied in the first 3 h of typical migraine
attacks (1.04 +/- 0.17 pg/ml). Nociceptin levels correlated with the frequency of
attacks in this group of migraineurs. Lower interictal nociceptin levels may
contribute to a defective regulation of trigeminovascular neurons in migraineurs 
which might be important in the pain process of migraine.

Publication Types: 
    Clinical Trial
    Controlled Clinical Trial

PMID: 15773823 [PubMed - indexed for MEDLINE]

1877: Cephalalgia. 2005 Apr;25(4):244-8.

Comment in:
    Cephalalgia. 2005 Apr;25(4):241-3.

Cluster headache and paroxysmal hemicrania: differential diagnosis.

Zidverc-Trajkovic J, Pavlovic AM, Mijajlovic M, Jovanovic Z, Sternic N, Kostic
VS.

Department of Cerebrovascular Disorders and Headache, Institute of Neurology,
Clinical Centre of Serbia, 11000 Belgrade, Serbia and Montenegro.
jzidverc@sezampro.yu

The utility of the differences between cluster headache (CH) and paroxysmal
hemicrania (PH) is limited by the considerable overlap of their clinical
characteristics. We compared 54 patients with CH and eight patients with PH in
terms of demographic features, characteristics of headache attacks, associated
autonomic features, temporal forms of disorders, and response to verapamil.
According to our results, clinical features that distinguished CH and PH patients
were: maximal pain localization, ocular in CH patients and extra-ocular in PH
group; mean attack duration was longer and mean attack frequency was lower in CH 
patients in comparison with PH patients. Conjuctival injection was the only
autonomic sign seen more frequently in CH patients. There were more CH patients
with episodic and more PH patients with unremitting form of the disorder in
examined groups. Although statistical analysis pointed out a significant
difference between these clinical features, there was no clinical characteristic 
that exclusively belonged to one of these headache entities. Demographic
characteristics (age, gender, social background), the other headache attack
features (nocturnal attacks, interattack tenderness), the other autonomic signs, 
as well as the response to verapamil did not differ significantly between two
groups.

Publication Types: 
    Clinical Trial
    Controlled Clinical Trial

PMID: 15773821 [PubMed - indexed for MEDLINE]

1878: Int J Neurosci. 2005 Jan;115(1):119-27.

Closure of a patent foramen ovale: effective therapy of migraine and occipital
stroke.

Finsterer J, Sommer O, Stiskal M, Stöllberger C, Baumgartner H.

Neurological Hospital Rosenhügel, Vienna, Austria. duarte@aonmail.at

Whether stroke in a patient with migraine and patent foramen ovale (PFO) is due
to PFO or migraine is difficult to decide. In a 33-year-old woman with migraine
with aura, a visual field defect developed acutely. Neurological investigation
revealed double vision when looking to the left and exaggerated patella tendon
reflexes. Since then the patient complained about permanent visual impairment.
CT- and MRI-scans of the brain showed a right occipital ischemic stroke.
Intensive search for risk factors revealed cigarette smoking and chronic
hypovolemia On transesophageal echocardiography an inter-atrial hypermobile
septum and a PFO were detected. The patient underwent closure of the PFO by means
of an Amplatzer PFO occluder nine weeks after the stroke. Since then she did not 
experience a further cerebrovascular event or migraine attack. This case shows
that in a patient with PFO and migraine with aura, stroke may be attributable to 
migraine rather than to PFO. Occlusion of the PFO may reduce the frequency and
intensity of migraine attacks.

Publication Types: 
    Case Reports

PMID: 15768856 [PubMed - indexed for MEDLINE]

1879: J Manag Care Pharm. 2005 Mar;11(2):137-44.

Costs and utilization of triptan users who receive drug prophylaxis for migraine 
versus triptan users who do not receive drug prophylaxis.

Etemad LR, Yang W, Globe D, Barlev A, Johnson KA.

Ingenix, Inc.,12125 Technology Dr., MN002-0258, Eden Prairie, MN 55344, USA.
lida.etemad@ingenix.com

OBJECTIVES: The objectives were 2-fold: (1) to describe the utilization patterns 
of new users of triptan therapy and (2) to measure the direct (pharmacy and
medical) costs of migraine-related health care services in moderate-to-severe
migraine patients treated with drug prophylaxis compared with migraine patients
who are not treated with drug prophylaxis. METHODS: A retrospective
administrative database study was conducted from the perspective of a managed
care health plan. Patients initiating triptan therapy were identified, and
utilization in the 12 months following initiation of drug therapy was determined.
In addition, moderate-to-severe migraine patients were identified based on the
quantity of triptan medication dispensed. Patients were classified as utilizing
or not utilizing migraine prophylaxis. Migraine-specific health services costs in
the 12 months following identification were determined. A multivariate ordinary
least squares regression model was constructed to determine the impact of the use
of drug prophylaxis on total cost. Utilizing the model, the difference in health 
services costs was predicted for each subject and the average treatment effect
was computed. RESULTS: Thirty-nine percent of new triptan users received only 1
triptan claim during the 12-month follow-up period, accounting for 11.5% of the
total triptan cost incurred by the health plan for this cohort. For new triptan
users, triptan use in the first or second quarter was correlated with triptan use
in the entire 12-month follow-up period (r = 0.187 and 0.279, respectively). The 
mean migrainerelated pharmacy cost per patient during the follow-up was $871;
however, continuous users had mean costs ($1,505) nearly 3 times the mean costs
for new users ($506, P<0.05). The average treatment effect of drug prophylaxis in
moderate-to-severe migraine patients was a decrease of $560 ($514-$607) per
patient per year in 1998-2001 dollars. CONCLUSION: High utilizers of migraine
therapy can be identified early in treatment. Drug prophylaxis for migraine is
cost saving, and an intervention program that increases the use of migraine
prophylaxis in potential candidates could be cost beneficial.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 15766320 [PubMed - indexed for MEDLINE]

1880: J Manag Care Pharm. 2005 Mar;11(2):124-36.

Prevalence and burden of illness of migraine in managed care patients.

Kobak KA, Katzelnick DJ, Sands G, King M, Greist JJ, Dominski M.

Dean Foundation for Health Education and Research, 2711 Allen Blvd., Middleton,
WI 53562, USA. ken.kobak@deancare.com

OBJECTIVE: To determine the 3-month prevalence rate of migraine in a health
maintenance organization (HMO) population, using a 2-stage screening process and 
neurologist exam, and to examine the burden of illness associated with both
previously diagnosed and previously undiagnosed migraine in this population
METHODS: A migraine assessment was sent to a random sample of 1,000 HMO patients 
between April 1999 and January 2000. Those screening positive and a random sample
of those screening negative for migraine were evaluated by neurologists using a
structured diagnostic assessment. Then, those diagnosed to have migraines by the 
study's neurologists completed a battery of 3 questionnaires, evaluating
severity, distress, and impairment RESULTS: Of 1,000 questionnaires sent, 753
(75.3%) were returned. The estimate of prevalence of migraine in this population 
ranged from 21.4% (adjusted for response bias) to 27.8% (unadjusted for selection
bias). Only 48% of respondents had been previously diagnosed with migraine. The
typical migraine caused moderate-to-severe distress in 69%, and 66% had definite 
or extreme interference in their social or occupational functioning. The average 
migraineur missed 7.6 hours of work due to migraine in the past 3 months.
Previously undiagnosed migraine was associated with substantial impairment, with 
58% of responders reporting interference with daily activities and 54% reporting 
moderate or greater distress. There was no significant difference between
previously diagnosed and undiagnosed migraineurs on 3 outcome measures: pain,
interference, or days of missed work. A higher proportion of previously diagnosed
migraineurs (84%) reported moderate or greater distress compared with undiagnosed
migraineurs (54%, P=0.002). CONCLUSIONS: Using a neurologist exam, the
researchers found that the prevalence of migraine headaches was higher than
previously reported. About one half of migraineurs had been previously
undiagnosed. Undiagnosed migraine is associated with significant pain, distress, 
and dysfunction and is similar in these respects to diagnosed migraine. Increased
public education and physician education on migraine are warranted.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 15766319 [PubMed - indexed for MEDLINE]

1881: Am J Emerg Med. 2005 Mar;23(2):149-54.

Canadian Headache Society criteria for the diagnosis of acute migraine headache
in the ED--do our patients meet these criteria?

Fiesseler FW, Riggs RL, Holubek W, Eskin B, Richman PB.

Department of Emergency Medicine, Morristown Memorial Hospital, NJ 07962, USA.
fredf@garden.net

INTRODUCTION: We previously reported that many patients who present to the ED
with "migraine" headache do not meet the International Headache Society criteria 
(IHSC) for the diagnosis of acute migraine. Objective The aim of the study was to
compare the frequency for which ED patients with migraine headache meet the
Canadian Headache Society criteria (CHSC) vs the IHSC. METHODS: This was a
prospective, observational study, performed at a community ED. Consecutive
patients who presented to study authors with a chief complaint of headache were
enrolled. Historical/clinical data were collected on a standardized form.
Ninety-five percent confidence intervals (95% CIs) were calculated and Fisher
exact test was used as appropriate. RESULTS: One hundred eighty-nine patients
were enrolled in this study. Mean age was 38 years. Females comprised 69% of
patients. Thirty-seven percent of patients had prior ED visits for headaches. A
positive family history of migraines was present in 35% of patients. Diagnostic
imaging was previously performed in 44 of the enrollees to evaluate the cause of 
their headaches. A total of 43 (23%) patients had a prior diagnosis of migraine. 
Overall CHSC was met in 18% of patients, compared with 15% of patients who met
IHSC. Discharge diagnosis of migraine was made in 41% of patients. Of these
patients, 33% met CHSC and 28% met IHSC (P=.30). For patients with discharge
diagnosis of migraine, 33% of females and 36% of males fit CHSC (P=.53), whereas 
26% and 36% met IHSC (P=.34), respectively. For patients with a prior diagnosis
of migraine, 32% met CHSC and 26% met IHSC (P=.24). Patients with a prior
diagnosis of migraine and/or a discharge diagnosis of migraine met CHSC 31% (95% 
CI, 22%-40%) of the time vs 25% for the IHSC (95% CI, 16%-34%) (P=.26). Four
patients without a discharge and/or previous diagnosis of migraine met CHSC; 3
met IHSC. CONCLUSIONS: In our study population, only a minority of patients with 
headache who have prior diagnosis and/or ED diagnosis of migraine headache met
CHSC. The utility of CHSC and/or IHSC to standardize ED patients for headache
research may be limited.

Publication Types: 
    Comparative Study
    Evaluation Studies

PMID: 15765334 [PubMed - indexed for MEDLINE]

1882: Clin Pharmacokinet. 2005;44(3):237-46.

Clinical pharmacokinetics of almotriptan, a serotonin 5-HT(1B/1D) receptor
agonist for the treatment of migraine.

McEnroe JD, Fleishaker JC.

Clinical Pharmacology Unit, Pharmacia, Inc., Kalamazoo, Michigan, USA.

The pharmacokinetics of almotriptan are linear over a range of oral doses up to
200mg in healthy volunteers. The compound has a half-life of approximately 3
hours. Almotriptan is well absorbed after oral administration and the mean
absolute bioavailability is 69.1%. Maximal plasma concentrations are achieved
between 1.5 and 4 hours after dose administration; however, within 1 hour after
administration, plasma concentrations are approximately 68% of the value at 3
hours after administration. Food does not significantly affect almotriptan
absorption. Almotriptan is not highly protein bound and is extensively
distributed in the body. Approximately 50% of an almotriptan dose is excreted
unchanged in the urine; this is the predominant single mechanism of elimination. 
Renal clearance is mediated, in part, through active tubular secretion, while the
balance of the almotriptan dose is metabolised to inactive compounds. The
predominant route of metabolism is via monoamine oxidase-A, and cytochrome P450
(CYP) mediated oxidation (via CYP3A4 and CYP2D6) occurs to a minor extent.
Almotriptan clearance is moderately reduced in elderly subjects, but the
magnitude of this effect does not warrant a dose reduction. Sex has no
significant effect on almotriptan pharmacokinetics. Almotriptan pharmacokinetic
parameters do not differ between adolescents and adults, and absorption is not
affected during a migraine attack. As expected, renal dysfunction results in
reduced clearance of almotriptan. Patients with moderate-to-severe renal
dysfunction should use the lowest dose of almotriptan and the total daily dose
should not exceed 12.5 mg. Similar dosage recommendations are valid for patients 
with hepatic impairment, based on the clearance mechanisms for almotriptan.
Drug-drug interaction studies were conducted between almotriptan and the
following compounds: fluoxetine, moclobemide, propranolol, verapamil and
ketoconazole. No significant pharmacokinetic or pharmacodynamic interactions with
almotriptan were observed for fluoxetine or propranolol. Almotriptan clearance
was reduced, to a modest degree, by moclobemide and verapamil, which was
consistent with the contribution of monoamine oxidase-A and CYP3A4 to the
metabolic clearance of almotriptan. Although ketoconazole has a greater effect on
almotriptan clearance than verapamil, no dosage adjustment is required when
almotriptan is given with these drugs.

Publication Types: 
    Review

PMID: 15762767 [PubMed - indexed for MEDLINE]

1883: J Neurol. 2005 Sep;252(9):1026-32. Epub 2005 Mar 11.

The use of multiattribute decision models in evaluating triptan treatment options
in migraine.

Ferrari MD, Goadsby PJ, Lipton RB, Dodick DW, Cutrer FM, McCrory D, Williams P.

Dept. of Neurology, Leiden University Medical Centre, 9600, 2300 RC Leiden, The
Netherlands. M.D.Ferrari@LUMC.NL

BACKGROUND : The physician treating patients with migraine is now able to choose 
from among seven triptans-almotriptan, eletriptan, frovatriptan, naratriptan,
rizatriptan, sumatriptan and zolmitriptan. These differ, to greater or lesser
degrees, on a range of clinical attributes important for treatment selection.
OBJECTIVE : To outline the basic principles of Multiattribute Decision Making
(MADM) and describe how one such method-TOPSIS (Technique for Order Preference by
Similarity to the Ideal Solution)-can be applied to evaluate the currently
available triptans. METHODS : In an example application, summary data from a
recent meta-analysis of 53 published and unpublished placebo-controlled trials of
the oral triptans were combined in TOPSIS models with computer-generated
attribute importance weights representing the entire range of possible values,
That is, the relative performance of the triptans was explored across all
logically possible combinations of relative importance of the treatment
attributes available from the meta-analysis, and uncertainty was assessed based
on the confidence intervals from the meta-analysis. RESULTS : When compared
across the entire range of values for relative attribute importance, almotriptan,
eletriptan and rizatriptan were more similar to a hypothetical ideal triptan and 
were more likely to appear in the top three closest to the hypothetical ideal,
than were naratriptan, sumatriptan, and zolmitriptan. CONCLUSION : Using the
TOPSIS model, almotriptan, eletriptan and rizatriptan were more likely to appear 
in the top three closest to the hypothetical ideal triptan.

PMID: 15761676 [PubMed - indexed for MEDLINE]

1884: Braz J Med Biol Res. 2005 Mar;38(3):469-75. Epub 2005 Mar 8.

Effect of Sapindus trifoliatus on hyperalgesic in vivo migraine models.

Arulmozhi DK, Veeranjaneyulu A, Bodhankar SL, Arora SK.

New Chemical Entity Research, Lupin Research Park, Village Nande, Taluk Mulshi,
Pune, Maharashtra, India. adk_bits@yahoo.com

Phytotherapies have offered alternative sources of therapy for migraine and
gained much importance in prophylactic treatment. Sapindus trifoliatus is a
medium-sized deciduous tree growing wild in south India that belongs to the
family Sapindaceae. The pericarp is reported for various medicinal properties. A 
thick aqueous solution of the pericarp is used for the treatment of hemicrania,
hysteria or epilepsy in folklore medicine. We have investigated the
antihyperalgesic effects of the lyophilized aqueous extract of S. trifoliatus in 
animal models predictive of experimental migraine models using morphine
withdrawal-induced hyperalgesia on the hot-plate test and on 0.3% acetic
acid-induced abdominal constrictions in adult male Swiss albino mice. The extract
significantly (N = 10, P < 0.05) increased the licking latency in the hot-plate
test when administered i.p. at 10 mg/kg (6.70 +/- 0.39 s in saline control vs
18.76 +/- 0.96 s in S. trifoliatus-treated animals) and significantly (N = 10, P 
< 0.001) reduced the abdominal constrictions when administered i.p. at 2 and 10
mg/kg (40.20 +/- 1.36 in saline control vs 30.20 +/- 1.33 and 23.00 +/- 0.98 for 
2 and 10 mg/kg, i.p., respectively, in S. trifoliatus-treated animals).
Furthermore, when administered i.p. at 20 and 100 mg/kg, the extract
significantly (N = 10, P < 0.05) inhibited the apomorphine-induced climbing
behavior in mice (climbing duration 15.75 +/- 5.0 min for saline control vs 11.4 
+/- 1.28 and 3.9 +/- 1.71 min for 20 and 100 mg/kg, respectively, in S.
trifoliatus-treated animals). In receptor radioligand-binding studies, the
extract exhibited affinity towards D2 receptors. The findings suggest that
dopamine D2 antagonism could be the mechanism involved in the antihyperalgesic
activity of the aqueous extract of S. trifoliatus.

PMID: 15761628 [PubMed - indexed for MEDLINE]

1885: J Pain Palliat Care Pharmacother. 2004;18(4):31-45.

Serotonin mechanisms in pain and functional syndromes: management implications in
comorbid fibromyalgia, headache, and irritable bowl syndrome - case study and
discussion.

Smith NL.

University of Utah, School of Medicine, USA. smithnlee@aol.com

A young woman presented with multiple central hypersensitivity disorders,
including fibromyalgia, headache, pelvic pain and several smooth muscle spasm
disorders, including irritable bowel syndrome, irritable bladder and Raynaud's
phenomenon. She also had significant fatigue and sleep problems. Her case
illustrates the importance and surprising frequency of atypical bipolar mood
disorders in people with multiple central hypersensitivity pain disorders,
especially with depression and anxiety resistant to antidepressant treatment.
Considering neurological mechanisms common to her overlapping disorders was very 
helpful in guiding treatment choices. This experience illustrates the value of
serotonin receptor type 2 (5HT2) inhibition with atypical neuroleptics, of neural
cation channel and glutamate inhibition with anticonvulsants, and the potential
usefulness of antidepressants after establishing 5HT2 control to enhance downward
inhibitory tracts. Medications with combined usefulness for both bipolar mood and
pain disorders were highly effective for her multiple hypersensitivity problems.

Publication Types: 
    Case Reports

PMID: 15760806 [PubMed - indexed for MEDLINE]

1886: Pediatr Clin North Am. 2005 Feb;52(1):9-24, vii.

Common medical problems of the college student.

Ellen Rimsza M, Kirk GM.

School of Health Services Administration and Policy, Student Health and Wellness 
Center, W.P. Carey School of Business, Arizona State University Main Campus, PO
Box 872104, Tempe, AZ 85287-2104, USA.

The college health physician cares for college students who present with a wide
variety of medical disorders. This article reviews the management of four common 
medical problems: infectious mononucleosis, asthma, migraine headaches, and
urinary tract infections. College students can become ill, and it is important
that they have health care services designed to deal with their health care
issues.

Publication Types: 
    Review

PMID: 15748922 [PubMed - indexed for MEDLINE]

1887: Stud Health Technol Inform. 2004;103:81-92.

Development of an expert system for differentiating tension type headaches from
migraines.

Kopec D, Shagas G, Selman J, Reinharth D, Tamang S.

Department of Computer and Information Science, Brooklyn College, New York, USA.

We created a program, written in the CLIPS language for expert systems, to
distinguish migraines from headaches. The system can be web-based, takes seconds 
to input data and quickly converges to the correct diagnosis. Over time such an
application can result in enormous savings to doctors, patients, and health care 
institutions.

PMID: 15747909 [PubMed - indexed for MEDLINE]

1888: Eur Heart J. 2005 Aug;26(15):1533-7. Epub 2005 Mar 3.

Comment in:
    Eur Heart J. 2005 Dec;26(24):2746-7.    Eur Heart J. 2005 Jul;26(14):1446; author reply 1446-7.    Eur Heart J. 2006 Jul;27(14):1756-7.

The influence of percutaneous atrial septal defect closure on the occurrence of
migraine.

Mortelmans K, Post M, Thijs V, Herroelen L, Budts W.

Department of Cardiology, Internal Medicine, University Hospital Gasthuisberg,
Herestraat 49, B-3000 Leuven, Belgium.

AIMS: Percutaneous patent foramen ovale closure seems to influence migraine. We
wanted to observe the effect of percutaneous atrial septal defect (ASD) closure
on migraine. METHODS AND RESULTS: All patients (>16 years of age) with a
percutaneous ASD closure were selected from our database (n=114). A questionnaire
about headache before and after closure was sent. According to the criteria of
the International Headache Society, two neurologists diagnosed migraine with and 
without aura (MA+ and MA-, respectively). McNemar paired chi(2) and Wilcoxon
signed rank tests were used where applicable. Seventy-five patients (66%, 59
females, mean age 51+/-19 years) responded and were included in the study. An
Amplatzer ASD occluder was used in all. Median follow-up time was 29 months (IQ1 
and IQ3, 18 and 39 months, respectively). The prevalence of MA- and MA+ changed
from 19 (14/75) and 11% (8/75), respectively, before closure to 12 (9/75) and 15%
(11/75), respectively, after closure (P=0.18 and P=0.55, respectively, vs. before
closure). In 12 patients who suffered from migraine before closure (n=4 and 8,
MA+ and MA-, respectively), migraine disappeared. In this subgroup, the frequency
of migraine attacks decreased significantly (P=0.01). New-onset migraine was
noted in 10 patients (n=7 and 3, MA+ and MA-, respectively). CONCLUSION:
Percutaneous ASD closure was not related to a decrease in prevalence of migraine.
In a subgroup, patients who suffered from typical migraine before ASD closure,
the frequency of migraine attacks decreased significantly. The reason for the
new-onset migraine remains unexplained. A larger study sample will be necessary
to determine these findings.

PMID: 15746154 [PubMed - indexed for MEDLINE]

1889: J Biol Chem. 2005 May 6;280(18):17678-86. Epub 2005 Mar 2.

Specific kinetic alterations of human CaV2.1 calcium channels produced by
mutation S218L causing familial hemiplegic migraine and delayed cerebral edema
and coma after minor head trauma.

Tottene A, Pivotto F, Fellin T, Cesetti T, van den Maagdenberg AM, Pietrobon D.

Department of Biomedical Sciences, University of Padova, CNR Institute of
Neuroscience, Viale G. Colombo 3, 35121 Padova, Italy.

Mutation S218L in the Ca(V)2.1 alpha(1) subunit of P/Q-type Ca(2+) channels
produces a severe clinical phenotype in which typical attacks of familial
hemiplegic migraine (FHM) triggered by minor head trauma are followed, after a
lucid interval, by deep (even fatal) coma and long lasting severe cerebral edema.
We investigated the functional consequences of this mutation on human Ca(V)2.1
channels expressed in human embryonic kidney 293 cells and in neurons from
Ca(V)2.1 alpha(1)(-/-) mice by combining single channel and whole cell patch
clamp recordings. Mutation S218L produced a shift to lower voltages of the single
channel activation curve and a consequent increase of both single channel and
whole cell Ba(2+) influx in both neurons and human embryonic kidney 293 cells.
Compared with the other FHM-1 mutants, the S218L shows one of the largest gains
of function, especially for small depolarizations, which are insufficient to open
the wild-type channel. S218L channels open at voltages close to the resting
potential of many neurons. Moreover, the S218L mutation has unique effects on the
kinetics of inactivation of the channel because it introduces a large component
of current that inactivates very slowly, and it increases the rate of recovery
from inactivation. During long depolarizations at voltages that are attained
during cortical spreading depression, the extent of inactivation of the S218L
channel is considerably smaller than that of the wild-type channel. We discuss
how the unique combination of a particularly slow inactivation during cortical
spreading depression and a particularly low threshold of channel activation might
lead to delayed severe cerebral edema and coma after minor head trauma.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 15743764 [PubMed - indexed for MEDLINE]

1890: Curr Neurol Neurosci Rep. 2005 Mar;5(2):93-8.

Menstrual migraine.

Recober A, Geweke LO.

Department of Neurology, Division of Head and Facial Pain, University of Iowa
Hospitals and Clinics, 200 Hawkins Drive, 2 RCP, Iowa City, IA 52242, USA.

Migraine is a common disorder that is disproportionately prevalent in women,
especially during the reproductive years. Hormonal changes may play a role in the
etiology of migraine, as many women note that their migraine attacks occur in
temporal relationship with their menses. The Headache Classification Subcommittee
of the International Headache Society has recently defined menstrual and
menstrually related migraine. We review the most relevant and recent literature
on menstrual migraine, with a special focus on pathophysiology and therapy.
Although the pathogenesis of menstrual and menstrually related migraine is not
well understood, estrogen withdrawal seems to play an important role as a trigger
for menstrual migraine attacks. The therapeutic approach also may differ from the
treatment of nonmenstrual migraine. Some patients do not require prophylaxis when
they can abort their attacks effectively, whereas others may benefit from
perimenstrual prophylaxis or standard migraine prophylaxis.

Publication Types: 
    Review

PMID: 15743545 [PubMed - indexed for MEDLINE]

1891: Curr Neurol Neurosci Rep. 2005 Mar;5(2):86-92.

Migraine headache: options for acute treatment.

Taylor FR.

Headache Clinic and Research Center, Park Nicollet Health Services, 6490
Excelsior Boulevard, Minneapolis, MN 55426, USA. taylof@parknicollet.com

The optimal acute treatment of migraine requires recognition of the multitude of 
migraine presentations, the frequency of total attacks, and number of days of
headache disability. These initial diagnostic steps are initiated in the waiting 
room, but phase-specific and stratified treatment selection requires having
mutual understanding, trust, and belief through extensive discussion. The
imperative acute treatment goal must be to treat early, but not too often, a fact
represented by a 75% or better occurrence of pain freedom at 2 hours with two or 
fewer drug doses averaging 2 or fewer days a week. Migraine-specific therapy best
wins the race against time and allodynia. Employing this formulary, multiple
triptan formulations and phase and stratified patient-centered therapy creates
success.

Publication Types: 
    Review

PMID: 15743544 [PubMed - indexed for MEDLINE]

1892: Acta Neurol Belg. 2004 Dec;104(4):161-4.

Is Helicobacter pylori infection a risk factor for migraine? A case-control
study.

Tunca A, Türkay C, Tekin O, Kargili A, Erbayrak M.

Department of Neurology, Fatih University Medical School, Ankara, Turkey.
etunca@e-kolay.net

BACKGROUND: The relation between Helicobacter pylori and Migraine and usefulness 
of the eradication treatment on headache is controversial. The aim of this study 
was to determine whether Helicobacter pylori infection is a risk factor for
migraine and whether the eradication of the bacterium can reduce frequency,
duration and severity of clinical attacks of the disease. METHODS: A total 70
consecutive patients with migraine with aura and without aura who came to
Gastroenterology polyclinic with various complaints were enrolled in the study
and compared with a group of 60 matched controls. Helicobacter pylori infection
was diagnosed by histopathological biopsies, which was taken by endoscopy
(Olympus-GIFXQ240 endoscope). The diagnosis and classification of migraine was
made according to the International Headache Society (IHS) criteria. We assessed 
the frequency, duration and severity of clinical attacks of migraine before and
after eradication treatment. The eradication control of Helicobacter pylori was
made by Helicobacter pylori fecal antigen test by PCR after 2 months. RESULTS:
Helicobacter pylori positiveness is more relevant in the migranous patients
compared with controls. 84.6% of patients with eradication treatment and 75% of
classically treated patients informed to get benefit from the treatment.
CONCLUSION: Helicobacter pylori should be examined in migranous patients and
eradication of the infection may be helpful for the treatment of the disease.

PMID: 15742606 [PubMed - indexed for MEDLINE]

1893: J Ethnopharmacol. 2005 Mar 21;97(3):491-6.

Pharmacological studies of the aqueous extract of Sapindus trifoliatus on central
nervous system: possible antimigraine mechanisms.

Arulmozhi DK, Veeranjaneyulu A, Bodhankar SL, Arora SK.

New Chemical Entity Research, Lupin Research Park, Village Nande, Taluk Mulshi,
Pune 411 042, Maharashtra, India.

The aqueous extract of pericarp of fruits of Sapindus trifoliatus (ST) Linn.,
family Sapindaceae was evaluated for its potential effects on central nervous
system in mice. The extract at doses 20 and 100 mg/kg, i.p. significantly (p <
0.001) reduced the spontaneous locomotor activity and at 100 mg/kg, increased the
thiopental-induced sleeping time. In rota-rod motor co-ordination test, ST at 100
mg/kg, i.p. significantly (p < 0.05-0.01) reduced the endurance time. Further ST 
exhibited no protection against maximal electroshock (MES)- and
pentylenetetrazole (PTZ)-induced convulsions in mice. In receptor radioligand
binding studies, ST exhibited affinity towards dopaminergic, alpha-adrenergic and
muscarnic receptors. The findings suggest that, ST may possess principles with
potential neuroleptic properties.

Publication Types: 
    Comparative Study

PMID: 15740885 [PubMed - indexed for MEDLINE]

1894: Acta Neurol Scand. 2005 Apr;111(4):233-7.

Headache and transient focal neurological symptoms during pregnancy, a
prospective cohort.

Ertresvåg JM, Zwart JA, Helde G, Johnsen HJ, Bovim G.

Department of Neurology and Clinical Neurosphysiology, St Olavs University
Hospital, Trondheim, Norway.

OBJECTIVE: The main purpose of the present prospective study was to evaluate the 
course of migraine and non-migrainous headache during pregnancy and to estimate
the occurrence of self-reported transient focal neurological symptoms. MATERIAL
AND METHODS: In total 1631 (77%) pregnant women completed the study and were
followed-up during pregnancy. The first questionnaire (Q1) was sent together with
the appointment letter and delivered at the time of ultrasound screening. The
second questionnaire (Q2), to be filled in during pregnancy, was delivered at the
time of birth. Q1 and Q2 covered questions about headache, transient neurological
symptoms, and other background and demographic data. Subjects reporting transient
sensory, motor or visual disturbances were also interviewed by phone in order to 
achieve a more precise description of the symptoms. RESULTS: A total of 58%
subjects with migraine reported not having migraine or no headache at all during 
pregnancy. Among individuals with non-migrainous headache 25% reported not having
any headaches, while 1.9% of the subjects without headache experienced headache
attacks during pregnancy that fulfilled the criteria for migraine. Individuals
without headache or with non-migrainous headache reported significantly less
sensory, motor and visual disturbances during pregnancy compared with migraine
subjects. More than 60% of those with possible aura phenomenon were migraine
patients, while symptoms of peripheral or non-neurological origin were more
common among headache free or those with non-migrainous headache. CONCLUSION:
Transient neurological symptoms were less common among individuals without or
with non-migrainous headache compared with migraine. This may indicate that there
is an increased susceptibility of unknown cause for these symptoms among migraine
patients during pregnancy.

PMID: 15740574 [PubMed - indexed for MEDLINE]

1895: Acta Psychiatr Scand. 2005 Apr;111(4):310-5.

Risk factors associated with migraine or chronic daily headache in out-patients
with major depressive disorder.

Hung CI, Wang SJ, Hsu KH, Juang YY, Liu CY.

Department of Psychiatry, Chang Gung Memorial Hospital and Chang Gung University 
School of Medicine, Taoyuan, Taiwan.

OBJECTIVE: This study investigated independent comorbidities and factors
associated with migraine and chronic daily headache (CDH) in out-patients with
major depressive disorder (MDD). METHOD: Consecutive psychiatric out-patients
fulfilling the DSM-IV criteria of MDD were enrolled. Headaches were diagnosed
based on the criteria proposed by the second edition of the International
Classification of the Headache Disorders. Psychiatric comorbidities were checked 
using the Mini International Neuropsychiatric Interview. Scores of the Hamilton
Depression Rating Scale (HAMD) and duration of major depressive episodes (MDE)
were evaluated. Multivariate logistic regression was used to decide risk factors.
RESULTS: One hundred and fifty-one patients (34 men and 117 women) participated
in the study, among which 73 (48.3%) reported a history of migraine and 32
(21.2%) reported CDH during this MDE. Higher HAMD scores, female gender, and
chronic depression were independently associated with migraine or CDH.
CONCLUSION: For MDD patients with a higher depressive severity and longer
duration of MDE, especially female gender, surveillance of migraine and CDH might
be indicated.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 15740467 [PubMed - indexed for MEDLINE]

1896: Neurology. 2005 Feb 22;64(4):713-5.

Efficacy of coenzyme Q10 in migraine prophylaxis: a randomized controlled trial.

Sándor PS, Di Clemente L, Coppola G, Saenger U, Fumal A, Magis D, Seidel L,
Agosti RM, Schoenen J.

Headache and Pain Unit, Neurology Department, University Hospital Zurich,
Frauenklinikstrasse 26, 8091 Zurich, Switzerland.

Riboflavin, which improves energy metabolism similarly to coenzyme Q10 (CoQ10),
is effective in migraine prophylaxis. We compared CoQ10 (3 x 100 mg/day) and
placebo in 42 migraine patients in a double-blind, randomized, placebo-controlled
trial. CoQ10 was superior to placebo for attack-frequency, headache-days and
days-with-nausea in the third treatment month and well tolerated;
50%-responder-rate for attack frequency was 14.4% for placebo and 47.6% for CoQ10
(number-needed-to-treat: 3). CoQ10 is efficacious and well tolerated.

Publication Types: 
    Clinical Trial
    Comparative Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 15728298 [PubMed - indexed for MEDLINE]

1897: Neurology. 2005 Feb 22;64(4):614-20.

Comment in:
    Neurology. 2005 Nov 22;65(10):1683; author reply 1683.

Cardiovascular risk factors and migraine: the GEM population-based study.

Scher AI, Terwindt GM, Picavet HS, Verschuren WM, Ferrari MD, Launer LJ.

Laboratory of Epidemiology, Demography, and Biometry, National Institute on
Aging, National Institutes of Health, Bethesda, MD, USA. ascher@usuhs.mil

BACKGROUND: Migraine, particularly with aura, is a risk factor for early-onset
ischemic stroke. The underlying mechanisms are unknown, but may in part be due to
migraineurs having an increased risk profile for cardiovascular disease. In this 
study, the authors compare the cardiovascular risk profile of adult migraineurs
to that of nonmigraineurs. METHODS: Participants (n = 5,755, 48% men, age 20 to
65 years) are from the Genetic Epidemiology of Migraine (GEM) study, a
population-based study in the Netherlands. A total of 620 current migraineurs
were identified: 31% with aura (MA), 64% without aura (MO), and 5% unclassified. 
Controls were 5,135 individuals without lifetime migraine. Measured
cardiovascular risk factors included blood pressure (BP), serum total and
high-density lipoprotein cholesterol (TC, HDL), smoking, oral contraceptive use, 
and the Framingham risk score for myocardial infarction or coronary heart disease
(CHD) death. RESULTS: Compared to controls, migraineurs were more likely to smoke
(OR = 1.43 [1.1 to 1.8]), less likely to consume alcohol (OR = 0.58 [0.5 to
0.7]), and more likely to report a parental history of early myocardial
infarction. Migraineurs with aura were more likely to have an unfavorable
cholesterol profile (TC > or = 240 mg/dL [OR = 1.43 (0.97 to 2.1)], TC:HDL ratio 
> 5.0 [OR = 1.64 (1.1 to 2.4)]), have elevated BP (systolic BP > 140 mm Hg or
diastolic BP > 90 mm Hg [OR = 1.76 (1.04 to 3.0)]), and report a history of early
onset CHD or stroke (OR = 3.96 [1.1 to 14.3]); female migraineurs with aura were 
more likely to be using oral contraceptives (OR = 2.06 [1.05 to 4.0]). The odds
of having an elevated Framingham risk score for CHD were approximately doubled
for the migraineurs with aura. CONCLUSIONS: Migraineurs, particularly with aura, 
have a higher cardiovascular risk profile than individuals without migraine.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 15728281 [PubMed - indexed for MEDLINE]

1898: Neurology. 2005 Feb 22;64(4):608-13.

Comment in:
    Neurology. 2005 Feb 22;64(4):592-3.

1H-MRS alterations in the cerebellum of patients with familial hemiplegic
migraine type 1.

Dichgans M, Herzog J, Freilinger T, Wilke M, Auer DP.

Department of Neurology, Klinikum Grosshadern, Ludwig Maximilians University,
Munich, Germany. mdichgans@nefo.med.uni-muenchen.de

BACKGROUND: About 20% of patients with familial hemiplegic migraine (FHM) develop
progressive cerebellar signs. Genetic studies have established an association
with mutations in the CACNA1A gene. However, the mechanisms underlying cerebellar
involvement are largely unknown. OBJECTIVE: To use proton MR spectroscopy
(1H-MRS) to investigate metabolic alterations in the cerebellum as well as
cortical regions known to be involved in the propagation of migraine aura.
METHODS: Fifteen CACNA1A mutation carriers from three FHM families and 17 healthy
control subjects were studied. Eleven patients had clinical signs of cerebellar
involvement. LCModel fits were used to estimate absolute concentrations of
N-acetyl aspartate (NAA), myo-inositol (mI), glutamate (Glu), choline-containing 
compounds, total creatine, and lactate in the superior cerebellar vermis (SCV),
parietal cortex, and occipital cortex. To control for atrophy effects, automated 
image segmentation was performed using SPM99. The brain parenchyma fraction (BPF)
was determined for all three regions. RESULTS: Compared with controls, the brain 
parenchyma fraction (BPF), NAA, and Glu were significantly reduced and mI was
significantly elevated in the SCV of patients with FHM. In contrast, no
metabolite alterations were found in supratentorial regions. BPF and NAA in the
SCV significantly correlated with cerebellar scores, in particular, gait ataxia. 
CONCLUSIONS: The findings suggest that there is a regionally distinct neuronal
impairment in the superior cerebellar vermis that exceeds macroscopic tissue
loss. Correlations with clinical scores emphasize the functional relevance of
localized atrophy (brain parenchyma fraction) and N-acetyl aspartate levels.
These measures may be useful to monitor disease progression. The observed
reduction in glutamate may in part reflect impaired glutamatergic
neurotransmission.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 15728280 [PubMed - indexed for MEDLINE]

1899: Neurology. 2005 Feb 22;64(4):600-7.

Comment in:
    Neurology. 2005 Feb 22;64(4):590-1.

Long-term effects of migraine on cognitive function: a population-based study of 
Danish twins.

Gaist D, Pedersen L, Madsen C, Tsiropoulos I, Bak S, Sindrup S, McGue M,
Rasmussen BK, Christensen K.

Danish Twin Register & Epidemiology, Institute of Public Health, University of
Southern Denmark. dg@dadlnet.dk

OBJECTIVE: To investigate the cognitive functioning of migraineurs vs
nonmigraineurs in a large population-based sample of middle-aged twins where
headache diagnoses were established by neurologists. METHODS: Twins identified
through the population-based Danish Twin Registry participated in face-to-face
structured interviews, which included cognitive tests and two previously
validated questions screening for migraine. Twins who screened positive for
migraine and their co-twins were invited to participate in a telephone-based
interview conducted by neurologists, who established headache diagnoses according
to the International Headache Society criteria. Cognitive scores on fluency,
digit span, delayed word recall, and symbol digit substitution test were compared
between migraineurs and nonmigraineurs. Comparisons within monozygotic and
dizygotic same sex twin pairs discordant for migraine were also performed.
RESULTS: Of the 1,789 twins who were eligible for inclusion in the present study,
1,393 (77.8%) were interviewed. A diagnosis of migraine was established in 536
twins (migraine without aura n = 347; migraine with aura n = 157). Average scores
on cognitive tests in twins with migraine or one of the migraine subtypes did not
differ from those of nonmigraineurs in any of the tests. Comparisons within twin 
pairs discordant for migraine produced highly comparable results. Adjustment for 
possible confounders and stratification by cumulated number of lifetime attacks
did not influence the results. CONCLUSIONS: A lifetime diagnosis of migraine was 
not associated with cognitive deficits in middle-aged subjects.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't
    Twin Study

PMID: 15728279 [PubMed - indexed for MEDLINE]

1900: Ear Nose Throat J. 2004 Dec;83(12):814-5.

Migraine and benign paroxysmal positional vertigo: an outcome study of 476
patients.

Uneri A.

Neurotology and Balance Center, Institute of Neurologic Sciences, Marmara
University, Istanbul, Turkey. cuneri@superonline.com

To investigate whether migraine is more common in patients with benign paroxysmal
positional vertigo (BPPV) than in the general population, the author conducted a 
retrospective study of 476 patients with BPPV seen over 12 years at a tertiary
referral center. Records of patients with a confirmed diagnosis of BPPV followed 
for 1 to 7 years were reviewed. The typical history of BPPV and the
characteristic torsional positional nystagmus were identified in all patients. A 
modified Epley maneuver was performed for all patients with posterior
semicircular canal BPPV, with a 98% success rate. The survey consisted of
detailed patient questionnaires and vestibular tests. Migraine and motion
sickness were three times more common in patients with BPPV than in the general
population. A family history of migraine (58.4%) and vertigo (44.9%) was also
more common in patients than in a control group.

PMID: 15724736 [PubMed - indexed for MEDLINE]

1901: Br J Gen Pract. 2005 Feb;55(511):87-93.

A qualitative study of migraine involving patient researchers.

Belam J, Harris G, Kernick D, Kline F, Lindley K, McWatt J, Mitchell A, Reinhold 
D.

School of Psychology, University of Exeter, Exeter.

BACKGROUND: Migraine is poorly managed in primary care despite a high level of
morbidity. The majority of sufferers use non-prescription medications and are
reluctant to seek help but the reasons for this are not understood. AIM: The aim 
of this study was to develop a research partnership between migraine sufferers
and healthcare professionals to synthesise tacit and explicit knowledge in the
area. Building upon this partnership, a further aim was to explore what it is to 
suffer with migraine from patients' perspectives in order to inform health
service delivery. DESIGN: Qualitative interview study involving healthcare
professionals and patient researchers. SETTING: A purposeful sample of eight
migraine sufferers who had attended a local intermediate care headache clinic.
METHOD: A consensual qualitative approach. RESULTS: Migraine had a high and
unrecognised impact on quality of life. 'Handling the beast' was a central
metaphor that resonated with the experience of all sufferers who sought to
control their problem in different ways. Three major themes were identified:
making sense of their problem; actively doing something about it either through
self-help or professional advice; being resigned to it. CONCLUSION: Despite a
significant impact on the quality of life of migraine sufferers and their
families, their needs remain largely unmet. Useful insights can be obtained when 
patients and professionals work together in true partnership but the time and
effort involved should not be underestimated. Further research is needed to
identify why there are major deficiencies in delivering care in this common
problem.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 15720928 [PubMed - indexed for MEDLINE]

1902: J Am Coll Cardiol. 2005 Feb 15;45(4):493-5.

Comment in:
    J Am Coll Cardiol. 2005 Feb 15;45(4):496-8.

Migraine headache relief after transcatheter closure of patent foramen ovale.

Reisman M, Christofferson RD, Jesurum J, Olsen JV, Spencer MP, Krabill KA, Diehl 
L, Aurora S, Gray WA.

Cardiovascular Research, Swedish Medical Center.

OBJECTIVES: The purpose of this study was to determine the effects of
transcatheter patent foramen ovale (PFO) closure on migraine frequency in
patients with paradoxical cerebral embolism. BACKGROUND: The prevalence of
migraine headache is higher in cryptogenic stroke patients with PFO than in the
general population. Previous studies have suggested that closure of the PFO may
reduce migrainous symptoms. METHODS: Between April 2001 and December 2003, 162
consecutive patients with paradoxical cerebral embolism underwent transcatheter
PFO closure for prevention of recurrent cryptogenic stroke or transient ischemic 
attack. A one-year retrospective analysis of migraine symptoms before and after
PFO closure was performed. RESULTS: Active migraine was present in 35% (57 of
162) of patients, and 68% (39 of 57) experienced migrainous aura; 50 patients
were available for analysis at one year. Complete resolution of migraine symptoms
occurred in 56% (28 of 50) of patients, and 14% (7 of 50) of patients reported a 
significant (>or=50%) reduction in migraine frequency. Patients reported an 80%
reduction in the mean number of migraine episodes per month after PFO closure
(6.8 +/- 9.6 before closure vs. 1.4 +/- 3.4 after closure, p < 0.001). Results
were independent of completeness of PFO closure at one year. CONCLUSIONS: In
patients with paradoxical cerebral embolism, migraine headaches are more frequent
than in the general population, and transcatheter closure of the PFO results in
complete resolution or marked reduction in frequency of migraine headache.

PMID: 15708692 [PubMed - indexed for MEDLINE]

1903: J Am Coll Cardiol. 2005 Feb 15;45(4):489-92.

Comment in:
    J Am Coll Cardiol. 2005 Aug 16;46(4):737-8; author reply 738-9.    J Am Coll Cardiol. 2005 Feb 15;45(4):496-8.

Association of interatrial shunts and migraine headaches: impact of transcatheter
closure.

Azarbal B, Tobis J, Suh W, Chan V, Dao C, Gaster R.

Department of Medicine, University of California Los Angeles, David Geffen School
of Medicine, Los Angeles, California, USA.

OBJECTIVES: To examine the relationship between patent foramen ovale (PFO) or
atrial septal defect (ASD) with the incidence of migraine headache (MHA) and
assess whether closure of the interatrial shunt in patients with MHA would result
in improvement of MHA. BACKGROUND: Migraine headache is present in 12% of adults 
and has been associated with interatrial communications. This study examined the 
relationship between PFO or ASD with the incidence of MHA and assessed whether
closure of the interatrial shunt in patients with MHA would result in improvement
of MHA. METHODS: A sample of 89 (66 PFO/23 ASD) adult patients underwent
transcatheter closure of an interatrial communication using the CardioSEAL (n =
22), Amplatzer PFO (n = 43), or the Amplatzer ASD (n = 24) device. RESULTS:
Before the procedure, MHA was present in 42% of patients (45% of patients with
PFO and 30% of patients with ASD). At three months after the procedure, MHA
disappeared completely in 75% of patients with MHA and aura and in 31% of
patients with MHA without aura. Of the remaining patients, 40% had significant
improvement (>or=2 grades by the Migraine Disability Assessment Questionnaire) of
MHA. CONCLUSIONS: Transcatheter closure of PFO or ASD results in complete
resolution of MHA in 60% of patients (75% of patients with migraine and aura) and
improvement in symptoms in 40% of the remaining patients. Interatrial
communications may play a role in the etiology of MHA either through paradoxic
embolism or humoral factors that escape degradation in bypassing the pulmonary
circulation. A randomized trial is needed to determine whether transcatheter
closure of interatrial shunts is an effective treatment for MHA.

PMID: 15708691 [PubMed - indexed for MEDLINE]

1904: J Affect Disord. 2005 Feb;84(2-3):233-42.

Is migraine in unipolar depressed patients a bipolar spectrum trait?

Oedegaard KJ, Fasmer OB.

Department of Psychiatry, Haukeland Hospital, University of Bergen, N-5021
Bergen, Norway. keti@haukeland.no

BACKGROUND: It is well known that affective disorders and migraine often coexist 
in the same patients, and some information is available indicating that migraine 
is particularly prevalent in bipolar II disorder. The aims of this study were to 
compare the clinical features in unipolar depressed patients with and without
comorbid migraine to bipolar patients. METHODS: Semi-structured interview of 201 
patients with major affective disorders, using DSM-IV criteria for affective
disorders combined with Akiskal's criteria for affective temperaments, and
IHS-criteria for migraine. RESULTS: Compared to the group of patients having
unipolar depressions without comorbid migraine (n = 51) the group with unipolar
depression and migraine (n = 63) had a higher number of depressive episodes (4.5 
vs. 2.5, P = 0.017), significantly higher prevalences of affective temperaments
(46% vs. 16%, P = 0.001), irritability (70% vs. 45%, P = 0.008), seasonal
variation (22% vs. 5%, P = 0.017), agoraphobia (44% vs. 26%, P = 0.036), asthma
(25% vs. 6%, P = 0.006) and migraine in family (59% vs. 29%, P = 0.002). The
clinical features of unipolar depressed patients with comorbid migraine resemble 
the bipolar II patients (n = 51) in this sample. LIMITATIONS: Non-blind,
cross-sectional assessment. CONCLUSIONS: These results indicate that there may be
important clinical differences between unipolar depressed patients with and
without comorbid migraine, possibly indicating that migraine in depressed
patients is a bipolar spectrum trait.

PMID: 15708421 [PubMed - indexed for MEDLINE]

1905: Clin Neurol Neurosurg. 2005 Feb;107(2):82-7.

Comment in:
    Clin Neurol Neurosurg. 2005 Dec;108(1):109-10; reply 111-2.

Migraine-related vertigo: towards a distinctive entity.

Crevits L, Bosman T.

Department of Neurology, Oto-Neuro-Ophthalmology Unit, Ghent University Hospital,
B-9000 Ghent, Belgium. luc.crevits@ugent.be

Both migraine and vertigo are common complaints. Although they may coincide by
chance, there is growing evidence for a clinical entity of recurrent vestibular
symptoms related to migraine. This syndrome implies a possible causal
relationship although the pathophysiology of migraine-related vertigo has not
been fully elucidated. A migrainous aseptic inflammation is thought to create a
central sensitivity that spreads from the trigeminal to the vestibular system.
Diagnostic criteria for migraine-related vertigo are proposed. Treatment is based
on anti-vertiginous drugs for acute interventions and prophylactic measures as
are taken for migraine headaches. Multicenter, prospective controlled studies are
highly warranted.

Publication Types: 
    Review

PMID: 15708220 [PubMed - indexed for MEDLINE]

1906: Brain. 2005 Apr;128(Pt 4):932-9. Epub 2005 Feb 10.

A PET study exploring the laterality of brainstem activation in migraine using
glyceryl trinitrate.

Afridi SK, Matharu MS, Lee L, Kaube H, Friston KJ, Frackowiak RS, Goadsby PJ.

Headache Group, Institute of Neurology and The National Hospital for Neurology
and Neurosurgery, Queen Square, London, UK.

Migraine is a common disabling condition likely to be associated with dysfunction
of brain pathways involved in pain and other sensory modalities. A cardinal,
indeed signature, feature of the disorder that led to its name is that the pain
may be lateralized. H(2)15O-labelled PET was used to study 24 migraineurs and
eight healthy controls. The migraineurs were divided into three groups according 
to the site of their headache: right, left or bilateral. In each group, a
migraine was induced using a glyceryl trinitrate (GTN) infusion. The subjects
were scanned at predefined points: pre-infusion, during GTN, during migraine and 
post-migraine. SPM99 software was used to analyse the data. Significant brainstem
activation was seen in the dorsal lateral pons (P < 0.05 after small volume
correction) during the migraine state versus the pain-free state when comparing
migraineurs with controls. When each group was analysed separately, to
investigate laterality, it was found that the dorsal pontine activation was
ipsilateral in the right-sided and left-sided groups and bilateral in the
bilateral headache group with a left-sided preponderance. Consistent with
previous work, the activation persisted after pain was controlled by sumatriptan.
These results suggest that lateralization of pain in migraine is due to
lateralized brain dysfunction.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 15705611 [PubMed - indexed for MEDLINE]

1907: Headache. 2005 Feb;45(2):166-7.

Migraine, botulinum toxin type-A, and the disappearing sebaceous cyst.

Turner IM, Agrillo T.

Botulinum toxin type-A has been used with increasing frequency as a migraine
prophylactic agent. A recent case of ours had an unexpected beneficial effect on 
a local comorbid condition.

Publication Types: 
    Case Reports
    Letter

PMID: 15705125 [PubMed - indexed for MEDLINE]

1908: Headache. 2005 Feb;45(2):156-62.

Triptan nonresponder studies: implications for clinical practice.

Dodick DW.

Department of Neurology, Mayo Clinic, Scottsdale, Arizona, USA.

The maximum absolute response rate with oral triptans, as measured in clinical
trials by the incidence of relief from migraine pain at 2 hours after taking
medication, is approximately 70%. Therefore around 30% of patients fail to
respond to a particular triptan. Nonresponse is likely to be due to a variety of 
factors, including low and inconsistent absorption, use of the medication late in
an attack, inadequate dosing, and variability in individual response. Evidence
from recent clinical trials, however, confirms the common clinical observation
that patients with a poor response to one triptan can benefit from subsequent
treatment with a different triptan. Two-hour pain-relief rates of 25% to 81%
using alternative triptans (naratriptan, almotriptan, eletriptan, zolmitriptan,
and rizatriptan) have been reported in patients who were described as poor
responders to sumatriptan. Physicians should remain vigilant in assessing the
response to acute therapy and take advantage of simple clinical questionnaires
that have been developed to facilitate the recognition of those patients who
require and may benefit from a change in acute therapy.

Publication Types: 
    Comparative Study

PMID: 15705122 [PubMed - indexed for MEDLINE]

1909: Headache. 2005 Feb;45(2):144-52.

The efficacy and safety of venlafaxine in the prophylaxis of migraine.

Ozyalcin SN, Talu GK, Kiziltan E, Yucel B, Ertas M, Disci R.

Department of Algology, Istanbul, Turkey.

OBJECTIVE: To evaluate the efficacy and safety of venlafaxine in the prophylaxis 
of migraine. BACKGROUND: The efficacy of venlafaxine, which is selectively
effective on the serotonergic and noradrenergic mechanisms, on various headaches 
and chronic pain syndromes has been demonstrated. To our knowledge, this is the
first placebo-controlled, double-blind, randomized study of two different doses
of venlafaxine for migraine treatment. METHODS: In this prospective study, 60
migraine patients without aura were randomly assigned to venlafaxine XR 75 mg,
venlafaxine XR 150 mg, or placebo. The frequency of headache attacks, the
severity and the duration of attacks, and analgesic use were monitored every 2
weeks for 2 months. Adverse events and patient satisfaction were also evaluated
during these visits. At the end of the 2 months, global efficacy and tolerance
were investigated. RESULTS: A significant difference was observed between the
venlafaxine 150 mg and placebo groups in the number of headache attacks (P=
.006). According to patient satisfaction comparisons, the active drug groups were
significantly different when compared with placebo (P= .001 at visit 2 and visit 
6). When the global efficacy was considered, 80% of patients in the 75-mg group
and 88.2% of the patients in the 150-mg group evaluated treatment benefits as
either good or very good. CONCLUSIONS: Venlafaxine was more effective than
placebo and is safe and well tolerated as migraine prophylaxis.

Publication Types: 
    Clinical Trial
    Comparative Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 15705120 [PubMed - indexed for MEDLINE]

1910: Headache. 2005 Feb;45(2):137-43.

Effect of low-intensity acenocoumarol on frequency and severity of migraine
attacks.

Wammes-van der Heijden EA, Smidt MH, Tijssen CC, van't Hoff AR, Lenderink AW,
Egberts AC.

Utrecht Institute for Pharmaceutical Sciences, Pharmacoepidemiology and
Pharmacotherapy, Utrecht, The Netherlands.

OBJECTIVE: To investigate the effect of low-intensity acenocoumarol treatment
(target INR 1.5 to 2.0) on the frequency and severity of migraine attacks.
BACKGROUND: The positive effect of anticoagulation on migraine has been described
in case reports and observational studies. METHODS: We conducted a randomized,
open, crossover study in migraine patients. After a run-in period of 8 weeks, all
patients received acenocoumarol or propranolol during a period of 12 weeks and,
after a washout period of 2 weeks, propranolol or acenocoumarol during a second
period of 12 weeks. RESULTS: Nineteen patients fulfilling the criteria were
included. In 12 patients with complete data collection, only one good responder
could be noted. In the other patients, treatment with low-intensity acenocoumarol
did not show improvement of migraine symptoms compared with the run-in period.
Treatment with propranolol showed a trend towards improvement compared with the
run-in period. No serious adverse events were observed. CONCLUSIONS: Overall,
low-intensity acenocoumarol treatment has no prophylactic effect in migraine
patients.

Publication Types: 
    Clinical Trial
    Comparative Study
    Randomized Controlled Trial

PMID: 15705119 [PubMed - indexed for MEDLINE]

1911: Headache. 2005 Feb;45(2):132-6.

A highly polymorphic poly-glutamine stretch in the potassium channel KCNN3 in
migraine.

Mössner R, Weichselbaum A, Marziniak M, Freitag CM, Lesch KP, Sommer C, Meyer J.

Department of Psychiatry, University of Würzburg, Germany.

Objective: The present study is designed to further elucidate the molecular
genetic basis of migraine with and without aura. BACKGROUND: Migraine is a common
disease of as yet unknown etiology. Interest in ion channels in migraine has been
spurred by molecular genetic findings in familial hemiplegic migraine, since
familial hemiplegic migraine type 1 is caused by mutations in the calcium channel
gene CACNA1A. METHODS: Given this role of ion channels in migraine, we assessed
the potassium channel KCNN3 as a candidate gene for common migraine. We analyzed 
the highly polymorphic repeat region coding for a poly-glutamine stretch, which
constitutes part of the cytoplasmic tail of the channel protein. RESULTS: We
found an excess of the allele coding for 15 poly-glutamines in migraine patients.
CONCLUSIONS: The potassium channel KCNN3 may thus be of pathophysiological
importance in migraine with and without aura.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 15705118 [PubMed - indexed for MEDLINE]

1912: Headache. 2005 Feb;45(2):118-26.

Comment in:
    Headache. 2005 Feb;45(2):103-4.

Clinical characteristics and patterns of medication use of migraneurs in Latin
America from 12 cities in 6 countries.

Morillo LE, Alarcon F, Aranaga N, Aulet S, Chapman E, Conterno L, Estevez E,
Garcia-Pedroza F, Garrido J, Macias-Islas M, Monzillo P, Nunez L, Plascencia N,
Rodriguez C, Takeuchi Y; Latin American Migraine Study Group.

Neuroscience Department, Hospital Universitario de San Ignacio, Bogota, Colombia.
lmorillo@javeriana.edu.co

OBJECTIVE: The objective of this study was to document the clinical
characteristics of migraine and patterns of medication use in residents > or =15 
years old in 12 Latin American urban communities. BACKGROUND: Few large-scale
population studies have established the symptoms and disability associated with
migraine with or without aura in Latin American urban communities or the pattern 
of medication use in these regions. METHODS: In this study, subjects in 12 urban 
communities, from 6 Latin American countries, were surveyed with a validated
face-to-face interview questionnaire based on International Headache Society
criteria for migraine. The questionnaire was completed during face-to-face
interviews with headache sufferers within selected households and included
questions about migraine symptoms, migraine-related disability, and the use of
health-care resources and medications to treat migraines. RESULTS: Of the 8618
people available for screening, 62% suffered from headaches. Of individuals with 
migraine, 42% reported consulting a health-care professional about their
headaches. Of the migraineurs, 94.2% reported moderate to severe pain. Associated
symptoms of nausea or vomiting, photophobia, phonophobia, and osmophobia were
common during migraine attacks in 30.3, 76.4, 85.1, and 47.7% of subjects,
respectively. The majority of subjects suffered between one and eight migraines
each month. Although no previous diagnosis of migraine was reported by 65% of
headache sufferers, migraineurs lost an average of 8 days in the preceding 3
months in any of the following areas: school, work, household chores, and/or
social, family, or leisure activities. The agents used most widely to treat
migraine were paracetamol and salicylates, while nonsteroidal anti-inflammatory
drugs, dypirone, and ergotamines were also commonly used. Medication use varied
widely among countries, but was predominantly nonprescription. CONCLUSIONS:
Migraine is a common disorder in Latin American urban communities imposing
significant burden on individuals, families, and communities. The magnitude of
the impact and the range of activities affected by migraine are similar to those 
of previous reports in other regions. The preponderance of nonprescription
medications and the scarcity of migraine-specific triptans from the study
findings are especially striking.

Publication Types: 
    Multicenter Study
    Research Support, Non-U.S. Gov't

PMID: 15705116 [PubMed - indexed for MEDLINE]

1913: Headache. 2005 Feb;45(2):106-17.

Comment in:
    Headache. 2005 Feb;45(2):103-4.

Prevalence of migraine in Latin America.

Morillo LE, Alarcon F, Aranaga N, Aulet S, Chapman E, Conterno L, Estevez E,
Garcia-Pedroza F, Garrido J, Macias-Islas M, Monzillo P, Nunez L, Plascencia N,
Rodriguez C, Takeuchi Y; Latin American Migraine Study Group.

Neuroscience Department, Hospital University de San Ignacio, Bogota, Colombia.
lmorillo@javeriana.edu.co

OBJECTIVE: To determine the 1-year point prevalence of migraine among residents >
or =15 years old in 12 Latin American urban communities, and record medical
consultation preferences of the identified migraineurs. BACKGROUND: Prevalence of
migraine with or without aura in Latin American urban communities has not been
established by large-scale population studies. METHODS: A validated face-to-face 
interview questionnaire based on International Headache Society criteria was
completed for all headache sufferers within selected households, in a
cross-sectional study. The randomly selected populations were representative of
urban communities from the six participating Latin American countries. The
questionnaire used was identical in each of the six participating countries.
RESULTS: Of the 8618 people available for screening, 62% reported headache and
2637 completed interview questionnaires. Age-adjusted 1-year prevalence of
migraine with or without aura for each country was (female/male, %): Argentina
6.1/3.8, Brazil 17.4/7.8, Colombia 13.8/4.8, Ecuador 13.5/2.9, Mexico 12.1/3.9,
and Venezuela 12.2/4.7. Migraine prevalence was highest in women aged 30 to 50
years. In the year prior to the study, 42% of individuals interviewed and
identified with migraine reported consulting a health professional about their
headaches, most frequently (14%) a general practitioner. No previous diagnosis of
migraine was reported by 65% of individuals with headache. CONCLUSIONS: In
agreement with previous epidemiologic reports, migraine is also a common disorder
in Latin American urban communities and predominantly affects women aged 30 to 50
years. Consultation preferences are also similar to those of previous reports.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 15705115 [PubMed - indexed for MEDLINE]

1914: Eur J Paediatr Neurol. 2005;9(1):23-6. Epub 2004 Dec 25.

Efficacy of flunarizine in the prophylaxis of cyclical vomiting syndrome and
abdominal migraine.

Kothare SV.

Department of Pediatrics, Division of Neurology, St Christopher's Hospital for
Children, Drexel University College of Medicine, Erie Avenue at Front Street,
Philadelphia, PA 19134, USA. sanjeevkothare@drexel.edu

Cyclical vomiting syndrome (CVS), and abdominal migraine (AM) are relatively
unusual periodic syndromes, generally believed to be migraine equivalents, and
are characterized by recurrent and severe paroxysmal episodes of vomiting and/or 
abdominal pain lasting hours to days, separated by weeks to months of no
symptoms. Flunarizine is a calcium channel-blocking agent that has been used
successfully as a prophylactic agent in the prevention of both childhood and
adult-onset migraine syndromes. The purpose of this study was to evaluate the
efficacy of flunarizine as a prophylactic/preventive agent in the treatment of
CVS and AM. Eight children with CVS and 10 children with AM were included in the 
study. The mean dose of flunarizine was 5 mg/day in children with CVS, and 7.5
mg/day in children with AM. Follow-up ranged from 6 to 24 months (mean 13
months). There was a 57% reduction in frequency and 44% reduction in duration of 
attacks of CVS, and a 61% reduction in frequency and 51% reduction in duration of
attacks of AM. Sixty-four percent of patients with CVS and AM had history of
episodic recurrent headaches with 60% reduction in frequency of attacks on
treatment. Flunarizine showed to be equally efficacious than previously tried
therapies in the prophylaxis of a small cohort of patients with CVS and AM.

PMID: 15701563 [PubMed - indexed for MEDLINE]

1915: Curr Med Res Opin. 2004 Dec;20(12):2021-9.

Effects of a fast disintegrating/rapid release oral formulation of sumatriptan on
functional ability in patients with migraine.

Barbanti P, Carpay JA, Kwong WJ, Ahmad F, Boswell D.

Department of Neurological Sciences, La Sapienza University, Rome, Italy.

BACKGROUND: A new oral form of sumatriptan has been developed to facilitate
tablet disintegration and drug dispersion and to mitigate the effects of gastric 
stasis that can accompany migraine. OBJECTIVE: To evaluate the effects on
functional ability of the new fast disintegrating/rapid release formulation of
sumatriptan. METHODS: Sumatriptan 50 mg (n = 137), 100 mg (n = 142), or placebo
(n = 153) was administered early when pain was mild for the acute treatment of a 
single migraine attack in a randomized, double-blind, parallel-group,
placebo-controlled clinical trial. For this report, main health-outcomes
endpoints (which were secondary endpoints for this clinical trial that was
primarily designed to assess pain-free efficacy) included functional ability
measured through 2 h postdose on a 5-point scale and lost time equivalents, a
composite measure of migraine-associated time missed from activities, and reduced
effectiveness at activities through 24 h postdose. RESULTS: Normal functional
ability was restored in a significantly (p < 0.05) greater percentage of patients
treated with sumatriptan than placebo beginning 45 min postdose for sumatriptan
100 mg and 1 h postdose for sumatriptan 50 mg. During the 24 h after initial
dosing, the median (range) lost time equivalents for the combination of paid work
activities and activities outside of paid work were significantly lower in the
groups treated with sumatriptan (1.1 [0-10] sumatriptan 100 mg; 0.8 [0-36]
sumatriptan 50 mg) compared with placebo (2.9 [0-24]) (p < or = 0.01 each
sumatriptan group versus placebo). The corresponding mean +/- SD values for lost 
time equivalents were 1.9 +/- 2.3 and 2.5 +/- 4.7 for sumatriptan 100 mg and 50
mg, respectively, compared with 3.5 +/- 4.3 for placebo. CONCLUSION: A new oral
sumatriptan formulation confers rapid, sustained restoration of functional
ability in the acute treatment of migraine so that patients can return rapidly to
normal functioning at work and outside of work.

Publication Types: 
    Clinical Trial
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 15701219 [PubMed - indexed for MEDLINE]

1916: Neurology. 2005 Feb 8;64(3):561-3.

Predicting menstrual migraine with a home-use fertility monitor.

MacGregor EA, Frith A, Ellis J, Aspinall L.

The City of London Migraine Clinic, 22 Charterhouse Square, London, EC1M 6DX, UK.
anne.macgregor@bartsandthelondon.nhs.uk

A home-use fertility monitor was used to time perimenstrual prophylaxis in 27
women with menstrual or menstrually related migraine. Cycle length variability
was mostly caused by follicular phase variability; the postovulatory luteal phase
was relatively constant. The monitor accurately identified ovulation in >90% of
cycles, enabling prediction of menstruation and precise timing of perimenstrual
prophylaxis. Ninety-seven percent of women found the monitor useful in predicting
menstrual migraine attacks.

Publication Types: 
    Evaluation Studies
    Research Support, Non-U.S. Gov't

PMID: 15699399 [PubMed - indexed for MEDLINE]

1917: Neurology. 2005 Feb 8;64(3):463-8.

Comment in:
    Neurology. 2005 Oct 25;65(8):1339-40; author reply 1339-40.    Neurology. 2005 Oct 25;65(8):1339-40; author reply 1339-40.

A trial of metoclopramide vs sumatriptan for the emergency department treatment
of migraines.

Friedman BW, Corbo J, Lipton RB, Bijur PE, Esses D, Solorzano C, Gallagher EJ.

Department of Emergency Medicine, Albert Einstein College of Medicine, Montefiore
Medical Center, 111 E. 210 St., Bronx, NY 10467, USA. befriedm@montefiore.org

OBJECTIVE: To compare the efficacy of 20 mg of IV metoclopramide, given up to
four times over 2 hours as needed for persistent headache, with 6 mg of
subcutaneous sumatriptan for the emergency department treatment of migraine
headaches. METHODS: This was a randomized, double-blind, clinical trial with two 
intervention arms. The primary endpoint was change in pain intensity as measured 
by an 11-point pain scale at 2 hours. Secondary endpoints included change in pain
intensity at 24 hours and rates of pain-free headache relief at 2 and 24 hours.
RESULTS: Two hundred two patients were screened, and 78 of 91 eligible patients
were randomized. The two groups had comparable pain scores at baseline. By 2
hours, the change in pain intensity for the metoclopramide group was 7.2 compared
with 6.3 for the sumatriptan group (95% CI for difference: -0.2 to 2.2). When
compared at 24 hours, the metoclopramide group had improved by 6.1 compared with 
baseline and the sumatriptan group had improved by 5.0 (95% CI for difference:
-0.6 to 2.8). At 2 hours, pain-free rates were 59% in the metoclopramide arm and 
35% in the sumatriptan arm (95% CI for difference of 24%: 2 to 46%). The most
common side effects at both time points were weakness, dizziness, and drowsiness,
which were distributed evenly between the two groups. There were no reports of
chest pain within the first 2 hours. The incidence of restlessness, stiffness,
and abnormal movements was distributed equally between the two groups.
CONCLUSIONS: When compared at 2 and 24 hours, aggressive (20 mg dosed up to four 
times) IV metoclopramide and 6 mg of subcutaneous sumatriptan relieved migraine
headache pain comparably. Some secondary endpoints suggest that metoclopramide
may be the preferable therapy for migraines presenting to the emergency
department.

Publication Types: 
    Clinical Trial
    Comparative Study
    Randomized Controlled Trial

PMID: 15699376 [PubMed - indexed for MEDLINE]

1918: Proc Natl Acad Sci U S A. 2005 Feb 15;102(7):2590-5. Epub 2005 Feb 7.

Effects of familial hemiplegic migraine type 1 mutations on neuronal P/Q-type
Ca2+ channel activity and inhibitory synaptic transmission.

Cao YQ, Tsien RW.

Department of Molecular and Cellular Physiology, Beckman Center, Stanford
University School of Medicine, Stanford, CA 94305-5345, USA.

Inhibitory synapses play key roles in the modulatory circuitry that regulates
pain signaling and generation of migraine headache. A rare, dominant form of this
common disease, familial hemiplegic migraine type 1 (FHM1), arises from missense 
mutations in the pore-forming alpha1A subunit of P/Q-type Ca2+ channels. These
channels are normally vital for presynaptic Ca2+ entry and neurotransmitter
release at many central synapses, raising questions about effects of FHM1
mutations on neuronal Ca2+ influx and inhibitory and excitatory
neurotransmission. We have expressed the four original FHM1 mutant channels in
hippocampal neurons from alpha1A knockout mice. Whole-cell recordings indicated
that FHM1 mutant channels were less effective than wild-type channels in their
ability to conduct P/Q-type current, but not generally different from wild type
in voltage-dependent channel gating. Ca2+ influx triggered by action potential
waveforms was also diminished. In keeping with decreased channel activity, FHM1
mutant channels were correspondingly impaired in supporting the P/Q-type
component of inhibitory neurotransmission. When expressed in wild-type inhibitory
neurons, FHM1 mutant channels reduced the contribution of P/Q-type channels to
GABAergic synaptic currents, consistent with a competition of mutant and
endogenous channels for P/Q-specific slots. In all cases, N-type channels took up
the burden of supporting transmission and homeostatic mechanisms maintained
overall synaptic strength. The shift to reliance on N-type channels greatly
increased the susceptibility to G protein-coupled modulation of
neurotransmission, studied with the GABAB agonist baclofen. Thus,
mutant-expressing synapses might be weakened in a heightened state of
neuromodulation like that provoked by triggers of migraine such as stress.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 15699344 [PubMed - indexed for MEDLINE]

1919: Psychiatry Res. 2005 Jan 30;133(1):101-6.

Frontal lobe dysfunction in patients with chronic migraine: a
clinical-neuropsychological study.

Mongini F, Keller R, Deregibus A, Barbalonga E, Mongini T.

Department of Clinical Pathophysiology, Headache and Facial Pain Unit, University
of Turin, 14 Corso Dogliotti, I-10126 Torino, Italy. franco.mongini@unito.it

Neuropsychological tests have demonstrated a frontal lobe dysfunction in several 
psychiatric and neurological disorders. Our purpose was to examine whether
similar functional differences would be found in patients with chronic migraine. 
The Gambling Task (GT), the Tower of Hanoi-3 (TOH-3) and the Object Alternation
Test (OAT) were administered to 23 female patients previously treated for chronic
migraine and to 23 healthy women who were similar to the patients in age and
educational level, and the mean test scores of the two groups were compared
(Student's t and Pearson correlation coefficient). The patient group scored
significantly higher than the controls on the TOH-3 and, especially, the OAT. In 
the patients, no significant relationship was found between the
neuropsychological test scores and those for the Minnesota Multiple Personality
Inventory (MMPI), the Spielberg State-Trait Anxiety Inventory (STAI), and the
Beck Depression Inventory (BDI). In conclusion, the data suggest a relation
between chronic headache and dorsolateral function (as tested by the TOH-3) and
orbitofrontal function (as tested by the OAT). The decision-making function
related to ventromedial prefrontal cortex (tested by the GT) did not show a
statistically significant difference between patients and controls. These
neuropsychological findings seem to be partly independent of the patient's
psychological traits and psychiatric disorders.

Publication Types: 
    Comparative Study

PMID: 15698682 [PubMed - indexed for MEDLINE]

1920: Med J Aust. 2005 Feb 7;182(3):103-4.

Is migraine a progressive disorder? Considering the clinical implications of new 
research data on migraine and brain lesions.

Goadsby PJ.

Considering the clinical implications of new research data on migraine and brain 
lesions.

Publication Types: 
    Editorial
    Review

PMID: 15698351 [PubMed - indexed for MEDLINE]

1921: CNS Drugs. 2005;19(2):125-36.

Speed of onset, efficacy and tolerability of zolmitriptan nasal spray in the
acute treatment of migraine: a randomised, double-blind, placebo-controlled
study.

Dodick D, Brandes J, Elkind A, Mathew N, Rodichok L.

Department of Neurology, Mayo Clinic College of Medicine, Scottsdale, Arizona
85259, USA. Dodick.David@mayo.edu

INTRODUCTION: Migraine is a common, disabling condition that has a significant
impact on patients and relatives, and is a considerable economic burden on
society. Migraine patients want fast-acting treatments with high efficacy.
Previous studies have demonstrated that orally administered formulations of
zolmitriptan are rapidly and highly effective in the acute treatment of migraine.
The objective of this study was to assess the efficacy, speed of onset and
tolerability of the nasal spray formulation of zolmitriptan in migraine
treatment. METHODS: This multicentre, randomised, double-blind study recruited
2122 patients (aged 18-65 years) who had an established diagnosis of migraine
(according to International Headache Society criteria), with or without aura.
Patients were randomised to receive zolmitriptan 5mg nasal spray or placebo to
treat up to two migraine attacks within 15 minutes of headache pain becoming
moderate or severe. The primary endpoint was headache response (reduction in
migraine pain from severe/moderate to mild/none) at 2 hours, 1 hour, 30 minutes
and 15 minutes post-dose (analysed using a step-down approach). Secondary
endpoints included headache response at 4 hours, pain-free rates at 30 minutes
and 1, 2 and 4 hours, and sustained headache response and pain-free status at 24 
hours post-dose. RESULTS: The headache response rate at 2 hours post-dose was
66.2% for the zolmitriptan group, compared with 35.0% for the placebo group (p < 
0.001). Zolmitriptan nasal spray also produced significantly higher headache
response rates than placebo at all earlier timepoints assessed, starting as early
as 15 minutes post-dose (p < 0.001). Similar results were obtained for the
analysis of the first attack. Significantly higher pain-free rates were obtained 
with zolmitriptan nasal spray, compared with placebo, from 15 minutes post-dose
onward (p < 0.005). Zolmitriptan nasal spray was also significantly superior to
placebo for headache response at 4 hours, sustained headache response at 24 hours
and sustained pain-free rate at 24 hours.Zolmitriptan nasal spray was well
tolerated, with most adverse events being of short duration and mild or moderate 
intensity. CONCLUSIONS: Zolmitriptan nasal spray is highly effective in the acute
treatment of migraine and has a very fast onset of action, producing significant 
headache response and pain-free rates as early as 15 minutes post-dose (the
earliest assessment in this study). In addition to the very fast onset of action,
zolmitriptan nasal spray produced significantly higher sustained headache
response and pain-free rates at 24 hours post-dose compared with placebo. These
desirable efficacy outcomes were combined with good tolerability.

Publication Types: 
    Clinical Trial
    Comparative Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 15697326 [PubMed - indexed for MEDLINE]

1922: J Neurol Sci. 2005 Feb 15;228(2):149-53. Epub 2004 Dec 24.

Monoamine oxidases A and B gene polymorphisms in migraine patients.

Filic V, Vladic A, Stefulj J, Cicin-Sain L, Balija M, Sucic Z, Jernej B.

Laboratory of Neurochemistry and Molecular Neurobiology, Dept. of Molecular
Biology, Rudjer Boskovic Institute, Bijenicka 54, Zagreb HR-10000, Croatia.

Abnormal cortical activity and brainstem functioning are considered the possible 
etiopathogenetic factors of migraine. Monoamine oxidase A and B (MAO-A and -B)
regulate the levels of monoamine neurotransmitters, so changes in their activity 
could participate in migraine pathogenesis. We have investigated the possible
association of MAO-A and -B alleles and haplotypes with two common types of
migraine, i.e. migraine without aura (MO) and migraine with aura (MA), on the
sample of 110 migraineours (80 MO and 30 MA) and 150 controls. MAO-A promoter and
MAO-B intron 13 polymorphisms were genotyped by the PCR-based methods. In
addition, we have reevaluated the reported association between MAO-B intron 13
polymorphism and platelet MAO-B activity. The platelet MAO-B activity was
determined fluorimetrically using kynuramine as a substrate. We have found a
tendency toward association of the shorter variant of MAO-A gene promoter with
migraine without aura in male subjects. Regarding investigated MAO-B
polymorphism, no association with migraine or with platelet MAO-B activity was
found. The suggestive association of the variant in MAO-A gene with migraine is
considered worthy of independent replication. On the other hand, further studies 
on MAO-B polymorphism in migraine do not seem promising.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 15694196 [PubMed - indexed for MEDLINE]

1923: J Clin Neurophysiol. 2005 Jan-Feb;22(1):65-7.

Cortical hyperexcitability in migraine patients before and after sodium valproate
treatment.

Bowyer SM, Mason KM, Moran JE, Tepley N, Mitsias PD.

Henry Ford Health System, Detroit, Michigan, USA. drsusan@umich.edu

DC-magnetoencephalography (DC-MEG)waveforms arising during migraine aura were
used to determine the effectiveness of prophylactic medication therapy on
neuronal hyperexcitability. Nine patients were prescribed valproate (Depakote)
for migraine prophylaxis. MEG scans were recorded during visual stimulation
before commencing medication and again after 30 days of daily use of valproate.
Cortical brain activity was recorded during stimulation with a black-and-white
circular checkerboard pattern alternating at 8 Hz and were analyzed with
MR-FOCUSS. Large-amplitude DC-MEG signals, imaged to extended areas of occipital 
cortex, were seen before therapy. After 30 days of prophylactic treatment,
reduced DC-MEG shifts in the occipital cortex and reduced incidence of migraine
attacks were observed. Using visual stimulation, the authors demonstrated the
hyperexcitability of widespread regions throughout occipital cortex in migraine
patients, explaining the susceptibility for triggering spreading cortical
depression and migraine aura. This study confirms that MEG can noninvasively
determine the status of neuronal excitability before and after therapy. This
finding may be helpful in determining which prophylactic medications will be most
effective in reducing hyperexcitability in particular patients.

Publication Types: 
    Clinical Trial
    Comparative Study
    Research Support, U.S. Gov't, P.H.S.

PMID: 15689715 [PubMed - indexed for MEDLINE]

1924: Cephalalgia. 2005 Mar;25(3):219-24.

Painful stimulation of the temple during optokinetic stimulation triggers
migraine-like attacks in migraine sufferers.

Granston A, Drummond PD.

School of Psychology, Murdoch University, Western Australia.

To determine whether motion sickness induced by optokinetic stimulation would
trigger migraine-like attacks, 27 migraine sufferers and 23 controls attended the
laboratory up to three times at intervals of at least 3 weeks. On one occasion
subjects experienced up to 15 min of optokinetic stimulation, followed by three
30-s applications of ice to the temple at 4-min intervals. On another occasion,
the ice applications preceded and accompanied optokinetic stimulation. On a third
occasion, one hand was immersed in ice water for 30 s, three times at 4-min
intervals before and during optokinetic stimulation. Subjects recorded headache
activity in a diary over the course of the study. None of the controls
experienced a migraine-like attack at any stage of the experiment. In migraine
sufferers, the incidence of migraine-like attacks was greater than the expected
daily incidence of 8% after sessions that involved painful stimulation of the
temple during or after optokinetic stimulation (44% and 28% of the group,
respectively) (P<0.001). In contrast, migraine-like attacks developed in only 13%
of migraine sufferers after the session that involved immersing the hand in ice
water during optokinetic stimulation (not significant). The development of nausea
and headache during optokinetic stimulation increased the likelihood of
migraine-like attacks afterwards. These findings indicate that motion sickness
and head pain increase susceptibility to migrainous attacks in migraine
sufferers, and suggest that the symptoms of migraine build upon each other in a
vicious circle. Thus, targeting multiple symptoms should be more effective than
targeting individual symptoms, both for preventing and treating attacks of
migraine.

Publication Types: 
    Clinical Trial
    Controlled Clinical Trial
    Research Support, Non-U.S. Gov't

PMID: 15689198 [PubMed - indexed for MEDLINE]

1925: Cephalalgia. 2005 Mar;25(3):214-8.

Patterns of specific antimigraine drug use--a study based on the records of 18
community pharmacies.

Lohman JJ, van der Kuy-de Ree MM; the Group of Co-operating Pharmacists
Sittard-Geleen and its environs.

Department of Clinical Pharmacy, Maasland Hospital, Sittard, the Netherlands.
j.lohman@orbisconcern.nl

The objective of this study was, first, to characterize the usage patterns of
specific antimigraine drugs, and second, to compare these in patients with one
type of drug with patients with two or more types of drug. Dispensing data on
triptans and ergotamine were collected from community pharmacy records over a
1-year period. In a population of approximately 168,000 specific antimigraine
medication has been dispensed to 2343 patients (1.4%). Oral dosage forms were
prescribed in most prescriptions (77.1%), subcutaneous injections in 9.7%, rectal
suppositories in 7.1% and nasal sprays in 6.1%. We identified 292 patients
(12.5%) to whom more than one type of drug was dispensed. Multiple drugs patients
showed significantly higher drug consumption and deviating patterns of specific
antimigraine drug usage, receiving significantly more non-oral dosage forms
(32.8% vs. 20.4%, P<0.001). Our data indicate substantially suboptimal treatment 
of migraine patients.

PMID: 15689197 [PubMed - indexed for MEDLINE]

1926: Cephalalgia. 2005 Mar;25(3):199-204.

A randomized prospective placebo-controlled study of intravenous magnesium
sulphate vs. metoclopramide in the management of acute migraine attacks in the
Emergency Department.

Cete Y, Dora B, Ertan C, Ozdemir C, Oktay C.

Department of Emergency Medicine, Akdeniz University School of Medicine, Antalya,
Turkey. ycete@akdeniz.edu.tr

The objective of this randomized, placebo-controlled, double-blind study was to
determine the effectiveness of intravenous magnesium sulphate and intravenous
metoclopramide in the treatment of acute migraine attacks in the Emergency
Department when compared with placebo. Adult patients who presented to the
Emergency Department with a headache that met International Headache Society
(IHS) criteria for acute migraine were infused with either 10 mg of intravenous
metoclopramide, 2 g of intravenous magnesium sulphate or normal saline over 10
min. At 0, 15, and 30 min, patients were asked to rate their pain on a standard
visual analogue scale. At 30 min, patients were asked in a standard manner about 
the need for rescue medication. Adverse affects were also recorded. Patients were
followed up by telephone within 24 h for any recurrence after discharge. The
primary endpoint of the study was the difference in pain relief between the
groups at 30 min. Of the 120 patients who met IHS criteria, seven were excluded
from the study due to insufficient data. The number of patients, gender, age and 
initial visual analogue scale (VAS) scores were comparable between groups. Each
group experienced more than a 25-mm improvement in VAS score at 30 min. However, 
there was no significant difference detected in the mean changes in VAS scores
for pain. The rescue medication requirement was higher in the placebo group. The 
recurrence rate in 24 h was similar between the groups. Although patients
receiving placebo required rescue medication more than the others, metoclopramide
and magnesium have an analgesic effect similar to placebo in migraine attacks.

Publication Types: 
    Clinical Trial
    Comparative Study
    Randomized Controlled Trial

PMID: 15689195 [PubMed - indexed for MEDLINE]

1927: Cephalalgia. 2005 Mar;25(3):184-90.

Recognition and management of migraine in primary care: influence of functional
impact measured by the headache impact test (HIT).

De Diego EV, Lanteri-Minet M.

Department of Evaluation and Treatment of Pain, Hospital Pasteur, Nice, France.

The objective of the present study was to investigate the influence of
headache-related disability on the recognition and management of migraine by
French general practitioners (GPs). Forty-nine teaching GPs at the Faculty of
Medicine in the Nice-Sophia-Antipolis University were involved in this study. On 
one day, each patient who presented during the surgery hours of these GPs was
invited to complete a questionnaire aimed at identifying if he/she was a headache
sufferer and, if so, whether the headache corresponded to migraine and had an
impact on his/her functional ability. Functional disability was measured by the
short-form of the Headache Impact Test (HIT-6). Being blind to the patients'
responses, the GPs completed a questionnaire for each patient aimed at
identifying if he/she considered the patient to suffer from migraine and, if so, 
whether he/she managed the patient for migraine. A total of 696 patients were
included in this study and 289 (41.52%) of them had episodic headache. According 
to the new International Headache Society (IHS) criteria, 113 (16.24%) patients
suffered from headache without migrainous features and 176 (25.29%) patients were
migraine sufferers (migraine according to IHS categories 1.1 and 1.2.1: 11.21%,
and probable migraine according to IHS categories 1.6.1 and 1.6.2: 14.08%). The
mean HIT score of these migraine sufferers was 59.1+/-8.8 and 50% of them
presented with a very severe impact score (HIT score>60). Among the 176 migraine 
sufferers, 105 (59.7%) were not recognized as having migraine, 21 (11.9%) were
recognized as having migraine but without migraine management and 50 (28.4%) were
recognized as having migraine with migraine management. Recognition of migraine
by GPs was statistically associated with the HIT score (OR=1.105, 95% CI:
1.056-1.157, P<0.001) and with the 1.1 and 1.2.1 IHS diagnostic categories
(OR=2.942, 95% CI: 1.286-5.025, P=0.0107) whereas management of patients
recognized as having migraine was only associated with the patient's age
(OR=1.051, 95% CI: 1.000-1.104, P=0.0486). These results indicate that the
continuing medical education of GPs should focus on the diagnosis of migraine and
its impact on the lifestyle of the patient.

Publication Types: 
    Clinical Trial

PMID: 15689193 [PubMed - indexed for MEDLINE]

1928: Cephalalgia. 2005 Mar;25(3):179-83.

Sumatriptan causes parallel decrease in plasma calcitonin gene-related peptide
(CGRP) concentration and migraine headache during nitroglycerin induced migraine 
attack.

Juhasz G, Zsombok T, Jakab B, Nemeth J, Szolcsanyi J, Bagdy G.

Laboratory of Neurochemistry and Experimental Medicine, and Department of
Vascular Neurology, Faculty of Medicine, Semmelweis University, National
Institute of Psychiatry and Neurology, Budapest, Hungary.

Sumatriptan-induced changes in plasma calcitonin gene-related peptide (CGRP)
concentration and headache intensity were investigated in 19 female migraineurs
during nitroglycerin-induced migraine attack. Sumatriptan nasal spray was
administered 120 min after the onset of the attack. Blood samples were obtained
immediately before and 60 min after sumatriptan administration. In those subjects
whose migraine attack improved considerably 60 min after the treatment the plasma
CGRP concentration decreased significantly (P<0.05). In contrast, plasma CGRP
concentration failed to change in patients whose headache did not improve. In
addition, plasma CGRP concentrations showed significant positive correlations
with the headache scores both 60 and 120 min after sumatriptan administration
(P<0.05). According to our results plasma CGRP concentration decreases parallel
to headache intensity during sumatriptan treatment and this decrease in CGRP
predicts effectiveness of antimigraine drug therapy. This supports that one of
the main effects of triptans is to decrease CGRP release.

Publication Types: 
    Clinical Trial
    Controlled Clinical Trial
    Research Support, Non-U.S. Gov't

PMID: 15689192 [PubMed - indexed for MEDLINE]

1929: Cephalalgia. 2005 Mar;25(3):165-78.

Comment in:
    Cephalalgia. 2005 Nov;25(11):1099-100.

Psychiatric comorbidity in migraine: a review.

Radat F, Swendsen J.

Chronic Pain Treatment Unit, Centre Hospitalo-universitaire, Bordeaux, France.
francoise.radat@chu-bordeaux.fr

Investigations of migraine comorbidity have confirmed its association with
diverse psychiatric conditions. This association appears to be strongest for
major depression and anxiety disorders (particularly panic and phobia), but
increased comorbidity has also been reported with substance abuse and certain
mood disorders. This literature also indicates that greater psychiatric
comorbidity exists for migraine sufferers with aura than without. Some support is
found for the notion that psychiatric comorbidity is higher in transformed
migraine than in simple migraine (particularly in the case of chronic substance
abuse). However, research into the possible mechanisms underlying these
associations remains limited. Studies examining the order of onset and the
cross-transmission of migraine and psychiatric disorders in families have been
unable to distinguish fully between causal and common aetiological models of
association. The conclusions are discussed in light of both methodological and
conceptual issues relevant to understanding migraine comorbidity.

PMID: 15689191 [PubMed - indexed for MEDLINE]

1930: Eur J Pharmacol. 2005 Jan 31;508(1-3):231-8. Epub 2005 Jan 6.

Evaluation of the anti-emetic potential of anti-migraine drugs to prevent
resiniferatoxin-induced emesis in Suncus murinus (house musk shrew).

Cheng FH, Andrews PL, Moreaux B, Ngan MP, Rudd JA, Sam TS, Wai MK, Wan C.

Emesis Research Group, Department of Pharmacology, Faculty of Medicine, The
Chinese University of Hong Kong, Shatin, New Territories, Hong Kong SAR, China.

Activation of vanilloid receptors has commonly been used to facilitate neurogenic
inflammation and plasma exudation to model components of the pathogenesis of
migraine; however, these studies have been performed mainly in species lacking
the emetic reflex. In the present studies, therefore, we used Suncus murinus, a
species of insectivore capable of emesis, to investigate if the vanilloid
receptor agonist resiniferatoxin is capable of modeling the emesis associated
with migraine. Resiniferatoxin (100 nmol/kg, s.c.) induced an emetic response
that was antagonized significantly (P<0.05) by ruthenium red (1-3 micromol),
(2R-trans)-4-[1-[3,5-bis(trifluromethyl)benzoyl]-2-(phenylmethyl)-4-piperidinyl]-
N-(2,6-dimethylphenyl)-1-acetamide (S)-hydroxybutanedioate (R116301; 10-100
micromol/kg), and scopolamine (1 micromol/kg), but not by dihydroergotamine
(0.3-3 micromol/kg), sumatriptan (1-10 micromol/kg), methysergide (1-10
micromol/kg), tropanyl 3,5-dichlorobenzoate (MDL72222; 3-30 micromol/kg),
ondansetron (0.3-3 micromol/kg), metoclopramide (3-30 micromol/kg), domperidone
(3-30 micromol/kg), diphenhydramine (1-10 micromol/kg), or indomethacin (3-30
micromol/kg). The failure of a wide range of representative anti-migraine drugs
to reduce retching and vomiting limits the use of this model to
identify/investigate novel treatments for the emesis (and nausea) associated with
migraine attacks in humans. However, the results provide further evidence for the
involvement of a novel vanilloid receptor in resiniferatoxin-induced emesis and
implicate both tachykinins and acetylcholine in the pathway(s) activated by
resiniferatoxin in S. murinus.

Publication Types: 
    Comparative Study

PMID: 15680276 [PubMed - indexed for MEDLINE]

1931: Eur J Neurol. 2005 Feb;12(2):108-17.

Patient preference for eletriptan 80 mg versus subcutaneous sumatriptan 6 mg:
results of a crossover study in patients who have recently used subcutaneous
sumatriptan.

Schoenen J, Pascual J, Rasmussen S, Sun W, Sikes C, Hettiarachchi J.

Department of Neurology, University of Liège, CHR Citadelle, Boulevard du
XIIemede Ligne, 1-B-4000 Liège, Belgium. jean.schoenen@chrcitadelle.be

This current randomized, open-label, crossover study evaluated preference for
oral eletriptan 80 mg compared with subcutaneous sumatriptan 6 mg (suma-sc)
amongst patients (n = 311) meeting IHS criteria for migraine who had recently
used suma-sc, and found it well tolerated. Three attacks were treated on each
study medication. Assessment of subjective preference was evaluated, after which 
patients freely chose which study medication they wished to use to treat each of 
three additional migraine attacks. A slight majority (50.6%) preferred or greatly
preferred eletriptan, whilst 43% preferred suma-sc. When permitted to choose
between eletriptan and suma-sc for subsequent treatment, 78% of patients who had 
preferred eletriptan took eletriptan during the extension phase for all three of 
their attacks, whilst only 37% of patients who preferred suma-sc took suma-sc for
all of their extension-phase attacks (P < 0.05). Secondary efficacy measures
showed comparable efficacy for each study medication, except for faster headache 
response and pain-free rates favor of suma-sc, and a significantly lower
recurrence rate on eletriptan (25% vs. 40%; P < 0.05). The results of this study 
suggest that eletriptan is a strong alternative option for patients who have been
prescribed suma-sc.

Publication Types: 
    Clinical Trial
    Comparative Study
    Multicenter Study
    Randomized Controlled Trial

PMID: 15679698 [PubMed - indexed for MEDLINE]

1932: South Med J. 2005 Jan;98(1):23-7.

The clinical properties of a migrainous population in eastern Turkey-Erzurum.

Aygül R, Deniz O, Koçak N, Orhan A, Ulvi H.

Department of Neurology, Atatürk University Faculty of Medicine, Erzurum, Turkey.
raygul@atauni.edu.tr

OBJECTIVES: The purpose of this study was to determine the clinical and
demographic characteristics of patients with migraine headache, in the vicinity
of Erzurum, Turkey. METHODS: A uniform questionnaire was given to 185 patients
diagnosed as having migraine according to the International Headache Society
diagnostic criteria between August 2001 and July 2002. One hundred forty five
females (78.4%) and 40 males (21.6%) were included in the study. The male to
female ratio was 1:3.2. The mean age of the cases was 32.4 +/- 10.2 years and the
mean age of onset was 22.8 +/- 9.1 years. RESULTS: One hundred and thirty seven
patients (74.6%) fulfilled the criteria for migraine without aura (MwA) whereas
forty-eight patients (25.4%) fulfilled the criteria for migraine with aura (MA). 
The males had been suffering from migraine headaches for a mean of 8.3 +/- 6.3
years versus a mean of 9.3 +/- 7.6 years in females. More than half (61.4%) of
the females were housewives, and 84.3% of the cases were living in urban areas.
About half (48.7%) of them had at least 11 years of education, most (79.5%)
reported low or medium income level. Also, 70.8% were married. There was a high
rate of headache in family history (72.4%). A majority of patients (75.7%)
complained of severe headaches. One fourth (24.9%) had more than three attacks
per month. Headache was unilateral in 71.9% and was throbbing in 77.8%. In 117
patients (63.2%) the symptoms were aggravated by physical activity. Attacks were 
accompanied by nausea in 84.9%, vomiting in 50.3%, photophobia in 80.0%, and
phonophobia in 78.4%. In 58% of the cases, the headache was severe enough to
disturb daily activities. CONCLUSIONS: This study showed that migraine is more
commonly seen in urban areas, in females, and is associated with high education
plus low income, and is comprised of a wide complex of symptoms.

PMID: 15678636 [PubMed - indexed for MEDLINE]

1933: Med Lett Drugs Ther. 2005 Jan 31;47(1201):9-10.

Topiramate (Topamax) for prevention of migraine.

[No authors listed]

Topiramate is the second antiepileptic drug, after valproate, to be approved by
the FDA for prevention of migraine. There is no evidence that it is more
effective than a beta-blocker for this indication, and it is much more expensive.
Topiramate can cause cognitive impairment and weight loss. No studies have
compared it to valproate for this indication.

PMID: 15678014 [PubMed - indexed for MEDLINE]

1934: Cardiol Clin. 2005 Feb;23(1):91-6.

Patent foramen ovale: does it play a role in the pathophysiology of migraine
headache?

Beda RD, Gill EA Jr.

Division of Cardiology, Department of Medicine, University of Washington School
of Medicine, 1959 Pacific Avenue NE, Seattle, WA 98195, USA.

Migraine headaches have a high prevalence rate in the general population and
account for significant morbidity, lost productivity, health care visits, and
dollars spent. Increasingly, emerging data show a link between migraine headache,
especially migraine headaches with aura, and patent foramen ovale (PFO). Closure 
of PFO as a cure for migraine headache is a tantalizing idea; this article
examines the data supporting that possibility including studies showing
improvement in migraine headache after PFO closure and case reports in which
migraine headaches worsened after closure of an atrial septal defect.

Publication Types: 
    Review

PMID: 15676272 [PubMed - indexed for MEDLINE]

1935: Nutr J. 2005 Jan 26;4:3.

The treatment of migraines and tension-type headaches with intravenous and oral
niacin (nicotinic acid): systematic review of the literature.

Prousky J, Seely D.

Department of Clinical Education, The Canadian College of Naturopathic Medicine, 
1255 Sheppard Avenue East, Toronto, Ontario, M2K 1E2, Canada. jprousky@ccnm.edu

BACKGROUND: Migraine and tension-type headaches impose a tremendous economic
drain upon the healthcare system. Intravenous and oral niacin has been employed
in the treatment of acute and chronic migraine and tension-type headaches, but
its use has not become part of contemporary medicine, nor have there been
randomized controlled trials further assessing this novel treatment. We aimed to 
systematically review the evidence of using intravenous and/or oral niacin as a
treatment for migraine headaches, tension-type headaches, and for headaches of
other etiologic types. METHODS: We searched English and non-English language
articles in the following databases: MEDLINE (1966-February 2004), AMED
(1995-February 2004) and Alt HealthWatch (1990-February 2004). RESULTS: Nine
articles were found to meet the inclusion criteria and were included in this
systematic review. Hypothetical reasons for niacin's effectiveness include its
vasodilatory properties, and its ability to improve mitochondrial energy
metabolism. Important side effects of niacin include flushing, nausea and
fainting. CONCLUSION: Although niacin's mechanisms of action have not been
substantiated from controlled clinical trials, this agent may have beneficial
effects upon migraine and tension-type headaches. Adequately designed randomized 
trials are required to determine its clinical implications.

Publication Types: 
    Review

PMID: 15673472 [PubMed - indexed for MEDLINE]

1936: Neuroimage. 2005 Feb 15;24(4):1025-31. Epub 2005 Jan 5.

Functional 1H-MRS findings in migraine patients with and without aura assessed
interictally.

Sarchielli P, Tarducci R, Presciutti O, Gobbi G, Pelliccioli GP, Stipa G, Alberti
A, Capocchi G.

Neuroscience Department, University of Perugia, Policlinico Monteluce, Via E Dal 
Pozzo, 06126 Perugia, Italy. neuro.pg@tiscalinet.it

The present study was aimed at investigating changes in brain metabolites due to 
visual cortex activation in migraineurs and normal subjects by (1)H-magnetic
resonance spectroscopy (MRS). Twenty-two migraine patients with aura, 22 migraine
patients without aura, and 10 control subjects were assessed. The volume of
interest (about 8 cm(3)) was placed on the visual cortex area and the visual
stimulus was applied using MR-compatible goggles with a flashing red light at a
frequency of 8 Hz and an intensity of 14 lx. Data were acquired over 36'40". The 
experimental time course was: baseline phase, from 0 to 3'40" (1 spectrum); on
phase (flashing light condition), from 3'40" to 29'20" (1540") (7 spectra), and
off phase, from 29'20" to the end of the experiment at 36'40" (2 spectra). The
main result of photic stimulation in patients with migraine with aura is the more
consistent decrease (-14.61%) of the N-acetylaspartate (NAA) signal, which is
significantly greater than that found in migraine patients without aura and
control subjects. A parallel slight increase in the lactate peak was also
detected. The above findings support little differences in brain metabolites
between the two patient groups assessed in interictal periods, which suggests a
less efficient mitochondrial functioning in migraine with aura patients.

Publication Types: 
    Clinical Trial

PMID: 15670679 [PubMed - indexed for MEDLINE]

1937: Acta Neurol Taiwan. 2004 Dec;13(4):158-69.

Clinical advances in the preventive treatment of migraine.

Mannix LK.

Headache Associates, Ohio, USA. lkmannix@aol.com

Evidence is emerging on the physiological processes underlying episodic migraine 
and the rationale for preventive treatment. Objectives for preventive treatment
include limiting future pain and disability and potentially modulating the course
of disease progression. Many factors influence medication choice for patients
such as migraine type, patient preference, co-existing conditions, and medication
side effects. In this paper, frequently prescribed treatment options for migraine
prevention are reviewed. Most headache preventive medications treat other medical
disorders and are found serendipitously to be beneficial in migraine or other
headache disorders. A new treatment option is topiramate, with proven safety and 
efficacy across the largest controlled migraine prevention trials conducted to
date. New clinical information is enhancing patient care and enabling clinicians 
to ease the burden of migraine worldwide.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 15666691 [PubMed - indexed for MEDLINE]

1938: Pediatr Neurol. 2005 Feb;32(2):131-3.

Migraine-like attacks in child with Sturge-Weber syndrome without facial nevus.

Taddeucci G, Bonuccelli A, Polacco P.

Department of Pediatrics, Section of Pediatric Neurology, University of Studies
of Pisa, Via Fermi 9, 56126 Pisa, Italy.

The Sturge-Weber syndrome was recently subdivided into type I (facial and
leptomeningeal angioma, possible glaucoma), type II (facial angioma, without
evident endocranial involvement), and type III (exclusive leptomeningeal
angioma). Thus far in the literature only 24 cases of Sturge-Weber syndrome type 
III have been reported. This study presents a case of a 2-year 9-month-old child 
with normal psychomotor development and skin free (no angiomas), who presented
repeated episodes of severe headache, vertiginous symptoms, vomiting, and
drowsiness, separated by complete recovery. The cranial computed tomography and
magnetic resonance imaging with gadolinium revealed left occipital leptomeningeal
angiomatosis with calcifications, suggesting a diagnosis of Sturge-Weber syndrome
type III. Considering the normal psychomotor development, the improved
electroencephalographic reports between the episodes, and the absence of
hypoperfusion areas on single-photon emission computed tomography at 30 months of
follow-up, the symptomatology appears an expression of migraine-like symptoms
resulting from vasomotor disturbances within and around the angioma, more than an
expression of partial seizures arising through an epileptic focus in the ischemic
region around the vascular malformation.

Publication Types: 
    Case Reports

PMID: 15664776 [PubMed - indexed for MEDLINE]

1939: Headache. 2005 Jan;45(1):80-1.

Cluster-like headache aura status.

Langedijk M, van der Naalt J, Luijckx GJ, De Keyser J.

Department of Neurology, University Hospital Groningen, Groningen, The
Netherlands.

We describe a patient with successive attacks (40 to 90 minutes) of cluster-like 
headache associated with aphasia, and contralateral hemihypesthesia and
hemiplegia. The condition can best be described as cluster-like headache aura
status.

Publication Types: 
    Case Reports

PMID: 15663619 [PubMed - indexed for MEDLINE]

1940: Headache. 2005 Jan;45(1):47-52.

Migraine therapy: a survey of pharmacists' knowledge, attitudes, and practice
patterns.

Wenzel RG, Lipton RB, Diamond ML, Cady R.

Diamond Headache Clinic Inpatient Unit, Pharmacy Dept. St. Joseph Hospital,
Chicago, Illnois, USA.

OBJECTIVE: Study pharmacists' knowledge, attitudes, and practice patterns with
regard to migraine therapy. BACKGROUND: Pharmacists interact with headache
sufferers at least 53,000 times daily, thus are well positioned to improve the
less than optimal medication management of these disorders. Methods.-Two hundred 
self-administered surveys, distributed at a migraine symposium, assessing
pharmacists' demographic characteristics and level of agreement or disagreement
with treatment approaches were conducted. RESULTS: A total of 171 useable surveys
(86%) were received. Of the sample, 35% were community pharmacists, 29% were
hospital pharmacists, and the remainder were from other work environments.
Exclusively among community pharmacists, 80% feel that headache is an important
part of their practice, 85% make between one and five over-the-counter (OTC)
headache product suggestions per day, and 12% make six or more daily OTC
recommendations. Among all the sample's pharmacists, more than half feel migraine
patients should try OTC drugs prior to prescription medications, only half ask
patients about headache-related morbidity, and one-third feel migraine-specific
medications should be reserved only for patients who initially fail nonspecific
drugs. Few pharmacists utilize published migraine treatment guidelines.
Approximately two-thirds of pharmacists do not feel migraine is a neurobiological
illness. The majority is comfortable with their ability to identify people
needing a physician referral. CONCLUSIONS: Our results show pharmacists,
particularly those in community pharmacies, interact with headache sufferers
multiple times daily. Most pharmacists were neither familiar with nor practice
migraine therapies endorsed by evidence-based guidelines. Further training of
pharmacists is warranted.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 15663613 [PubMed - indexed for MEDLINE]

1941: Headache. 2005 Jan;45(1):42-6.

Comparison of intravenous valproate with intravenous lysine-acetylsalicylic acid 
in acute migraine attacks.

Leniger T, Pageler L, Stude P, Diener HC, Limmroth V.

Department of Neurology, University of Essen, Hufelandstr.55, 45122 Essen,
Germany.

OBJECTIVE: The study compared efficacy and tolerability of intravenous valproate 
(iVPA) with intravenous lysine-acetylsalicylic acid (iLAS) in acute migraine
attacks. Background.-iLAS has been proven to be a highly effective treatment in
acute migraine attacks, but it is not available in many countries and
contraindicated in patients with asthma or peptic ulcers. Current data suggest
that iVPA may be effective in the treatment of acute migraine attacks.
DESIGN/METHODS: In this randomized, double-blind, parallel-group phase-II study, 
40 patients with acute migraine attacks (onset <5 hours, severe or moderate
headache on a four-point IHS scale) alternately received iVPA 800 mg or iLAS 1000
mg. Primary outcome criteria were the percentage of patients reporting pain
relief after 1 hour and patients who remained sustained pain free for 24 hours
following drug administration. Secondary outcome criteria were relief of pain and
associated migrainous symptoms (nausea, photophobia, and phonophobia) at 1, 2,
24, and 48 hours following drug administration. RESULTS: There were no
significant differences in demographic and clinical features between both
treatment groups. Percentage of pain relief after 1 hour in the iVPA and iLAS
groups were 25% and 30%, respectively, and of sustained pain free for 24 hours
were 20% and 30%, respectively, without significant differences (P = 1 and P=
.72, respectively). Both drugs improved associated migrainous symptoms without
significant differences at the different time points, but again with a trend in
favor of iLAS. No adverse events were observed. CONCLUSION: Both drugs were
effective in acute migraine attacks with a trend in favor of iLAS. As both drugs 
were well tolerated, further studies with higher doses of iVPA for the treatment 
of acute migraine attacks are recommended.

Publication Types: 
    Clinical Trial
    Clinical Trial, Phase II
    Comparative Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 15663612 [PubMed - indexed for MEDLINE]

1942: Headache. 2005 Jan;45(1):32-6.

Migraine prevalence and some related factors in Turkey.

Celik Y, Ekuklu G, Tokuç B, Utku U.

Department of Neurology, Trakya University School of Medicine, Erdirne, Turkey.

OBJECTIVES: The aim of our study is to determine the prevalence of migraine in
Provincial Center of Edirne. METHODS: A systematic random sample of 386
inhabitants over 14 years old were interviewed face to face. Diagnosis of
migraine was based on the International Headache Society (IHS) classification.
RESULTS: Migraine was identified in 77 subjects (60 female, 17 male). The
lifetime prevalence of migraine was found to be 19.9% (95% CI: 18.3-21.5) (9.34% 
(95% CI: 8.6-10) in males, 29.3% (95% CI: 27-31.6) in females). CONCLUSIONS:
These results show that while migraine prevalence in Turkish females is higher
than that reported in previous studies from Europe and United States, lifetime
prevalence is similar in all populations.

PMID: 15663610 [PubMed - indexed for MEDLINE]

1943: Headache. 2005 Jan;45(1):25-31.

Low income and education levels may cause medication overuse and chronicity in
migraine patients.

Atasoy HT, Unal AE, Atasoy N, Emre U, Sumer M.

Department of Neurology, Zonguldak Karaelmas University Faculty of Medicine,
Zonguldak, Turkey.

BACKGROUND: Frequent analgesic drug intake, especially in migraine patients, may 
induce the risk of medication overuse headache (MOH). The various conditions that
may affect the development and the features of MOH have not been determined yet. 
AIM: To compare MOH patients with migraine as pre-existing headache and episodic 
migraine patients according to socioeconomic and educational variables. METHODS: 
Forty-six MOH patients with migraine as pre-existing headache and 61 migraine
patients were included into study. The headache characteristics, socioeconomic
and educational variables of MOH and migraine groups and subgroups divided
according to the education (low/high education subgroups), and income (low/high
income subgroups) levels were evaluated. RESULTS: We found that mean duration of 
education was shorter in MOH patients than migraine patients. There was a
negative correlation between duration of education and duration of MOH. The mean 
duration of MOH was longer and rate of low-income level was higher in patients
with low-education level. The duration of education was lower in MOH patients
with low income. The frequency of migraine attacks and low-income rate was also
higher in low-educated migraine patients. The duration of education was shorter
in migraine patients with low income. CONCLUSION: We report that migraineurs with
low socioeconomic status may have risk of developing MOH. A better identification
of patients at risk of drug-associated headache may contribute to improved health
in a group of patients with MOH.

Publication Types: 
    Comparative Study

PMID: 15663609 [PubMed - indexed for MEDLINE]

1944: Headache. 2005 Jan;45(1):17-24.

Zolmitriptan nasal spray exhibits good long-term safety and tolerability in
migraine: results of the INDEX trial.

Dowson AJ, Charlesworth BR, Green J, Färkkilä M, Diener HC, Hansen SB, Gawel M;
INDEX Study Group.

King's Headache Services, King's College Hospital, London, UK

BACKGROUND: Previous studies have shown that zolmitriptan 5 mg nasal spray has a 
fast onset of action, high efficacy, and good tolerability in the acute treatment
of migraine. Objective.-This open-label, noncomparative, multicenter,
multinational phase III study was designed to further evaluate the long-term
safety and tolerability of zolmitriptan 5 mg nasal spray in a population of
migraineurs largely naive to triptan nasal sprays who treated multiple migraine
attacks over a 1-year period. METHODS: Patients were required to have an
established diagnosis of migraine with or without aura (based on International
Headache Society criteria), a high frequency of migraine attacks, and were
allowed to treat migraine with any baseline headache intensity. A secondary
objective of the study was to assess the long-term efficacy of zolmitriptan nasal
spray. A subgroup analysis aimed to determine whether rhinitis had any influence 
on outcomes of treatment. RESULTS: The safety population consisted of 538
patients who treated 20,717 migraine attacks with zolmitriptan 5 mg nasal spray. 
Overall, adverse events occurred in 32.8% of attacks, and led to treatment
withdrawal in 4.5% of patients. The most common adverse events were unusual taste
(19.0%) and paresthesia (6.8%). Adverse events were generally of mild intensity, 
transient, and well tolerated, showing a decline in incidence over time. Serious 
adverse events were rare. The presence of rhinitis and use of a second dose of
trial medication had no effect on the incidence of adverse events. At 2 hours,
53.8% of attacks treated with zolmitriptan nasal spray 5 mg were rendered pain
free. The highest 2-hour pain free rates were seen for headaches of mild baseline
intensity (83.3%), followed by headaches of moderate (56.5%), and severe (32.2%) 
baseline intensity. The 2-hour pain-free rate remained consistent throughout the 
study period. The presence of rhinitis had no effect on efficacy. CONCLUSIONS:
Zolmitriptan 5 mg nasal spray demonstrated a well-tolerated and efficacious
profile in the acute treatment of multiple migraine attacks over a 1-year period.

Publication Types: 
    Clinical Trial
    Clinical Trial, Phase III
    Multicenter Study

PMID: 15663608 [PubMed - indexed for MEDLINE]

1945: Headache. 2005 Jan;45(1):7-16.

Zolmitriptan 5 mg nasal spray: efficacy and onset of action in the acute
treatment of migraine--results from phase 1 of the REALIZE Study.

Gawel M, Aschoff J, May A, Charlesworth BR; REALIZE Study Team.

Department of Sunnybrook and Women's College Health Sciences Centre, Toronto,
Canada.

OBJECTIVES: The objective of phase 1 (reported here) of this two-phase study was 
to assess the efficacy of zolmitriptan 5 mg nasal spray, in terms of ability to
provide relief from all migraine symptoms, in a controlled setting, designed to
replicate clinical practice. BACKGROUND: Zolmitriptan nasal spray has been shown 
to be fast acting and highly effective in the treatment of migraine, as assessed 
using standard endpoints, such as headache response and pain-free rates. METHODS:
In the double-blind first phase of the study, patients with migraine were
randomized to receive zolmitriptan 5 mg nasal spray or placebo to treat a single 
migraine attack. Attacks were treated according to patients' normal patterns of
use, in order to closely reflect clinical practice; that is, no specific regimen 
was dictated in terms of time to treatment or at what level of pain intensity the
headache should be treated. Patients could take a second dose of study medication
or an agreed escape medication if adequate pain relief had not been achieved 2
hours after the first dose. The primary efficacy endpoint was total symptom
relief (freedom from pain, nausea, photophobia, and phonophobia) 1 hour after the
first dose. Secondary efficacy endpoints included headache response, pain-free
status and sustained pain-free status, and ability to perform normal activities. 
RESULTS: The intention-to-treat population comprised 461 zolmitriptan nasal spray
recipients and 451 placebo recipients. The total symptom relief rate 1 hour
post-dose was significantly higher in the zolmitriptan 5 mg nasal spray group
than in the placebo group (14.5% vs. 5.1%; P < .0001); the difference between the
groups was significant from 30 minutes post-dose. Treatment with zolmitriptan
nasal spray, compared with placebo, also produced a higher headache response rate
from 10 minutes post-dose (15.1% vs. 9.1%; P = .0079) and a higher pain-free rate
from 30 minutes post-dose (7.7% vs. 3.2%; P = .0039). Zolmitriptan nasal spray
was also significantly superior to placebo in terms of sustained pain-free status
and patients' ability to perform normal activities. Zolmitriptan nasal spray was 
well tolerated. CONCLUSIONS: These findings confirm the efficacy demonstrated by 
zolmitriptan nasal spray in previous clinical trials.

Publication Types: 
    Clinical Trial
    Comparative Study
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 15663607 [PubMed - indexed for MEDLINE]

1946: Headache. 2005 Jan;45(1):3-6.

Correlation between lipophilicity and triptan outcomes.

Pascual J, Muñoz P.

University Hospital M de Valdecilla, 39008 Santander, Spain.

BACKGROUND: It has been suggested that triptans achieving higher central nervous 
system (CNS) levels should have an advantage in efficacy, if central actions are 
important. Objective.-Our aim was to correlate the efficacy and tolerability
results of triptans with their lipophilicity. METHODS: Data for response and pain
free at 2 hours, recurrence, adverse events (AE), CNS AE, and chest symptoms
taken from Ferrari et al's meta-analysis publications for the recommended doses
of oral triptans were correlated with their lipophilicity coefficients
(logD(pH)7.4 = -2.1 almotriptan < -1.5 sumatriptan < -1.0 zolmitriptan < -0.7
rizatriptan < -0.2 naratriptan < 0.5 eletriptan). RESULTS: We found no
significant correlation between lipophilicity coefficients and any of the
analyzed parameters. There was, however, some correlation between lipophilicity
and CNS AE (P = .09, r = 0.74) and, to a lesser degree, with a reduction in
recurrence rate (r = -0.36). The r values for response and pain free with placebo
correction ranged from 0.04 to 0.34, suggesting almost no correlation between
lipophilicity and efficacy variables. CONCLUSIONS: According to this analysis, a 
higher lipophilicity does not seem crucial to improve triptan efficacy. This
physico-chemical property, however, correlates with higher CNS AE and, possibly, 
lower recurrence rates.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 15663606 [PubMed - indexed for MEDLINE]

1947: Cephalalgia. 2005 Feb;25(2):124-31.

Placebo effects in oral triptan trials: the scientific and ethical rationale for 
continued use of placebo controls.

Loder E, Goldstein R, Biondi D.

Pain and Headache Management Programs, Spaulding Rehabilitation Hospital and
Harvard Medical School, Boston, USA. eloder@partners.org

The aim of this study was to determine the characteristics of placebo effects in 
acute migraine treatment trials of triptans performed over 12 years and assess
whether the use of placebo controls in trials of acute migraine treatment remains
ethically and scientifically appropriate. We conducted a search for all
controlled trials published in English between January 1991 and April 2002 in
which adult subjects with migraine were randomly assigned to receive an oral
triptan or placebo for the acute treatment of a migraine attack. Thirty-one
trials met our criteria for inclusion. Placebo results for each study and pooled 
placebo results were calculated for the endpoints of headache response, pain-free
response and adverse events. Heterogeneity was assessed using the Q statistic,
and meta-regression using prespecified covariates was performed to investigate
heterogeneity. The study results show a significant degree of heterogeneity.
Efforts to explain heterogeneity with available data were not successful, with
the exception of adverse event rates to placebo, for which study location (Europe
vs. North America) partially explained differences in study results. AE rates
were lower in European studies than in North American studies. Across all
studies, the mean proportion of subjects who experienced a treatment response at 
two hours to placebo was 28.48 +/- 8.73% (range 17-50%). The mean proportion of
subjects who experienced an adverse event to placebo was 23.40 +/- 14.05% (range 
4.86-74%). The mean proportion of subjects who experienced a pain-free response
to placebo at two hours was 6.08 +/- 4.43% (range 5-17%). Results of studies
allowing use of prophylaxis did not differ significantly from those that did not 
allow prophylaxis. Placebo effects appear to be enhanced in studies involving
children and adolescents. In contrast to an earlier, smaller review, our results 
do not suggest that randomization ratios influence placebo rates. We conclude
that placebo effects in published trials of acute migraine medications are highly
variable and often substantial. This variability in placebo response means that
active control equivalence trials or the use of historical controls will not
provide adequate proof of the safety or efficacy of new drugs, and will not
differentiate between drugs that are active vs. placebo but of unknown efficacy
relative to each other. The potential for approval of ineffective drugs,
inability to compare results of studies performed in different locations, and
poor characterization of the tolerability and safety profiles of new drugs
represent a greater danger to migraineurs than does the limited-duration use of
placebo in carefully monitored clinical trials of consenting subjects. These
observations support the view that the inclusion of a placebo group remains of
major scientific and ethical importance in trials of migraine medications.

Publication Types: 
    Meta-Analysis

PMID: 15658949 [PubMed - indexed for MEDLINE]

1948: Cephalalgia. 2005 Feb;25(2):117-23.

Variability of reported headache symptoms and diagnosis of migraine at 12 months.

Nachit-Ouinekh F, Chrysostome V, Henry P, Sourgen C, Dartigues JF, El Hasnaoui A.

University Victor Segalen, INSERM U 593, Bordeaux, France. fatima.nachit@noos.fr

Assignment of a diagnosis of migraine has been formalized in diagnostic criteria 
proposed by the International Headache Society. The objective of the present
study is to determine the reproductibility of the formal diagnosis of migraine in
a cohort of headache sufferers over a one-year period. The study was performed in
a community cohort taking part in a long-term prospective health survey, the
GAZEL study. Two thousand five hundred individuals reporting headache in the
GAZEL cohort were sent two postal questionnaires concerning headache symptoms and
features at 12-monthly intervals. Replies to the questions allowed a migraine
diagnosis to be attributed retrospectively using an algorithm based on the IHS
classification scheme. The response rate was 82% for the first questionnaire and 
69% for both questionnaires. Of the 1733 subjects providing information at both
time-points, the agreement rate for the diagnosis of strict migraine (IHS
categories 1.1 or 1.2) was 77.7% (kappa = 0.48), with 62.2% of the patients with 
this diagnosis (IHS categories 1.1 or 1.2) at Month 0 retaining the same
diagnosis at Month 12. When diagnostic criteria were widened to include IHS
category 1.7 (migrainous disorder), the agreement rate of the diagnosis was
similar at 77.6% (kappa = 0.52), but 82% of the patients with this diagnosis (IHS
categories 1.1 or 1.2 or 1.7) at Month 0 now retained the same diagnosis at Month
12. In conclusion, the one-year reproducibility of reporting of migraine headache
symptoms is only moderate, varies between symptoms, and leads to instability in
the formal assignment of a migraine headache diagnosis and to diagnostic drift
between headache types. This finding is compatible with the continuum model of
headache, where headache attacks can vary along a severity continuum from
episodic tension-type headaches to full-blown migraine attacks.

PMID: 15658948 [PubMed - indexed for MEDLINE]

1949: Cephalalgia. 2005 Feb;25(2):87-100.

An assessment of the burden of migraine using the willingness to pay model.

Hamelsky SW, Lipton RB, Stewart WF.

Bristol-Myers Squibb, Hillside, NJ 07205, USA. sandra.hamelsky@bms.com

Willingness to pay methods measure treatment preferences and also measure the
burden of illness in economic terms. We used a contingent valuation method to
measure migraine sufferers' willingness to pay (WTP) for acute medication for
their most severe headache attacks, based on various profiles of treatment
benefits and the characteristics of the migraine sufferer. Subjects were
identified from a population-based database of migraine sufferers, previously
recruited by random digit dialing. Telephone interviews (n = 1428) were used to
gather demographic and headache characteristics. Subjects who met the
International Headache Society criteria for migraine with or without aura and
satisfied the other inclusion criteria based on telephone interview (n = 312)
were invited to participate in a mailed questionnaire study. The questionnaire
was mailed to the 310 subjects who agreed to participate and 201 (65%) surveys
were returned. The survey included questions on the demographics, the migraine
characteristics, and the psychological disposition of the respondents. WTP for an
acute migraine treatment with 14 different hypothetical treatment profiles was
explored. Responders and non-responders to the survey were generally similar. The
newly designed WTP questionnaire had high internal consistency (Cronbach's alpha 
0.90) and test-retest reliability (Spearman's correlation coefficients
0.71-0.77). Study subjects were willing to pay a median price of US 5 dollars for
a migraine treatment that provided complete relief in 30 min and worked 100% of
the time, with no side-effects and no headache recurrence. Median WTP decreased
as treatment attributes deviated from this ideal. For example, WTP declined to a 
median of US 1 dollar for complete relief in 2 h and to US 0.25 dollars for
complete relief in 4 h. All of the medication attributes powerfully influenced
WTP. Several variables predicted WTP including current payment for medication,
MIDAS (Grade III), and those with headaches of long duration. Subjects who
employed a greater number of coping skills were less willing to pay. Patient
demographics and migraine severity predict WTP, but treatment attributes were
also important. As treatment improves, WTP for migraine medications is likely to 
increase.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 15658945 [PubMed - indexed for MEDLINE]

1950: Cephalalgia. 2005 Feb;25(2):82-6.

Vagus nerve stimulation relieves chronic refractory migraine and cluster
headaches.

Mauskop A.

State University of New York, Downstate Medical Center, Brooklyn, NY, USA.

Anticonvulsant and antidepressant medications have demonstrated efficacy in
migraine treatment. Vagus nerve stimulation (VNS) is an effective treatment for
drug-refractory epilepsy and possibly depression and it also has documented
analgesic effects. These observations suggested a possible role for VNS in
treating severe refractory headaches, and led to a trial of VNS in patients with 
such headaches. VNS was implanted in four men and two women with disabling
chronic cluster and migraine headaches. In one man and one woman with chronic
migraines VNS produced dramatic improvement with restoration of ability to work. 
Two patients with chronic cluster headaches had significant improvement of their 
headaches. VNS was well tolerated in five patients, while one developed nausea
even at the lowest current strength. In conclusion, VNS may be an effective
therapy for intractable chronic migraine and cluster headaches and deserves
further trials.

Publication Types: 
    Case Reports
    Clinical Trial

PMID: 15658944 [PubMed - indexed for MEDLINE]

1951: Neurogenetics. 2005 Feb;6(1):17-23. Epub 2005 Jan 15.

Investigation of hormone receptor genes in migraine.

Colson NJ, Lea RA, Quinlan S, MacMillan J, Griffiths LR.

Genomics Research Centre, School of Health Science, Griffith University, Gold
Coast, Queensland, Australia.

Migraine is a common neurological condition with a complex mode of inheritance.
Steroid hormones have long been implicated in migraine, although their role
remains unclear. Our investigation considered that genes involved in hormonal
pathways may play a role in migraine susceptibility. We therefore investigated
the androgen receptor (AR) CAG repeat, and the progesterone receptor (PR) PROGINS
insert by cross-sectional association analysis. The results showed no association
with the AR CAG repeat in our study group of 275 migraineurs and 275 unrelated
controls. Results of the PR PROGINS analysis showed a significant difference in
the same cohort, and in an independent follow-up study population of 300
migraineurs and 300 unrelated controls. Analysis of the genotypic risk groups of 
both populations together indicated that individuals who carried the PROGINS
insert were 1.8 times more likely to suffer migraine. Interaction analysis of the
PROGINS variant with our previously reported associated ESR1 594A variant showed 
that individuals who possessed at least one copy of both risk alleles were 3.2
times more likely to suffer migraine. Hence, variants of these steroid hormone
receptor genes appear to act synergistically to increase the risk of migraine by 
a factor of three.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 15654614 [PubMed - indexed for MEDLINE]

1952: J Neurol Neurosurg Psychiatry. 2005 Feb;76(2):212-7.

Sensitivity and specificity of the new international diagnostic criteria for
migraine with aura.

Eriksen MK, Thomsen LL, Olesen J.

Danish Headache Center, University of Copenhagen, Department of Neurology,
Glostrup Hospital, Nordre Ringvej 57, DK-2600 Glostrup, Denmark.
kirchmann@dadlnet.dk

OBJECTIVES: Since 1998, migraine with aura (MA) has been diagnosed according to
the operational diagnostic criteria of the International Headache Society
(ICHD-1). Here we present the data underlying the new criteria for MA in the
ICHD-2 classification. METHODS: Sensitivity of the new criteria was tested in
patients with MA and specificity in patients with reversible non-aura visual
disturbances. The diagnoses in both groups of patients were made in a validated
semistructured physician-conducted interview. We tested five sets of criteria for
sensitivity and specificity comparing with the diagnosis according to the ICHD-1 
in 200 patients and the selected set of criteria in 274 additional patients.
RESULTS: Four sets of criteria had sensitivity/specificity of 46%/100%, 71%/100%,
62%/95%, and 99%/76%. Sensitivity of the selected set of criteria was 84% (95% CI
79% to 90%) and specificity 97% (95% CI 95% to 99%). According to these criteria 
at least two of the following should be fulfilled: homonymous visual or
unilateral sensory symptoms; at least one aura symptom develops gradually over > 
or =5 minutes and/or different symptoms occur in succession over > or =5 minutes;
each symptom lasts > or =5 and < or =60 minutes. In the additional sample
sensitivity of the selected criteria was 90% (95% CI 86% to 94%) and specificity 
96% (95% CI 91% to 100%). CONCLUSIONS: The diagnostic criteria for MA selected
for ICHD-2 had high sensitivity and specificity. The ICHD-2 criteria are more
operational and probably delineate a more homogeneous sample of patients than the
ICHD-1. The ICHD-2 for MA is intended equally for research and clinical practice 
and can be used at different levels of specialisation.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Validation Studies

PMID: 15654035 [PubMed - indexed for MEDLINE]

1953: Prog Neurobiol. 2004 Dec;74(6):351-61.

A computational perspective on migraine aura.

Dahlem MA, Chronicle EP.

Department of Neurology II, Otto-von-Guericke University, Magdeburg, Germany.
dahlem@ifn-magdeburg.de

The classical visual aura of migraine is characterized by a unilateral
hallucination, composed of a zigzag fortification pattern followed by a trailing 
scotoma. This pattern usually starts in central vision, expands and spreads to
the periphery, and then disappears. We review a number of historical attempts to 
explain the migraine aura in terms of brain events, then summarize recent
theories of the pathophysiology of the aura. We describe an approach to the
computational modeling of migraine aura, based on the principles of (a) cortical 
organization, and (b) active wave propagation in an excitable medium. We
demonstrate correspondences between properties of the model system and aspects of
the pathophysiology of the aura. The simulations produced by the model are in
agreement with descriptions and drawings of visual aura from migraine patients.
We outline several testable predictions stemming from the implementation of the
model, and explain how model-based empirical research has the capacity to (a)
improve recording of the phenomena of the visual aura, (b) improve understanding 
of the spatio-temporal dynamics of other types of aura, in particular
somatosensory and dysphasic aurae, and (c) clarify the theoretical requirements
for the initiation of aura in the brain.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 15649581 [PubMed - indexed for MEDLINE]

1954: Ann Pharmacother. 2005 Feb;39(2):274-9. Epub 2005 Jan 11.

Health food stores' recommendations for nausea and migraines during pregnancy.

Buckner KD, Chavez ML, Raney EC, Stoehr JD.

College of Health Sciences, Midwestern University, Glendale, AZ 85308-6814, USA. 
jstoeh@midwestern.edu

BACKGROUND: Many pregnant women use dietary supplements during pregnancy;
however, relatively scant information is available on the safety of these
products. Consumers of dietary supplements often rely on employees of health food
stores to provide recommendations. OBJECTIVE: To evaluate recommendations made by
health food store employees in the Phoenix metropolitan area regarding treatment 
of nausea/vomiting and migraines during pregnancy. METHODS: Phone calls were made
by a disguised shopper to 155 health food stores in the greater Phoenix area. The
caller posed as a woman 8 weeks' pregnant asking for recommendations for
treatment of nausea/vomiting and migraines. Responses and recommendations were
recorded and then compared with current scientific evidence obtained during a
search of the literature using MEDLINE (1966-September 2004) as to whether or not
the supplements and the methods of their use during pregnancy were
contraindicated. RESULTS: Eighty-nine percent of stores offered recommendations
for nausea/vomiting, and 82% provided recommendations for migraines. The use of
ginger was the most recommended therapy for nausea/vomiting. Only 3.6% of
respondents recommended correct usage, but failed to supply the correct dosage
and duration. A total of 15 of 278 (5%) recommendations, for both nausea/vomiting
and migraines, were for products contraindicated in pregnancy. CONCLUSIONS: In
light of the increased use of dietary supplements by women during pregnancy, the 
willingness of personnel in health food stores to make any recommendations should
foster concerns by patients and healthcare providers alike. Use of dietary
supplements contraindicated in pregnancy could cause significant harm to the
mother and/or fetus. Studies are needed to address the need for more stringent
guidelines regarding health food stores and their recommendations.

PMID: 15644475 [PubMed - indexed for MEDLINE]

1955: Neurosci Lett. 2005 Feb 10;374(2):129-31.

Association of the insertion/deletion polymorphism of the angiotensin
I-converting enzyme gene in patients of migraine with aura.

Kowa H, Fusayasu E, Ijiri T, Ishizaki K, Yasui K, Nakaso K, Kusumi M, Takeshima
T, Nakashima K.

Department of Neurology, Institute of Neurological Sciences, Faculty of Medicine,
Tottori University, 36-1 Nishi-cho, Yonago, 683-8504, Japan.
norkowa@grape.med.tottori-u.ac.jp

Recently, several angiotensin I-converting enzyme (ACE) inhibitors and an
angiotensin II receptor blocker were demonstrated to have a clinically important 
prophylactic effect in migraine. ACE is one of the key enzymes in the
rennin-angiotensin-aldosterone system, which modulates vascular tension and blood
pressure. In humans, serum ACE levels are strongly genetically determined.
Individuals who were homozygous for the deletion (D) allele showed increased ACE 
activity levels. To investigate the role of ACE polymorphism in headache, we
analyzed the ACE insertion (I)/deletion (D) genotypes of 54 patients suffering
from migraine with aura (MwA), 122 from migraine without aura, 78 from
tension-type headache (TH), and 248 non-headache healthy controls. The ACE D
allele were significantly more frequent in the MwA than controls (p<0.01). The
incidence of the D/D genotype in MwA (25.9%) was significantly higher than that
in controls (12.5%; p<0.01; odds ratio=5.26, 95% confidence interval: 1.69-16.34,
adjusted for age and gender). No differences in the remaining groups were found. 
Our results support the conclusion that the D allele and the D/D genotype in the 
ACE gene is a genetic risk factor for Japanese MwA. There seems to be a possible 
relationship between ACE activity and the pathogenesis of migraine.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 15644278 [PubMed - indexed for MEDLINE]

1956: Acta Neurol Scand. 2005 Feb;111(2):102-7.

Impairment of parasympathetic baroreflex responses in migraine patients.

Sanya EO, Brown CM, von Wilmowsky C, Neundörfer B, Hilz MJ.

Autonomic laboratory, Department of Neurology, University of Erlangen-Nuremberg, 
Germany. emanuelosanya@yahoo.com

OBJECTIVES: The aim of this study was to assess baroreflex regulation of the
heart rate and blood vessels in migraine patients in comparison with healthy
controls. METHODS: In 30 migraine patients who were in a headache-free phase,
aged 34 +/- 2 years, and 30 healthy controls, aged 34 +/- 3 years, we applied
oscillatory neck suction at 0.1 Hz to assess the sympathetic modulation of the
heart and blood vessels and at 0.2 Hz to assess the effect of parasympathetic
stimulation on the heart. Breathing was paced at 0.25 Hz. Electrocardiographic
RR-intervals, blood pressure and respiration were continuously recorded.
Responses to the baroreflex stimulations were assessed as the changes in power of
the RR-interval and blood pressure fluctuations at the relevant stimulating
frequency from the baseline values. RESULTS: Systolic and diastolic blood
pressure responses to the 0.1 Hz neck suction pressure were not significantly
different between the patients and controls. The RR-interval oscillatory response
to 0.2 Hz neck suction was significantly less (P < 0.05) in the migraine patients
(4.45 +/- 0.27 ln ms2) compared with the controls (5.48 +/- 0.36 ln ms2).
CONCLUSION: These results suggest that baroreflex-mediated cardiovagal responses 
are reduced in migraine patients. However, the sympathetic-mediated baroreflex
control of the blood vessels is intact in the migraine patients. The autonomic
nervous system may have a role in the pathophysiology of migraine.

PMID: 15644069 [PubMed - indexed for MEDLINE]

1957: J Occup Environ Med. 2005 Jan;47(1):34-40.

Performance decrements resulting from illness in the workplace: the effect of
headaches.

Pransky GS, Berndt E, Finkelstein SN, Verma S, Agrawal A.

Liberty Mutual Research Institute, Hopkinton, Massachusetts and Harvard School of
Public Health, Boston, Massachusetts 01748, USA. glenn.pransky@libertymutual.com

OBJECTIVES: Studies on the impact of illness on work productivity are important
to rationally allocate healthcare resources and to design programs to mitigate
these effects. This investigation was conducted to develop and apply daily
measures of illness episodes, and to collect subjective and objective data on
work performance impacts. Medical bill reviewers completed daily responses to a
questionnaire about headache manifestations, severity, and speed of work using
interactive voice response (IVR). Of 134 eligible enrolled subjects, 117 (86%)
provided at least 30 daily reports over 3 months. Their responses were matched to
difficulty-adjusted objective measures: daily output, time on the system, and
productivity. Respondents were clinically classified as migraineurs (n = 56),
other headache disorders (n = 47), or having no headache disorder (n = 14). Each 
headache episode was classified as a migraine or nonmigraine headache based on
reported manifestations. RESULTS: The three groups were similar in a variety of
demographic factors, and mean subject-specific measures of speed, output, and
productivity. In a multivariate model using general estimating equations, only
episode severity (not type of headache or person-specific diagnosis) was found to
be associated with a significant decrement in speed or productivity. The
self-reported decrement in speed (approximately 20%) was much greater than the
actual measured effect on productivity (approximately 8%). Intensive daily diary 
collection by IVR on symptoms and work performance is feasible. However, analysis
of detailed daily objective productivity data can be complex, with significant
unmeasured sources of variance. Severity may be a more important determinant of
headache effect on work performance than specific diagnosis. Future studies on
illness episodes and work performance should measure informal accommodations that
may enable employees to compensate for episodic illnesses.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 15643157 [PubMed - indexed for MEDLINE]

1958: Neurology. 2005 Jan 11;64(1):157-9.

A functional serotonin transporter gene polymorphism is associated with migraine 
with aura.

Marziniak M, Mössner R, Schmitt A, Lesch KP, Sommer C.

Department of Neurology, University of Würzburg, Germany.
dr.martin.marziniak@uniklinik-saarland.de

An association study was performed in 197 migraineurs with regard to a functional
serotonin (5-HT) transporter (5-HTT) gene promoter polymorphism that leads to low
or high 5-HT uptake activity. The frequency of the less active short allele was
increased in migraineurs with aura but not in migraineurs without aura in
comparison with the control population (p < 0.001). This indicates that the 5-HTT
may be involved in the polygenic etiology of migraine with aura.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 15642926 [PubMed - indexed for MEDLINE]

1959: Bull Soc Sci Med Grand Duche Luxemb. 2004;(2):103-8.

Treatment of migraine related vertigo with lamotrigine an observational study.

Bisdorff AR.

Department of Neurology, Centre Hospitalier Emile Mayrisch, Esch-sur-Alzette.
alexbis@pt.lu

Migraine is a common cause of vertigo. The vertigo symptoms often occur
independently of the headaches and have very variable duration and phenomenology.
Treatment usually consists in giving prophylactic anti-migraineous medication.
The anti-epileptic drug Lamotrigine (LTG) has been reported to be effective in
treating migraine auras, isolated auras and to some extend migraine headaches. In
this retrospective observational study, 19 patients, 6 male and 13 female, aged
52.3 years (range 28-84) treated with LTG and suffering from migraine and
migraine related vertigo were evaluated. After a titration phase of 4 weeks
patients took 100 mg of Lamotrigine per day in a single dose and were followed up
for 3-4 months. The average vertigo frequency per month was significantly reduced
from 18.1 to 5.4, the average headache frequency per month was reduced from 8.7
to 4.4 without reaching statistical significance. Lamotrigine at a daily dose of 
100 mg seems to be effective in the treatment of migraine related vertigo. The
effect on vertigo was more marked than on headaches.

PMID: 15641316 [PubMed - indexed for MEDLINE]

1960: Int J Neurosci. 2004 Nov;114(11):1391-9.

Personality, depression, and anxiety as risk factors for chronic migraine.

Karakurum B, Soylu O, Karataş M, Giray S, Tan M, Arlier Z, Benli S.

Department of Neurology, Medical Research Center, Baskent University, Adana,
Turkey. bkarakurum@hotmail.com

This article evaluated risk factors such as personality, depression, and anxiety 
in relation to migraine transformation in Turkish patients. Thirty-seven patients
with chronic migraine and 50 patients with episodic migraine were investigated
The scores for hysteria, hypochondriasis, psychasthenia, depression, and social
introversion were all significantly higher in the chronic-migraine group than the
episodic-migraine group. Seventy-four percent of the chronic-migraine group and
26% of the episodic-migraine group had depression. Eighty percent of the
chronic-migraine group and 36% of the episodic-migraine group had anxiety. The
results suggest that depression, anxiety, and personality characteristics such as
hysteria, hypochondriasis, psychasthenia, depression, and social introversion may
be associated with chronic migraine in Turkish patients.

Publication Types: 
    Comparative Study

PMID: 15636352 [PubMed - indexed for MEDLINE]

1961: Neurologist. 2005 Jan;11(1):19-29.

Migraine and cerebral white matter lesions: when to suspect cerebral autosomal
dominant arteriopathy with subcortical infarcts and leukoencephalopathy
(CADASIL).

Gladstone JP, Dodick DW.

Mayo Clinic College of Medicine, Department of Neurology, 13400 E. Shea Blvd.,
Scottsdale, AZ 85259, USA. jon.gladstone@utoronto.ca

BACKGROUND: Patients with migraine are at an increased risk for white matter
lesions, typically multiple, small, punctate hyperintensities in the deep or
periventricular white matter, best observed on magnetic resonance imaging
utilizing T2-weighted or FLAIR sequences. The underlying pathogenesis of white
matter lesions in migraineurs is unknown, and the lesions are usually nonspecific
and of unclear clinical significance. REVIEW SUMMARY: Often the presence of white
matter lesions causes uncertainty for physicians and anxiety for patients and may
lead to a variety of diagnostic tests and treatments. Occasionally, white matter 
lesions may represent a secondary cause for headaches such as CADASIL (cerebral
autosomal dominant arteriopathy with subcortical infarcts and
leukoencephalopathy). CADASIL is underrecognized and underdiagnosed; it should be
suggested by (i) 1 or more of recurrent subcortical ischemic strokes (especially 
before age 60 and in the absence of vascular risk factors), migraine (especially 
with aura, including atypical or prolonged auras) and/or early cognitive decline 
or subcortical dementia; (ii) bilateral, multifocal, T2/FLAIR hyperintensities in
the deep white matter and periventricular white matter with lesions involving the
anterior temporal pole, external capsule, basal ganglia, and/or pons; and (iii)
an autosomal-dominant family history of migraine, early-onset stroke, or
dementia. The clinical spectrum of CADASIL is broad, and there is a poor
genotype-phenotype correlation. In certain individuals or families, migraine may 
be the only clinical manifestation. CONCLUSIONS: While the prevalence of
nonspecific white matter lesions in migraineurs is increased, the white matter
lesions may occasionally represent a secondary cause for headache such as
CADASIL. Greater awareness of the unique clinical, neuroimaging, and pathologic
features, as well as the availability of diagnostic genetic testing, should
enhance the recognition and diagnosis of this fascinating condition.

Publication Types: 
    Review

PMID: 15631641 [PubMed - indexed for MEDLINE]

1962: Curr Pain Headache Rep. 2005 Feb;9(1):65-70.

Efficacy of intravenous diphenhydramine versus intravenous DHE-45 in the
treatment of severe migraine headache.

Swidan SZ, Lake AE 3rd, Saper JR.

Chelsea Community Hospital, Department of Pharmaceutical Care Services, 775 South
Main Street, Chelsea, MI 48118, USA. sswidan@umich.edu

This study was conducted to compare the efficacy of intravenous diphenhydramine
with dihydroergotamine mesylate (DHE-45; Novartis International AG, Switzerland) 
in the treatment of severe, refractory, migraine headache. A retrospective review
was conducted to include eighty randomly chosen patients who were admitted to the
Michigan Head Pain & Neurological Institute's inpatient program at Chelsea
Community Hospital. Patients had received nine doses of diphenhydramine or nine
doses of DHE-45 during a 3-day period. Patients receiving DHE-45 also received
metoclopramide (Reglan; AH Robins Company, Inc., Richmond, VA) as prophylaxis for
nausea. Demographics, headache diagnosis, psychiatric discharge diagnoses,
abortive medications, and adverse events were recorded and assessed.

Publication Types: 
    Comparative Study

PMID: 15625028 [PubMed - indexed for MEDLINE]

1963: Curr Pain Headache Rep. 2005 Feb;9(1):47-52.

Cosensitization of pain and psychiatric comorbidity in chronic daily headache.

Cady R, Farmer K, Dexter JK, Schreiber C.

Headache Care Center, 3805 South Kansas Expressway, Springfield, MO 65807, USA.
rcady@primarycarenet.org

Chronic migraine occurs in approximately 20% of migraineurs, typically developing
over a period of many years. The pathophysiology of this transformation is
unknown. However, experts have associated chronic headache with analgesic
overuse, physical injury, and psychologic trauma. Research in post-traumatic
stress disorder has found that hippocampal sensitivity to stress alters and often
amplifies future pain behaviors. Although the most obvious difference between
migraine and chronic migraine is the frequency of headaches, this article
discusses chronic migraine as a more pervasive neurologic disease in which the
patient's neurologic and psychologic function fails to return to a normal
baseline. The sensory and affective components of pain are cosensitized,
producing other neurologic and psychologic symptoms during and between episodes
of headache. A staging paradigm is suggested that defines patients and assesses
their overall neurologic function. The goal of this classification is to identify
cosensitization early and pinpoint migraine patients who are at risk of
developing chronic migraine.

Publication Types: 
    Review

PMID: 15625025 [PubMed - indexed for MEDLINE]

1964: Prof Nurse. 2004 Dec;20(4):36-7.

Diagnosis and preventive approaches in the management of migraine.

Bhola R.

The National Hospital for Neurology and Neurosurgery, London.
r.bhola@ion.ucl.ac.uk

Migraine is a common and disabling condition, yet it is under-diagnosed and
under-treated worldwide. While the mechanisms are not fully understood, new
diagnostic techniques are beginning to provide a better understanding of the
condition. Some treatment options to improve the quality of life of those
affected are discussed.

PMID: 15624619 [PubMed - indexed for MEDLINE]

1965: Neurol Sci. 2004 Dec;25(5):245-50.

Topiramate in migraine prophylaxis: a randomised double-blind versus placebo
study.

Mei D, Capuano A, Vollono C, Evangelista M, Ferraro D, Tonali P, Di Trapani G.

Center for the Study of Headaches, Policlinico Universitario Agostino Gemelli,
Istituto di Neurologia, L.go Agostino Gemelli 8, I-00168 Rome, Italy.
alessandro.capuano@libero.it

The objectives of this paper are to evaluate the efficacy and tolerability of
topiramate, given at the dose of 100 mg/day, in the prophylactic treatment of
migraine. The hypothesis that migraine is the result of a condition of neuronal
hyperexcitability and the quest for drugs that are able to limit the number of
crises justifies the attempt to utilise the new antiepileptic drugs in the
prophylaxis of this pathology, which is so important due to its high prevalence
and due to the high disability it causes. The study was randomised double-blind
versus placebo, lasting 16 weeks, and was preceded by a run-in period of 4 weeks.
One hundred and fifteen patients were randomly allocated to treatment with
topiramate (TPM) or placebo: 35 patients completed the study in the TPM group and
37 patients in the placebo group. At the end of the double-blind phase of study, 
in the TPM group, we recorded a significant reduction in the frequency of
migraine crises (from 5.26 at baseline to 2.60 in the last 4 weeks), a
significant reduction in the quantity of symptomatic drugs taken as compared to
the placebo control group (from 6.17+/-1.80 SD to 2.57+/-0.80) and a significant 
downward trend in the number of days of disability over the 16-week period of
therapy. In the TPM group, side effects were transient and well tolerated. TPM
has thus proven its efficacy and tolerability in the prophylaxis of migraine.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial

PMID: 15624081 [PubMed - indexed for MEDLINE]

1966: Neurology. 2004 Dec 28;63(12):2240-4.

Petasites hybridus root (butterbur) is an effective preventive treatment for
migraine.

Lipton RB, Göbel H, Einhäupl KM, Wilks K, Mauskop A.

Department of Neurology, Albert Einstein College of Medicine, 1165 Morris Park
Ave., Rousso Bldg., Rm. 332, Bronx, NY 10461, USA. rlipton@aecom.yu.edu

OBJECTIVE: To evaluate the clinical efficacy of a standardized special root
extract from the plant Petasites hybridus as a preventive therapy for migraine.
METHODS: This is a three-arm, parallel-group, randomized trial comparing
Petasites extract 75 mg bid, Petasites extract 50 mg bid, or placebo bid in 245
patients with migraine. Eligible patients met International Headache Society
criteria for migraine, were ages 18 to 65, and had at least two to six attacks
per month over the preceding 3 months. The main outcome measure was the decrease 
in migraine attack frequency per month calculated as percentage change from
baseline over a 4-month treatment period. RESULTS: Over 4 months of treatment, in
the per-protocol analysis, migraine attack frequency was reduced by 48% for
Petasites extract 75 mg bid (p = 0.0012 vs placebo), 36% for Petasites extract 50
mg bid (p = 0.127 vs placebo), and 26% for the placebo group. The proportion of
patients with a > or =50% reduction in attack frequency after 4 months was 68%
for patients in the Petasites extract 75-mg arm and 49% for the placebo arm (p < 
0.05). Results were also significant in favor of Petasites 75 mg at 1, 2, and 3
months based on this endpoint. The most frequently reported adverse reactions
considered possibly related to treatment were mild gastrointestinal events,
predominantly burping. CONCLUSIONS: Petasites extract 75 mg bid is more effective
than placebo and is well tolerated as a preventive therapy for migraine.
Petasites 50 mg PO bid was not significantly more effective than placebo on the
primary study endpoints.

Publication Types: 
    Clinical Trial
    Comparative Study
    Randomized Controlled Trial

PMID: 15623680 [PubMed - indexed for MEDLINE]

1967: Neurology. 2004 Dec 28;63(12):2233-9.

Comment in:
    Neurology. 2004 Dec 28;63(12):2209-10.    Neurology. 2005 Jun 14;64(11):1989; author reply 1989.

Migraine and other headaches: associations with Rose angina and coronary heart
disease.

Rose KM, Carson AP, Sanford CP, Stang PE, Brown CA, Folsom AR, Szklo M.

Department of Epidemiology, School of Public Health, University of North Carolina
at Chapel Hill, 137 E. Franklin St., Suite 306, Chapel Hill, NC 27514, USA.
kathryn_rose@unc.edu

OBJECTIVE: To examine the association between a lifetime history of migraines and
other headaches with and without aura and Rose angina and coronary heart disease 
(CHD). METHODS: Participants were 12,409 African American and white men and women
from the Atherosclerosis Risk in Communities Study, categorized by their lifetime
history of headaches lasting > or =4 hours (migraine with aura, migraine without 
aura, other headaches with aura, other headaches without aura, no headaches).
Gender-specific associations of headaches with Rose angina and CHD, adjusted for 
sociodemographic and cardiovascular disease risk factors, were evaluated using
Poisson regression. RESULTS: Participants with a history of migraines and other
headaches were more likely to have a history of Rose angina than those without
headaches. The associations were stronger for migraine and other headaches with
aura (prevalence ratio [PR] = 3.0, 95% CI = 2.4, 3.7 and PR = 2.0, 95% CI = 1.5, 
2.7 for women; PR = 2.2, 95% CI = 1.2, 3.9 and PR = 2.4, 95% CI = 1.4, 3.9 for
men) than for migraine and other headaches without aura (PR = 1.5, 95% CI = 1.2, 
1.9 and PR = 1.3, 95% CI = 1.1, 1.6 for women; PR = 1.9, 95% CI = 1.2, 2.9 and OR
= 1.4, 95% CI = 1.0, 1.8 for men). In contrast, migraine and other headaches were
not associated with CHD, regardless of the presence of aura. CONCLUSIONS: The
lack of association of migraines with coronary heart disease suggests that the
association of migraine with Rose angina is not related to coronary artery
disease. Future research assessing other common underlying pathologic mechanisms 
is warranted.

Publication Types: 
    Comparative Study
    Multicenter Study
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 15623679 [PubMed - indexed for MEDLINE]

1968: Neurology. 2004 Dec 28;63(12):2215-24.

Practice parameter: pharmacological treatment of migraine headache in children
and adolescents: report of the American Academy of Neurology Quality Standards
Subcommittee and the Practice Committee of the Child Neurology Society.

Lewis D, Ashwal S, Hershey A, Hirtz D, Yonker M, Silberstein S; American Academy 
of Neurology Quality Standards Subcommittee; Practice Committee of the Child
Neurology Society.

Division of Child Neurology, Department of Pediatrics, Children's Hospital of the
King's Daughters, Eastern Virginia Medical School, Norfolk, USA.

OBJECTIVE: To review evidence on the pharmacologic treatment of the child with
migraine headache. METHODS: The authors reviewed, abstracted, and classified
relevant literature. Recommendations were based on a four-tiered scheme of
evidence classification. Treatment options were separated into medications for
acute headache and preventive medications. RESULTS: The authors identified and
reviewed 166 articles. For acute treatment, five agents were reviewed.
Sumatriptan nasal spray and ibuprofen are effective and are well tolerated vs
placebo. Acetaminophen is probably effective and is well tolerated vs placebo.
Rizatriptan and zolmitriptan were safe and well tolerated but were not superior
to placebo. For preventive therapy, 12 agents were evaluated. Flunarizine is
probably effective. The data concerning cyproheptadine, amitriptyline, divalproex
sodium, topiramate, and levetiracetam were insufficient. Conflicting data were
found concerning propranolol and trazodone. Pizotifen, nimodipine, and clonidine 
did not show efficacy. CONCLUSIONS: For children (>age 6 years), ibuprofen is
effective and acetaminophen is probably effective and either can be considered
for the acute treatment of migraine. For adolescents (>12 years of age),
sumatriptan nasal spray is effective and should be considered for the acute
treatment of migraine. For preventive therapy, flunarizine is probably effective 
and can be considered, but is not available in the United States. There are
conflicting or insufficient data to make any other recommendations for the
preventive therapy of migraine in children and adolescents. For a clinical
problem so prevalent in children and adolescents, there is a disappointing lack
of evidence from controlled, randomized, and masked trials.

Publication Types: 
    Guideline
    Practice Guideline
    Review

PMID: 15623677 [PubMed - indexed for MEDLINE]

1969: Plast Reconstr Surg. 2005 Jan;115(1):1-9.

Comprehensive surgical treatment of migraine headaches.

Guyuron B, Kriegler JS, Davis J, Amini SB.

Case Western Reserve University and the American Migraine Center, Zeeba Clinic,
Cleveland, Ohio, USA. bguyuron@aol.com

The purpose of this study was to investigate the efficacy of surgical
deactivation of migraine headache trigger sites. Of 125 patients diagnosed with
migraine headaches, 100 were randomly assigned to the treatment group and 25
served as controls, with 4:1 allocation. Patients in the treatment group were
injected with botulinum toxin A for identification of trigger sites. Eighty-nine 
patients who noted improvement in their migraine headaches for 4 weeks underwent 
surgery. Eighty-two of the 89 patients (92 percent) in the treatment group who
completed the study demonstrated at least 50 percent reduction in migraine
headache frequency, duration, or intensity compared with the baseline data; 31
(35 percent) reported elimination and 51 (57 percent) experienced improvement
over a mean follow-up period of 396 days. In comparison, three of 19 control
patients (15.8 percent) recorded reduction in migraine headaches during the
1-year follow-up (p < 0.001), and no patients observed elimination. All variables
for the treatment group improved significantly when compared with the baseline
data and the control group, including the Migraine-Specific Questionnaire, the
Migraine Disability Assessment score, and the Short Form-36 Health Survey. The
mean annualized cost of migraine care for the treatment group (925 dollars) was
reduced significantly compared with the baseline expense (7612 dollars) and the
control group (5530 dollars) (p < 0.001). The mean monthly number of days lost
from work for the treatment group (1.2) was reduced significantly compared with
the baseline data (4.41) and the control group (4.4) (p = 0.003). The common
adverse effects related to injection of botulinum toxin A included discomfort at 
the injection site in 27 patients after 227 injections (12 percent), temple
hollowing in 19 of 82 patients (23 percent), neck weakness in 15 of 55 patients
(27 percent), and eyelid ptosis in nine patients (10 percent). The common
complications of surgical treatment were temporary dryness of the nose in 12 of
62 patients who underwent septum and turbinate surgery (19.4 percent), rhinorrhea
in 11 (17.7 percent), intense scalp itching in seven of 80 patients who underwent
forehead surgery (8.8 percent), and minor hair loss in five (6.3 percent).
Surgical deactivation of migraine trigger sites can eliminate or significantly
reduce migraine symptoms. Additional studies are necessary to clarify the
mechanism of action and to determine the long-term results.

Publication Types: 
    Clinical Trial
    Comparative Study
    Randomized Controlled Trial

PMID: 15622223 [PubMed - indexed for MEDLINE]

1970: Clin Neuropharmacol. 2004 Nov-Dec;27(6):278-80.

Open-label zonisamide for refractory migraine.

Drake ME Jr, Greathouse NI, Renner JB, Armentbright AD.

Ohio State University, Columbus, Ohio 43210, USA. medrake1@pol.net

OBJECTIVES: Zonisamide is a novel anticonvulsant drug with multiple mechanisms of
action, many of which may confer efficacy in the treatment of migraine headaches.
This study investigated the use of open-label zonisamide in treating patients
with refractory migraine headaches. METHODS: Thirty-four migraine patients were
initiated on a 100-mg/day zonisamide dosage, which was titrated to 400 mg/day as 
tolerated. Mean headache severity, frequency, and duration were assessed before
and 1, 2, and 3 months after initiation of zonisamide therapy. RESULTS:
Statistically significant improvements in headache severity (P <0.01), duration
(P <0.05), and frequency (P <0.05) were evident after 1 month of zonisamide
therapy and were carried through month 3 of treatment. Zonisamide was well
tolerated, with only 4 patients (11.8%) discontinuing for adverse events,
including dysphoria (n=2) and difficulty concentrating (n=2). Other adverse
events were transient and tolerable. CONCLUSIONS:: These results suggest that
zonisamide may be a safe and effective adjunctive agent for migraine prevention. 
Double-blind studies are warranted to confirm these findings.

Publication Types: 
    Clinical Trial
    Clinical Trial, Phase II
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 15613932 [PubMed - indexed for MEDLINE]

1971: Cephalalgia. 2005 Jan;25(1):75-8.

Referred cutaneous allodynia in a migraine patient without simultaneous headache.

Ashkenazi A, LoPinto C, Young WB.

Jefferson Headache Center, Thomas Jefferson University, Philadelphia, PA 19107,
USA. avi.ashkenazi@mail.tju.edu

Cutaneous allodynia has been described in migraine. We report on a 39-year-old
woman with migraine with aura who had cutaneous allodynia to both dynamic (brush)
and static (pressure) mechanical stimulation between attacks. For both sensory
modalities, the evoked pain on allodynia testing was located to the right frontal
area (the location of her usual migraine headache), contralaterally to the
stimulated skin area. There was no allodynia when the right frontal area was
stimulated directly. We suggest the term 'referred allodynia' for this phenomenon
and discuss possible mechanisms for its occurrence.

Publication Types: 
    Case Reports

PMID: 15606575 [PubMed - indexed for MEDLINE]

1972: Cephalalgia. 2005 Jan;25(1):60-7.

Time perception in migraine sufferers: an experimental matched-pairs study.

Anagnostou E, Mitsikostas DD.

Department of Neurology, Athens Naval Hospital, Athens, Greece.
evan73@ath.forthnet.gr

Despite occasional case reports, the influence of migraine on time perception has
not been systematically investigated. We used an experimental technique to study 
the estimation of auditory duration in 40 migraineurs at different tone intervals
in the ms and in the 1-s range and compared their performance with 40 matched
normal subjects. With a time awareness questionnaire we also evaluated the
subjective experience of elapsing time for long durations involving long-term
memory processes. Migraine did not influence temporal judgements in either of the
tests, suggesting that migraineurs do not generally over- or underestimate
temporal events. The subgroup of migraineurs with a depressive disorder, however,
showed a marked speeding up of their internal timekeeping mechanisms, pointing to
depression as an important covariable in time perception.

Publication Types: 
    Comparative Study

PMID: 15606572 [PubMed - indexed for MEDLINE]

1973: Cephalalgia. 2005 Jan;25(1):56-9.

Persistent aura without infarction: decription of the first case studied with
both brain SPECT and perfusion MRI.

Relja G, Granato A, Ukmar M, Ferretti G, Antonello RM, Zorzon M.

Department of Clinical Medicine and Neurology, Headache Centre, University of
Trieste, Trieste, Italy.

To the best of our knowledge, persistent visual symptoms, lasting months or years
without evidence of infarction, a rare complication of migraine with aura, has
been reported in only 20 patients. We report the case of a 43-year-old woman with
a 31-year history of migraine with typical visual aura. At presentation, she
experienced a visual aura in her right hemifield followed by a pulsating
headache. The visual symptoms persisted. There were no abnormal findings on
neurological and ophthalmological examinations, EEG, visual evoked potentials
(VEPs), brain computed tomography and magnetic resonance imaging (MRI). Both
brain single photon emission computed tomography (SPECT) and brain perfusion MRI 
revealed decreased left fronto-parieto-occipital and right occipital blood
perfusion. A perfusion MRI, performed 7 months after symptom onset and almost
complete extinction of symptoms, was normal. As previously reported, we
demonstrated a cortical hypoperfusion by SPECT in a case of persistent visual
aura. For the first time this finding was confirmed by perfusion MRI.

Publication Types: 
    Case Reports
    Research Support, Non-U.S. Gov't

PMID: 15606571 [PubMed - indexed for MEDLINE]

1974: Cephalalgia. 2005 Jan;25(1):48-55.

Octreotide is not effective in the acute treatment of migraine.

Levy MJ, Matharu MS, Bhola R, Meeran K, Goadsby PJ.

Headache Group, Institute of Neurology, London, UK.

The aim of this study was to determine whether subcutaneous octreotide is
effective for the treatment of acute migraine. Patients with migraine with and
without aura as classified by the International Headache Society were recruited
to a double-blind placebo-controlled crossover study. Patients were instructed to
treat two attacks of at least moderate pain severity, with at least a 7 day
interval, using subcutaneous 100 microg octreotide or matching placebo. The
primary endpoint was the headache response defined as: severe or moderate pain
becomes mild or nil, at 2 h. The primary endpoint was analysed using a Multilevel
Analysis approach. Secondary end-points included associated symptoms and a
four-point functional disability score. The study was powered to detect a 30%
difference at an alpha of 0.05 and a beta of 0.8. A total of 51 patients were
recruited, of whom 42 provided efficacy data on an attack treated with octreotide
and 41 with placebo. Modelling the headache response as a binomial determined by 
treatment, using the patient as the level 2 variable, and considering a possible 
period effect, and sex and migraine type as other variables of interest,
subcutaneous octreotide was not significantly superior to placebo. The two hour
headache response rates were 20% for placebo and 14% for octreotide, whilst the
two hour pain free rates were 7% and 2%, respectively. Subcutaneous octreotide
100 microg is not effective in the acute treatment of migraine when compared to
placebo.

Publication Types: 
    Clinical Trial
    Comparative Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 15606570 [PubMed - indexed for MEDLINE]

1975: Cephalalgia. 2005 Jan;25(1):16-22.

Painful stimulation of the temple induces nausea, headache and extracranial
vasodilation in migraine sufferers.

Drummond PD, Granston A.

School of Psychology, Murdoch University, Western Australia.
p.drummond@murdoch.edu.au

To determine whether painful stimulation of the temple would induce nausea, ice
was applied to the temple for 30 s, three times at 4-min intervals in 23 migraine
sufferers and 22 age- and sex-matched controls. On one occasion, the ice was
applied in the presence of residual motion sickness induced by optokinetic
stimulation. On another occasion, the ice application was not preceded by
optokinetic stimulation (the baseline condition). In the baseline condition,
nausea had developed in migraine sufferers but not controls by the third
application of ice. In the presence of residual motion sickness, each painful
stimulus intensified nausea and headache in migraine sufferers whereas symptoms
were minimal in controls. Changes in frontotemporal pulse amplitude were
monitored with photoelectric pulse transducers. The extracranial blood vessels
dilated in migraine sufferers but not controls before the first application of
ice in the baseline condition, presumably due to anticipatory anxiety. In
contrast, the ice application did not provoke extracranial vasodilation in either
group after optokinetic stimulation. The findings show that susceptibility to
nausea and stress-induced extracranial vascular hyper-reactivity are associated
with the migraine predisposition. They also suggest that head pain might
intensify gastrointestinal disturbances during attacks of migraine.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 15606565 [PubMed - indexed for MEDLINE]

1976: Cephalalgia. 2005 Jan;25(1):1-11.

Preventive treatment of migraine: effect on weight.

Young WB, Rozen TD.

Jefferson Headache Center, Department of Neurology, Thomas Jefferson University
Hospital, Philadelphia, PA 19107, USA. william.b.young@jefferson.edu

Weight gain is a side-effect commonly associated with drugs used for headache
prophylaxis. Weight gain can adversely affect patient health, exacerbate comorbid
metabolic disorders and encourage noncompliance. Few studies have been conducted 
specifically on the effect of headache medications on weight, and it is important
for physicians to have accurate information about weight-gain side-effects when
identifying appropriate pharmacological regimens. This review discusses the
potential effects on weight of the more common headache medications.

Publication Types: 
    Review

PMID: 15606563 [PubMed - indexed for MEDLINE]

1977: Brain. 2005 Feb;128(Pt 2):365-74. Epub 2004 Dec 15.

Acute migrainous vertigo: clinical and oculographic findings.

von Brevern M, Zeise D, Neuhauser H, Clarke AH, Lempert T.

Neurologische Klinik, Charité, Campus Virchow-Klinikum, Augustenburger Platz 1,
13353 Berlin, Germany. michael.von_brevern@charite.de

Migrainous vertigo (MV) is an increasingly recognized cause of episodic vertigo. 
However, the pathophysiology of MV is still a matter of speculation and it is not
known to what extent the dysfunction is located in the central or peripheral
vestibular system. The aim of this prospective study was to describe the clinical
spectrum of acute MV and to clarify which structures of the vestibular system are
involved. Testing of 20 patients with acute MV included neuro-otological
examination, recording of spontaneous and positional nystagmus with 3D
video-oculography, and audiometry. Pathological nystagmus was observed in 70% of 
patients during acute MV: six had isolated spontaneous nystagmus, five had
isolated positional nystagmus and three had a combination of the two. Only a few 
patients showed additional ocular motor deficits. Imbalance was observed in all
patients except one. Hearing was not affected in any patient during the attack.
The findings during acute MV point to central-vestibular dysfunction in 10
patients (50%) and to peripheral vestibular dysfunction in three patients (15%). 
In the remaining seven patients (35%) the site of involvement could not be
determined with certainty. MV should be considered in the differential diagnosis 
of vertigo with spontaneous and positional nystagmus and can present both as a
central and a peripheral vestibular disorder.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 15601663 [PubMed - indexed for MEDLINE]

1978: BMJ. 2005 Jan 8;330(7482):63. Epub 2004 Dec 13.

Erratum in:
    BMJ. 2005 Feb 12;330(7487):345.    BMJ. 2005 Mar 12;330(7491):596.

Comment in:
    BMJ. 2005 Jan 8;330(7482):54-5.

Risk of ischaemic stroke in people with migraine: systematic review and
meta-analysis of observational studies.

Etminan M, Takkouche B, Isorna FC, Samii A.

Division of Epidemiology, Royal Victoria and Vancouver Hospitals, Canada.
Mahyar.etminan@mail.mcgill.ca

OBJECTIVE: To explore the association between migraine and risk of ischaemic
stroke. DESIGN: Systematic review and meta-analysis. DATA SOURCES: Observational 
studies published between 1966 and June 2004 (identified through Medline and
Embase) that examined the association between migraine and risk of ischaemic
stroke. RESULTS: 14 studies (11 case-control studies and 3 cohort studies) were
identified. These studies suggest that the risk of stroke is increased in people 
with migraine (relative risk 2.16, 95% confidence interval 1.89 to 2.48). This
increase in risk was consistent in people who had migraine with aura (relative
risk 2.27, 1.61 to 3.19) and migraine without aura (relative risk 1.83, 1.06 to
3.15), as well as in those taking oral contraceptives (relative risk 8.72, 5.05
to 15.05). CONCLUSIONS: Data from observational studies suggest that migraine may
be a risk factor in developing stroke. More studies are needed to explore the
mechanism of this potential association. In addition, the risk of migraine among 
users of oral contraceptives must be further investigated.

Publication Types: 
    Meta-Analysis
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, Non-P.H.S.
    Research Support, U.S. Gov't, P.H.S.
    Review

PMID: 15596418 [PubMed - indexed for MEDLINE]

1979: Cephalalgia. 2004;24 Suppl 2:24-30.

Clinical benefits of early triptan therapy for migraine.

Láinez M.

Department of Neurology, Hospital Clínico Universitario, University of Valencia, 
Valencia, Spain. jlaineza@meditex.es

The introduction of the triptans brought advances in achieving complete and
sustained pain resolution in migraine patients, compared with
non-migraine-specific treatments. However, sustained pain-free rates for triptans
recorded in many clinical trials are still relatively low. This may be due to
study participants being treated late into the attack, when pain is already
moderate or severe. Studies with almotriptan have shown that efficacy is enhanced
when treatment is given early in a migraine attack while pain is still mild,
compared with later administration when pain intensity is greater. Developments
in our understanding of migraine pathophysiology provide a rationale for this
phenomenon, with improved efficacy seen when abortive treatment is administered
before central sensitization develops. A limited window of therapeutic
opportunity exists early in an attack to improve the outcome of triptan
treatment. Early intervention is recommended to avoid the significant pain and
disability commonly associated with moderate or severe migraine.

Publication Types: 
    Review

PMID: 15595991 [PubMed - indexed for MEDLINE]

1980: Cephalalgia. 2004;24 Suppl 2:16-23.

Clinical profile and practice experience of almotriptan.

Gendolla A.

University Clinic and Policlinic of Essen, Essen, Germany.
astrid.gendolla@uni-essen.de

Patients expect their acute migraine treatment to have a rapid onset of action,
achieve complete pain relief that is sustained for 24 h, and to have a good
tolerability profile. Almotriptan has a favourable pharmacokinetic profile that
translates clinically to a rapid onset of action and consistent absorption
regardless of age, sex, food intake and status of the acute migraine attack. In
addition, almotriptan is not associated with any clinically relevant drug-drug
interactions. Pain-free status at 2 h postdose is achieved by approximately 39%
of patients receiving almotriptan in clinical trials. Recurrence of headaches
within 24 h is low with almotriptan (<22%). Almotriptan has a sustained pain-free
rate of 25-27%, which in a meta-analysis of triptans was superior to sumatriptan 
100 mg. Almotriptan therapy is associated with a low incidence of adverse events,
including those affecting the central nervous system and chest.

Publication Types: 
    Review

PMID: 15595990 [PubMed - indexed for MEDLINE]

1981: Cephalalgia. 2004;24 Suppl 2:8-15.

What do patients want from acute migraine treatment?

Gallagher R.

UMDNJ-SOM University Headache Center, Moorestown, New Jersey 08057, USA.
gallagrm@umdnj.edu

Clinical observations have shown that migraine is a progressive disorder, both
within an acute attack, and within the disease itself. Rates of diagnosis for
migraine have increased in the last decade, but more than half of migraineurs
remain undiagnosed. Patient expectations of migraine therapies have also
increased (patients require rapid and sustained pain relief with a treatment that
has good tolerability), and can differ greatly from those of physicians.
Management decisions should be made with these expectations in mind, to enhance
patient outcomes and compliance with treatment. Improved understanding of acute
migraine attack pathophysiology has led to the strategy of early treatment to
modify both the progression of the current attack and, potentially, the
progression of the disease itself in the individual. The triptans are effective
acute migraine therapies. Each agent has its own distinct profile of efficacy and
tolerability, enabling individualization of treatment.

Publication Types: 
    Review

PMID: 15595989 [PubMed - indexed for MEDLINE]

1982: Cephalalgia. 2004;24 Suppl 2:2-7.

Migraine pathophysiology and its clinical implications.

Silberstein SD.

Jefferson Headache Center, Philadelphia, PA, USA.

The vascular hypothesis of migraine has now been superseded by a more integrated 
theory that involves both vascular and neuronal components. It has been
demonstrated that the visual aura experienced by some migraineurs arises from
cortical spreading depression, and that this neuronal event may also activate
perivascular nerve afferents, leading to vasodilation and neurogenic inflammation
of the meningeal blood vessels and, thus, throbbing pain. The involvement of the 
parasympathetic system supplying the meninges also causes increased vasodilation 
and pain. As an acute attack progresses, sensory neurones in the trigeminal
nucleus caudalis become sensitized, resulting in the phenomenon of cutaneous
allodynia. Triptans may act at several points during the progression of a
migraine attack. However, the development of central sensitization impacts upon
the effectiveness of triptan therapy.

Publication Types: 
    Review

PMID: 15595988 [PubMed - indexed for MEDLINE]

1983: Funct Neurol. 2004 Jul-Sep;19(3):197-202.

The efficacy and safety of dipyrone (Novalgin) tablets in the treatment of acute 
migraine attacks: a double-blind, cross-over, randomized, placebo-controlled,
multi-center study.

Tulunay FC, Ergün H, Gülmez SE, Ozbenli T, Ozmenoğlu M, Boz C, Erdemoglu AK,
Varlikbas A, Göksan B, Inan L.

Department of Pharmacology and Clinical Pharmacology, Ankara University School of
Medicine, Ankara, Turkey. tulunay@dialup.ankara.edu.tr

Dipyrone, an effective analgesic drug, is widely used in the management of
headache. However, few studies have evaluated its efficacy and safety in
migraine. We aimed to assess the efficacy and safety of 1 g dipyrone (Novalgin,
two 500 mg tablets) on pain and related symptoms in acute migraine attacks with
or without aura in a double-blind, cross-over, randomized, placebo-controlled,
multi-center study design. Seventy-three migraine with or without aura patients, 
diagnosed according to the IHS criteria, were randomized to receive dipyrone (for
2 attacks) and placebo (for 1 attack). Pain intensity was measured on a
four-point verbal pain scale before and 1, 2, 4 and 24 hours after drug intake.
Significant improvement of pain was achieved with dipyrone compared to placebo at
all time points measured. Both patient and physician evaluations were
significantly in favor of dipyrone. Side effects were few and trivial in both
groups. We conclude that dipyrone is an effective, safe and cost-effective option
in acute migraine management.

Publication Types: 
    Clinical Trial
    Comparative Study
    Multicenter Study
    Randomized Controlled Trial

PMID: 15595715 [PubMed - indexed for MEDLINE]

1984: Can J Neurol Sci. 2004 Nov;31(4):451-9.

Progress in clinical neurosciences: Migraine-stroke: a causal relationship, but
which direction?

Kern RZ.

Division of Neurology, Mount Sinai Hospital, Toronto, Ontario, Canada.

A significant association between migraine and ischemic stroke has been
demonstrated in population and case-control studies. The risk of ischemic stroke 
appears to be higher in migraine with aura (MWA) than migraine without aura
(MwoA). Migraine-stroke comprises a number of distinct entities, including
migrainous infarction, in which ischemic stroke occurs during an attack of MWA
and migraine-related stroke, in which the causal link is less clear. Migrainous
infarction accounts for only one-third of migraine-stroke, strokes may occur
during attacks of MwoA, and a number of cerebrovascular disorders may present as 
MWA or MwoA. Migraine may occur as a consequence of conditions that are known to 
cause stroke; therefore it remains to be determined whether migraine predisposes 
to stroke in the absence of any known disease associations, if it is an
epiphenomenon of an underlying stroke diathesis, or if it requires the presence
of another stroke risk factor to produce cerebral ischemia. Furthermore, it is
unclear if ischemia results in migraine more often than migraine results in
ischemia. Careful clinical studies that evaluate this bidirectional relationship 
are needed to determine why migraine patients are subject to a higher risk of
ischemic stroke.

Publication Types: 
    Review

PMID: 15595247 [PubMed - indexed for MEDLINE]

1985: Int J Clin Pract. 2004 Oct;58(10):913-9.

Efficacy and tolerability of sumatriptan tablets administered during the
mild-pain phase of menstrually associated migraine.

Landy S, Savani N, Shackelford S, Loftus J, Jones M.

Wesley Headache and Neurology Clinic, 8000 Centerview Parkway, Suite 101,
Memphis, TN 38018, USA. wesleyhead@aol.com

Two randomised, double-blind, parallel-group, placebo-controlled clinical trials 
were conducted to assess the efficacy of sumatriptan tablets, 50mg and 100mg, for
treatment during the mild-pain phase of a menstrually associated migraine among
patients who typically experienced moderate to severe migraine preceded by an
identifiable phase of mild pain. Subjects (n = 403 in Study 1 and n = 349 in
Study 2) treated one menstrually associated migraine on an outpatient basis. The 
results demonstrate that sumatriptan tablets, 50 mg or 100 mg, were significantly
more effective than placebo at conferring pain-free response 1 h and 2 h
post-dose; migraine-free response (i.e. no pain and no associated symptoms) 2 h
post-dose; returning patients to normal functioning 2 h post-dose; and conferring
sustained freedom from pain from 2 through 24 h post-dose. Although the studies
were not designed or statistically powered to show differences between the
sumatriptan doses, a trend for slightly higher efficacy was observed for the
100-mg dose compared with the 50-mg dose on many measures. Both doses of
sumatriptan were well-tolerated. The only adverse events reported in more than 2%
of subjects in a treatment group were nausea, paresthesia, dizziness and
malaise/fatigue, all of which were reported at incidences comparable to or
slightly higher than those with placebo. Considered in the context of other
findings, these data suggest that--with menstrually associated migraine as with
non-menstrual migraine--optimal therapeutic benefit of sumatriptan tablets may be
realised when they are administered during the mild-pain phase of an attack
rather than delaying treatment until headache is moderate or severe.

Publication Types: 
    Clinical Trial
    Multicenter Study
    Randomized Controlled Trial

PMID: 15587768 [PubMed - indexed for MEDLINE]

1986: South Med J. 2004 Nov;97(11):1069-77.

Diagnosis and management of migraine headaches.

Lawrence EC.

Department of General Internal Medicine, New Mexico Veteran Administration
Medical Center, University of New Mexico Health Sciences Center, Albuquerque, NM 
87108, USA. Elawrence@salud.unm.edu

Migraine headaches afflict approximately 6% of men and 18% of women in the United
States, and cost billions of dollars each year in lost productivity, absenteeism,
and direct medical expendi tures. Despite its prevalence and the availability of 
therapeutic op tions, many patients do not seek treatment, and among those who
do, a significant portion are misdiagnosed. Correct diagnosis can be made by
identifying the historic and physical examination finding that distinguish
primary headache disorders from secondary head ache disorders, as well as the key
clinical features that distinguis migraine headaches from other types. Once
diagnosis is made, im proper or inadequate management of headache pain, related
symp toms such as nausea, and the possible aggravating side-effects of
pharmacologic therapies represent further obstacles to effective ther apy.
Dissatisfaction with migraine therapy on the basis of these factors is common.
Among abortive therapy options there are de livery methods available which may
avoid aggravating symptom such as nausea. Recommended pharmacologic agents
include non steroidal anti-inflammatory drugs, intranasal butorphanol, ergota
mine and its derivatives, and the triptans. Indications for prophylac tic in
addition to abortive therapy include the occurrence o headaches that require
abortive therapy more than twice a week, tha do not respond well to abortive
therapy, and which are particularly severe. Research is ongoing in the
pathophysiology of migraines evaluation of nonpharmacologic treatment modalities,
assessment of new drug therapies, and validation of headache guidelines.

Publication Types: 
    Case Reports
    Review

PMID: 15586597 [PubMed - indexed for MEDLINE]

1987: Am J Hum Genet. 2005 Feb;76(2):327-33. Epub 2004 Dec 7.

A new susceptibility locus for migraine with aura in the 15q11-q13 genomic region
containing three GABA-A receptor genes.

Russo L, Mariotti P, Sangiorgi E, Giordano T, Ricci I, Lupi F, Chiera R, Guzzetta
F, Neri G, Gurrieri F.

Institute of Medical Genetics, Catholic University, Rome, Italy.

Migraine is the most common type of chronic episodic headache. Several
population-based family studies have suggested a strong genetic predisposition to
migraine, especially migraine with aura (MA). Although several susceptibility
loci have been identified, none of the numerous studies performed to date have
led to the identification of a gene responsible for the more common forms of
migraine. GABA-A receptors and their modulator sites seem to be involved in the
pathophysiological events that underlie migraine. We report on clinical and
molecular data from a total of 10 families with MA, in which MA segregates as an 
autosomal dominant trait and presents with homogeneous clinical features. After
excluding linkage with the known candidate loci, we used a functional candidate
approach and genotyped these families with markers from the 15q11-q13 genomic
region, which contains the genes encoding GABA-A receptor subunits. Evidence of
linkage was obtained with a parametric two-point linkage analysis (maximum LOD
score of 5.56 at a recombination fraction of 0.001 for marker GABRB3) and was
supported by multipoint analysis (maximum LOD score of 6.54 between markers
D15S113 and D15S1019). The critical region spanned 3.6 Mb. These results provide 
the basis for further investigation of the hypothesized relationship between a
GABA-A receptor dysfunction and migraine.

PMID: 15586324 [PubMed - indexed for MEDLINE]

1988: CNS Drugs. 2004;18(15):1149-63.

The PROMISE study: PROphylaxis of MIgraine with SEglor (dihydroergotamine
mesilate) in French primary care.

Pradalier A, Lantéri-Minet M, Géraud G, Allain H, Lucas C, Delgado A.

Centre Migraines et Céphalées, Louis Mourier Hospital, Colombes, France.
secretariat.medecine4@lmr.ap-hop-paris.fr

INTRODUCTION: Seglor capsules, a unique modified-release formulation of
dihydroergotamine mesilate, have long been in clinical use in France for migraine
prophylaxis. The aim of the PROMISE (PROphylaxis of MIgraine with SEglor) study
was to establish the efficacy and tolerability of Seglor in the prevention of
migraine in a general practice setting. METHODS: The PROMISE study was a double
blind, placebo-controlled, parallel-group study carried out in primary care
practice. It included 363 migraine patients treated with Seglor or placebo for 5 
months after a 1-month placebo run-in phase. RESULTS: Migraine attack frequency
(primary efficacy criterion) decreased markedly in the two treatment groups so
that the difference in favour of Seglor did not reach statistical significance.
However, most secondary outcome measures (duration of single attack, total
duration of attacks over 1 month, consumption of mild opiate analgesics,
subjective improvement) improved to a significantly greater degree in patients
receiving Seglor than in those receiving placebo. In the 84.5% of patients who
had impaired quality of life at entry, the percentage of reduction in attack
frequency and most other efficacy measures showed significant improvement with
Seglor. The safety profile for Seglor was comparable to that of placebo.
CONCLUSION: These results support the effectiveness of Seglor in patients with
migraine-related quality-of-life impairment. The findings of the PROMISE study
also suggest that patients' quality of life should be assessed systematically
before initiating a preventive treatment for migraine.

Publication Types: 
    Clinical Trial
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 15581385 [PubMed - indexed for MEDLINE]

1989: CNS Drugs. 2004;18(15):1133-41.

Acute treatment of migraine with zolmitriptan 5 mg orally disintegrating tablet.

Spierings EL, Rapoport AM, Dodick DW, Charlesworth B.

Brigham and Women's Hospital, Boston, Massachusetts 02481-2106, USA.
espierings@partners.org

OBJECTIVE: To determine the speed of onset of headache response and duration of
response with zolmitriptan 5 mg orally disintegrating tablet (ODT) in the acute
treatment of migraine.BACKGROUND: Rapid pain relief is important for migraine
sufferers. The early efficacy (30 minutes) of the 5 mg dose of the zolmitriptan
ODT formulation was evaluated.METHODS: In this double-blind, parallel-group
trial, 670 patients were randomised to receive either zolmitriptan 5 mg ODT
(n=329) or matching placebo (n=341) to treat two migraine headaches of moderate
or severe intensity. RESULTS: Zolmitriptan 5 mg ODT was significantly more
effective than placebo in achieving a headache response (reduction in migraine
headache intensity from moderate or severe to mild or no pain) at 30 minutes
(16.5% vs 12.5%; p=0.048; primary endpoint), 1 hour (p <0.0001), and 2 hours (p
<0.0001). Significantly more patients achieved a sustained headache response for 
24 hours with zolmitriptan 5 mg ODT than with placebo (42.5% vs 16.4%; p
<0.0001). Zolmitriptan 5 mg ODT also produced a higher pain-free rate than
placebo at all timepoints (0.5, 1 and 2 hours post-dose), with the differences
becoming significant at 1 hour. Adverse events were reported by 37.7% of the
patients treated with zolmitriptan 5 mg ODT and 18.1% of the patients treated
with placebo. Those that occurred most often for the patients treated with
zolmitriptan 5 mg ODT were tightness (7.0%), dizziness (6.7%), somnolence (6.7%) 
and paraesthesias (6.1%). CONCLUSIONS: A significant headache response as early
as 30 minutes post-dose and good maintenance of this headache response at 24
hours makes zolmitriptan 5 mg ODT an excellent acute treatment for migraine.
Together with the relatively low adverse event rate, these data demonstrate that 
zolmitriptan 5 mg ODT is a valuable therapy for migraine sufferers.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial

PMID: 15581383 [PubMed - indexed for MEDLINE]

1990: Postgrad Med J. 2004 Dec;80(950):720-3.

Rofecoxib versus ibuprofen for acute treatment of migraine: a randomised placebo 
controlled trial.

Misra UK, Jose M, Kalita J.

Department of Neurology, Sanjay Gandhi Post Graduate Institute of Medical
Sciences, Lucknow, India. ukmisra@sgpgi.ac.in

BACKGROUND: Rofecoxib is a potent cyclo-oxygenase-2 inhibitor with a long
duration of action. Its role in migraine has not been systematically evaluated.
AIM: To study the efficacy of rofecoxib in migraine. METHOD: In a randomised
placebo controlled trial rofecoxib 25 mg, ibuprofen 400 mg, and placebo were
compared regarding their efficacy in relieving acute migraine attack. Migraine
patients with 2-6 attacks per month were recruited. Headache severity, functional
disability, and severity of associated symptoms were graded on a 0-3 scale. The
primary endpoint was pain relief at two hours. Relief of associated symptoms and 
sustained pain relief for 24 hours were also noted. RESULT: One hundred and
twenty four patients were randomised into rofecoxib (42), ibuprofen (40), and
placebo (42) groups. One hundred and one patients were followed up: 33 on
rofecoxib, 35 ibuprofen, and 33 placebo. Patients' ages ranged from 16-62 (mean
31.4) years, and 83 were females. Pain relief at two hours was noted in 45.5% on 
rofecoxib, 55.6% on ibuprofen, and 9.1% in the placebo group. The associated
symptoms at two hours were reduced in 39.4% on rofecoxib, 50% on ibuprofen, and
9.1% in the placebo group. Sustained 24 hour pain relief was noted in 36.4% on
rofecoxib, 41% on ibuprofen, and 6.1% in the placebo group. In the ibuprofen
group, five patients had abdominal pain but there were no side effects in those
on rofecoxib or in the control group. Both rofecoxib and ibuprofen were
significantly effective in relieving pain, associated symptoms at two hours, and 
in sustained pain relief. There was no significant difference between rofecoxib
and ibuprofen in aborting acute migraine attacks. CONCLUSIONS: Both ibuprofen and
rofecoxib were superior to placebo in aborting an acute migraine attack, and
there was no significant difference in their efficacy in an acute migraine
attack.

Publication Types: 
    Clinical Trial
    Comparative Study
    Randomized Controlled Trial

PMID: 15579612 [PubMed - indexed for MEDLINE]

1991: Brain. 2005 Jan;128(Pt 1):86-97. Epub 2004 Dec 1.

Propranolol modulates trigeminovascular responses in thalamic ventroposteromedial
nucleus: a role in migraine?

Shields KG, Goadsby PJ.

Headache Group, Institute of Neurology and The National Hospital for Neurology
and Neurosurgery, London, UK.

Migraine is a common, debilitating condition affecting up to 15% of the
population. The ventroposteromedial nucleus of the thalamus relays trigeminal
sensory input to the primary somatosensory cortex. In vivo electrophysiological
recordings were made from the cell bodies of thalamocortical relay neurons in
rats. We investigated whether microiontophoretic ejection of beta antagonists
could inhibit thalamocortical activity in response to superior sagittal sinus
(SSS) stimulation. We also studied 'postsynaptic' actions of these drugs through 
their modulatory actions on L-glutamate-evoked third order neuronal firing.
Propranolol inhibited responses to SSS stimulation (P < 0.001) and L-glutamate
ejection (P < 0.001). This was due to an action on beta receptors as it could be 
partially reversed by co-ejection of isoproterenol (SSS, P = 0.02; L-glutamate, P
= 0.006). Serotonin (5-HT) receptor antagonism did not contribute to
propranolol's action since the 5-HT1A receptor antagonist, (S)-WAY 100135 (P =
0.2), and the 5-HT1B/1D receptor antagonist, GR127935 (P = 0.6), did not affect
L-glutamate-evoked neuronal firing. Atenolol inhibited both responses (SSS, P =
0.003; L-glutamate, P < 0.001). The beta2 antagonist ICI 118,551 had no effect
(SSS, P = 0.9; L-glutamate, P = 0.4), nor did the beta2 agonist procaterol (SSS, 
P = 0.6; L-glutamate, P = 0.9). SR 59230A (beta3 antagonist) also produced no
significant inhibition (SSS, P = 0.7; L-glutamate, P = 0.2), indicating an
inhibitory role for beta1 antagonists only. beta Blockers therefore may exert
some of their therapeutic effects in migraine through beta1 adrenoceptor
antagonist actions in the thalamus. Thalamic involvement in migraine is
attractive given the complex and widespread nature of the sensory disturbance.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 15574468 [PubMed - indexed for MEDLINE]

1992: J Oral Maxillofac Surg. 2004 Dec;62(12):1453-6.

Lower-half facial migraine: a report of 11 cases.

Peñarrocha M, Bandrés A, Peñarrocha M, Bagán JV.

School of Dentistry, University of Valencia, Spain. Miguel.penarrocha@uv.es

PURPOSE: Vascular pain of the face constitutes a variant of pain of the head, and
includes migraine, cluster headache, paroxysmal hemicrania, and a facial variant 
of the so-called lower-half migraine. Lower-half facial migraine is a condition
difficult to classify; according to the international classifications it could
not be found as an individual entity. The objective of the present study is to
determine the difficulties we encountered in diagnosis, the ineffective
treatments provided, and the pharmacologic treatment effect. PATIENTS AND
METHODS: A study is made of 11 cases of lower-half facial migraine, corresponding
to 10 women and 1 man (mean age, 35 years), commenting on the clinical
characteristics of the disorder and its treatment options. The location of the
pain often mimics dental pain, and can lead to a mistaken diagnosis and to the
application of inappropriate therapeutic measures. Forty-five percent of the
patients had a history of endodontic treatment before the development of pain in 
the initially affected quadrant. Once the pain had developed, extractions were
carried out in 36% of cases in an unsuccessful attempt to secure symptom relief. 
Our pharmacologic treatment consisted of ergotamine in 9 cases and the remaining 
2 patients received indomethacin. RESULTS: Nine patients (82%) improved as a
result of treatment, with an important reduction in the frequency of the pain
episodes and intensity of pain. One patient failed to respond to ergotamine,
while another patient failed to improve with indomethacin. Both were prescribed
only minor analgesics. CONCLUSION: The treatment of migraine occurring in the
face is no different than that provided for pain occurring in the head.

PMID: 15573344 [PubMed - indexed for MEDLINE]

1993: Clin Neurol Neurosurg. 2004 Dec;107(1):44-8.

Venlafaxine versus amitriptyline in the prophylactic treatment of migraine:
randomized, double-blind, crossover study.

Bulut S, Berilgen MS, Baran A, Tekatas A, Atmaca M, Mungen B.

Department of Neurology, Faculty of Medicine, Firat University, TR 23119 Elazig, 
Turkey. serpilbulut@firat.edu.tr

In patients with migraine with or without aura the prophylactic effect of
amitriptyline (AMT) and venlafaxine (VLF) was compared in a randomized
double-blind crossover study. Intolerable side effects resulted in drop out of
five patients on AMT (due to hypersomnia, difficulty in concentration and
orthostatic hypotension) and one patient on VLF (because of nausea and vomiting).
Following the run-in period the patients (n = 52) were randomly treated with one 
of the study medications for 12 weeks. After a wash-out period lasting 4 weeks
the patients were treated with the other drug for further 12 weeks. Both drugs
had significant beneficial effect on pain parameters. Total number of side
effects of VLF was low when compared with the side effect profile of AMT. In
conclusion, it is suggested that VLF may be considered for the prophylaxis of
migraine because of its low and/or tolerable side effect properties.

Publication Types: 
    Clinical Trial
    Comparative Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 15567552 [PubMed - indexed for MEDLINE]

1994: Cephalalgia. 2004 Dec;24(12):1057-66.

Sumatriptan (5-HT1B/1D-agonist) causes a transient allodynia.

Linde M, Elam M, Lundblad L, Olausson H, Dahlöf CG.

Gothenburg Migraine Clinic, Gothenburg, Sweden. mattias.linde@neuro.gu.se

Unpleasant sensory symptoms are commonly reported in association with the use of 
5-HT1B/1D-agonists, i.e. triptans. In particular, pain/pressure symptoms from the
chest and neck have restricted the use of triptans in the acute treatment of
migraine. The cause of these triptan induced side-effects is still unidentified. 
We have now tested the hypothesis that sumatriptan influences the perception of
tactile and thermal stimuli in humans in a randomized, double-blind,
placebo-controlled cross-over study. Two groups were tested; one consisted of 12 
(mean age 41.2 years, 10 women) subjects with migraine and a history of cutaneous
allodynia in association with sumatriptan treatment. Twelve healthy subjects
(mean age 38.7 years, 10 women) without migraine served as control group. During 
pain- and medication-free intervals tactile directional sensibility, perception
of dynamic touch (brush) and thermal sensory and pain thresholds were studied on 
the dorsal side of the left hand. Measurements were performed before, 20, and 40 
min after injection of 6 mg sumatriptan or saline. Twenty minutes after
injection, sumatriptan caused a significant placebo-subtracted increase in
brush-evoked feeling of unpleasantness in both groups (P < 0.01), an increase in 
brush-evoked pain in migraineurs only (P = 0.021), a reduction of heat pain
threshold in all participants pooled (P = 0.031), and a reduction of cold pain
threshold in controls only (P = 0.013). At 40 min after injection, no differences
remained significant. There were no changes in ratings of brush intensity,
tactile directional sensibility or cold or warm sensation thresholds. Thus,
sumatriptan may cause a short-lasting allodynia in response to light dynamic
touch and a reduction of heat and cold pain thresholds. This could explain at
least some of the temporary sensory side-effects of triptans and warrants
consideration in the interpretation of studies on migraine-induced allodynia.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial

PMID: 15566420 [PubMed - indexed for MEDLINE]

1995: Cephalalgia. 2004 Dec;24(12):1024-30.

Comment in:
    Cephalalgia. 2004 Dec;24(12):1013-5.

Clinical implications of migraine in systemic lupus erythematosus: relation to
cumulative organ damage.

Appenzeller S, Costallat LT.

Unit of Rheumatology, Department of Internal Medicine State University of
Campinas Faculty of Medical Sciences, Campinas, Brazil. appenzel@unicamp.br

The aim of this study was to determine the clinical implications of migraine in
systemic lupus erythematosus (SLE) using the cumulative organ damage scores
(SLICC-DI). Eighty SLE, 40 rheumatoid arthritis (RA) patients and 40 controls
(non SLE, nor RA out-patients), all women, were included. Migraine was defined
according to the International Headache Society (IHS) criteria for
neuropsychiatric SLE. Disease activity was measured by MEX-SLEDAI and cumulative 
organ damage by SLICC-DI. Statistics were obtained by Chi-square and Fischer's
exact tests. anova was used for comparing means. Migraine was identified in 42.5%
of SLE patients, compared to 12.5% of RA patients (P < 0.05) and 10.0% (P < 0.05)
in the control group. In the SLE group, a significant association between
migraine and Raynaud's phenomenon (P = 0.003, OR = 10.1; 95%CI 2.9-35) and
antiphospholipid antibodies (P = 0.0012; OR = 7.5; 95%CI 2.5-22.9) was noted. SLE
patients with active migraine had higher MEX-SLEDAI scores than SLE patients
without migraine. SLE patients with past history of migraine had significantly
higher SLICC scores than SLE patients without migraine. History of migraine was
associated with greater organ damage. Active migraine was associated with higher 
disease activity, antiphospholipid antibodies and worsening of Raynaud's
phenomenon. The increased cumulative organ damage in SLE patients with past
history of migraine justifies the routine evaluation of migraine in clinical
practice.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 15566416 [PubMed - indexed for MEDLINE]

1996: Cephalalgia. 2004 Dec;24(12):1016-23.

Sporadic hemiplegic migraine.

Thomsen LL, Olesen J.

Danish Headache Centre, University of Copenhagen and Department of Neurology,
Glostrup University Hospital, Glostrup, Copenhagen, 2600 Denmark. LLT@dadlnet.dk

Sporadic hemiplegic migraine (SHM) is defined as migraine attacks associated with
some degree of motor weakness/hemiparesis during the aura phase and where no
first degree relative (parent, sibling or child) has identical attacks. The
present review deals with recent scientific studies according to which: The SHM
prevalence is estimated to be 0.005%; SHM patients have clinical symptoms
identical to patients with familial hemiplegic migraine (FHM) and significantly
different from patients with migraine with typical aura (typical MA); SHM
affected had no increased risk of migraine without aura (MO), but a highly
increased risk of typical MA compared to the general population; SHM patients
only rarely have mutations in the FHM gene CACNA1A; SHM attacks in some cases can
be treated with Verapamil. The reviewed data underlie the change in the
International Classification of Headache Disorders 2nd edition where SHM became
separated from migraine with typical aura or migraine with prolonged aura. All
cases with motor weakness should be classified as either FHM or SHM.

Publication Types: 
    Review

PMID: 15566415 [PubMed - indexed for MEDLINE]

1997: Brain. 2005 Jan;128(Pt 1):98-103. Epub 2004 Nov 24.

Comment in:
    Brain. 2005 Sep;128(Pt 9):E36; author reply E37.

Somatosensory evoked high-frequency oscillations reflecting thalamo-cortical
activity are decreased in migraine patients between attacks.

Coppola G, Vandenheede M, Di Clemente L, Ambrosini A, Fumal A, De Pasqua V,
Schoenen J.

Headache Research Unit, University Department of Neurology, University of Liège, 
CHR Citadelle, Liège, Belgium.

A deficit of habituation in cortical information processing, including
somatosensory evoked potentials (SSEPs), is the most consistent
neurophysiological abnormality in migraine patients between attacks. To explore
further the mechanisms underlying this interictal neural dysfunction, we have
studied the high-frequency oscillations (HFOs) embedded in SSEPs because they are
thought to reflect spike activity in thalamo-cortical cholinergic fibres (early
HFOs) and in cortical inhibitory GABAergic interneurons (late HFOs). Untreated
migraine patients with (MA) and without (MO) aura were recorded during (n = 13:
nine MO, four MA) and between attacks (n = 29: 14 MO, 15 MA) and compared with
healthy volunteers. SSEPs were filtered off-line (digital band-pass between 450
and 750 Hz) to extract the two HFO bursts from the broad-band contralateral N20
somatosensory cortical response obtained by median nerve stimulation. In both
migraine groups, amplitudes and latencies of conventional broad-band SSEPs
recorded interictally from cervical and parietal active electrodes were not
significantly different from those found in healthy volunteers. In contrast,
maximum peak-to-peak amplitude and area under the rectified curve of the early
HFO burst were significantly smaller in both MA and MO patients than in healthy
volunteers. There was no significant difference in the later HFO burst between
migraineurs and healthy volunteers. During attacks, all electrophysiological
measurements in migraineurs were similar to those found in healthy volunteers.
Thalamo-cortical activation, as reflected by the early SSEP HFO burst, may thus
be reduced in migraine interictally, but normalizes during an attack, whereas
intracortical inhibition, as indexed by the late HFO burst, is normal at any
time. This supports the hypothesis that the habituation deficit in migraineurs is
due to a reduced pre-activation level of sensory cortices and not to increased
cortical excitability or reduced intracortical inhibition.

PMID: 15563513 [PubMed - indexed for MEDLINE]

1998: Neurology. 2004 Nov 23;63(10):1942-3.

Comment in:
    Neurology. 2005 May 10;64(9):1666-7; author reply 1666-7.

Single-fiber EMG in familial hemiplegic migraine.

Terwindt GM, Kors EE, Vein AA, Ferrari MD, van Dijk JG.

Department of Neurology, Leiden University Medical Center, Albinusdreef 2, 2300
RC Leiden, The Netherlands. G.M.Terwindt@lumc.nl

Twelve familial hemiplegic migraine (FHM) patients (6 with the I1811L mutation in
CACNA1A, 3 with M731T mutation in ATP1A2, and 3 without known mutations) and 10
control subjects underwent single-fiber EMG. Mean jitter did not differ
significantly between patients and control subjects or among patients. No
blocking was found. The results suggest that neuromuscular function is normal in 
FHM.

Publication Types: 
    Comparative Study

PMID: 15557518 [PubMed - indexed for MEDLINE]

1999: BMJ. 2004 Dec 11;329(7479):1369-73. Epub 2004 Nov 18.

Comment in:
    ACP J Club. 2005 May-Jun;142(3):77.

Parenteral metoclopramide for acute migraine: meta-analysis of randomised
controlled trials.

Colman I, Brown MD, Innes GD, Grafstein E, Roberts TE, Rowe BH.

Department of Psychiatry, University of Cambridge, Cambridge CB2 2QQ.

OBJECTIVE: To assess the evidence from controlled trials on the efficacy and
tolerability of parenteral metoclopramide for acute migraine in adults. DATA
SOURCES: Cochrane Central Register of Controlled Trials, Medline, Embase, LILACS,
CINAHL, conference proceedings, clinical practice guidelines, and other sources. 
SELECTION CRITERIA: Randomised controlled trials of parenteral metoclopramide for
acute migraine in adults. RESULTS: We reviewed 596 potentially relevant abstracts
and found 13 eligible trials totalling 655 adults. In studies comparing
metoclopramide with placebo, metoclopramide was more likely to provide
significant reduction in migraine pain (odds ratio 2.84, 95% confidence interval 
1.05 to 7.68). Used as the only agent, metoclopramide showed mixed effectiveness 
when compared with other single agents. Heterogeneity of studies for combination 
treatment prevented statistical pooling. Treatments that did include
metoclopramide were as, or more, effective than comparison treatments for pain,
nausea, and relapse outcomes reported in all studies. CONCLUSIONS: Metoclopramide
is an effective treatment for migraine headache and may be effective when
combined with other treatments. Given its non-narcotic and antiemetic properties,
metoclopramide should be considered a primary agent in the treatment of acute
migraines in emergency departments.

Publication Types: 
    Meta-Analysis
    Research Support, Non-U.S. Gov't

PMID: 15550401 [PubMed - indexed for MEDLINE]

2000: Neurol Sci. 2004 Oct;25 Suppl 3:S93-6.

The physiopathology of migraine: the contribution of genetics.

Montagna P.

Department of Neurological Sciences, University of Bologna Medical School, Via U.
Foscolo 7, I-40123 Bologna, Italy. pmontagn@neuro.unibo.it

Recent advances in the studies of the genetic liability to migraine include the
discovery of two genes responsible for familial hemiplegic migraine (FHM) and the
analysis of several sites of linkage or genetic association for the so-called
typical migraines, e. g., migraine with (MA) and without aura (MO). The 2 genes
implicated in the genetics of FHM are CACNA1A for FHM1 and ATP1A2 for FHM2. It is
still unclear how dysfunction in these genes may trigger attacks of migraine with
hemiplegic features and, in at least part of the families with FHM, also
paroxysmal or progressive ataxia and epileptic seizures. It appears that
mutations in CACNA1A responsible for FHM1 alter calcium influx and calcium
currents in neurons, possible factors of spreading depression like events. On the
other hand, abnormal regulation of intracellular calcium concentrations could
alter neurotransmitter release and other cellular functions. In the case of
ATP1A2 mutations, haplo-insufficiency of the gene has been hypothesised to result
in abnormal potassium level regulation because of faulty Na/K exchange with
subsequent depolarisation and increased liability to spreading depression, or/and
in abnormal calcium levels because of the concomitant activation of the Na/Ca
exchanger, with a mechanism therefore comparable to that at work in FHM1. Much
more work is clearly necessary to elucidate these pathophysiological mechanisms; 
advances in genetics however may represent important steps in the clarification
of the physiopathology of the migraine attack.

Publication Types: 
    Review

PMID: 15549578 [PubMed - indexed for MEDLINE]

2001: Neurol Sci. 2004 Oct;25 Suppl 3:S300-1.

Migrainous cerebral infarction: case reports.

Frigerio R, Santoro P, Ferrarese C, Agostoni E.

Department of Neuroscience and Biomedical Technologies, University of
Milano-Bicocca, Monza, Italy.

Migraine is a common and chronic disorder. It is considered benign but several
studies have suggested it as a rare risk factor for ischaemic stroke. The
association is still conflicting and seems to be restricted to particular
subgroups of patients (i.e., women under the age of 45, with migraine with aura, 
and particularly ones who smoke and use oral contraceptives). The pathogenetic
mechanisms underlying this condition are not known. We describe 6 cases of
migrainous stroke fully meeting the diagnostic criteria of the International
Headache Society (IHS). For each patient, demographic and anamnestic data,
clinical features, results of laboratory tests and neuroimaging findings were
recorded. Five of the 6 cases were women (median age of 29, range from 23 to 40).
The man was 36. All patients fulfilled the IHS criteria for migraine with aura.
At the time of the event, 2 patients were taking oral contraceptives and smoked, 
one patient smoked and three patients had no vascular risk factors. The stroke
manifested as homonymous hemianopia in 3 patients, lower homonymous quadrantopia 
in 1 patient and sensory symptom in 1 patient. The neurological examination was
normal in 1 case. All patients underwent several tests with negative results:
blood test (antithrombin III, protein C or S, autoantibodies), transthoracic and 
transoesophageal echocardiography, extracranial and intracranial Doppler
sonography, and angiography which was not performed in 1 patient. All patients
had a cerebral infarct visible on neuroimaging study (MRI): posterior cerebral
artery in 4, middle cerebral artery in 1 and anterior cerebral artery in 1. We
support the findings reported by others that migrainous stroke is more common in 
young women affected by migraine with aura. In consideration of the high
prevalence of migraine in the population, further research is indicated and
necessary to establish if migraine is independent from other vascular risk
factors.

Publication Types: 
    Case Reports

PMID: 15549569 [PubMed - indexed for MEDLINE]

2002: Neurol Sci. 2004 Oct;25 Suppl 3:S291-2.

Migraine, daily chronic headache and fibromyalgia in the same patient: an
evolutive "continuum" of non organic chronic pain? About 100 clinical cases.

Centonze V, Bassi A, Cassiano MA, Munno I, Dalfino L, Causarano V.

Headache Unit, Internal Medicine P.O. F. Jaia, Conversano (BA), Italy.
vincenzocentonze@inwind.it

Aim of this study is to evaluate if migraine, daily chronic headache and
fibromyalgia in the same patient can be considered as an evolutive continuum of
non organic chronic pain. Therefore, migraine, daily chronic headache and
fibromyalgia should be considered the expression of chronic antinociceptive
system alteration.

Publication Types: 
    Clinical Trial

PMID: 15549565 [PubMed - indexed for MEDLINE]

2003: Neurol Sci. 2004 Oct;25 Suppl 3:S288-90.

Visual evoked potentials in migraine.

Spreafico C, Frigerio R, Santoro P, Ferrarese C, Agostoni E.

Divisione di Neurologia, Ospedale Niguarda, Piazza Ospedale Maggiore 3, I-20162
Milan, Italy. chiara.spr@tiscali.it

Migraine is a chronic disorder. Visual symptoms and hypersensitivity to light
stimuli are common. The aim of this study is the analysis of visual system in
migraineurs by visual evoked potentials (VEP). We studied 53 migraineurs (21 with
prophylactic migraine treatment and 32 without preventive therapy) and 20 healthy
control subjects. We found lower P100 latencies in migraineurs without therapy
compared to controls. In treated patients, P100 latencies showed the same trend
seen in the control group. We speculate a different responsiveness of the visual 
system in migraineurs probably due to a dysmodulation of sensor input leading to 
facilitation of visual processing.

Publication Types: 
    Clinical Trial

PMID: 15549564 [PubMed - indexed for MEDLINE]

2004: Neurol Sci. 2004 Oct;25 Suppl 3:S285-7.

Cortical function abnormalities in migraine: neurophysiological and
neuropsychological evidence from reaction times and event-related potentials to
the Stroop test.

Annovazzi P, Colombo B, Bernasconi L, Schiatti E, Comi G, Leocani L.

Department of Neurology, I.R.C.C.S. San Raffaele, Via Olgettina 48, I-20132
Milan, Italy.

Cortical hyperexcitability was studied in migraine patients using reaction times 
(RT's) and Event-Related Potentials (ERP) to the Stroop test. We found a slower
RTs in patients if compared to controls, supporting the hypothesis of a mild
cortical functions impairment even in interictal periods in this group of
patients.

Publication Types: 
    Clinical Trial

PMID: 15549563 [PubMed - indexed for MEDLINE]

2005: Neurol Sci. 2004 Oct;25 Suppl 3:S283-4.

Visually evoked phase synchronisation changes of alpha rhythm in migraine.
Correlations with clinical features.

de Tommaso M, Stramaglia S, Marinazzo D, Guido M, Lamberti P, Livrea P.

Department of Neurological and Psychiatric Sciences, University of Bari,
Policlinico, Piazza Giulio Cesare 11, I-70124 Bari, Italy.
m.detommaso@neurol.uniba.it

We investigate phase synchronisation in EEG recordings from migraine patients. We
use the analytic signal technique, based on the Hilbert transform, and find that 
migraine brains are characterised by enhanced alpha band phase synchronisation in
the presence of visual stimuli. In migraine, the brain synchronises to the idling
rhythm of the visual areas under certain photic stimulations;
hypersynchronisation of the alpha rhythm may suggest a state of cortical
hypoexcitability during the interictal phase of migraine.

PMID: 15549562 [PubMed - indexed for MEDLINE]

2006: Neurol Sci. 2004 Oct;25 Suppl 3:S276-8.

Identifying patients who require a change in their current acute migraine
treatment: the Migraine Assessment of Current Therapy (Migraine-ACT)
questionnaire.

Dowson AJ, D'Amico D, Tepper SJ, Baos V, Baudet F, Kilminster S.

The King's Headache Service, King's College Hospital, Denmark Hill, London SE5
9RS, UK. AndyDowson@psim-limited.com

The aim of the study was to design and test a new, easy to use, assessment tool, 
the Migraine Assessment of Current Therapy (Migraine-ACT), for identifying
patients who require a change in their acute treatment. A 27-item questionnaire
was developed by an international advisory board including questions formulated
in four domains: headache impact, global assessment of relief, consistency of
response and emotional response. Migraine patients entered a multinational,
prospective study to investigate the test-retest reliability and construct
validity of the tool, which was completed by the patients on two occasions.
Test-retest reliability was assessed by Pearson's and by Spearman correlation
coefficients. Construct validity was assessed by correlating patients' answers to
the 27-item questionnaire with those of well-reported measures: SF-36, MIDAS and 
Migraine Therapy Assessment Questionnaire (MTAQ). The test-retest reliability of 
the 27 initial questions ranged from good to excellent. Correlations of all items
with SF-36, MIDAS and MTAQ scores--assessed by discriminatory t-tests--indicated 
that the following 4 were the most discriminating items: Does your migraine
medication work consistently, in the majority of your attacks? Does the headache 
pain disappear within 2 hours? Are you able to function normally within 2 hours? 
Are you comfortable enough with your medication to be able to plan your daily
activities? The 4-item Migraine-ACT is a brief, simple, and reliable assessment
tool to identify patients who require a change in their acute migraine treatment,
and can be recommended for primary care physicians, neurologists and headache
clinicians.

PMID: 15549559 [PubMed - indexed for MEDLINE]

2007: Neurol Sci. 2004 Oct;25 Suppl 3:S274-5.

MIDAS questionnaire in the emergency setting.

Aliprandi A, Frigerio R, Santoro P, Frigo M, Iurlaro S, Vaccaro M, Tremolizzo L, 
Beghi E, Ferrarese C, Agostoni E.

Department of Neurology, S. Gerardo Hospital, University of Milano-Bicocca, Via
Donizetti 106, I-20052 Monza (MI), Italy.

Migraine is a common disorder and is a major cause of disability and loss of
working performance in western countries. Therefore, many tools have been
developed to assess migraine related disability. Among these, the Migraine
Disability Assessment (MIDAS) questionnaire has been shown to be of particular
interest, as it is valid, reliable and useful for therapeutic decisions. In this 
pilot study, we address the validity of the MIDAS questionnaire in an unselected 
population of migraine patients in the emergency setting. We found that the MIDAS
scores in the emergency room were similar to those collected in a specialised
headache centre. This result suggests that the MIDAS questionnaire could be
reliably used in the emergency setting, hence avoiding unnecessary delays in the 
treatment of migraine patients.

Publication Types: 
    Clinical Trial

PMID: 15549558 [PubMed - indexed for MEDLINE]

2008: Neurol Sci. 2004 Oct;25 Suppl 3:S272-3.

Chronic migraine with medication overuse: treatment outcome and disability at 3
years follow-up.

Usai S, Grazzi L, Andrasik F, D'Amico D, Rigamonti A, Bussone G.

Headache Centre, National Neurological Institute C. Besta, Via Celoria 11,
I-20133 Milan, Italy. s_usai@tin.it

Patients with chronic migraine and medication overuse are particularly difficult 
to treat. No clear consensus exists about treatment strategies to be used and
little data exists about the functional impact of headache in these patients. The
purpose of the study was to determine (1) the clinical course of a sample of
chronic migraine patients with medication overuse 36 months following treatment
intervention and (2) whether functional impairment, assessed by the Migraine
Disability Assessment (MIDAS) questionnaire, improved upon treatment. Of 106
patients meeting the criteria for chronic migraine with medication overuse
(according to Silberstein and Lipton), 71 went on to complete a structured
inpatient treatment, consisting of medication withdrawal and then prophylactic
treatment. As a group, the patients were significantly improved at 36-month
follow-up, with respect to 2 headache parameters (days of headache per month and 
number of used medications per month assessed by the diary card) and 2 measures
of functional impact extracted from the MIDAS questionnaire (MIDAS total score
and frequency of headache). Chronic migraine accompanied with medication overuse 
led to considerable disability prior to treatment. However, notable improvement
both in headache parameters and in disability measures occurred concurrently with
treatment. This suggests that successful treatment has more wide-ranging positive
benefits beyond mere symptom reduction. To our knowledge, this is the first
investigation where the MIDAS questionnaire has been used as an outcome measure
in patients with chronic headache to assess disability during such a long
follow-up period.

PMID: 15549557 [PubMed - indexed for MEDLINE]

2009: Neurol Sci. 2004 Oct;25 Suppl 3:S267-9.

Picotamide in migraine aura prevention: a pilot study.

Allais G, D'Andrea G, Airola G, De Lorenzo C, Mana O, Benedetto C.

Woman's Headache Center, Department of Gynecology and Obstetrics, University of
Turin, Via Ventimiglia 3, I-10126 Turin, Italy. gb.allais@tiscali.it

In an open, preliminary trial we evaluated the use of picotamide, an antiplatelet
drug, in the prophylactic treatment of migraine aura (MA). Twenty-two women
suffering from migraine with typical aura or MA without headache, diagnosed
according to International Headache Society criteria, entered a nine-month study.
They underwent a three-month run-in period free of prophylactic drugs, followed
by a six-month treatment period (subdivided in two trimesters, TI and TII) with
300 mg of picotamide administered twice daily. A detailed diary reporting
neurological symptoms, duration and frequency of MA was compiled by patients
along the trial time. The number of MA significantly decreased during treatment
(from 6.85+/-3.82 in the run-in trimester to 2.85+/-2.72 during TI and to
2.55+/-2.89 during TII). Also, MA duration was decreased significantly, being
36.75+/-20.28 min during run-in, 20.00+/-16.94 during TI and 17.75+/-16.26 during
TII. In 25% of patients MA totally disappeared. The number and the features of
aura neurological symptoms were also positively modified by the use of
picotamide. No serious adverse event was provoked by picotamide administration.
Picotamide is effective in reducing MA frequency, duration and symptomatology.
The effect is clearly evident in the first trimester of treatment and is
maintained with no further modifications during the second trimester.

Publication Types: 
    Clinical Trial

PMID: 15549555 [PubMed - indexed for MEDLINE]

2010: Neurol Sci. 2004 Oct;25 Suppl 3:S261-2.

MIDAS questionnaire modification for a new MIDAS junior questionnaire: a clinical
experience at the Neurological Institute "C. Besta".

Grazzi L.

Headache Centre, National Neurological Institute C. Besta, Via Celoria 11,
I-20133 Milan, Italy. liciagrazzi@mac.com

During the last decade researchers have begun to employ standardised
methodologies to investigate the global impact of primary headaches.
Disease-specific instruments have been developed to measure headache-related
disability. The MIDAS questionnaire, which is the most extensively studied of
these instruments, was designed to assess the overall impact of headaches over
the 3 months before compilation. The MIDAS questionnaire is an optimal tool to
assess headache-related disability in adults in relation to patients' daily
activities. Primary headaches are a recurrent problem for children and
adolescents. Forty percent of children have experienced headaches by the age of 7
years increasing to 75% by the age of 15. In a recent report we determined the
suitability of the MIDAS questionnaire in its original form for assessing
disability in children and adolescents suffering from different kinds of
headache. This was the first step of a line of research aimed to develop a new
MIDAS questionnaire adapted for young patients. In this second study the aims
were: (1) to produce a new version of the MIDAS questionnaire specific for young 
patients suffering from different forms of headache; (2) to assess the
reliability of this new instrument; (3) to assess its sensitivity to treatment
intervention.

PMID: 15549553 [PubMed - indexed for MEDLINE]

2011: Neurol Sci. 2004 Oct;25 Suppl 3:S258-60.

ID-migraine.

Rapoport AM, Bigal ME.

Department of Neurology, Columbia University College of Physicians & Surgeons,
New York, NY, USA. alanrapoport@nech.net

Migraine is a highly prevalent and disabling illness that remains substantially
undiagnosed in primary care. Validated migraine screening tools are of potential 
value in addressing this important barrier for migraine treatment. Herein we
briefly discuss reasons for screening migraine in the primary care setting, and
focus on the ID-migraine, a validated migraine screening tool.

PMID: 15549552 [PubMed - indexed for MEDLINE]

2012: Neurol Sci. 2004 Oct;25 Suppl 3:S251-2.

Workplace disability in migraine: an Italian experience.

D'Amico D, Genco S, Perini F.

National Neurological Institute C. Besta, Via Celoria 11, I-20133 Milan, Italy.
damicodo@tiscali.it

Workplace disability due to migraine has not been extensively researched in
non-English speaking countries. We assessed the repercussions of headache, and
particularly of migraine, on work in a sample of employees from an Italian
company (Bulgari). Information was obtained through a self-answering
questionnaire in "all headaches" sufferers, and through direct interview in
migraine sufferers (diagnosis according to IHS criteria). Headache frequency,
pain intensity and headache-related disability were higher in migraineurs than in
"all headaches" sufferers. About a quarter of migraineurs missed at least one day
in the three months prior to the interview due to headache, and around 10% lost
two or more days over the same period. Moore than 50% of migraineurs reported 1-7
days per month at work with headache, with reduction in productivity level by 50%
or more in 15% of respondents. Our data confirmed that headaches, and
particularly migraine, cause a considerable reduction in workplace productivity. 
Workplace interventions to effectively manage migraine are needed.

PMID: 15549550 [PubMed - indexed for MEDLINE]

2013: Neurol Sci. 2004 Oct;25 Suppl 3:S249-50.

Measure of negative impact of migraine on daily activities, social relationships 
and therapeutic approach.

Frediani F, Martelletti P, Bussone G.

Neurological Department, Policlinico S. Pietro, Via Forlanini 15, I-24036 Ponte
S. Pietro (BG), Italy. fabio_frediani@yahoo.it

The study has been conducted in 9 European countries, interviewing 200 women in
each country, aged 18-35, in fully working or studying period, to get a total of 
1810 people. Migraine or severe headache was recognised and patients were studied
to understand their behaviour. The features and severity of headache, the use of 
different drugs, the relationship between physicians and patients, the disability
during attacks, the psychological aspects and the feeling of impotence that
migraine patients experienced during their lives, are analysed and reported.

PMID: 15549549 [PubMed - indexed for MEDLINE]

2014: Neurol Sci. 2004 Oct;25 Suppl 3:S244-5.

Topiramate in migraine prevention: evidence-based medicine from clinical trials.

Silberstein SD.

Department of Neurology, Thomas Jefferson University Hospital, Philadelphia, PA
19107, USA. Stephen.Silberstein@jefferson.edu

The importance of evidence-based medicine is often underestimated when migraine
preventive treatments are chosen. Evidence from large, well-conducted,
placebo-controlled trials of sufficient duration should be given particular
consideration when evaluating the efficacy, tolerability and safety of a
medication for a broad range of patients. Pizotifen, propranolol, flunarizine,
amitriptyline, divalproex sodium and topiramate have all been evaluated for
efficacy in migraine prevention in double-blind, placebo-controlled trials. The
largest clinical programme in migraine prevention, studying these or any other
agents, was comprised of 2 pivotal trials, as well as other studies, evaluating
topiramate for preventive therapy in migraine. Results from these trials
indicated that topiramate (100 mg/day) has proven safety and efficacy in migraine
prevention. Response rates were high, and onset of action usually occurred within
the first month of treatment. Therefore, topiramate has demonstrated safety and
represents an effective option in the prevention of migraine, as supported by
extensive clinical research.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 15549548 [PubMed - indexed for MEDLINE]

2015: Neurol Sci. 2004 Oct;25 Suppl 3:S242-3.

Treatment strategies in migraine patients.

D'Amico D.

National Neurological Institute C Besta, Via Celoria 11, I-20133 Milan, Italy.
damicodo@tiscali.it

The goal of migraine treatment is to alleviate the symptoms of acute attacks and 
improve patients' quality of life. Therapeutic options and strategies principally
rely on three types of approach: correction of causative factors; acute treatment
of attacks; and prophylaxis. The quality of evidence supporting efficacy,
personal experience, tolerability and safety profiles must guide the choice of a 
particular medication; nonetheless, we ought to keep in mind that therapeutic
options should also be customised to target the individual patient, both in terms
of personal characteristics and underlying comorbidities. Also, the framework of 
information the patient is given represents an essential component of migraine
management, along with his/her active involvement in the therapeutic program and 
schedule.

PMID: 15549547 [PubMed - indexed for MEDLINE]

2016: Neurol Sci. 2004 Oct;25 Suppl 3:S239-41.

Pathophysiology of migraine.

Bussone G.

National Neurological Institute C Besta, Via Celoria 11, I-20133 Milan, Italy.
bussone@istituto-besta.it

The exact pathogenesis of migraine remains to be determined. In particular there 
is increasing evidence for the neural basis of migraine. We now have a body of
data supporting the concept of central neuronal hyperexcitability as a pivotal
physiological disturbance predisposing to migraine. The reasons for increased
neuronal excitability may be multifactorial. Most recently, abnormality of
calcium channels has been introduced as a potential mechanism of interictal
neuronal excitability. Mutant voltage gated P/Q type calcium channel genes likely
influence presynaptic neurotransmitter release, possibly of excitatory amino-acid
systems or inhibitory. It could therefore be hypothesised that genetic
abnormalities result in a lowered threshold of response to trigger factors. There
is also evidence from spectroscopic studies that magnesium is low in migraine. We
currently conceive of a migraine attack as originating in the brain. Triggers of 
an attack initiate a depolarising neuroelectric and metabolic event likened to
the spreading depression of Leao. This event activates the headache and
associated features of the attack by mechanisms that remain to be determined, but
appear to involve either peripheral trigeminovascular or brain stem pathways, or 
both. Excitability of cell membranes, perhaps in part genetically determined, is 
the brain's route of susceptibility to attacks. Factors that increase or decrease
neuronal excitability constitute the threshold for triggering attacks.

PMID: 15549546 [PubMed - indexed for MEDLINE]

2017: Neurol Sci. 2004 Oct;25 Suppl 3:S234-5.

An updated review of migraine and co-morbid psychiatric disorders.

Torelli P, D'Amico D.

Headache Centre, Section of Neurology, Department of Neuroscience, University of 
Parma, I-43100 Parma, Italy. paolatorelli@libero.it

General population studies suggest a non-casual association (co-morbidity)
between migraine, major depression and anxiety disorders (panic attack disorder, 
obsessive-compulsive disorder, generalised anxiety disorder). The risk of
developing affective and anxiety disorders has not increased uniformly in the
different migraine subtypes, but it is more elevated in migraine with aura
patients. The relationship between migraine and depression is "bi-directional"
(i. e., migraineurs have a more than three-fold risk of developing depression
compared with non-migraine patients, while depression patients that have never
suffered from migraine before have a more than three-fold risk of developing
migraine compared with non-depressed patients) and specific (i. e., the presence 
of migraine or severe non-migraine headache increases a patient's risk of
developing depression or panic attack disorder, whereas the presence of
depression or panic attack disorder is associated with a greater risk of
developing migraine, but not severe non-migraine headache). The association
described in this review has significant pathogenetic, clinical and therapeutical
implications.

PMID: 15549545 [PubMed - indexed for MEDLINE]

2018: Neurol Sci. 2004 Oct;25 Suppl 3:S229-31.

Update on menstrual migraine: from clinical aspects to therapeutical strategies.

Allais G, Benedetto C.

Woman's Headache Center, Department of Gynecology and Obstetrics, University of
Turin, Via Ventimiglia 3, I-10126 Turin, Italy. gb.allais@tiscali.it

Migraine occurrence is strongly influenced by the hormonal fluctuations of the
female reproductive cycle; at least 60% of women affected by migraine relate the 
periodicity of their attacks to the menstrual cycle. The so-called menstrual
migraine, which occurs immediately before, during or at the end of the menstrual 
flow, has been a largely undefined condition, including some clinical subtypes
which are not well defined. In the last edition of the International
Classification of Headache Disorders (ICHD-II), menstrual migraine gained new
attention in the Appendix, where three clinical patterns were pointed out: pure
menstrual migraine without aura; menstrually related migraine without aura and
non-menstrual migraine without aura. Menstrual migraine attacks show severe
intensity, long duration (lasting even more than 72 h), marked unresponsiveness
to pharmacological treatments, and present higher recurrence rate and
work-related disability than non-menstrual attacks. The pharmacological treatment
of menstrual migraine can require specific cyclic prophylactic approaches
(non-steroidal anti-inflammatory drugs, coxibs, magnesium, long half-life
triptans or oestrogen supplements in various formulations), but usually the low
frequency of attacks suggests a first approach with specific symptomatic drugs.
Preference should be given to triptans, due to their specificity in controlling
migraine pain and its accompanying symptomatology; among them, in particular for 
sumatriptan, many specific studies proved a real effectiveness in the management 
of acute menstrual migraine attack.

Publication Types: 
    Review

PMID: 15549543 [PubMed - indexed for MEDLINE]

2019: Neurol Sci. 2004 Oct;25 Suppl 3:S211-4.

Oral contraceptives in women with migraine: balancing risks and benefits.

Allais G, De Lorenzo C, Mana O, Benedetto C.

Woman's Headache Center, Department of Gynecology and Obstetrics, University of
Turin, Via Ventimiglia 3, I-10126 Turin, Italy. gb.allais@tiscali.it

Oral contraceptives (OCs) are a safe and highly effective method of birth
control, but can also be associated with some risks, mainly a potential
thrombotic risk. OCs may condition the course of headache and sometimes start it,
but their influence on the clinical evolution of migraine is not easily
assessable. The last Classification of Headache Disorders of the International
Headache Society clearly identifies an "exogenous hormone-induced headache" that 
could be triggered by intake of OCs. Old high-dose OCs could effectively worsen
headache in a significant proportion of patients, but the newest formulations
influence headache course to a lesser extent. In any case, while an increase in
migraine frequency or intensity do not oblige the cessation of OCs, experiencing 
a migraine aura for the first time, or even a clear worsening of a preexistent
aura suggest discontinuation of OCs. Even if both migraine and OCs intake are
associated with an increased risk of ischaemic stroke, migraine per se is not a
contraindication for OCs use; however, patients suffering from migraine with aura
generally show a greater thrombotic risk than women with migraine without aura.
Other risk factors (patient's age, tobacco use, hypertension, hyperlipidaemia,
obesity and diabetes) must be carefully considered when prescribing OCs in
migraine patients. Furthermore, all OCs, even those with low oestrogen content,
are a major risk for venous thrombosis, particularly in women with hereditary
thrombophilia. A thorough laboratory control of the genetics of prothrombotic
factors and coagulative parameters should precede any decision of OCs
prescription in migraine patients.

Publication Types: 
    Review

PMID: 15549539 [PubMed - indexed for MEDLINE]

2020: Neurol Sci. 2004 Oct;25 Suppl 3:S177-85.

Preventive migraine therapy: what is new.

Rapoport AM, Bigal ME.

Department of Neurology, Columbia University College of Physicians and Surgeons, 
New York, NY, USA.

In this paper we review new treatment options for migraine prevention. Because we
focus on new drugs, some of the data we present herein were acquired in well
design double blind, controlled studies, while the efficacy of other medication
is supported only by open, uncontrolled trials (noted in the text wherever
appropriate).

Publication Types: 
    Review

PMID: 15549532 [PubMed - indexed for MEDLINE]

2021: Neurol Sci. 2004 Oct;25 Suppl 3:S129-31.

The role of cardiac diseases in the comorbidity between migraine and stroke.

Pierangeli G, Cevoli S, Zanigni S, Sancisi E, Monaldini C, Donti A, Ribani MA,
Montagna P, Cortelli P.

Dipartimento di Scienze Neurologiche, Università di Bologna, Via U. Foscolo 7,
I-40123 Bologna, Italy. pierangeli@neuro.unibo.it

Several case-control and cohort studies have suggested an association between
migraine and stroke. A significantly higher risk for stroke was found in women
under the age of 45 years and for the subgroup with migraine with aura, the
posterior circulation being significantly more frequently involved. The link
between cardiac diseases and the comorbidity migraine-stroke has been evaluated
considering both possible relationships: a higher prevalence of a vascular
disease involving both heart and brain in migraineurs, or a cardiac disorder,
more prevalent in migraineurs, with a possible aetiological role in migraine
attacks.

Publication Types: 
    Review

PMID: 15549521 [PubMed - indexed for MEDLINE]

2022: Neurol Sci. 2004 Oct;25 Suppl 3:S126-8.

Coagulation abnormalities in migraine and ischaemic cerebrovascular disease: a
link between migraine and ischaemic stroke?

Moschiano F, D'Amico D, Ciusani E, Erba N, Rigamonti A, Schieroni F, Bussone G.

L. Mandic Hospital, Via L. Mandic 1, Merate (LC), Italy.
fmoschiano.merate@ospedale.lecco.it

Migraine, particularly migraine with aura, is a risk factor for ischaemic stroke.
The mechanisms underlying this association are obscure. One hypothesis is that
shared risk factors may be the cause of this association. Over the last decade,
studies have suggested an association between migraine and genetic abnormalities 
in coagulation factors which play an important role in stroke pathogenesis.
Although the results of studies on various prothrombotic conditions are
conflicting, findings suggest a higher frequency of some genetic abnormalities in
migraine with aura patients. Thus, persistent hypercoagulability may explain the 
tendency for these patients to develop thromboembolic cerebrovascular events,
especially when they are exposed to additional procoagulant stresses. Further
studies on larger samples are required to test this hypothesis.

PMID: 15549520 [PubMed - indexed for MEDLINE]

2023: Neurol Sci. 2004 Oct;25 Suppl 3:S123-5.

Migraine and stroke.

Agostoni E, Fumagalli L, Santoro P, Ferrarese C.

Stroke Unit, Headache Center, Department of Neurology, University of
Milano-Bicocca, Ospedale San Gerardo, Via Donizetti 106, I-20052 Monza (MI),
Italy. e.agostoni@libero.it

The association between migraine and stroke is a dilemma for neurologists.
Migraine is associated with an increased stroke risk and it is considered an
independent risk factor for ischaemic stroke in a particular subgroup of
patients. The pathogenesis is not known but several studies report some common
biochemical mechanisms between the two diseases. A classification of
migraine-related stroke that encompasses the full spectrum of the possible
relationship between migraine and stroke has been proposed and it includes three 
main entities: coexisting stroke and migraine, stroke with clinical features of
migraine, and migraine-induced stroke. The concept of migraine-induced stroke is 
well represented by migrainous infarction; it is described in the revised
classification of the International Headache Society (IHS), and it represents the
strongest demonstration of the relationship between ischaemic stroke and
migraine. A very interesting common condition in stroke and migraine is patent
foramen ovale (PFO) which could play a pathogenetic role in both disorders. The
association between migraine and cervical artery dissection (CAD) is reported in 
recent studies. Migraine is more frequent in patients with CAD. This supports the
hypothesis that an underlying arterial wall disease could be a predisposing
condition for migraine. The neuroradiological evidence of subclinical lesions
most typical in the white matter and in the posterior artery territories in
patients with migraine, opens a new field of research. In conclusion the
association between migraine and stroke remains conflicting. Solving the above
mentioned issues is fundamental to understanding the epidemiologic, pathogenetic 
and clinical aspects of migraine-related stroke.

PMID: 15549519 [PubMed - indexed for MEDLINE]

2024: Neurol Sci. 2004 Oct;25 Suppl 3:S113-8.

Acute drug treatment of migraine attack.

Narbone MC, Abbate M, Gangemi S.

A.O.U. G. Martino, Clinica Neurologica I, Via C. Valeria, Contesse, I-98124
Messina, Italy. mcnarbone@yahoo.it

The availability of an effective drug for attack treatment is a main need of
migraine patients. Symptomatic therapy of migraine now includes three main
classes of drugs: ergot alkaloids, nonsteroidal antiinflammatory drugs (NSAIDs)
and triptans. Clinical randomised placebo-controlled trials affirmed the efficacy
and tolerability of these drugs, when used at the recommended doses and in the
absence of contraindications. The efficacy data from comparative trials showed a 
trend in favour of triptans vs. ergot alkaloids, but failed to show significant
differences between triptans and NSAIDs. However, clinical practice experience of
most headache clinicians suggests that triptans provide superior efficacy in
comparison with nonspecific agents, mainly in that they better satisfy migraine
patient expectations. In fact, these selective specific antimigraine drugs are an
advance in acute migraine treatment.

Publication Types: 
    Review

PMID: 15549517 [PubMed - indexed for MEDLINE]

2025: Curr Opin Pediatr. 2004 Dec;16(6):628-36.

Toward the definition of childhood migraine.

Lewis DW.

Division of Pediatric Neurology, Children's Hospital of the King's Daughters,
Eastern Virginia Medical School, Norfolk, Virginia 23509, USA. dlewis@chkd.com

PURPOSE OF REVIEW: The intent of this review is to provide an update on the
current understanding of the diagnostic criteria, classification,
pathophysiology, evaluation, and management of pediatric migraine. RECENT
FINDINGS: The International Headache Society has recently revised its diagnostic 
criteria and classification system in the 2004 International Criteria for
Headache Disorders. These new criteria have incorporated many developmentally
sensitive changes that will allow broader application in children and
adolescents. Appreciation of the new classification system requires understanding
of current views of the pathophysiology of migraine. Migraine is now viewed as an
inherited disorder with a primary neuronal initiation of a cascade of
neurochemical processes culminating in a spreading wave of cortical neuronal
depolarization and regional oligemia. The evaluation of a child with headache
begins with a thorough medical history and complete physical and neurologic
examination. One of the key questions for the bedside clinician is when to
perform further diagnostic studies. Extensive review concludes that the role of
further ancillary diagnostic studies, specifically EEG and neuroimaging, is
limited. The management of pediatric migraine requires a balance of biobehavioral
measures coupled with agents for acute treatment and, if needed, daily preventive
medicines. The pharmacologic management of pediatric migraine has been subjected 
to thorough review, and controlled data unfortunately are limited. The most
rigorously studied agents for the acute treatment of migraine are ibuprofen,
acetaminophen, and sumatriptan nasal spray, all of which have shown safety and
efficacy in controlled trials. For preventive or prophylactic treatment in the
population of children and adolescents with frequent, disabling migraine,
flunarizine (not available in the United States) is the most efficacious agent,
but encouraging data are emerging regarding the use of several antiepileptic
agents such as topiramate, disodium valproate, levetiracetam, the antihistamine
cyproheptadine, and the antidepressant amitriptyline. SUMMARY: Recent literature 
has reshaped the definition, evaluation, and management of pediatric migraine.

Publication Types: 
    Review

PMID: 15548924 [PubMed - indexed for MEDLINE]

2026: Otol Neurotol. 2004 Nov;25(6):987-92.

Comment in:
    Otol Neurotol. 2005 May;26(3):553-4.

Audiometric findings of patients with migraine-associated dizziness.

Battista RA.

Department of Clinical Otolaryngology, Northwestern University, Chicago, Illinois
60521, USA. robert_battista@rush.edu

OBJECTIVE: The objective of this study was to determine whether the audiometric
findings of migraine-associated dizziness could be used to better distinguish
migraine-associated dizziness from Meniere's disease. STUDY DESIGN: A
retrospective chart review. SETTING: Tertiary, otology/neurotology practice.
PATIENTS: Two groups of patients were studied, a migraine-associated dizziness
and a Meniere's disease group. There were 76 and 34 patients in the
migraine-associated dizziness and Meniere's disease groups, respectively.
INTERVENTIONS: None. MAIN OUTCOME MEASURES: Initial and follow-up pure-tone
average and low-frequency pure-tone average were recorded for both groups.
Independent samples t tests were used to test for mean differences in pure-tone
average and low-frequency pure-tone average. RESULTS: Pure-tone average and
low-frequency pure-tone average were significantly worse for patients in the
Meniere's disease group at both the initial and follow-up assessments. Three
patients in the migraine-associated dizziness group had an elevated pure-tone
average (>/=26 dB) and/or low-frequency pure-tone average at initial and/or
follow-up assessment. The remaining 73 migraine-associated dizziness patients had
normal hearing. In the Meniere's disease group, only two patients had a normal
pure-tone average and low-frequency pure-tone average at both initial and
follow-up evaluations. The hearing difference between the two groups was
significant even when controlling for age and duration of dizziness symptoms.
CONCLUSION: Audiometric findings of patients with migraine-associated dizziness
are most often normal. Unlike Meniere's disease, the sensorineural hearing loss
in migraine-associated dizziness rarely progresses. These audiometric findings
may help to distinguish migraine-associated dizziness from Meniere's disease when
diagnostic ambiguity exists between these two diagnoses.

Publication Types: 
    Case Reports

PMID: 15547431 [PubMed - indexed for MEDLINE]

2027: J Neurol Sci. 2004 Dec 15;227(1):95-100.

Investigation of the low-density lipoprotein receptor gene and cholesterol as a
risk factor for migraine.

Curtain R, Lea RA, Quinlan S, Bellis C, Tajouri L, Hughes R, Macmillan J,
Griffiths LR.

Genomics Research Centre, School of Health Science, Griffith University, Gold
Coast, Queensland, Australia.

The Low-Density Lipoprotein Receptor (LDLR) gene is a cell surface receptor that 
plays an important role in cholesterol homeostasis. We investigated the (TA)n
polymorphism in exon 18 of the LDLR gene on chromosome 19p13.2 performing an
association analysis in 244 typical migraine-affected patients, 151 suffering
from migraine with aura (MA), 96 with migraine without aura (MO) and 244
unaffected controls. The populations consisted of Caucasians only, and controls
were age- and sex-matched. The results showed no significant difference between
groups for allele frequency distributions of the (TA)n polymorphism even after
separation of the migraine-affected individuals into subgroups of MA and MO
affected patients. This is in contradiction to Mochi et al. who found a positive 
association of this variant with MO. Our study discusses possible differences
between the two studies and extends this research by investigating circulating
cholesterol levels in a migraine-affected population.

Publication Types: 
    Comparative Study

PMID: 15546598 [PubMed - indexed for MEDLINE]

2028: J Neurol Sci. 2004 Dec 15;227(1):67-71.

rTMS of the prefrontal cortex in the treatment of chronic migraine: a pilot
study.

Brighina F, Piazza A, Vitello G, Aloisio A, Palermo A, Daniele O, Fierro B.

Neurophysiological Unit, University of Palermo, Palermo, Italy.

A recent fMRI study showed that dorsolateral prefrontal cortex (DLPFC) exerts an 
inhibitory control on pain pathways in humans. We investigated whether
high-frequency rTMS over left DLPFC could ameliorate chronic migraine. Treatment 
consisted of 12 rTMS sessions, delivered in alternate days over left DLPFC. Sham 
rTMS was used as placebo. Eleven patients were randomly assigned to the rTMS
(n=6) or to the placebo (n=5) treatment. Measures of attack frequency, headache
index, number of abortive medications (outcome measures) were recorded in the
month before, during and in the month after treatment. Subjects treated by rTMS
showed a significant reduction of the outcome measures during and in the month
after the treatment as compared to the month before treatment. No significant
differences in the outcome measures were observed in the placebo group.
High-frequency rTMS over left DLPFC was able to ameliorate chronic migraine. This
is in agreement with the suggested role of DLPFC in pain control.

Publication Types: 
    Clinical Trial
    Comparative Study
    Randomized Controlled Trial

PMID: 15546593 [PubMed - indexed for MEDLINE]

2029: Headache. 2004 Nov-Dec;44(10):1050-5.

Pharmacoeconomics: the cost of prophylactic migraine treatments.

Adelman LC, Adelman JU, Freeman MC, Von Seggern RL.

Headache Wellness Center, Greensboro, NC, USA.

Migraine preventive medications considered effective reduce headache frequency by
50 percent in approximately 50 percent of treated patients. In spite of similar
effectiveness, these medications vary tremendonsly in their prices. Knowledge of 
medication prices and employing cost-effective strategies may greatly reduce
treatment costs.

PMID: 15546274 [PubMed - indexed for MEDLINE]

2030: Headache. 2004 Nov-Dec;44(10):1048-50.

New onset migraine with aura following head injury: a case report.

Husid MS.

Walton Headache Center, Augusta, GA, USA.

A patient is described who developed recurrent headaches following a traumatic
injury in the vicinity of the right greater occipital nerve (GON) that fulfill
IHS criteria for migraine with aura. Both aura and headache can be triggered by
pressure over the GON and relieved by local anesthetic blockade.

Publication Types: 
    Case Reports

PMID: 15546273 [PubMed - indexed for MEDLINE]

2031: Headache. 2004 Nov-Dec;44(10):1029-37.

Comment in:
    Headache. 2006 Jan;46(1):180-1; author reply 181-2.

Dextroamphetamine pilot crossover trials and n of 1 trials in patients with
chronic tension-type and migraine headache.

Haas DC, Sheehe PR.

Department of Neurology, University Health Care Center, State University of New
York Upstate Medical University, Syracuse, NY 13202, USA.

OBJECTIVE: To examine the preventive effects of dextroamphetamine in select small
groups of patients with chronic tension-type and migraine headache. BACKGROUND:
Neither amphetamine nor methylphenidate is used as a headache preventive. This
study was undertaken after a chance observation led one of us to prescribe
dextroamphetamine with apparent successes in specific patients with chronic
tension-type or migraine headaches. METHODS: Two pilot trials were done. Trial 1 
tested patients who were taking dextroamphetamine, while Trial 2 tested patients 
who had never taken this drug. Each trial obtained full data on eight subjects
with chronic tension-type headache and eight subjects with migraine headache. A
randomized, double-blinded, controlled, multiple-crossover design was used.
Subjects took capsules containing dextroamphetamine or equi-stimulatory caffeine 
(the control) during four alternating 20-day periods. Trial 1 subjects took their
pretrial dextroamphetamine dose at breakfast and lunch. Trial 2 subjects took 10 
mg at these times. Subjects recorded the integer from 0 to 3 that represented
their headache intensity during the previous 24 hours. The subject's data were
the average daily headache grade for the two dextroamphetamine periods and for
the two caffeine periods. The differential effect of amphetamine and caffeine on 
each group of eight subjects and on each individual was analyzed by t-tests.
RESULTS: In both trials, the tension-type and migraine groups had lower mean
daily headache grades in the amphetamine than in the caffeine periods. P values
for these differences indicated that there were real drug effects, on the
average, in the migraine groups (P<.05) and suggestive but inconclusive effects
in the tension-type groups (P<.10). The individual n of 1 analyses showed that
five tension-type and three migraine subjects in Trial 1 and three tension-type
and three migraine subjects in Trial 2 had considerably lower mean daily headache
grades on amphetamine with P values indicating, at various levels of significance
(from P<.05 to P<.001), real amphetamine effects. Twelve of the remaining 18
patients had lower, albeit not significant, mean daily grades with amphetamine.
No subject in either trial had a significantly lower mean daily headache grade on
caffeine. CONCLUSIONS: Dextroamphetamine had real preventive effects on chronic
tension-type and migraine headaches in some subjects. These results should
encourage other investigators to study its effects on these headaches.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial

PMID: 15546268 [PubMed - indexed for MEDLINE]

2032: Headache. 2004 Nov-Dec;44(10):1024-8.

Preventing disturbing migraine aura with lamotrigine: an open study.

Pascual J, Caminero AB, Mateos V, Roig C, Leira R, García-Moncó C, Laínez MJ.

University Hospital M. de Valdecilla, Neurology, Santander, Cantabria, Spain.

BACKGROUND: Lamotrigine has been suggested as possibly effective for preventing
migraine aura. OBJECTIVE: To describe our experience with a series of patients
with disturbing migraine aura treated with lamotrigine. METHODS: The members of
the Headache Group of the Spanish Society of Neurology were sent an ad hoc
questionnaire to collect patients treated with lamotrigine due to disturbing
migraine aura. The main outcome parameter ("response") was a >50% reduction in
the mean frequency of migraine auras at 3 to 6 months of treatment. RESULTS: A
total of 47 patients had been treated with lamotrigine due to severe migraine
aura. Three could not complete the protocol as a result of developing skin
rashes. Thirty (68%) patients responded. These were 21 females and 9 males whose 
ages ranged from 19 to 71 years. Eight suffered from migraine with "prolonged"
aura, 8 typical aura with migraine headache (but had frequent episodes including 
speech symptoms), 6 basilar-type migraine, 6 typical aura without headache, and 2
hemiplegic migraine. Fifteen had been previously treated, without response, with 
other preventatives. The mean monthly frequency of migraine auras in these 30
patients changed from 4.2 (range: 1 to 15) to 0.7 (range: 0 to 6). Response was
considered as excellent (>75% reduction) in 21 cases (70% of responders). Auras
reappeared in 2 months in 9 out of 13 patients where lamotrigine was stopped, and
ceased as soon as this drug was reintroduced. CONCLUSIONS: Lamotrigine should be 
considered in clinical practice for the preventive treatment of selected patients
with disturbing migraine auras. Lamotrigine seems worthy of a controlled trial as
prophylaxis of migraine aura.

Publication Types: 
    Clinical Trial

PMID: 15546267 [PubMed - indexed for MEDLINE]

2033: Headache. 2004 Nov-Dec;44(10):1019-23.

Comment in:
    Headache. 2005 Jun;45(6):763-4; author reply 764.

Osmophobia and taste abnormality in migraineurs: a tertiary care study.

Kelman L.

Headache Center of Atlanta, Atlanta, GA 30342, USA.

OBJECTIVES: This study assesses osmophobia and taste abnormality for the first
time in a large sample of migraine patients. METHODS: Seven hundred and twenty
seven migraineurs were evaluated. Osmophobia, taste abnormality, and perfume or
odor trigger were graded from 0 to 3. RESULTS: In patients with data, 24.7% of
673 patients complained of osmophobia (12.5% occasional, 7% frequent, and 5.2%
very frequent) and 24.6% of 505 of taste abnormality (13.5% occasional, 6.1%
frequent, and 5.0% very frequent). Perfume or odor trigger of acute migraine
occurred in 45.5% of 724 patients (22.7% occasional, 10.2% frequent, and 12.6%
very frequent). Perfume or odor trigger was associated with osmophobia in 61.5%
and taste abnormality 62.1%. Osmophobia without taste abnormality occurred in
28.3% and taste abnormality without osmophobia in 40.3%. A greater percentage of 
females than males had osmophobia (25.7 vs. 17.5), taste abnormality (25.4 vs.
17.9), and perfume or odor trigger (49.3 vs. 22.1), all P<.0001. CONCLUSIONS:
Osmophobia and taste abnormality occur in about one quarter of migraineurs during
an acute migraine attack while perfume or odor trigger migraine in almost 50% of 
patients. Osmophobia and taste abnormality in the acute migraine attack, as well 
as perfumes or odor as a migraine trigger, are more common in females than in
males.

PMID: 15546266 [PubMed - indexed for MEDLINE]

2034: Headache. 2004 Nov-Dec;44(10):994-1004.

Genomic abnormalities in patients with migraine and chronic migraine: preliminary
blood gene expression suggests platelet abnormalities.

Hershey AD, Tang Y, Powers SW, Kabbouche MA, Gilbert DL, Glauser TA, Sharp FR.

Children's Hospital Medical Center, Department of Neurology, Cincinnati, OH, USA.

BACKGROUND: Migraine has strong genetic and environmental components and may also
be a significant contributor to chronic migraine (CM). It is hypothesized that
gene expression changes in peripheral blood cells can be used to detect the
interaction of these influences. OBJECTIVE: Distinct genomic expression patterns 
for migraine and CM will be present. These genomic profiles will help clarify the
interactions of inheritance and environment. This initial study begins to examine
the feasibility of peripheral blood cell genomic analysis to assist in the
understanding of the pathophysiology of migraine and CM. METHODS: Blood samples
from patients were obtained either during an acute migraine or CM. Genomic
expression patterns were analyzed using Affymetrix U95A microarrays. RESULTS:
Expression patterns of 7 migraine and 15 CM patients were compared to four
distinct control groups (total patients, n=56) including healthy subjects. A
group of platelet genes were upregulated in both migraine and CM samples.
Different gene expression patterns were also seen between migraine and CM. A
group of immediate early genes including c-fos and cox-2 were expressed at higher
levels in migraine, whereas specific mitochondrial genes were expressed at higher
levels in CM. CONCLUSIONS: Increased expression of platelet genes in patients
with migraine and CM suggests similar underlying pathophysiology. The differences
seen between migraine and CM in other genes suggest an overlapping but not
identical pathophysiology. Further genomic profiling studies will help define
these relationships and provide further insights into headache pathogenesis.

Publication Types: 
    Comparative Study
    Research Support, N.I.H., Extramural
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 15546262 [PubMed - indexed for MEDLINE]

2035: Headache. 2004 Nov-Dec;44(10):983-93.

Somatic symptoms in headache patients: the influence of headache diagnosis,
frequency, and comorbidity.

Maizels M, Burchette R.

Kaiser Permanente, Family Practice, Woodland Hills, CA, USA.

BACKGROUND: Mood disorders of anxiety and depression are well known to be
comorbid with primary headache disorders. Less is known of the comorbidity of
other somatic symptoms with headache. METHODS: Headache Clinic patients were
screened with the Primary Care Evaluation of Mental Disorders (PRIME-MD), a
multidimensional psychiatric screening tool. The prevalence of somatic symptoms
was compared by headache diagnosis, frequency of severe headache, and psychiatric
diagnosis. Follow-up data were obtained 6 months after consultation. RESULTS:
Clinical diagnoses and PRIME-MD data were available for 289 patients. Associated 
somatic symptoms were more frequent in patients with chronic migraine (mean 5.5, 
P<.001) and chronic daily headache (CDH) (6.3, P=.008) compared to episodic
migraine (4.0); in patients with severe headache >2 days per week compared to
<or=2 days per week (6.15 vs. 4.15, P<.001); and in patients with a clinical
diagnosis of anxiety or depression, or both, compared to no anxiety or
depression, (5.7, P=.05, 5.2, P<.05, and 6.8, P<.001, respectively, vs. 4.5). The
most common specific symptoms were fatigue (73%), sleep difficulty (60%), and
nausea/indigestion (55%). Compared to a primary care sample, patients with severe
headache >2 days per week had significantly higher somatic counts (P=.01).
Six-month follow-up data were available for 140 patients. Associated symptoms
decreased both for patients with and without decrease in severe headache
frequency (mean reduction of 1.0, P=.01 and 0.8, P=.003, respectively).
CONCLUSION: Associated somatic symptoms are more common in patients with chronic 
migraine and CDH, with more frequent severe headaches, and with associated
anxiety or depression. Patients with episodic migraine have similar somatic
prevalence as a previously studied primary care population. The spectrum of
headache disorders may be characterized as showing increasing somatic prevalence 
as headaches, particularly severe headaches, become more frequent.

Publication Types: 
    Comparative Study

PMID: 15546261 [PubMed - indexed for MEDLINE]

2036: Headache. 2004 Nov-Dec;44(10):978-82.

Assessment of adverse events associated with triptans--methods of assessment
influence the results.

Sheftell FD, Feleppa M, Tepper SJ, Rapoport AM, Ciannella L, Bigal ME.

New York Medical College, Psychiatry, New York, NY, USA.

BACKGROUND: A recent study conducted in triptan-naive migraine patients showed
that tolerability was the second most important attribute of an acute treatment. 
However, the proportion of patients reporting side effects after any acute
treatment may vary with regard to the method of assessment. OBJECTIVES: To
contrast two methods of assessing adverse events (prompted and unprompted) in
those with headache using triptans. METHODS: This study was conducted in two
sites, a headache center in the United States, and a neurology office focusing on
headache in Italy. We prospectively surveyed 415 adults with headache, who had
been using the same triptan for at least 3 months. Participants were asked about 
their headache and treatment history. Subjects then completed a standardized
questionnaire, assessing adverse events in two different ways. First, subjects
were asked if they had any adverse events when using the triptan. After returning
the first part of the questionnaire, subjects received a second form, where 49
possible adverse events were listed. We contrasted and correlated both sets of
answers. RESULTS: Most patients (U.S.=74.9%, Italy=65.5%) reported no side
effects in the unprompted questionnaire. However, most of them (U.S.=62.9%,
Italy=54.1%) reported at least one side effect in the prompted questionnaire.
Most patients that reported side effects in the unprompted questionnaire said
they had just one adverse event, while most reported two or more side effects in 
the prompted questionnaire. Both in the unprompted and in the prompted
questionnaires, most side effects were rated as mild or moderate. Interestingly, 
31 (7.5%) subjects (pooling data from both sites together) graded their adverse
events as severe in the prompted questionnaire, but had not self-reported them.
CONCLUSIONS: (1) When assessing adverse events, the method of data collection may
dramatically influence the results. (2) From those subjects who did not
self-report adverse events after using a triptan, most of them will report
positively if presented with a list of side effects.

Publication Types: 
    Comparative Study
    Multicenter Study

PMID: 15546260 [PubMed - indexed for MEDLINE]

2037: Headache. 2004 Nov-Dec;44(10):969-77.

Long-term tolerability of sumatriptan nasal spray in adolescent patients with
migraine.

Natarajan S, Jabbour JT, Webster CJ, Richardson MS.

Department of Pediatric Neurology, Le Bonheur Children's Hospital, Memphis, TN,
USA.

OBJECTIVE: This 1-year, open-label, multicenter study was designed to assess the 
long-term tolerability and efficacy of sumatriptan nasal spray 20 mg in
adolescent patients with migraine. METHODS: A prospective, multicenter,
open-label study was conducted in patients aged 12 to 17 years who were allowed
to treat an unlimited number of migraines at severe, moderate, or mild pain
intensity with sumatriptan nasal spray for up to 1 year. All patients started the
study at the 20-mg dose of sumatriptan nasal spray. Dose could be adjusted
downward to 5 mg at the discretion of the investigator to optimize therapy.
RESULTS: A total of 484 adolescent migraineurs treated 4676 migraines with
sumatriptan nasal spray 20 mg (3593 during the first 6 months and 1083 during the
second 6 months). A total of 3940 migraines and 699 migraines were treated with
one and two 20-mg doses of sumatriptan nasal spray, respectively. Only 10
patients (treating 42 migraines) took the 5-mg dose of sumatriptan nasal spray.
The overall percentage of migraines treated with either one 20-mg dose or one,
two, or three 20-mg doses with at least 1 drug-related adverse event was 19%. The
most common specific drug-related adverse event was unpleasant taste, reported in
17% of migraines. No other single drug-related adverse event was reported in more
than 1% of migraines over the 1-year treatment period. When unpleasant taste was 
excluded from the adverse-event tabulations, the percentages of migraines with at
least 1 drug-related adverse event after one or one, two, or three 20-mg doses
declined to 4% and 3%, respectively. No patient experienced any drug-related
changes in 12-lead ECGs, vital signs, or nasal assessments; and no clinically
meaningful changes in clinical laboratory values were observed. Across all
migraines with evaluable efficacy data (n=4334), headache relief was reported in 
43% of migraines at 1 hour and in 59% at 2 hours after dosing with sumatriptan
nasal spray 20 mg. Of the 2561 migraines with headache relief 2 hours postdose,
headache recurrence was reported within 24 hours of initial dosing in 7% of
migraines. None of the efficacy or tolerability results varied as a function of
time in the study (ie, first 6 months vs. second 6 months). CONCLUSION:
Sumatriptan nasal spray 20 mg is generally well tolerated and may be beneficial
during long-term use by adolescent migraineurs ages 12 to 17 years.

Publication Types: 
    Clinical Trial
    Multicenter Study

PMID: 15546259 [PubMed - indexed for MEDLINE]

2038: Headache. 2004 Nov-Dec;44(10):961-8.

Chemokine levels in the jugular venous blood of migraine without aura patients
during attacks.

Sarchielli P, Alberti A, Vaianella L, Pierguidi L, Floridi A, Mazzotta G, Floridi
A, Gallai V.

Neurologic Clinic, Department of Neuroscience, Institute of Clinical and Applied 
Biochemistry, University of Perugia, Italy.

OBJECTIVE: To investigate changes in the levels of calcitonin gene-related
peptide and its intracellular messenger cyclic adenosine monophosphate in serial 
samples of internal jugular blood taken from migraine patients without aura
assessed during attacks, and to assess their relationship with the levels of
IL-8, MCP-1, and RANTES in the same samples. BACKGROUND: Calcitonin gene-related 
peptide, the marker of trigeminovascular activation, is released in both the
internal and external jugular venous blood of migraine patients during attacks.
Experimental evidence demonstrated that when released from C-type sensory neurons
in inflammatory pain models, it differentially induced expression of neutrophil
chemotactic chemokine IL-8, but not monocyte chemotactic chemokine MCP-1 or
lymphocyte chemotactic chemokine RANTES. These chemokines were never investigated
in migraine. DESIGN/METHODS: Eight migraine without aura patients were admitted
to the hospital during the attacks. Internal jugular venous blood samples were
taken immediately after catheter insertion, at the 1st, 2nd, and 4th hours after 
attack onset, and within 2 hours from its cessation. The levels of the sensory
neuropeptide calcitonin gene-related peptide and the messenger cyclic adenosine
monophosphate were measured by RIA method, and those of IL-8, MCP-1, and RANTES
were measured by ELISA method. RESULTS: Higher calcitonin gene-related peptide
levels were found in the internal jugular venous blood of migraine without aura
patients compared with the time of catheter insertion (ANOVA: P<.0001) with a
peak at the first hour (52.6+/-9.2 ng/mL). A transient increase in IL-8 was
observed at the 2nd and 4th hours (P<.01 and P<.002, respectively), whereas no
changes in the levels of MCP-1 and RANTES were found at any time of the study.
The increase in IL-8 was accompanied by a parallel increase in cyclic adenosine
monophosphate. CONCLUSIONS: The present study confirms previous findings of an
increase in calcitonin gene-related peptide in internal jugular venous blood of
migraine without aura patients during attacks. The transient increase in the
levels of IL-8 concurs with the results of recent experimental research showing a
calcitonin gene-related peptide-induced activation of IL-8 gene expression, but
not RANTES and MCP-1, via the transcriptional factor AP-2, which mediates
transduction in response to cyclic adenosine monophosphate. Although IL-8 is
transiently increased during migraine attacks, an accumulation of leukocytes
secondary to neurogenic inflammation is unlikely, as it is for other inflammatory
events, because they are self limiting. Other events, including nitric oxide
production, may contribute to counteract meningeal transvascular leukocyte
migration during migraine attacks, as suggested by the model of sterile
inflammation.

Publication Types: 
    Comparative Study

PMID: 15546258 [PubMed - indexed for MEDLINE]

2039: Headache. 2004 Nov-Dec;44(10):947-60.

Topographic and dipolar analysis of laser-evoked potentials during migraine
attack.

de Tommaso M, Guido M, Libro G, Losito L, Difruscolo O, Puca F, Specchio LM,
Carella A.

Department of Neurologic and Psychiatric Sciences, University of Bari, Bari,
Italy.

OBJECTIVE: The aim of this study was to perform further evaluation of
laser-evoked potentials (LEPs) during migraine attacks using multichannel
recording and topographic analysis. Specifically, this study aimed to confirm the
pattern previously observed in acute migraine, while also defining the components
of LEPs that are mainly modified during headache, as well as the correlation
between features of LEPs and clinical variables. In addition, we aimed to conduct
a dipolar source analysis of the main LEP waves in migraine patients to check the
variability in the source location of LEPs during acute migraine. BACKGROUND: An 
amplitude enhancement of LEPs was previously detected during migraine attack
using a single scalp derivation on the vertex; hyperalgesia to heat stimuli was
also detected for both the face and hand. METHODS: Eighteen patients suffering
from migraine without aura were analyzed. The supraorbital zones and the dorsum
of the hand were stimulated on both the symptomatic and nonsymptomatic sides in
all patients. The LEPs were recorded via 25 scalp electrodes. Dipolar source
analysis of the P2 components was performed using a spherical model in all
patients and using a realistic Magnetic Resonance model in four patients.
RESULTS: During attacks, the later waves, and particularly the P2 component, were
significantly enhanced; the amplitude of the P2 component obtained during the
attack by stimulation of the supraorbital zone on the side of the headache was
significantly correlated with the intensity of pain and the frequency of
headache. In our patients, the P2 wave was generated in the anterior cingulate
cortex, with a shift toward its rostrocaudal portion, and was mainly devoted to
elaboration of the emotive compound of pain during migraine attack. CONCLUSIONS: 
Cortical activation by laser stimuli during migraine attack was confirmed. This
effect was more pronounced in patients with a higher frequency of migraine
attacks. This may be due to a lack of inhibitory control over the transmission of
pain to the cortex. The increased activation of cortical areas devoted to
attention and emotion may be linked to headache.

Publication Types: 
    Comparative Study

PMID: 15546257 [PubMed - indexed for MEDLINE]

2040: Neuropsychobiology. 2004;50(4):322-8.

Comment in:
    Neuropsychobiology. 2007;55(2):121-2.

Evaluation of the prophylactic efficacy of amitriptyline and citalopram, alone or
in combination, in patients with comorbidity of depression, migraine, and
tension-type headache.

Rampello L, Alvano A, Chiechio S, Malaguarnera M, Raffaele R, Vecchio I,
Nicoletti F.

Department of Neurosciences, University of Catania, Catania, Italy.
rampello@unict.it

Antidepressants are used to treat chronic daily headache disorders such as
migraine and chronic tension-type headache (TTH), which are often associated with
depression and anxiety. Here, we studied the efficacy and tolerability of
amitriptyline and citalopram, given alone or in combination, in patients with
'triple' comorbidity of depression, TTH, and migraine. Eighty-eight patients were
enrolled in the study and randomly divided into two groups. The first group
received amitriptyline and the second citalopram for 16 weeks. Patients were
assessed at weeks 0, 4, 8, and 16. The two drugs were equally efficacious in
relieving depressive symptoms, although amitriptyline was more efficacious than
citalopram in reducing migraine and TTH attacks. Patients who did not respond to 
monotherapy (<30% of improvement in the clinical scores) were treated with a
combination of the two drugs for 16 additional weeks. In these selected patients,
the combined treatment produced a substantial improvement in depression, migraine
and TTH without producing major side effects such as those commonly related to
the 'serotonergic' syndrome. The results indicate that a combined therapy with
amitriptyline and citalopram may be particularly beneficial for patients with
TTH, migraine and comorbid depression that do not respond to monotherapy.

Publication Types: 
    Clinical Trial
    Comparative Study
    Randomized Controlled Trial

PMID: 15539864 [PubMed - indexed for MEDLINE]

2041: Curr Med Res Opin. 2004 Nov;20(11):1805-14.

The impact of a worksite migraine intervention program on work productivity,
productivity costs, and non-workplace impairment among Spanish postal service
employees from an employer perspective.

Vicente-Herrero T, Burke TA, Laínez MJ.

Correos y Telégrafos de España, Valencia, Spain.

BACKGROUND: Migraine is associated with a significant productivity loss to
employers, who may benefit from making a migraine intervention available to their
employees. OBJECTIVE: To evaluate changes in migraine-related productivity and
non-workplace impairment associated with a migraine intervention program from the
employer perspective. METHODS: This was a pre-test post-test study of Spanish
Postal Service employees with migraine. The intervention consisted of counseling 
from occupational health physicians and rizatriptan 10 mg for symptomatic
treatment of two subsequent migraine headaches. Physicians also prescribed
additional medications for migraine prophylaxis, treatment of tension headaches, 
and rescue medications. Migraine-related work loss and non-workplace impairment
(interference with daily and social activities) were self-reported at baseline
(pre-intervention) and separately following each migraine headache
(post-intervention) with the aid of a diary. Migraine-related work loss was
reported as work loss due to absenteeism, reduced productivity while at work, and
the sum of the two (total lost work day equivalents [LWDE]). An employer
perspective was taken for the cost analysis, and thus productivity costs were the
only costs considered. RESULTS: A total of 436 patients comprised the population 
for analysis. The number of migraine-related LWDE per migraine attack were 0.48
days per migraine headache in the month before the intervention, decreasing to
0.20 days and 0.07 days per migraine headache during the first and second
migraine headaches following the intervention (p < 0.0001 vs. baseline). Total
migraine-related productivity costs per migraine headache were 34 euros/patient
before the intervention, decreasing to 14 euros/patient and 5 euros/patient
during the first and second headaches following the intervention (p < 0.0001).
Non-workplace activity impairment was also significantly reduced (p < 0.0001)
following the intervention. The main limitations of the study were the lack of a 
parallel control group and the potential for differential recall bias between the
usual care and the intervention periods. In addition, the results may not be
generalizable to other employers or other countries. CONCLUSION: This study
documents the value of a workplace migraine intervention program, which focused
on migraine prevention and rizatriptan-based symptomatic treatment. It also
highlights the important role occupational health clinics can play in helping
employers and employees reduce the burden of migraine.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 15537481 [PubMed - indexed for MEDLINE]

2042: Curr Med Res Opin. 2004 Nov;20(11):1777-83.

Migraine treatment strategies: the global Migraine And Zolmitriptan Evaluation
(MAZE) survey--phase IV.

MacGregor EA, Brandes J, Gendolla A, Giammarco R.

City of London Migraine Clinic, London, UK. migraine@colmc.org.uk

OBJECTIVE: To determine which medications UK migraineurs have access to and
assess the usage of these products in a 'real-life' setting. RESEARCH DESIGN AND 
METHODS: Data were collected using an online questionnaire, which subjects were
directed to by advertisements in pharmacies, a UK national newspaper, on the
internet and information on the Migraine Action Association website and
newsletters. Respondents were eligible for inclusion if attacks fulfilled
International Headache Society criteria for migraine and/or if previously
diagnosed by a physician as having migraine. MAIN OUTCOME MEASURES: Respondents
were asked to specify which products had been prescribed or purchased for
migraine treatment. The pattern of use of these products was determined,
including the reasons why respondents chose particular products to treat attacks.
RESULTS: Of 3072 eligible respondents, the majority had purchased a variety of
over-the-counter (OTC) medicines for treatment of attacks. Eighty-seven per cent 
had been diagnosed by a physician and were prescribed multiple products (average 
1.68); 45% received triptans, but 26% were still prescribed products that were
also available OTC. Over half (52%) of respondents initially used an OTC medicine
to treat the last migraine attack. However, 73% required a second dose/product,
mainly as a result of lack of efficacy of the first dose/product. Respondents
using triptans were less likely to require a second dose/product than those not
using triptans (52% vs. 78%, respectively). The two main reasons for choosing a
triptan to treat an attack were the need for quick control and the severity of
the attack. Satisfaction with regard to migraine medication was higher among
triptan-users than nontriptan users. CONCLUSIONS: Medicines that are available
OTC are often used as first-line therapy for migraine despite many migraineurs
having access to prescription therapies such as triptans. Many migraineurs
require a second dose/product, possibly indicating sub-optimal treatment
efficacy. Physicians should consider the range of migraine-specific treatments
available, including triptans, in order to develop a treatment plan that is based
on the patient's needs and preferences.

Publication Types: 
    Clinical Trial
    Clinical Trial, Phase IV
    Research Support, Non-U.S. Gov't

PMID: 15537478 [PubMed - indexed for MEDLINE]

2043: Clin Ther. 2004 Sep;26(9):1533-45.

Priorities for triptan treatment attributes and the implications for selecting an
oral triptan for acute migraine: a study of US primary care physicians (the
TRIPSTAR Project).

Cutrer FM, Goadsby PJ, Ferrari MD, Lipton RB, Dodick DW, McCrory D, Williams P.

Department of Neurology, Mayo Clinic, Rochester, Minnesota 55905, USA.
Cutrer.Michael@mayo.edu

BACKGROUND: Physicians treating patients with migraine can now choose from among 
7 triptans, which differ on a range of attributes that may be important for
treatment selection. OBJECTIVE: The aims of this study were to determine the
relative importance of treatment attributes of the available triptans and assess 
their impact on deciding the most appropriate treatment for a particular patient 
with migraine. METHODS: As part of the TRIPSTAR project, US primary care
physicians were surveyed to elicit their views on the relative importance of a
prespecified set of treatment attributes for making treatment choices in clinical
practice. The treatment attributes assessed were those for which data from
controlled clinical trials were available for subsequent comparison. The
resulting attribute-importance weights were then combined with data on the
performance of individual triptans across these attributes in a multiattribute
decision model to assist selection of an oral triptan. RESULTS: Efficacy
attributes were considered more important than tolerability or consistency of
effect in selecting an oral triptan. For triptan-naive but not
triptan-experienced patients, tolerability was considered significantly more
important than consistency (30% [95% CI, 27%-34%] vs 21% [19%-24%]). Sustained
pain-free status and freedom from cardiovascular (chest) adverse events were the 
most important efficacy and tolerability attributes for both patient categories. 
When the relative importance of the treatment attributes was combined in a
multiattribute decision model with meta-analysis data from controlled trials,
almotriptan, eletriptan, and rizatriptan were significantly closer to the
hypothetical ideal triptan than the reference product, sumatriptan 100 mg.
CONCLUSION: Multiattribute decision-making models (such as that used in the
TRIPSTAR project) that determine and apply the relative importance of treatment
attributes to drug selection have considerable potential value as a decision
support tool in the treatment of acute migraine.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 15531016 [PubMed - indexed for MEDLINE]

2044: Acta Cardiol. 2004 Oct;59(5):569-70.

Migraine headache induced recurrent atrial fibrillation: a case report.

Turhan H, Riza Erbay A, Yetkin E.

drhturhan@yahoo.com

A variety of symptoms that accompany migraine are mediated by the autonomic
nervous system. The autonomic nervous system has long been known to play a
potentially important role in the occurrence of atrial fibrillation. Clinically
significant effects on cardiac rhythm are uncommon during migraine attacks. In
the present case, we report a man who experienced recurrent episodes of atrial
fibrillation, which were likely secondary to the vomiting component of migraine.

Publication Types: 
    Case Reports

PMID: 15529565 [PubMed - indexed for MEDLINE]

2045: Otolaryngol Head Neck Surg. 2004 Nov;131(5):736-9.

Intracranial blood flow velocities and CO2 reactivity in diagnosing
migraine-related dizziness.

Le TT, Burch CM, Sargent EW.

Department of Otolaryngology-Head and Neck Surgery, St. Louis University, MO,
USA.

OBJECTIVE: Migraine-related dizziness can present with or without headache, often
making diagnosis difficult. Flow velocity and CO 2 reactivity testing using
transcranial Doppler (TCD) measurement of intracranial blood flow has been
described as abnormal in patients with classic or common migraine. This study
sought to determine the utility, if any, of this noninvasive technique in the
diagnosis of migraine-related dizziness. STUDY DESIGN AND SETTING: A prospective,
controlled study in academic neurotology and neurology practices was conducted.
Nine patients with migraine-related dizziness and 10 patients with no history of 
migraine or dizziness were tested with transcranial Doppler ultrasound in a
blinded fashion. RESULTS: No statistically significant differences in
intracranial blood flow velocities or in cerebrovascular reactivity to hypocapnia
were found between patients and controls. CONCLUSIONS: Assessment of intracranial
blood flow velocity and CO 2 reactivity using TCD does not help in the diagnosis 
of migraine-related dizziness. SIGNIFICANCE: A reliable objective test for the
diagnosis of migraine-related dizziness remains elusive, and the diagnosis of
this patient group continues to be suboptimal.

Publication Types: 
    Clinical Trial
    Controlled Clinical Trial

PMID: 15523457 [PubMed - indexed for MEDLINE]

2046: MedGenMed. 2004 Jul 14;6(3):48.

Weight variations in patients receiving topiramate migraine prophylaxis in a
tertiary care setting.

Krymchantowski A, Tavares C.

Headache Center of Rio, Department of Neurology, Universidade Federal Fluminense,
Niteroi, Brazil.

BACKGROUND: Migraine is a highly prevalent chronic neurologic disorder. Frequent 
headache attacks require prophylactic treatment, and side effects are limiting
prescribing factors among traditional agents for migraine prophylaxis.
Beta-blockers, antidepressants, calcium channel blockers, and anticonvulsants
have been used since the 1960s, and their efficacy has been demonstrated in
several controlled studies. However, weight gain commonly occurs with most of
these drugs and makes adherence to treatment a troublesome issue for many
patients. Topiramate is a new anticonvulsant with proven efficacy in migraine and
other conditions, which reportedly confers weight loss in patients receiving
doses up to 300 mg/day. OBJECTIVE: The aim of this study was to evaluate
adherence, weight loss, tolerability, and response to topiramate in adult
migraineurs receiving treatment in a tertiary care center. METHODS: During a
2,5-year period, all patients receiving topiramate for migraine were evaluated
after 3 months of treatment. The parameters evaluated were adherence to
treatment, frequency in reduction of attacks > 50%, the presence and amount of
weight loss, and adverse events. RESULTS: Among 175 patients included, 134
(76.6%) adhered to the regimen, whereas 4% interrupted before the 3-month
evaluation and 19.4% did not return for follow-up. Among the 134 patients
evaluated, 82 (61.2%) revealed headache-frequency reduction > 50%; 105 (78.4%)
patients experienced weight loss (range 1-10 kg; average, 3.4 kg). The most
frequent side effects were paresthesia (39.6%); emotional disturbances, including
depression, irritability, and anxiety (17.9%); thinking impairment (12.7%);
memory disturbances (12.7%); and altered taste (11.9%). CONCLUSION: Despite
methodologic limitations, we conclude that good adherence to topiramate in a
"real-world" headache clinic occurred in most of the study participants. The
majority of patients also experienced weight loss and reductions in headache
frequency, with an acceptable side-effect profile.

Publication Types: 
    Clinical Trial

PMID: 15520672 [PubMed - indexed for MEDLINE]

2047: Hum Reprod. 2004 Dec;19(12):2927-32. Epub 2004 Oct 28.

Increased frequency of migraine among women with endometriosis.

Ferrero S, Pretta S, Bertoldi S, Anserini P, Remorgida V, Del Sette M, Gandolfo
C, Ragni N.

Department of Obstetrics and Gynaecology, San Martino Hospital, University of
Genoa, Largo R. Benzi 1, 16132 Genoa, Italy. simone.ferrero@fastwebnet.it

BACKGROUND: Our aim is to assess the prevalence and characteristics of headache
in patients with endometriosis compared with women without this disease. METHODS:
One hundred and thirty-three women with histologically proven endometriosis and
166 controls were interviewed by a neurologist experienced in headache diagnosis;
the headache disorders were classified according to the 1988 International
Headache Society criteria. RESULTS: The prevalence of migraine was significantly 
higher among women with endometriosis [n = 51, 38.3%; 95% confidence interval
(CI) 30.1-47.2%] than in controls (n = 25, 15.1%; 95% CI 10.0-21.4%) (P < 0.001).
Migraine with aura was observed in 18 women with endometriosis (13.5%) and in two
controls (1.2%; P < 0.001). The age at migraine onset was significantly lower in 
women with endometriosis than in controls (16.4 versus 21.9 years; P = 0.001). No
significant difference was observed in pain intensity and attack frequency
between the two groups; a trend for women with endometriosis to have longer
unmedicated attacks was observed. No significant correlation was observed between
attack frequency, unmedicated headache duration, migraine intensity and the
severity of endometriosis. CONCLUSION: Migraine is more frequent in women with
endometriosis than in controls, although its presence and characteristics are not
related to the severity of endometriosis.

PMID: 15513980 [PubMed - indexed for MEDLINE]

2048: Ann Med. 2004;36(6):462-73.

The molecular genetics of migraine.

Wessman M, Kaunisto MA, Kallela M, Palotie A.

Biomedicum Helsinki, Research Program in Molecular Medicine, University of
Helsinki, Helsinki, Finland. maija.wessman@hus.fi

Within the past decade it has been possible to identify susceptibility gene loci 
that predispose to migraine using genetic markers distributed across the human
genome. Five new loci with significant linkage to common types of
migraine--migraine with or without aura--have been identified on four different
chromosomes using a genome-wide screen approach. So far, only the locus on 4q has
been replicated but no specific, disease-causing mutations have been described in
these common forms of migraine. The best genetic evidence providing molecular
insight into migraine still comes from the mutations detected in a rare Mendelian
form of migraine with aura--familial hemiplegic migraine (FHM). In 50%-70% of FHM
families, mutations in the calcium channel gene CACNA1A in chromosome 19p13 have 
been identified. In some families, mutations in the ATP1A2 gene encoding the
alpha2 subunit of the Na+, K+-ATPase are associated with FHM, linked to 1q23.
Here we discuss the current knowledge of the heritability of migraine and rare
migraine variants as models for understanding the pathophysiology of common
migraine and animal models that might contribute to understanding common forms of
migraine.

Publication Types: 
    Review

PMID: 15513297 [PubMed - indexed for MEDLINE]

2049: Semin Ophthalmol. 2003 Dec;18(4):210-7.

Migraine with and without headache.

Freedom T, Jay WM.

Departments of Neurology, Loyola University Medical Center, Maywood, IL, USA.
tfreedom@enh.org

Transient visual and neurological episodes are relatively common and can occur
for the first time in middle and old age. In many cases these transient events
are migraine auras. An aura is a transient, stereotypical, visual or neurological
episode usually lasting 4 to 60 minutes in duration. Migraine is usually, but not
always, associated with headache and can be accompanied by systemic and autonomic
symptoms. Diagnosis is dependent on International Headache Society criteria. The 
pathophysiology is believed to involve neurovascular mechanisms. There is a
hereditary component to migraine. When migraine auras occur in the absence of
headache they are termed acephalgic migraines. Late onset migraine accompaniment 
is an acephalgic migraine that presents in middle-aged and older adults. It is
usually benign. Migraines can be mimicked by other more serious conditions. Most 
patients with a stable migraine pattern and normal neurological evaluation do not
require further testing. Some patients with atypical presentation, older age, or 
suspected secondary causes need further investigation.

Publication Types: 
    Case Reports
    Review

PMID: 15513008 [PubMed - indexed for MEDLINE]

2050: Drugs Today (Barc). 2004 Jul;40(7):577-88.

Genes and migraine.

Baloh RW.

Department of Neurology, UCLA School of Medicine, Los Angeles, California
90095-1769, USA. rwbaloh@ucla.edu

Migraine is not a disease but a syndrome that undoubtedly has multiple causes.
Several migraine syndromes have a clear autosomal dominant pattern of
inheritance, and recently, mutations have been found in two different genes in
families with hemiplegic migraine. Familial aggregation and twin studies in
families with other more common migraine syndromes (i.e., migraine without aura
and migraine with aura) show that genetic factors are important, although the
mode of inheritance is not always clear. Numerous candidate genes have been
identified based on clinical features of migraine and the known functions of the 
different genes. Recently genome-wide scans in families with migraine without
aura and migraine with aura have identified susceptibility loci for these common 
syndromes. However, none of the numerous studies performed to date provide
convincing evidence for a gene responsible for the common varieties of migraine.

Publication Types: 
    Review

PMID: 15510232 [PubMed - indexed for MEDLINE]

2051: Curr Pain Headache Rep. 2004 Dec;8(6):435-42.

Prioritizing treatment attributes and their impact on selecting an oral triptan: 
results from the TRIPSTAR Project.

Dodick DW, Lipton RB, Ferrari MD, Goadsby PJ, McCrory D, Cutrer FM, Williams P.

Department of Neurology, Mayo Clinic Scottsdale, AZ 85259, USA.
Dodick.David@mayo.edu

Seven oral triptans, which differ on a range of attributes important for
treatment selection, are now available for treating migraine. US neurologists
were surveyed to assess the relative importance of treatment attributes,
prespecified by clinical relevance and availability of controlled study data, for
selecting among oral triptans. Using a multiattribute decision model, we combined
these data on the importance of treatment attributes with information on the
relative performance of the oral triptans derived from a recent meta-analysis of 
controlled clinical trials.

Publication Types: 
    Review

PMID: 15509456 [PubMed - indexed for MEDLINE]

2052: J Ethnopharmacol. 2004 Dec;95(2-3):239-45.

In vitro pharmacological investigations of Sapindus trifoliatus in various
migraine targets.

Arulmozhi DK, Sridhar N, Bodhankar SL, Veeranjaneyulu A, Arora SK.

New Chemical Entity Research, Lupin Research Park, Village Nande, Taluk Mulshi,
Pune 411042, Maharashtra, India.

Phytotherapies have offered alternative sources of therapy for migraine and
gained much importance in prophylactic treatment. The aqueous extract of pericarp
of fruits of Sapindus trifoliatus Linn (ST), family Sapindaceae was evaluated for
its affinity for 5-HT(1B/1D) receptors in rabbit saphenous vein,
alpha-adrenoceptors in rabbit aorta, GABA receptors in guinea pig ileum, 5-HT(2B)
receptors in rat fundus and vanilloid receptors in guinea pig trachea. The
calcium blocking effect was studied in rabbit aorta while the modulatory role of 
ST on platelet serotonin release was evaluated in human platelets. The aqueous
extract of Sapindus trifoliatus exhibited significant 5-HT(2B) receptor
inhibition and moderate platelet serotonin release inhibition.

Publication Types: 
    Comparative Study
    In Vitro

PMID: 15507343 [PubMed - indexed for MEDLINE]

2053: Neurology. 2004 Oct 26;63(8):1432-8.

Prevalence and impact of migraine and probable migraine in a health plan.

Patel NV, Bigal ME, Kolodner KB, Leotta C, Lafata JE, Lipton RB.

AdvancePCS, Albert Einstein College of Medicine, Bronx, NY 10461, USA.

BACKGROUND: A large number of headache sufferers with features of migraine fail
to meet criteria for strict migraine (SM; migraine with or without aura) but do
meet criteria for probable migraine (PM). OBJECTIVES: To estimate the prevalence 
of PM, to compare the epidemiologic profiles of SM and PM, and to assess the
disability and impact on the health-related quality of life (HRQoL) of these
patients. METHODS: Computer-assisted telephone interviews in a sample recruited
from a mixed model health maintenance organization were used. SM, PM, and control
subjects were identified. Also assessed were demographic features, disability,
HRQoL, and depression. RESULTS: The 1-year prevalence for SM was 14.7% (19.2% in 
women and 6.6% in men); for PM, it was 14.6% (15.9% in women, 12.6% in men). Most
subjects with PM (82%) did not meet the associated symptom criteria for migraine.
HRQoL was reduced in the PM, SM, and all migraine (AM; SM and PM pooled together)
groups compared with controls. The proportion of subjects with high disability
was elevated in PM (13%), SM (31%), and AM (22%) groups vs controls (3.7%; p <
0.0001). CONCLUSIONS: Within a health plan, probable migraine is a prevalent form
of migraine, with symptom and epidemiologic profiles that overlap with strict
migraine. Although strict migraine prevalence was consistent with previous
studies, a probable migraine prevalence higher than previously reported was
found, perhaps reflecting a difference between health plan and population
samples.

PMID: 15505161 [PubMed - indexed for MEDLINE]

2054: J Clin Epidemiol. 2004 Sep;57(9):962-72.

Pharmacy and medical claims data identified migraine sufferers with high
specificity but modest sensitivity.

Kolodner K, Lipton RB, Lafata JE, Leotta C, Liberman JN, Chee E, Moon C.

AdvancePCS, 11350 McCormick Road, Executive Plaza II, Suite 1000, Hunt Valley, MD
21031, USA. theresa.tate@caremark.com

OBJECTIVE: Claims data are often used to identify and monitor individuals with
particular conditions, but many health conditions are not easily recognizable
from claims data alone. Patient characteristics routinely available in claims
data were used to develop model-based claims signatures to identify migraineurs. 
STUDY DESIGN AND SETTING: A validated telephone interview was administered to
23,299 continuously enrolled managed care members aged 18-55 to identify 1,265
migraineurs and 1,178 controls. Responses were linked to medical and prescription
claims. Claims variables were evaluated for sensitivity, specificity, and
positive and negative predictive value in predicting migraine status. Regression 
models for predicting migraine status were developed. RESULTS: Regression-based
claims signature models were successful in case-finding, as indicated by fairly
sizable odds ratios (OR). In the full model (including demographic, medical,
pharmacy, and comorbidity claims variables), a claim for a migraine drug, gender,
and a claims-based headache diagnosis were strongly associated with migraine case
status (OR=3.9, 3.2, and 3.0, respectively). CONCLUSION: Using either medical or 
pharmacy claims provided highly specific and moderately sensitive case-findings. 
Strategies that combined medical and pharmacy information improved sensitivity
and may increase the usefulness of claims for identifying migraine and improving 
the quality of migraine care.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 15504639 [PubMed - indexed for MEDLINE]

2055: Qual Life Res. 2004 Oct;13(8):1489-93.

Development and testing of the Japanese version of the migraine-specific quality 
of life instrument.

Ohbu S, Igarashi H, Okayasu H, Sakai F, Green J, Heller RF, Fukuhara S, Patrick
DL.

Department of Neurology, Yokohama Municipal Citizen's Hospital, Yokohama, Japan. 
sadaohbu@vesta.dti.ne.jp

We developed and tested a version of the migraine-specific quality of life
(MSQOL) instrument for use in Japan. The MSQOL was translated into Japanese,
evaluated by physicians and nurses who has experienced migraine headaches,
'backtranslated', approved by the author of the original version, and tested in
70 out-patients with migraine. There were no ceiling or floor effects. All three 
subscales were found to be internally consistent: alpha > or = 0.76. The
patients' scores were similar to those reported in the user's manual, with the
exception of a difference of about 11 points on the Avoidance Behaviors subscale.
Some correlations between MSQOL scores and SF-36 scores were statistically
significant, although none exceeded 0.52. Linear associations between some
measures of symptoms and some MSQOL scales were statistically significant, but
those associations were consistent neither for the two kinds of symptom reports
(severity and frequency) nor across all MSQOL subscales. Low MSQOL scores in
early 1999 correlated with more return visits for medication and with greater
amounts of triptan (anti-migraine) medication in 2001 and 2002. Overall, we
interpret these results as indicating that, while they cannot be used as
substitutes for reports of symptoms, scores on the Japanese version of the MSQOL 
can be used to assess the impact of migraine headaches on patients' lives.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Validation Studies

PMID: 15503844 [PubMed - indexed for MEDLINE]

2056: J Pain. 2004 Oct;5(8):413-9.

Indomethacin, alone and combined with prochlorperazine and caffeine, but not
sumatriptan, abolishes peripheral and central sensitization in in vivo models of 
migraine.

Ghelardini C, Galeotti N, Grazioli I, Uslenghi C.

Department of Preclinical and Clinical Pharmacology, University of Florence,
Firenze, Italy.

Recently it has been proposed that the throbbing pain of migraine is mediated by 
sensitization of peripheral trigeminovascular neurons, and that cutaneous
allodynia of migraine is mediated by sensitization of central trigeminovascular
neurons, and, moreover, that the triptans are less effective in aborting a
migraine attack if the central sensitization is already established. The
combination of indomethacin, prochlorperazine, and caffeine (IndoProCaf) is a
drug of well-established use in the acute treatment of migraine. The aim of this 
study was to investigate whether the 3 active principles of IndoProCaf, alone and
combined, compared to sumatriptan, were able to abolish the peripheral
sensitization induced by kainic acid and the central sensitization induced by
N-methyl-D-aspartate (NMDA) in in vivo models of hyperalgesia. The study showed
that indomethacin or IndoProCaf is able to abolish both the kainic acid-induced
and the NMDA-induced hyperalgesia. If administered at different times, IndoProCaf
was always effective in reversing the kainic acid-induced hyperalgesia.
Sumatriptan was not able to reverse either the kainic acid-induced or the
NMDA-induced hyperalgesia. The efficacy of indomethacin, alone and combined with 
prochlorperazine and caffeine, in abolishing peripheral and central sensitization
in in vivo models of hyperalgesia is a further explanation of the clinical
efficacy of IndoProCaf in the treatment of migraine. PERSPECTIVE: This study
suggests that, although triptans were shown to be able to abort migraine attacks 
only if given before the establishment of cutaneous allodynia and central
sensitization, IndoProCaf should be able to abort migraine attacks independently 
from the time of administration, because it is able to abolish an already
established peripheral and central sensitization.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 15501422 [PubMed - indexed for MEDLINE]

2057: Heart. 2004 Nov;90(11):1315-20.

Comment in:
    Heart. 2004 Nov;90(11):1245-7.

Inheritance of persistent foramen ovale and atrial septal defects and the
relation to familial migraine with aura.

Wilmshurst PT, Pearson MJ, Nightingale S, Walsh KP, Morrison WL.

The Royal Shrewsbury Hospital, Shrewsbury SY3 8XQ, UK.
peter.wilmshurst@rsh.nhs.uk

OBJECTIVE: To determine whether smaller atrial shunts (large persistent foramen
ovale (PFO) and small atrial septal defect (ASD)) are inherited and whether this 
has a role in the inheritance of migraine with aura. METHODS: Contrast
echocardiography was used to detect atrial shunts in 71 relatives of 20 probands 
with a significantly sized atrial shunt (large PFO or ASD). Four families with
three generations, 14 families with two generations, and two sibships were
studied. The contrast echocardiograms were performed blind to history of
migraine. A consultant neurologist, who was blinded to cardiac findings,
categorised migraine symptoms in subjects. RESULTS: The occurrence of atrial
shunts was consistent with autosomal dominant inheritance. Usually shunts were
large PFOs, but in some cases they were ASDs. There was also evidence that
inheritance of more complex congenital heart disease may be related to the
inheritance of PFOs. When the proband had migraine with aura and an atrial shunt,
15 of the 21(71.4%) first degree relatives with a significant right to left shunt
also had migraine with aura compared with three of 14 (21.4%) without a
significant shunt (p < 0.02). CONCLUSIONS: There is dominant inheritance of
atrial shunts. This is linked to inheritance of migraine with aura in some
families.

PMID: 15486131 [PubMed - indexed for MEDLINE]

2058: Psychiatry Clin Neurosci. 2004 Oct;58(5):536-43.

Temperament and character profiles of patients with tension-type headache and
migraine.

Boz C, Velioglu S, Ozmenoglu M, Sayar K, Alioglu Z, Yalman B, Topbas M.

Department of Neurology, Medical Faculty of Karadeniz Technical University,
Trabzon, Turkey. cavitb@yahoo.com

The aim of this present study was to evaluate the temperament and character
profiles of persons with tension-type headache (TTH) and migraine, and to compare
the results with those of healthy controls. The study population consisted of 81 
patients with TTH (60 female, 21 male) and 56 patients with migraine (34 female, 
17 male) aged 18-50 years, according to the criteria of the International
Headache Society with age and gender - matched healthy control subjects (54
female, 28 male). All participants were instructed to complete a
self-administered 240-item temperament and character inventory (TCI)
questionnaire and Beck Depression Inventory (BDI). The TCI assesses four
dimensions of temperament, namely, novelty seeking (NS), harm avoidance (HA),
reward dependence (RD), and persistence (P), and three dimensions of character,
being self-directedness (SD), cooperativeness (C) and self-transcendence (ST).
According to the TCI biosocial model, the temperament dimension HA is suggested
to indicate central serotonergic turnover, which is further correlated with
depressive state. It was found that mean BDI scores were significantly higher in 
patients with TTH and migraine than in those of the controls. The BDI scores were
positively correlated with HA scores (r = 0.295, P < 0.001) and negatively
correlated with SD (r = -0.386, P < 0.001) and C scores (r = -0.164, P= 0.016).
Multivariate analysis showed that BDI scores had significant covariation for HA, 
SD and C. Despite using the BDI score as a covariate, TTH patients had higher HA 
scores (P = 0.01) than did the control subjects. No significant differences were 
found between the groups regarding main NS, RD, P, SD, C and ST scores. Based on 
the main results of this study, it is suggested that higher serotonergic activity
related to HA scores in TTH patients and their relationship with depressive
symptomatology supports the role of central serotonergic involvement in TTH.

PMID: 15482586 [PubMed - indexed for MEDLINE]

2059: J Gen Intern Med. 2004 Oct;19(10):1005-12.

The medical care utilization and costs associated with migraine headache.

Elston Lafata J, Moon C, Leotta C, Kolodner K, Poisson L, Lipton RB.

Henry Ford Health System, Detroit, MI, USA. jlafata1@hfhs.org

OBJECTIVE: To describe the medical care use and costs associated with migraine.
DESIGN: Retrospective case-control design in which migraine case status was
ascertained via validated telephone interview and linked with comprehensive
claims data. Unadjusted and adjusted use and cost differences by migraine status 
were evaluated using exponential score tests and generalized estimating
equations. SETTING AND PATIENTS: We interviewed 8,579 individuals to identify
migraine cases (N = 1,265) and a random sample of nonmigraine controls (N =
1,178) among eligible health plan enrollees aged 18 to 55. MEASURES: Survey
responses were used to categorize individuals meeting the International Headache 
Society's diagnostic criteria for migraine with or without aura as migraine cases
and to collect information on comorbid psychiatric symptoms. Claims data were
used to compile annual medical and pharmaceutical use and costs, presence of
migraine diagnosis, and other diagnosed comorbidities. RESULTS:
Interview-ascertained migraine cases used more outpatient visits (9.1 vs 6.8; P <
.01), were more likely to be seen in the emergency department (20.7% vs 17.6%; P 
< .05), and were admitted to the hospital more (4.5% vs 2.8%; P < .05) compared
to nonmigraine controls. Cases incurred significantly higher medical care costs
($2,761 vs $2,064; P < .01). Multivariable model results indicate that much of
this increase in costs is due to the presence of major depressive symptoms as
well as other diagnosed comorbidities that are more common among those with
migraine. CONCLUSIONS: By combining validated telephone survey information to
identify migraine cases and controls with comprehensive claims data, we found
migraine cases incur higher medical care costs compared to controls. These
increased costs are associated with the presence of psychiatric symptoms and
other comorbidities.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 15482552 [PubMed - indexed for MEDLINE]

2060: Cephalalgia. 2004 Nov;24(11):973-9.

Cephalic venous congestion aggravates only migraine-type headaches.

Chou CH, Chao AC, Lu SR, Hu HH, Wang SJ.

The Department of Neurology, Yuan-Shan Veterans Hospital, I-Lan, Taiwan.

We performed the Queckenstedt's (Q)-test (compression over bilateral internal
jugular veins) and a sham test on 33 patients with migraine attacks (coded as 1.1
based on headache classification proposed by International Headache Society
(IHS)), 15 with migrainous attacks (IHS code 1.7), and 15 with tension-type
headache (IHS code 2.1) in both supine and sitting positions. 'Migrainous
headache' (code 1.7) was defined if the headache characteristics fulfilled all
but one criteria for 'migraine without aura'. Migraine sufferers reported a
marked increase in headache intensity after a 30-second Q-test in both supine and
sitting positions. Aggravation was greater in the supine position. The intensity 
increase was not demonstrated in the sham test, or in patients with migrainous
attacks or tension-type headaches after the Q-test. Patients with acute migraine 
thus appear more sensitive to increased cerebral venous pressure or intracranial 
pressure. The discrepancy of intensity changes between supine and sitting
positions may reflect different amount of venous return through the internal
jugular veins.

Publication Types: 
    Comparative Study

PMID: 15482361 [PubMed - indexed for MEDLINE]

2061: Cephalalgia. 2004 Nov;24(11):960-6.

Prevalence of migraine in a rural area in South Tanzania: a door-to-door survey.

Dent W, Spiss H, Helbok R, Matuja W, Scheunemann S, Schmutzhard E.

Department of Neurology, University Hospital Innsbruck, Innsbruck, Austria.
wolfgang.dent@macnews.de

We set out to assess the prevalence during the previous year of migraine in a
rural area surrounding the Mnero Diocesan Hospital in Southern-Tanzania. A
door-to-door survey from August until December 1999 using a questionnaire based
on the criteria of the International Headache Society (IHS), including 1047
households with 3351 persons, was done, consisting of a screening dialogue with a
representative family member followed by a face-to-face interview with the
affected subject. Of the 3351 participants (female 1876; male 1475; age > 10
years), 23.1% had suffered from headache during the past year; overall prevalence
of migraine was 5.0% (female 7.0%; male 2.6%); 1.4% reported migraine without
aura (female 1.8%; male 0.9%); and 3.6% reported migraine with aura (female 5.2%,
male 1.6%). The peak prevalence was found in female persons in the fourth
(11.1%), in male persons in the third decade of life (3.8%). Compared with other 
African surveys, the prevalence rate of migraine headache in South Tanzania is
slightly higher than among Ethiopian and Zimbabwean Africans.

Publication Types: 
    Comparative Study

PMID: 15482359 [PubMed - indexed for MEDLINE]

2062: Cephalalgia. 2004 Nov;24(11):947-54.

Placebo-controlled comparison of effervescent acetylsalicylic acid, sumatriptan
and ibuprofen in the treatment of migraine attacks.

Diener HC, Bussone G, de Liano H, Eikermann A, Englert R, Floeter T, Gallai V,
Göbel H, Hartung E, Jimenez MD, Lange R, Manzoni GC, Mueller-Schwefe G, Nappi G, 
Pinessi L, Prat J, Puca FM, Titus F, Voelker M; EMSASI Study Group.

Department of Neurology, University Essen, Germany. h.diener@uni-essen.de

Acetylsalicylic acid (ASA) in combination with metoclopramide has been frequently
used in clinical trials in the acute treatment of migraine attacks. Recently the 
efficacy of a new high buffered formulation of 1000 mg effervescent ASA without
metoclopramide compared to placebo has been shown. To further confirm the
efficacy of this new formulation in comparison with a triptan and a nonsteroidal 
anti-inflammatory drug (ibuprofen) a three-fold crossover, double-blind,
randomized trial with 312 patients was conducted in Germany, Italy and Spain.
Effervescent ASA (1000 mg) was compared to encapsulated sumatriptan (50 mg),
ibuprofen (400 mg) and placebo. The percentage of patients with reduction in
headache severity from moderate or severe to mild or no pain (primary endpoint)
was 52.5% for ASA, 60.2% for ibuprofen, 55.8% for sumatriptan and 30.6% for
placebo. All active treatments were superior to placebo (P < 0.0001), whereas
active treatments were not statistically different. The number of patients who
were pain-free at 2 h was 27.1%, 33.2%, 37.1% and 12.6% for those treated with
ASA, ibuprofen, sumatriptan or placebo, respectively. The difference between ASA 
and sumatriptan was statistically significant (P = 0.025). With respect to other 
secondary efficacy criteria and accompanying symptoms no statistically
significant differences between ASA and ibuprofen or sumatriptan were found.
Drug-related adverse events were reported in 4.1%, 5.7%, 6.6% and 4.5% of
patients treated with ASA, ibuprofen sumatriptan or placebo. This study showed
that 1000 mg effervescent ASA is as effective as 50 mg sumatriptan and 400 mg
ibuprofen in the treatment of migraine attacks regarding headache relief from
moderate/severe to mild/no pain at 2 h. Regarding pain-free at 2 h sumatriptan
was most effective.

Publication Types: 
    Clinical Trial
    Comparative Study
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 15482357 [PubMed - indexed for MEDLINE]

2063: Cephalalgia. 2004 Nov;24(11):940-6.

The place of osmophobia and taste abnormalities in migraine classification: a
tertiary care study of 1237 patients.

Kelman L.

Headache Center of Atlanta, Atlanta, GA 30342, USA. lkelman@mindspring.com

This study evaluates osmophobia and taste abnormalities in relationship to
sensitivity and specificity in the classification of migraine. Consecutive
International Headache Society (IHS) classified patients (n = 1237) were
evaluated. Symptoms were graded from 0 to 3. Osmophobia and taste abnormalities
were tested for sensitivity and specificity in migraine diagnosis. The patients
were 85.4% female and their mean age was 38.1 years. Of 673 patients 24.7%
complained of osmophobia, and 24.6% of 505 complained of taste abnormalities. In 
the absence of nausea and vomiting the combinations of two symptoms gave the
following sensitivity and specificity percentages, respectively: photophobia and 
phonophobia, 10.6 and 84.9; photophobia and osmophobia, 1.1 and 99.0; phonophobia
and osmophobia, 1.1 and 98.6; photophobia and taste abnormality, 9.6 and 99.0;
phonophobia and taste abnormality, 9.6 and 98.8; and osmophobia and taste
abnormality, 4.2 and 99.4. Osmophobia and taste abnormalities were demonstrated
to be very specific in diagnosing migraine IHS 1.1-1.6, but very insensitive.

Publication Types: 
    Comparative Study

PMID: 15482356 [PubMed - indexed for MEDLINE]

2064: Cephalalgia. 2004 Nov;24(11):925-33.

Comment in:
    Cephalalgia. 2004 Nov;24(11):915-7.

Early treatment of a migraine attack while pain is still mild increases the
efficacy of sumatriptan.

Scholpp J, Schellenberg R, Moeckesch B, Banik N.

Medical Department, GlaxoSmithKline, Muenchen, Germany. Joachim.Scholpp@dgn.de

To investigate the hypothesis that early treatment of a migraine attack with
sumatriptan, while pain is still mild, results in higher pain free rates in
comparison to delayed treatment, when pain is at least moderate, we performed a
prospective, controlled and open label study. Migraineurs with or without aura
who fulfilled the diagnostic criteria recommended by the International Headache
Society were enrolled in the study and randomly assigned to either 'early' or
'late' treatment with sumatriptan 100 mg tablets. In the early treatment group
significantly more patients were pain free at all times measured during two hours
after dosing than in the late treatment group. Furthermore, patients in the early
treatment group became pain free significantly sooner after dosing than patients 
who delayed treatment. It is concluded that migraineurs, who are able to
differentiate between a migraine attack and other forms of headache, benefit from
early intervention with sumatriptan 100 mg tablets.

Publication Types: 
    Clinical Trial
    Comparative Study
    Multicenter Study
    Randomized Controlled Trial

PMID: 15482353 [PubMed - indexed for MEDLINE]

2065: Cephalalgia. 2004 Nov;24(11):918-24.

Comment in:
    Cephalalgia. 2004 Nov;24(11):915-7.

Benefits of treating highly disabled migraine patients with zolmitriptan while
pain is mild.

Klapper J, Lucas C, Røsjø Ø, Charlesworth B; ZODIAC study group.

Colorado Neurology and Headache Center, Denver 80218, USA. jkheaddoc@aol.com

Clinical trials of migraine therapy often require treatment when migraine pain
intensity is moderate or severe, but many physicians find this practice
artificial and patients often prefer to treat while pain is mild. This
randomized, placebo-controlled study assessed the efficacy of zolmitriptan 2.5 mg
in treating migraine while pain is mild, in patients who typically experience
migraine attacks that are initially mild, but progress to moderate or severe. The
intent-to-treat population comprised 280 patients (138 zolmitriptan; 148
placebo), with mean MIDAS grades of 29.6 (zolmitriptan) and 27.6 (placebo).
Zolmitriptan 2.5 mg provided a significantly higher pain-free rate at 2 h (43.4% 
vs. 18.4% placebo; P < 0.0001). Significantly fewer zolmitriptan patients
reported progression of headache pain to moderate or severe intensity 2 h
postdose (53.7% vs. 70.4% placebo; P < 0.01), or required further medication
within 24 h (46.4% vs. 71.1% placebo; P < 0.0001). The efficacy of zolmitriptan
was more pronounced in patients treating during the first 15 min following pain
onset. Adverse events were reported in 31.2% of patients treated with
zolmitriptan (vs. 11.3% for placebo), and the incidence was lower in patients who
treated early after attack onset. Zolmitriptan provides high efficacy when
treating migraine while pain is mild, with the clinical benefits being more
pronounced when treating early after migraine onset.

Publication Types: 
    Clinical Trial
    Comparative Study
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 15482352 [PubMed - indexed for MEDLINE]

2066: Exp Brain Res. 2005 Feb;161(1):34-8. Epub 2004 Oct 12.

Facilitatory effects of 1 Hz rTMS in motor cortex of patients affected by
migraine with aura.

Brighina F, Giglia G, Scalia S, Francolini M, Palermo A, Fierro B.

Department of Neurology, Ophthalmology, Otology and Psychiatry, University of
Palermo, Via G. La Loggia 1, 90129 Palermo, Italy.

We previously showed paradoxical facilitatory effects of low-frequency repetitive
transcranial magnetic stimulation (rTMS) on striate and extrastriate cortex of
patients suffering migraine with aura. In this study we evaluated the effects of 
1 Hz rTMS on the excitability of inhibitory and facilitatory circuits of motor
cortex to explore whether the abnormal pattern of excitability extends beyond the
sensory cortex also involving motor areas in migraine with aura. Nine patients
affected by migraine with aura and eight healthy controls entered into the study.
The hot spot for activation of the right abductor pollicis brevis (APB) was
checked by means of a figure-of-eight coil and motor threshold (MT) recorded on
this point. Nine hundred magnetic stimuli at 1 Hz frequency and 90% MT intensity 
were delivered at the hot spot. Before and after rTMS, intracortical inhibitory
and facilitatory circuit excitability was assessed by means of a paired pulse
paradigm (conditioning stimulus 80% MT and test stimulus 120% MT) with two
different interstimulus intervals: 2 ms (inhibitory) and 10 ms (facilitatory).
Amplitude of the responses was expressed as the percentage of motor evoked
potential (MEP) to test stimulus alone. Results showed that in basal condition
migraineurs present significantly reduced levels of intracortical inhibition
(ICI) compared to controls. More importantly, opposite results were obtained in
migraineurs with respect to controls when 1 Hz rTMS was applied. Specifically,
whereas intracortical facilitation (ICF) significantly decreased in controls, it 
significantly increased in migraineurs. ICI levels were not significantly
affected by low-frequency stimulation. Our results showed that motor as well as
sensory cortex of migraine patients present an abnormal modulation of cortical
excitability, where a relevant role is likely played by the inefficiency of
inhibitory circuits.

Publication Types: 
    Comparative Study

PMID: 15480599 [PubMed - indexed for MEDLINE]

2067: Clin Ther. 2004 Aug;26(8):1305-18.

French guidelines for the diagnosis and management of migraine in adults and
children.

Géraud G, Lantéri-Minet M, Lucas C, Valade D; French Society for the Study of
Migraine Headache (SFEMC).

Department of Neurology, Rangueil Hospital, Toulouse, France.
geraud.g@chu-toulouse.fr

BACKGROUND: The French Recommendations for Clinical Practice: Diagnosis and
Therapy of Migraine are guidelines concerning the overall management of patients 
with migraine, including diagnostic and therapeutic strategies and assessment of 
disability. OBJECTIVE: This article summarizes the guidelines as they apply to
adults and children, and proposes future direction for steps toward optimal
treatment of migraine in patients in France. METHODS: The recommendations were
categorized into 3 levels of proof (A-C) according to the National Agency for
Accreditation and Evaluation in Health (ANAES) methodology and were based on a
professional consensus reached among members of the Working Group and the
Guidelines Review Group of the ANAES. RESULTS: The International Headache Society
diagnostic criteria for migraine should be used in routine clinical practice.
Recommended agents for the treatment of migraine in adults include nonsteroidal
anti-inflammatory drugs, acetylsalicylic acid (ASA) monotherapy or in combination
with metoclopramide, acetaminophen monotherapy, triptans, ergotamine tartrate,
and dihydroergotamine mesylate. Patients should use the medication as early as
possible after the onset of migraine headache. For migraine prophylaxis in
adults, the following can be used: propranolol, metoprolol, oxetorone, or
amitriptyline as first-line treatment, and pizotifen, flunarizine, valproate
sodium, or topiramate as second-line treatment. Migraine in children can be
distinguished from that in adults by shorter duration (2-48 hours in children
aged <15 years), more frequent bilateral localization, frequent predominant
gastrointestinal disturbances, and frequent pallor hailing the onset of the
attack. The following drugs are recommended in children and adolescents:
ibuprofen in children aged >6 months, diclofenac in children weighing >16 kg,
naproxen in children aged >6 years or weighing >25 kg, ASA alone or in
combination with metoclopramide, acetaminophen alone or in combination with
metoclopramide, and ergotamine tartrate in children aged >10 years. CONCLUSIONS: 
These guidelines are intended to help general practitioners to manage migraine
patients according to the rules of evidence-based medicine.

Publication Types: 
    Guideline
    Practice Guideline

PMID: 15476911 [PubMed - indexed for MEDLINE]

2068: Arq Neuropsiquiatr. 2004 Sep;62(3B):774-7. Epub 2004 Oct 5.

Depression and migraine.

Galego JC, Cipullo JP, Cordeiro JA, Tognola WA.

Departamento de Ciências Neurológicas, Faculdade de Medicina de São José do Rio
Preto (FAMERP), São José do Rio Preto SP, Brazil. jcgalego@uol.com.br

The objective of this study was to evaluate both the presence and intensity of
depressive symptoms in patients with episodic migraine (EM) and transformed
migraine (TM) or chronic migraine, comparing them with a control group. Beck
Depression Inventory (BDI) was used for this purpose. The median of BDI score of 
the control group was significantly lower than the EM and TM groups (p<0.0005).
Either the EM or the TM did not show any significant difference in relation to
the median of BDI scores (p=0.12). The TM group showed a higher frequency of
severe depression when analyzed qualitatively by dependence analysis. Symptoms of
severe depression by means of qualitative analysis may strengthen a co-morbidity 
between depression and transformed migraine. This association might be considered
rather a factor of TM perpetuation than a risk factor for the transformation of
EM into TM.

PMID: 15476067 [PubMed - indexed for MEDLINE]

2069: Brain. 2004 Nov;127(Pt 11):2459-69. Epub 2004 Oct 7.

Hyperexcitability of the primary somatosensory cortex in migraine--a
magnetoencephalographic study.

Lang E, Kaltenhäuser M, Neundörfer B, Seidler S.

Department of Neurology, University of Erlangen-Nuremberg, Schwabachanlage 6,
D-91054 Erlangen, Germany. eberhard.lang@rzmail.uni-erlangen.de

The excitability of the cerebral cortex in the interictal state of migraine
appears to be fundamental in the brain's susceptibility to migraine attacks.
Subpopulations of cortical neurons are reported to have different physiological
response properties to different interstimulus intervals (ISIs) and, hence, may
be differentially altered or modulated in migraine. The aim of this study
therefore was to evaluate response characteristics of temporally and spatially
defined neuronal subpopulations in the cortex of migraineurs. To this end, we
measured, by means of magnetoencephalography (37-channel neuromagnetometer), the 
response properties of the early components of the somatosensory evoked magnetic 
fields following electrical stimulation of the median nerve, the N20m and P35m,
at ISIs ranging between 0.3 and 6 s. As a measure of the number of excited
neurons underlying the N20m and P35m, we evaluated the root mean square (r.m.s.) 
of the deflections across all 37 channels at the corresponding latencies and the 
corresponding dipole moment of the equivalent current dipole (ECD strength).
Twenty consecutive women with at least three migraine attacks/month (range
3-8/month) fulfilling the International Headache Society criteria and 20
age-matched healthy women were included in the study. In migraineurs, the r.m.s. 
and ECD strength of N20m was increased at all ISIs (r.m.s., P < 0.05; ECD
strength, P < 0.01) and positively related to the mean attack frequency (r.m.s., 
R(s) = 0.6, P < 0.01; ECD strength, R(s) = 0.5, P < 0.05). In contrast, the
r.m.s. and ECD strength of P35m did not differ significantly between migraineurs 
and control subjects and did not correlate significantly with the frequency of
migraine attacks. Responses to different ISIs did not differ significantly
between migraineurs and control subjects. The r.m.s. of N20m was stable for ISIs 
between 0.5 and 6 s and decreased significantly at an ISI of 0.3 s. In contrast, 
the r.m.s. of P35m decreased continuously as the ISI was decreased below 6 s and 
this reached significance for an ISI of < or =1 s. Habituation of N20m or P35m,
i.e. a decrease in response magnitude following repetitive stimulation over time,
was not found in either the control subjects or in the migraineurs. It is
concluded that the population of neurons in the primary somatosensory cortex
underlying the N20m are hyperexcitable and that this hyperexcitability is linked 
to the frequency of migraine attacks. This hyperexcitability appears not to be
related to habituation since habituation was not found in the control subjects.
In contrast, the magnitude of P35m is not pathophysiologically linked to the
interictal state of migraine. Furthermore, the cellular mechanisms causing
ISI-dependent depression of N20m and P35m are not altered in migraine.

PMID: 15471903 [PubMed - indexed for MEDLINE]

2070: Eur J Neurol. 2004 Oct;11(10):671-7.

No effect of eletriptan administration during the aura phase of migraine.

Olesen J, Diener HC, Schoenen J, Hettiarachchi J.

Department of Neurology, Glostrup Hospital, Copenhagen, Denmark.
jeol@glostruphosp.kbhamt.dk

Migraine aura is a warning sign readily recognized by patients. From the onset of
aura it takes 30-60 min before the headache phase starts. Administration of acute
medication during aura should provide sufficient time to achieve therapeutic
plasma levels, counteracting the headache. To test this hypothesis we evaluated
the efficacy of eletriptan 80 mg taken during aura. Patients met International
Headache Society diagnostic criteria for migraine with aura, with an attack
frequency of at least one per month and with aura occurring in > 50% of recent
attacks. Of 123 patients randomized, 87 (71%) were treated with a double-blind,
one attack, during the aura phase before headache, dose of either eletriptan 80
mg (n = 43; 74% female; mean age, 40 years), or placebo (n = 44; 82% female; mean
age, 40 years). The primary outcome measure was the proportion of patients not
developing moderate-to-severe headache within 6 h post-dose. There was no
significant difference in the proportion of patients developing
moderate-to-severe headache on eletriptan (61%) versus placebo (46%). Eletriptan 
was well tolerated and did not prolong the aura phase. Typical transient triptan 
adverse events were observed; most were mild-to-moderate in intensity. This study
confirms the findings of two studies showing that triptans are ineffective but
safe when given during the migraine aura phrase.

Publication Types: 
    Clinical Trial
    Comparative Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 15469451 [PubMed - indexed for MEDLINE]

2071: Eur J Pharmacol. 2004 Oct 1;500(1-3):315-30.

Calcitonin gene-related peptide and its role in migraine pathophysiology.

Arulmani U, Maassenvandenbrink A, Villalón CM, Saxena PR.

Department of Pharmacology, Cardiovascular Research Institute "COEUR", Erasmus
MC, University Medical Centre Rotterdam, P.O. Box 1738, Rotterdam 3000 DR, The
Netherlands.

Migraine is a common neurological disorder that is associated with an increase in
plasma calcitonin gene-related peptide (CGRP) levels. CGRP, a neuropeptide
released from activated trigeminal sensory nerves, dilates intracranial blood
vessels and transmits vascular nociception. Therefore, it is propounded that: (i)
CGRP may have an important role in migraine pathophysiology, and (ii) inhibition 
of trigeminal CGRP release or CGRP-induced cranial vasodilatation may abort
migraine. In this regard, triptans ameliorate migraine headache primarily by
constricting the dilated cranial blood vessels and by inhibiting the trigeminal
CGRP release. In order to explore the potential role of CGRP in migraine
pathophysiology, the advent of a selective CGRP receptor antagonist was
obligatory. The introduction of di-peptide CGRP receptor antagonists, namely
BIBN4096BS (1-piperidinecarboxamide,
N-[2-[[5-amino-1-[[4-(4-pyridinyl)-1-piperazinyl]carbonyl] pentyl]
amino]-1-[(3,5-dibromo-4-hydroxyphenyl)
methyl]-2-oxoethyl]-4-(1,4-dihydro-2-oxo-3(2H)-quinazolinyl)-, [R-(R*,S*)]-), is 
a breakthrough in CGRP receptor pharmacology and can be used as a tool to
investigate the role of CGRP in migraine headaches. Preclinical investigations in
established migraine models that are predictive of antimigraine activity have
shown that BIBN4096BS is a potent CGRP receptor antagonist and that it has
antimigraine potential. Indeed, a recently published clinical study has reported 
that BIBN409BS is effective in treating acute migraine attacks without
significant side effects. The present review will discuss mainly the potential
role of CGRP in the pathophysiology of migraine and the various treatment
modalities that are currently available to target this neuropeptide.

Publication Types: 
    Review

PMID: 15464043 [PubMed - indexed for MEDLINE]

2072: Curr Med Res Opin. 2004 Oct;20(10):1595-604.

The impact of migraine on work, family, and leisure among young women -- a
multinational study.

Dueland AN, Leira R, Burke TA, Hillyer EV, Bolge S.

Sandvika Neurologic Service, Sandvika, Norway.

OBJECTIVE: To assess the impact of migraine on work, family, and leisure among
young women who were employed full or part time, or as a full-time student.
RESEARCH DESIGN AND METHODS: This cross-sectional telephone survey with 6-month
recall was conducted in Israel and eight European countries (Finland, Germany,
Greece, Italy, Norway, Spain, Sweden, and The Netherlands). Random-digit dialing 
was used to identify study participants: women 18-35 years of age with migraine, 
who used medication to treat their migraine, and who were employed or full-time
students. RESULTS: Of 1810 participants, 42% self-reported having a physician
diagnosis of migraine. During the prior 6 months, 46% of participants missed at
least 1 day of work or school and 74% were prevented from functioning fully at
work or school because of migraine. Mean work/school absenteeism due to migraine 
was 1.9 days over 6 months (range, 0.8 days in Sweden to 2.8 days in Norway).
Over half of participants reported one or more occurrences of being unable to
spend time with family or friends (62%) or being unable to enjoy recreational or 
leisure activities (67%) because of migraine. The percentage of study
participants using triptans was lowest in southern Europe and highest in the
Nordic countries, ranging from 1% in Greece to 50% in Sweden. Country, age,
marital status, physician diagnosis of migraine, and number of migraines or
severe headaches in the prior year were independent predictors of the mean number
of days of migraine-related work loss. Migraine-related work loss was lowest in
Sweden and greatest in Greece, Israel, and The Netherlands. Higher work loss was 
recorded for those 18-24 years of age; those who were separated, widowed, or
divorced; those with migraine diagnosed by a physician; and those with more
frequent migraines or severe headaches (> or =24/year). The 6-month recall period
used when estimating patient-reported work loss, and identifying participants
with migraine based on self-reported migraine or severe headache, were the most
important limitations of the study. CONCLUSIONS: We found substantial
migraine-related impairment of productivity at work and school as well as of
family and leisure time among young women in Israel and eight European countries.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 15462692 [PubMed - indexed for MEDLINE]

2073: Neurogenetics. 2004 Sep;5(3):177-85. Epub 2004 Jul 31.

Erratum in:
    Neurogenetics. 2005 Sep;6(3):169. Liana, Veneziano [corrected to Veneziano,
Liana]; Giovanni, Antonini [corrected to Antonini, Giovanni]; Paola, Giunti
[corrected to Giunti, Paola].

A G301R Na+/K+ -ATPase mutation causes familial hemiplegic migraine type 2 with
cerebellar signs.

Spadaro M, Ursu S, Lehmann-Horn F, Veneziano L, Antonini G, Giunti P, Frontali M,
Jurkat-Rott K.

Department of Neurological Sciences, 1st Medical School, La Sapienza University, 
Rome, Italy.

Familial hemiplegic migraine (FHM) is an autosomal dominant subtype of migraine
with hemiparesis during the aura. In over 50% of cases the causative gene is
CACNA1A (FHM1), which in some cases produces a phenotype with cerebellar signs,
including ataxia and nystagmus. Recently, mutations in ATP1A2 on chromosome 1q23 
encoding a Na+/K+ -ATPase subunit were identified in four families (FHM2). We now
describe an FHM2 pedigree with a fifth ATP1A2 mutation coding for a G301R
substitution. The phenotype was particularly severe and included hemiplegic
migraine, seizure, prolonged coma, elevated temperature, sensory deficit, and
transient or permanent cerebellar signs, such as ataxia, nystagmus, and
dysarthria. A mild crossed cerebellar diaschisis during an attack further
supported the clinical evidence of a cerebellar deficit. This is the first report
suggesting cerebellar involvement in FHM2. A possible role for CACNA1A in
producing the phenotype in this family was excluded by linkage studies to the
FHM1 locus. The study of this family suggests that the absence of cerebellar
signs may not be a reliable indicator to clinically differentiate FHM2 from FHM1.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 15459825 [PubMed - indexed for MEDLINE]

2074: Stroke. 2004 Nov;35(11 Suppl 1):2652-6. Epub 2004 Sep 30.

Estrogens, migraine, and stroke.

Bousser MG.

Department of Neurology, Lariboisière Hospital, 2 Rue Ambroise Paré, Paris Cédex 
10, France 75571. mg.bousser@lrb.ap-hop-paris.fr

Epidemiological studies suggest the existence of close but complex relationships 
between estrogens, migraine, and stroke in women before menopause. Migraine,
particularly without aura, is strongly influenced by estrogens as illustrated by 
the frequency of onset at puberty, of menstrual migraine, and of improvement
during pregnancy. Migraine, particularly with aura, is a risk factor for ischemic
stroke with a relative risk of 3, further increased by tobacco smoking and oral
contraceptive use. The pathophysiological mechanism underlying these close
relationships remains unknown. In practice, given the very low absolute risk of
stroke in young women, there is no systematic contraindication to oral
contraceptive use in young female migraineurs but rather a firm recommendation
for no smoking and for the use of low-estrogen-content pills or progestogens
only, particularly in migraine with aura.

Publication Types: 
    Review

PMID: 15459439 [PubMed - indexed for MEDLINE]

2075: South Med J. 2004 Sep;97(9):819-22.

A novel specific prophylaxis for menstrual-associated migraine.

Calhoun AH.

Department of Neurology, University Headache Clinic, University of North Carolina
at Chapel Hill, 3114 Bioinformatics Bldg., Campus Box 7025, Chapel Hill, NC
27599-7025, USA.

OBJECTIVES: Few migraine prophylactic therapies have demonstrated a 50% reduction
in headaches. Even when successful, the economic burden of prophylaxis can
discourage widespread usage. This article presents a pilot study of a novel,
effective, specific, and inexpensive prophylactic strategy for
menstrual-associated migraine. MATERIALS AND METHODS: Eleven women with
menstrual-associated migraine and fewer than 14 days of headache per month were
identified from prospective enrollment at a gynecology practice and retrospective
chart review at a headache center. Exclusion criteria included current use of
prophylactic therapy for migraine. METHODS: Patients received open-label therapy 
with an oral contraceptive containing 20 microg ethinyl estradiol on days 1 to
21, supplemented with 0.9 mg conjugated equine estrogens on days 22 to 28.
Headache intensity and bleeding were recorded in diaries that plotted headache
days by oral contraceptive pill days. RESULTS: All of the patients achieved at
least a 50% reduction in number of headache days per cycle (mean 77.9%
reduction); 10 of the 11 women achieved at least a 50% reduction in weighted
headache score (mean 76.3% reduction). CONCLUSIONS: All currently available
estrogen-containing oral contraceptives produce a premenstrual fall in ethinyl
estradiol concentration equal to or greater than 20 microg. Estrogen
supplementation during the placebo week can reduce the magnitude of this fall to 
less than 20 microg. When the decline is limited to the equivalent of 10 microg
ethinyl estradiol, menstrual-associated migraine is prevented. At an average cost
of six dollars per headache-day prevented, this represents an effective and
inexpensive strategy for a common migraine trigger.

Publication Types: 
    Clinical Trial

PMID: 15455962 [PubMed - indexed for MEDLINE]

2076: Pharmacoeconomics. 2004;22(15):985-99.

Economic impact of migraine and other episodic headaches in France: data from the
GRIM2000 study.

Pradalier A, Auray JP, El Hasnaoui A, Alzahouri K, Dartigues JF, Duru G, Henry P,
Lantéri-Minet M, Lucas C, Chazot G, Gaudin AF.

Hôpital Louis Mourier, Colombes, France.
secretariat.medecine4@lmr.ap-hop-paris.fr

BACKGROUND: Migraine is a prevalent and incapacitating condition that affects
individuals in the prime of their productive life, thus generating an economic
burden for both society and healthcare systems. The direct annual healthcare
costs of migraine in France were assessed over 10 years ago, and the current
study updates these figures. OBJECTIVE: The objective of this study was to
determine the economic cost (primarily direct costs) of migraine and other
episodic headache in France based on a general population survey of headache, the
GRIM2000 (Groupe de Researche Interdisciplinaire sur la Migraine). DESIGN: From a
representative general population sample of 10,585 individuals aged > or = 15
years in France in 1999, 1486 individuals experiencing headaches were identified 
and interviewed regarding healthcare resource consumption in the previous 6
months. By applying unit costs to the resource data, costings (in 1999 values)
were determined for physician consultations, hospitalisation, medication use and 
diagnostic/laboratory tests, and evaluated from a healthcare system perspective. 
Information on absenteeism and lost productivity was derived from the Migraine
Disability Assessment Score (MIDAS) questionnaire. RESULTS: The prevalence of
migraine (including migrainous disorder) was determined to be 17%. Total annual
direct healthcare costs were estimated to be Euros 128 per individual with
migraine in 1999, corresponding to Euros 1044 million when extrapolated to all
individuals experiencing migraine and aged > or = 15 years. Around two-thirds of 
this cost accrued to the social security system (Euros 698 million; Euros 85 per 
individual). The total annual direct cost of other forms of episodic headache was
much lower at Euros 28 per individual (social security cost Euros 18); with a
prevalence of 9.2%, the annual national direct cost for other forms of episodic
headache totalled Euros 124 million. The principal cost element was physician
consultations. However, it was found that many individuals had never consulted a 
physician for their headaches, and self-medication contributed substantially to
the medication costs (the second greatest cost factor for migraine). The cost per
individual rose steeply with increasing severity of headache. CONCLUSIONS: The
direct healthcare costs of migraine do not seem to have risen significantly over 
the past decade. A small minority of individuals with more severe headaches
consume most of the healthcare resources devoted to migraine, while most
individuals generate relatively low direct costs. The total annual direct costs
in France for migraine are almost 10-fold higher than those of other episodic
headache.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 15449963 [PubMed - indexed for MEDLINE]

2077: Am J Med Genet B Neuropsychiatr Genet. 2005 Jan 5;132B(1):85-9.

Chromosome 19p13 loci in Finnish migraine with aura families.

Kaunisto MA, Tikka PJ, Kallela M, Leal SM, Papp JC, Korhonen A, Hämäläinen E,
Harno H, Havanka H, Nissilä M, Säkö E, Ilmavirta M, Kaprio J, Färkkilä M, Ophoff 
RA, Palotie A, Wessman M.

Biomedicum Helsinki, Research Program in Molecular Medicine, University of
Helsinki, Helsinki, Finland.

Chromosomal area 19p13 contains two migraine associated genes: a Ca(v)2.1
(P/Q-type) calcium channel alpha(1) subunit gene, CACNA1A, and an insulin
receptor gene, INSR. Missense mutations in CACNA1A cause a rare Mendelian form of
migraine, familial hemiplegic migraine type 1 (FHM1). Contribution of CACNA1A
locus has also been studied in the common forms of migraine, migraine with (MA)
and without aura (MO), but the results have been contradictory. The role of INSR 
is less well established: A region on 19p13 separate from CACNA1A was recently
reported to be a major locus for migraine and subsequently, the INSR gene was
associated with MA and MO. Our aim was to clarify the role of these loci in MA
families by analyzing 72 multigenerational Finnish MA families, the largest
family sample so far. We hypothesized that the potential major contribution of
the 19p13 loci should be detected in a family sample of this size, and this was
confirmed by simulations. We genotyped eight polymorphic microsatellite markers
surrounding the INSR and CACNA1A genes on 757 individuals. Using parametric and
non-parametric linkage analysis, none of the studied markers showed any evidence 
of linkage to MA either under locus homogeneity or heterogeneity. However,
marginally positive lod scores were observed in three families, and thus for
these families the results remain inconclusive. The overall conclusion is that
our study did not provide evidence of a major MA susceptibility region on 19p13
and thus we were not able to replicate the INSR locus finding. Copyright 2004
Wiley-Liss, Inc.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 15449251 [PubMed - indexed for MEDLINE]

2078: J Biol Chem. 2004 Dec 10;279(50):51844-50. Epub 2004 Sep 23.

Familial hemiplegic migraine type 1 mutations K1336E, W1684R, and V1696I alter
Cav2.1 Ca2+ channel gating: evidence for beta-subunit isoform-specific effects.

Müllner C, Broos LA, van den Maagdenberg AM, Striessnig J.

Abteilung Pharmakologie und Toxikologie, Institut für Pharmazie, Universität
Innsbruck, Peter-Mayrstrasse 1/I, A-6020 Innsbruck, Austria.

Mutations in the Cav2.1 alpha1-subunit of P/Q-type Ca2+ channels cause human
diseases, including familial hemiplegic migraine type-1 (FHM1). FHM1 mutations
alter channel gating and enhanced channel activity at negative potentials appears
to be a common pathogenetic mechanism. Different beta-subunit isoforms (primarily
beta4 and beta3) participate in the formation of Cav2.1 channel complexes in
mammalian brain. Here we investigated not only whether FHM1 mutations K1336E
(KE), W1684R (WR), and V1696I (VI) can affect Cav2.1 channel function but focused
on the important question whether mutation-induced changes on channel gating
depend on the beta-subunit isoform. Mutants were co-expressed in Xenopus oocytes 
together with beta1, beta3, or beta4 and alpha2delta1 subunits, and channel
function was analyzed using the two-electrode voltage-clamp technique. WR shifted
the voltage dependence for steady-state inactivation of Ba2+ inward currents
(IBa) to more negative voltages with all beta-subunits tested. In contrast, a
similar shift was observed for KE only when expressed with beta3. All mutations
promoted IBa decay during pulse trains only when expressed with beta1 or beta3
but not with beta4. Enhanced decay could be explained by delayed recovery from
inactivation. KE accelerated IBa inactivation only when co-expressed with beta3, 
and VI slowed inactivation only with beta1 or beta3. KE and WR shifted channel
activation of IBa to more negative voltages. As the beta-subunit composition of
Cav2.1 channels varies in different brain regions, our data predict that the
functional FHM1 phenotype also varies between different neurons or even within
different neuronal compartments.

Publication Types: 
    In Vitro
    Research Support, Non-U.S. Gov't

PMID: 15448138 [PubMed - indexed for MEDLINE]

2079: Headache. 2004 Oct;44(9):930-2.

Carotid artery dissection in ergotamine abuse.

Akova-Oztürk E, Husstedt IW, Ringelstein EB, Evers S.

The case of a 65-year-old male migraine patient with spontaneous internal carotid
artery dissection is presented. He had been abusing ergotamine compounds for
several years on at least 15 days per month. A possible association between
arterial dissection and ergotamine abuse is discussed.

Publication Types: 
    Case Reports
    Letter

PMID: 15447707 [PubMed - indexed for MEDLINE]

2080: Headache. 2004 Oct;44(9):916-23.

Headache profile in patients with idiopathic hypertrophic cranial
pachymeningitis.

Wang YJ, Fuh JL, Lirng JF, Lu SR, Wang SJ.

Department of Neurology, National Yang-Ming University School of Medicine,
Taipei, Taiwan.

BACKGROUND: Idiopathic hypertrophic cranial pachymeningitis (IHCP) is an uncommon
disorder due to localized or diffuse thickening of the dura mater. While headache
is the most common manifestation, the clinical characteristics of the headache in
IHCP have not been well characterized. METHODS: From 1996 to 2002, 6 consecutive 
patients with IHCP presenting with headache were reviewed (3 women, 3 men; mean
age: 49 years). Diagnosis was based on characteristic neuroimaging findings and
the exclusion of secondary causes of cranial pachymeningitis. This study reported
the headache characteristics, neuroimaging features, and longitudinal follow-up. 
RESULTS: Chronic daily headache, especially chronic migraine, was the most common
headache pattern observed (4/6 patients). Lateralization of headache location
appeared to correlate with the distribution of the hypertrophied dural lesions.
Diagnostic delay was due to failure to evaluate with gadolinium-enhanced MRI.
After treatment, headache (5/6, 83%) and neurologic deficits (2/3, 67%) improved 
in most patients; however, follow-up MRIs (n = 5) showed deterioration in 3
patients. CONCLUSION: The headache of IHCP is typically a chronic daily headache,
often resembling chronic migraine. Correspondingly, IHCP should be considered in 
the differential diagnosis of refractory chronic daily headache, with or without 
associated cranial neuropathy or other associated neurologic deficits. The
typical imaging finding on gadolinium-enhanced MRI is localized or diffuse
pachymeningitis and failure to order a gadolinium-enhanced MRI is the primary
reason for delayed diagnosis. Despite symptomatic improvement on longitudinal
follow-up, the MRI abnormalities may not improve in parallel with the clinical
symptoms.

PMID: 15447702 [PubMed - indexed for MEDLINE]

2081: Headache. 2004 Oct;44(9):911-5.

Familial hemiplegic migraine, neuropsychiatric symptoms, and Erdheim-Chester
disease.

Black DF, Kung S, Sola CL, Bostwick MJ, Swanson JW.

Mayo Clinic, Neurology, Rochester, MN 55905, USA.

We report the occurrence of unilateral cerebral hemisphere edema with subsequent 
cortical laminar necrosis in the setting of familial hemiplegic migraine (FHM)
and permanent neurologic sequelae after resolution of an attack in 1 patient.
Contemporaneous with this severe attack of FHM, the patient was found to exhibit 
multiple systemic and neurological symptoms referable to Erdheim-Chester disease 
(a rare non-Langerhans cell histiocytosis) that was confirmed by bone biopsy.
This case demonstrates the severity possible with a migrainous infarction
associated with FHM. The co-occurrence of two such rare entities in 1 patient
suggests a possible relationship.

Publication Types: 
    Case Reports

PMID: 15447701 [PubMed - indexed for MEDLINE]

2082: Headache. 2004 Oct;44(9):900-7.

Migraine treatment with rizatriptan and non-triptan usual care medications: a
pharmacy-based study.

Cady R, Martin V, Adelman J, Diamond M, Sajjan S, Hu XH.

Headache Care Center, Primary Care Network, Inc., Springfield, MO, USA.

OBJECTIVE: To compare the effectiveness of rizatriptan to other non-triptan
medications in the relief of migraine headache in usual care settings.
BACKGROUND: Although rizatriptan has been shown to provide effective relief of
migraine symptoms in clinical trials, limited data exist directly comparing its
effectiveness with non-triptan medications. METHODS: Migraineurs aged 18 to 55
who had been prescribed a new antimigraine drug (rizatriptan 10 mg or a selected 
class of non-triptan oral medications) were recruited to participate in the study
through a national retail pharmacy chain. Participants completed a baseline
questionnaire at the enrollment and reported their treatment experiences by
filling out the treatment diary after using the newly prescribed medication. The 
treatment outcomes of patients receiving rizatriptan were compared with those
receiving non-triptan medications. Logistic regression analysis was applied to
test statistical significance with adjustment for potential confounding factors. 
RESULTS: Of the 728 patients who entered the study, 693 (95.2%) completed the
treatment diary. Patients treated with rizatriptan (192) and non-triptans (501)
reported the following outcomes, respectively--onset of headache relief within 30
minutes post-dose: 25% versus 18%; self-defined significant headache relief
within 2 hours post-dose: 71% versus 54%; pain free or mild pain at 2 hours
post-dose: 58% versus 47%; completely symptom-free within 2 hours of post-dose:
32% versus 20%; return to usual activities within 2 hours post-dose: 39% versus
35%; and satisfied with treatment: 67% versus 55% (P <.05 in all comparisons with
exception of returning to usual activities). CONCLUSION: Rizatriptan was
significantly more effective than non-triptans in the relief of migraine
headaches for patients obtaining prescribed migraine medications from a retail
pharmacy. Additional studies at other usual care settings may be needed to
confirm the findings.

Publication Types: 
    Clinical Trial
    Comparative Study
    Controlled Clinical Trial
    Research Support, Non-U.S. Gov't

PMID: 15447699 [PubMed - indexed for MEDLINE]

2083: Headache. 2004 Oct;44(9):891-9.

Rizatriptan 5 mg for the acute treatment of migraine in adolescents: results from
a double-blind, single-attack study and two open-label, multiple-attack studies.

Visser WH, Winner P, Strohmaier K, Klipfel M, Peng Y, McCarroll K, Cady R, Lewis 
D, Nett R; Rizatriptan Protocol 059 and 061 Study Groups.

Merck Research Laboratories, West Point, PA 19486, USA.

OBJECTIVE: To examine the short- and long-term efficacy and tolerability of
rizatriptan 5 mg in adolescents with migraine. METHODS: Two studies were
conducted in patients aged 12 to 17 years. The first study was a randomized,
double-blind, placebo-controlled, single-attack study followed by a randomized,
1-year, open-label extension. The second study was a randomized, 1-year,
open-label study. In the single-attack study, patients treated a moderate or
severe migraine headache and up to two recurrences with rizatriptan 5-mg tablets 
(n = 234) or placebo (n = 242). Patients were instructed to use the study
medication only on nonschool days. Headache severity, associated symptoms, and
functional disability were assessed by the patient at 0.5, 1, 1.5, 2, 3, and 4
hours after the initial dose. In the 1-year studies, patients treated up to 6
migraine attacks per month with rizatriptan 5-mg tablets (n = 273), rizatriptan
5-mg wafers (n = 281), or standard care therapy (n = 132). Headache severity was 
assessed by the patient at 2 hours after the initial dose. In all studies, the
primary efficacy measure was pain relief at 2 hours post dose. RESULTS: In the
single-attack study, the proportion of patients with pain relief at 2 hours was
not significantly different between rizatriptan 5 mg (68.2%) and placebo (68.8%).
Fewer patients than expected (about 30%) treated their migraine attacks on the
weekend. Among these patients, the proportion with pain relief at 2 hours was
significantly higher in the rizatriptan group than in the placebo group (74% vs. 
58%, P = 0.022). In the multiple-attack studies, pain relief at 2 hours was
achieved in significantly more attacks treated with rizatriptan 5-mg tablet (77%)
or with rizatriptan 5-mg wafer (77%) than with standard care (64%). Rizatriptan 5
mg was well tolerated in both the studies, with an adverse event profile not
significantly different from that of placebo or standard care. CONCLUSIONS:
Rizatriptan 5 mg was not more effective than placebo in the treatment of a single
migraine attack in adolescents, but appeared to be more effective than standard
care for treating multiple attacks occurring over 1 year in these patients.
Rizatriptan 5 mg was well tolerated in adolescents during short-term and
long-term use.

Publication Types: 
    Clinical Trial
    Comparative Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 15447698 [PubMed - indexed for MEDLINE]

2084: Headache. 2004 Oct;44(9):885-90.

Comment in:
    Headache. 2006 Mar;46(3):531.

A combination of riboflavin, magnesium, and feverfew for migraine prophylaxis: a 
randomized trial.

Maizels M, Blumenfeld A, Burchette R.

Kaiser Permanente, Family Practice, Woodland Hills, CA, USA.

OBJECTIVE: To determine the efficacy for migraine prophylaxis of a compound
containing a combination of riboflavin, magnesium, and feverfew. BACKGROUND:
Previous studies of magnesium and feverfew for migraine prophylaxis have found
conflicting results, and there has been only a single placebo-controlled trial of
riboflavin. DESIGN/METHODS: Randomized double-blind placebo-controlled trial of a
compound providing a daily dose of riboflavin 400 mg, magnesium 300 mg, and
feverfew 100 mg. The placebo contained 25 mg riboflavin. The study included a
1-month run-in phase and 3-month trial. The protocol allowed for 120 patients to 
be randomized, with a preplanned interim analysis of the data after 48 patients
had completed the trial. RESULTS: Forty-nine patients completed the 3-month
trial. For the primary outcome measure, a 50% or greater reduction in migraines, 
there was no difference between active and "placebo" groups, achieved by 10 (42%)
and 11 (44%), respectively (P=.87). Similarly, there was no significant
difference in secondary outcome measures, for active versus placebo groups,
respectively: 50% or greater reduction in migraine days (33% and 40%, P=.63); or 
change in mean number of migraines, migraine days, migraine index, or triptan
doses. Compared to baseline, however, both groups showed a significant reduction 
in number of migraines, migraine days, and migraine index. This effect exceeds
that reported for placebo agents in previous migraine trials. CONCLUSION:
Riboflavin 25 mg showed an effect comparable to a combination of riboflavin 400
mg, magnesium 300 mg, and feverfew 100 mg. The placebo response exceeds that
reported for any other placebo in trials of migraine prophylaxis, and suggests
that riboflavin 25 mg may be an active comparator. There is at present
conflicting scientific evidence with regard to the efficacy of these compounds
for migraine prophylaxis.

Publication Types: 
    Clinical Trial
    Comparative Study
    Randomized Controlled Trial

PMID: 15447697 [PubMed - indexed for MEDLINE]

2085: Headache. 2004 Oct;44(9):873-84.

Quantifying headache symptoms and other headache features from chart notes.

Hasse LA, Ritchey PN, Smith R.

Department of Family Medicine, College of Medicine, University of Cincinnati, OH 
45221-0378, USA.

OBJECTIVES: To describe a method for quantifying headache symptoms/features in
family practice charts for patients diagnosed with headache NOS (not otherwise
specified, ICD-9: 784) and to determine the share of NOS headache diagnoses with 
clinical data strongly suggestive of migraine or probable migraine headache.
BACKGROUND: Headache is one of the most common pain symptoms that brings patients
to a family physician. However, the majority of headache sufferers do not receive
a specific headache diagnosis when they visit physicians. METHODS: We examined
the chart notes of 454 patients exclusively diagnosed with one or more ICD-9
coded headache NOS diagnoses from July 1, 1995 through December 31, 1999 at a
large suburban, university-affiliated practice. We developed a template
containing 20 headache items combining International Headache Society diagnostic 
criteria and additional headache symptoms/features, and decision rules for coding
symptoms/features and collected data from patient charts. We then developed
decision rules and reclassified NOS headaches into categories strongly suggestive
of migraine, probable migraine headache, or other diagnosis. Our main outcome
measure is the consistency in the application of decision rules and diagnostic
criteria. RESULTS: With this method we estimate 3 in 10 (29%) headache NOS
patients may have had migraine (8%) or probable migraine headache (21%).
Reclassified migraine visits averaged 6.5 migraine symptoms and reclassified
probable migraine headache visits 4.7 migraine symptoms. Logistic regression
analysis supports the consistency of diagnostic criteria for classifying headache
based on coded symptoms/features--our model correctly predicted 96% of visits.
Evidence of physical examination was recorded at 75% of visits suggesting that
physician attention is focused on elimination of secondary headache. CONCLUSIONS:
We think the use of our rigorous procedures reveals that a substantial amount of 
migraine and probable migraine headache may be missed in everyday practice. We
hope our findings will provide a basis for the development of diagnostic methods 
more closely suited to the needs of nonspecialists, and contribute to a better
standard of care for headache patients seen in primary care practice. Finally, we
are hopeful that other researchers will consider using our template and guideline
procedures in their efforts to identify diagnostic patterns and study headache
and other health problems.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 15447696 [PubMed - indexed for MEDLINE]

2086: Headache. 2004 Oct;44(9):865-72.

Comment in:
    Headache. 2005 May;45(5):615-6; discussion 616-7.

The premonitory symptoms (prodrome): a tertiary care study of 893 migraineurs.

Kelman L.

Headache Center of Atlanta, GA 30342, USA.

OBJECTIVES: This study of premonitory symptoms in migraine was performed to
document the frequency, duration, and types of symptoms in a large group of
migraine patients. BACKGROUND: Prodrome importance continues to be debated.
Intervention early in the migraine attack is assuming more importance and
necessitates better knowledge of the prodrome. METHODS: A total of 893 migraine
patients (IHS 1.1-1.7) were evaluated at first visit. Prodrome frequency,
duration, and characteristics were analyzed in the total migraine population IHS 
1.1-1.7 and IHS 1.1-1.6 migraine. RESULTS: A total of 32.9% of IHS migraine
1.1-1.6 patients reported prodrome symptoms with an average of 9.42 hours. IHS
1.1-1.7 migraine reported 29.7% and 6.8 hours, respectively. The most commonest
symptoms were tiredness, mood change, and gastrointestinal symptoms; all three of
these symptoms were present together in 17% of the patients with prodrome. The
duration of prodrome was less than 1 hour in 45.1%, 1-2 hours in 13.6%, 2-4 hours
in 15.0%, 4-12 hours in 13.1%, and greater than 12 hours in 13.2%. IHS 1.1-1.7
patients showed similar findings. IHS 1.1-1.6 patients with prodrome differed
from patients without prodrome in having more triggers as a whole (P <.01), more 
individual triggers including alcohol (P <.01), hormones (P <.01), light (P
<.001), not eating (P <.05), perfume (P <.01), stress (P <.01), and weather
changes (P <.05), a longer duration of aura (P <.05), longer time between aura
and headache (P <.05), more aura with no headache (P <.05), longer time to peak
of headache (P <.05), longer time to respond to triptan (P <.05), longer maximum 
duration of headache (P <.05), and more headache associated nausea (P <.05), more
headache associated running of the nose or tearing of the eyes (P <.05), more
postdrome syndrome (P <.05), and longer duration of postdrome syndrome (P <.001).
CONCLUSIONS: This study provides a portrait of prodrome in a large cohort of
patients. It highlights differences between patients with prodrome and patients
not having prodrome, and it draws attention to the potential of preventing the
headache phase of the acute migraine attack.

PMID: 15447695 [PubMed - indexed for MEDLINE]

2087: Headache. 2004 Oct;44(9):856-64.

Prevalence and diagnosis of migraine in patients consulting their physician with 
a complaint of headache: data from the Landmark Study.

Tepper SJ, Dahlöf CG, Dowson A, Newman L, Mansbach H, Jones M, Pham B, Webster C,
Salonen R.

The New England Center for Headache, Stamford, CT, USA.

CONTEXT: Headache experts have suggested that to improve the recognition of
migraine, patients with a stable pattern of episodic, disabling headache and a
normal physical exam should be considered to have migraine in the absence of
contradictory evidence. The premise upon which this approach is based-that is,
that episodic, recurrent primary headache in the clinic is usually migraine-has
not been evaluated in prospective clinical studies. OBJECTIVES: To (1) evaluate
the diagnoses of patients consulting their physician with primary episodic
headache and (2) compare clinic diagnoses and patient self-diagnoses with
International Headache Society (IHS) headache diagnoses assigned on the basis of 
longitudinal data from patient diaries. DESIGN: Prospective, open-label study.
During the screening visit, patients self-reported a headache diagnosis and then 
were assigned a headache diagnosis by their physician following his or her
customary practice. Patients with a new physician diagnosis of migraine or
nonmigraine primary headache were given diaries to record headache symptoms for
up to 3 months or 6 attacks. Members of an expert panel, unaware of the clinic
diagnosis, used diary data to assign a headache diagnosis to each attack and to
each patient. SETTING: One hundred twenty-eight (128) practices in 15 countries
including the United States. PATIENTS: A total of 1203 male and female patients
between 18 and 65 years of age who consulted their physician with headache as a
primary or secondary complaint. RESULTS: Overall, 94% of patients with a
physician diagnosis of nonmigraine primary headache or a new clinic diagnosis of 
migraine had IHS-defined migraine (76%) or probable migraine (migrainous) (18%)
headache on the basis of longitudinal diary data. A new clinic diagnosis of
migraine was almost always correct: 98% of patients with a clinic diagnosis of
migraine had IHS-defined migraine (87% of patients) or probable migraine (11% of 
patients) headache on the basis of longitudinal diary data. On the other hand,
review of diaries of patients with a clinic diagnosis of nonmigraine revealed
that 82% of these patients had IHS-defined migraine (48%) or probable migraine
(34%) headache. Altogether, one in four patients (25%) with IHS-defined migraine 
according to longitudinal diary data did not receive a clinic diagnosis of
migraine. CONCLUSIONS: These findings support the diagnostic approach of
considering episodic, disabling primary headaches with an otherwise normal
physical exam to be migraine in the absence of contradictory evidence. If in
doubt of diagnosis or when assigning a nonmigraine diagnosis, strong
consideration should be given to the use of a diary to confirm primary headache
diagnosis.

Publication Types: 
    Clinical Trial
    Comparative Study
    Multicenter Study
    Research Support, Non-U.S. Gov't

PMID: 15447694 [PubMed - indexed for MEDLINE]

2088: Curr Med Res Opin. 2004 Sep;20(9):1465-72.

Randomized, placebo-controlled comparison of early use of frovatriptan in a
migraine attack versus dosing after the headache has become moderate or severe.

Cady R, Elkind A, Goldstein J, Keywood C.

Headache Care Center, Primary Care Network, Inc., Springfield, MO, USA.
rcady@primarycarenet.org

OBJECTIVE: To evaluate whether frovatriptan would provide greater relief if given
early during a migraine attack. RESEARCH DESIGN AND METHODS: Adults with a
history of migraine of at least 1 year, and who had 2-8 headaches in the previous
month were recruited from 19 US centres for a prospective, placebo-controlled
crossover study over 2 migraine attacks. Dose 1 was taken at the onset of mild
migraine headache, Dose 2 was taken at least 2 h later if the headache progressed
to moderate/severe. Patients were randomized to receive Dose 1 frovatriptan then 
Dose 2 placebo or Dose 1 placebo followed by Dose 2 frovatriptan. Treatment order
was reversed for the second attack. This schedule enabled a comparison of
frovatriptan with placebo and a comparison of early and later treatment with
frovatriptan. MAIN OUTCOME MEASURES: Freedom from pain at 2 h for frovatriptan
versus placebo as Dose 1; use of Dose 2 and/or rescue medication, pain severity, 
functional impairment and headache recurrence. RESULTS: In 241 patients who each 
treated 2 migraine attacks, Dose 1 frovatriptan was more effective than placebo
in terms of the proportion of patients who were pain free at 2 h (28% vs 20%, p =
0.04). This benefit was sustained up to 4 h post-dose (p = 0.003). Early use of
frovatriptan significantly reduced re-medication (p < 0.001). Twenty-four-hour
headache recurrence was low in both early (4%) and later use (6%) groups.
Sustained pain-free response occurred in 40% of frovatriptan early use patients
compared with 31% of later use patients (p < 0.05). Early use prevented headache 
progression: 69%-78% had mild/no headache 2-4 h after Dose 1 frovatriptan
compared with 54%-63% taking Dose 1 placebo (p < 0.001). Early use reduced pain
burden and functional disability (p < or = 0.001). More patients rated early use 
of frovatriptan as excellent or good (57% vs 46%). CONCLUSIONS: Early use of
frovatriptan resulted in a higher, earlier and sustained pain-free response,
prevented progression to moderate/severe headache and reduced pain burden and
functional disability.

Publication Types: 
    Clinical Trial
    Comparative Study
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 15383196 [PubMed - indexed for MEDLINE]

2089: Eur J Neurol. 2004 Sep;11(9):583-91.

New international classification of migraine with aura (ICHD-2) applied to 362
migraine patients.

Eriksen MK, Thomsen LL, Olesen J.

Danish Headache Center, Department of Neurology, Glostrup Hospital, University of
Copenhagen, Copenhagen, Denmark. kirchmann@dadlnet.dk

The International Classification of Headache Disorders 2nd edition (ICHD-2)
subdivides migraine with aura (MA) differently from the ICHD-1 and includes new
diagnostic criteria. The aim of the present study was to evaluate how the new
classification works in practice and in comparison with the ICHD-1. The patients 
were recruited from a screen of the Danish National Patient Registry and from
Danish neurologists. We included 362 patients diagnosed with MA according to the 
ICHD-1 in a validated semistructured physician-conducted interview. According to 
the ICHD-2, 89% (322 of 362) had MA and 11% (40 of 362) had probable MA. The MA
patients had one or more ICHD-2 subtype of MA: 54% (173 of 322) had typical aura 
with migraine headache (MA-MH), 40% (129 of 322) had typical aura with
non-migraine headache (MA-NMH), 37% (120 of 322) had aura without headache
(MA-WOH), and 7% (26 of 322) had basilar-type migraine (MA-B). Of patients with
MA-MH 34% (59 of 173) had co-occurrence of MA-WOH, 9% (16 of 173) had
co-occurrence of MA-B and 5% (8 of 173) had co-occurrence of both MA-WOH and
MA-B. Of patients with MA-NMH 27% (35 of 129) had co-occurrence of MA-WOH. Only
6% (18 of 322) of the MA patients had exclusively MA-WOH and <1% (2 of 322) had
exclusively MA-B. Patients with MA-MH had an earlier age at onset (P = 0.044), an
increased lifetime number of MA attacks (P = 0.054) and a higher co-occurrence of
migraine without aura (P = 0.002) than patients with MA-NMH. Patients with MA-B
tended to have an earlier age at onset and more severe attacks and patients with 
MA-WOH had a higher age at onset and less severe attacks than patients with
MA-MH. The variations between ICHD-2 subtypes of MA indicate that patients with
similar subtype of MA share phenotype and very likely have similar underlying
aetiology.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 15379737 [PubMed - indexed for MEDLINE]

2090: Cephalalgia. 2004 Oct;24(10):894-9.

Validation of a migraine screening questionnaire in a Colombian university
population.

Rueda-Sánchez M, Díaz-Martínez LA.

School of Medicine, Universidad Autónoma de Bucaramanga, Campus El Bosque,
Colombia. mrueda@unab.edu.co

In studies of migraine prevalence, it is important to be aware of the
discriminative capacity of the test used. We set out to validate a Spanish
translation of Michel's Standardized Migraine Diagnosis Questionnaire. The
questionnaire was applied on all active students of the School of Psychology of
the Universidad Autónoma de Bucaramanga, Colombia. A neurologist interviewed a
random sample to substantiate the diagnosis of migraine. Cronbach's alpha was
calculated and factors analysis was made in order to estimate internal
consistency, test-retest to find reproducibility, and ROC curve and diagnostic
indicators were calculated to estimate the criteria validity. Of 357 students
that answered the questionnaire, 188 (52.7%) were selected at random to attend an
appointment with a neurologist, but only 170 had this interview. Cronbach's alpha
on these 357 questionnaires is 0.7497. All the questions on the questionnaire
represented two main factors. This test had sensitivity in 37.9% [95% confidence 
interval (CI) 25.8, 51.7], specificity in 99.1% (95% CI 94.4, 100), positive
predictive value in 95.7% (95% CI 76.0, 99.8), and negative predictive value in
75.5% (95% CI 67.6, 82.1) for 17 or more points. The area below ROC curve is
0.8529 (95% CI 0.8035, 0.9217). Among 84 students who took the questionnaire a
second time, the average score on the first survey was 12.33 +/- 7.46 points,
while the average score on the second take was 11.26 +/- 7.85 (P = 0.069).
Agreement for migraine is 83.3% (95% CI 73.6, 90.6; Cohen's kappa = 0.6650 +/-
0.1061). The Spanish translation of Michel's Questionnaire is easy to answer and 
has good internal consistency, but its reproducibility and sensibility are
modest; however, the ROC curve is acceptable to discriminate migraine patients
from normal subjects.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't
    Validation Studies

PMID: 15377322 [PubMed - indexed for MEDLINE]

2091: Cephalalgia. 2004 Oct;24(10):888-93.

Efficacy of phenazone in the treatment of acute migraine attacks: a double-blind,
placebo-controlled, randomized study.

Göbel H, Heinze A, Niederberger U, Witt T, Zumbroich V.

Kiel Pain Clinic, Germany. hg@schmerzklinik.de

In this study we compared the efficacy of 1000 mg phenazone with that of placebo 
in the treatment of acute migraine attacks in a randomized double-blind,
placebo-controlled study of 208 patients. The main target criterion was the
number of patients with a pain reduction from severe or moderate to slight or no 
pain 2 h after taking the pain medication. The percentage of patients satisfying 
the main target criterion was 48.6% for phenazone and 27.2% (P < 0.05) for
placebo. Freedom from pain after 2 h was reported by 27.6% with phenazone
treatment and 13.6% (P < 0.05) with placebo. Compared with placebo, the phenazone
treatment also resulted in a significant improvement in the associated migraine
symptoms of nausea, phonophobia and photophobia. Of patients treated with
phenazone 11.4%, and 5.8% of those treated with placebo reported adverse events. 
There was no significant difference between the groups with regard to numbers of 
patients with adverse events. No serious adverse events occurred. The results
show that phenazone at a dosage of 1000 mg is effective and well tolerated in the
treatment of acute migraine attacks.

Publication Types: 
    Clinical Trial
    Comparative Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 15377321 [PubMed - indexed for MEDLINE]

2092: Cephalalgia. 2004 Oct;24(10):875-82.

A double-blind study of SB-220453 (Tonerbasat) in the glyceryltrinitrate (GTN)
model of migraine.

Tvedskov JF, Iversen HK, Olesen J.

Copenhagen Headache Centre, Department of Neurology, Glostrup Hospital,
University of Copenhagen, Denmark. tvedskov@dadlnet.dk

The need for experimental migraine models increases as therapeutic options widen.
In the present study, we investigated SB-220453 for efficacy in the
glyceryltrinitrate (GTN) human experimental migraine model. SB-220453 is a novel 
benzopyran compound, which in animal models inhibits neurogenic inflammation,
blocks propagation of spreading depression and inhibits trigeminal nerve ganglion
stimulation-induced carotid vasodilatation. We included 15 patients with migraine
without aura in a randomized double-blind crossover study. SB-220453 40 mg or
placebo was followed by a 20-min GTN infusion. Headache, scored 0-10, was
registered for 12 h, and fulfillment of International Headache Society (IHS)
criteria was recorded until 24 h. Four subjects had a hypotensive episode after
SB-220453 plus GTN but none after GTN alone. The reaction was unexpected, since
animal models and previous human studies had shown no vascular or sympaticolytic 
activity with SB-220453. The study was terminated prematurely due to this
interaction. GTN was consistent in producing headache and migraine that resembled
the patients' usual spontaneous migraine. Nine patients had GTN on both study
days. Peak headache score showed a trend towards reduction after SB-220453
compared with placebo (median 4 vs. 7, P = 0.15). However, no reduction was seen 
in the number of subjects experiencing delayed headache (8 vs. 8), number of
subjects reporting migraine (6 vs. 8), migraine attacks fulfilling IHS criteria
1.1 or 1.7 (6 vs. 7) or IHS 1.1 alone (4 vs. 5). SB-220453 had no significant
pre-emptive anti-migraine activity compared with placebo in this human model of
migraine. Interaction between SB-220453 and GTN was discovered. This is important
for the future development of the compound and underlines the usefulness of
experimental migraine models.

Publication Types: 
    Clinical Trial
    Comparative Study
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 15377319 [PubMed - indexed for MEDLINE]

2093: Cephalalgia. 2004 Oct;24(10):844-9.

Development of a patient-based grading scale for PedMIDAS.

Hershey AD, Powers SW, Vockell AL, LeCates SL, Segers A, Kabbouche MA.

Division of Neurology, Cincinnati Children's Hospital Medical Center, OH
45229-3039, USA.

The objective was to develop and validate a patient-based grading scale for
PedMIDAS. PedMIDAS was administered to 329 children, who rated their overall
disability based on the adult MIDAS grades. This patient-based rating and
PedMIDAS scores were compared to develop the grading scale. Headache disability
was rated little to none, 49.5%; mild, 26.7%; moderate, 15.8%; and severe, 7.9%, 
with PedMIDAS raw scores of 4.9 +/- 6.3, 17.8 +/- 14.9, 40.6 +/- 34.2, and 91.4
+/- 69.8. Convergence of these results yielded an empirically derived grading
system: Grade I, 0-10; II, 11-30; III, 31-50 and IV, > 50. Higher grades
corresponded to an increased need for prophylactic treatment. A patient-based
grading scale further increases the utility of PedMIDAS in assessing migraine
disability in children, so that it can be widely used in routine clinical
evaluation and management.

Publication Types: 
    Comparative Study
    Validation Studies

PMID: 15377315 [PubMed - indexed for MEDLINE]

2094: Cephalalgia. 2004 Oct;24(10):838-43.

Botulinum toxin A in the prophylactic treatment of migraine--a randomized,
double-blind, placebo-controlled study.

Evers S, Vollmer-Haase J, Schwaag S, Rahmann A, Husstedt IW, Frese A.

Department of Neurology, University of Münster, Germany. everss@uni-muenster.de

Botulinum toxin A has been suggested to be effective in the prophylactic
treatment of migraine. However, only very few randomized, double-blind,
placebo-controlled studies are available. We designed such a study with a
specific focus on different injection sites. Sixty patients with a migraine
according to the criteria of the International Headache Society were randomly
assigned to receive either placebo in the frontal and neck muscles, or to receive
16 U botulinum toxin A in the frontal muscles and placebo in the neck muscles, or
to receive in total 100 U botulinum toxin A in the frontal and neck muscles. The 
observation period was 3 months. In both treatment groups, 30% of patients showed
a reduction of migraine frequency in month 3 by at least 50% compared with
baseline, in the placebo group 25% of the patients showed such a reduction (P =
0.921). There were no significant differences between the three study groups with
respect to reduction of migraine frequency, number of days with migraine, and the
number of total single doses to treat a migraine attack. In the post hoc
analysis, the reduction of all accompanying symptoms was significantly higher in 
the 16 U treatment group compared with the placebo group. In the 100 U treatment 
group significantly more adverse events occurred compared with the placebo group.
All adverse events were mild and transient. Our study did not show any efficacy
of botulinum toxin A in the prophylactic treatment of migraine. Only accompanying
symptoms were significantly reduced in the 16 U but not in the 100 U treatment
group. Future studies should focus on the efficacy of botulinum toxin A in
specific subgroups of patients, on the efficacy of repetitive injections, and on 
other injection sites.

Publication Types: 
    Clinical Trial
    Comparative Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 15377314 [PubMed - indexed for MEDLINE]

2095: Cephalalgia. 2004 Oct;24(10):831-7.

Estimation of antiphospholipid antibodies in a prospective longitudinal study of 
children with migraine.

Avcin T, Markelj G, Niksic V, Rener-Primec Z, Cucnik S, Zupancic M, Rozman B,
Neubauer D.

Department of Allergology, Rheumatology and Clinical Immunology, University
Children's Hospital, Ljubljana, Slovenia. tadej.avcin@siol.net

The aim of this study was to determine the prevalence and clinical significance
of antiphospholipid antibodies (aPL) in children with migraine. The values of
anticardiolipin (aCL) and antibeta2 glycoprotein I (antibeta2GPI) antibodies were
assayed by an ELISA method in 52 children with migraine and 22 children with
tension-type headache. The control group consisted of 61 apparently healthy
children at regular preventive visits. Two monoclonal beta2GPI dependent aCL
(HCAL and EY2C9) were used as calibrators. Lupus anticoagulant (LA) was
determined by a modified dilute Russell viper venom time test. Persistently
positive aPL were observed during the follow-up in 16.3% of children with
migraine (9.3% for aCL, 7.0% for antibeta2GPI and 0% for LA) and in 16.7% of
children with tension-type headache (11.1% for aCL, 5.6% for antibeta2GPI and 0% 
for LA). The prevalence of aPL did not differ significantly between patient
groups and healthy children. The prevalence of aPL does not appear to be
increased in an unselected group of children with migraine, however, the possible
role of aPL in individual cases of paediatric migraine can not be excluded.

Publication Types: 
    Comparative Study

PMID: 15377313 [PubMed - indexed for MEDLINE]

2096: Can J Neurol Sci. 2004 Aug;31(3):324-7.

Prevalence of reported migraine headaches in Canadian adolescents.

Gordon KE, Dooley JM, Wood EP.

Division of Pediatric Neurology, Department of Pediatrics, Dalhousie University, 
and IWK Health Centre, Halifax, Nova Scotia, Canada.

OBJECTIVE: To examine self-reported prevalence data for migraine among adolescent
Canadians and to explore how reported migraine treatment varies by age. METHODS: 
We analyzed the microdata files of the Canadian National Population Health Survey
(1996-1997). Respondents reported whether they had "migraine headaches diagnosed 
by a health professional". They also reported whether they received "any
treatment or medication for migraine headaches", with treatments subdivided into 
drug, diet or "other". RESULTS: 99.9% of 173,216 eligible respondents reported
whether they had migraine headaches. Migraine was reported by 2.4% of Canadian
youth aged 12-14 years and by 5.0% of 15-19 year-olds compared to 7.2% of adults 
aged > or = 20 years of age (p< 0.0001, chi-square). Active treatment was used by
51.0% - higher by females (53.1%) than males (44.7%) (p<0.0001 chi-square).
Treatment was used by 45.1% of 12-14 year-olds, by 45.7% of 15-19 year-olds and
by 51.5% of those > or = 20 years (p=0.0027). The nature of the active treatment 
choice (drug, diet or other) did not significantly vary within the age groups
studied. CONCLUSIONS: We present robust estimates of self-report diagnosed
migraine prevalence, derived from a large nationally representative population
survey. Estimates of the prevalence of active treatment for migraine provide
insight into the burden of migraine within this population.

PMID: 15376475 [PubMed - indexed for MEDLINE]

2097: Can J Neurol Sci. 2004 Aug;31(3):315-8.

Mixed migraine and tension-type: a common cause of recurrent headache in
children.

Seshia SS.

Manitoba Clinic, Winnipeg, MB, Canada.

OBJECTIVE: Determine relative frequency of recurrent headache (HA) types in
children and adolescents referred to a pediatric neurologist. METHODS AND
SUBJECTS: Study design: Prospective, sequential, and observational. Setting:
Private practice Pediatric Neurology Clinic in a Canadian city (Winnipeg).
Patients and data collection: Information on those referred with HA between
September 1998 and December 2001 was entered on data sheets. Patients were
followed up for one month to four years. RESULTS: Three hundred and twenty (69%) 
of 463 referred with HA had recurrent HA. There were 172 males (54%) and 148
(46%) females. Their ages ranged from two years to 19 years (median: 11 years).
They had had their HA disorder for one month to 14 years (median: two years)
prior to assessment. Migraine was the main HA type in 124 (38%), tension-type
headache (TTH) in 57 (18%) and mixed migraine and TTH in 101 (32%). Thus, 101
(45%) of 225 with migraine as one HA type also had TTH. CONCLUSIONS: Tension-type
headache and migraine frequently co-exist and may represent a distinct headache
type, at least in children; the association will likely influence response of
affected children and adolescents to specific migraine treatments in clinical
trials or practice.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 15376473 [PubMed - indexed for MEDLINE]

2098: Int J Clin Pract. 2004 Aug;58(8):795-800.

The therapeutic profile of zolmitriptan in clinical practice.

Diener HC, Evers S, Gendolla A.

Department of Neurology, University Essen, Essen, Germany. h.diener@uni-essen

The efficacy and tolerability of the 5-HT1B/1D-receptor agonist zolmitriptan was 
evaluated in an open post-marketing surveillance study in 12,919 patients,
treating 36,510 migraine attacks. Mean visual analogue scale scores for pain
decreased (6.9-2.2; 68% improvement) and scores for impairment of normal
activities decreased (6.6-2.2; 67% improvement) at 2 h after dose. Non-headache
symptoms of migraine resolved in 73-86% of attacks. Improvement was achieved
within 2 h in >80% of attacks and within 1 h in 37% of attacks. This high level
of efficacy was achieved with a single 2.5 mg dose in 95% of attacks. Compared
with previous migraine treatments, 85% of patients preferred zolmitriptan for
efficacy and 56% for better tolerability. Corresponding preference rates were 87 
and 63% when compared with ergot alkaloids. Adverse events occurred in 2% of
patients and were either typical class effects or known symptoms and
complications of migraine. These results provide evidence for the high efficacy
and good tolerability of the 2.5 mg dose of zolmitriptan in clinical practice in 
migraine. Zolmitriptan was very well tolerated, with patients expressing a
distinct preference for zolmitriptan over previous treatments.

Publication Types: 
    Multicenter Study
    Research Support, Non-U.S. Gov't

PMID: 15372853 [PubMed - indexed for MEDLINE]

2099: Int J Clin Pract. 2004 Aug;58(8):758-63.

Switching patients with migraine from sumatriptan to other triptans increases
primary care costs.

Savani N, Martin A, Browning D.

Colne House Surgery, Rickmansworth, Hertfordshire, UK.
naren.savani@gp-e82083.nhs.uk

Treatment of migraine with triptans is highly effective, although cost
considerations may prompt a change in therapy. This retrospective database
analysis of 3196 patients with migraine, established on sumatriptan therapy,
found that 54% of the 292 experiencing a triptan switch returned to sumatriptan
within 15 months, suggesting that the alternative was less acceptable. Excluding 
patients with unusually high use of triptans (> or = 208 tablets/year), switching
therapy resulted in a significant increase of pounds sterling 53/patient in total
costs, compared with patients continuing on sumatriptan (p = 0.014). Cost savings
(pounds sterling 17/patient over 15 months) were observed only among the 41% of
patients in whom the initial switch was successful and did not result in a
further switch or return to sumatriptan. Among patients who were relatively low
cost initially, switching resulted in increased costs, irrespective of the
outcome. This study suggests that there is no economic justification for
switching from sumatriptan to another triptan.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 15372848 [PubMed - indexed for MEDLINE]

2100: Am J Med Genet A. 2004 Nov 15;131(1):50-8.

Mitochondrial DNA control region sequence variation in migraine headache and
cyclic vomiting syndrome.

Wang Q, Ito M, Adams K, Li BU, Klopstock T, Maslim A, Higashimoto T, Herzog J,
Boles RG.

Division of Medical Genetics, Childrens Hospital Los Angeles, California, USA.

Migraine headache is a very common condition affecting about 10% of the
population that results in substantial morbidity and economic loss. The two most 
common variants are migraine with (MA) and without (MO) aura. Often considered to
be a migraine-like variant, cyclic vomiting syndrome (CVS) is a predominately
childhood condition characterized by severe, discrete episodes of nausea,
vomiting, and lethargy. Disease-associated mitochondrial DNA (mtDNA) sequence
variants are suggested in common migraine and CVS based upon a strong bias
towards the maternal inheritance of disease, and several other factors. Temporal 
temperature gradient gel electrophoresis (TTGE) followed by cyclosequencing and
RFLP was used to screen almost 90% of the mtDNA, including the control region
(CR), for heteroplasmy in 62 children with CVS and neuromuscular disease (CVS+)
and in 95 control subjects. One or two rare mtDNA-CR heteroplasmic sequence
variants were found in six CVS+ and in zero control subjects (P = 0.003). These
variants comprised 6 point and 2 length variants in hypervariable regions 1 and 2
(HV1 and HV2, both part of the mtDNA-CR), one half of which were clustered in the
nt 16040-16188 segment of HV1 that includes the termination associated sequence
(TAS), a functional location important in the regulation of mtDNA replication.
Based upon our findings, sequencing and statistical analysis looking for
homoplasmic nucleotide changes was performed in HV1 among 30 CVS+, 30
randomly-ascertained CVS (rCVS), 18 MA, 32 MO, and 35 control haplogroup H cases.
Within the nt 16040-16188 segment, homoplasmic sequence variants were three-fold 
more common relative to control subjects in both CVS groups (P = 0.01 combined
data) and in MO (P = 0.02), but not in MA (P = 0.5 vs. control subjects and 0.02 
vs. MO). No group differences were noted in the remainder of HV1. We conclude
that sequence variation in this small "peri-TAS" segment is associated with CVS
and MO, but not MA. These variants likely constitute risk factors for disease
development. Our findings are consistent with previous data demonstrating
progression of CVS into MO in many cases, and the co-segregation in a maternal
inheritance pattern of CVS and MO within families. A mitochondrial component in
the pathogenesis of migraine and CVS has therapeutic implications, especially
concerning the avoidance of fasting. (c) 2004 Wiley-Liss, Inc.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 15368478 [PubMed - indexed for MEDLINE]

2101: J Chin Med Assoc. 2004 Jun;67(6):263-7.

Intraerythrocyte antioxidant enzyme activities in migraine and tension-type
headaches.

Bolayir E, Celik K, Kugu N, Yilmaz A, Topaktas S, Bakir S.

Department of Neurology, Cumhuriyet University, Faculty of Medicine, Sivas,
Türkiye. ebol@mynet.com

BACKGROUND: The pathophysiology of migraine and other headaches is still unknown,
and research is mostly done on neurotransmitter, biochemical and vascular
mechanisms. The aim of this study was to examine the role of antioxidant enzymes 
in the pathophysiology of headache in the interictal period of the pain process. 
METHODS: In this study, glutathione peroxidase, catalase and superoxide dismutase
enzyme activities were investigated in 88 cases, which included 11 migraine cases
with aura, 17 migraine without aura, 32 chronic type tension headache and 28
control cases. RESULTS: In migraine cases, superoxide dismutase and glutathione
peroxidase enzyme activities were statistically lower than in the tension
headache and control groups. The differences between tension-type headache and
control groups were found statistically insignificant. CONCLUSIONS: Low
intraerythrocytes, superoxide dismutase and glutathione peroxidase levels may
play an important role in the etiology of migraine.

Publication Types: 
    Comparative Study

PMID: 15366402 [PubMed - indexed for MEDLINE]

2102: Neurology. 2004 Sep 14;63(5):848-52.

Clinical recognition of allodynia in migraine.

Mathew NT, Kailasam J, Seifert T.

Houston Headache Clinic, 1213 Hermann Dr., Houston, TX 77004, USA.
ntmathew@houstonheadacheclinic.com

BACKGROUND: Allodynia, a manifestation of central sensitization, is not routinely
evaluated during clinical interviews even though its therapeutic implications are
known. OBJECTIVE: To assess the frequency and manifestations of allodynia in a
clinic-based migraine population. METHODS: A total of 295 consecutive
International Headache Society migraine patients were evaluated using a
semistructured questionnaire. RESULTS: A total of 157 (53.3%) reported allodynia.
A total of 133 (84.7% of those with allodynia) had cephalic, 54 (18%) had both
cephalic and extracephalic, and 24 (8.5%) exhibited pure extracephalic allodynia.
Prominent scalp symptoms were sensitivity to touch; soreness or tenderness;
difficulty brushing, combing, or washing hair; difficulty lying with head resting
on the side of allodynia; and circumscribed area of hypersensitivity and
tenderness. Scalp allodynia was ipsilateral to predominant headache side in the
majority and occurred at the height of headache. Extracephalic allodynia of the
upper extremities occurred in 72, toes in 6. Truncal allodynia occurred in some. 
Age range and age at onset of migraine were identical in allodynic and
non-allodynic patients. Patients with allodynia were on an average 8 years older 
than non-allodynic patients (p < 0.05). Correlation was found between the
duration of illness as well as frequency of migraine attacks and allodynia.
Frequent migraineurs exhibited prolonged allodynia. CONCLUSIONS: Clinically
detectable allodynia, which occurs with high frequency in migraineurs, should
become part of the clinical evaluation because of its implications in early
treatment with triptans, recurrence of headache, consistency of response to
triptans, and development of chronicity of migraine.

PMID: 15365135 [PubMed - indexed for MEDLINE]

2103: Arch Neurol. 2004 Sep;61(9):1366-8.

Migraine is associated with magnetic resonance imaging white matter
abnormalities: a meta-analysis.

Swartz RH, Kern RZ.

Division of Neurology, Department of Medicine, Mount Sinai Hospital, University
of Toronto, Toronto, Ontario M5G 1X5, Canada.

BACKGROUND: There is controversy as to whether migraine is associated with white 
matter abnormalities (WMAs) on magnetic resonance images. These abnormalities may
be important as a risk factor for future stroke. Further, it is controversial
whether any increased risk of WMAs is attributable to comorbidities such as
vascular disease. METHODS: A meta-analysis of published case-control studies was 
undertaken to address the relationship between migraine and magnetic resonance
imaging WMAs. Seven studies were identified. Data from studies reporting the
incidence of magnetic resonance imaging WMAs in those with migraine and
appropriate control populations were used to calculate odds ratios for WMAs in
migraine for each study. A stratified meta-analysis was performed using studies
that did and did not exclude subjects with disease comorbidities. RESULTS: The
summary odds ratio shows that those with migraine are at increased risk for WMAs 
(odds ratio, 3.9 [95% confidence interval, 2.26-6.72]). The risk does not differ 
between studies that included subjects with comorbidities and those that did not.
CONCLUSION: This meta-analysis demonstrates that subjects with migraine are at
higher risk of having WMAs on magnetic resonance images than those without
migraine. This increased risk is present even in younger individuals who do not
have co-occurring cerebrovascular disease risk factors. Prospective studies are
needed to determine whether the increased risk of stroke in migraine is mediated 
or foreshadowed by the presence of WMAs.

Publication Types: 
    Meta-Analysis
    Review

PMID: 15364681 [PubMed - indexed for MEDLINE]

2104: Arch Intern Med. 2004 Sep 13;164(16):1769-72.

Comment in:
    Arch Intern Med. 2005 Apr 25;165(8):954; author reply 954-5.

Prevalence of migraine in patients with a history of self-reported or
physician-diagnosed "sinus" headache.

Schreiber CP, Hutchinson S, Webster CJ, Ames M, Richardson MS, Powers C.

Headache Care Center, Springfield, MO, USA.

BACKGROUND: Symptoms referable to the sinus area are frequently reported during
migraine attacks, but are not recognized in diagnostic criteria. Underrecognition
of migraine may be partly attributed to a variable clinical presentation, and
migraines with "sinus" symptoms contribute to this problem. This study was
conducted to determine the prevalence of migraine-type headache (International
Headache Society [IHS]-defined migraine without aura [IHS 1.1], migraine with
aura [IHS 1.2], or migrainous disorder [IHS 1.7]) in patients with a history of
self-described or physician-diagnosed "sinus" headache. METHODS: During a clinic 
visit, patients with a history of "sinus" headache, no previous diagnosis of
migraine, and no evidence of infection were assigned an IHS headache diagnosis on
the basis of headache histories and reported symptoms. RESULTS: A total of 2991
patients were screened. The majority (88%) of these patients with a history of
self-described or physician-diagnosed "sinus" headache were diagnosed at the
screening visit as fulfilling IHS migraine criteria (80% of patients) or
migrainous criteria (8% of patients). The most common symptoms referable to the
sinus area reported by patients at screening were sinus pressure (84%), sinus
pain (82%), and nasal congestion (63%). CONCLUSIONS: In this study, 88% of
patients with a history of "sinus" headache were determined to have migraine-type
headache. In patients with recurrent headaches without fever or purulent
discharge, the presence of sinus-area symptoms may be part of the migraine
process. Migraine should be included in the differential diagnosis of these
patients.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 15364670 [PubMed - indexed for MEDLINE]

2105: Curr Pain Headache Rep. 2004 Oct;8(5):410-6.

Cortical spreading depression: its role in migraine pathogenesis and possible
therapeutic intervention strategies.

Parsons AA.

Neurology and GI Centre of Excellence for Drug Discovery, New Frontiers Science
Park, GlaxoSmithKline, Harlow, Essex CM19 5AW, UK. Andrew_A_Parsons@gsk.com

Cortical spreading depression (CSD) is a well-characterized phenomenon in
experimental animals. Recent data show that CSD actually can occur in the injured
human brain and compelling evidence is accumulating to support the concept that
CSD is responsible for migraine aura. The aim of this review is to highlight
recent key advances regarding our understanding of CSD in animal and human
studies and its relevance to the pathophysiology of migraine and its potential
treatment options.

Publication Types: 
    Review

PMID: 15361327 [PubMed - indexed for MEDLINE]

2106: Curr Pain Headache Rep. 2004 Oct;8(5):393-8.

Post-triptan era for the treatment of acute migraine.

Goadsby PJ.

Institute of Neurology, Queen Square, London WC1N 3BG, UK. peterg@ion.ucl.ac.uk

There now is one realized and several attractive targets for the treatment of
acute attacks of migraine that will follow and augment the use of serotonin
5-HT1B/1D receptor agonists, the triptans. Calcitonin gene-related peptide (CGRP)
receptor blockade recently has been shown to be an effective acute antimigraine
strategy; therefore, blockade of CGRP release by inhibition of trigeminal nerves 
would seem a logical approach. A number of targets are reviewed in this article
including serotonin 5-HT1F and 5-HT1D receptors, adenosine A1 receptors,
nociceptin, vanilloid TRPV1 receptors, and anandamide CB1 receptors. Development 
of one or more such compound offers the exciting prospect of new
non-vasoconstrictor treatments for migraine and cluster headache.

Publication Types: 
    Review

PMID: 15361324 [PubMed - indexed for MEDLINE]

2107: Scand J Caring Sci. 2004 Sep;18(3):294-303.

Migraine and chronic daily headache management: a qualitative study of patients' 
perceptions.

Peters M, Abu-Saad HH, Vydelingum V, Dowson A, Murphy M.

European Institute of Health and Medical Sciences, University of Surrey, Surrey, 
UK.

AIM: The aim of the study was to gain insight into the patients' perceptions of
migraine and chronic daily headache (CDH) management. METHODS: Thirteen,
semi-structured and individual interviews with seven migraine and five CDH
patients were carried out and analysed in QSR NUD*IST5, using a grounded theory
methodology. RESULTS: The participants described using five areas of management: 
1) health care use; 2) medication use; 3) alternative therapies; 4) social
support; and 5) lifestyle and self-help. The participants described their
expectations, preferences, worries and (dis)satisfaction in relation to these
five areas of management. The participants adapted headache management to suit
their needs and preferences, making migraine and CDH management highly individual
and giving the headache patient a central role within their own care. CONCLUSION:
Health care is changing towards a greater involvement of the patients in their
own care. Therefore, it is important to increase understanding of the patients'
perspective of chronic diseases, including migraine and CDH. The results from
this study inform health care professionals of the range of their patients' needs
and preferences. This knowledge can be used to shape clinical practice, to
develop patient education programmes and to further research efforts into issues 
that are important to the headache patient.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 15355524 [PubMed - indexed for MEDLINE]

2108: Forsch Komplementarmed Klass Naturheilkd. 2004 Aug;11 Suppl 1:30-5.

Treatment outcomes in patients with migraine: an ex-post-facto comparison of two 
in-patient facilities.

Weidenhammer W, Linde K, Melchart D.

Zentrum für naturheilkundliche Forschung, II. Med. Klinik und Poliklinik,
Technische Universitat München, Kaiserstrasse 9, D-80801 Munich, Germany.
Wolfgang.Weidenhammer@lrz.tu-muenchen.de

BACKGROUND: In two hospitals we performed an open, prospective observational
study on patients with chronic headache as a measure of internal quality
assurance using identical methods. Available data were subordinately analysed in 
order to compare both studies. QUESTIONS: Are the patient samples of both
hospitals comparable? If not, which form of statistical adjustment is
recommended? Are there differences in the outcome measures of both facilities?
METHODS: The outcomes were defined as differences between baseline values and
values at discharge from hospital, respectively 6 months after. Frequency of
headache attacks, intensity of pain, intensity of general complaints as well as
of concomitant symptoms, and quality of life were determined in advance as
dependent variables. To compare both patient groups univariate analysis of
variance without and with inclusion of covariates were used. For calculating
propensity scores (conditional probability of belonging to one of two groups) a
logistic regression with the same covariates serving as independent variables was
performed. PATIENTS: 426 patients with the main diagnosis "Migraine" and complete
data sets concerning the covariates were selected for analysis. 87% of patients
are female, the mean age is 45.5 +/- 11.7 years (range 14-73 yrs). RESULTS: 4 out
of 11 potential covariates show statistically significant differences between the
patients of both hospitals. Correct classification of patients by means of the
propensity score succeeds in 67%. Comparing the outcomes at discharge from
hospital, significant differences between both groups exist which are, with one
exception, not affected by controlling for covariates. 6 months after discharge
two of the initial differences between both patient groups are no longer present.
These findings are independent from the statistical technique of risk adjustment.
CONCLUSIONS: Because of the observed differences between both patient groups it
is recommended to adjust data by regression analysis in order to enhance
comparability. The choice for one of the two proposed techniques is secondary.
With respect to the analyses clear differences between both hospitals exist in
short-term outcomes, disappearing 6 months later. Copyright 2004 S. Karger GmbH, 
Freiburg

Publication Types: 
    Comparative Study

PMID: 15353900 [PubMed - indexed for MEDLINE]

2109: Lupus. 2004;13(7):501-5.

Headaches in patients with systemic lupus erythematosus: a comparative study.

Whitelaw DA, Hugo F, Spangenberg JJ, Rickman R.

Department of Rheumatology, Stellenbosch University and Tygerberg Academic
Hospital, Tygerberg, South Africa. dwhit@sun.ac.za

The incidence and nature of headaches in 85 systemic lupus erythematosus (SLE)
patients attending an outpatient clinic were studied and compared to those
experienced by 61 nurses. The two groups were similar in age, sex and ethnicity. 
Test-retest assessment of reliability gave both groups 95% confidence limits of
0.09-0.21. Thirty-two (38%) patients developed migrainous headaches and nine
(10%) stress headaches with the onset of lupus. In the control group, four (6%)
developed migraine and 40 (66%) developed stress headaches on commencing work. We
could not document any association of headaches with flares of systemic disease, 
the ACA syndrome, Raynaud's phenomenon or increased SLEDAI score. We conclude
that migrainous headaches are more common in lupus patients than healthy
controls, but in an outpatient setting are not statistically associated with
flares of systemic disease.

Publication Types: 
    Comparative Study

PMID: 15352420 [PubMed - indexed for MEDLINE]

2110: J Clin Pharmacol. 2004 Oct;44(10):1158-65.

Pharmacokinetics of frovatriptan in adolescent migraineurs.

Elkind AH, Wade A, Ishkanian G.

Elkind Headache Center, 12 North 7th Avenue, Mount Vernon, NY 10550, USA.

Frovatriptan is a selective 5-HT(1B/1D) receptor agonist available for acute
treatment of migraine in adults (18 years and older). The objective of this study
was to determine key pharmacokinetic parameters of frovatriptan in adolescent
migraineurs after a single 2.5-mg oral dose and to compare these results with
those from an earlier study completed in adults. Subjects were stratified by age 
(12-14 and 15-17 years) and gender, and serial blood and urine samples were
collected over 48 hours. A total of 25 subjects (13 male, 12 female) completed
the study. Pharmacokinetic profiles for adolescent subjects were similar to those
observed in adults. The median tmax ranged from 2 (male subjects) to 3 (female
subjects) hours. The AUC0-24h and Cmax were slightly lower in adolescent subjects
as compared with adults. As seen in adults, AUC0-24h and Cmax values were
approximately 2-fold higher in females than in their male counterparts (AUC mean 
range 40.5-59.8 ng x h/mL vs 21.2-23.5 ng x h/mL and Cmax mean range 4.02-6.14 vs
ng x h/mL 2.52-2.99 ng/mL, in female and male adolescent subjects, respectively).
Elimination was biphasic, with an approximate terminal elimination half-life
(t(1/2)) between 12.2 and 25.5 hours. Renal clearance was similar in adolescents 
and adults, being somewhat higher in female than male subjects. Frovatriptan was 
well tolerated with no serious or treatment-related adverse effects. In addition,
there were no clinically significant changes in safety parameters. Overall, the
pharmacokinetic profile of frovatriptan in adolescents (12-17 years) is similar
to that seen in adults, and dosing adjustments are unlikely to be needed.
Copyright 2004 American College of Clinical Pharmacology

Publication Types: 
    Clinical Trial
    Comparative Study
    Controlled Clinical Trial
    Research Support, Non-U.S. Gov't

PMID: 15342617 [PubMed - indexed for MEDLINE]

2111: Headache. 2004 Sep;44(8):801-5.

Mechanism of action of botulinum toxin type A in migraine prevention: a pilot
study.

Smuts JA, Schultz D, Barnard A.

Department of Neurology and Neurophysiology, University of Pretoria, South
Africa.

OBJECTIVE: The main objective of this study is to determine whether change in
migraine frequency is correlated with a denervation pattern of the corrugator
muscle after local botulinum toxin type A injections. BACKGROUND: Recent studies 
suggest botulinum toxin type A is effective in preventing migraine. Relaxation of
the corrugator muscle may be one of multiple targets of botulinum toxin type A in
relieving migraine pain. METHODS: The pretreatment amplitude of the compound
muscle action potential (CMAP) was obtained in 10 patients with a migraine
frequency of two to six attacks per month following stimulation of the temporal
branch of the facial nerve. Patients were subsequently injected with 20 units of 
botulinum toxin type A at predefined sites in the procerus and corrugator
muscles. CMAP was obtained on days 7, 30, 60, and 90 after injection. Migraine
frequency, as reported in headache diaries, was compared with the amplitudes
obtained. RESULTS: A 50% decrease in CMAP was demonstrated in the total group by 
day 7. Maximal decline of CMAP was observed by day 30, and was sustained at day
60. Migraine frequency declined by 50% or more in 7 of 10 patients by day 60.
Migraine response to botulinum toxin type A treatment did not correlate with the 
denervation pattern. CONCLUSION: Relaxation of the corrugator muscles is not
solely responsible for the pain relief in migraine patients treated with
botulinum toxin type A.

Publication Types: 
    Clinical Trial
    Research Support, Non-U.S. Gov't

PMID: 15330827 [PubMed - indexed for MEDLINE]

2112: Headache. 2004 Sep;44(8):786-93.

Validity and reliability of the Turkish Migraine Disability Assessment (MIDAS)
questionnaire.

Ertaş M, Siva A, Dalkara T, Uzuner N, Dora B, Inan L, Idiman F, Sarica Y, Selçuki
D, Sirin H, Oğuzhanoğlu A, Irkeç C, Ozmenoğlu M, Ozbenli T, Oztürk M, Saip S,
Neyal M, Zarifoğlu M; Turkish MIDAS group.

Department of Neurology, Faculty of Medicine, University of Istanbul, Turkey.

OBJECTIVES: The aim of this study is to assess the comprehensibility, internal
consistency, patient-physician reliability, test-retest reliability, and validity
of Turkish version of Migraine Disability Assessment (MIDAS) questionnaire in
patients with headache. BACKGROUND: MIDAS questionnaire has been developed by
Stewart et al and shown to be reliable and valid to determine the degree of
disability caused by migraine. DESIGN AND METHODS: This study was designed as a
national multicenter study to demonstrate the reliability and validity of Turkish
version of MIDAS questionnaire. Patients applying to 17 Neurology Clinics in
Turkey were evaluated at the baseline (visit 1), week 4 (visit 2), and week 12
(visit 3) visits in terms of disease severity and comprehensibility, internal
consistency, test-retest reliability, and validity of MIDAS. Since the severity
of the disease has been found to change significantly at visit 2 compared to
visit 1, test-retest reliability was assessed using the MIDAS scores of a
subgroup of patients whose disease severity remained unchanged (up to +/-3 days
difference in the number of days with headache between visits 1 and 2). RESULTS: 
A total of 306 patients (86.2% female, mean age: 35.0 +/- 9.8 years) were
enrolled into the study. A total of 65.7%, 77.5%, 82.0% of patients reported that
"they had fully understood the MIDAS questionnaire" in visits 1, 2, and 3,
respectively. A highly positive correlation was found between physician and
patient and the applied total MIDAS scores in all three visits (Spearman
correlation coefficients were R= 0.87, 0.83, and 0.90, respectively, P <.001).
Internal consistency of MIDAS was assessed using Cronbach's alpha and was found
at acceptable (>0.7) or excellent (>0.8) levels in both patient and physician
applied MIDAS scores, respectively. Total MIDAS score showed good test-retest
reliability (R= 0.68). Both the number of days with headache and the total MIDAS 
scores were positively correlated at all visits with correlation coefficients
between 0.47 and 0.63. There was also a moderate degree of correlation (R= 0.54) 
between the total MIDAS score at week 12 and the number of days with headache at 
visit 2 + visit 3, which quantify headache-related disability over a 3-month
period similar to MIDAS questionnaire. CONCLUSION: These findings demonstrated
that the Turkish translation is equivalent to the English version of MIDAS in
terms of internal consistency, test-retest reliability, and validity. Physicians 
can reliably use the Turkish translation of the MIDAS questionnaire in defining
the severity of illness and its treatment strategy when applied as a
self-administered report by migraine patients themselves.

Publication Types: 
    Multicenter Study
    Research Support, Non-U.S. Gov't
    Validation Studies

PMID: 15330825 [PubMed - indexed for MEDLINE]

2113: Headache. 2004 Sep;44(8):780-5.

Epidemiology and symptomatology of migraine among school children: Denizli urban 
area in Turkey.

Zencir M, Ergin H, Sahiner T, Kiliç I, Alkiş E, Ozdel L, Gürses D, Ergin A.

Department of Public Health, Pamukkale University, Denizli, Turkey.

OBJECTIVE: This study was aimed at finding the prevalence, associated factors,
and symptomatology of migraine among 5 to 8 grades of secondary and 9 to 11
grades of high school children (age range between 11 and 18 years old) in the
Denizli urban area in the western part of Turkey. BACKGROUND: Data from the
developed countries indicate that migraine is the most common cause of recurrent 
headaches in children. Also, childhood migraine is sufficiently severe to prevent
the half of the suffering children from carrying on their usual daily activities.
METHODS: A cross-sectional school-based study was conducted between May 2000 and 
June 2000. There were 2,490 participants selected by a multistage stratified
clustered sampling procedure. A validated self-administered questionnaire
designed according to the International Headache Society criteria was given to
the school children of age between 11 and 18 years. RESULTS: Overall migraine
prevalence was 8.8%; it was 6.7% in boys and 11.0% in girls (OR: 1.7; 95% CI: 1.3
to 2.3). Among girls, the highest prevalence (17.7%) occurred at 15 years of age,
but among boys, the highest prevalence (11.9%) occurred at 16 years of age. Of
children with migraine, 56.5% had a positive family history, and only 29.1%
visited a doctor for headache. CONCLUSION: Migraine is a common health problem
among school children in Denizli urban area and it often goes underdiagnosed.

PMID: 15330824 [PubMed - indexed for MEDLINE]

2114: Headache. 2004 Sep;44(8):767-71.

Comment in:
    Headache. 2005 Mar;45(3):255-6; author reply 256-7.    Headache. 2005 Mar;45(3):255; author reply 256-7.

Local inflammation as a mediator of migraine and tension-type headache.

Friedman MH.

New York Medical College, Valhalla, USA.

OBJECTIVE: To demonstrate the relationship of migraine and tension-type headache 
to a localized maxillary gingival inflammation. BACKGROUND: Intraoral tenderness 
has been observed consistently in the most common types of primary headache
disorders. The laterality and degree of tenderness is related to laterality and
severity of reported symptoms, both during headache and in the interictal state. 
METHODS: Bilateral posterior maxillary palpation and local temperature recordings
were performed during unilateral migraine and tension-type headache. Local
anti-inflammatory techniques, ie, local chilling and a topical anti-inflammatory 
gel, were used in these tender areas in episodic migraine and tension-type
headache patients. RESULTS: Ipsilateral intraoral tenderness and increased local 
temperature were consistently observed during unilateral migraine and
tension-type headache, suggesting local inflammation. Intraoral chilling and
topical application of a nonsteroidal anti-inflammatory drug were highly
effective for the treatment of migraine and tension-type headache, both in the
acute phase and for headache prevention. CONCLUSION: These results suggest that a
local intraoral inflammation may be associated with the pathogenesis of these
common headaches.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial

PMID: 15330822 [PubMed - indexed for MEDLINE]

2115: Headache. 2004 Sep;44(8):762-6.

Oral transmucosal fentanyl citrate for the treatment of migraine headache pain in
outpatients: a case series.

Landy SH.

Wesley Headache Clinic, Memphis, TN 38018, USA.

BACKGROUND: Migraine headache pain that does not respond to traditional
antimigraine medications frequently requires treatment in the emergency
department (ED) with parenteral opioids. Rapid onset of pain relief in an
outpatient setting for migraine headache is the primary objective of patients and
clinicians. Oral transmucosal fentanyl citrate (OTFC; ACTIQ) is a novel opioid
product designed to deliver rapid analgesia to patients who experience
breakthrough pain (BTP). OBJECTIVE: To evaluate the effectiveness, tolerability, 
and patient satisfaction with OTFC for the outpatient treatment of acute,
refractory migraine headache pain. PATIENTS AND METHODS: Twenty patients with
recurrent acute, refractory migraine headaches who had been referred to this
headache clinic are reported in this case series. All patients had a history of
tolerating parenteral opioids in the ED when experiencing refractory migraine
pain and had been treated with outpatient opioid therapies in attempts to manage 
their migraine pain. Patients were prescribed OTFC (400 microg) as rescue
treatment for moderate or severe migraine headache pain as outpatients. Patients 
were instructed to self-administer OTFC at home and complete a diary recording:
pain intensity (11-point scale; 10 = worst pain imaginable to 0 = no pain) before
and 15, 30, 60, and 120 minutes after OTFC; satisfaction with the effectiveness
of OTFC (selecting 1 of 7 categories ranging from "very dissatisfied" through
"very satisfied") rated at 120 minutes; and adverse events. RESULTS: Eighteen
patients (13 female) experienced a migraine and self-administered OTFC. OTFC
successfully treated migraine episodes in all 18 outpatients; no patient went to 
an ED. OTFC rapidly reduced pain intensity, with significant improvement at 15
minutes that was sustained and provided progressively more pain relief at 30, 60,
and 120 minutes (all P <.01). Mean (SEM) pain intensity significantly declined
from 8.83 (0.35) pretreatment to 2.28 (0.67) at 120 minutes, an average reduction
of 75% (P <.01). Patients' satisfaction ratings with OTFC were overwhelmingly
positive, with 94% being satisfied and more than half (56%) being "very
satisfied." Three (17%) patients experienced nausea, two (11%) somnolence, and
one (6%) each itching, vomiting, and dry mouth. All adverse events were mild or
moderate in severity. CONCLUSIONS: OTFC rapidly and significantly relieved acute,
refractory migraine pain in outpatients, prevented the need for an ED visit, and 
was associated with high patient satisfaction ratings. The rapid onset of
migraine headache pain relief in this case series is consistent with the
analgesic effect reported with the use of OTFC in patients with BTP. OTFC was
well tolerated in these patients who had a history of tolerating parenteral
opioids in the ED when experiencing refractory migraine pain and had been treated
with outpatient opioid therapies in attempts to manage their migraine pain. OTFC 
may be effective for outpatient treatment of acute, refractory migraine headache 
pain. Further controlled studies are warranted.

Publication Types: 
    Clinical Trial
    Research Support, Non-U.S. Gov't

PMID: 15330821 [PubMed - indexed for MEDLINE]

2116: Headache. 2004 Sep;44(8):747-61.

Posterior hypothalamic and brainstem activation in hemicrania continua.

Matharu MS, Cohen AS, McGonigle DJ, Ward N, Frackowiak RS, Goadsby PJ.

Institute of Neurology, Headache Group, London, United Kingdom.

OBJECTIVE: To determine the brain structures involved in mediating the pain of
hemicrania continua using positron emission tomography. BACKGROUND: Hemicrania
continua is a strictly unilateral, continuous headache of moderate intensity,
with superimposed exacerbations of severe intensity that are accompanied by
trigeminal autonomic features and migrainous symptoms. The syndrome is
exquisitely responsive to indomethacin. Its clinical phenotype overlaps with that
of the trigeminal autonomic headaches and migraine in which the hypothalamus and 
the brainstem, respectively, have been postulated to play central
pathophysiologic roles. We hypothesized, based on the clinical phenotype, that
hemicrania continua may involve activations in the hypothalamus, or dorsal
rostral pons, or both. METHODS: Seven patients with hemicrania continua were
studied in two sessions each. In one session, the patients were scanned during
baseline pain and when rendered completely pain free after being administered
indomethacin 100 mg intramuscularly. In the other session, the patients were
scanned during baseline pain and when still in pain after being administered
placebo intramuscularly. Seven age- and sex-matched nonheadache subjects acted as
the control group. The scan images were processed and analyzed using SPM99.
RESULTS: There was a significant activation of the contralateral posterior
hypothalamus and ipsilateral dorsal rostral pons in association with the headache
of hemicrania continua. In addition, there was activation of the ipsilateral
ventrolateral midbrain, which extended over the red nucleus and the substantia
nigra, and bilateral pontomedullary junction. No intracranial vessel dilatation
was obvious. CONCLUSIONS: This study demonstrated activations of various
subcortical structures, in particular the posterior hypothalamus and the dorsal
rostral pons. If posterior hypothalamic and brainstem activation are considered
as markers of trigeminal autonomic headaches and migrainous syndromes,
respectively, then the activation pattern demonstrated in hemicrania continua
mirrors the clinical phenotype, with its overlap with trigeminal autonomic
headaches and migraine.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial

PMID: 15330820 [PubMed - indexed for MEDLINE]

2117: Optometry. 2000 Jun;71(6):381-9.

Migraine aura without headache: prevalence and risk factors in a primary eye care
population.

Fleming JB, Amos AJ, Desmond RA.

Department of Optometry, School of Optometry, University of Alabama at
Birmingham, 35294-0010, USA.

BACKGROUND: Although migraine headache has received substantial attention in the 
scientific literature, migraine aura without headache (MAWOH) has not been
investigated frequently. A general population survey study estimated the lifetime
prevalence of MAWOH to be 1% in males and 3% in females. Anecdotal evidence has
suggested that MAWOH is encountered by primary eye care practitioners more
frequently than these rates suggest. This study is the first investigation of
this condition in a primary eye care population. METHODS: A written questionnaire
was used to survey 1,000 patients, ages 18 years and older, presenting for a
comprehensive eye examination in the Primary Care Optometry Service of the School
of Optometry, University of Alabama at Birmingham. Cases were identified by the
presence of visual sensations consistent with MAWOH. RESULTS: Of the primary eye 
care population surveyed, 6.5% reported experiencing visual sensations consistent
with MAWOH. The prevalence in males was 2.9% and in females, 8.6%. A multivariate
analysis revealed that female gender (odds ratio [OR] = 2.3), history of migraine
headaches (OR = 3.2), and history of childhood motion sickness (OR = 2.7) were
significantly related to MAWOH. CONCLUSIONS: The prevalence of MAWOH is higher in
an adult primary eye care population than previously reported in a general
population study.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 15326888 [PubMed - indexed for MEDLINE]

2118: Optometry. 2000 Jun;71(6):372-80.

Clinical description and review of migraine aura without headache.

Amos JF, Fleming JB.

Department of Optometry, School of Optometry, University of Alabama at
Birmingham, Birmingham, Alabama 35294-0010, USA.

BACKGROUND: Migraine aura without headache (MAWOH) is a type of migraine that
seems to be reported more frequently in ophthalmic than neurologic or general
medical practice. The clinical characteristics of this condition are described
relative to its relationship with other forms of migraine, patient age, gender
distribution, laterality, personal or family history, visual aura, and
precipitating factors. As a result of its prevalence, it is a condition with
which every optometrist and ophthalmologist should be familiar. Since MAWOH is a 
common cause of photopsia and transient vision loss, it is also important to
consider it in the differential diagnosis of these conditions-especially in older
patients. METHODS: The clinical investigations of MAWOH by prospective and
retrospective case series are reviewed. This review includes an analysis by study
of the number of patients, migraine history, and type of visual symptom.
Comparison of clinical characteristics is used to distinguish MAWOH from other
types of migraine. CONCLUSION: Migraine aura without headache is a type of
migraine that is reported frequently in ophthalmic practice. Because it is
related to photopsia and/or transient vision loss, specific clinical procedures
should be performed to assist in the differential diagnosis of these conditions.

Publication Types: 
    Review

PMID: 15326887 [PubMed - indexed for MEDLINE]

2119: Curr Neurol Neurosci Rep. 2004 Sep;4(5):391-7.

Retinal, ophthalmic, or ocular migraine.

Pradhan S, Chung SM.

Departments of Ophthalmology and Neurology, Saint Louis University School of
Medicine, 1755 South Grand Boulevard, Saint Louis, MO 63104, USA.

Ocular migraine, an uncommon cause of transient monocular visual loss, is an
entity physicians should be able to recognize in order to provide appropriate
treatment and to avoid unnecessary testing. The following text provides an
overview of ocular migraine, including discussion of accepted terminology,
clinical presentation, and pathophysiology. An ocular and systemic differential
diagnosis, appropriate evaluation, therapy, and prognosis are also discussed.

PMID: 15324606 [PubMed - indexed for MEDLINE]

2120: Phys Rev Lett. 2004 Jul 16;93(3):038103. Epub 2004 Jul 15.

Steady-state visual evoked potentials and phase synchronization in migraine
patients.

Angelini L, de Tommaso M, Guido M, Hu K, Ivanov PCh, Marinazzo D, Nardulli G,
Nitti L, Pellicoro M, Pierro C, Stramaglia S.

TIRES: Center of Innovative Technologies for Signal Detection and Processing,
University of Bari, Italy.

We investigate phase synchronization in EEG recordings from migraine patients. We
use the analytic signal technique, based on the Hilbert transform, and find that 
migraine brains are characterized by enhanced alpha band phase synchronization in
the presence of visual stimuli. Our findings show that migraine patients have an 
overactive regulatory mechanism that renders them more sensitive to external
stimuli.

Publication Types: 
    Research Support, U.S. Gov't, P.H.S.

PMID: 15323876 [PubMed - indexed for MEDLINE]

2121: Curr Vasc Pharmacol. 2003 Mar;1(1):71-84.

Migraine: pathophysiology, pharmacology, treatment and future trends.

Villalón CM, Centurión D, Valdivia LF, de Vries P, Saxena PR.

Departamento de Farmacobiología, CINVESTAV-IPN, Czda. de los Tenorios 235, Col.
Granjas Coapa, Deleg. Tlalpan, CP 14330, México DF, México.
carlos_villalon@infosel.net.mx

Migraine treatment has evolved into the scientific arena, but it seems still
controversial whether migraine is primarily a vascular or a neurological
dysfunction. Irrespective of this controversy, the levels of serotonin
(5-hydroxytryptamine; 5-HT), a vasoconstrictor and a central neurotransmitter,
seem to decrease during migraine (with associated carotid vasodilatation) whereas
an i.v. infusion of 5-HT can abort migraine. In fact, 5-HT as well as ergotamine,
dihydroergotamine and other antimigraine agents invariably produce
vasoconstriction in the external carotid circulation. The last decade has
witnessed the advent of sumatriptan and second generation triptans (e.g.
zolmitriptan, rizatriptan, naratriptan), which belong to a new class of drugs,
the 5-HT1B/1D/1F receptor agonists. Compared to sumatriptan, the
second-generation triptans have a higher oral bioavailability and longer plasma
half-life. In line with the vascular and neurogenic theories of migraine, all
triptans produce selective carotid vasoconstriction (via 5-HT1B receptors) and
presynaptic inhibition of the trigeminovascular inflammatory responses implicated
in migraine (via 5-HT1D/5-ht1F receptors). Moreover, selective agonists at 5-HT1D
(PNU-142633) and 5-ht1F (LY344864) receptors inhibit the trigeminovascular system
without producing vasoconstriction. Nevertheless, PNU-142633 proved to be
ineffective in the acute treatment of migraine, whilst LY344864 did show some
efficacy when used in doses which interact with 5-HT1B receptors. Finally,
although the triptans are effective antimigraine agents producing selective
cranial vasoconstriction, efforts are being made to develop other effective
antimigraine alternatives acting via the direct blockade of vasodilator
mechanisms (e.g. antagonists at CGRP receptors, antagonists at 5-HT7 receptors,
inhibitors of nitric oxide biosynthesis, etc). These alternatives will hopefully 
lead to fewer side effects.

Publication Types: 
    Historical Article
    Research Support, Non-U.S. Gov't
    Review

PMID: 15320857 [PubMed - indexed for MEDLINE]

2122: Plast Reconstr Surg. 2004 Sep 1;114(3):652-7; discussion 658-9.

Surgical treatment of migraine headaches by corrugator muscle resection.

Dirnberger F, Becker K.

Department of Plastic Surgery, Wilhelminenspital, Vienna, Austria.
dr.dirnberger@aon.at

The authors, a plastic surgeon (Dirnberger) and a neurologist (Becker), conducted
this study after reading the article by of Bahman Guyuron et al. in the August
2000 issue of Plastic and Reconstructive Surgery (106: 429, 2000). Sixty patients
were operated on between June of 2001 and June of 2002; postoperative follow-up
ranged between 6 and 18 months. Patients' charts were reviewed to confirm the
diagnosis of migraine headache according to the criteria of the International
Headache Society. Sixty patients (13 men and 47 women) from Austria and four
neighboring countries took part in the study. The patients were divided into
three groups, based on the severity of their migraines: group A comprised
patients with up to 4 days of migraine per month; group B included patients with 
5 to 14 days of migraine per month; and group C was composed of patients with
more than 15 days of headache per month ("permanent headache") or evidence of
drug abuse and drug-related headaches. The effectiveness of the operation was
evaluated using the following factors: percentage reduction of headache days;
percentage reduction of drugs; percentage reduction of side effects, severity of 
headaches, and response to drugs; and patient grade of personal satisfaction,
using a scale from 1 to 5 [1 = excellent (total elimination of migraine headache)
to 5 = insufficient or no improvement]. From the entire group of 60 patients, 17 
(28.3 percent) reported a total relief from migraine, 24 (40 percent) reported an
essential improvement, and 19 (31.7 percent) reported minimal or no change.
Patients with a rather mild form of migraine headache had a much better chance
(almost 90 percent in group A and 75 percent in group B) to experience an
improvement or total elimination of migraine than those patients (n = 27) from
group C with severe migraine, "permanent headaches," and drug-induced headaches. 
Contrary to the reports by Guyuron, 11 patients who had a very favorable response
immediately and in the first weeks after the operation experienced a gradual
return of their headaches to preoperative intensity after about 4 postoperative
weeks. After 3 months, the results in all patients could be declared permanent.
All side effects, such as paraesthesia in the frontal region, disappeared in all 
patients within 3 to 9 months.

PMID: 15318040 [PubMed - indexed for MEDLINE]

2123: J Neurol. 2004 Aug;251(8):973-6.

Hereditary patterns of Belgrade university female students with migraine and
nonmigraine primary headache.

Vlajinac HD, Dzoljic ED, Sipetic SB, Kostic VS.

Institute of Epidemiology, Belgrade University, School of Medicine, Visegradska
26, 11000 Belgrade, Serbia and Montenegro. sandragru@ptt.yu

Various studies have provided evidence that migraine is a multifactorial genetic 
disorder. The aim of the present study was to compare hereditary patterns of
female students with migraine (245 subjects) and non-migraine primary headaches
(1053 subjects). The prevalence study was performed combined with a case-control 
study. Migraineurs had significantly more frequently one or more first-degree
and/or second-degree relatives with migraine. Students with menstrual migraine,
in comparison with other subtypes of migraine (with the exception of premenstrual
migraine), had significantly more frequently > or = 2 relatives with migraine.
Among students with non-migraine primary headaches, those with menstrually
related headache had more frequently relatives with migraine in comparison with
students suffering from menstrually unrelated nonmigraine headache. The results
obtained are in line with the results of genetic epidemiologic studies suggesting
that genetic factors play a role in the occurrence of migraine.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 15316802 [PubMed - indexed for MEDLINE]

2124: J Neurol. 2004 Aug;251(8):943-50.

Topiramate in migraine prophylaxis--results from a placebo-controlled trial with 
propranolol as an active control.

Diener HC, Tfelt-Hansen P, Dahlöf C, Láinez MJ, Sandrini G, Wang SJ, Neto W,
Vijapurkar U, Doyle A, Jacobs D; MIGR-003 Study Group.

Department of Neurology, University Essen, Hufelandstr 55, 45122 Essen, Germany. 
h.diener@uni-essen.de

Topiramate (TPM) has shown efficacy in migraine prophylaxis in two large
placebo-controlled, dose-ranging trials. We conducted a randomised, double-blind,
multicentre trial to evaluate the efficacy and safety of two doses of topiramate 
vs placebo for migraine prophylaxis, with propranolol (PROP) as an active
control. Subjects with episodic migraine with and without aura were randomised to
TPM 100 mg/d, TPM 200 mg/d, PROP 160 mg/d (active control), or placebo. The
primary efficacy measure was the change in mean monthly migraine frequency from
the baseline phase relative to the double-blind treatment phase. Five hundred and
seventy-five subjects were enrolled from 61 centres in 13 countries. TPM 100 mg/d
was superior to placebo as measured by reduction in monthly migraine frequency,
overall 50% responder rate, reduction in monthly migraine days, and reduction in 
the rate of daily rescue medication use. The TPM 100 mg/d and PROP groups were
similar with respect to reductions in migraine frequency, responder rate,
migraine days, and daily rescue medication usage. TPM 100 mg/d was better
tolerated than TPM 200 mg/d, and was generally comparable to PROP. No unusual or 
unexpected safety risks emerged. These findings demonstrate that TPM 100 mg/d is 
effective in migraine prophylaxis. TPM 100 mg/d and PROP 160 mg/d exhibited
similar efficacy profiles.

Publication Types: 
    Clinical Trial
    Comparative Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 15316798 [PubMed - indexed for MEDLINE]

2125: Ann Pharmacother. 2004 Oct;38(10):1726-30. Epub 2004 Aug 17.

Treatment of migraine headaches with sumatriptan in pregnancy.

Hilaire ML, Cross LB, Eichner SF.

University of Tennessee Family Practice Center, Memphis, TN, USA.
mhilaire@utmem.edu

OBJECTIVE: To review the literature for treatment of migraine headaches with
sumatriptan during pregnancy. DATA SOURCES: Studies and reports were located in
International Pharmaceutical Abstracts (1970-September 2003) and MEDLINE
(1966-week 3 September 2003). DATA SYNTHESIS: Research has been performed to
evaluate the risk of teratogenesis after sumatriptan exposure in pregnant
patients. Data have been collected in areas including placental transmission of
sumatriptan, prospective pregnancy registries, open-labeled and controlled
prospective studies, and a retrospective prescription-linked study. As of August 
6, 2004, no randomized controlled trials have been conducted with exposure to
sumatriptan during pregnancy. CONCLUSIONS: Teratogenesis occurs in approximately 
150 000 births per year which represents an incidence of 3-5%. Available
literature to date indicates that exposure to sumatriptan during pregnancy has no
additional risk of birth defects compared with the incidence in the general
population.

Publication Types: 
    Review

PMID: 15316107 [PubMed - indexed for MEDLINE]

2126: Ophthalmic Physiol Opt. 2004 Sep;24(5):369-83.

The optometric correlates of migraine.

Harle DE, Evans BJ.

The Institute of Optometry, 56-62 Newington Causeway, London, UK.
dharle@ioo.org.uk

Migraine is a common, chronic, multi-factorial, neuro-vascular disorder typically
characterised by recurrent attacks of unilateral, pulsating headache and
autonomic nervous system dysfunction. Migraine may additionally be associated
with aura; those focal neurological symptoms that may precede or sometimes
accompany the headache. This review describes the optometric aspects of migraine 
headache. There have been claims of a relationship between migraine headaches and
errors of refraction, binocular vision anomalies, pupil anomalies, visual field
changes and pattern glare. The quality of the evidence for a relationship between
errors of refraction and binocular vision and migraine is poor. The quality of
the evidence to suggest a relationship between migraine headache and pupil
anomalies, visual field defects and pattern glare is stronger. In particular the 
link between migraine headache and pattern glare is striking. The therapeutic use
of precision-tinted spectacles to reduce pattern glare (visual stress) and to
help some migraine sufferers is described.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 15315651 [PubMed - indexed for MEDLINE]

2127: Cephalalgia. 2004 Sep;24(9):735-9.

Cerebrospinal fluid glutamate levels in chronic migraine.

Peres MF, Zukerman E, Senne Soares CA, Alonso EO, Santos BF, Faulhaber MH.

Hospital Israelita Albert Einstein, Instituto de Ensino e Pesquisa, São Paulo,
Brazil.

Both preclinical and clinical data link glutamate to the migraine
pathophisiology. Altered plasma, platelets and cerebrospinal (CSF) glutamate
levels have been reported in migraine patients. Chronic migraine is comorbid with
several conditions. It has been recently shown chronic migraine comorbidity with 
fibromyalgia. The objective of this study was to study cerebrospinal fluid
glutamate levels in chronic migraine patients with and without fibromyalgia. We
studied 20 chronic migraine patients, with and without fibromyalgia, compared to 
age-sex matched controls. CSF glutamate levels were measured by HPLC. CSF
glutamate demonstrated significantly higher levels in patients with fibromyalgia 
compared to those without fibromyalgia. Patients overall had higher CSF glutamate
levels than controls. Mean pain score correlated with glutamate levels in chronic
migraine patients. Tender points, the hallmark of fibromyalgia, can be considered
as pressure allodynia, and is probably mediated by central sensitization, with
increase in CSF glutamate levels. We postulate chronic migraine patients with
fibromyalgia, in addition to have more disabling headaches, suffer from a more
severe central sensitization process. This subtype of patients may respond to
medications modulating glutamate receptors. Headache intensity correlate with
glutamate levels in chronic migraine patients. Copyright 2004 Blackwell
Publishing Ltd

Publication Types: 
    Comparative Study

PMID: 15315529 [PubMed - indexed for MEDLINE]

2128: Cephalalgia. 2004 Sep;24(9):728-34.

The aura: a tertiary care study of 952 migraine patients.

Kelman L.

Headache Center of Atlanta, Atlanta, Georgia 30342, USA. lkelman@mindstring.com

The aim of this study was to document the frequency and types of aura symptoms,
to define the relationship between aura symptoms and to define the aura frequency
in different migraine types. In 952 migraine patients, aura frequency, duration, 
time to headache, characteristics and percentage of headaches with aura were
analysed. Thirty-eight percent of IHS 1.1-1.5 patients reported aura, 38.1% of
females and 33.0% of males. Average percentage of aura occurrence with headache
was 19.7% of headaches, average aura duration 27.3 min and aura was followed by
headache in 10.4 min on average. Visual disturbances occurred in 92.1% and aura
without visual aura was rare. Aura frequency was headache-type dependent. The
highest frequency of aura was seen in the more 'full-blown' migraine attack.
Visual aura is the overwhelming aura symptom. Even in patients with aura the
percentage of aura with migraine attacks is limited. Copyright 2004 Blackwell
Publishing Ltd

Publication Types: 
    Comparative Study

PMID: 15315528 [PubMed - indexed for MEDLINE]

2129: Cephalalgia. 2004 Sep;24(9):707-16.

Characteristics of menstrual and nonmenstrual attacks in women with menstrually
related migraine referred to headache centres.

Granella F, Sances G, Allais G, Nappi RE, Tirelli A, Benedetto C, Brundu B,
Facchinetti F, Nappi G.

Department of Neurosciences, Neurology Unit, University of Parma, Parma, Italy.

Aim of this study was to determine whether menstrual attacks differ from
nonmenstrual attacks (NMA) as regards clinical features or response to abortive
treatment in women affected by menstrually related migraine (MRM) referred to
tertiary care centres. Sixty-four women with MRM were enrolled in a 2-month diary
study. Perimenstrual attacks were split into three groups--premenstrual (PMA),
menstrual (MA) and late menstrual (LMA)--and compared to nonmenstrual ones.
Perimenstrual attacks were significantly longer than NMA. No other migraine
attack features were found to differ between the various phases of the cycle.
Migraine work-related disability was significantly greater in PMA and MA than in 
NMA. Acute attack treatment was less effective in perimenstrual attacks.
Pain-free at 2 h after dosage was achieved in 13.5% of MA (OR 0.41; 95% CI 0.22, 
0.76) vs. 32.9% of NMA. We concluded that, in MRM, perimenstrual attacks are
longer and less responsive to acute attack treatment than NMA. Copyright 2004
Blackwell Publishing Ltd

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 15315526 [PubMed - indexed for MEDLINE]

2130: Cephalalgia. 2004 Sep;24(9):700-6.

Cerebrovascular response to repetitive visual stimulation in interictal migraine 
with aura.

Nedeltchev K, Arnold M, Schwerzmann M, Nirkko A, Lagger F, Mattle HP,
Sturzenegger M.

Department of Neurology, University Hospital of Bern, Bern, Switzerland.

Cortical hypersensitivity and absent habituation to different stimuli have been
observed in migraine patients. These features might also be transmitted to the
cerebral vasoreactivity, but results are conflicting so far. Transcranial Doppler
ultrasound (TCD) was used to assess cerebral blood flow velocity (CBFV) changes
in the middle (MCA) and posterior cerebral arteries (PCA) in relation to
repetitive checkerboard visual stimulation. Stimulation consisted of 10
consecutive cycles, each comprising 10 s stimulation and 10 s rest. TCD
recordings were analysed using stimulus-related averaging algorithm. Data of 19
interictal migraineurs with aura were compared to those of 19 headache-free
healthy volunteers. The CBFV increase in PCA and in MCA during visual stimulation
was significantly larger and steeper in migraineurs than in controls (P = 0.017
and P = 0.005). The response in PCA remained stable over the 10 stimulation
cycles, both in migraineurs and in controls. The response in MCA was stable only 
in migraineurs. In controls it decreased over the last 5 stimulation cycles
compared with the first 5 cycles (P = 0.04). Migraineurs with aura exhibit a
larger cerebrovascular response to repetitive visual stimulation compared to
headache-free subjects. A reduced adaptation to environmental stimuli in migraine
is suggested, since there was no habituation in migraineurs in contrast to
healthy controls. Copyright 2004 Blackwell Publishing Ltd

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 15315525 [PubMed - indexed for MEDLINE]

2131: Acta Neurol Taiwan. 2004 Mar;13(1):20-3.

Migrainous infarction involving two different arterial territories: report of two
cases.

Tang SC, Jeng JS, Liu HM, Yip PK.

Department of Neurology, National Taiwan University Hospital, Taipei, Taiwan.

It is reasonable to speculate that migrainous infarction may develop in different
territories of cerebral arteries. However, this condition was rarely reported
before. Here we described two patients (one woman, 29 year-old; one man, 47
year-old) with a history of migraine with aura, had ischemic strokes during the
migraine attack. The ischemic stroke of the female patient involved the
territories of the posterior cerebral and anterior choroidal arteries; whereas
the male patient had two episodes of ischemic strokes, involving the territories 
of the middle and posterior cerebral arteries sequentially. Both patients
recovered well during the follow-up periods. We suggest that migrainous
infarction can involve different arterial territories.

Publication Types: 
    Case Reports

PMID: 15315297 [PubMed - indexed for MEDLINE]

2132: Arch Neurol. 2004 Aug;61(8):1237-40.

Migraine with aura and brain magnetic resonance imaging abnormalities in patients
with CADASIL.

Vahedi K, Chabriat H, Levy C, Joutel A, Tournier-Lasserve E, Bousser MG.

Service de Neurologie, Assistance Publique--Hôpitaux de Paris, Hôpital
Lariboisière, Paris, France. katayoun.vahedi@lrb.ap-hop-paris.fr

BACKGROUND: Migraine with aura (MA) is one of the clinical hallmarks of CADASIL
(cerebral autosomal dominant arteriopathy with subcortical infarcts and
leukoencephalopathy), a small vessel disease of the brain caused by mutations in 
the NOTCH3 gene, but its exact mechanisms are unknown. OBJECTIVES: To describe
the patterns of MA in CADASIL and to compare brain magnetic resonance signal
abnormalities between CADASIL patients with and without MA. DESIGN: Comparison of
brain magnetic resonance signal abnormalities between cases and controls.
SETTING: Patients with CADASIL seen at Lariboisière Hospital. PATIENTS: Forty-one
CADASIL patients with MA and 31 age-matched CADASIL controls without MA. RESULTS:
The mean age at onset of MA was significantly younger in women compared with men 
and occurred a mean of 15 years prior to stroke onset. A majority of patients
(56%) reported at least 1 migraine attack with atypical aura. All CADASIL
patients either with or without MA had white matter signal abnormalities on
T2-weighted imaging. There was no difference in the frequency and distribution of
brain signal abnormalities between CADASIL patients with and without MA.
CONCLUSIONS: In CADASIL, MA is characterized by an unusually high frequency of
attacks of migraine with atypical aura. The distribution and extent of magnetic
resonance signal abnormalities did not differ according to migraine phenotype.

Publication Types: 
    Comparative Study

PMID: 15313840 [PubMed - indexed for MEDLINE]

2133: Int J Clin Pract. 2004 Jul;58(7):695-705.

Frovatriptan succinate, a 5-HT1B/1D receptor agonist for migraine.

Balbisi EA.

St John's University, College of Pharmacy and Allied Health Professions, and
Ambulatory Medicine, Queens Hospital Center, jamaica, New York 11439, USA.
balbisie@stjohns.edu

Frovatriptan succinate is one of the most recent serotonin receptor agonists to
receive FDA, approved labelling for use in the acute management of migraine with 
or without aura in adults. The mechanism of action of frovatriptan is thought to 
be similar to that of a serotonin agonist. However, frovatriptan has distinctive 
pharmacokinetic and pharmacologic properties, chiefly, a high affinity for
serotonin receptors 1B and 1D and a long elimination half-life; frovatriptan was 
shown to be more selective for cerebral than coronary arteries, a property which 
makes frovatriptan more favourable in patients at risk of coronary artery
disease. Additionally, frovatriptan has a half-life of approximately 25 h,
substantially longer than that of any other agent within its class. This property
makes frovatriptan suitable for patients who typically suffer migraines of long
duration and/or those who suffer migraine recurrence. The efficacy of
frovatriptan in the treatment of acute migraine was demonstrated in five
double-blind, randomised, placebo-controlled trials. At 2h, headache response
rates for frovatriptan 2.5 mg ranged from 38 to 40% compared to 22-35% for
placebo. Headache recurrence for frovatriptan 2.5 mg at 24h ranged from 9 to 14% 
compared with 18% in placebo subjects. Frovatriptan has no clinically significant
pharmacokinetic interactions with drugs used for migraine prophylaxis or with
commonly prescribed medications. Adverse effects of frovatriptan including
dizziness, paresthesia, dry mouth, fatigue and flushing were generally mild and
well tolerated. Given the fact that patient response to serotonin agonists is
individualised, and selecting an effective agent may involve trial and error,
frovatriptan is a welcome alternative in the acute management of migraine.

Publication Types: 
    Comparative Study
    Review

PMID: 15311727 [PubMed - indexed for MEDLINE]

2134: J Biol Chem. 2004 Oct 15;279(42):43692-6. Epub 2004 Aug 11.

Kinetic alterations due to a missense mutation in the Na,K-ATPase alpha2 subunit 
cause familial hemiplegic migraine type 2.

Segall L, Scanzano R, Kaunisto MA, Wessman M, Palotie A, Gargus JJ, Blostein R.

Department of Biochemistry, McGill University, Montreal, Quebec H3G 1A4, Canada.

A number of missense mutations in the ATP1A2 gene, which encodes the Na,K-ATPase 
alpha2 subunit, have been identified in familial hemiplegic migraine with aura.
Loss of function and haploinsufficiency have been the suggested mechanisms in
mutants for which functional analysis has been reported. This paper describes a
kinetic analysis of mutant T345A, recently identified in a detailed genetic
analysis of a large Finnish family (Kaunisto, M. A., Harno, H., Vanmolkot, K. R.,
Gargus, J. J., Sun, G., Hamalainen, E., Liukkonen, E., Kallela, M., van den
Maagdenberg, A. M., Frants, R. R., Farkkila, M., Palotie, A., and Wessman, M.
(2004) Neurogenetics 5, 141-146). Introducing T345A into the conserved rat alpha2
enzyme does not alter cell growth or catalytic turnover but causes a substantial 
decrease in apparent K+ affinity (2-fold increase in K0.5(K+)). In view of the
location of Thr-345 in the cytoplasmic stalk domain adjacent to transmembrane
segment 4, the 2-fold increase in K0.5(K+) is probably due to T345A replacement
altering K+ occlusion/deocclusion. Faster K+ deocclusion of the mutant via the
E2(K) + ATP --> E1.ATP + K+ partial reaction is evidenced in (i) a marked
increase (300%) in K+ stimulation of Na-ATPase at micromolar ATP, (ii) a 4-fold
decrease in KATP, and (iii) only a modest increase (approximately 3-fold) in I50 
for vanadate, which was used as a probe of the steady state E1/E2 conformational 
equilibrium. We suggest that the decreased apparent K+ affinity is the basis for 
a reduced rate of extracellular K+ removal, which delays the recovery phase of
nerve impulse transmission in the central nervous system and, thereby, the
clinical picture of migraine with aura. This is the first demonstration of a
mutation that leads to a disease associated with a kinetically altered but fully 
functional Na,K-ATPase, refining the molecular mechanism of pathogenesis in
familial hemiplegic migraine.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 15308625 [PubMed - indexed for MEDLINE]

2135: J Affect Disord. 2004 Aug;81(2):157-60.

Migraine headache and mood disorders: a descriptive study in an outpatient
psychiatric population.

Franchini L, Bongiorno F, Dotoli D, Rainero I, Pinessi L, Smeraldi E.

Istituto Scientifico H. San Raffaele, Department of Neuropsychiatric Sciences,
School of Medicine, Università Vita e Salute, Via Stamira d'Ancona 20, 20127
Milan, Italy. franchini.linda@hsr.it

BACKGROUND: Information is sparse concerning migraine distribution in mood
disorder subjects based mainly on psychiatric disorder. METHODS: In a sample of
283 normothymic mood disorder outpatients on maintenance treatment with serotonin
reuptake inhibitors (SSRIs) or lithium, we investigated migraine distribution and
clinical variables possibly related to comorbidity risk between mood disorder and
migraine. RESULTS: Some 26.8% of the sample met criteria for migraine with
migraine age of onset earlier than mood disorder age of onset; familiarity for
mood disorder and migraine was strictly related to comorbidity risk in probands. 
Long-term treatment with lithium salts subjectively improved migraine outcome.
CONCLUSIONS: These results could support the bidirectional association between
the two clinical forms, considering the familial and pharmacological patterns.

PMID: 15306142 [PubMed - indexed for MEDLINE]

2136: Neurology. 2004 Aug 10;63(3):520-4.

Predicting the response to sumatriptan: the Sumatriptan Naratriptan Aggregate
Patient Database.

Christoph-Diener H, Ferrari M, Mansbach H; SNAP Database Study Group.

Dept. of Neurology, University of Essen, Hufelandstr. 55, 45147 Essen, Germany.
h.diener@uni-essen.de

OBJECTIVE: The efficacy and tolerability profiles of sumatriptan and other
5HT(1B/1D) agonists (triptans) have been well established. However, the
determinants for optimal response to sumatriptan are unknown. The Sumatriptan
Naratriptan Aggregate Patient (SNAP) database contains data from 128 clinical
trials including 28,407 migraine sufferers treating over 130,000 attacks. The
authors analyzed these data to identify factors predicting response (headache
relief and pain-free response) to sumatriptan. METHODS: The authors assessed 24
possible univariate predictors of headache response in 3,706 patients (18 years
and older) receiving sumatriptan tablets 100 mg or placebo in a double-blind
study using recursive partitioning and logistic regression techniques. RESULTS:
The authors found seven predictors of headache relief 2 hours postdose. Moderate 
pain at baseline was the strongest predictor (adjusted p = 3.32 x 10(-35)),
followed by absence of a disability requiring bedrest (adjusted p = 3.11 x
10(-18)). Other predictors included absence at baseline of vomiting, pulsating
pain, nausea, or photophobia/phonophobia, and onset of headache during daytime
hours. Logistic regression confirmed that treatment with sumatriptan was the
strongest predictor of headache relief, with significant baseline covariates
being pain severity, level of disability, and presence or absence of vomiting. A 
similar pattern of results was reported for predictors of pain-free response 2
hours after taking sumatriptan. CONCLUSIONS: Pretreatment pain severity is the
most important predicting factor for response to sumatriptan in migraine attacks:
the lower baseline severity, the better.

Publication Types: 
    Clinical Trial
    Controlled Clinical Trial
    Research Support, Non-U.S. Gov't

PMID: 15304585 [PubMed - indexed for MEDLINE]

2137: J Occup Environ Med. 2004 Aug;46(8):812-7.

Triptan therapy impacts health and productivity.

Weaver MB, Mackowiak JI, Solari PG.

GlaxoSmithKline, Research Triangle Park, North Carolina 27709-3398, USA.
Mary.B.Weaver@gsk.com

New sumatriptan users in a California health plan were surveyed on the impact of 
migraine using a newly developed migraine impact measure, the Headache Impact
Test-6. Productivity and satisfaction with migraine therapy also were assessed.
After sumatriptan was initiated, participants reported significantly fewer
workdays missed, fewer days worked with headache, and greater productivity while 
headache symptoms were present. In addition, almost 50% less members used
narcotics/opioids, while the frequency, duration, and severity of migraines
decreased. Initiation of sumatriptan therapy is associated with improvements in
absenteeism and presenteeism, clinical outcomes (Headache Impact Test-6), and
satisfaction. The benefits of triptan therapy extend to the employer, who sees a 
decrease in lost productivity, fewer emergency room visits, and less narcotics
use in employees with migraine. Managed care organizations that provide this
pharmacotherapy may foster greater satisfaction among members and employer
customers.

PMID: 15300133 [PubMed - indexed for MEDLINE]

2138: Curr Opin Investig Drugs. 2004 Jul;5(7):731-5.

CGRP receptor antagonists: a new choice for acute treatment of migraine?

Durham PL.

Southwest Missouri State University, Department of Biology, 225 Temple Hall,
Springfield, MO 65804, USA. pauldurham@smsu.edu

The neuropeptide calcitonin gene-related peptide (CGRP) is believed to play a
central role in the underlying pathology of migraine. Serum levels of CGRP,
elevated during a migraine attack, return to normal as pain alleviates. Recently,
a causative role for CGRP in migraine has been suggested. Based on these
findings, it was proposed that blockade of postsynaptic CGRP receptors, and hence
the physiological effects of CGRP, should effectively abort a migraine attack.
This review will discuss the therapeutic potential of olcegepant, the first
non-peptide CGRP receptor antagonist available for human studies, within the
context of current neurovascular theories on migraine pathology.

Publication Types: 
    Review

PMID: 15298069 [PubMed - indexed for MEDLINE]

2139: Neuron. 2004 Aug 5;43(3):387-400.

Presynaptic Ca2+ channels compete for channel type-preferring slots in altered
neurotransmission arising from Ca2+ channelopathy.

Cao YQ, Piedras-Rentería ES, Smith GB, Chen G, Harata NC, Tsien RW.

Department of Molecular and Cellular Physiology, Beckman Center, Stanford
University School of Medicine, Stanford, CA 94305, USA.

Several human channelopathies result from mutations in alpha1A, the pore-forming 
subunit of P/Q-type Ca2+ channels, conduits of presynaptic Ca2+ entry for evoked 
neurotransmission. We found that wild-type human alpha1A subunits supported
transmission between cultured mouse hippocampal neurons equally well as
endogenous mouse alpha1A, whereas introduction of impermeant human alpha1A
hampered the effect of endogenous subunits. Thus, presynaptic P/Q-type channels
may compete for channel type-preferring "slots" that limit their synaptic
effectiveness. The existence of slots generates predictions for how
neurotransmission might be affected by changes in Ca2+ channel properties, which 
we tested by studying alpha1A mutations that are associated with familial
hemiplegic migraine type 1 (FHM1). Mutant human P/Q-type channels were impaired
in contributing to neurotransmission in precise accord with their deficiency in
supporting whole-cell Ca2+ channel activity. Expression of mutant channels in
wild-type neurons reduced the synaptic contribution of P/Q-type channels,
suggesting that competition for type-preferring slots might support the dominant 
inheritance of FHM1. Copyright 2004 Cell Press

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 15294146 [PubMed - indexed for MEDLINE]

2140: Pain. 2004 Aug;110(3):675-80.

Glyceryl trinitrate triggers premonitory symptoms in migraineurs.

Afridi SK, Kaube H, Goadsby PJ.

Headache Group, Institute of Neurology, The National Hospital for Neurology and
Neurosurgery, Queen Square, WC1N 3BG London, UK.

Studying attacks of migraine is considerably hampered by its fundamentally
episodic nature. Developing approaches to triggering migraine reliably is
important for advancing understanding of the disorder by facilitating its study. 
Based on the work of the Copenhagen Group we administered an intravenous infusion
of 0.5 microg/kg/min glyceryl trinitrate (GTN) to 44 migraineurs, 23 migraine
without aura, 21 migraine with aura, and to 12 healthy controls. We sought to
characterise the GTN-induced migraine in terms of the clinical features of the
attacks and reproducibility of triggering, and included a non-migraine control
group for the purpose of comparing any effects to exclude an ordering effect. Of 
the 44 patients administered GTN, 33 had a migraine attack fulfilling
International Headache Society criteria. Thirty-two attacks were of migraine
without aura and one of migraine with aura. Twelve patients described typical
premonitory symptoms, which have not been previously documented with GTN-induced 
migraine. A repeat attack was triggered in all subjects but one. In one case a
visual aura was also triggered both times. Our study shows that GTN-induced
triggering is common in our patients, and remarkably reproducible. The data will 
facilitate the use of the GTN model in studies requiring extensive planning, such
as brain imaging, or where preventive questions are at issue. We also report the 
first patient with a reproducible GTN-triggered migraine with aura.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 15288408 [PubMed - indexed for MEDLINE]

2141: Acta Neurol Scand. 2004 Sep;110(3):137-43.

TRIPSTAR: prioritizing oral triptan treatment attributes in migraine management.

Goadsby PJ, Dodick DW, Ferrari MD, McCrory DC, Williams P.

Institute of Neurology, The National Hospital for Neurology and Neurosurgery,
London, UK. peterg@ion.ucl.ac.uk

Migraine can be associated with severe pain and is often very disabling. Optimal 
treatment should provide rapid and sustained, complete pain relief, be well
tolerated and restore normal function. The seven commercially available triptans 
show differences in performance on individual treatment attributes. The TRIPSTAR 
multiattribute decision model compares the profiles of the oral triptans, using
efficacy and tolerability data weighted for importance, to identify if measurable
differences are clinically relevant. Application of the TRIPSTAR model was
demonstrated at the Migraine Trust International Symposium 2002, where delegates 
collectively prioritized treatment attributes according to the needs of a
specific patient case history. The TRIPSTAR model identified the preferred
triptans for this patient. These three triptans, almotriptan 12.5 mg, eletriptan 
80 mg and rizatriptan 10 mg, standout in a triptan meta-analysis, three TRIPSTAR 
surveys and in a demonstration of the TRIPSTAR model at a symposium in the USA.
Taken together the findings suggest that some differences amongst triptans may be
relevant in clinical practice.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 15285768 [PubMed - indexed for MEDLINE]

2142: J Clin Neurophysiol. 2004 Mar-Apr;21(2):99-104.

Changes in cortical dynamics in the preictal stage of a migraine attack.

Fritzer G, Strenge H, Göder R, Gerber WD, Aldenhoff J.

Department of Psychiatry and Psychotherapy, Christian Albrechts University, Kiel,
Germany. fritzer@psychiatry.uni-kiel.de

Neurophysiologic studies suggest that migraineurs without aura have a dysfunction
of cortical information processing in the pain-free interval. In this study, the 
advanced method of nonlinear multielectrode sleep-EEG analysis is used to
investigate changes of cortical activity in the preictal time span. Five patients
(four women, one man; age range, 29 to 58 years) experiencing migraine without
aura participated in the study. The patients spent two blocks in the sleep
laboratory. The first block was taken in a headache-free interictal time
interval, and the second block when the onset of a migraine attack was most
likely. After a nocturnal migraine attack, the patient was asked to mark the
maximum of migraine pain in a surface-head scheme. The comparison of preictal and
interictal EEGs enabled the authors to obtain a topographical view of changes in 
cortical dynamics. In each patient map, an area was found that displayed a
pronounced focus indicating the region of maximum change in dimensional
complexity. It shows a clearly recognizable correspondence with the scalp
topography of the later pain perception. These findings indicate an association
between cortical status and pain lateralization in the preictal time span.

Publication Types: 
    Clinical Trial

PMID: 15284600 [PubMed - indexed for MEDLINE]

2143: Brain. 2004 Sep;127(Pt 9):2099-108. Epub 2004 Jul 28.

Autonomic asymmetry in migraine: augmented parasympathetic activation in left
unilateral migraineurs.

Avnon Y, Nitzan M, Sprecher E, Rogowski Z, Yarnitsky D.

Department of Neurology, Rambam Medical Center, Technion, Haifa, Israel.

Brain autonomic control is asymmetrical, the left hemisphere affecting
predominantly parasympathetic function and the right hemisphere affecting
predominantly sympathetic function. It is not known whether the extent of
autonomic activation is altered in migraine, although the fact that some
migraineurs express parasympathetic features such as facial flushing, lacrimation
and rhinorrhoea might suggest increased parasympathetic activation. We instilled 
diluted soapy eyedrops and measured (i) the trigemino-parasympathetic reflex by
the vasodilator response of forehead skin bilaterally using photoplethysmography;
(ii) the somato-sympathetic reflex by vasoconstriction in the index finger; and
(iii) heart rate response. We studied 14 left-sided and 15 right-sided unilateral
migraineurs outside attacks. We found that left-side migraineurs had
significantly higher bilateral parasympathetic vasodilatation, regardless of the 
stimulation or measurement side (+60.1 +/- 6.4%) compared with right-side
migraineurs (+41.9 +/- 6.4%, P < 0.05). Sympathetic vasoconstriction, however,
was similar for the two groups (left, -15.9 +/- 4.2%; right, -17.7 +/- 4.1%, NS).
Bradycardia was significantly more pronounced for the left-side migraineurs
(interbeat, RR interval increase of +6.2 +/- 1.1% versus +3.1 +/- 1.1%, P <
0.04). We conclude that unilateral left-side migraineurs have increased
parasympathetic activation in response to pain compared with right-side
migraineurs. Sympathetic responses were similar in the two groups and seemed not 
to be affected by migraine side. Since cranial parasympathetic activity induces
cerebral vasodilatation, this augmentation might be an inherent part of the
migraine pathophysiology in these patients.

PMID: 15282213 [PubMed - indexed for MEDLINE]

2144: Neurology. 2004 Jul 27;63(2):351-3.

Comment in:
    Neurology. 2004 Jul 27;63(2):202-3.

Prevalence of migraine on each day of the natural menstrual cycle.

MacGregor EA, Hackshaw A.

City of London Migraine Clinic and Department of Gynaecology, St. Bartholomew's
Hospital, London, UK.

Diary data from 155 women were analyzed using within-woman analysis. Compared
with all other times of the cycle, migraine was 1.7 times more likely to occur
during the 2 days before menstruation and 2.1 times more likely to be severe and 
2.5 times more likely to occur during the first 3 days of menstruation and 3.4
times more likely to be severe. This confirms that migraine at menstruation is
different from nonmenstrual attacks, even within individuals.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 15277635 [PubMed - indexed for MEDLINE]

2145: Neurology. 2004 Jul 27;63(2):348-50.

Elicited repetitive daily blindness: a new familial disorder related to migraine 
and epilepsy.

Le Fort D, Safran AB, Picard F, Bouchardy I, Morris MA.

dominiquelefort@hotmail.com

The authors report a family affected by multiple daily episodes of transient
visual loss, elicited repetitive daily blindness (ERDB); the onset was early in
life, and the disease followed a benign course. ERDB is associated with childhood
epilepsy and familial hemiplegic migraine, apparently segregating as a monogenic,
autosomal dominant condition with variable expression. Genetic linkage to CACNA1A
was excluded.

Publication Types: 
    Case Reports

PMID: 15277634 [PubMed - indexed for MEDLINE]

2146: Neurology. 2004 Jul 27;63(2):261-9.

Comment in:
    Neurology. 2004 Jul 27;63(2):202-3.    Neurology. 2005 Mar 8;64(5):931; author reply 931.

A randomized trial of frovatriptan for the intermittent prevention of menstrual
migraine.

Silberstein SD, Elkind AH, Schreiber C, Keywood C.

Thomas Jefferson University, Philadelphia, PA, USA.
Stephen.Silberstein@Jefferson.edu

BACKGROUND: Menstrually associated migraine (MAM) is often prolonged and
difficult to manage with conventional therapies. Frovatriptan is a new selective 
5HT(1B/1D) receptor agonist indicated for short-term management of migraine. It
has a long half-life and good tolerability. These characteristics suggest that
frovatriptan may be useful for the intermittent prevention of MAM. METHODS: The
study was a randomized, double-blind, placebo-controlled, three-way crossover
design. Patients treated each of three perimenstrual periods (PMPs) with placebo,
frovatriptan 2.5 mg QD, and frovatriptan 2.5 mg BID. The 6-day treatment started 
2 days before the anticipated start of MAM headache. The primary efficacy
endpoint was incidence of MAM headache during the 6-day PMP. RESULTS: The
population comprised 546 women (mean age, 37.6 years). Use of frovatriptan
reduced the occurrence of MAM headache. The incidence of MAM headache during the 
6-day PMP was 67% for placebo, 52% for frovatriptan 2.5 mg QD, and 41% for
frovatriptan 2.5 mg BID. Both frovatriptan regimens were superior to placebo (p <
0.0001), and the BID regimen was superior to the QD regimen (p < 0.001). Both
frovatriptan regimens also reduced MAM severity (p < 0.0001), duration (p <
0.0001), and the use of rescue medication (p < 0.01 QD; p < 0.0001 BID) in a
dose-dependent manner. The incidence and type of adverse events for both regimens
were similar to placebo and consistent with those reported for short-term
migraine management. CONCLUSION: Frovatriptan given prophylactically for 6 days
was effective in reducing the incidence of menstrually associated migraine. More 
than half of patients who used frovatriptan 2.5 mg BID had no menstrually
associated migraine headache during the 6-day perimenstrual period. The findings 
are consistent with the long duration of action and good tolerability of
frovatriptan observed in short-term migraine management.

Publication Types: 
    Clinical Trial
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 15277618 [PubMed - indexed for MEDLINE]

2147: Funct Neurol. 2004 Apr-Jun;19(2):101-5.

Relationship between clinical variables and cognitive performances in migraineurs
with and without aura.

Le Pira F, Lanaia F, Zappalà G, Morana R, Panetta MR, Reggio E, Reggio A.

Department of Neurosciences, University of Catania, Italy. lepira@unict.it

Conflicting data on cognitive defects in migraine could be explained by
differences in the clinical variables of the populations studied. We investigated
21 patients with migraine with aura and 24 with migraine without aura, diagnosed 
according to the International Headache Society criteria. The patients were
submitted to a comprehensive battery of neuropsychological tests and grouped
according to attack frequency and side of pain. Attack frequency was not
associated with significant differences in any of the tasks, while location of
pain was found to be significantly related to poorer performance on both the
immediate and delayed recall of Rey Complex Figure in migraineurs both with and
without aura, and a significant relationship between side of pain and number of
clusters in the second trial of California Verbal Learning Test was found only in
migraine with aura patients. The finding of worse performances in patients with
right-sided pain seems to support a right hemisphere dysfunction hypothesis.

PMID: 15274516 [PubMed - indexed for MEDLINE]

2148: CNS Drugs. 2004;18(10):671-85.

Intranasal medications for the treatment of migraine and cluster headache.

Rapoport AM, Bigal ME, Tepper SJ, Sheftell FD.

Columbia University College of Physicians & Surgeons, New York, NY, USA.
alanrapoport@nech.net

Intranasal medications for the treatment of headache have recently received
increased attention. This paper reviews intranasal formulations of a variety of
available medications (dihydroergotamine mesylate [dihydroergotamine mesilate],
sumatriptan, zolmitriptan, butorphanol, capsaicin and lidocaine [lignocaine]) and
one experimental medication (civamide, a cis-isomer of capsaicin) for the
treatment of migraine and cluster headache. Although the efficacy of intranasal
agents varies with the product used, intranasal delivery may be both convenient
and more effective than other modes of drug delivery for a variety of reasons:
(i) intranasal administration bypasses small bowel gastrointestinal tract
absorption, which is often significantly delayed during the acute phase of a
migraine attack; (ii) nauseated patients may prefer non-oral formulations as they
decrease the chance of vomiting and are more rapidly effective; (iii) intranasal 
administration causes no pain or injection site reaction and is easier and more
convenient to administer than injection or suppository and so may be used earlier
in a migraine attack, resulting in better efficacy; (iv) intranasal medication
produces the same number or fewer adverse events than injections; and (v)
intranasal formulations offer a more rapid onset of action than oral medications,
for some of the above reasons and, as such, may be more useful in patients with
cluster headache, although this needs to be verified. However, it is important to
emphasise that a preference study showed that most patients prefer oral tablets
to an intranasal formulation. Also, some nasal preparations have significant
adverse effects or are not well absorbed and therefore do not work consistently; 
others are more challenging to administer as a result of their delivery
apparatus. Nevertheless, it is our opinion that nasal preparations increase
therapeutic options and may result in faster response times and better efficacy
than oral formulations and better patient satisfaction than injectable
preparations.

Publication Types: 
    Review

PMID: 15270595 [PubMed - indexed for MEDLINE]

2149: Cochrane Database Syst Rev. 2004;(3):CD003226.

Comment in:
    ACP J Club. 2005 Jan-Feb;142(1):21.

Anticonvulsant drugs for migraine prophylaxis.

Chronicle E, Mulleners W.

Department of Psychology, University of Hawaii at Manoa, 2430 Campus Road,
Honolulu, Hawaii, USA, 96822.

BACKGROUND: Anticonvulsant drugs seem to be useful in clinical practice for the
prophylaxis of migraine. This might be explained by a variety of actions of these
drugs in the central nervous system that are probably relevant to the
pathophysiology of migraine. OBJECTIVES: To describe and assess the evidence from
controlled trials on the efficacy and tolerability of anticonvulsants for
preventing migraine attacks in adult patients with migraine. SEARCH STRATEGY: We 
searched MEDLINE (from 1966 on) and the Cochrane Central Register of Controlled
Trials (CENTRAL). Date of most recent search: April 2003. Additional information 
was gained from hand-searching specialist headache journals; correspondence with 
pharmaceutical companies, authors of reports, and experts in the field; and a
wide variety of review articles and book chapters. SELECTION CRITERIA: Studies
were required to be prospective, controlled trials of self-administered drug
treatments taken regularly to prevent the occurrence of migraine attacks and/or
to reduce the intensity of those attacks. DATA COLLECTION AND ANALYSIS: Studies
were selected and data extracted by two independent reviewers. For migraine
frequency data, standardized mean differences (SMDs) were calculated for
individual studies and pooled across studies. For dichotomous data on significant
reduction in migraine frequency, odds ratios (ORs) and numbers-needed-to-treat
(NNTs) were similarly calculated. Adverse events were analyzed by calculating
numbers-needed-to-harm (NNHs) for studies using similar agents. MAIN RESULTS:
Fifteen papers were included in the review. Of these, 14 reported trials
comparing anticonvulsants with placebo, as follows: four trials of divalproex
sodium, three trials of topiramate, two trials of sodium valproate, two trials of
gabapentin, and one trial each of carbamazepine, clonazepam, and lamotrigine. One
paper reported a trial of sodium valproate versus an active comparator,
flunarizine, and one trial of divalproex sodium versus placebo included a
comparison against propranolol, also an active comparator. Data from 2024
patients were considered. Analysis of data from eight trials (n = 841)
demonstrates that anticonvulsants, considered as a class, reduce migraine
frequency by about 1.4 attacks per 28 days as compared to placebo (SMD -0.60; 95%
confidence interval [CI] -0.93 to -0.26). Data from 10 trials (n = 1341) show
that anticonvulsants, considered as a class, also more than double the number of 
patients for whom migraine frequency is reduced by 50% or more, relative to
placebo (OR 3.90; 95% CI 2.61 to 5.82; NNT 3.8; 95% CI 3.2 to 4.6). For seven
trials of sodium valproate and divalproex sodium, NNHs for five clinically
important adverse events ranged from 6.6 to 16.3. For the three trials of
topiramate, NNHs for eight adverse events (100-mg dose) ranged from 2.4 to 32.9. 
REVIEWERS' CONCLUSIONS: Anticonvulsants appear to be both effective in reducing
migraine frequency and reasonably well tolerated. There is noticeable variation
among individual agents, but there are insufficient data to know whether this is 
due to chance or variation in true efficacy. Neither clonazepam nor lamotrigine
was superior to placebo (one trial each). Relatively few robust trials are
available for agents other than sodium valproate/divalproex sodium. Two recently 
published and large trials of topiramate demonstrated reasonable efficacy, and
one further trial of this agent is anticipated in the near future.

Publication Types: 
    Meta-Analysis
    Review

PMID: 15266476 [PubMed - indexed for MEDLINE]

2150: Curr Med Res Opin. 2004 Jul;20(7):1143-50.

Erratum in:
    Curr Med Res Opin. 2004 Oct;20(10):1689.

Impact of migraine on patients and their families: the Migraine And Zolmitriptan 
Evaluation (MAZE) survey--Phase III.

MacGregor EA, Brandes J, Eikermann A, Giammarco R.

City of London Migraine Clinic, London, UK.

OBJECTIVE: To investigate the impact of migraine on migraineurs and their
families and evaluate migraineurs' preference for different treatment
formulations. This study also assessed the prevalence and impact of migraine with
menstruation. METHODS: Participants (n = 1028) from around the world (USA [39%], 
Canada [20%], Europe [37%] and other countries [4%]) completed an online
questionnaire. Of these, 866 were migraineurs and 162 were non-migraineurs living
with/related to migraineurs. Migraineurs were identified based on responses to a 
modified Kiel questionnaire and/or diagnosis of migraine by a doctor. Disability 
was quantified using the Migraine Disability Assessment Scale (MIDAS). RESULTS:
Migraineurs missed more days from family/leisure activities than from work/school
(mean 4.2 vs 2.4 days) in the previous 3 months. On an additional 6.2 days within
the 3-month period, productivity at work/school was reduced by at least half.
Inability and reduced ability (by at least half) to perform household work were
reported on 6.0 and 6.5 days, respectively. Of the women surveyed, 51% identified
menstruation as a trigger for attacks and 6% reported attacks solely with
menstruation (i. e. attacks occurred during menstruation on at least 9 out of 10 
occasions), the latter associated with a higher pain score than other attacks.
Living with or being related to a migraineur decreased nonmigraineurs' ability to
participate in home/family life (moderate/great impact 49%) and social/leisure
activities (moderate/great impact 47%). In a tradeoff analysis, 60% of treatment 
choice was driven by formulation type and 40% was driven by speed of onset. As
migraine disability increased, speed of onset became more important. CONCLUSIONS:
This study confirms the significant burden of migraine on patients and
families/cohabitants, highlighting not only reduced productivity and absences
from work/school, but also time missed from family/social occasions. Many women
identify menstruation to be associated with more painful attacks. Overall, in
terms of treatment choice, formulation type was a more important driver than
speed of onset; however, as migrainerelated disability escalates, speed of onset 
becomes more important. To optimise migraine management, treatment choice should 
be based on individual patients' needs and preferences.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 15265259 [PubMed - indexed for MEDLINE]

2151: Curr Med Res Opin. 2004 Jul;20(7):1125-35.

Identifying patients who require a change in their current acute migraine
treatment: the Migraine Assessment of Current Therapy (Migraine-ACT)
questionnaire.

Dowson AJ, Tepper SJ, Baos V, Baudet F, D'Amico D, Kilminster S.

King's College Headache Service, King's College Hospital, London, UK.

BACKGROUND: Currently available measures of the efficacy of acute migraine
medications are not frequently used in primary care. They may be too burdensome
and complicated for routine use. OBJECTIVES: To design and test a new, easy to
use, 4-item assessment tool, the Migraine Assessment of Current Therapy
(Migraine-ACT) questionnaire for use by clinicians, to quickly evaluate how a
recently prescribed acute medication is working, and to identify patients who
require a change of their current acute treatment. METHODS: A 27-item
Migraine-ACT questionnaire was developed by an international advisory board of
headache specialists. Questions were formulated in four domains: headache impact,
global assessment of relief, consistency of response and emotional response. All 
these are clinically important measures of migraine severity and treatment
outcome. All questions were dichotomous and answered by yes or no. Patients (n = 
185) attending secondary care headache clinics who were diagnosed with migraine
according to International Headache Society criteria entered a multinational,
prospective, observational study to investigate the test-retest reliability and
construct validity of the 27-item Migraine-ACT. Patients completed the
Migraine-ACT on two occasions, separated by a 1-week interval, and test-retest
reliability was assessed by Pearson product moment and Spearman rank measures.
Construct validity was assessed by correlating patients' answers to the 27-item
Migraine-ACT with those to other questionnaires (individual domains and total
scores) conceptually related to it; the Short-Form 36 quality of life
questionnaire (SF-36), the Migraine Disability Assessment (MIDAS) questionnaire
and the Migraine Therapy Assessment Questionnaire (MTAQ). Discriminatory t-tests 
were used to identify the four Migraine-ACT questions (one in each domain) which 
discriminated best between the domains of the SF36, MIDAS, and MTAQ. These four
items constituted the final 4-item Migraine-ACT. RESULTS: The test-retest
reliability of the 27 Migraine-ACT questions ranged from good to excellent, and
correlation coefficients were highly significant for all items. The consistency
of reporting the yes and no answers was also excellent. Correlations of
Migraine-ACT items with SF-36 and MIDAS items and SF-36, MIDAS and MTAQ total
scores indicated that the following were the most discriminating items, in the
respective four domains, and constitute the final Migraine-ACT questionnaire:
Consistency of response: Does your migraine medication work consistently, in the 
majority of your attacks? Global assessment of relief: Does the headache pain
disappear within 2 h? Impact: Are you able to function normally within 2 h?
Emotional response: Are you comfortable enough with your medication to be able to
plan your daily activities? The 4-item Migraine-ACT was shown to be highly
reliable (Spearman/Pearson measure r = 0.82). The individual questions, and the
total 4-item Migraine-ACT score, showed good correlation with items of the SF-36,
MIDAS and MTAQ questionnaires, particularly with the total MTAQ and SF-36 scores.
CONCLUSIONS: The 4-item Migraine-ACT questionnaire is an assessment tool for use 
by primary care physicians to identify patients who require a change in their
current acute migraine treatment. It is brief and simple to complete and score,
and has demonstrated reliability, accuracy and simplicity. Migraine-ACT can
therefore be recommended for everyday clinical use by clinicians.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Validation Studies

PMID: 15265257 [PubMed - indexed for MEDLINE]

2152: Cephalalgia. 2004 Aug;24(8):663-8.

Interictal lack of habituation of mismatch negativity in migraine.

de Tommaso M, Guido M, Libro G, Losito L, Difruscolo O, Sardaro M, Puca FM.

Department of Neurological and Psychiatric Sciences University of Bari, Italy.
m.detommaso@neurol.uniba.it

The aim was to study mismatch negativity features and habituation during the
interictal phase of migraine. In migraine patients, a strong negative correlation
has been found between the initial amplitude of long latency auditory-evoked
potentials and their amplitude increase during subsequent averaging. We studied
12 outpatients with a diagnosis of migraine without aura recorded in a
headache-free interval and 10 gender- and age-matched healthy volunteers not
suffering from any recurrent headache. The experiment consisted of two sequential
blocks of 2000 stimulations, during which 1800 (90%) recordings for standard
tones and 200 (10%) for target tones were selected for averaging. The latency of 
the N1 component was significantly increased in migraine patients in respect of
controls in both the first and second repetitions; the MMN latency was increased 
in the second repetition. In the control group the MMN amplitude decreased on
average by 3.2 +/- 1.4 microV in the second trial, whereas in migraine patients
it showed a slight increase of 0.21 +/- 0.11 microV in the second repetition. The
MMN latency relieved in the second trial was significantly correlated with the
duration of illness in the migraine patients (Spearman correlation coefficient:
0.69; P < 0.05). The increases in N1 latency and MMN latency and amplitude, the
latter correlated with duration of illness, seemed to be due to a reduced
anticipatory effect of stimulus repetition in migraine patients. This suggests
that such hypo-activity of automatic cortical processes, subtending the
discrimination of acoustic stimuli, may be a basic abnormality in migraine,
developing in the course of the disease.

PMID: 15265055 [PubMed - indexed for MEDLINE]

2153: Cephalalgia. 2004 Aug;24(8):657-62.

Differences of anti-nociceptive mechanisms of migraine drugs on the trigeminal
pain processing during and outside acute migraine attacks.

Katsarava Z, Limmroth V, Baykal O, Akguen D, Diener HC, Kaube H.

Institute of Neurology, The National Hospital for Neurology and Neurosurgery,
Queen Square, London, UK. zaza.katsarava@uni-essen.de

The aim of this study was to investigate central anti-nociceptive mechanisms of
i.v. acetylsalicylic acid (ASA) and oral zolmitriptan (ZOL) in migraine patients 
and healthy subjects using the 'nociceptive' blink reflex (nBR). Twenty-eight
migraine patients received ASA (n = 14, 1000 mg i.v) or ZOL (n = 14, 5 mg p.o)
during the acute migraine attack and interictally. Thirty healthy subjects
received either ASA or ZOL vs. placebo using a double blind cross over design.
nBR was recorded in all patients and subjects before, 60 and 90 min after
treatment. ASA and ZOL did not inhibit nBR responses in healthy subjects. Both
ASA and ZOL suppressed nBR responses (ASA by 68%, ZOL by 78%) only during the
acute attack but not interictally. The data suggest, that the anti-nociceptive
effects of migraine drugs on the trigeminal nociceptive processing are different 
during and outside an acute migraine attack.

Publication Types: 
    Clinical Trial
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 15265054 [PubMed - indexed for MEDLINE]

2154: Cephalalgia. 2004 Aug;24(8):639-44.

A randomized, double blind study of the prophylactic effect of hyperbaric oxygen 
therapy on migraine.

Eftedal OS, Lydersen S, Helde G, White L, Brubakk AO, Stovner LJ.

Department of Circulation and Imaging, Norwegian University of Science and
Technology, Trondheim, Norway.

In a double blind, placebo-controlled study to assess the prophylactic effect of 
hyperbaric oxygen therapy on migraine, 40 patients were randomly assigned to a
treatment group receiving three sessions of hyperbaric oxygen, or a control group
receiving three hyperbaric air treatments. The patients were instructed to keep a
standardized migraine diary for eight weeks before and after the treatment.
Thirty-four patients completed the study. Our primary measure of efficacy was the
difference between pre- and post-treatment hours of headache per week. The
results show a nonsignificant reduction in hours of headache for the hyperbaric
oxygen group compared to the control group. Levels of endothelin-1 in venous
blood before and after treatment did not reveal any difference between the
hyperbaric oxygen and control groups. We conclude that the tested protocol does
not show a significant prophylactic effect on migraine and does not influence the
level of endothelin-1 in venous blood.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 15265052 [PubMed - indexed for MEDLINE]

2155: Cephalalgia. 2004 Aug;24(8):623-30.

Platelet-activating factor (PAF) in internal jugular venous blood of migraine
without aura patients assessed during migraine attacks.

Sarchielli P, Alberti A, Coppola F, Baldi A, Gallai B, Floridi A, Floridi A,
Capocchi G, Gallai V.

Department of Neuroscience, Institute of Clinical and Applied Biochemistry,
University of Perugia, Perugia, Italy. neuro.pg@tiscalinet.it

The aim of the study was to verify the production of PAF and the activity of PAF 
acetyl-hydrolase (PAF-AH), the enzyme involved in the catabolism of this
phospholipid mediator, in migraine attacks. Their levels were determined during
migraine crises in serial samples of internal jugular venous blood taken from
five migraine patients without aura, who were admitted to the hospital during the
crises. Internal jugular venous blood samples were taken immediately after
catheter insertion at 1, 2, and 4 h after attack onset, and within 2 h from its
cessation. PAF was purified by high-performance liquid chromatography (HPLC) and 
determined by radioimmunoassay method. The enzymatic activity of PAF-AH was
measured by reverse-phase HPLC, based on the derivatization with
7-diethylaminocoumarin-3-carbonylazide. In the internal jugular venous blood of
migraine patients without aura (MO), an increase was observed in PAF levels,
which was already evident at the time of catheter insertion (885.6 +/- 82.8) and 
at the first hour (868.4 +/- 65.24) (ANOVA: P < 0.0001). PAF levels remained
elevated through the second (746.8 +/- 82.95), fourth (700.6 +/- 34.93) and sixth
hours (644.4 +/- 42.85), and then decreased at the end of the attack, reaching
levels significantly lower than those measured at the time of catheter insertion 
(565.5 +/- 38.34). The activity of PAF-AH showed an opposite trend with higher
values at the first hour and significantly lower values at the second and fourth 
hours from the beginning of the migraine attack (ANOVA: P < 0.02). The increased 
production of PAF may account for persistent platelet activation during migraine 
crises, even in the presence of an increased production of nitric oxide (NO)
end-products which, on the other hand, should instead intervene in counteracting 
and limiting platelet activation. Potential sources of PAF production are the
endothelial cells from cerebral vessels, stimulated by trigeminal neuropeptides, 
platelets themselves, and mast cells, as suggested by the neurogenic inflammation
model.

Publication Types: 
    Comparative Study

PMID: 15265050 [PubMed - indexed for MEDLINE]

2156: J Am Acad Nurse Pract. 2004 Jun;16(6):251-6.

Evidenced-based use of botanicals, minerals, and vitamins in the prophylactic
treatment of migraines.

Rios J, Passe MM.

University of Texas at Austin School of Nursing, USA. janie_rios01@yahoo.com

PURPOSE: To analyze evidence-based information about alternative prophylactic
pharmacological migraine treatments utilizing feverfew, butter-bur, magnesium,
and riboflavin and to discuss the mechanism of action, dosage recommendations,
side effects, and contraindications for each treatment. DATA SOURCES: Data
obtained via electronic databases and professional medical references.
CONCLUSIONS: Current clinical data support the use of fever-few, butterbur,
magnesium, and riboflavin in migraine prophylaxis; however, studies are limited
but promising regarding the participants' perceived relief. Studies with rigorous
methodologies and larger sample sizes are needed to further support the safe and 
effective use of these treatments. IMPLICATIONS FOR PRACTICE: With increased
patient access to information regarding alternative migraine treatments, nurse
practitioners (NPs) and other health care providers must be knowledgeable about
evidence-based data regarding these alternative treatments to appropriately offer
safe patient care.

Publication Types: 
    Review

PMID: 15264611 [PubMed - indexed for MEDLINE]

2157: Neurobiol Dis. 2004 Aug;16(3):500-5.

Hypothalamic activation after stimulation of the superior sagittal sinus in the
cat: a Fos study.

Benjamin L, Levy MJ, Lasalandra MP, Knight YE, Akerman S, Classey JD, Goadsby PJ.

Headache Group, Institute of Neurology and The National Hospital for Neurology
and Neurosurgery, London WC1N 3BG, UK.

Clinical observations, particularly of the premonitory phase of migraine, suggest
the involvement of the hypothalamus in the earliest phases of an attack.
Stimulation of the superior sagittal sinus (SSS) in humans produces head pain and
permits study of the activated trigeminovascular system in experimental settings.
The distribution of neurons expressing the protein product (Fos) of the c-fos
immediate early gene was examined in the hypothalamus of anaesthetised
(alpha-chloralose) cats. Animals were studied after either 2-h stimulation of the
SSS or sham stimulation. Fos protein was detected using immunohistochemistry, and
positive neurons were plotted onto standardised templates and counted by a
blinded observer. In response to electrical stimulation of the superior sagittal 
sinus, we found significant activation of the supra-optic nucleus (SON) rising
from 3 (0-13) (median, 95% confidence interval) to 53 (31-78; P = 0.005)
fos-positive cells. In the posterior hypothalamic area (Hp), fos-positive cells
rose from 4 (0-14) to 35 (17-45; P = 0.015) Taken together with other
physiological studies, the data are consistent with a role for hypothalamic
structures in the modulation of trigeminovascular nociceptive afferent
information, and thus for a role in headache.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 15262261 [PubMed - indexed for MEDLINE]

2158: Clin Neurophysiol. 2004 Aug;115(8):1857-62.

Somatosensory evoked high-frequency oscillations in migraine patients.

Sakuma K, Takeshima T, Ishizaki K, Nakashima K.

Section of Environment and Health Science, Department of Biological Regulation,
School of Health Sciences, Faculty of Medicine, Tottori University, 86
Nishimachi, Yonago, Japan. neurol@smile.ocn.ne.jp

OBJECTIVE: To explore additional evidence concerning generators of somatosensory 
evoked high-frequency oscillations (HFOs). METHODS: We recorded HFOs in migraine 
patients. Subjects were 19 healthy normal subjects and 19 migraineurs. Electrical
stimuli were delivered alternately to the right and left median nerves at their
wrists. EEGs were recorded from C3'-Fz, C4'-Fz, Erb1-Erb2, Erb2-Erb1 and Cv6-Fz
using a 0.3 Hz low-frequency filter and a 3000 Hz high-frequency filter.
Responses to 5000 stimuli were averaged. For separation of HFOs from underlying
N20, the digitized wide-band signals were digitally bandpass filtered (400-800
Hz) and averaged. RESULTS: There were no significant differences in peak
latencies and amplitudes for N9, N13, N20 and P25 components between normal
controls and migraineurs. Root-mean-square amplitudes for HFOs in migraineurs
were significantly diminished compared with normal controls. CONCLUSIONS: A
diminished inhibitory mechanism in the somatosensory system may exist in
migraineurs. It remains to determine what cell populations contribute to
generating HFOs. SIGNIFICANCE: This indicates that there is a dysfunction in
cortical information processing in the somatosensory cortex of migraineurs.

Publication Types: 
    Comparative Study

PMID: 15261864 [PubMed - indexed for MEDLINE]

2159: Eur J Med Res. 2004 May 28;9(5):279-81.

Questionning aggravation of the headache during migraine attacks.

Selekler HM, Kavuk I, Agelink MW, Komsuoglu S.

University of Kocaeli, Medical Faculty, Department of Neurology, Derince 41900,
Kocaeli, Turkey. macitselekler@hotmail.com

While questioning patients about aggravation of the headache by routine physical 
activity, sensitivity of walking stairs and lifting a heavy object versus head
movements and bending down in terms of aggravating the headache was aimed to be
determined. Eighty-one migraine patients were questioned about the aggravation of
their headaches with two sets of question groups. (The first set: walking stairs 
and lifting a heavy object; The second set: rotating the head side to side and
bending down). 38 and 72 patients gave clear answers to the first and second set 
of questions respectively. Clear information was obtained from the first and
second group of questions by 38 and 72 patients respectively. Some patients with 
severe migraine headaches may prevent themselves from rigorous daily activities
while they could bend or make sudden head movements inadvertently during the
attack. We think that aggravation of the headache due to head movements or
bending down during migraine attacks seems more sensitive than walking stairs or 
lifting a heavy object to migraine patients.

Publication Types: 
    Comparative Study

PMID: 15257883 [PubMed - indexed for MEDLINE]

2160: Eur J Neurol. 2004 Jul;11(7):475-7.

High-dose riboflavin treatment is efficacious in migraine prophylaxis: an open
study in a tertiary care centre.

Boehnke C, Reuter U, Flach U, Schuh-Hofer S, Einhäupl KM, Arnold G.

Department of Neurology, Charité, Humboldt University of Berlin, Berlin, Germany.

The aim of this study was to investigate the efficacy of riboflavin for the
prevention of migraine. An open label study was performed in a specialized
outpatient clinic. Patients received 400 mg riboflavin capsules per day. Headache
frequency, duration, intensity and the use of abortive drugs were recorded at
baseline and 3 and 6 months after treatment. Headache frequency was significantly
reduced from 4 days/month at baseline to 2 days/month after 3 and 6 months (P <
0.05). The use of abortive drugs decreased from 7 units/month to 4.5 units/month 
after 3 and 6 months of treatment (P < 0.05). In contrast, headache hours and
headache intensity did not change significantly. We could demonstrate a
significant reduction of headache frequency following riboflavin treatment. In
addition, the number of abortive anti-migraine tablets was reduced. In line with 
previous studies our findings show that riboflavin is a safe and well-tolerated
alternative in migraine prophylaxis.

Publication Types: 
    Clinical Trial

PMID: 15257686 [PubMed - indexed for MEDLINE]

2161: Hypertens Res. 2004 Jun;27(6):441-6.

Efficacy of candesartan in the treatment of migraine in hypertensive patients.

Owada K.

Department of Internal Medicine, Aoyama Hospital, Tokyo, Japan.
1730nuro@tmd.ac.jp

Triptans are usually administered for migraine, but cannot be given to patients
with malfunctioning cardiac or cerebral vascular systems, which commonly
accompany hypertension. This article focuses on 8 cases in which treatment with
candesartan was successful in reducing both the incidence and severity of
headache in hypertensive patients with migraine. The cases reported in this
article showed a mean improvement in Migraine Disability Assessment score from
29.4 to 9 points and in blood pressure from 154.9/90.4 to 129.5/81.9mmHg,
suggesting that candesartan is an extremely attractive option for the treatment
of migraine. Although recent studies have reported the efficacy of candesartan
for treating migraine, there has been no description of its potential advantages 
over other prophylactic drugs. The present study included patients who could not 
tolerate triptans for whom triptans were contraindicated, several patients for
whom other migraine prophylactic drugs showed little or no effect, and one
patient for whom candesartan was prescribed initially for hypertension, but was
also found to be therapeutic for migraines. Thus candesartan is considered to be 
a unique, attractive choice of prophylactic agent for migraine complicated by
hypertension.

Publication Types: 
    Case Reports

PMID: 15253110 [PubMed - indexed for MEDLINE]

2162: Epileptic Disord. 2004 Jun;6(2):57-75.

Antiepileptic drugs: indications other than epilepsy.

Spina E, Perugi G.

Section of Pharmacology, Department of Clinical and Experimental Medicine and
Pharmacology, University of Messina, Italy. espina@unime.it

Antiepileptic drugs (AEDs) are increasingly used for the treatment of several
non-epileptic neurological conditions and psychiatric disorders. Most of the
information available on the use of these agents in clinical disorders outside
epilepsy is from case series, uncontrolled studies or small randomised clinical
trials, and their apparent efficacy requires confirmation through well designed, 
large, phase III trials. With regard to neurological conditions other than
epilepsy, experimental evidence for the efficacy of AEDs is only available for
the treatment of patients with trigeminal neuralgia, neuropathic pain syndromes, 
migraine and essential tremor. Carbamazepine is commonly prescribed as first-line
therapy for patients with trigeminal neuralgia. Gabapentin has been recently
marketed for the management of neuropathic pain syndromes, particularly diabetic 
neuropathy and postherpetic neuralgia. Valproic acid (sodium valproate), in the
form of divalproex sodium, is approved for migraine prophylaxis. Primidone can be
considered a valuable option for the treatment of essential tremor. AEDs are also
used to treat psychiatric conditions, in particular bipolar disorder. So far, the
most commonly utilized AEDs in the treatment of this disorder have been
carbamazepine and valproic acid, which have showed an antimanic efficacy and a
probable long-term, mood-stabilizing effect in many bipolar patients, including
those refractory or intolerant to lithium. The availability of a new generation
of AEDs has broadened the therapeutic options in bipolar disorder. Lamotrigine,
oxcarbazepine, gabapentin and topiramate appear to be promising in the treatment 
of refractory bipolar disorder, as a monotherapy as well as in combination with
traditional mood stabilizers. In addition, newer AEDs appear to have a more
favourable tolerability and drug interaction profile as compared to older
compounds, so thus improving compliance to treatment. Copyright John Libbey
Eurotext 2003.

Publication Types: 
    Review

PMID: 15246950 [PubMed - indexed for MEDLINE]

2163: Clin Ter. 2004 Feb-Mar;155(2-3):79-87.

Antiepileptic drugs in migraine prophylaxis: state of the art.

Capuano A, Vollono C, Mei D, Pierguidi L, Ferraro D, Di Trapani G.

Neurology Institute, Headache Center, Università Cattolica Sacro Cuore Roma,
Italia.

Antiepileptic drugs have proven their efficacy in the prophylactic treatment of
migraine. Our study comprises a clinical trial that examines the efficacy of
gabapentin and topiramate and a description of the pharmacologic characteristics 
and the efficacy of tiagabine, lamotrigine, levetiracetam and zonisamide.
Antiepileptic drugs have multiple modes of action which can explain their
efficacy in reducing neuronal excitability which is proven in epilepsy and
postulated in migraine. The relationship between epilepsy and migraine has, in
fact, been much debated but never convincingly proven. Antiepileptic drugs could 
be useful in migraine prophylaxis as some of these have determined a reduction in
the monthly frequency and intensity of crises in subjects suffering from migraine
with and without aura. These are the aims that have been proposed by the U.S.
Headache Consortium Evidence-Based Guidelines. Further double-blind
placebo-controlled studies are necessary in order to assess their safety and
efficacy.

Publication Types: 
    Review

PMID: 15244112 [PubMed - indexed for MEDLINE]

2164: Eur Neurol. 2004;52(1):50-6. Epub 2004 Jul 5.

Efficacy of 1,000 mg effervescent acetylsalicylic acid and sumatriptan in
treating associated migraine symptoms.

Diener HC, Eikermann A, Gessner U, Göbel H, Haag G, Lange R, May A,
Müller-Schwefe G, Voelker M.

Department of Neurology, University of Essen, Hufelandstrasse 55, DE-45147 Essen,
Germany. h.diener@uni-essen.de

Recently a new effervescent acetylsalicylic acid (ASA) tablet with high buffering
capacity has been developed. In this double-blind, 3-arm, multicenter,
parallel-group study, 433 patients were treated either with 1,000 mg effervescent
ASA or 50 mg encapsulated sumatriptan or placebo. The primary endpoint was the
percentage of patients with complete remission of the 3 accompanying symptoms
nausea, photophobia and phonophobia within 2 h after intake of the study drug.
43.8% of patients treated with ASA, 43.7% of patients treated with sumatriptan
and 30.9% of patients treated with placebo showed complete remission of all 3
accompanying symptoms (p < 0.05 for ASA and sumatriptan vs. placebo). Both active
treatments were superior to placebo regarding the individual symptoms photophobia
and phonophobia, but not for nausea. The percentage of patients with reduction in
headache severity from moderate or severe to mild or no pain (secondary
objective) was 49.3% for ASA, 48.8% for sumatriptan and 32.9% for placebo. All
active treatments were superior to placebo (p < 0.05). 25.3, 24.4 and 14.5% of
patients treated with ASA, sumatriptan or placebo were pain free at 2 h.
Drug-related adverse events were reported in 3.9, 4.7 and 6.7% of patients
treated with placebo, ASA or sumatriptan. The study showed that administration of
effervescent ASA leads to remission of the migraine symptoms nausea, photophobia 
and phonophobia, reduces migraine headache and is comparable to sumatriptan.
Copyright 2004 S. Karger AG, Basel

Publication Types: 
    Clinical Trial
    Comparative Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 15240983 [PubMed - indexed for MEDLINE]

2165: Br J Pharmacol. 2004 Aug;142(7):1053-4. Epub 2004 Jul 5.

Comment on:
    Br J Pharmacol. 2004 Aug;142(7):1171-81.

Calcitonin gene-related peptide (CGRP) antagonists: blockers of neuronal
transmission in migraine.

Brain SD.

Centre for Cardiovascular Biology and Medicine, King's College, Guy's Campus,
London SE1 1UL. sue.brain@kcl.ac.uk

The neuropeptide calcitonin gene-related peptide (CGRP) is a potent vasodilator
that is contained in and released from sensory nerves. CGRP has been implicated
in migraine, and the nonpeptide CGRP antagonist BIBN4096BS has been shown to be
effective in clinical trials in migraine. To date, it has been largely assumed
that the CGRP antagonist is effective due to its ability to block vasodilator
activity. Goadsby and co-workers present data that now suggest that CGRP
antagonists may also block neuronal transmission in migraine. Copyright 2004
Nature Publishing Group

Publication Types: 
    Comment

PMID: 15237096 [PubMed - indexed for MEDLINE]

2166: Laryngoscope. 2004 Jul;114(7):1305-9.

Vestibular evoked myogenic potentials in basilar artery migraine.

Liao LJ, Young YH.

Department of Otolaryngology, National Taiwan University Hospital and National
Taiwan University College of Medicine, Taipei, Taiwan.

OBJECTIVES/HYPOTHESIS: Because the sacculocollic reflex is a descending pathway
passing through the territory of basilar artery, the aim of the study was to
investigate whether hypoperfusion affects this pathway by applying vestibular
evoked myogenic potential (VEMP) testing in patients with basilar artery
migraine. STUDY DESIGN: A prospective study from May 2000 to April 2002. METHODS:
Twenty patients were diagnosed as having basilar artery migraine according to the
criteria of the International Headache Society and literature. Eight were male
and 12 were female patients, and their ages ranged from 9 to 48 years (mean age, 
40 y). Each patient underwent a battery of audio-vestibular tests. RESULTS:
Electronystagmography disclosed abnormal eye tracking test in six patients (30%),
and there were abnormal optokinetic nystagmus test results in nine patients
(45%). Caloric test revealed canal paresis in seven patients, directional
preponderance in four patients, and normal responses in nine patients (45%).
Vestibular evoked myogenic potential testing disclosed absent vestibular evoked
myogenic potentials in seven patients and delayed vestibular evoked myogenic
potentials in two patients, with one patient showing absent vestibular evoked
myogenic potentials on one side and delayed vestibular evoked myogenic potentials
on the other side. The remaining 10 patients (50%) had bilateral normal
vestibular evoked myogenic potentials. Five patients had preserved both caloric
and VEMP test responses, six patients displayed absent caloric and VEMP test
responses, and the remaining nine patients had either abnormal caloric test
responses or abnormal vestibular evoked myogenic potentials, exhibiting a
nonsignificant relationship between caloric test responses and vestibular evoked 
myogenic potentials. Relief of headache and vertigo was achieved after 3 months
of medication. Ten asymptomatic patients with either absent or delayed vestibular
evoked myogenic potentials before treatment underwent follow-up VEMP test, and
nine patients (90%) displayed normal vestibular evoked myogenic potentials
bilaterally. CONCLUSION: Vestibular evoked myogenic potential testing evaluates
the sacculocollic reflex, which descends through the lower brainstem. Some
patients with basilar artery migraine have absent or delayed vestibular evoked
myogenic potentials, presumably because the descending pathway from the saccule
through the brainstem to cranial nerve XI is interrupted, which is attributed to 
hypoperfusion in the territory of the basilar artery. After 3 months of
medication, recovery of normal vestibular evoked myogenic potentials in an
asymptomatic patient indicates reversible ischemia in the territory of the
basilar artery.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 15235366 [PubMed - indexed for MEDLINE]

2167: Curr Pain Headache Rep. 2004 Aug;8(4):310-4.

Vestibular migraine.

Troost BT.

Department of Neurology, Wake Forest University Health Sciences Center, Medical
Center Boulevard, Winston-Salem, NC 27157, USA. ttroost@wfubmc.edu

Vestibular symptoms such as vertigo and dizziness are quite common in migraine.
There is no specific category in the new International Headache Society
Classification for vestibular migraine. However, given the symptomatology often
described, it would fit best under basilar-type migraine, even though by
definition monosymptomatic attacks with rotational vertigo for a few seconds to
minutes do not strictly fit the criteria. Vestibular migraine must be regarded as
a migraine equivalent because it is a prominent symptom in many migraineurs.

Publication Types: 
    Review

PMID: 15228892 [PubMed - indexed for MEDLINE]

2168: Curr Pain Headache Rep. 2004 Aug;8(4):306-9.

Ophthalmoplegic migraine.

Levin M, Ward TN.

Section of Neurology, Dartmouth Hitchcock Medical Center, One Medical Center
Drive, Lebanon, NH 03756, USA. Morris.Levin@hitchcock.org

Ophthalmoplegic migraine is a rare condition, previously thought to represent a
variant of migraine. Recent observations regarding its usual clinical
presentation and common magnetic resonance imaging findings have given rise to
speculation that this illness is more likely to represent an inflammatory cranial
neuropathy. The recent revision of the International Headache Classification has 
reclassified ophthalmoplegic migraine from a subtype of migraine to the category 
of neuralgia. In this article, potential pathophysiological mechanisms are
discussed. The typical clinical presentation of ophthalmoplegic migraine
generally involves transient migraine-like headache accompanied by often
long-lasting oculomotor, abducens or, rarely, trochlear neuropathy with diplopia 
and (if oculomotor nerve is involved) pupillary abnormalities and ptosis.
Ophthalmoplegic migraine generally occurs in children, but a number of adult
cases have been reported. Prognosis is good because symptoms almost always
resolve, but, after several episodes, some deficits may persist. Differential
diagnosis is rather large, although most other possible causes of ophthalmoplegia
and headache have distinctive presentations or can be excluded with fairly
straightforward diagnostic testing. Optimal prophylactic and acute treatment is
still unclear, but migraine prophylactic medications such as b blockers and
calcium channel blockers have been proposed. Steroids have been used with mixed
results.

Publication Types: 
    Review

PMID: 15228891 [PubMed - indexed for MEDLINE]

2169: J Manag Care Pharm. 2004 May-Jun;10(3):259-65.

Comment in:
    J Manag Care Pharm. 2004 May-Jun;10(3):266, 268-9.

A comparison of the cost-effectiveness of almotriptan and sumatriptan in the
treatment of acute migraine using a composite efficacy/tolerability end point.

Williams P, Reeder CE.

PAREXEL International, The Quays, 101-105 Oxford Rd., Uxbridge, Middlesex, UB8
1LZ, UK. paul.williams@parexel.com

OBJECTIVE: To use a composite efficacy/tolerability end point to compare the
cost-effectiveness, from the perspective of a U.S. health care payer, of
almotriptan and sumatriptan in the treatment of an acute migraine attack.
METHODS: The composite end point.Sustained pain free and No Adverse Events.
(SNAE) was created from the sustained pain free and adverse event rates obtained 
in a meta-analysis of 53 placebo-controlled trials of oral triptans. The total
direct cost of treating a single migraine attack was calculated from published
sources. RESULTS: In the base-case analysis, the average cost-effectiveness
ratios (CERs) were 82 US dollars , 133 US dollars , and 138 US dollars (per
attack at which SNAE is achieved, 2004 prices) for almotriptan 12.5 mg,
sumatriptan 50 mg, and sumatriptan 100 mg, respectively; the incremental CERs for
almotriptan 12.5 mg were 12 US dollars and 16 US dollars (compared with
sumatriptan 50 mg and sumatriptan 100 mg, respectively) per incremental attack at
which SNAE is achieved. Sensitivity analyses were conducted to explore the impact
of (1) relaxing the base-case assumptions (independence of efficacy and
tolerability, uniform apportionment of health service use costs across attacks,
number of tablets used to treat 1 attack); (2) varying input costs; and (3)
uncertainty in the efficacy and tolerability estimates from the meta-analysis. In
all of these sensitivity analyses, almotriptan 12.5 mg remained cost effective
compared with sumatriptan 50 mg and 100 mg. CONCLUSION: Almotriptan was
economically superior to sumatriptan in the treatment of a migraine attack.

Publication Types: 
    Comparative Study
    Meta-Analysis
    Research Support, Non-U.S. Gov't

PMID: 15228377 [PubMed - indexed for MEDLINE]

2170: BMC Neurol. 2004 Jun 28;4:10.

Rizatriptan versus rizatriptan plus rofecoxib versus rizatriptan plus tolfenamic 
acid in the acute treatment of migraine.

Krymchantowski AV, Bigal ME.

Department of Neurology, Universidade Federal Fluminense, Niterói, Brazil.
abouchkrym@globo.com

BACKGROUND: Rizatriptan is an effective and fast acting drug for the acute
treatment of migraine. Some nonsteroidal anti-inflammatory drugs (NSAID) have
also demonstrated efficacy in treating migraine attacks. There is evidence that
the combination of a triptan and a NSAID decreases migraine recurrence in
clinical practice. The primary aim of this randomized open label study was to
assess the recurrence rates in migraine sufferers acutely treated with
rizatriptan (RI) alone vs. rizatriptan plus a COX-2 enzyme inhibitor (rofecoxib, 
RO) vs. rizatriptan plus a traditional NSAID (tolfenamic acid, TO). We were also 
interested in comparing the efficacy rates within these three groups. METHODS: We
assessed 45 patients from a headache clinic in Rio de Janeiro (35 women and 10
men, ages 18 to 65 years, mean 37 years). Patients with IHS migraine were
randomized to one out of 3 groups, where they had to treat 6 consecutive moderate
or severe attacks in counterbalanced order. In group 1, patients treated the
first two attacks with 10 mg RI, the third and fourth attacks with RI + 50 mg RO 
and the last attacks with RI + 200 mg of TA. In group 2, we began with RI + TA,
followed by RI, and RI + RO. Group 3 treated in the following order: RI + RO, RI 
+ TA, RI alone. The presence of headache, nausea and photophobia at 1, 2 and 4
hours, as well as recurrence and side effects were compared. RESULTS: A total of 
33 patients finished the study, treating 184 attacks. The pain-free rates at 1
hour were: RI: 15.5%; RI + RO: 22.6%; RI + TA: 20.3%(NS). Pain-free rates at 2 h 
were: RI: 37.9%; RI + RO: 62.9%, and RI + TA: 40.6% (p = 0.008 for RI vs. RI +
RO; p = 0.007 for RI + RO vs. RI + TA, NS for RI vs RI + TA). At 4 h, pain-free
rates were: RI: 69%; RI + RO: 82.3%; RI + TA: 78.1% (NS for all comparisons). The
combination of RI + RO was superior to RI and to RI + TA in regard of the absence
of nausea and photophobia at 4 hours. Recurrence (after being pain-free at 2 h)
was observed in 50% of patients treated with RI, in 15,4% of those treated with
RI + RO, and in 7,7% of those treated with RI + TA. CONCLUSIONS: Despite the
methodological limitations of this study, the combination of RI and RO revealed a
higher response rate at 2 hours. Recurrence was also clearly decreased with both 
combinations in relation to the use of RI alone. Controlled studies are necessary
to provide additional evidence.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial

PMID: 15222892 [PubMed - indexed for MEDLINE]

2171: Dermatol Clin. 2004 Apr;22(2):167-75.

Botulinum neurotoxin for the treatment of migraine and other primary headache
disorders.

Blumenfeld AM, Dodick DW, Silberstein SD.

Department of Neurology, Kaiser Permanente, 4405 Vandever Avenue, San Diego, CA
92120, USA. Andrew.m.Blumenfeld@kp.org

Clinical data and experience to date have demonstrated that BoNT-A is an
effective and well-tolerated therapy for the prevention of migraine and other
headache disorders. It has a long duration of action that may last over 4 months 
with no systemic or serious AEs. Several issues remain to be defined, however,
including dosing, location, and number of injections; optimal dilution of BoNT-A;
specific headache types that respond best to BoNT-A; and long-term efficacy and
safety. Data from ongoing well-designed trials that include a larger patient
population investigating these issues may confirm a role for BoNT-A as a
first-line agent for migraine prevention. Neurotoxin therapy is part of a broader
headache management approach. Because the injection techniques for headache are
unique and vary depending on the primary headache disorder being treated and the 
location and pattern of pain referral, the use of BoNT-A for headache is not
simply an extension of its use for cosmesis. The use of BoNT-A in the overall
management of primary headache disorders should be reserved for medical
practitioners who not only have experience with BoNT-A injections, but possess
the expertise in the diagnosis and management of complex headache disorders.
Educating patients and addressing headache triggers and optimizing acute
treatment improve the outcome of any preventive program.

Publication Types: 
    Review

PMID: 15222577 [PubMed - indexed for MEDLINE]

2172: Arch Neurol. 2004 Jun;61(6):926-8.

No mutations in CACNA1A and ATP1A2 in probands with common types of migraine.

Jen JC, Kim GW, Dudding KA, Baloh RW.

Department of Neurology, University of California, Los Angeles, Los Angeles, CA
90095, USA. jjen@ucla.edu

BACKGROUND: Mutations in CACNA1A, encoding a neuronal calcium channel subunit,
and ATP1A2, encoding a catalytic subunit of a sodium-potassium-ATPase, have been 
found in some families with dominantly inherited hemiplegic migraine. OBJECTIVE: 
To determine the prevalence of mutations in these genes in individuals with
different migraine syndromes. DESIGN: Prospective screening study. SETTING:
University outpatient neurology clinic.Subjects Probands of 19 families with
hemiplegic migraine, 7 with basilar migraine, 25 with migraine without aura, and 
18 with migraine with aura, as well as 40 unaffected relatives of probands.
INTERVENTIONS: All known exons and flanking introns of CACNA1A and ATP1A2 were
subjected to denaturing high-performance liquid chromatography analysis of
polymerase chain reaction-amplified genomic DNA. Exons with atypical elution
patterns were sequenced by standard techniques. MAIN OUTCOME MEASURES: Presence
of mutations in CACNA1A and ATP1A2. RESULTS: A single mutation (T666M) was found 
in CACNA1A in a patient with hemiplegic migraine and ataxia. No other mutation
was identified in either gene. The frequency of a previously reported intronic
insertion in ATP1A2 was not significantly different between patients with
migraine and control subjects. CONCLUSION: These 2 genes are not associated with 
more common migraine syndromes and are not the most common hemiplegic migraine
genes.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 15210532 [PubMed - indexed for MEDLINE]

2173: Headache. 2004 Jul-Aug;44(7):678-83.

Disability in chronic migraine patients with medication overuse: treatment
effects at 1-year follow-up.

Grazzi L, Andrasik F, D'Amico D, Usai S, Kass S, Bussone G.

Neurological Institute "C.Besta," Milan, Italy.

OBJECTIVE: To determine (1) the clinical course of a sample of chronic migraine
patients with drug overuse 6 and 12 months following in-patient treatment and (2)
whether functional impairment, assessed by the Migraine Disability Assessment
(MIDAS) questionnaire, improved upon treatment. BACKGROUND: Patients with chronic
migraine and medication overuse are particularly difficult to treat (prophylactic
medications that otherwise are effective become ineffective; discontinuation of
the offending medication can lead to withdrawal headache; physical and emotional 
dependence can be present, as well as increased psychological involvement;
initial treatment gains can be difficult to maintain). METHODS: Of the 106
patients meeting criteria for chronic migraine with medication overuse, 84 went
on to complete a structured in-patient treatment, consisting of medication
withdrawal and then prophylactic treatment. RESULTS: As a group, the patients
were improved at both 6- and 12-month follow-up, with respect to two headache
parameters (frequency and medication use) and three measures of functional impact
extracted from the MIDAS questionnaire (Total Score, Headache Frequency, and
Headache Intensity). CONCLUSION: Chronic migraine accompanied with medication
overuse led to the considerable disability prior to treatment. However, notable
improvement occurred coincident with the treatment. This suggests that successful
treatment has more wide-ranging positive benefits beyond mere symptom reduction. 
To our knowledge, this is the first investigation where the MIDAS questionnaire
has been used prospectively as an outcome measure in patients with chronic
migraine and medication overuse to assess disability subsequent to a
semi-standardized treatment program.

Publication Types: 
    Comparative Study

PMID: 15209690 [PubMed - indexed for MEDLINE]

2174: Headache. 2004 Jul-Aug;44(7):674-7.

Study of mitochondrial DNA mutations in patients with migraine with prolonged
aura.

Rozen TD, Shanske S, Otaegui D, Lu J, Young WB, Bradley K, DiMauro S, Silberstein
SD.

Department of Neurology, Michigan Head-Pain and Neurological Institute, Ann Arbor
48104, USA.

Ten patients with migraine with prolonged aura were studied for the presence of
mitochondrial DNA point mutations utilizing DNA isolated from blood and hair
samples. We analyzed for nine point mutations reported in patients with MELAS
(A3243G, C3256T, T3271C, T3291C, A5814G, T8356C, T9957C, G13513A, and A13514G)
and three secondary LHON mutations (T4216C, A4917G, and G13708A). None of the
patients tested had any of these mutations in mitochondrial DNA. However, one
patient was found to have a tRNA(Gln) A4336G mitochondrial DNA variant. From this
study it appears that migraine with prolonged aura is not an oligosymptomatic
form of MELAS and is not related to secondary LHON mutations. The significance of
the tRNA A4336G variant is unknown.

PMID: 15209689 [PubMed - indexed for MEDLINE]

2175: Headache. 2004 Jul-Aug;44(7):669-73.

Early treatment of migraine with rizatriptan: a placebo-controlled study.

Mathew NT, Kailasam J, Meadors L.

Houston Headache Clinic, Texas 77004, USA.

OBJECTIVE: To evaluate the efficacy of rizatriptan when administered early during
a migraine attack. BACKGROUND: Several studies indicate that triptans are more
efficacious when administered early during a migraine attack, when the pain is
still mild. METHODS: One hundred and twelve rizatriptan-naïve patients aged 20 to
64 years with a history of migraine with or without aura that progressively
worsened when left untreated were instructed to treat a total of three migraine
attacks with either rizatriptan 10 mg or placebo as early as possible during each
attack. Seventy-four patients (68 women and 6 men) were assigned to use the
active drug and 38 (35 women and 3 men) to placebo. The primary efficacy endpoint
was pain-free response at 2 hours after administration of the study drug.
Secondary efficacy measures were pain-free response at 1 hour and sustained
pain-free response lasting between 2 and 24 hours. RESULTS: A total of 216
attacks were treated in the rizatriptan group and 109 in the placebo group.
Pain-free response at 2 hours after early treatment was noted in 151 (70%) of
attacks in the rizatriptan group and in 24 (22%) in the placebo group (P < .01). 
Pain-free response at 1 hour occurred in 97 (45%) and 9 (8%) attacks,
respectively (P < .01). When the attacks were categorized by headache severity at
the time of treatment, the pain-free response at 2 hours was higher for mild
attacks than for moderate or severe attacks (P < .01). Sustained pain-free
response after treatment was significantly higher for attacks treated with
rizatriptan (60%) than for those treated with placebo (17%) (P < .001). Adverse
events were observed in 62 patients in the rizatriptan group and 15 in the
placebo group. Only 1 patient taking rizatriptan discontinued the study because
of adverse events, and no serious adverse events were reported. CONCLUSIONS:
Rizatriptan is significantly more likely than placebo to produce a pain-free
response within 2 hours when the drug is administered early in the migraine
attack, when pain is mild rather than moderate or severe.

Publication Types: 
    Clinical Trial
    Controlled Clinical Trial
    Research Support, Non-U.S. Gov't

PMID: 15209688 [PubMed - indexed for MEDLINE]

2176: Headache. 2004 Jul-Aug;44(7):661-8.

Patterns of use of triptans and reasons for switching them in a tertiary care
migraine population.

Sheftell FD, Feleppa M, Tepper SJ, Volcy M, Rapoport AM, Bigal ME.

Department of Psychiatry, New York Medical College, NY, USA.

OBJECTIVE: To assess the reasons for switching triptans within migraine patients 
presenting to a specialty clinic. DESIGN AND METHODS: We reviewed data of
migraineurs who (1) were currently using a triptan as acute treatment medication 
for migraine, and (2) had previously used at least one other triptan, or a
different triptan formulation. All subjects were followed for at least 1 year.
For every triptan/formulation used, the reasons for discontinuation were
obtained. RESULTS: Our sample consisted of 386 patients, 339 of whom (87.8%) were
females. Sumatriptan was first used by 349 (90.4%); zolmitriptan, by 238 (61.5%);
rizatriptan, by 195 (50.5%); naratriptan, by 137 (35.4%); and almotriptan, by 31 
(8.0%). Almotriptan was excluded from this analysis because of our small sample. 
We found significant differences among those who wanted to try another triptan to
see if it would be better in those who first used sumatriptan 25 mg, compared to 
those first using sumatriptan 50 mg (P = .01), sumatriptan 100 mg (P < .001),
sumatriptan nasal spray (NS) (P < .001), sumatriptan subcutaneous (SC) (P <
.001), zolmitriptan 5 mg (P < .001), rizatriptan 10 mg (P < .001), and
naratriptan (P = .001). Patients using rizatriptan, sumatriptan NS, and
sumatriptan SC had significantly lower rates of reporting this answer. Subjects
first using naratriptan were less likely to report recurrence than those using
sumatriptan 25 mg (P = .004), sumatriptan 50 mg (P = .0005), sumatriptan 100 mg
(P = .003), zolmitriptan (P = .02), and rizatriptan (P = .006). Incomplete relief
was more frequently reported by those first using sumatriptan 25 mg and
naratriptan. Inconsistency was a reason for switching in those initially using
sumatriptan NS, sumatriptan 25 mg, and naratriptan and less frequently reported
in those using zolmitriptan and sumatriptan SC. Side effects were major factors
for those first using sumatriptan 100 mg, NS, and SC, and less for those using
naratriptan and sumatriptan 25 mg. From those subjects that initially used
sumatriptan SC and were switched to a different triptan or formulation, 19.5%
returned to sumatriptan SC; for the other triptans/formulations, the percentages 
were: sumatriptan 25 mg, 7.8%; sumatriptan 50 mg or 100 mg, 42.3%; sumatriptan
NS, 17.7%; zolmitriptan, 17.6%; rizatriptan, 16.5%; naratriptan, 9.4%. For those 
who used more than three triptans/formulations, the last triptan used was:
sumatriptan, 29.5%; zolmitriptan, 31.8%; rizatriptan, 25.0%; naratriptan, 12.5%. 
CONCLUSIONS: A variety of treatment attributes are important in determining the
reasons involved in switching a triptan. To assess this attributes can provide
additional information to supplement the traditional tests of efficacy provided
by randomized clinical trials.

PMID: 15209687 [PubMed - indexed for MEDLINE]

2177: Headache. 2004 Jul-Aug;44(7):652-60.

When to stress over triptans: a Markov analysis of cardiovascular risk in
migraine treatment.

Orlando LA, Matchar DB.

Duke University Medical Center, Durham VA, NC, USA.

BACKGROUND: Migraines affect 10% of the U.S. population and the episodes are
frequently associated with significant disability. Triptans, 5HT1 receptor
agonists, can be highly effective in treating pain and reducing disability.
However, reports of cardiac events associated with triptan ingestion have led to 
concerns about its use in the face of possible cardiac disease. OBJECTIVE: Should
a patient without known cardiovascular disease (CAD) and moderately severe to
severe migraines undergo cardiovascular testing prior to the initiation of
triptan therapy? DESIGN: A Markov model of migraine and cardiac disease using
DATA 4.0. Three strategies were compared: (1) use triptans without further
evaluation (TREAT); (2) test, then treat if negative (TEST); and (3) avoid
triptans (NOTRIPTAN). Triptans were prohibited if a cardiac event occurred. DATA:
Model inputs were derived from the literature and subjected to sensitivity
analyses across all possible values. TIME HORIZON: Markov cycle is 1 week.
OUTCOMES: The primary outcomes of interest were quality-adjusted life expectancy,
in years (QALYs) and the impact of various cardiovascular risk levels on the
preferred strategy. RESULTS: For the base case results were TREAT 19.4 QALYs,
TEST 19.2, NOTRIPTAN 19.1. When altering CAD probability: TREAT dominated from 0 
to 87%, TEST 87% to 97%, and NOTRIPTAN above 97%. Results were robust during
sensitivity analyses. CONCLUSIONS: This analysis suggests that even for
individuals with a relatively high risk of CAD it is not beneficial to perform
cardiac testing, nor to avoid triptans. The exact level of cardiac risk at which 
testing should be considered is probably at or above 87%.

Publication Types: 
    Comparative Study

PMID: 15209686 [PubMed - indexed for MEDLINE]

2178: Headache. 2004 Jul-Aug;44(7):642-51.

Severe vascular events in migraine patients.

Velentgas P, Cole JA, Mo J, Sikes CR, Walker AM.

Ingenix Epidemiology, Auburndale, MA 02466, USA.

OBJECTIVE: To estimate rates of vascular events in relation to dispensing of
triptans and ergot alkaloids among migraineurs, and to compare these rates with
those of nonmigraineurs. CONTEXT: It has been speculated that the use of triptans
or ergot alkaloid drugs might increase risk of ischemic events through
vasoconstriction. Design: A retrospective cohort study of 130,411 migraineurs and
130,411 age-, sex-, and health plan-matched nonmigraineurs who were members of
UnitedHealthcare during 1995 through 1999. The data source for this study was
Ingenix's research database containing pharmacy and medical claims for
UnitedHealthcare members, and the National Death Index. MAIN OUTCOME MEASURES:
Incidence of cardiovascular and cerebrovascular events and mortality. RESULTS:
Migraineurs and nonmigraineurs had identical rates of myocardial infarction: 1.4 
per 1000 person-years. Migraineurs were 67% more likely to suffer a stroke than
nonmigraineurs (adjusted relative risk [RR] 1.67, 95% confidence interval [CI]
1.31-2.13), and had higher rates of unstable angina and transient ischemic
attacks. There was no increase in risk of myocardial infarction with current
(adjusted RR 0.80, 95% CI 0.58-1.11) or recent (adjusted RR 1.15, 95% CI
0.71-1.87) triptan use. Neither current (adjusted RR 0.90, 95% CI 0.64-1.26) nor 
recent (adjusted RR 0.84, 95% CI 0.46-1.55) triptan use was associated with risk 
of stroke. Current users of ergot alkaloids were somewhat more likely to have a
stroke than other migraineurs (adjusted RR 1.49, 95% CI 0.93-2.41), but there was
no dose-response relationship. CONCLUSIONS: Use of triptans is not associated
with increased risk of any ischemic events, including myocardial infarction and
stroke, or mortality. Consistent with previous studies, migraineurs in general
have an elevated risk of stroke, but not myocardial infarction, compared with
nonmigraineurs.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 15209685 [PubMed - indexed for MEDLINE]

2179: Pharmacoeconomics. 2004;22(9):591-603.

The burden of migraine in Spain: beyond direct costs.

Badia X, Magaz S, Gutiérrez L, Galván J.

Health Outcomes Research Europe, Barcelona, Spain.

OBJECTIVE: To estimate the economic burden of migraine in Spain, from the
societal perspective. METHODS: The Spanish 2001 annual direct (pharmacy, primary 
care, specialist and emergency room visits) and indirect (missed workdays and
reduced work performance) costs were calculated using the prevalence approach.
The human-capital method was used to calculate indirect costs. The sources used
were published epidemiological and resource use studies using the International
Headache Society diagnostic criteria from official and unofficial databases.
RESULTS: The Spanish population with migraine was estimated to be 3,617,600
patients, 92.5% being of a working age. The economic burden of migraine was about
euro 1076 million. The direct costs represented only 32.0% of the total burden
(euro 344 million), 39.2% being for primary care visits, 28.7% for specialist
visits, 20.5% for emergency room visits and a further 11.7% for migraine-specific
prescription drugs (serotonin 5-HT(1B/1D) receptor agonists [triptans] 10.8%,
ergots 0.9%). The indirect cost was estimated at euro 732 million annually,
representing euro 453.55 per working patient with migraine. CONCLUSIONS: As in
many other developed countries, migraine represents a considerable economic
burden in Spain, especially in terms of productivity losses. Therefore,
activities should be specifically directed at reducing the indirect costs, and
effective treatments, which significantly reduce productivity losses, should be
publicly promoted.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 15209528 [PubMed - indexed for MEDLINE]

2180: Eur J Pain. 2004 Aug;8(4):307-14.

Migraine and tension headache in children under 6 years of age.

Balottin U, Nicoli F, Pitillo G, Ferrari Ginevra O, Borgatti R, Lanzi G.

Child Neuropsychiatry Unit, University of Insubria, Macchi Foundation Hospital,
Varese 21100, Italy. balottin@unipv.it

OBJECTIVE: To investigate the clinical features of idiopathic headache with early
onset, whose presence is probably underestimated by parents and physicians and
the influence of environmental and psychological factors on headache in children.
METHODS: We report on a prospective longitudinal evaluation of 35 consecutive
children referred to the Neuropsychiatry Departments of the Universities of
Varese and Pavia (mean age at the first observation: 4 years and 7 months, range:
12 months-6 years; mean age at onset: 4 years and 2 months, range: 10 months-6
years) presenting with headache symptomatology. Mean duration of clinical
follow-up: 9.5 months. The diagnosis based on the IHS criteria was then compared 
to the intuitive clinical diagnosis made in accordance with alternative case
definitions. We examined our patients for the presence of early developmental
disorders and interictal somatic disorders. We also studied the role of
psychosocial factors at the onset and in the course of headache. RESULTS:
Diagnosis: migraine without aura in two cases, episodic tension headache in four 
cases, migrainous disorders not fulfilling above criteria in eight cases,
headache of the tension-type not fulfilling above criteria in 12 cases and
headache not classifiable in nine cases. Clinical features of headache are
described in the text. Early developmental disorders (0-2 years), such as eating 
difficulties and sleep disorders, were detected in 18/35 children. Among patients
older than 2 years, we also detected interictal somatic disorders (20 cases) such
as sleep disorders, eating difficulties, enuresis and idiopathic vomiting. In
14/35 subjects, we identified psychosocial components playing a significant role 
at the onset of, and during, the headache. CONCLUSIONS: A better clinical
definition of the disorder would make it easier to identify very young affected
children and consequently to plan more specific therapeutic interventions, taking
into account environmental and psychological factors. A diagnosis of idiopathic
headache becomes particularly significant: according to our cases, despite their 
being limited in number, migraine and tension headache can be considered also as 
indices of individual or family related problems requiring appropriate
psychiatric or psychological intervention. This stresses the need for a
multidisciplinary team of specialists that would include a psychologist/
psychiatrist or headache specialist with specific training in psychiatry.

PMID: 15207511 [PubMed - indexed for MEDLINE]

2181: Eur Arch Psychiatry Clin Neurosci. 2004 Jun;254(3):182-6.

Alexithymic features in migraine patients.

Muftuoglu MN, Herken H, Demirci H, Virit O, Neyal A.

Department of Neurology, Gaziantep University School of Medicine, Turkey.
neyal@superonline.com

The aims of the present study were 1) to investigate the alexithymic features in 
migraine patients and, 2) if alexithymia has any relation with the results of
other psychological scales that are widely used in clinical practice to describe 
the psychopathologies, such as depression and anxiety. Demographic and clinical
data of 50 cases with migraine without aura and 50 normal volunteers were
supplied. All cases completed the Beck Depression Inventory, Hamilton Depression 
Rating Scale, State and Trait Anxiety Inventory and Toronto Alexithymia Scale.
Migraine patients were significantly more depressive, anxious and alexithymic
than the control group; there was no correlation between TAS scores and
demographic variables; not depression but anxiety was significantly correlated
with alexithymia in the migraine group, whereas none of the scores were found to 
be related to alexithymia in controls. According to our results, alexithymia is a
frequent finding in migraine patients and is associated with anxiety to a
considerable extent but not with depression.

Publication Types: 
    Comparative Study

PMID: 15205972 [PubMed - indexed for MEDLINE]

2182: J Neurol Neurosurg Psychiatry. 2004 Jul;75(7):984-7.

Platelet-leukocyte interaction and platelet activation in migraine: a link to
ischemic stroke?

Zeller JA, Frahm K, Baron R, Stingele R, Deuschl G.

Department of Neurology, Christian Albrechts University Kiel, Kiel, Germany.
j.zeller@neurologie.uni-kiel.de

OBJECTIVES: Migraine has been identified as an independent risk factor for
ischemic stroke. Both neurogenic inflammation and platelet activation have been
linked to the pathophysiology of migraine. Increased platelet activation results 
in up-regulation of specific binding to leukocytes which promotes
pro-inflammatory leukocyte secretion and their tethering to endothelium, a
mechanism that has been demonstrated in stroke and which could provide a link to 
migraine. We aimed to determine whether platelet-leukocyte aggregation is
increased in migraine patients outside an acute attack. METHODS: Seventy two
patients with migraine according to IHS criteria were compared to a control group
(n = 72). Whole blood flow cytometry was used to quantify the activation
dependent P selectin on the platelet, and to assess the fraction of platelets
bound to the different leukocyte subsets. RESULTS: Migraine patients showed
significantly more platelet-leukocyte aggregates compared to the control subjects
(p = 0.003). This effect was driven by an increased polymorphonuclear
cell-platelet aggregation (p = 0.003) whereas platelet aggregation with monocytes
and lymphocytes was not. Platelet activation was also increased (p = 0.001).
CONCLUSIONS: In migraine pro-inflammatory platelet adhesion to leukocytes occurs 
during the headache free interval similar to that seen in acute coronary and
cerebrovascular syndromes. This may suggest a link between migraine and stroke on
a cellular level.

PMID: 15201354 [PubMed - indexed for MEDLINE]

2183: Curr Med Res Opin. 2004 Jun;20(6):803-9.

Pharmacokinetic profile of a new form of sumatriptan tablets in healthy
volunteers.

Walls C, Lewis A, Bullman J, Boswell D, Summers SJ, Dow A, Sidhu J.

GlaxoSmithKline, Harlow and Stockley Park, UK. christine.walls@gsk.com

OBJECTIVE: Rapid delivery of migraine-specific medication to its site(s) of
action is thought to be crucial in preventing or minimizing sensitization of
central pain pathways and thereby in optimizing pain-free outcomes in patients
with migraine. Sumatriptan has been developed as a new tablet formulation to
enhance the rate of systemic drug delivery by improving tablet disintegration and
drug dispersion relative to those of conventional tablets. These enhanced
formulation characteristics may be beneficial during occurrences of the gastric
stasis that can accompany migraine. METHODS: This randomized, open-label, 4-way
crossover study (n = 32) was conducted to determine whether the new formulation
of sumatriptan 50 and 100 mg is bioequivalent to sumatriptan conventional tablets
and to compare the pharmacokinetic profiles of the new formulation and the
conventional tablet during the early (0-2 h) postdose interval in healthy
volunteers. Pharmacokinetics during the early post-dose interval are important in
determining a drug's onset of action, an important parameter to patients with
migraine. RESULTS: The results confirm that the new formulation of sumatriptan
and sumatriptan conventional tablets are bioequivalent as demonstrated by the
finding that the 90% confidence intervals for the sumatriptan area under the
concentration time curve to infinity and to the last evaluable time point (AUC(0-
infinity ) and AUC(0-t), respectively) and maximum plasma concentration (C(max)) 
fell within the predetermined bounds defining bioequivalence (0.80-1.25) for both
doses. Pharmacokinetic parameters measured early (0-2 h) after dosing reveal
slightly faster absorption, on average, of the new sumatriptan formulation than
sumatriptan conventional tablets although high intersubject variability was
observed. For the new sumatriptan formulation, AUC(0-2) (AUC up to 2 h post dose)
was, on average, 1% greater (50 mg) and 8% greater (100 mg) and maximal
sumatriptan levels were attained, on average, 10 min earlier (50 mg) and 15 min
earlier (100 mg) compared with the conventional tablet. Other measures including 
AUC(0-0.5) (AUC to 30 min post-dose), times to achieve sumatriptan concentrations
of 5 and 10 ng/mL, and mean percentage C(max) 15, 20 and 30 min post-dose
demonstrate an observable improvement in rate of drug absorption for the new form
of sumatriptan compared with conventional tablets. CONCLUSION: The new form of
sumatriptan is bioequivalent to sumatriptan conventional tablets and is absorbed 
more quickly than conventional tablets.

Publication Types: 
    Clinical Trial
    Comparative Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 15200736 [PubMed - indexed for MEDLINE]

2184: Vitam Horm. 2004;69:297-312.

Role of magnesium, coenzyme Q10, riboflavin, and vitamin B12 in migraine
prophylaxis.

Bianchi A, Salomone S, Caraci F, Pizza V, Bernardini R, D'Amato CC.

Department of Pharmaceutical Sciences, University of Salerno, 84084 Fisciano,
Italy.

Migraine is a neurovascular syndrome characterized by recurrent headache
associated with other symptoms, eventually preceded by aura. This chapter reviews
the involvement of some mineral, coenzyme, and vitamin defects in the
pathogenesis of migraine headaches and focuses on their potential therapeutic use
in the preventive treatment for migraine. The therapeutic potential of magnesium,
coenzyme Q(10), riboflavin, and vitamin B(12) can be cautiously inferred from
some published open clinical trials; it should, however, be considered that
double-blind randomized larger studies are needed to correctly estimate the
impact of the placebo effect in these promising therapies.

Publication Types: 
    Review

PMID: 15196887 [PubMed - indexed for MEDLINE]

2185: Cephalalgia. 2004 Jul;24(7):603-4.

Hemicrania continua postpartum.

Spitz M, Peres MF.

Hospital Israelita Albert Einstein, São Paulo, Brazil.

Hemicrania continua is a common, but unrecognized headache disorder. We describe 
two patients with hemicrania continua whose symptoms started in the postpartum
period, coined as hemicrania continua postpartum.

Publication Types: 
    Case Reports

PMID: 15196303 [PubMed - indexed for MEDLINE]

2186: Cephalalgia. 2004 Jul;24(7):596-602.

LY293558, a novel AMPA/GluR5 antagonist, is efficacious and well-tolerated in
acute migraine.

Sang CN, Ramadan NM, Wallihan RG, Chappell AS, Freitag FG, Smith TR, Silberstein 
SD, Johnson KW, Phebus LA, Bleakman D, Ornstein PL, Arnold B, Tepper SJ,
Vandenhende F.

Massachusetts General Hospital, Boston, USA.

Glutamatergic hyperactivity is implicated migraine pathogenesis. Also, LY293558, 
an alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)/kainate (KA)
receptor antagonist, is effective in preclinical models of migraine. We therefore
tested LY293558 in acute migraine. We conducted a randomized, triple-blind,
parallel-group, double-dummy, multicentre trial of 1.2 mg/kg intravenous (IV)
LY293558, 6 mg subcutaneous (SC) sumatriptan, or placebo in the treatment of
acute migraine. The primary efficacy variable was the headache response rate,
i.e. headache score improvement from moderate/severe at baseline to mild/none at 
2 h. Of 45 enrolled patients, 44 patients (20M:24F; mean age +/- SD = 40 +/- 9
years) completed the study. Response rates were 69% for LY293558 (P = 0.017 vs.
placebo), 86% for sumatriptan (P < 0.01 vs. placebo) and 25% for placebo.
LY293558 and sumatriptan were superior to placebo (P < 0.01 for all comparisons) 
on all other measures of improvement in pain and migraine associated symptoms.
Fifteen percent of patients who took LY293558 reported adverse events (AEs) (n = 
2; one mild, one severe). Fifty-three percent of patients who took sumatriptan (n
= 8; seven mild, one moderate) and 31% of those who received placebo reported AEs
(n = 5; four mild, one severe). The efficacy and safety results of LY293558 in
this small migraine proof of concept trial, together with supportive preclinical 
data, provide evidence for a potential role of nonvasoactive AMPA/KA antagonists 
in treating migraine. Larger trials are needed to further test the hypothesis.

Publication Types: 
    Clinical Trial
    Comparative Study
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 15196302 [PubMed - indexed for MEDLINE]

2187: Cephalalgia. 2004 Jul;24(7):576-85.

The prophylactic effect of valproate on glyceryltrinitrate induced migraine.

Tvedskov JF, Thomsen LL, Iversen HK, Gibson A, Wiliams P, Olesen J.

Danish Headache Centre, University of Copenhagen. tvedskov@dadlnet.dk

In this study the human glyceryltrinitrate (GTN) model of migraine was for the
first time used to test the effect of a prophylactic drug. We chose to test
valproate due to its well documented effect as a migraine prophylactic drug.
Efficacy of this compound would support the usefulness of the model in
prophylactic antimigraine drug development. Twelve patients with migraine without
aura were included in a randomized double blind crossover study. Valproate 1000
mg or placebo was given daily, each for a minimum of 13 days. On the last
treatment day of each arm a 20 min intravenous infusion of GTN (0.25
microg/kg/min) was given. Headache was registered for 12 h after the infusion and
headache intensity was scored on a scale from 0 to 10. Fulfillment of IHS
criteria was recorded for 24 h. The middle cerebral arteries were evaluated by
transcranial Doppler and the diameter of the superficial temporal and radial
arteries were measured with high frequency ultrasound. GTN evoked migraine
fulfilling IHS criteria 1.1 in 6 patients after placebo and in 2 patients after
valproate (P = 0.125). Including additionally 3 patients on placebo and 1 patient
on valproate who felt they had suffered a migraine attack, but who had as
associated symptoms only photophobia or phonophobia, a significant reduction in
the number of patients with induced migraine after valproate was seen (P =
0.031). Median peak headache intensity was 1 (range 0-9) after valproate compared
to 4.5 (range 0-8) after placebo (P = 0.120). Pretreatment with valproate as
compared to placebo reduced the velocity in both middle cerebral arteries after
GTN (left P = 0.021, right P = 0.031). No effect of valproate was seen in the
diameter of the superficial temporal artery (P = 0.781) or the radial artery (P =
0.367) before or after GTN. The study indicates that a prophylactic effect of
valproate may be demonstrated using the GTN human migraine model. Although, all
headache parameters were reduced after valproate compared to placebo, only one
parameter was statistically significantly reduced probably because of the small
number of patients. The size of the effect was similar to that of valproate in
clinical trials. The GTN model may therefore be a valid tool for testing new
prophylactic antimigraine drugs.

Publication Types: 
    Clinical Trial
    Comparative Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 15196300 [PubMed - indexed for MEDLINE]

2188: Cephalalgia. 2004 Jul;24(7):564-75.

Clinical characteristics of 362 patients with familial migraine with aura.

Eriksen MK, Thomsen LL, Andersen I, Nazim F, Olesen J.

Danish Headache Center, University of Copenhagen. kirchmann@dadlnet.dk

The objectives of the present study were to describe the clinical characteristics
of patients with severe familial non-hemiplegic migraine with aura (NHMA) and to 
compare these data to those from cases in previous population-based Danish
studies using the same methodology. NHMA families were recruited from the Danish 
patient registry and from Danish neurology practices. A total of 362 NHMA
patients were diagnosed according to the 1988 International Headache Society
criteria using a validated semistructured physician-conducted interview. Visual
aura occurred in almost every NHMA attack. In aura without headache visual aura
occurred primarily in isolation. Aura without headache was most common in older, 
male patients. Several clinical characteristics of familial NHMA differed from
migraine with aura in the general population: firstly, the age at onset was
lower, secondly, the age at cessation was higher, thirdly, aura symptoms were
more severe and finally, the co-occurrence of migraine without aura was higher in
familial NHMA. There seems to be a correlation between more severe symptoms and
familial aggregation. These results have both clinical and scientific
implications.

Publication Types: 
    Comparative Study

PMID: 15196299 [PubMed - indexed for MEDLINE]

2189: Cephalalgia. 2004 Jul;24(7):554-63.

Auditory event-related potentials and reaction times in migraine children.

Buodo G, Palomba D, Sarlo M, Naccarella C, Battistella PA.

Department of General Psychology, University of Padova, Italy.
giulia.buodo@unipd.it

Cognitive processing was investigated interictally in 18 children with migraine
without aura and 18 age-matched controls by measuring event-related potentials
(ERPs) and reaction times (RTs) during an acoustic oddball paradigm. Results
showed that N100 amplitude evoked by frequent stimuli was significantly smaller
in patients compared with controls. Habituation of target P300 amplitude was
observed in patients but not in controls. Mean RTs were equivalent in the two
groups, but migraine children made more errors than controls.

Publication Types: 
    Comparative Study

PMID: 15196298 [PubMed - indexed for MEDLINE]

2190: Cephalalgia. 2004 Jul;24(7):547-53.

Plasma levels of cAMP, cGMP and CGRP in sildenafil-induced headache.

Kruuse C, Frandsen E, Schifter S, Thomsen LL, Birk S, Olesen J.

Danish Headache Centre, University of Copenhagen. ckruuse@dadlnet.dk

Sildenafil, a selective inhibitor of the cyclic guanosine monophosphate (cGMP)
degrading phosphodiestrase 5 (PDE5), induced migraine without aura in 10 of 12
migraine patients and in healthy subjects it induced significantly more headache 
than placebo. The aim of the present study was to determine whether the
pain-inducing effects of sildenafil would be reflected in plasma levels of
important signalling molecules in migraine: cGMP, cyclic adenosine monophosphate 
(cAMP) and calcitonin gene-related peptide (CGRP). Ten healthy subjects (four
women, six men) and 12 patients (12 women) suffering from migraine without aura
were included in two separate double-blind, placebo-controlled, cross-over
studies in which placebo or sildenafil 100 mg was administered orally. Plasma
levels of CGRP, cAMP and cGMP were determined in blood from the antecubital vein.
Despite the ability of sildenafil to induce headache and migraine, no significant
differences in plasma levels of CGRP, cGMP and cAMP were detected after
sildenafil compared with placebo. In conclusion, plasma levels of CGRP, cGMP and 
cAMP remain normal during sildenafil-induced headache or migraine. However, since
previous studies indicate an important role of these signalling molecules, the
present study questions whether cAMP and cGMP in peripheral blood can be used for
monitoring pathophysiological events in headache and migraine mechanisms.

Publication Types: 
    Clinical Trial
    Comparative Study
    Controlled Clinical Trial
    Research Support, Non-U.S. Gov't

PMID: 15196297 [PubMed - indexed for MEDLINE]

2191: Cephalalgia. 2004 Jul;24(7):540-6.

Comparison of rizatriptan 5 mg and 10 mg tablets and sumatriptan 25 mg and 50 mg 
tablets.

Kolodny A, Polis A, Battisti WP, Johnson-Pratt L, Skobieranda F; Rizatriptan
Protocol 052 Study Group.

Merck & Co., Inc., West Point, PA 19486, USA.

This randomized, double-blind, two-attack, placebo-controlled, crossover study
explored the efficacy and tolerability of rizatriptan 10 mg compared with
sumatriptan 50 mg as well as rizatriptan 5 mg compared with sumatriptan 25 mg in 
the acute treatment of migraine. Following randomization to one of six possible
treatment sequences, patients (n = 1447) treated two sequential attacks, of
moderate or severe intensity, separated by at least 5 days. Patients assessed
pain severity, migraine-associated symptoms, and functional disability at 0.5, 1,
1.5, and 2 h post treatment. Compared with placebo, all treatments were
effective. On the primary endpoint of time to pain relief, rizatriptan 10 mg was 
not statistically different from sumatriptan 50 mg [odds ratio (OR) 1.10, P =
0.161], and rizatriptan 5 mg was statistically superior to sumatriptan 25 mg (OR 
1.22, P = 0.007). In general, rizatriptan 10 mg and 5 mg treatment resulted in
improvement compared with the corresponding doses of sumatriptan on measures of
pain severity, migraine symptoms, and functional disability and the 5-mg dose
reached statistical significance on almost all measures. All treatments were
generally well tolerated.

Publication Types: 
    Clinical Trial
    Comparative Study
    Multicenter Study
    Randomized Controlled Trial

PMID: 15196296 [PubMed - indexed for MEDLINE]

2192: Cephalalgia. 2004 Jul;24(7):533-9.

Familial hemiplegic migraine: follow-up findings of diffusion-weighted magnetic
resonance imaging (MRI), perfusion-MRI and [99mTc] HMPAO-SPECT in a patient with 
prolonged hemiplegic aura.

Oberndorfer S, Wöber C, Nasel C, Asenbaum S, Lahrmann H, Fueger B, Grisold W.

Neurological Department, Kaiser-Franz-Josef-Spital, University of Vienna,
Austria. stefan.oberndorfer@wienkav.at

Familial hemiplegic migraine (FHM) is a rare inherited autosomal dominant
disorder. Migraine aura may last up to several weeks and then resolve without
sequel. We report a 21-year-old male with FHM since the age of 3 years.
Diffusion-weighted magnetic resonance imaging (DWI), perfusion-MR imaging (P-MRI)
and [99mTc] hexamethyl-propyleneamine-oxime-single photon emission tomography
(HMPAO-SPECT) were performed on day 2, when he was somnolent with right-sided
hemiplegia, on day 9 when a mild hemiparesis was still present and on day 24
after recovery. The right central region showed normal findings in DWI, whereas
P-MRI and SPECT revealed hyperperfusion on day 2, less marked on day 9, and
normal findings on day 24. In conclusion, this case report indicates for the
first time, by means of SPECT, P-MRI and DWI studies, that even extremely
long-lasting migraine aura is not associated with cerebral ischaemia. Therefore, 
it supports the revised International Headache Society criteria where the term
'persistent' aura is proposed.

Publication Types: 
    Case Reports

PMID: 15196295 [PubMed - indexed for MEDLINE]

2193: Cephalalgia. 2004 Jul;24(7):528-32.

Flunarizine effects on oxidative stress in migraine patients.

Ciancarelli I, Tozzi-Ciancarelli MG, Di Massimo C, Marini C, Carolei A.

Department of Neurology, University of L'Aquila, Italy.

Prophylactic activity of flunarizine in migraine is attributed to its antioxidant
properties and to the relief of cerebral vasospasm in which nitric oxide (NO) is 
involved. We investigated the antimigraine activity of flunarizine and its
influence on NO and oxidative marker bioavailability in 25 subjects suffering
from migraine without aura and in 25 healthy controls. Urinary samples collected 
before and after treatment with flunarizine (5 mg orally per day for 6 months)
were assayed for NO stable metabolites (NOx) and thiobarbituric acid reactive
substances (TBARS). Urinary levels of NOx and TBARS were higher in migraine
sufferers before treatment than in healthy controls. No differences were observed
in NOx levels in migraine sufferers, before and after flunarizine treatment;
urinary TBARS levels were decreased after flunarizine treatment (P < 0.05) and
remained persistently higher than in healthy controls (P < 0.05). Our results
suggest that flunarizine did not prevent NO-mediated vasodilatation, while it
proved effective in limiting the oxidative reactions occurring in migraine
sufferers.

Publication Types: 
    Comparative Study

PMID: 15196294 [PubMed - indexed for MEDLINE]

2194: Neuroreport. 2004 Jun 28;15(9):1409-12.

The anti-migraine agent sumatriptan induces a calcium-dependent discharge in
meningeal sensory neurons.

Strassman AM, Levy D.

Department of Anesthesia and Critical Care, Beth Israel Deaconess Medical Center 
and Harvard Medical School, 330 Brookline Ave, Boston, MA 02215, USA.
Andrew.Strassman@bidmc.harvard.edu

The anti-migraine agent sumatriptan constricts cerebral blood vessels, and also
blocks neuropeptide release from meningeal sensory neurons. We investigated
whether sumatriptan can also affect neuronal discharge, by recording the activity
of dural primary afferent neurons during dural application of sumatriptan in
anesthetized rats. Sumatriptan (0.24-24 microM) induced a concentration-dependent
increase in ongoing discharge. The discharge occurred only in the presence of
calcium. The suppressive effect of calcium removal was not a result of a general 
decrease in excitability, because calcium removal produced a pronounced increase 
in mechanically evoked discharge. The excitatory effect on dural afferent
discharge might underlie the initial worsening of the headache that can occur
following sumatriptan administration, prior to the subsequent onset of headache
relief.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 15194863 [PubMed - indexed for MEDLINE]

2195: Brain Res. 2004 Jul 9;1013(2):188-93.

GABAA receptor modulation of trigeminovascular nociceptive neurotransmission by
midazolam is antagonized by flumazenil.

Storer RJ, Akerman S, Shields KG, Goadsby PJ.

Headache Group, Institute of Neurology and The National Hospital for Neurology
and Neurosurgery, Queen Square, London WC1N 3BG, UK.

Studies of the pharmacology of trigeminocervical neurons with input from
intracranial pain-producing structures have enhanced the understanding of the
basic neurobiology of primary headache, such as migraine. Clinical observations
of the treatment of migraine with medicines acting at the gamma-aminobutyric acid
(GABA) GABAA receptor have lead to studies of their effects on models of
trigeminovascular nociception. Extracellular recordings were made from neurons in
the trigeminocervical complex activated by supramaximal electrical stimulation of
superior sagittal sinus (SSS) in the cat. Intravenous administration of the
benzodiazepine receptor agonist midazolam, resulted in a dose-dependent
inhibition of superior sagittal sinus evoked trigeminocervical nucleus activity. 
The inhibition at 50 microg/kg midazolam was 65+/-11% compared to the baseline
response (n=11). Intravenous administration of the benzodiazepine receptor
antagonist flumazenil, resulted in a dose-dependent recovery of superior sagittal
sinus evoked trigeminocervical nucleus activity. At a dose of 50 microg/kg, there
was a 64+/-5% recovery (n=6). The data demonstrate a potent, reproducible effect 
of facilitation of GABA transmission at the GABAA receptor that results in
inhibition of trigeminovascular nociceptive transmission. These data are
consistent with the useful clinical effects reported with compounds that can
augment GABAergic transmission in the central nervous system (CNS).

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 15193528 [PubMed - indexed for MEDLINE]

2196: Curr Atheroscler Rep. 2004 Jul;6(4):320-5.

Headache and the risk of stroke.

Jousilahti P.

Department of Public Health, University of Helsinki, PO Box 41, FIN-00014,
Helsinki, Finland. pekka.jousilahti@ktl.fi

Several studies have suggested that migraine is a risk factor for stroke. The
association between migraine and the risk of stroke has been observed most often 
among premenopausal women but also in some studies among men. The association may
be stronger among women who smoke and among women using oral contraceptives
compared with nonsmokers and nonusers. Classic migraine with aura may be a more
powerful predictor of stroke than common migraine without aura. Findings of a
recent population-based study suggest that subclinical brain lesions are more
common among migraine patients, particularly among those with aura, than among
the control subjects. Two cohort studies have shown that chronic non-specific
headache also is related to increased stroke risk. The effect of treatment of
migraine and other types of headache on the risk of stroke is not known. Even
though the relative risk of stroke may be fairly high among migraine patients,
the absolute risk is usually low due to low baseline risk among young people.

Publication Types: 
    Review

PMID: 15191708 [PubMed - indexed for MEDLINE]

2197: Clin Neuropharmacol. 2004 May-Jun;27(3):137-40.

Phyto-oestrogens in the prophylaxis of menstrual migraine.

Ferrante F, Fusco E, Calabresi P, Cupini LM.

Clinica Neurologica, Universita' di Roma Tor Vergata, Roma, Italy.

BACKGROUND: Falling levels of estrogen is the major provocative factor in
migraine associated with menstruation. OBJECTIVE: We assessed the efficacy of the
combination of two phyto-oestrogens, as perimenstrual, prophylactic treatment of 
menstrual migraine and tested their effect on cerebral haemodynamic. SUBJECTS AND
METHODS: Women with a history of menstrual migraine (i.e., attacks occurring
exclusively on day 1+/-2 days of menstruation and at no other time of the cycle) 
were included in the study. Eleven women fulfilling the inclusion criteria
underwent to a 3-month cyclic treatment with 56 mg of genisteine and 20 mg of
diadzeine per day. Transcranial doppler evaluation (TCD) was performed at
baseline and after treatment. RESULTS: Among the ten women who completed the
study the average number of days with migraine during the baseline period
decreased significantly after 3 months of therapy (P < 0.005). There were no
major side-effects. Therapy did not affect cerebral blood flow velocities.
CONCLUSIONS: Phyto-oestrogens appear to be an effective treatment in menstrual
migraine prophylaxis. This effect seems to be unrelated to cerebral hemodynamic. 
Placebo-controlled trials on larger number of patients are necessary to confirm
our findings.

Publication Types: 
    Clinical Trial
    Comparative Study

PMID: 15190238 [PubMed - indexed for MEDLINE]

2198: J Am Acad Child Adolesc Psychiatry. 2004 Apr;43(4):412-9.

Psychiatric symptoms in children with primary headache.

Anttila P, Sourander A, Metsähonkala L, Aromaa M, Helenius H, Sillanpää M.

Department of Child and Adolescent Health Care, Turku City Hospital, Finland.
pirjoa.anttila@pp.finnet.fi

OBJECTIVE: To examine the association of psychiatric symptoms with migraine and
tension-type headache in children. METHOD: A questionnaire completed by 1,135
Finnish children in the sixth grade identified 154 children with migraine, 138
with tension-type headache, and 407 children who were headache-free. Seventy
children were randomly selected from each group and evaluated by a structured
interview to confirm headache type, resulting in a sample of 59 children with
migraine, 65 with tension-type headache, and 59 without headache. The children
completed the Children's Depression Inventory, and the parents completed the
Child Behavior Checklist and General Functioning scale of the McMaster Family
Assessment Device. RESULTS: Children with migraine had significantly higher
levels of total, internalizing, and somatic symptoms, as well as social and
family problems, than those without headache and had higher levels of somatic
symptoms than children with tension-type headache. Children with tension-type
headache had significantly higher levels of somatic symptoms and family problems 
than those without headache. CONCLUSIONS: The association between psychiatric
symptoms and headaches shows differences between different headache types.
However, a minority of children with migraine or tension-type headache have high 
levels of psychiatric symptoms.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 15187801 [PubMed - indexed for MEDLINE]

2199: Headache. 2004 Jun;44(6):596-602.

Comment in:
    Headache. 2005 Jul-Aug;45(7):960; author reply 960.

The effect of weather on headache.

Prince PB, Rapoport AM, Sheftell FD, Tepper SJ, Bigal ME.

Department of Pediatrics, Children's Hospital, Boston, MA, USA.

OBJECTIVES: To assess headache patients' beliefs about how strongly weather
affects their headaches; To objectively investigate the influence of multiple
weather variables on headache. DESIGN AND METHODS: Our sample consisted of 77
migraineurs seen in a headache clinic, who provided headache calendars for a
period ranging from 2 to 24 months. Our study was divided into two phases. First,
each patient was given a questionnaire assessing their beliefs about how strongly
(if so) weather affected their headaches. Second, weather data were collected
from the National Weather Service, from three reporting stations central to the
residences of the study participants. Analysis was performed on 43 variables to
generate three meteorological factors. Linear regression was used to assess the
relationship between headache and these three factors. Factor 1 represents a
function of absolute temperature and humidity. Factor 2 represents a changing
weather pattern. Factor 3 represents barometric pressure. RESULTS: Of the 77
subjects in the study, 39 (50.6%), were found to be sensitive to weather, but 48 
(62.3%) thought they were sensitive to weather conditions (P < 0.05). Thirty
(38.9%) were sensitive to one weather factor and 9 (11.7%) to two factors.
Twenty-six (33.7%) were sensitive to factor 1; 11 (14.3%) to factor 2; 10 (12.9%)
to factor 3. CONCLUSIONS: Our study supports the influence of weather variables
on headache. We showed that patients are susceptible to multiple weather
variables and that more patients thought weather was a trigger than was the case.

Publication Types: 
    Comparative Study

PMID: 15186304 [PubMed - indexed for MEDLINE]

2200: Headache. 2004 Jun;44(6):581-6.

Montelukast for migraine prophylaxis: a randomized, double-blind,
placebo-controlled study.

Brandes JL, Visser WH, Farmer MV, Schuhl AL, Malbecq W, Vrijens F, Lines CR,
Reines SA; Protocol 125 study group.

Nashville Neuroscience Group, Nashville, TN, USA.

OBJECTIVE: To evaluate the efficacy and tolerability of montelukast 20 mg in the 
prophylactic treatment of migraine. BACKGROUND: A previous small open-label study
in migraine patients suggested prophylactic efficacy for montelukast, an
antagonist of the cysteinyl leukotriene receptor that is used in the treatment of
asthma. We sought to confirm these findings in a randomized controlled trial.
METHODS: This multicenter, randomized, double-blind, placebo-controlled,
parallel-groups study enrolled adult migraine outpatients who experienced > or =3
and < or =8 migraine attacks per month for the last 6 months. Patients were
entered into a 2-month, single-blind, placebo run-in phase. Only patients who
experienced > or =3 migraine attacks in the second month were eligible to enter
the subsequent 3-month, double-blind treatment phase of the study. The primary
efficacy endpoint was the percentage of patients reporting at least a 50%
decrease in migraine attack frequency per month during the double-blind treatment
period (months 3-5) compared to baseline (run-in month 2). RESULTS: A total of 93
patients were randomized to montelukast 20 mg and 84 patients to placebo at the
end of the placebo run-in month 2; 76 patients on montelukast and 72 patients on 
placebo completed the double-blind treatment period. Over 3 months of treatment, 
there was no significant difference between the two groups in the percentage of
patients who reported at least a 50% decrease in migraine attack frequency per
month: 15.4% for montelukast versus 10.3% for placebo (P= .304). In addition,
montelukast 20 mg was not significantly superior to placebo on any of the
secondary endpoints. There were no differences between treatment groups for
adverse events. CONCLUSION: Montelukast 20 mg was well tolerated in migraine
patients but was not an effective prophylactic for prevention of migraine.

Publication Types: 
    Clinical Trial
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 15186302 [PubMed - indexed for MEDLINE]

2201: Headache. 2004 Jun;44(6):571-80.

Impact of headache on quality of life in a general population survey in France
(GRIM2000 Study).

Duru G, Auray JP, Gaudin AF, Dartigues JF, Henry P, Lantéri-Minet M, Lucas C,
Pradalier A, Chazot G, El Hasnaoui A.

Université Claude Bernard, Lyon, France.

OBJECTIVES: The objectives of this study were to determine the impact of headache
on health-related quality of life in a nationwide sample of the French general
population using a disease-specific measure, the Qualité de Vie et Migraine
(QVM), to compare quality of life in subjects reporting different headache to
types, and to evaluate the relationship between quality of life and severity,
frequency, associated disability, and treatment responsiveness of headaches.
METHODS: The QVM questionnaire was included within a large epidemiological survey
of 1486 headache sufferers. Diagnosis was assigned retrospectively using an
algorithm based on the International Headache Society classification. Headache
severity was assessed with the MIGSEV scale and disability with the MIDAS scale. 
RESULTS: The mean global QVM score in the sample was 80.2. Quality of life was
poorer in subjects with chronic daily headache (QVM score: 66.2) than in those
with migraine (QVM score: 76.7), while those with other forms of episodic
headache had the best quality of life (QVM score: 91.7). Quality-of-life scores
were correlated with frequency, severity, disability, and treatment resistance of
headaches (P <.001). CONCLUSION: The QVM scale is a sensitive tool to measure
health-related quality of life in headache sufferers in the general population.

Publication Types: 
    Comparative Study

PMID: 15186301 [PubMed - indexed for MEDLINE]

2202: Headache. 2004 Jun;44(6):562-70.

The medical costs of migraine and comorbid anxiety and depression.

Pesa J, Lage MJ.

Health Economics and Outcomes Research, AstraZeneca, Willmington, DE, USA.

OBJECTIVE: To examine the direct medical costs associated with migraine, when
diagnosed alone and in conjunction with anxiety and/or depression in adults and
children. BACKGROUND: Migraine is a common disorder that can often be accompanied
by comorbid anxiety and/or depression. Given the prevalence of migraine and the
likelihood for comorbid conditions, it is not surprising that migraine is
extremely costly for society. METHODS: Migraine cohorts were identified in a
1999-2000 database capturing inpatient, outpatient, and prescription drug
services from approximately 45 large employers. Four cohorts of adults (migraine 
only, migraine and anxiety, migraine and depression, migraine and both
conditions), and two cohorts of children (migraine only, migraine and anxiety
and/or depression), were compared to respective "healthy" cohorts. t-statistics
were used to capture differences in costs between the migraine cohorts and the
healthy cohorts whereas ANOVA was used to test for differences in costs between
subgroups of migraine sufferers. RESULTS: Compared to nonmigraineurs, adults and 
children with migraine had significantly higher total direct medical costs in all
examined categories (P < .0001) (7,089 US Dollars vs US Dollars adults; 4,272 US 
Dollars vs 1,400 US Dollars children). For adults, the presence of depression
and/or anxiety along with migraine equated to significantly greater total direct 
medical costs when compared to their matched healthy cohorts (P < .0001) (12,642 
US Dollars vs 5,179 US Dollars anxiety; 11,290 US Dollars vs 3,135 US Dollars
depression). Children with migraine and either anxiety or depression (or both)
incurred an average of 9,875 US Dollars in total direct medical costs as compared
with only 1,165 US Dollars for healthy comparators. For children and adults, the 
presence of comorbid anxiety or depression was associated with significantly
higher medical costs when compared to migraine alone (P < .0001). CONCLUSIONS:
This analysis quantifies the economic impact of a migraine diagnosis for both
adults and children. The results of this analysis demonstrate that individuals
identified as migraineurs have significantly higher medical costs than healthy
comparators, with or without comorbid anxiety and/or depression. This study also 
suggests that clinicians should be aware that while proper treatment of migraine 
with effective acute and prophylactic therapy is important, attention must also
be directed to comorbid conditions.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 15186300 [PubMed - indexed for MEDLINE]

2203: Headache. 2004 Jun;44(6):545-54.

Relaxation treatment administered by school nurses to adolescents with recurrent 
headaches.

Fichtel A, Larsson B.

Department of Public Health and Caring Sciences, Uppsala Science Park, Sweden.

OBJECTIVE: To study the outcome of two different forms of relaxation training
administered by school nurses to adolescents suffering from recurrent headaches
in an effectiveness study. METHODS: A total of 11 school nurses were randomized
to administer one of the two treatments to 63 adolescents. A post hoc group with 
42 untreated subjects, matched for headache diagnosis, sex, and age were included
as a control group. RESULTS: The results showed no pre-post differences in
headache reduction between the treatment groups, however, subjects treated with
either of the two relaxation approaches were significantly more improved than
those in the post hoc group on total headache activity and headache-free days.
Clinical improvement (at least 50% improvement) was attained among 19% of the
treated subjects as compared to 7% for those in the post hoc group, a
nonsignificant difference. Higher functional disability predicted a worse
outcome, and positive self-statements predicted better outcome. Altogether, these
variables accounted for 29% of the outcome variance in the total headache
activity. CONCLUSIONS: In the present study, outcomes of relaxation training as
administered by school nurses were not found to be as powerful as similar
treatments provided for adolescents with migraine or tension-type headache in the
previous controlled studies of clinic as well as school samples. It is likely
that the school nurses need to be more thoroughly trained and informed to achieve
cost-effective improvement. Presently, it is suggested that the relaxation
training should not be used as a part of regular treatment in the school health
care for adolescents with recurrent headaches until further evidence is provided.

Publication Types: 
    Clinical Trial
    Comparative Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 15186298 [PubMed - indexed for MEDLINE]

2204: Neurology. 2004 Jun 8;62(11):1926-31.

Migraine practice patterns among neurologists.

Lipton RB, Bigal ME, Rush SR, Yenkosky JP, Liberman JN, Bartleson JD, Silberstein
SD.

Department of Neurology, Albert Einstein College of Medicine, Bronx, NY 10461,
USA. Rlipton@aecom.yu.edu

OBJECTIVE: To assess the attitudes, knowledge, and practice patterns of US
neurologists regarding migraine management relative to the US Headache Consortium
Guidelines (the Guidelines). METHODS: Two samples of 600 neurologists each were
selected from the American Academy of Neurology membership database. The first
group received a Migraine Attitudes, Knowledge, and Practice Patterns (MKAPP)
Survey. The second group received a Clinical Vignette (CV) Survey, presenting two
patient histories and correspondent questions. RESULTS: The MKAPP Survey showed
that most neurologists felt that migraine was primarily a disease of the brain
with a well-established neurobiological basis (69%) and an important part of
their practice (60%). Most (53%) indicated that they routinely used neuroimaging 
in evaluating severe headache, an approach not recommended by the Guidelines.
Most favored acute treatment limits, but 36% did not agree with the Guidelines
that acute treatment should be limited to 2 or 3 days/week. In the CV Survey, for
vignette 1, most (91%) correctly diagnosed migraine, 31% requested neuroimaging
in the absence of indications, 64% appropriately recommended a triptan, and 45%
recommended a preventive medication in the absence of indications. For vignette
2, 78% diagnosed migraine, 71% appropriately ordered neuroimaging, 80%
appropriately recommended a preventive medication, and 38% prescribed a triptan
in face of clear contraindication. CONCLUSIONS: Educational initiatives aiming to
increase the awareness of the Guidelines among neurologists should highlight the 
full range of migraine symptoms that support the diagnosis, appropriate use of
neuroimaging, indications for preventive treatments, issues of triptan
cardiovascular safety, and preventing rebound headaches.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 15184590 [PubMed - indexed for MEDLINE]

2205: Neurosci Lett. 2004 Jun 17;363(3):272-5.

Nitroglycerin induces migraine headache and central sensitization phenomena in
patients with migraine without aura: a study of laser evoked potentials.

de Tommaso M, Libro G, Guido M, Difruscolo O, Losito L, Sardaro M, Cerbo R.

Neurologic and Psychiatric Sciences Department, University of Bari, Bari, Italy. 
m.detommaso@neurol.uniba.it

In migraineurs nitroglycerin (NTG) induces severe delayed headache, resembling
spontaneous migraine attacks. The aim of the present study was to evaluate NTG
laser evoked potentials (LEP) features amplitude and pain sensation to laser
stimuli during NTG-induced headache. Nine patients were selected. Headache was
induced by oral administration of 0.6 mg of NTG; signals were recorded through
disk electrodes placed at the vertex and referred to linked earlobes. CO(2)-LEPs 
delivered by stimulation of the dorsum of both hands and the right and left
supraorbital zones were evaluated after the onset of moderate or severe headache 
resembling spontaneous migraine and at least 72 h after the end of the headache
phase. Patients exhibited a significant heat pain threshold reduction and an LEPs
amplitude increment during headache when both the supraorbital zones were
stimulated. NTG appeared to support a reliable experimental model of migraine,
based on the neuronal effects on the integrative-nociceptive structures. The LEPs
facilitation during NTG-induced headache may be subtended by a hyperactivity of
nociceptive cortex as well as by a failure of pain-inhibitory control.

Publication Types: 
    Comparative Study

PMID: 15182958 [PubMed - indexed for MEDLINE]

2206: Manag Care. 2004 May;13(5):45-51.

Advances in migraine management: implications for managed care organizations.

Dodick DW, Lipsy RJ.

Department of Neurology, Mayo Clinic, Scottsdale, 13400 East Shea Boulevard,
Scottsdale, AZ 85259, USA. Dodick.David@mayo.edu

Migraine headache is a disabling disease that poses a significant societal
burden. Stratified care and early intervention are current strategies for
migraine management. It has been shown that early treatment with triptans in
select patients can improve treatment outcomes. Triptans are selective 5-HT
receptor agonists that are specific and effective treatments in the management of
migraine, and they meet the acute treatment goal of rapid relief with minimal
side effects. Triptans are associated with improved quality of life. Factors such
as speed of onset, need for a second triptan dose, and patient satisfaction
should be considered in the selection of a specific triptan treatment.
Appropriate treatment can decrease costs. The patient's migraine history and
response to prior therapy should be considered when selecting acute treatment.
Cost-effectiveness models can be used to understand the effect of treatment
choices on health care budgets. The direct cost per migraine episode, driven
primarily by the need for rescue medications, is important to include in economic
models. All aspects of effectiveness (efficacy, tolerability, and cost) should be
considered to reduce overall managed care expenditures for migraine treatment.
The improved clinical profiles of the triptans provide substantial value to
managed care organizations.

PMID: 15181689 [PubMed - indexed for MEDLINE]

2207: Ann Neurol. 2004 Jun;55(6):884-7.

Alternating hemiplegia of childhood or familial hemiplegic migraine? A novel
ATP1A2 mutation.

Swoboda KJ, Kanavakis E, Xaidara A, Johnson JE, Leppert MF, Schlesinger-Massart
MB, Ptacek LJ, Silver K, Youroukos S.

Department of Neurology, University of Utah School of Medicine, Salt Lake City,
UT 84132, USA. Swoboda@genetics.utah.edu

Alternating hemiplegia of childhood (AHC) is typically distinguished from
familial hemiplegic migraine (FHM) by infantile onset of the characteristic
symptoms and high prevalence of associated neurological deficits that become
increasingly obvious with age. Expansion of the clinical spectrum in FHM recently
has begun to blur the distinction between these disorders. We report a novel
ATP1A2 mutation in a kindred with features that bridge the phenotypic spectrum
between AHC and FHM syndromes, supporting a possible common pathogenesis in a
subset of such cases. Mutation analysis in classic sporadic AHC patients and in
an additional five kindreds in which linkage to the ATP1A2 locus could not be
excluded failed to identify additional mutations.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 15174025 [PubMed - indexed for MEDLINE]

2208: Prim Care. 2004 Jun;31(2):277-92, vi.

Migraine diagnosis and treatment.

Loder E.

Harvard Medical School, 25 Shattuck Street, Boston, MA 02114, USA.
eloder@partners.org

Migraine is a prevalent condition that causes significant disability in otherwise
healthy persons. Diagnosis is clinical, based on recognition of a constellation
of signs and symptoms. Treatment includes nonpharmacologic management, including 
lifestyle alterations,abortive treatment of individual attacks, and preventive
medications for patients with frequent or troublesome attacks. Guidelines are
available that summarize the quality of evidence for individual interventions,
but treatment must be individualized.

Publication Types: 
    Review

PMID: 15172507 [PubMed - indexed for MEDLINE]

2209: Curr Opin Neurol. 2004 Jun;17(3):289-93.

Migraine aura: new information on underlying mechanisms.

Sánchez-del-Rio M, Reuter U.

Headache Program, Department of Neurology, Hospital Ruber Internacional, Madrid, 
Spain and Department of Neurology, Charité, Universitätsmedizin Berlin, Berlin,
Germany. msanchezdelrio@ruberinternacional.es

PURPOSE OF REVIEW: Since the initial description of cortical spreading depression
by Leao, evidence that cortical spreading depression is the underlying
pathomechanism of migraine aura has increased. The purpose of this review is to
describe the ultimate genetic and molecular mechanisms of migraine aura. RECENT
FINDINGS: It has been debated how a primarily cortical phenomenon (aura phase)
may activate trigeminal fibres (headache phase). Recent data have demonstrated a 
link between cortical events and activation of the pain-sensitive structures of
the dura mater. The initial cortical hyperperfusion in cortical spreading
depression is partly mediated by the release of trigeminal and parasympathetic
neurotransmitters from perivascular nerve fibres, whereas delayed meningeal blood
flow increase is mediated by a trigeminal-parasympathetic brainstem connection.
With regard to molecular mechanisms, cortical spreading depression upregulates a 
variety of genes coding for COX-2, TNF-alpha and IL-1beta, galanin or
metalloproteinases. The activation of metalloproteinases leads to leakage of the 
blood-brain barrier, allowing potassium, nitric oxide, adenosine and other
products released by cortical spreading depression to reach and sensitize the
dural perivascular trigeminal afferents. In familial hemiplegic migraine, new
mutations have been described in chromosome 1q23, leading to a haploinsufficiency
of the sodium/potassium pump, producing an increase in intracellular calcium,
similar to the CACNA1A mutation. SUMMARY: Recent studies have helped unravel the 
basic mechanisms involved in migraine aura. Far from being a simple phenomenon, a
sequence of events leads from the cortex to the activation of pain-sensitive
structures. The role of the brainstem is still poorly described. The
identification of target molecules may provide new therapies.

Publication Types: 
    Review

PMID: 15167063 [PubMed - indexed for MEDLINE]

2210: Curr Opin Neurol. 2004 Jun;17(3):283-8.

Recent findings in headache genetics.

Kors EE, Vanmolkot KR, Haan J, Frants RR, van den Maagdenberg AM, Ferrari MD.

Department of Neurology and Human Genetics, Leiden University Medical Center,
Leiden, The Netherlands.

PURPOSE OF REVIEW: The progress in headache genetics, especially migraine
genetics, recently jumped ahead with some major discoveries. RECENT FINDINGS:
Family and epidemiological studies further strengthen the genetic contribution to
migraine and two recent observations gave new molecular insights in the disease. 
Studies on the genetics of familial hemiplegic migraine revealed, in addition to 
the previously identified familial hemiplegic migraine type 1 gene CACNA1A on
chromosome 19, the familial hemiplegic migraine type 2 gene ATP1A2, encoding the 
alpha2-subunit of sodium/potassium pumps. Recent genome screens in families with 
migraine identified susceptibility loci on chromosomes 4, 6, 11 and 14. SUMMARY: 
The findings in familial hemiplegic migraine confirm that dysfunction in ion
transport is a key factor in migraine pathophysiology and might help us in the
elucidation of migraine molecular pathways. The identification of several
migraine susceptibility loci underline its genetically complex nature.

Publication Types: 
    Review

PMID: 15167062 [PubMed - indexed for MEDLINE]

2211: Pediatr Neurol. 2004 May;30(5):356-7.

Familial retinal migraines.

Lewinshtein D, Shevell MI, Rothner AD.

Department of Neurology/Neurosurgery, McGill University, Montreal, Quebec,
Canada.

Approximately 25% of sufferers of retinal migraine are thought to have a positive
family history. Retinal migraines can cause both transient, and rarely permanent,
unilateral monocular visual loss. This report of familial retinal migraines
furthers our understanding of this particular migraine subtype. Two families with
retinal migraines are reported suggesting an autosomal-dominant inheritance
pattern with variable expression and penetrance.

Publication Types: 
    Case Reports
    Research Support, Non-U.S. Gov't

PMID: 15165640 [PubMed - indexed for MEDLINE]

2212: Pharmacotherapy. 2004 May;24(5):638-48.

Migraine headache misconceptions: barriers to effective care.

Wenzel R, Dortch M, Cady R, Lofland JH, Diamond S.

Diamond Headache Clinic Inpatient Unit, Saint Joseph Hospital, Resurrection
Health Care, Chicago, Illinois 60657, USA. rwenz@hotmail.com

Migraine headaches affect 12% of the adult population in the United States and
cause a significant economic loss due to decreased workplace productivity
Although interactions between pharmacists and individuals with headache are
common, few pharmacists receive adequate training regarding migraine therapy. We 
refute several misconceptions that hinder effective care, such as that migraine
is a vascular disease, triptans cause rampant cardiacrelated morbidity and even
mortality, a best oral triptan exists, sinus and tension headaches are prevalent,
and migraine is a minor economic problem. Our pathophysiologic understanding
demonstrates that migraine is a neurologic process of the trigeminovascular
system, of which vascular effects are secondary. This process can result in a
myriad of clinical signs and symptoms, often leading to a misdiagnosis of sinus
or tension headache. The last decade's experience with triptans in more than half
a billion people worldwide reveals a benign adverse-effect profile, particularly 
when taken early in an attack. Published reports and real-world experiences
illustrate that these drugs do not merit fears of triptan-induced cardiac
consequences in appropriately selected individuals. Society's productivity loss
due to migraine is measured in billions of dollars. Restoring a patient's ability
to function normally is now recognized as the primary treatment goal, not merely 
relieving pain. Thus, the overreliance on "pain killer" drugs such as
butalbital-containing products and the continued underutilization of
migraine-specific drugs need to be addressed. Opportunities exist for pharmacists
and other health care providers to dispel continually propagated migraine
misconceptions and familiarize themselves with advances in therapy. Such actions 
will benefit patients, the health care system, and society as a whole.

Publication Types: 
    Research Support, U.S. Gov't, P.H.S.
    Review

PMID: 15162898 [PubMed - indexed for MEDLINE]

2213: Neuro Endocrinol Lett. 2004 Feb-Apr;25(1-2):31-9.

Republished in:
    Neuro Endocrinol Lett. 2008 Apr;29(2):192-200.

Clinical endocannabinoid deficiency (CECD): can this concept explain therapeutic 
benefits of cannabis in migraine, fibromyalgia, irritable bowel syndrome and
other treatment-resistant conditions?

Russo EB.

GW Pharmaceuticals, 2235 Wylie Avenue, Missoula, MT 59802, USA.
erusso@montanadsl.net

OBJECTIVES: This study examines the concept of clinical endocannabinoid
deficiency (CECD), and the prospect that it could underlie the pathophysiology of
migraine, fibromyalgia, irritable bowel syndrome, and other functional conditions
alleviated by clinical cannabis. METHODS: Available literature was reviewed, and 
literature searches pursued via the National Library of Medicine database and
other resources. RESULTS: Migraine has numerous relationships to endocannabinoid 
function. Anandamide (AEA) potentiates 5-HT1A and inhibits 5-HT2A receptors
supporting therapeutic efficacy in acute and preventive migraine treatment.
Cannabinoids also demonstrate dopamine-blocking and anti-inflammatory effects.
AEA is tonically active in the periaqueductal gray matter, a migraine generator. 
THC modulates glutamatergic neurotransmission via NMDA receptors. Fibromyalgia is
now conceived as a central sensitization state with secondary hyperalgesia.
Cannabinoids have similarly demonstrated the ability to block spinal, peripheral 
and gastrointestinal mechanisms that promote pain in headache, fibromyalgia, IBS 
and related disorders. The past and potential clinical utility of cannabis-based 
medicines in their treatment is discussed, as are further suggestions for
experimental investigation of CECD via CSF examination and neuro-imaging.
CONCLUSION: Migraine, fibromyalgia, IBS and related conditions display common
clinical, biochemical and pathophysiological patterns that suggest an underlying 
clinical endocannabinoid deficiency that may be suitably treated with cannabinoid
medicines.

Publication Types: 
    Review

PMID: 15159679 [PubMed - indexed for MEDLINE]

2214: Neurology. 2004 May 25;62(10):1857-61.

Variability of familial hemiplegic migraine with novel A1A2 Na+/K+-ATPase
variants.

Jurkat-Rott K, Freilinger T, Dreier JP, Herzog J, Göbel H, Petzold GC, Montagna
P, Gasser T, Lehmann-Horn F, Dichgans M.

Department of Applied Physiology, Ulm University, Germany.
karin.jurkat-rott@medizin.uni-ulm.de

A1A2 Na+/K+-ATPase mutations cause familial hemiplegic migraine type 2 (FHM2).
The authors identified three putative A1A2 mutations (D718N, R763H, P979L) and
three that await validation (P796R, E902K, X1021R). Ten to 20% of FHM cases may
be FHM2. A1A2 mutations have a penetrance of about 87%. D718N causes frequent,
long-lasting HM, and P979L may cause recurrent coma. D718N and P979L may
predispose to seizures and mental retardation. A1A2 does not play a major role in
sporadic HM; only one variant, R383H, occurred in 1 of 24 cases.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 15159495 [PubMed - indexed for MEDLINE]

2215: Neurology. 2004 May 25;62(10):1695-700.

Comment in:
    Neurology. 2004 May 25;62(10):1662-3.

Use of narcotic analgesics in the emergency department treatment of migraine
headache.

Colman I, Rothney A, Wright SC, Zilkalns B, Rowe BH.

Department of Psychiatry, Cambridge University, UK.

OBJECTIVE: Treatment of acute migraine headache with narcotics is potentially
ineffective and may lead to abuse. The authors examined the treatment practice
variation across five linked EDs in one Canadian center, focusing on the use of
narcotic analgesics and factors associated with their use. METHODS: Five hundred 
acute migraine headache patient charts were randomly selected from five Canadian 
EDs. Charts underwent a structured review to determine medication use. Data were 
analyzed, comparing those who received narcotics as first-line treatment with
those who did not, using chi(2) and t-tests and logistic regression. RESULTS: The
majority of patients (59.6%) received narcotics as first-line treatment. Numerous
factors were associated with first-line narcotic treatment. Having taken
antiheadache medications prior to ED presentation (odds ratio [OR]: 2.63; 95% CI:
1.53, 4.51) and hospital of presentation being other than Hospital A (e.g.,
Hospital D, OR: 6.32; 95% CI: 2.76, 14.46) increased the odds of receiving
first-line narcotics. Having received a more urgent triage score (OR: 0.4; 95%
CI: 0.24, 0.65) or having a longer duration of headache (OR: 0.994; 95% CI: 0.99,
0.99) decreased the odds of receiving first-line narcotics. CONCLUSIONS: Acute
migraine management in these EDs does not meet current consensus guidelines.
Factors associated with narcotic use are predictable, and a concerted effort to
replace narcotics with more evidence-based first-line treatments is needed.

Publication Types: 
    Multicenter Study
    Research Support, Non-U.S. Gov't
    Review

PMID: 15159464 [PubMed - indexed for MEDLINE]

2216: Clin Dermatol. 2004 Jan-Feb;22(1):76-81.

Botulinum neurotoxin for the treatment of migraine and other primary headache
disorders.

Dodick D, Blumenfeld A, Silberstein SD.

Department of Neurology, Mayo Clinic, Scottsdale, AZ 85259, USA.
dodick.david@mayo.edu

Botulinum toxin A (BoNT/A), a neurotoxin, is effective for treating a variety of 
disorders of involuntary muscle contraction, including cervical dystonia,
blepharospasm and hemifacial spasm. It inhibits neurouscular signaling by
blocking the release of acetylcholine at the neuromuscular junction. The
biological effects of the toxin are transient with normal neuronal signaling
returning within approximately 3-6 months post injection. Recently, clinical
findings suggest that BoNT/A may inhibit pain associated with migraine and other 
headache types. The mechanism by which this toxin inhibits pain is under
investigation, recent findings suggest that it inhibits the release of
neurotransmitters from nociceptive nerve terminals and in this way may exert an
analgesic effect. A number of retrospective open-label chart reviews and three
placebo-controlled double-blind trials have demonstrated that localized
injections of BTX-A significantly reduce migraine frequency, severity, and
migraine-associated disability. The majority of patients in these studies
experienced no BoNT/A mediated side effects; however, a small percentage of
patients did report transient minor side effects including blepharoptosis,
dipolpia, and injection-site weakness. Currently there are several large-scale
randomized, placebo-controlled clinical trials in progress evaluating the
efficacy, optimal dosing and side effect profile of this toxin as a novel
treatment for migraine and other headache types. These studies may provide
further evidence that BoNT/A is an effective option for the preventive treatment 
of migraine.

Publication Types: 
    Review

PMID: 15158549 [PubMed - indexed for MEDLINE]

2217: Lancet Neurol. 2004 Jun;3(6):354-61.

Oestrogen and attacks of migraine with and without aura.

MacGregor EA.

City of London Migraine Clinic and the Department of Gynaecology, St
Bartholomew's Hospital, London, UK. anne.macgregor@bartsandthelondon.nhs.uk

During women's reproductive years, migraine is three times more common than in
men of a similar age. Although this female preponderance is commonly assumed to
be associated with the additional trigger of fluctuating sex hormones of the
menstrual cycle, few studies have been done to confirm or refute this. This
review is confined to the relation between oestrogen and attacks of migraine. The
evidence for an association between oestrogen "withdrawal" and attacks of
migraine without aura is presented, as well as evidence for an association
between high oestrogen states and attacks of migraine with aura. Only clinical
data are presented here.

Publication Types: 
    Review

PMID: 15157850 [PubMed - indexed for MEDLINE]

2218: Cephalalgia. 2004 Jun;24(6):503-7.

Lack of interaction between a polymorphism in the dopamine D2 receptor gene and
the clinical features of migraine.

Rebaudengo N, Rainero I, Parziale A, Rosina F, Pavanelli E, Rubino E, Mazza C,
Ostacoli L, Furlan PM.

Neurology Service, Gradenigo Hospital, Turin, Italy.

The purpose of this study was to evaluate whether a particular genotype of the
dopamine D2 receptor (DRD2) gene would affect the clinical features of migraine. 
In a group of 118 migraineurs (55 migraine with aura and 63 migraine without aura
patients), we tested the association of the biallelic C/T NcoI DRD2 polymorphism 
with several characteristics of the disease. Genotype and allele frequencies
resulted similarly distributed in migraine with aura and migraine without aura
patients (chi2 = 1.58, P = 0.45 and chi2 = 0.09, P = 0.77, respectively). The
different DRD2 genotypes (C/C, C/T and T/T) had no significant effects on age at 
onset of migraine, presence of premonitory phenomena, frequency of headache
attacks, associated symptoms, psychological features and quality of life of our
migraine patients. The results of our study do not support a role for the DRD2
gene in modifying the clinical features of migraine. Copyright Blackwell
Publishing Ltd.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 15154861 [PubMed - indexed for MEDLINE]

2219: Cephalalgia. 2004 Jun;24(6):491-4.

MTHFR T677 homozygosis influences the presence of aura in migraineurs.

Oterino A, Valle N, Bravo Y, Muñoz P, Sánchez-Velasco P, Ruiz-Alegría C, Castillo
J, Leyva-Cobián F, Vadillo A, Pascual J.

Service of Neurology, University Hospital Marqués de Valdecilla, Santander,
Spain. oterinoa@unican.es

It has been suggested that folate metabolism could be involved in migraine
pathogenesis. We analysed the 5',10'-methylenetetrahydrofolate reductase (MTHFR) 
genotypic distribution in a large migraine sample. We genotyped 230 migraine
patients (152 migraine without aura (MO) and 78 migraine with aura (MA)) and 204 
nonheadache controls. The incidence of TT homozygosis for migraine in general
(12%), MO (9%) and MA (18%) did not significantly differ from that found in
healthy controls (13%). Differences were significant when the frequency of TT
homozygosis between MA and MO (P = 0.03, OR = 2.34, 95% CI = 1.04-5.26) was
compared. There was a tendency for a higher frequency of the MTHFR T allele in
the MA group (42%) as compared to MO (29%) and controls (36%). These differences 
were significant only in the case of MA vs. MO (P = 0.006, OR = 1.75, 95% CI =
1.15-2.65). These results could indicate that the MTHFR C677T polymorphism,
causing mild hyperhomocystinaemia, might be a genetic risk factor for
experiencing aura among migraineurs. Overall, however, there was no association
between migraine and the C677T MTHFR polymorphism. Copyright Blackwell Publishing
Ltd.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 15154859 [PubMed - indexed for MEDLINE]

2220: Cephalalgia. 2004 Jun;24(6):483-90.

Transformed migraine and medication overuse in a tertiary headache
centre--clinical characteristics and treatment outcomes.

Bigal ME, Rapoport AM, Sheftell FD, Tepper SJ, Lipton RB.

Department of Neurology, Albert Einstein College of Medicine, Bronx, New York,
USA. mbigal@aecom.yu.edu

Studies suggest that a substantial proportion of headache sufferers presenting to
headache clinics may overuse acute medications. In some cases, overuse may be
responsible for the development or maintenance of a chronic daily headache (CDH) 
syndrome. The objectives of this study are to evaluate patterns of analgesic
overuse in patients consulting a headache centre and to compare the outcomes in a
group of patients who discontinued medication overuse to those of a group who
continued the overuse, in patients with similar age, sex and psychological
profile. We reviewed charts of 456 patients with transformed migraine (TM) and
acute medication overuse defined by one of the following criteria: 1. Simple
analgesic use (>1000 mg ASA/acetaminophen) > 5 days/week; 2. Combination
analgesics use (caffeine and/or butalbital) > 3 tablets a day for > 3 days a
week; 3. Opiate use > 1 tablet a day for > 2 days a week; 4. Ergotamine tartrate 
use: 1 mg PO or 0.5 mg PR for > 2 days a week. For triptans, we empirically
considered overuse > 1 tablet per day for > 5 days per week. Patients who were
able to undergo detoxification and did not overuse medication (based on the above
definition) after one year of follow-up were considered to have successful
detoxification (Group 1). Patients who were not able to discontinue offending
agents, or returned to a pattern of medication overuse within one year were
considered to have unsuccessful detoxification (Group 2). We compared the
following outcomes after one year of follow-up: Number of days with headache per 
month; Intensity of headache; Duration of headache; Headache score (frequency x
intensity). The majority of patients overused more than one type of medication.
Numbers of tablets taken ranged from 1 to 30 each day (mean of 5.2). Forty-eight 
(10.5%) subjects took >10 tablets per day. Considering patients seen in the last 
5 years, we found the following overused substances: Butalbital containing
combination products, 48%; Acetaminophen, 46.2%; Opioids, 33.3%; ASA, 32.0%;
Ergotamine tartrate, 11.8%; Sumatriptan, 10.7%; Nonsteroidal anti-inflammatory
medications other than ASA, 9.8%; Zolmitriptan, 4.6%; Rizatriptan, 1.9%;
Naratriptan, 0.6%. Total of all triptans, 17.8%. Of 456 patients, 318 (69.7%)
were successfully detoxified (Group 1), and 138 (30.3%) were not (Group 2). The
comparison between groups 1 and 2 after one year of follow-up showed a decrease
in the frequency of headache of 73.7% in group 1 and only 17.2% in group 2 (P <
0.0001). Similarly, the duration of head pain was reduced by 61.2% in group 1 and
14.8% in group 2 (P < 0.0001). The headache score after one year was 18.8 in
group 1 and 54 in group 2 (P < 0.0001). A total of 225 (70.7%) successfully
detoxified subjects in Group 1 returned to an episodic pattern of migraine,
compared to 21 (15.3%) in Group 2 (P < 0.001). More rigorous prescribing
guidelines for patients with frequent headaches are urgently needed. Successful
detoxification is necessary to ensure improvement in the headache status when
treating patients who overuse acute medications. Copyright Blackwell Publishing
Ltd.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 15154858 [PubMed - indexed for MEDLINE]

2221: Cephalalgia. 2004 Jun;24(6):455-65.

Attitudes and burden of disease among self-considered migraineurs--a nation-wide 
population-based survey in Sweden.

Linde M, Dahlöf C.

Gothenburg Migraine Clinic, Gothenburg, Sweden. mattias.linde@neuro.gu.se

The authors have earlier reported a 1-year prevalence of 13.2 +/- 1.9% for
migraine in Sweden. This is a subsequent extensive postal survey of the burden of
disease and attitudes among migraineurs in a sample (n = 423, 23% men and 77%
women, aged 18-74 years) randomly recruited from all main regions of the country,
representative of adults in the general Swedish population with self-considered
migraine. Results are presented only from participants who after analysis of
symptoms were found to fulfil the International Headache Society's migraine
criteria. In order to assess headache duration open-mindedly, the strict time
criterion 4-72 h was deliberately disregarded as an inclusion criterion.
Individuals who did not consider themselves to have migraine were excluded. Less 
than half of the group (45%) had received a diagnosis of migraine from a
physician. Accordingly, a large number of individuals that would not have come to
attention in a clinic-based study have been included. The mean attack frequency
was 1.3 per month, and the number of attacks per year in Swedish adults is
approximately 10 million. A minority (27%) of sufferers have a majority (68%) of 
all attacks. The mean attack duration was 19 h. A considerable number of
individuals reported attacks < 4 h (15.8%) or > 72 h (6.4%). Less than half of
the individuals recovered completely between the attacks. Despite this, only
every fourth (27%) participant was currently consulting a physician (6%
regularly; 21% occasionally). Most of the migraineurs reported absence from
school or work, a negative influence of migraine on the most important aspects of
life, and an interest in testing other treatments for migraine during the last
year. Of those (n = 231) migraineurs who had consulted a physician, about 60%
were satisfied with information given or treatment offered. This implies,
however, that there is still room for improvement in the management of migraine
in Sweden. Copyright Blackwell Publishing Ltd.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 15154855 [PubMed - indexed for MEDLINE]

2222: Cephalalgia. 2004 Jun;24(6):425-38.

Assessment of anti-migraine potential of a novel alpha-adrenoceptor agonist
S19014: effects on porcine carotid and regional haemodynamics and human coronary 
artery.

Kapoor K, Willems EW, Maassen VanDenBrink A, Heiligers JP, Cordi AA,
Vayssettes-Courchay C, Verbeuren TJ, Villalón CM, Saxena PR.

Department of Pharmacology, Cardiovascular Research Institute 'COEUR', Erasmus
MC, University Medical Center Rotterdam, Rotterdam, the Netherlands.

Taking into account the drawbacks associated with the use of triptans, attempts
are being made to explore other avenues for the treatment of migraine. Recently, 
it has been shown that both alpha1- and alpha2-adrenoceptors mediate the
constriction of porcine carotid arteriovenous anastomoses, which has effectively 
served as an experimental model predictive of anti-migraine activity. The present
study investigated the effects of a novel alpha-adrenoceptor agonist S19014
(spiro[(1,3-diazacyclopent-1-ene)-5 : 2'-(4',5'-dimethylindane)] fumarate) on
carotid and systemic haemodynamics in anaesthetized pigs, and on human isolated
coronary arteries. Increasing doses of S19014 (1-30 micro g/kg, i.v.) produced a 
dose-dependent initial short-lasting vasopressor response and a decrease of total
carotid blood flow and conductance. The carotid blood flow and conductance
changes were exclusively due to constriction of carotid arteriovenous anastomoses
(capillary blood flow increased) and were accompanied by an increase in
arterio-jugular venous oxygen saturation difference. Whereas prazosin (100 micro 
g/kg, i.v.) was ineffective, rauwolscine (300 micro g/kg, i.v.) attenuated the
responses to S19014. The compound did not much affect the distribution of cardiac
output to peripheral organs when compared with the vehicle group. Furthermore,
S19014 only slightly contracted the human isolated coronary artery and its
contractions, contrary to those of sumatriptan, were not increased in blood
vessels pre-contracted with U46619. These results suggest that (i) the systemic
and carotid vascular effects of S19014 are mainly mediated by
alpha2-adrenoceptors, and (ii) S19014 could be effective in the treatment of
migraine with an improved cardiovascular tolerance. Copyright Blackwell
Publishing Ltd.

Publication Types: 
    Comparative Study
    In Vitro
    Research Support, Non-U.S. Gov't

PMID: 15154852 [PubMed - indexed for MEDLINE]

2223: Am J Manag Care. 2004 May;10(5):313-20.

Comment in:
    Am J Manag Care. 2004 Jul;10(7 Pt 1):414.    Am J Manag Care. 2004 May;10(5):305-6.

The family impact and costs of migraine.

Stang PE, Crown WH, Bizier R, Chatterton ML, White R.

Galt Associates, Inc, Blue Bell, PA 19422, USA. pstang@galt-assoc.com

OBJECTIVE: To obtain information on migraine and its impact on the family,
particularly on the healthcare utilization and productivity of family members
without migraine. STUDY DESIGN: Retrospective study using linked medical and
pharmacy claims data that allowed identification of families and individuals with
migraine. PATIENTS AND METHODS: Families with at least 1 migraineur were matched 
with up to 3 nonmigraineur families on employer, age of migraineur, number of
family members, sex, and index date quarter. For a subset of employees, data on
short- and long-term disability as well as absenteeism also were evaluated to
determine the impact of migraine on these indirect costs. RESULTS: The total
healthcare costs of a family with a migraineur were 70% higher than those of the 
nonmigraine family, with most of the difference concentrated in outpatient costs.
The impact of having a migraineur in the family persisted even after controlling 
for other disorders and demographics in a multivariate model. Total healthcare
costs per family depended on which family member was the migraineur, and were
about dollars 600 higher when the sole migraineur was a child versus a parent and
almost dollars 2500 higher when both a parent and child were affected (compared
with families in which the sole migraineur was a child). Work absence days,
short-term disability, and workman's compensation days all were higher among
migraine families than among families without a migraineur. CONCLUSION: Migraine 
families incur far higher direct and indirect healthcare costs than nonmigraine
families, with variation depending on which family member is the clinically
detected migraineur.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 15152701 [PubMed - indexed for MEDLINE]

2224: Headache. 2004 May;44 Suppl 1:S31-9.

Cardiovascular risk assessment and triptans.

Papademetriou V.

Hypertension Research Center, Georgetown University, Wasington, DC 20422, USA.

Identifying the patient for whom triptans are contraindicated because of
recognized, diagnosed cardiovascular disease is relatively straightforward.
Determining whether a patient with potential unrecognized cardiovascular disease 
is an appropriate candidate for triptan therapy, however, constitutes a difficult
challenge, especially in the absence of a framework for workup of patients. This 
article discusses the pathophysiology of coronary heart disease and issues
involved in assessing cardiovascular risk, and it attempts to provide a framework
for cardiovascular risk assessment that can be applied to decisions for
prescribing triptans. Current guidelines for cardiovascular risk assessment allow
stratification of patients to low, intermediate, or high risk of coronary heart
disease events. This framework for risk assessment can be applied to decisions
for prescribing triptans. Cardiovascular risk-assessment algorithms discussed
elsewhere in this supplement suggest that patients at low risk (1 or no risk
factors) of coronary heart disease can be prescribed triptans without the need
for a more intensive cardiovascular evaluation. Conversely, patients with
established coronary heart disease or coronary heart disease risk equivalents
should not be prescribed triptans according to the current prescribing
recommendations. Patients at intermediate risk (2 or more risk factors) of
coronary heart disease require cardiovascular evaluation before triptans can be
prescribed. Current understanding suggests that the risk of future acute coronary
events is a function of the absolute number of vulnerable plaques present, a
variable that cannot be accurately determined using available technology or
risk-prediction models. Cardiovascular risk-assessment guidelines should be
evaluated in the context of this limitation.

Publication Types: 
    Review

PMID: 15149491 [PubMed - indexed for MEDLINE]

2225: Headache. 2004 May;44 Suppl 1:S20-30.

Cardiovascular tolerability and safety of triptans: a review of clinical data.

Dodick DW, Martin VT, Smith T, Silberstein S.

Department of Neurology, Mayo Clinic Scottsdale, AZ 85359, USA.

Triptans are not widely used in clinical practice despite their well-established 
efficacy, endorsement by the US Headache Consortium, and the demonstrable need to
employ effective intervention to reduce migraine-associated disability. Although 
the relatively restricted use of triptans may be attributed to several factors,
research suggests that prescribers' concerns about cardiovascular safety
prominently figure in limiting their use. This article reviews clinical
data--including results of clinical trials, postmarketing studies and
surveillance, and pharmacodynamic studies--relevant to assessing the
cardiovascular safety profile of the triptans. These data demonstrate that
triptans are generally well tolerated. Chest symptoms occurring during use of
triptans are usually nonserious and usually not attributed to ischemia. Incidence
of triptan-associated serious cardiovascular adverse events in both clinical
trials and clinical practice appears to be extremely low. When they do occur,
serious cardiovascular events have most often been reported in patients at
significant cardiovascular risk or in those with overt cardiovascular disease.
Adverse cardiovascular events also have occurred, however, in patients without
evidence of cardiovascular disease. Several lines of evidence suggest that
nonischemic mechanisms are responsible for sumatriptan-associated chest symptoms,
although the mechanism of chest symptoms has not been determined to date.
Importantly, most of the clinical trials and clinical practice data on triptans
are derived from patients without known cardiovascular disease. Therefore, the
conclusions of this review cannot be extended to patients with cardiovascular
disease. The cardiovascular safety profile of triptans favors their use in the
absence of contraindications.

Publication Types: 
    Review

PMID: 15149490 [PubMed - indexed for MEDLINE]

2226: Headache. 2004 May;44 Suppl 1:S5-12.

Are migraine and coronary heart disease associated? An epidemiologic review.

Rosamond W.

Deparment of Epidemiology, University of North Carolina at Chapel Hill, 27514,
USA.

In evaluating the cardiovascular risks of triptans (5-HT(1B/1D) agonists) for the
treatment of migraine, the possible relationship between migraine and
cardiovascular disease warrants careful assessment. The vascular nature of
migraine is compatible with the possibility that migraine is a manifestation of
cardiovascular disease or is linked to cardiovascular disease via a common
mechanism. If so, then migraine itself--independent of the use of triptans--may
be associated with an increased risk of cardiac events. This article considers
the epidemiologic literature pertinent to evaluating the association of migraine 
with coronary heart disease. The research reviewed herein fails to support an
association between migraine and coronary heart disease. First, data from several
large cohort studies show that the presence of migraine does not increase risk of
coronary heart disease. Furthermore, although migraineurs are generally more
likely than nonmigraineurs to report chest pain, the presence of chest pain in
most studies did not predict serious cardiac events such as myocardial
infarction. That the gender- and age-specific prevalence of migraine does not
overlap with that of coronary heart disease is also consistent with a lack of
association between migraine and atherosclerotic cardiovascular disease. While
migraine appears not to be associated with coronary heart disease, preliminary
evidence suggests a possible link of migraine with vasospastic disorders such as 
variant angina and Raynaud's phenomenon. These results warrant further
investigation in large prospective studies.

Publication Types: 
    Review

PMID: 15149488 [PubMed - indexed for MEDLINE]

2227: Arch Neurol. 2004 May;61(5):794-9.

The aura-headache connection in migraine: a historical analysis.

Spierings EL.

Department of Neurology, Brigham and Women's Hospital, Harvard Medical School,
Boston, Mass, USA.

A historical analysis is presented of insights into the pathogenetic mechanisms
related to the migraine aura and headache and how the mechanisms connect. In the 
traditional sequential concept, advanced through the work of Edward Liveing, MD, 
Harold G. Wolff, MD, and others, the mechanisms are considered causally
connected. A noncausal, parallel concept has been proposed as well and is
considered in light of the results of recent animal experimental studies.

Publication Types: 
    Historical Article

PMID: 15148162 [PubMed - indexed for MEDLINE]

2228: Acta Neurol Scand. 2004 Jun;109(6):407-9.

Serotonin 2C receptor gene Cys23Ser polymorphism: a candidate genetic risk factor
of migraine with aura in Japanese population.

Kusumi M, Araki H, Ijiri T, Kowa H, Adachi Y, Takeshima T, Sakai F, Nakashima K.

Department of Neurology, Institute of Neurological Sciences, Tottori University
Faculty of Medicine, Yonago, Japan. mkusumi@grape.med.tottori-u.ac.jp

OBJECTIVES: The goal of this study is to clarify the association between migraine
and Serotonin 2C receptor Cys23Ser polymorphism in Japanese population. MATERIALS
AND METHOD: This study included 37 individuals with migraine with aura (MWA), 80 
with migraine without aura, 43 with tension type headache (TH) and 360 with
controls. The genotypes of Cys23Ser polymorphism were confirmed by polymerase
chain reaction-restriction fragment length polymorphism techniques. RESULTS: The 
Ser allele frequency in control subjects is much less than that in Caucasian
population. The Ser allele frequency in patients with MWA was higher than that in
control subjects. CONCLUSION: The present study provides that 5HTR2c Cys23Ser
polymorphism may be associated with MWA in Japanese population. Copyright
Blackwell Munksgaard 2004

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 15147464 [PubMed - indexed for MEDLINE]

2229: Headache. 2004 May;44(5):440-2.

Venous angioma associated with atypical ophthalmoplegic migraine.

Berbel-Garcia A, Martinez-Salio A, Porta-Etessam J, Saiz-Diaz R, Gonzalez-León P,
Ramos A, Campollo J.

Department of Neurology, Hospital Mancha Centro, Alcazar de San Juan, Spain.

BACKGROUND: Ophthalmoplegic migraine is a rare syndrome in which episodic
headaches are associated with ophthalmoplegia. Several recent reports emphasize
the possibility, especially in atypical cases, of a heterogeneous type of
ophthalmoplegic migraine. METHODS: We describe the case of an 18-year-old woman
with recurrent episodic headache accompanied by binocular diplopia due to left
third cranial nerve palsy. The symptoms resolve in hours. A diagnosis of atypical
ophthalmoplegic migraine was established. RESULTS: Digital angiography revealed a
venous angioma draining into the left cavernous sinus. CONCLUSIONS: This case
reveals the importance of differential diagnosis in atypical migraine in which
the symptomatology could be secondary to intracranial lesions. We propose venous 
stasis as a cause of symptoms.

Publication Types: 
    Case Reports

PMID: 15147253 [PubMed - indexed for MEDLINE]

2230: Headache. 2004 May;44(5):426-35.

Understanding the patient with migraine: the evolution from episodic headache to 
chronic neurologic disease. A proposed classification of patients with headache.

Cady RK, Schreiber CP, Farmer KU.

Headache Care Center and Primary Care Network, Springfield, MO 65804, USA.

Traditionally, episodic primary headache disorders are characterized by a return 
of preheadache (normal) neurologic function between episodes of headache. In
contrast, patients with chronic headache often do not return to normal neurologic
function between headache attacks. This article proposes that the evolution from 
episodic migraine to chronic headache may parallel the neurologic disruption
observed during the progression of an acute migraine attack and that changes in
baseline neurologic function between episodes of headache may be a more sensitive
indicator of headache transformation than headache frequency alone. Early
recognition of nonheadache changes in nervous system function may offer a more
sensitive and specific approach to migraine prevention.

PMID: 15147250 [PubMed - indexed for MEDLINE]

2231: Headache. 2004 May;44(5):414-25.

Consensus statement: cardiovascular safety profile of triptans (5-HT agonists) in
the acute treatment of migraine.

Dodick D, Lipton RB, Martin V, Papademetriou V, Rosamond W, MaassenVanDenBrink A,
Loutfi H, Welch KM, Goadsby PJ, Hahn S, Hutchinson S, Matchar D, Silberstein S,
Smith TR, Purdy RA, Saiers J; Triptan Cardiovascular Safety Expert Panel.

Department of Neurology, Mayo Clinic Scottsdale, AZ 85259, USA.

BACKGROUND: Health care providers frequently cite concerns about cardiovascular
safety of the triptans as a barrier to their use. In 2002, the American Headache 
Society convened the Triptan Cardiovascular Safety Expert Panel to evaluate the
evidence on triptan-associated cardiovascular risk and to formulate consensus
recommendations for making informed decisions for their use in patients with
migraine. OBJECTIVE: To summarize the evidence reviewed by the Triptan
Cardiovascular Safety Expert Panel and their recommendations for the use of
triptans in clinical practice. PARTICIPANTS: The Triptan Cardiovascular Safety
Expert Panel was composed of a multidisciplinary group of experts in neurology,
primary care, cardiology, pharmacology, women's health, and epidemiology.
EVIDENCE AND CONSENSUS PROCESS: An exhaustive search of the relevant published
literature was reviewed by each panel member in preparation for an open
roundtable meeting. Pertinent issues (eg, cardiovascular pharmacology of
triptans, epidemiology of cardiovascular disease, cardiovascular risk assessment,
migraine) were presented as a prelude to group discussion and formulation of
consensus conclusions and recommendations. Follow-up meetings were held by
telephone. CONCLUSIONS: (1) Most of the data on triptans are derived from
patients without known coronary artery disease. (2) Chest symptoms occurring
during use of triptans are generally nonserious and are not explained by
ischemia. (3) The incidence of serious cardiovascular events with triptans in
both clinical trials and clinical practice appears to be extremely low. (4) The
cardiovascular risk-benefit profile of triptans favors their use in the absence
of contraindications.

Publication Types: 
    Consensus Development Conference
    Research Support, Non-U.S. Gov't
    Review

PMID: 15147249 [PubMed - indexed for MEDLINE]

2232: Headache. 2004 May;44(5):403-10.

Frovatriptan use in migraineurs with or at high risk of coronary artery disease.

Elkind AH, Satin LZ, Nila A, Keywood C.

Elkind Headache Center, Mount Vernon, NY 10550, USA.

OBJECTIVE: To investigate the cardiovascular effects of frovatriptan 2.5 mg
during a migraine attack in patients with, or at high risk of, coronary artery
disease. BACKGROUND: Rare occurrences of myocardial ischemia and coronary and
peripheral vasospasm associated with the use of sumatriptan have triggered
concern over the vasoconstrictor properties of the triptan class of drugs.
METHODS: This randomized, double-blind, placebo-controlled, parallel-group study 
was conducted in 14 US private headache referral centers or clinics. Seventy-five
patients, aged 18 years and older, with a history of migraine who were at high
risk (Framingham score > or =14) of or who had previously documented coronary
artery disease were evaluated. RESULTS: Incidence of clinically significant
electrocardiogram changes was higher at all time points postdose with placebo
than with frovatriptan, reaching statistical significance at 4 hours (40% versus 
19%, P=.026). Similar proportions of patients had ischemia documented on Holter
monitoring in the placebo (13%) and frovatriptan (11%) groups, and the incidence 
of arrhythmias was higher in the placebo group (11% versus 3%). There were no
clinically significant changes in heart rate or blood pressure in either group.
Adverse event profiles were similar for placebo and frovatriptan. CONCLUSIONS: In
this exploratory study of migraineurs with, or at high risk of, coronary artery
disease, frovatriptan 2.5 mg was well tolerated and not associated with an
increase in cardiovascular monitoring abnormalities.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 15147247 [PubMed - indexed for MEDLINE]

2233: Headache. 2004 May;44(5):399-402.

A thromboembolic predisposition and the effect of anticoagulants on migraine.

Wammes-van der Heijden EA, Tijssen CC, van't Hoff AR, Egberts AC.

Department of Pharmacoepidemiology and Pharmacotherapy, Utrecht Institute for
Pharmaceutical Sciences, The Netherlands.

OBJECTIVE: To investigate the presence of thromboembolic risk factors and the
effect of low-dose acenocoumarol therapy on migraine in patients who
spontaneously reported a reduction of their migraine attacks during previous
therapeutic use of anticoagulants. BACKGROUND: The positive effect of
anticoagulants on migraine has been described in case reports and observational
studies. It remains unclear whether this concerns only a select group of
migraineurs with certain common characteristics. METHODS: In 4 migraineurs with a
self-reported reduction of attack frequency during previous use of anticoagulants
(international normalization ratio [INR], 2.5:4.0), the presence of
thromboembolic risk factors and the effect of low-dose acenocoumarol therapy
(INR, 1.5:2.0) on migraine attacks were prospectively investigated in an open
study. RESULTS: All patients had one or more thromboembolic risk factors. Two
patients, both with factor V Leiden heterozygosity, experienced a clear
improvement of migraine during low-dose acenocoumarol therapy. CONCLUSIONS: Our
findings support the hypothesis that migraine, as a phenotype, has different
underlying mechanisms, amongst which a thromboembolic tendency. In this group of 
patients, oral anticoagulants may be a suitable form of migraine prophylaxis, but
this needs further clinical investigation.

Publication Types: 
    Clinical Trial

PMID: 15147246 [PubMed - indexed for MEDLINE]

2234: Headache. 2004 May;44(5):387-98.

Tools for diagnosing migraine and measuring its severity.

Lipton RB, Bigal ME, Amatniek JC, Stewart WF.

Department of Neurology, The Albert Einstein College of Medicine, Bronx, NY, USA.

Migraine remains substantially underdiagnosed and undertreated in the United
States. Tools to screen for migraine and to measure headache-related disability
can help address barriers to effective diagnosis and treatment. In this article, 
public health criteria for screening programs for any medical condition are first
reviewed. Modifications of these criteria for migraine and other chronic/episodic
disorders are then proposed. Migraine is assessed to determine how well it meets 
criteria for screening and the steps that are necessary before firm public policy
recommendations for screening for migraine are possible.

PMID: 15147245 [PubMed - indexed for MEDLINE]

2235: Curr Med Res Opin. 2004 May;20(5):659-69.

Cost effectiveness of oral triptan therapy: a trans-national comparison based on 
a meta-analysis of randomised controlled trials.

Belsey JD.

JB Medical Ltd, Sudbury, UK. jbelsey@jbmedical.com

OBJECTIVE: The objective of this study was to appraise the relative cost
effectiveness of oral triptan therapy in the management of acute migraine,
comparing the results obtained using drug cost data from six different countries,
USA, UK, Canada, Germany, Italy and The Netherlands. METHOD: A meta-analysis of
randomised placebo controlled trials of single dose oral triptans was carried out
in order to calculate aggregate Numbers Needed to Treat (NNT) for each triptan
and dose. Cost effectiveness ratios were then derived for each treatment by
applying mean drug acquisition costs for each country to these NNTs. Using a
graphical plot for each country, incremental cost effectiveness comparisons were 
then made versus sumatriptan 100 mg, the most commonly used oral triptan.
RESULTS: When analysed in terms of 2-h pain one country to another. When compared
to free outcomes, rizatriptan 10 mg and eletriptan 40 and 80 mg were the most
effective oral triptans. Rizatriptan 10mg has the most advantageous absolute cost
effectiveness ratio in all six countries studied, although levels of statistical 
significance compared to other agents varied from sumatriptan 100mg, rizatriptan 
10 mg and eletriptan 40 mg are most consistently the cost effective treatment
choices, both being cost dominant in five out of six countries studied.
CONCLUSIONS: There are systematic differences in triptan efficacy that have an
impact on treatment choice. Differences in pricing structure between countries
mean that hierarchies of cost effectiveness will vary. Country-specific data
should therefore be examined before defining treatment strategies.

Publication Types: 
    Meta-Analysis
    Research Support, Non-U.S. Gov't

PMID: 15140331 [PubMed - indexed for MEDLINE]

2236: Neurology. 2004 May 11;62(9):1552-7.

Randomized, placebo-controlled trial of rofecoxib in the acute treatment of
migraine.

Silberstein S, Tepper S, Brandes J, Diamond M, Goldstein J, Winner P, Venkatraman
S, Vrijens F, Malbecq W, Lines C, Visser WH, Reines S, Yuen E.

Jefferson Headache Center, Philadelphia, , PA 19107, USA.
Stephen.Silberstein@jefferson.edu

OBJECTIVE: To investigate the clinical profile of rofecoxib, a long-acting
(approximately 17-hour half-life) selective cyclo-oxygenase-2 inhibitor, for the 
acute treatment of migraine. METHODS: A randomized, double-blind,
placebo-controlled, parallel-group study was conducted. Patients age > or =18
treated a moderate or severe migraine headache with placebo (n = 182), rofecoxib 
25 mg (n = 183), or rofecoxib 50 mg (n = 192). The primary efficacy measure was
headache relief (mild or no pain) 2 hours after dose. RESULTS: The proportions of
patients with migraine headache relief at 2 hours after dose were 34.3% for
placebo, 54.0% for rofecoxib 25 mg (p < 0.001 vs placebo), and 56.7% for
rofecoxib 50 mg (p < 0.001 vs placebo). Rofecoxib 25 and 50 mg were superior to
placebo in providing pain freedom at 2 hours, 24-hour sustained headache relief, 
and 24-hour sustained pain freedom; in reducing photophobia, phonophobia, nausea 
(50 mg only), and functional disability at 2 hours after dose; and in improving
some quality-of-life scores over 24 hours. More patients on rofecoxib 50 mg
reported adverse events (39.6%) than patients on rofecoxib 25 mg (26.8%) or
placebo (23.6%) regardless of drug relatedness; however, the incidences of
drug-related adverse events were similar between treatment groups. These adverse 
events were generally mild or moderate in severity. The most commonly reported
adverse events were dry mouth, dizziness, somnolence, nausea, dyspepsia,
paresthesia, and asthenia, with similar incidences between treatment groups.
CONCLUSION: Rofecoxib 25 and 50 mg were effective and generally well tolerated
for the acute treatment of migraine attacks.

Publication Types: 
    Clinical Trial
    Comparative Study
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 15136680 [PubMed - indexed for MEDLINE]

2237: Cranio. 2004 Apr;22(2):132-6.

Role of the extracranial arteries in migraine headache: a review.

Shevel E, Spierings EH.

Johannesburg Branch, Headache Clinics International, Suite 256, P. Bag X2600,
Houghton 2041, South Africa. drshevel@headclin.com

The pain of the migraine headache is often so debilitating that it severely
compromises quality of life. The vascular component of the trigeminovascular
system has been implicated in the pain mechanism. There is, however, debate as to
whether the pain originates in the intracranial or extracranial vasculature or in
both. In this article, evidence is presented to suggest that the extracranial
arteries are the source of the pain in some migraine sufferers.

Publication Types: 
    Review

PMID: 15134413 [PubMed - indexed for MEDLINE]

2238: Neurogenetics. 2004 Jun;5(2):129-33. Epub 2004 May 7.

The estrogen receptor 1 G594A polymorphism is associated with migraine
susceptibility in two independent case/control groups.

Colson NJ, Lea RA, Quinlan S, MacMillan J, Griffiths LR.

Genomics Research Centre, School of Health Science, Griffith University, Gold
Coast, Queensland, Australia.

Migraine is a painful and debilitating disorder with a significant genetic
component. Steroid hormones, in particular estrogen, have long been considered to
play a role in migraine, as variations in hormone levels are associated with
migraine onset in many sufferers of the disorder. Steroid hormones mediate their 
activity via hormone receptors, which have a wide tissue distribution. Estrogen
receptors have been localized to the brain in regions considered to be involved
in migraine pathogenesis. Hence it is possible that genetic variation in the
estrogen receptor gene may play a role in migraine susceptibility. This study
thus examined the estrogen receptor 1 (ESRalpha) gene for a potential role in
migraine pathogenesis and susceptibility. A population-based cohort of 224
migraine sufferers and 224 matched controls were genotyped for the G594A
polymorphism located in exon 8 of the ESR1 gene. Statistical analysis indicated a
significant difference between migraineurs and non-migraineurs in both the allele
frequencies (P=0.003) and genotype distributions (P=0.008) in this sample. An
independent follow-up study was then undertaken using this marker in an
additional population-based cohort of 260 migraine sufferers and 260 matched
controls. This resulted in a significant association between the two groups with 
regard to allele frequencies (P=8 x 10(-6)) and genotype distributions (P=4 x
10(-5)). Our findings support the hypothesis that genetic variation in hormone
receptors, in particular the ESR1 gene, may play a role in migraine.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 15133719 [PubMed - indexed for MEDLINE]

2239: Neurogenetics. 2004 Jun;5(2):141-6. Epub 2004 May 7.

A novel missense ATP1A2 mutation in a Finnish family with familial hemiplegic
migraine type 2.

Kaunisto MA, Harno H, Vanmolkot KR, Gargus JJ, Sun G, Hämäläinen E, Liukkonen E, 
Kallela M, van den Maagdenberg AM, Frants RR, Färkkilä M, Palotie A, Wessman M.

Biomedicum Helsinki, Research Program in Molecular Medicine, University of
Helsinki, Helsinki, Finland. mari.kaunisto@hus.fi

Familial hemiplegic migraine (FHM), a rare autosomal dominant subtype of migraine
with aura, has been linked to two chromosomal loci, 19p13 and 1q23. Mutations in 
the Na+K+-ATPase alpha2 subunit gene, ATP1A2, on 1q23 have recently been shown to
cause familial hemiplegic migraine type 2 (FHM2). We sequenced the coding regions
of this gene in a Finnish chromosome 1q23-linked FHM family with associated
symptoms such as coma and identified a novel A1033G mutation in exon 9. This
mutation results in a threonine-to-alanine substitution at codon 345. This
residue is located in a highly conserved N-terminal region of the M4-5 loop of
the Na+,K+-ATPase. Furthermore, the T345A mutation co-segregated with the
disorder in our family and was not present in 132 healthy Finnish control
individuals. For these reasons it is most likely the FHM-causing mutation in this
family.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 15133718 [PubMed - indexed for MEDLINE]

2240: J Manipulative Physiol Ther. 2004 Mar-Apr;27(3):E5.

Treatment of bipolar, seizure, and sleep disorders and migraine headaches
utilizing a chiropractic technique.

Elster EL.

erin@erinelster.com

OBJECTIVE: To discuss the use of an upper cervical technique in the case of a
23-year-old male patient with rapid-cycling bipolar disorder, sleep disorder,
seizure disorder, neck and back pain, and migraine headaches. CLINICAL FEATURES: 
The patient participated in a high school track meet at age 17, landing on his
head from a height of 10 ft while attempting a pole vault. Prior to the accident,
no health problems were reported. Following the accident, the patient developed
numerous neurological disorders. Symptoms persisted over the next 6 years, during
which time the patient sought treatment from many physicians and other health
care practitioners. INTERVENTION AND OUTCOME: At initial examination, evidence of
a subluxation stemming from the upper cervical spine was found through
thermography and radiography. Chiropractic care using an upper cervical technique
was administered to correct and stabilize the patient's upper neck injury.
Assessments at baseline, 2 months, and 4 months were conducted by the patient's
neurologist. After 1 month of care, the patient reported an absence of seizures
and manic episodes and improved sleep patterns. After 4 months of care, seizures 
and manic episodes remained absent and migraine headaches were reduced from 3 per
week to 2 per month. After 7 months of care, the patient reported the complete
absence of symptoms. Eighteen months later, the patient remains asymptomatic.
CONCLUSION: The onset of the symptoms following the patient's accident, the
immediate reduction in symptoms correlating with the initiation of care, and the 
complete absence of all symptoms within 7 months of care suggest a link between
the patient's headfirst fall, the upper cervical subluxation, and his
neurological conditions. Further investigation into upper cervical trauma as a
contributing factor to bipolar disorder, sleep disorder, seizure disorder, and
migraine headaches should be pursued.

Publication Types: 
    Case Reports

PMID: 15129207 [PubMed - indexed for MEDLINE]

2241: Epidemiology. 2004 Mar;15(2):202-7.

Quantifying delay in access to new medical treatment: an application of risk
advancement period methodology.

Krobot KJ, Miller WC, Kaufman JS, Christensen DB, Preisser JS, Ibrahim MA.

Department of Epidemiology, School of Public Health, The University of North
Carolina at Chapel Hill, North Carolina, USA. kkrobot@web.de

BACKGROUND: We present a novel application of the concept of risk or rate
advancement to compute the extent of delay in adoption of an effective new drug
in 2 German health insurance systems. METHODS: We identified individuals with
migraines, age 18 to 65 years, in 371 primary care practices in Germany in 1994
(MediPlus, IMS Health database). These included 8173 persons covered under the
statutory health insurance system and 503 persons covered by private health
insurance. We derived risk and population risk advancement periods for
sumatriptan compared with nonserotoninergic acute migraine therapy using
multiplicative risk regression and generalized estimating equations, adjusted for
patient, physician, and practice cofactors. RESULTS: For patients at the mean age
of the cohort, 43 years of age, sumatriptan was prescribed 1.2 (95% confidence
interval [CI] = 0.3-2.0) years later among those in the statutory health
insurance system compared with those who had private insurance. The lag increased
by 0.6 (-0.1 to 1.3) years for every 10 years of patient age. In the age-mix of
our sample, access to the health benefits of sumatriptan therapy lagged nearly
1.5 years behind in the statutory health insurance system and for Germany as a
whole. CONCLUSIONS: Migraine patients' access to sumatriptan therapy lagged
substantially in the statutory health insurance system and in the country as a
whole. Risk advancement periods provide a useful methodology for communicating
major healthcare issues in a meaningful way to society and policymakers.

PMID: 15127913 [PubMed - indexed for MEDLINE]

2242: Eur J Paediatr Neurol. 2004;8(3):161-4.

Acute hemiparesis in a boy with type 1 diabetes.

Fernández-Mayoralas DM, Muñoz-Jareño N, Manzano-Palomo MS, Campos-Castelló J.

Servicio de Neuropediatría, Hospital Clínico Universitario San Carlos, Martín
Lagos s/n, E-28040 Madrid, Spain. dmfmayor@hotmail.com

Unlike the case in adult-onset diabetes, neurologic complications in children
with type 1 diabetes are uncommon. We report a case of a 14-year-old boy with
type 1 diabetes who presented at our emergency unit with acute hemiparesis and
intense headache without hypoglycaemia. Two hours after onset, the symptoms had
subsided. It is the intention of the authors to increase the awareness of this
association, whose prognosis is almost invariably good.

Publication Types: 
    Case Reports

PMID: 15120688 [PubMed - indexed for MEDLINE]

2243: Curr Pain Headache Rep. 2004 Jun;8(3):244-50.

Anticonvulsants in migraine.

Young WB, Siow HC, Silberstein SD.

Department of Neurology, Thomas Jefferson University Hospital, Jefferson Headache
Center, 111 South 11th Street, Gibbon Building, Suite #8130, Philadelphia, PA
19107, USA. william.b.young@jefferson.edu

Migraine is a common, disabling disorder that often requires preventive
treatment. The decision to treat migraine preventively generally is based on
disability, problems with acute medicines, patient preference, risk of acute
medication overuse, special circumstances, and concern that high migraine attack 
frequency may be a risk factor for chronic daily headache. Migraine and epilepsy 
are comorbid episodic central nervous system disorders that can have stereotyped 
symptoms with negative and positive phenomena. Controlled trials have
demonstrated the efficacy of anticonvulsants in migraine prevention. Valproic
acid, topiramate and, to a lesser extent, gabapentin, have demonstrated efficacy 
in randomized, placebo-controlled trials. Lamotrigine may be effective at
controlling migraine aura, but has not demonstrated effectiveness at controlling 
migraine headache. Anticonvulsants are a useful option for the preventive
treatment of migraine.

Publication Types: 
    Review

PMID: 15115645 [PubMed - indexed for MEDLINE]

2244: Curr Pain Headache Rep. 2004 Jun;8(3):238-43.

Toward a molecular genetic classification of familial hemiplegic migraine.

Haan J, Kors EE, van den Maagdenberg AM, Vanmolkot KR, Terwindt GM, Frants RR,
Ferrari MD.

Department of Neurology (K5Q), Leiden University Medical Centre, PO Box 9600,
2300 RC Leiden, The Netherlands.

The genetics of migraine is a fascinating and rapidly moving research area.
Familial hemiplegic migraine, a rare subtype of migraine with a Mendelian pattern
of inheritance, is caused by mutations in the chromosome 19 CACNA1A gene or in
the chromosome 1 ATP1A2 gene. Familial migraine variants are classified on the
basis of clinical, descriptive criteria, but this is insufficient. In the future,
a diagnostic classification based on mutation-analysis is needed.

Publication Types: 
    Review

PMID: 15115644 [PubMed - indexed for MEDLINE]

2245: Curr Pain Headache Rep. 2004 Jun;8(3):229-37.

Menstrual migraine: a review of prophylactic therapies.

Martin VT.

University of Cincinnati, Division of General Internal Medicine, 231 Albert Sabin
Way, Room 6603, Cincinnati, OH 45267-0535, USA. martindoc@pol.net

Menstrual migraine is commonly encountered in women who are experiencing attacks 
of migraine without aura. It remains controversial whether attacks of menstrually
associated migraine are more severe and have a longer duration than
non-menstrually associated attacks. The pathogenesis of menstrual migraine is not
understood completely, but it may be related to estrogen withdrawal or
prostaglandin release. Preventative therapies may be considered in those who have
failed abortive medications or have attacks lasting longer than 2 days. They can 
be administered short-term during the perimenstrual time period or continuously
throughout the menstrual cycle. Short-term prophylactics should be tried first
because menstrual migraines generally last for 1 to 4 days only. Continuous
prophylactics may be considered in those with attacks refractory to short-term
therapies.

Publication Types: 
    Review

PMID: 15115643 [PubMed - indexed for MEDLINE]

2246: Curr Pain Headache Rep. 2004 Jun;8(3):223-8.

Sporadic hemiplegic migraine.

Black DF.

Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA. black.david@mayo.edu

Hemiplegic migraine may be familial or sporadic. Both forms share a similar
spectrum of clinical presentations and genetic heterogeneity. Current data
support the concept that sporadic and familial cases should be thought of as
similar, but separate disorders. Sporadic cases are more difficult to diagnose
and often require several investigations to rule out more ominous possibilities. 
Therapeutic options are limited, but future genetic research may elucidate
pathophysiologic mechanisms that may, in turn, yield more specific treatments.

Publication Types: 
    Review

PMID: 15115642 [PubMed - indexed for MEDLINE]

2247: Curr Pain Headache Rep. 2004 Jun;8(3):219-22.

Pharmacokinetic studies in migraine: what questions should physicians ask?

Rolan P.

Department of Neurology, Manchester Royal Infirmary, Oxford Road, Manchester, UK.
P.Rolan@Medeval.com

Migraine is a benign self-limiting condition for which the objective of treatment
is to maximize the patient's quality of life by reducing the frequency of attacks
and attenuating the pain and suffering of an individual attack as quickly and
safely as possible. Evaluating the efficacy of antimigraine treatments,
particularly those for the management of the acute attack, is relatively easy
because acute symptomatic benefit is the criterion of success. For prophylaxis,
therapeutic success generally is measured by relatively simple parameters such as
attack frequency. Given that the clinical response to antimigraine therapies
relatively is readily assessed by history, the role of more sophisticated
investigations such as pharmacokinetic studies may not be immediately clear. This
paper aims to provide clinicians with a guide to interpretation of such studies.

Publication Types: 
    Review

PMID: 15115641 [PubMed - indexed for MEDLINE]

2248: Curr Pain Headache Rep. 2004 Jun;8(3):178-84.

Prophylactic migraine therapy: emerging treatment options.

Bigal ME, Krymchantowski AV, Rapoport AM.

Department of Neurology, Albert Einstein College of Medicine, 1165 Morris Park
Avenue, Bronx, NY 10461, USA. mbigal@aecom.yu.edu

In this paper, new treatment options for migraine prevention are reviewed. An
overview about migraine pathophysiology is provided and current indications for
migraine prevention and new and upcoming preventive medications are discussed
briefly. Data are presented on topiramate, levetiracetam, zonisamide, botulinim
toxin, tizanidine, nefazodone, lisinopril, candesartan, carabersat, petasites,
and coenzyme Q.

Publication Types: 
    Review

PMID: 15115635 [PubMed - indexed for MEDLINE]

2249: Med Sci Monit. 2004 May;10(5):CR197-201. Epub 2004 Apr 28.

Diagnosis of migrainous vertigo: validity of a structured interview.

Marcus DA, Kapelewski C, Rudy TE, Jacob RG, Furman JM.

Department of Anesthesiology & Critical Care Medicine, University of Pittsburgh
School of Medicine, PA, USA. MarcusD@anes.upmc.edu

BACKGROUND: Migraine and vestibular symptoms are co-morbid. Migraine is
increasingly recognized as a cause of benign, recurrent vertigo. Although the
International Headache Society does not currently include the diagnosis of
migrainous vertigo, specific criteria have been proposed and utilized in clinical
trials. MATERIAL/METHODS: Seventeen adult migraineurs were separately screened
for the diagnosis of migrainous vertigo using a standardized structured interview
for migrainous vertigo (SIM-V) and a clinical evaluation by an experienced
neurotologist. The SIM-V was administered by a nurse who read and recorded
subject responses, obtaining no additional information for the diagnosis of
migrainous vertigo. Comparison of diagnoses between clinician and SIM-V was made 
using Cohen's kappa reliability testing. Subjects were asked to return for a
second interview by the same nurse using the SIM-V, at least 2 weeks after the
initial assessment. Testing stability was evaluated by comparing diagnoses
obtained with each SIM-V administration. RESULTS: Cohen's kappa demonstrated
excellent test validity (kappa=0.75). Fourteen subjects returned for repeat
testing, with excellent retest stability (kappa=0.85). The additional three
subjects could not be relocated or were not interested in attending a retest
appointment. CONCLUSIONS: The SIM-V is an easy-to-administer screening tool for
the diagnosis of migrainous vertigo. Diagnostic comparison to a standard clinical
assessment shows good test validity. Retest stability was also demonstrated. The 
SIM-V may be a useful screening tool for migraineurs with an additional complaint
of dizziness.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 15114269 [PubMed - indexed for MEDLINE]

2250: Health Rep. 2001;12(2):23-40.

Migraine.

Gilmour H, Wilkins K.

Health Statistics Division, Statistics Canada, Ottawa, Ontario, K1A 0T6.
gilmhea@statcan.ca

OBJECTIVES: This article provides prevalence and incidence estimates of migraine 
among Canadians aged 12 or older. Associations with selected socio-demographic
factors and health characteristics are also examined. Selected health indicators 
and medication use, as well as health care use and attitudes, are discussed,
comparing migraineurs with non-migraineurs. DATA SOURCES: The findings are based 
on the cross-sectional and longitudinal household components of the first three
cycles (1994/95, 1996/97 and 1998/99) of Statistics Canada's National Population 
Health Survey. Information on hospital stays is from the 1997/98 Hospital
Morbidity Database, maintained by the Canadian Institute for Health Information. 
ANALYTICAL TECHNIQUES: Cross-tabulations were used to estimate the prevalence and
incidence of migraine. Associations of migraine with selected factors were
examined using generalized logistic regression. MAIN RESULTS: In 1998/99,
migraine was most prevalent among women, 25- to 54-year-olds, Whites, and
individuals in low-income households. The odds of being diagnosed with migraine
were higher for women with pre-existing sinusitis, bronchitis or emphysema,
compared with women without these conditions. The odds of this disorder for men
were associated with previously diagnosed arthritis or rheumatism.

PMID: 15112424 [PubMed - indexed for MEDLINE]

2251: Neurology. 2004 Apr 27;62(8):1399-401.

Comment in:
    Neurology. 2004 Nov 9;63(9):1760-1; author reply 1760-1.

Percutaneous closure of patent foramen ovale reduces the frequency of migraine
attacks.

Schwerzmann M, Wiher S, Nedeltchev K, Mattle HP, Wahl A, Seiler C, Meier B,
Windecker S.

Department of Cardiology, University Hospital, Bern, Switzerland.
markus.schwerzmann@uhn.on.ca

Among 215 patients referred for percutaneous closure of patent foramen ovale
(PFO) after presumed paradoxical embolism, we assessed the prevalence of
migraine. In the year prior to PFO closure, 48 (22%) patients had migraine, twice
the expected prevalence of 10 to 12% in the general European population. In
patients with migraine with aura, percutaneous PFO closure reduced the frequency 
of migraine attacks by 54% (1.2 +/- 0.8 vs 0.6 +/- 0.8 per month; p = 0.001) and 
in patients with migraine without aura by 62% (1.2 +/- 0.7 vs 0.4 +/- 0.4 per
month; p = 0.006). PFO closure did not have an effect on headache frequency in
patients with nonmigraine headaches (1.4 +/- 0.9 vs 1.0 +/- 0.9 per month; p =
NS).

PMID: 15111681 [PubMed - indexed for MEDLINE]

2252: Headache. 2004 Apr;44(4):328-32.

Validation of a brief nurse-administered migraine assessment tool.

Marcus DA, Kapelewski C, Jacob RG, Rudy TE, Furman JM.

Departments of Anesthesiology and Critical Care Medicine, University of
Pittsburgh (Pa) School of Medicine, USA.

OBJECTIVE: To validate a brief tool for screening migraine. BACKGROUND: Migraine 
is a common, but underdiagnosed condition. Effective utilization of nonphysician 
personnel to reliably screen patients for migraine may improve identification of 
migraineurs for clinical treatment and research. METHODS: An 8-question Migraine 
Assessment Tool (based on International Headache Society criteria) was designed
for administration by a nurse with no specialized headache training as a
pre-assessment for the diagnosis of migraine for use in either a research or
clinical environment. A community sample of 80 adults (71 women, 9 men; mean age,
33.7 years; 80% white, 14% African American, 2.5% Asian American) with
self-reported headache was recruited through advertisements. A headache
specialist independently diagnosed subjects using clinical assessment, and a
nurse who works in a balance disorder clinic used the Migraine Assessment Tool.
Agreement between physician and nurse-administered Migraine Assessment Tool
diagnoses was determined. Each subject returned in 2 to 4 weeks for a second
assessment, administered by the same nurse. Agreement between the 2 diagnoses
from the Migraine Assessment Tool was calculated. RESULTS: Comparison between
diagnosis by the physician versus the Migraine Assessment Tool revealed a
positive predictive value of 0.85; negative predictive value, 0.84; sensitivity, 
0.89; specificity, 0.79; and observed agreement, 0.85. Cohen's kappa reliability 
measure was 0.69, indicating good test reliability. Interestingly, in 8 of the 12
cases of disagreement, the examiner diagnosing nonmigraine diagnosed analgesic
overuse headache. Comparing diagnoses assigned by the 2 separate administrations 
of the Migraine Assessment Tool revealed a Cohen's kappa of 0.69. Notably, 9 of
the 12 cases of nonagreement on the 2 assessments were due to subjects endorsing 
analgesic overuse in only 1 of the 2 testing sessions. CONCLUSIONS: This study
showed good reliability and stability of a new, brief, nurse-administered
migraine questionnaire. In addition, the study also showed that consistency in
self-reporting analgesic overuse within individuals with headache is poor. This
suggests the need for repeat questioning about analgesic overuse on subsequent
appointments to ensure absence of analgesic overuse headache.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't
    Validation Studies

PMID: 15109357 [PubMed - indexed for MEDLINE]

2253: Headache. 2004 Apr;44(4):323-7.

Simple and efficient recognition of migraine with 3-question headache screen.

Cady RK, Borchert LD, Spalding W, Hart CC, Sheftell FD.

Headache Care Center, Primary Care Network, Inc, Springfield, MO 65804, USA.

OBJECTIVE: To correlate the results of a new 3-question headache screen to 3
established methods of diagnosing migraine: the International Headache Society
diagnostic criteria, physician's clinical impression, and presence of recurring
disabling headaches. BACKGROUND: A simple tool to recognize patients who
experience migraine may facilitate diagnosis of this debilitating and frequently 
undiagnosed condition. METHODS: Primary care physicians and neurologists in the
United States enrolled 3014 adults with a diagnosis of migraine based on one of
the following: International Headache Society criteria, an investigator's
clinical impression, or presence of recurring disabling headaches. Each patient
completed a 3-question headache screen: (1) Do you have recurrent headaches that 
interfere with work, family, or social functions? (2) Do your headaches last at
least 4 hours? (3) Have you had new or different headaches in the past 6 months? 
A diagnosis of migraine was suggested by a yes answer to questions 1 and 2 and a 
no answer to question 3. RESULTS: The 3-question headache screen identified
migraine in 77% of the study population; including 78% of the patients enrolled
based on International Headache Society criteria, 74% based on clinical
impression, and 68% because of recurring disabling headaches. CONCLUSIONS:
Positive 3-question headache screen results agreed well with migraine diagnoses
based on International Headache Society criteria, clinical impressions, and
presence of recurring disabling headaches. These findings support use of the
3-question headache screen to recognize migraine.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 15109356 [PubMed - indexed for MEDLINE]

2254: Headache. 2004 Apr;44(4):318-22.

Almotriptan improves response rates when treatment is within 1 hour of migraine
onset.

Dowson AJ, Massiou H, Lainez JM, Cabarrocas X.

King's Headache Services, King's College Hospital, London, UK.

BACKGROUND: Results from open-label trials with almotriptan and sumatriptan have 
shown higher response rates when treatment was initiated early after acute
migraine onset. OBJECTIVE: To investigate the temporal component of early
intervention by measuring 2-hour pain-free and sustained pain-free responses to
almotriptan and sumatriptan when the study drug was taken within 1 hour of onset 
of moderate to severe pain. METHODS: This was a post hoc analysis from a
double-blind, randomized, placebo-controlled trial of almotriptan and
sumatriptan. Men and women, 18 to 65 years of age, who met International Headache
Society criteria for migraine with or without aura were eligible. Patients were
randomized to receive a single oral dose of almotriptan 12.5 or 25 mg,
sumatriptan 100 mg, or placebo at the onset of a severe or moderate migraine
attack. For this post hoc analysis, the almotriptan 25-mg dose was excluded
because 12.5 mg is the recommended dose. The primary efficacy assessment was
sustained pain-free, defined as pain-free at 2 hours postdose with no recurrence 
from 2 to 24 hours and no use of rescue medication. Only patients who took study 
medication within 1 hour of migraine onset were included in the analysis.
RESULTS: Of the 475 patients involved in the original study, 253 (53.3%)
initiated treatment within the 0- to 1-hour interval. For these patients, 2-hour 
pain-free rates were 37.9% for almotriptan 12.5 mg (P=.016 versus placebo), 35.7%
for sumatriptan 100 mg (P=.028 versus placebo), and 18.9% for placebo. Only
almotriptan was significantly higher than placebo on the sustained pain-free
rate-34.7% (P=.022 versus placebo); the sustained pain-free rate for sumatriptan 
was 29.6% and for placebo, 17.0%. CONCLUSION: Initiation of treatment with
almotriptan 12.5 mg within the first hour after acute migraine onset resulted in 
a significantly higher sustained pain-free response compared with placebo. There 
was no significant difference in sustained pain-free rates between sumatriptan
and placebo. These results are consistent with those from a previous open-label
trial, and suggest that early intervention with almotriptan can improve clinical 
outcome.

Publication Types: 
    Clinical Trial
    Comparative Study
    Randomized Controlled Trial

PMID: 15109355 [PubMed - indexed for MEDLINE]

2255: Headache. 2004 Apr;44(4):311-7.

Familial migraine with aura: association study with 5-HT1B/1D, 5-HT2C, and hSERT 
polymorphisms.

Racchi M, Leone M, Porrello E, Rigamonti A, Govoni S, Sironi M, Montomoli C,
Bussone G.

Department of Applied and Experimental Pharmacology, University of Pavia, Italy.

BACKGROUND: The serotonergic system has a significant role in the pathophysiology
and pharmacology of migraine. OBJECTIVE: To study the association between the
occurrence of migraine with aura and 5-HT(1B/1D) and 5-HT(2C) receptor gene and
the human serotonin transporter (hSERT) gene polymorphisms in 18 unrelated
families with multiple affected members. METHOD: Two polymorphisms in the
5-HT(1B/1D) receptor gene and one polymorphism in the 5-HT(2C) receptor gene were
studied by restriction fragment length polymorphism analysis. Allelic variation
of the hSERT, with 9, 10, and 12 copies of a "repetitive element," was studied by
polymerase chain reaction amplification of the variable number tandem repeat
region. RESULTS: Allelic distribution of 5-HT(1B/1D) and 5-HT(2C) receptor gene
polymorphisms in affected patients did not differ in either of the control groups
(unaffected relatives or unrelated healthy individuals). A trend toward a
significant effect of the 12-repeat hSERT allele as a risk factor for migraine
with aura versus unrelated controls was observed. CONCLUSION: Our data do not
support the involvement of 5-HT(1B/1D) and 5-HT(2C) receptor gene polymorphisms
in migraine with aura, yet do suggest a possible role for a locus at or near the 
hSERT gene in the susceptibility to migraine with aura.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 15109354 [PubMed - indexed for MEDLINE]

2256: Headache. 2004 Apr;44(4):305-10.

Sympathetic skin response in migraineurs and patients with medication overuse
headache.

Atasoy HT, Atasoy N, Unal AE, Sumer M.

Zonguldak Karaelmas University, Faculty of Medicine, Department of Neurology,
Turkey.

BACKGROUND: Autonomic dysfunction has been reported in patients with migraine,
and it may play a role in promoting attacks. OBJECTIVE: To investigate changes in
the autonomic function of migraineurs and patients with medication overuse
headache via sympathetic skin response, and to determine whether psychiatric
comorbidity is related to any changes recorded. METHODS: A consecutive series of 
patients with migraine (n = 45) and medication overuse headache (n = 53) were
studied. Patients with other chronic diseases requiring medication were excluded.
Sympathetic skin response latencies and amplitudes from the patients with
headache (N = 98) and 40 healthy controls were compared statistically. RESULTS:
Sympathetic skin response latencies in patients with medication overuse headache 
and in migraineurs were significantly longer than in controls. To analyze the
effect of psychiatric comorbidity, patients with medication overuse headache and 
migraineurs were each divided into 2 groups: those with psychiatric comorbidity
and those without comorbidity. When the sympathetic skin response results of
these 4 groups were compared with controls, the only statistically significant
difference was between the sympathetic skin response latencies of controls and
the latencies of patients with psychiatric comorbidity. We could not find any
difference between the results from patients without psychiatric comorbidity and 
those of controls. CONCLUSION: Psychiatric disease may affect the results of
autonomic function testing in migraineurs and patients with medication overuse
headache. Consideration should be given to excluding patients with psychiatric
comorbidity from studies investigating autonomic dysfunction in patients with
headache.

Publication Types: 
    Comparative Study

PMID: 15109353 [PubMed - indexed for MEDLINE]

2257: Cochrane Database Syst Rev. 2004;(2):CD003225.

Propranolol for migraine prophylaxis.

Linde K, Rossnagel K.

Centre for Complementary Medicine Research, Department of Internal Medicine II,
Technische Universität, Kaiserstr. 9, München, Germany, 80801.

BACKGROUND: Propranolol is one of the most commonly prescribed drugs for migraine
prophylaxis. OBJECTIVES: We aimed to determine whether there is evidence that
propranolol is more effective than placebo and as effective as other drugs for
the interval (prophylactic) treatment of patients with migraine. SEARCH STRATEGY:
Potentially eligible studies were identified by searching MEDLINE/PubMed (1966 to
May 2003) and the Cochrane Central Register of Controlled Trials (Issue 2, 2003),
and by screening bibliographies of reviews and identified articles. SELECTION
CRITERIA: We included randomised and quasi-randomised clinical trials of at least
4 weeks duration comparing clinical effects of propranolol with placebo or
another drug in adult migraine sufferers. DATA COLLECTION AND ANALYSIS: Two
reviewers extracted information on patients, methods, interventions, outcomes
measured, and results using a pre-tested form. Study quality was assessed using
two checklists (Jadad scale and Delphi list). Due to the heterogeneity of outcome
measures and insufficient reporting of the data, only selective quantitative
meta-analyses were performed. As far as possible, effect size estimates were
calculated for single trials. In addition, results were summarised descriptively 
and by a vote count among the reviewers. MAIN RESULTS: A total of 58 trials with 
5072 participants met the inclusion criteria. The 58 selected trials included 26 
comparisons with placebo and 47 comparisons with other drugs. The methodological 
quality of the majority of trials was unsatisfactory. The principal shortcomings 
were high dropout rates and insufficient reporting and handling of this problem
in the analysis. Overall, the 26 placebo-controlled trials showed clear
short-term effects of propranolol over placebo. Due to the lack of studies with
long-term follow up, it is unclear whether these effects are stable after
stopping propranolol. The 47 comparisons with calcium antagonists, other
beta-blockers, and a variety of other drugs did not yield any clear-cut
differences. Sample size was, however, insufficient in most trials to establish
equivalence. REVIEWERS' CONCLUSIONS: Although many trials have relevant
methodological shortcomings, there is clear evidence that propranolol is more
effective than placebo in the short-term interval treatment of migraine. Evidence
on long-term effects is lacking. Propranolol seems to be as effective and safe as
a variety of other drugs used for migraine prophylaxis.

Publication Types: 
    Review

PMID: 15106196 [PubMed - indexed for MEDLINE]

2258: Drug Ther Bull. 2004 Apr;42(4):25-8.

Managing migraine in children.

[No authors listed]

Migraine is the most common cause of severe recurrent headache in children.
Around 1 in 10 schoolchildren in the UK has the condition and, on average, misses
almost 4 days of school a year because of it. In many, the paroxysmal headache
and accompanying symptoms are similar to those in adults, but there can be
differences. Here we discuss the management of migraine in childhood.

Publication Types: 
    Review

PMID: 15098282 [PubMed - indexed for MEDLINE]

2259: Arch Neurol. 2004 Apr;61(4):490-5.

Topiramate in migraine prevention: results of a large controlled trial.

Silberstein SD, Neto W, Schmitt J, Jacobs D; MIGR-001 Study Group.

Jefferson Headache Center, Thomas Jefferson University Hospital, Philadelphia,
PA19107, USA. stephen.silberstein@jefferson.edu

BACKGROUND: Open-label trials and small controlled studies report topiramate's
efficacy in migraine prevention. OBJECTIVE: To assess the efficacy and safety of 
topiramate as a migraine-preventive therapy. DESIGN: A 26-week, randomized,
double-blind, placebo-controlled study. SETTING: Outpatient treatment at 49 US
clinical centers.Patients Patients were aged 12 to 65 years, had a 6-month
International Headache Society migraine history, and experienced 3 to 12
migraines per month, but had 15 or fewer headache days per month during the
28-day baseline period. INTERVENTIONS: Participants were randomized to placebo or
topiramate, 50, 100, or 200 mg/d, titrated by 25 mg/wk to the assigned dose or as
tolerated in 8 weeks; maintenance therapy continued for 18 weeks. MAIN OUTCOME
MEASURES: The primary efficacy assessment was a reduction in mean monthly
migraine frequency across the 6-month treatment phase. Secondary end points were 
responder rate, time to onset of action, mean change in migraine days per month, 
and mean change in rescue medication days per month. RESULTS: Four hundred
eighty-seven patients were randomized, and 469 composed the intent-to-treat
population. The mean +/- SD monthly migraine frequency decreased significantly
for the 100-mg/d group (from 5.4 +/- 2.2 to 3.3 +/- 2.9; P <.001) and the
200-mg/d group (from 5.6 +/- 2.6 to 3.3 +/- 2.9; P <.001) vs the placebo group
(from 5.6 +/- 2.3 to 4.6 +/- 3.0); improvements occurred within the first
treatment month. Significantly more topiramate-treated patients (50 mg/d, 35.9%
[P =.04]; 100 mg/d, 54.0% [P <.001]; and 200 mg/d, 52.3% [P <.001]) exhibited a
50% or more reduction in monthly migraine frequency than placebo-treated patients
(22.6%). Adverse events included paresthesia, fatigue, nausea, anorexia, and
taste per version. CONCLUSION: Topiramate, 100 or 200 mg/d, was effective as a
preventive therapy for patients with migraine.

Publication Types: 
    Clinical Trial
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 15096395 [PubMed - indexed for MEDLINE]

2260: Cephalalgia. 2004 May;24(5):389-97.

An analysis of the factors associated with visual field deficits measured with
flickering stimuli in-between migraine.

McKendrick AM, Badcock DR.

School of Psychology, University of Western Australia, Crawley, Australia.
allisonm@psy.uwa.edu.au

We have previously demonstrated that perimetric performance measured with
flickering stimuli is not normal in some individuals who experience migraine with
aura in the period between their attacks. In this study, flicker perimetric
performance is measured in a broad group of migraineurs to determine whether the 
existence of such visual field deficits is dependent on the presence of visual
aura, is correlated with the duration of migraine history, or frequency of
attacks. Twenty-eight migraine with aura, 25 migraine without aura, and 24
non-headache control subjects participated. The performance of the migraine
groups was not significantly different from each other. The migraine groups
showed significantly lower general sensitivity across the visual field and higher
incidence of localized visual field deficits relative to controls. Both length of
migraine history and frequency of migraine occurrence over the past 12 months
were significantly correlated with lower general sensitivity to flickering visual
stimuli.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 15096228 [PubMed - indexed for MEDLINE]

2261: Cephalalgia. 2004 May;24(5):380-8.

Prevalence of headache in Swedish schoolchildren, with a focus on tension-type
headache.

Laurell K, Larsson B, Eeg-Olofsson O.

Department of Neuroscience, Uppsala University, Sweden.
Katarina.Laurell@nc.uas.lul.se

To estimate the prevalence of tension-type headache, migraine and other
headaches, 1850 schoolchildren, age 7-15 years, from the city of Uppsala, were
invited to complete a questionnaire. The response rate was 74.1%. To validate the
information from the questionnaires, 131 children and their parents were
interviewed. Using the criteria of the International Headache Society, the 1-year
prevalence of tension-type headache and migraine was 9.8 and 11.0%, respectively.
However, these prevalence rates increased considerably, to 23.0 and 17.0%,
respectively, when excluding the criteria defining the number of earlier episodes
and duration of headache. The prevalence of headache increased with age,
similarly in girls and boys up to 11 years, and thereafter only in girls. The
preponderance in teenage girls was even more pronounced for tension-type headache
than for migraine. Our results indicate an increase over time in headache
prevalence when compared with findings in a study conducted in the same city in
1955.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 15096227 [PubMed - indexed for MEDLINE]

2262: Cephalalgia. 2004 May;24(5):373-9.

The prevalence of migraine and tension-type headaches among adolescents in
Norway. The Nord-Trøndelag Health Study (Head-HUNT-Youth), a large
population-based epidemiological study.

Zwart JA, Dyb G, Holmen TL, Stovner LJ, Sand T.

Department of Clinical Neuroscience, Faculty of Medicine, Norwegian University of
Science and Technology, Trondheim, Norway. John-Anker.Zwart@medisin.ntnu.no

The aim of this study was to examine the prevalence of headache and primary
headache disorders like migraine and tension-type headaches among adolescents,
and to explore the differences in headache prevalence and frequency by gender and
age. This cross-sectional study was conducted in Nord-Trøndelag county, Norway,
during the years 1995-97. In total, 8984 (88%) out of 10 202 invited adolescents 
aged 12-19 years participated in the youth part of the Nord-Trøndelag Health
Study [Helseundersøkelsen i Nord-Trøndelag (HUNT)]. The total study population in
this study consisted of 8255 individuals after exclusion of invalid
questionnaires and students outside the target range of 13-18 years of age. The
students completed a comprehensive questionnaire, and one of the questions was
whether the students had experienced any headaches during the last 12 months. In 
addition, 5847 of these students were also subject to an interview in which they 
were asked whether they had experienced recurring headaches during the last year 
and, if so, were they classified as migraine (MI), tension-type headache (TTH) or
non-classifiable headache. In the total questionnaire-based population, 76.8%
reported having had headaches during the last 12 months (69.4% boys and 84.2%
girls). Among those who also were interviewed, 29.1% reported having recurrent
headaches (21.0% boys and 36.5% girls). The overall 1-year prevalence of migraine
was 7%, of tension-type headache 18%, and of non-classifiable headache 4.8%.
Higher prevalence rates were found for girls in all age groups and for all
headache categories. The overall frequency of recurrent headaches did not vary
significantly with age, but girls had significantly more frequent headaches than 
boys. We concluded that headache in general, and recurrent primary headache
disorders like migraine and tension-type headaches, are common somatic complaints
among Norwegian adolescents, especially among girls.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 15096226 [PubMed - indexed for MEDLINE]

2263: Cephalalgia. 2004 May;24(5):363-72.

Motion processing deficits in migraine.

McKendrick AM, Badcock DR.

School of Psychology, University of Western Australia, Crawley, Australia.
allisonm@psy.uwa.edu.au

This study was designed to determine whether cortical motion processing
abnormalities are present in individuals with migraine. Performance was measured 
using a visual motion coherence task (motion coherence perimetry, MCP) thought to
depend on the operation of cortical area V5. Motion coherence thresholds were
measured using stimuli composed of moving dots at 17 locations in the central +/-
20 degrees of visual field. Pre-cortical visual function was also measured using 
frequency doubling perimetry (FDP) at the same 17 locations. Several migraine
subjects demonstrated significant pre-cortical visual functional abnormalities,
however, most subjects had normal visual fields measured with FDP. Abnormal MCP
performance was measured in 15 of 19 migraine-with-aura subjects, and 11 of 17
migraine-without-aura subjects. A decreased ability to detect coherent motion may
possibly be explained by an increase in baseline neuronal noise, such as would be
consistent with the concept of cortical hyperexcitability in migraine.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 15096225 [PubMed - indexed for MEDLINE]

2264: Cephalalgia. 2004 May;24(5):339-46.

Patterns of functional brain organization and migraine.

Endicott NA.

Department of Research Assessment and Training, New York State Psychiatric
Institute, New York, NY, USA. je10@columbia.edu

The purpose of this study was to examine the relationship between the patterns of
functional organization of the brain, as evaluated by the number of anomalous
brain conditions or phenomena (ABCP), and the prevalence of migraine in a group
of 434 women with lifetime major depressive disorder. ABCP are conditions or
phenomena which are clearly related to brain function whose prevalence
significantly deviates from the statistical mean for the general population.
Eighteen ABCP (e.g. mixed or left handedness, enuresis after age 5, learning and 
speech disorders) were used in this study as 'markers' for their associated
patterns of functional brain organization. The relationship between the number of
ABCP and the prevalence of migraine was highly significant. The correlation
between the number of ABCP and the prevalence of migraine was 0.36 (P < 0.0001,
confidence interval 0.26, 0.43). The prevalence of migraine in patients with no
ABCP (n = 11) was 9%, while that of those with eight or more ABCP (n = 40) was
85%. This supports the hypothesis that there is a relationship between patterns
of functional brain organization and migraine prevalence.

PMID: 15096222 [PubMed - indexed for MEDLINE]

2265: Cephalalgia. 2004 May;24(5):333-8.

Short migraine attacks of less than 2 h duration in children and adolescents.

Abu-Arafeh I, Callaghan M.

Headache Clinic, Fraser of Allander Neurosciences Unit, Royal Hospital for Sick
Children, Glasgow, UK. iabuarafeh@aol.com

We studied the duration of migraine attacks among children and adolescents who
reported headache attacks lasting <2 h. Among the 720 children who attended our
specialist headache clinic, over a period of 6 years, 231 children had migraine
with or without aura fulfilling the International Headache Society (IHS) criteria
for the diagnosis of migraine. A further 15 children reported headache attacks
typical of migraine, but of duration <2 h. They were asked to fill prospective
headache diaries in order to determine with accuracy the duration of their
headache attacks. Ten (67%) of these children provided prospective fully
analysable headache diaries and recorded a total of 120 headache attacks, 66
attacks (55%) lasting for <1 h each, 30 attacks (25%) lasting between 1 and 2 h, 
and 24 attacks (20%) lasting >2 h. Patient-based analysis of the headache diaries
showed that only three children consistently had headache attacks lasting <1 h.
Seven children had some of their headache attacks lasting for at least 1 h and
four had some of their headache attacks lasting at least 2 h. This study shows
that headache attacks in children with migraine can be variable, and brief
attacks are rare. A combination of short (<1 h) and long (>2 h) attacks of
headache can coexist in the same patient. The IHS diagnostic criteria of 1988 for
migraine in children should therefore acknowledge such variation and allow
reduction of the duration of migraine attacks to 1 h.

PMID: 15096221 [PubMed - indexed for MEDLINE]

2266: Cephalalgia. 2004 May;24(5):321-32.

Comment in:
    Cephalalgia. 2006 May;26(5):628.

Double-blind clinical trials of oral triptans vs other classes of acute migraine 
medication - a review.

Lipton RB, Bigal ME, Goadsby PJ.

Department of Neurology, Albert Einstein College of Medicine, Bronx, New York
10461, USA. Rlipton@aecom.yu.edu

Although the migraine clinical trials literature is enormous, we identified only 
nine published double-blind studies which compare an oral triptan with a
non-triptan acute treatment. Of the nine comparative trials that met inclusion
criteria for this review, six compared sumatriptan with other drugs, zolmitriptan
was studied in two trials and eletriptan in one trial. In seven of the nine
studies reviewed herein, differences between active treatments on the primary
endpoints were not dramatic. Experience in clinical practice suggests that, for
many patients, oral triptans are superior to non-specific acute treatments,
creating a discrepancy between clinical trials results and clinical practice
experience. Four possible explanations for the disparities between clinical
trials and clinical practice are likely: (i) statistically significant
differences may not have emerged because the studies lack adequate statistical
power; (ii) patients treated with triptans in clinical practice may be relatively
more responsive to triptans and relatively less responsive to other agents than
those who participate in clinical trials (patient selection); (iii) headache
response at 2 h, as measured in clinical trials, may not fully capture the
benefits of triptans relative to other therapies, as assessed in clinical
practice; (iv) waiting until pain is moderate or severe, as required in clinical 
trials, may disadvantage triptans relative to comparators.

Publication Types: 
    Comparative Study
    Review

PMID: 15096220 [PubMed - indexed for MEDLINE]

2267: J Neuroimaging. 2004 Apr;14(2):158-61.

Cerebral vasospasm in childhood migraine during the intermigrainous period.

Boasso LE, Fischer AQ.

Child Neurology Center, Evans, Georgia, USA.

BACKGROUND AND PURPOSE: The aims of this study were to evaluate the changes in
intracranial hemodynamics and assess the presence of vasospasm in children with
migraine during the intermigrainous period. METHODS: Transcranial Doppler (TCD)
sonography findings, clinical examinations, and the vasospastic index of
Lindegaard were analyzed for children who fulfilled the criteria for childhood
migraine. The significance of the presence of vasospasm and abnormal hemodynamics
were statistically analyzed using the normal approximation to the binomial test
method. TCD sonography was performed using the standard published techniques for 
children. RESULTS: Sixty-two patients between the ages of 5 and 17 years who had 
undergone at least one TCD sonographic examination were selected for this study. 
A total of 113 TCD sonographic examinations were performed on the patients.
Elevated mean blood flow velocities were found in 23 of 62 patients (37%) (P <
.001). Early vasospasm was found in 4 of 62 patients (6.5%) (P < .001). Bruits
were noted in 35 of 62 patients (56%). CONCLUSIONS: This study raises the
possibility of cerebral vasospasm in the intermigrainous period in childhood
migraine. Further studies are needed to elaborate on the pathophysiology of
cerebrovascular behavior during this period. These findings may have a
significant impact on the current clinical treatment of childhood migraine.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 15095562 [PubMed - indexed for MEDLINE]

2268: Postgrad Med. 2004 Apr;115(4):55-8.

Is there an easy way to diagnose migraine? Challenges faced by primary care
physicians include lack of time, training.

Edmeads J.

University of Toronto, Faculty of Medicine, Sunnybrook and Women's College Health
Sciences Centre, 2075 Bayview Ave, Suite A233, Toronto, Ontario, Canada M4N 3M5. 
john.edmeads@sw.ca

Migraine is an important issue in primary care medicine because surveys in North 
America consistently show that about 6% of men and 18% of women experience these 
recurrent and often debilitating headaches. Of those identified by surveyors as
having migraine, only about 60% had consulted a physician about their headaches, 
and less than half of these patients reported having received a medical diagnosis
of migraine.

PMID: 15095536 [PubMed - indexed for MEDLINE]

2269: Postgrad Med. 2004 Apr;115(4):39-44, 47-50.

Migraine in special populations. Treatment strategies for children and
adolescents, pregnant women, and the elderly.

Gladstone JP, Eross EJ, Dodick DW.

Department of Neurology, Mayo Clinic Scottsdale, 13400 E Shea Blvd, Scottsdale,
AZ 85259, USA. gladstone.jonathan@mayo.edu

Although migraine is a common occurrence in children and adolescents, its
diagnosis and treatment present unique challenges. Migraine management in
pregnant women and the elderly can also be difficult and requires selection of
appropriate and safe medications for patients in these special circumstances. In 
this article, Drs Gladstone, Eross, and Dodick provide pearls for both abortive
and prophylactic treatments for migraine in these populations.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 15095535 [PubMed - indexed for MEDLINE]

2270: Postgrad Med. 2004 Apr;115(4):28-30, 33-4, 38 passim.

Effective treatment of migraine. Terminating acute attacks, reducing their
frequency.

Pringsheim T, Edmeads J.

University of Toronto, Faculty of Medicine.

Migraine is the headache most commonly encountered in primary care practice. In
one US population survey, 17.6% of women and 6% of men reported migraine.
Specific, effective treatment options for migraine are increasingly available,
helping to reinforce how important it is that this common and sometimes disabling
condition be recognized by primary care physicians.

PMID: 15095534 [PubMed - indexed for MEDLINE]

2271: Life Sci. 2004 May 14;74(26):3223-34.

Pharmacological analysis of the mechanisms involved in the tachycardic and
vasopressor responses to the antimigraine agent, isometheptene, in pithed rats.

Valdivia LF, Centurión D, Perusquía M, Arulmani U, Saxena PR, Villalón CM.

Farmacobiología, CINVESTAV-IPN, Tenorios 235, Col. Granjas-Coapa, 14330 México
DF, Mexico.

The present study set out to investigate the pharmacological profile of the
cardiovascular responses induced by the antimigraine agent, isometheptene, in
pithed rats. For this purpose, intravenous (i.v.) administration of blocking
doses of the antagonists prazosin (alpha1; 100 microg/kg), rauwolscine (alpha2;
300 microg/kg), the combination of prazosin (100 microg/kg) plus rauwolscine (300
microg/kg), propranolol (beta; 1000 microg/kg), ritanserin (5-HT2; 100 microg/kg)
or equivalent volumes of saline (1 ml/kg) were used. Isometheptene (0.03, 0.1,
0.3, 1 and 3 mg/kg, i.v.) produced dose-dependent increases in heart rate and
diastolic blood pressure which were highly reproducible as they remained
unaltered after saline. These tachycardic responses to isometheptene remained
unaffected after prazosin, rauwolscine, ritanserin or the combination prazosin
plus rauwolscine, but were abolished after propranolol. In contrast, the
isometheptene-induced vasopressor responses were not significantly modified after
the above doses of rauwolscine, ritanserin or propranolol, but were markedly
blocked after prazosin or the combination of prazosin plus rauwolscine; the
latter blockade did not significantly differ from that produced by prazosin
alone. Interestingly, in rats pretreated intraperitoneally (i.p.) with reserpine 
(5 mg/kg; -24 h), isometheptene-induced tachycardic responses were abolished
whereas the corresponding vasopressor responses were markedly attenuated and
subsequently blocked by prazosin. It is concluded that isometheptene-induced
tachycardic responses seem to involve only an indirect (tyramine-like action)
mechanism mediated by beta-adrenoceptors, whilst the corresponding vasopressor
responses are mediated by a predominantly indirect (tyramine-like action), as
well as a minor direct (alpha1-adrenoceptors), sympathomimetic mechanism.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 15094323 [PubMed - indexed for MEDLINE]

2272: Clin Neuropharmacol. 2004 Jan-Feb;27(1):30-2.

Dopaminergic hypersensitivity in patients with Parkinson disease and migraine.

Cubo E, Kompoliti K, Leurgans SE, Raman R.

Sanatorio del Rosario, Clinica de la Zarzuela, Department of Neurology, Madrid,
Spain. ecubo@inicia.es

Because migraine has been associated with dopaminergic receptor hypersensitivity,
the authors hypothesized that patients with Parkinson disease with current or
prior migraine have better dopaminergic response and less motor disability than
Parkinson disease patients without migraine. Twenty-eight patients with Parkinson
disease were included and matched (10 patients with migraine and 18 patients
without migraine). Patients with Parkinson disease and migraine showed greater
motor improvement during the ON state than patients without migraine with the
same medication exposure. These data support the hypothesis that migraine may be 
associated with dopaminergic hypersensitivity.

Publication Types: 
    Clinical Trial
    Comparative Study
    Controlled Clinical Trial

PMID: 15090934 [PubMed - indexed for MEDLINE]

2273: CNS Drugs. 2004;18(6):337-42.

Comment in:
    Eur J Neurol. 2006 May;13(5):552.

Central sensitisation and cutaneous allodynia in migraine: implications for
treatment.

Landy S, Rice K, Lobo B.

Wesley Headache Clinic and University of Tennessee Medical School, Memphis,
Tennessee, USA. wesleyhead@aol.com

Cutaneous allodynia, pain resulting from application of a non-noxious stimulus to
normal skin, is a recently described symptom of migraine, with a potential role
in directing optimal treatment for migraine attacks. Manifestations of cutaneous 
allodynia include discomfort when combing the hair, shaving, and wearing glasses,
contact lenses, earrings or tight clothing.The exact mechanism by which a
migraine attack is triggered is not known, but it has been theorised that, in
some patients, once the attack has begun, central neurons can propagate
information about the pain process without the need for further external stimuli.
This process is termed central sensitisation. The trigeminal nerves, which
innervate intracranial and extracranial tissues, account for head pain and other 
symptoms in migraine. The first-order neurons in the trigeminal ganglion receive 
input from the dural blood vessels, which is transmitted to second-order neurons 
in the trigeminal brain stem nuclear complex and is finally sent to the
third-order neurons in the thalamus. Studies in humans and animals have shown
that migraine pain progresses along this neural pathway, with throbbing head pain
occurring early in the attack (sensitisation of first-order neurons), followed by
central sensitisation and cutaneous allodynia within the referred pain area
(second-order) and finally extracephalic allodynia (third-order). The data also
indicate that once central sensitisation is established in the second- and
third-order neurons, migraine treatment designed to prevent the initiation of
central sensitisation can lessen the pain to some extent but cannot reverse it.
Thus, treatment affecting the initiation of central sensitisation should be
administered immediately after the onset of migraine pain to prevent intracranial
hypersensitivity and the establishment of allodynia.The serotonin 5-HT(1B/1D)
agonist anti-migraine agents (the 'triptans') block meningeal nociceptor
transmission at presynaptic sites in the dorsal horn. Studies have shown that
triptan therapy can abort pain prior to the development of central sensitisation,
but not after allodynia has been established. Therefore, in the subset of
patients who report symptoms of cutaneous allodynia with migraine attacks, early 
initiation of triptan therapy is currently the best intervention to achieve
rapid, complete and sustained pain relief.

Publication Types: 
    Review

PMID: 15089101 [PubMed - indexed for MEDLINE]

2274: J Neural Transm. 2004 May;111(5):603-9.

Association analysis of the functional monoamine oxidase A gene promotor
polymorphism in migraine.

Marziniak M, Mössner R, Benninghoff J, Syagailo YV, Lesch KP, Sommer C.

Department of Neurology, University of Würzburg, Würzburg, Germany.
dr.martin.marziniak@uniklinik-saarland.de

Migraine affects about 15% of the adult population. Serotonergic and dopaminergic
systems are believed to be involved in its pathophysiology. One of the key
enzymes in the degradation of serotonin and to a lesser extent of dopamine is
monoamine oxidase A (MAO-A). In this study we investigated a functionally
relevant gene-linked polymorphic repetitive sequence (LPR) located approximately 
1.2 kb upstream of the ATG codon in the MAO-A-promotor gene. 119 patients with
migraine and 229 controls were tested. The allelic distribution of the controls
and the migraine patients did not show significant differences with respect to
the low- and high-activity alleles. Moreover, effectiveness of the potent
serotonergic antimigraine agents, triptans, which are metabolized by MAO-A, was
clinically not affected by the MAO-A-LPR in our patients. These findings thus
indicate that there is no association between the functional MAO-A-LPR and
susceptibility to migraine.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 15088153 [PubMed - indexed for MEDLINE]

2275: Med Care. 2004 May;42(5):487-91.

The disparity in access to new medication by type of health insurance: lessons
from Germany.

Krobot KJ, Miller WC, Kaufman JS, Christensen DB, Preisser JS, Ibrahim MA.

Department of Epidemiology, School of Public Health, The University of North
Carolina at Chapel Hill, Chapel Hill, North Carolina, USA. kkrobot@web.de

BACKGROUND: Drug provision within the German statutory health insurance system
has undergone several reforms, including the introduction of drug macrobudgets in
1993. OBJECTIVE: The objective of this study was to investigate the extent to
which statutorily (SHI) and fully privately (PHI) health-insured patients were
provided with new medication recommended by professional bodies in an equitable
fashion using the example of migraine patients. RESEARCH DESIGN: We conducted a
retrospective cohort study. SETTING: A total of 367 primary-care practices
(MediPlus, IMS Health) in Germany in the second year of the HealthCare Structural
Reform Act were studied. SUBJECTS: Subjected consisted of 7703 SHI and 470 PHI
migraineurs (International Classification of Diseases, 10th edition G43) aged 18 
to 65 years at their first migraine prescription visit in 1994. OUTCOME MEASURE: 
We compared prescription of oral or subcutaneous serotonin 5HT1B/1D receptor
agonist sumatriptan with nonserotoninergic migraine therapy. RESULTS: In
multiplicative risk regression with variance estimation accounting for clustering
of patients within practices, PHI patients were 2.3 times (95% confidence
interval [CI], 1.6-3.3) more likely to receive sumatriptan than their SHI
counterparts at the mean age of the cohorts (43 years) adjusted for incident
versus prevalent migraine treatment, the gender of the patient, the age, gender, 
and primary care specialist group of the physician, and the type and the
community size class of the practice. This disparity widened by 38% (95% CI,
1-88%) every 10 years of patient age. CONCLUSION: Even though virtually everyone 
in Germany has health insurance and drug coverage, use of new and recommended
migraine medicines was less common among those with SHI compared with their
privately insured counterparts. Systematic studies of access to health care
recommended by professional bodies will be critically important to ensure
delivery of high-quality health care for all patients.

PMID: 15083110 [PubMed - indexed for MEDLINE]

2276: Med Hypotheses. 2004;62(5):766-9.

Erratum in:
    Med Hypotheses. 2004;63(1):179.

Brain blood perfusion hypothesis for migraine, anger, and epileptic attacks.

Sugahara H.

Department of Psychosomatic Medicine, Graduate School of Medical Sciences, Kyushu
University, 3-1-1 Maidashi, Higashi-Ku, Fukuoka 812-8582, Japan.
sugahara@cephal.med.kyushu-u.ac.jp

The common physiological rationale for migraine, anger, and epileptic attacks is 
discussed. The potential importance of homeostatic reactions in brain blood
perfusion is described. The author speculates that these attacks are induced to
meet some urgent biological needs. Each attack of migraine, anger, and epilepsy
results in increased regional cerebral blood flow, with hypoperfusion being shown
in inter-icteric states. This hypoperfusion may also be related to cerebral
ischemic disease, organic change, some critical condition, or vasoconstriction
due to sympathetic hyperactivity. Migraine attack is a subacute local vasomotor
response. In contrast, anger and epileptic attacks are different manifestations
of acute solemn general neuropsychiatric vasomotor reflexes. The newer paradigm
of the etiological integration of these three kinds of attacks based on cerebral 
hemodynamic change does not only explain the mechanism of seizure-producing
treatments such as electroconvulsive therapy, but also indicates the significance
of cerebral vasodilative demands for the particular treatment of migraine,
aggressive behavior, and epileptic seizures.

PMID: 15082103 [PubMed - indexed for MEDLINE]

2277: J Clin Neurosci. 2004 May;11(4):384-8.

Chronic migrainous vertigo.

Waterston J.

Departments of Neurology, Oto-neurology and Medicine, Monash University, Alfred
Hospital, Melbourne, Vic. 3004, Australia. jjwaters@bigpond.net.au

A series of 16 subjects is described who presented with chronic vertigo that was 
thought to be migrainous in nature. The vertigo occurred on a daily basis and had
been present for six months or more. Common symptoms included motion-induced
dizziness, positional vertigo and motion sensitivity. Investigations were
frequently normal apart from the finding of atypical positional nystagmus in four
subjects and unilateral vestibular hypofunction in two subjects. It was
frequently not possible to make a diagnosis of migraine on the basis of
International Headache Society criteria, however the dramatic beneficial response
to anti-migraine therapy supported the hypothesis that the vertigo was migrainous
in nature.

PMID: 15080953 [PubMed - indexed for MEDLINE]

2278: Drugs Today (Barc). 2003;39 Suppl D:37-41.

Current perspectives on effective migraine treatments: are small clinical
differences important for patients?

Ferrari MD.

Leiden University Medical Centre, Leiden, The Netherlands.

The introduction of 5-HT(1B/1D) agonists, i.e. triptans, the first drugs
specifically developed for the treatment of acute migraine, has revolutionized
the treatment of migraine attacks. Triptans have met the needs of many migraine
patients, however given the lack of direct comparative trials including all
triptans, a meta-analysis of results with all available triptans needed to be
conducted. Similar clinical trial design, patient population characteristics and 
main endpoints certainly facilitated the performance of this meta-analysis.
Results from 53 randomized, double-blind, controlled clinical trials on acute
triptan therapy in 24,089 patients were compared with respect to the main
efficacy and tolerability variables. At recommended doses, almotriptan 12.5 mg,
eletriptan 80 mg and rizatriptan 10 mg provided the highest likelihood of
consistent success. (c) 2003 Prous Science. All rights reserved.

Publication Types: 
    Review

PMID: 15071619 [PubMed - indexed for MEDLINE]

2279: Drugs Today (Barc). 2003;39 Suppl D:31-6.

Almotriptan: an effective and well-tolerated treatment for migraine pain.

Pascual J.

University Hospital Marques de Valdecilla, Santander, Spain.

The clinical data of almotriptan, the new selective 5-HT(1B/1D) agonist developed
for the symptomatic treatment of migraine, are reviewed here. The pharmacokinetic
performance of almotriptan is compared with that of other currently available
triptans. The dose exhibiting the best efficacy/tolerability ratio of almotriptan
is 12.5 mg. Efficacy of this almotriptan dose is comparable to that of the "gold"
standard triptan, but with a lower recurrence rate. Gender or the presence of
food in the stomach does not influence almotriptan's pharmacokinetic profile, and
no relevant interactions of almotriptan with other medications have been
reported. The tolerability of almotriptan is similar to that of placebo.
Almotriptan's high efficacy together with its excellent tolerability and safety
profile confirm this new 5-HT(1B/1D) agonist as a drug of choice for the
symptomatic treatment of migraine attacks. (c) 2003 Prous Science. All rights
reserved.

Publication Types: 
    Review

PMID: 15071618 [PubMed - indexed for MEDLINE]

2280: Drugs Today (Barc). 2003;39 Suppl D:25-9.

Migraine medication attributes are important for patient compliance.

Massiou H.

Hôpital Lariboisière, Paris, France.

The determinant of patient compliance with an anti-migraine drug is a complex
alchemy. Studies of patient needs consistently show that pain freedom, speed of
onset and no headache recurrence are important features of an anti-migraine
product. Adverse events are important in migraine management, and concerns about 
them may significantly affect patient compliance. A high efficacy/tolerance ratio
is definitely an essential factor, but irrational factors, such as the patient's 
expectations, knowledge, prejudices and concerns about the drug, may also
interfere. Patients' worries about such events may instigate avoidance of
prescription medicine that leads to increased intensity and duration of pain, an 
increased need to rest, reduced productivity and cancellation of social and
work-related activities. (c) 2003 Prous Science. All rights reserved.

Publication Types: 
    Review

PMID: 15071617 [PubMed - indexed for MEDLINE]

2281: Drugs Today (Barc). 2003;39 Suppl D:17-23.

Measuring disability and quality of life in migraine.

Dahlöf CG.

Institute of Clinical Neuroscience, Sahlgrenska University Hospital, Gothenburg, 
Sweden.

Although eight out of ten people suffer from different types of headaches, the
severity of their pain is often not communicated properly to their doctors.
Research shows that when doctors understand exactly how headaches are affecting
their patients, they are able to provide a better and fully successful treatment 
program. The magnitude of impact of migraine is generally measured through
self-administered questionnaires. Two reliable questionnaires for measuring
patients' disability and quality of life in migraine are the Migraine Disability 
Assessment Questionnaire (MIDAS) and the new Internet-based Headache Impact Test 
(HIT). (c) 2003 Prous Science. All rights reserved.

Publication Types: 
    Review

PMID: 15071616 [PubMed - indexed for MEDLINE]

2282: Drugs Today (Barc). 2003;39 Suppl D:11-6.

The neurologist-sufferer perspective: "migraine tears me away from my life".

Carter D.

Neurologist/Headache Specialist, Springfield, Missouri, USA.

The aim of this paper is to present--from both a patient and neurologist
perspective--the pattern of headaches over my lifetime. Migraine often does not
remain static, but changes depending on internal and external stimuli. Thus, in
my case, the pattern of headaches changed over the years from episodic,
predominantly exertional occipital headaches with holocranial spread in late
teens to chronic daily headache due to overuse of over-the-counter analgesics in 
young adulthood, and then to episodic migraine with occasional visual aura, and
finally to menstrual migraine and frequent headaches during the perimenopausal
years. Migraine sometimes provokes the development of several collateral comorbid
disorders, such as mitral valve prolapse, often occurring in response to new
environmental stimuli and worsening headaches. Finally, I present here my own
experience with preventative therapy and how new effective abortive agents, such 
as the triptans, have dramatically improved my quality of life. (c) 2003 Prous
Science. All rights reserved.

Publication Types: 
    Review

PMID: 15071615 [PubMed - indexed for MEDLINE]

2283: Drugs Today (Barc). 2003;39 Suppl D:3-9.

Patient-focused migraine management: establishing needs.

Dodick DW.

Mayo Medical School, Scottsdale, Arizona, USA.

Headache disorders represent a serious threat to the sufferer's quality of life
and normal day-to-day functioning. Headache generates a substantial disability
burden, being classified among the major public health disorders. There is no
doubt that the emergence of the triptan class in the early 1990s dramatically
advanced the treatment of migraine and has changed the perspective of the
migraine sufferer with respect to the treatment. Triptan therapies for migraine
relief have been proven to be safe and efficacious in clinical trials.
Nevertheless, endpoint-based clinical trials are focused more on specific
measures of efficacy and tolerability (e.g., relief, response and adverse event
rates), and less on the patient's feelings and quality of life. For instance, in 
the U.S. only 29% of migraine sufferers are very satisfied with their usual
treatment. The principal reasons for their dissatisfaction with therapy are as
follows: pain relief takes too long (87%), treatment does not relieve all the
pain (87%), treatment does not always work (85%), headache comes back (71%), and 
too many side effects (35%). Thus, this work is focused on patients' perspectives
on migraine therapies attempting to establish their needs and to find better
treatment possibilities for restoring patients' overall functionality. (c) 2003
Prous Science. All rights reserved.

Publication Types: 
    Review

PMID: 15071614 [PubMed - indexed for MEDLINE]

2284: Lancet. 2004 Jan 31;363(9406):381-91.

Comment in:
    Lancet. 2004 Apr 24;363(9418):1398-9; author reply 1399.    Lancet. 2004 Apr 24;363(9418):1398; author reply 1399.

Migraine.

Silberstein SD.

Jefferson Headache Centre, Thomas Jefferson University Hospital, Philadelphia,
PA, USA. Stephen.Silberstein@jefferson.edu

Migraine is a very common neurobiological headache disorder that is caused by
increased excitability of the CNS. It ranks among the world's most disabling
medical illnesses. Diagnosis is based on the headache's characteristics and
associated symptoms. The economic and societal effect of migraine is substantial:
it affects patients' quality of life and impairs work, social activities, and
family life. There are many acute and preventive migraine treatments. Acute
treatment is either specific (triptans and ergots) or non-specific (analgesics). 
Disabling migraine should be treated with triptans. Increased headache frequency 
is an indication for preventive treatment. Preventive treatment decreases
migraine frequency and improves quality of life. More treatments are being
developed, which provides hope to the many patients whose migraines remain
uncontrolled.

Publication Types: 
    Review

PMID: 15070571 [PubMed - indexed for MEDLINE]

2285: Nurse Pract. 2004 Apr;29(4):22-31; quiz 32-3.

Optimize migraine management in primary care.

Frazel JE.

Loyola University, Marcella Niehoff School of Nursing, Chicago, IL, USA.

Migraine attacks vary in frequency, severity, symptomatology, and degree of
disability. The episodic, heterogeneous nature of migraine can be a barrier to
the assessment of impact and optimal management. Migraine is often
under-diagnosed and undertreated. Optimizing migraine management requires a
systematic assessment of symptoms, including the degree of disability and
development of an individualized plan of care.

Publication Types: 
    Review

PMID: 15064570 [PubMed - indexed for MEDLINE]

2286: Facial Plast Surg Clin North Am. 2003 Nov;11(4):465-75.

Treatment of migraine headache with botulinum toxin type A.

Binder WJ, Blitzer A.

Department of Head and Neck Surgery, University of California at Los Angeles
School of Medicine, USA. WJBMD8@aol.com

Migraine is a common headache disorder with profound implications on patients'
quality of life and the overall health care system. Traditional treatment options
have been less than optimal and many migraine patients lack confidence in
over-the-counter and prescribed medications. BTX-A has shown promise as an
efficacious, well-tolerated, long-lasting preventive therapy. Completed
placebo-controlled trials showed that BTX-A injections for migraine resulted in
fewer headaches, reduced headache severity and duration, reduced
migraine-associated symptoms, and reduced use of migraine medications. Because
the administration of BTX-A is nonsystemic, reported adverse events have been
rare and mild. Larger trials are currently underway to further evaluate BTX-A
efficacy and to determine optimal dosing and injection sites.Based on the
collective experience of clinicians in neurology, facial plastic surgery, and
otolaryngology, as well as supporting evidence from completed and ongoing
clinical trials and theorized mechanism of action, an effective BTX-A approach
for treatment of migraine is emerging. With further refinement to its use as
prophylactic therapy, BTX-A can potentially be a primary option for candidate
migraine sufferers and prescribing clinicians.

Publication Types: 
    Review

PMID: 15062251 [PubMed - indexed for MEDLINE]

2287: Neurol Sci. 2004 Apr;25(1):8-12.

Persistent ocular motor disturbances in migraine without aura.

Wieser T, Wolff R, Hoffmann KP, Schulte-Mattler W, Zierz S.

Department of Neurology, Martin-Luther-Universität Halle/Wittenberg,
Ernst-Grube-Strasse 40, D-06097 Halle/Saale, Germany. thomas.wieser@web.de

Activation in the brain stem during attacks of migraine has been detected with
the use of functional imaging, suggesting an important role of the brain stem in 
this disorder. Recent findings showed permanent cerebellar signs in common forms 
of migraine. Both structures are involved in generating smooth pursuit eye
movements. The aim of this study was to investigate migraine patients by
electrooculography to identify persisting abnormalities that may provide a
clinical sign of continuous dysfunction of these structures. We investigated 25
patients with migraine without aura and 15 controls. Smooth pursuit was
pathologically changed, velocity gain was reduced and phase was significantly
altered in migraineurs as compared to controls. The data provide clinical
evidence of a persistent dysfunction in the brain stem and certain cerebellar
structures in migraine patients. This is consistent with previous studies
indicating an important role of the brain stem in generating migraine attacks.

PMID: 15060809 [PubMed - indexed for MEDLINE]

2288: BMC Med. 2004 Feb 12;2:3.

The methylenetetrahydrofolate reductase gene variant C677T influences
susceptibility to migraine with aura.

Lea RA, Ovcaric M, Sundholm J, MacMillan J, Griffiths LR.

Genomics Research Centre, School of Health Science, Griffith University,
Queensland, Australia. Rod.Lea@vuw.ac.nz <Rod.Lea@vuw.ac.nz>

BACKGROUND: The C677T variant in the methylenetetrahydrofolate reductase (MTHFR) 
gene is associated with increased levels of circulating homocysteine and is a
mild risk factor for vascular disease. Migraine, with and without aura (MA and
MO), is a prevalent and complex neurovascular disorder that may also be affected 
by genetically influenced hyperhomocysteinaemia. To determine whether the C677T
variant in the MTHFR gene is associated with migraine susceptibility we utilised 
unrelated and family-based case-control study designs. METHODS: A total of 652
Caucasian migraine cases were investigated in this study. The MTHFR C677T variant
was genotyped in 270 unrelated migraine cases and 270 controls as well as 382
affected subjects from 92 multiplex pedigrees. RESULTS: In the unrelated
case-control sample we observed an over-representation of the 677T allele in
migraine patients compared to controls, specifically for the MA subtype (40% vs. 
33%) (chi2 = 5.70, P = 0.017). The Armitage test for trend indicated a
significant dosage effect of the risk allele (T) for MA (chi2 = 5.72, P = 0.017).
This linear trend was also present in the independent family-based sample (chi2 =
4.25, Padjusted = 0.039). Overall, our results indicate that the T/T genotype
confers a modest, yet significant, increase in risk for the MA subtype (odds
ratio: 2.0 - 2.5). No increased risk for the MO subtype was observed (P > 0.05). 
CONCLUSIONS: In Caucasians, the C677T variant in the MTHFR gene influences
susceptibility to MA, but not MO. Investigation into the enzyme activity of MTHFR
and the role of homocysteine in the pathophysiology of migraine is warranted.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 15053827 [PubMed - indexed for MEDLINE]

2289: J Neurol Sci. 2004 Apr 15;219(1-2):101-6.

Cerebral vasoreactivity in Andeans and headache at sea level.

Appenzeller O, Passino C, Roach R, Gamboa J, Gamboa A, Bernardi L, Bonfichi M,
Malcovati L.

NMHEMC Research Foundation, Otto Appenzeller, 361, Big Horn Ridge Drive NE,
Albuquerque, NM 87122-1424, USA. ottoarun12@aol.com

Headache is common in Cerro de Pasco (CP), Peru (altitude 4338 m) and was present
in all patients with chronic mountain sickness (CMS) in CP reported here.
Forty-seven percent of inhabitants report headache. Twenty-four percent of men
have migraine with aura, with an average of 65 attacks a year. We assessed
vasoreactivity of the cerebral vessels to CO2 by rebreathing and to NO by the
administration of isosorbite dinitrate (IDN), a nitric oxide (NO) donor, using
transcranial Doppler ultrasound in the middle cerebral artery (MCA) in natives of
CP, some of whom suffered from CMS. We repeated the measurements in Lima
(altitude 150 m) in the same subjects within 24 h of arrival. Vasodilatation in
the middle cerebral artery supply territory in response to CO2 and NO, both
physiologic vasodilators, is defective in Andean natives at altitude and in the
same subjects at sea level. Incapacitating migraine can occur with impaired
cerebral vasoreactivity to physiologic vasodilators. We propose that
susceptibility to migraine might depend in part on gene expression with
consequent alterations of endothelial function.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, Non-P.H.S.
    Research Support, U.S. Gov't, P.H.S.

PMID: 15050445 [PubMed - indexed for MEDLINE]

2290: Ann Emerg Med. 2004 Apr;43(4):483-93.

Variability in emergency physician decision making about prescribing opioid
analgesics.

Tamayo-Sarver JH, Dawson NV, Cydulka RK, Wigton RS, Baker DW.

Case Western Reserve University School of Medicine, Cleveland, OH, USA.

STUDY OBJECTIVE: The purpose of this study is to determine what factors influence
emergency physicians' decisions to prescribe an opioid analgesic for 3 common,
painful conditions. METHODS: We developed items thought to influence the decision
to prescribe an opioid analgesic through a review of the literature, expert
consultation, and interviews with practicing emergency physicians. We developed a
baseline vignette and items expected to influence the decision for each of the 3 
conditions: migraine, back pain, and ankle fracture. We surveyed 650 physicians
randomly selected from the American College of Emergency Physicians. The
influence of individual items was explored through a univariate analysis of the
response distribution. Patterns were assessed by analytically creating scales.
RESULTS: We received responses from 398 (63%) of the 634 eligible physicians.
Physicians' likelihoods of prescribing an opioid showed marked variability, with 
at least 10% of physicians saying they were unlikely and 10% of physicians saying
they were likely to prescribe for each condition. Physician responses to
individual pieces of clinical information, such as the patient requesting
"something strong" for the pain, were also highly variable, with at least 10% of 
physicians saying they would be negatively influenced by this request and at
least 10% saying they would be positively influenced by it. CONCLUSION: Even when
faced with identical case scenarios, physicians' decisions to prescribe opioid
analgesics are highly variable. Moreover, the same clinical information, such as 
a patient requesting a strong analgesic, changes the likelihood of prescribing
opioids in opposite directions for different physicians.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 15039692 [PubMed - indexed for MEDLINE]

2291: Lancet Neurol. 2004 Apr;3(4):237-45.

Headache with focal neurological signs or symptoms: a complicated differential
diagnosis.

Schoenen J, Sándor PS.

Department of Neurology, Headache Research Unit, University of Liège, Belgium.
jean.schoenen@chrcitadelle.be

Headache syndromes can be associated with focal neurological symptoms or signs.
Good knowledge of primary headaches, a detailed history and a thorough clinical
examination are prerequisites for their differential diagnosis. The neurological 
symptoms produced by the migraine aura are the most characteristic and
recognisable. However, structural lesions, such as vascular malformations, can
produce similar symptoms to migraine with aura, which highlights that
paraclinical investigations are necessary in most patients with headache and
focal neurological symptoms. In this review, we provide an overview of the
differential diagnosis of the most common headache disorders with focal
neurological symptoms or signs to refresh the practising neurologist's
differential diagnostic knowledge for the clinical situation and to aid the
teaching of neurology residents.

Publication Types: 
    Review

PMID: 15039036 [PubMed - indexed for MEDLINE]

2292: Clin Ther. 2004 Feb;26(2):214-23.

Efficacy and tolerability of sumatriptan tablets in a fast-disintegrating,
rapid-release formulation for the acute treatment of migraine: results of a
multicenter, randomized, placebo-controlled study.

Carpay J, Schoenen J, Ahmad F, Kinrade F, Boswell D.

Department of Neurology, Hospital Gooi-Noord, Laren, The Netherlands.
jcarpay@gooi-noord.nl

BACKGROUND: Sumatriptan tablets have been developed in a fast-disintegrating,
rapid-release formulation designed to facilitate tablet disintegration and drug
dispersion and to potentially mitigate the effects of gastric stasis that can
accompany migraine. OBJECTIVE: This study was conducted to evaluate the efficacy 
and tolerability of sumatriptan 50- and 100-mg tablets in a fast-disintegrating, 
rapid-release formulation compared with those of placebo in patients with
migraine. METHODS: This clinical trial had a randomized, double-blind,
placebo-controlled, parallel-group design. Exclusion criteria included >6
migraines monthly during either of the 2 months before screening; uncontrolled
hypertension; suspected or confirmed cardiovascular or cerebrovascular disease;
and ophthalmic, basilar, or hemiplegic migraine. Sumatriptan 50 and 100 mg and
placebo were taken on an outpatient basis during the mild-pain phase of a single 
migraine attack. Patients recorded details of the treated migraine on a diary
card and rated pain severity immediately before dosing and 30 minutes, 45
minutes, 1 hour, and 2 hours after dosing using a 4-point scale (from 0 = none to
3 = severe). The primary efficacy end point was the proportion of patients who
were pain free 2 hours after dosing. Additional efficacy end points were the
proportion of patients who were pain free at 30 minutes, 45 minutes, and 1 hour
after dosing; the proportion who were migraine free through 2 hours after dosing;
and the proportion with a sustained pain-free response. RESULTS: Patients' mean
age ranged from 39.7 to 41.5 years across the 3 groups, and the majority were
women (79.7%-85.9%) and white (98.7%-100%). One hundred thirty-seven patients
received sumatriptan 50 mg, 142 sumatriptan 100 mg, and 153 placebo. In the
intent-to-treat population (n = 432), 51.1% of patients who received sumatriptan 
50 mg and 66.2% of patients who received sumatriptan 100 mg were pain free 2
hours after dosing, compared with 19.6% of the placebo group (P < 0.001, each
sumatriptan dose vs placebo). In an exploratory analysis, the 2-hour pain-free
rate with sumatriptan 100 mg was significantly better than that with sumatriptan 
50 mg (P = 0.007). Significantly more patients who received sumatriptan 100 mg
were pain free compared with placebo at 30 minutes (P < 0.01), 45 minutes (P <
0.001), and 1 hour after dosing (P < 0.001); similar pain-free results were
observed in patients who received sumatriptan 50 mg at 45 minutes (P < 0.05) and 
1 hour (P = 0.01). In the per-protocol population (n = 313), pain-free efficacy 2
hours after dosing was 52.7% with sumatriptan 50 mg and 74.8% with sumatriptan
100 mg, compared with 21.0% with placebo (P < 0.001, each sumatriptan dose vs
placebo). These rates were greater than those in the overall study population,
approximately 12.0% of whom treated moderate or severe pain. The only
drug-related adverse events reported in >/=3% of patients in any treatment group 
were nausea and vomiting (<1%, 5%, and 2% in the sumatriptan 50 and 100 mg and
placebo groups, respectively), chest symptoms (2%, 3%, and 0%), and malaise and
fatigue (1%, 3%, and <1%). No serious adverse events were reported. CONCLUSIONS: 
In this study, sumatriptan tablets in a fast-disintegrating, rapid-release oral
formulation provided pain-free efficacy in the acute treatment of migraine.
Efficacy was maximized with the 100-mg dose compared with the 50-mg dose, and by 
treating early when pain was mild. In the intent-to-treat population, 51.1% of
patients who received sumatriptan 50 mg and 66.2% of those who received
sumatriptan 100 mg were pain free 2 hours after dosing. In the per-protocol
population, 3 of 4 patients taking the 100-mg tablets for mild pain within 1 hour
of its onset were pain free at 2 hours. Sumatriptan tablets were generally well
tolerated.

Publication Types: 
    Clinical Trial
    Multicenter Study
    Randomized Controlled Trial

PMID: 15038944 [PubMed - indexed for MEDLINE]

2293: Neurology. 2004 Mar 23;62(6):883-7.

Nasal sumatriptan is effective in treatment of migraine attacks in children: A
randomized trial.

Ahonen K, Hämäläinen ML, Rantala H, Hoppu K.

Hospital for Children and Adolescents, Department of Clinical Pharmacology,
University of Helsinki, Finland. Kati.Ahonen@hus.fi

OBJECTIVE: To investigate the efficacy of nasal sumatriptan in migraine attacks
of children and adolescents. METHODS: A double-blind, placebo-controlled, two-way
crossover trial was conducted in three hospital outpatient departments, with 8 to
17 year olds diagnosed with migraine serving as subjects (International Headache 
Society 1988). A single dose of sumatriptan nasal spray and a matching placebo
were administered at home during two attacks. The sumatriptan dose was 10 mg for 
a body weight of 20 to 39 kg and 20 mg for those with a body weight of >/=="
BORDER="0">40 kg. The primary efficacy endpoint was headache relief by two grades
on a 5-grade face scale at 2 hours. RESULTS: Eighty-three patients used both
treatments and 11 only the first. At 2 hours, the primary endpoint was reached
nearly twice as often after sumatriptan (n = 53/83; 64%) as after placebo (n =
32/83; 39%) (p = 0.003). Already at 1 hour, headache relief was seen more often
after sumatriptan (n = 42/83; 51%) than after placebo (n = 24/83; 29%) (p =
0.014). The difference was even more obvious in patients who received the 20-mg
dose as well as in the intention-to-treat analyses (n = 94). Other endpoints,
including child's preference and using rescue medication, also favored
sumatriptan. The most common adverse effect was a bad taste after sumatriptan,
reported in 29% (n = 26/90) of the attacks. No serious adverse effects were
observed. CONCLUSION: Nasal sumatriptan is an effective and well-tolerated
treatment for migraine attacks in children over 8 years of age.

Publication Types: 
    Clinical Trial
    Multicenter Study
    Randomized Controlled Trial

PMID: 15037686 [PubMed - indexed for MEDLINE]

2294: Invest Ophthalmol Vis Sci. 2004 Apr;45(4):1061-70.

Decreased visual field sensitivity measured 1 day, then 1 week, after migraine.

McKendrick AM, Badcock DR.

School of Psychology, University of Western Australia, Crawley, Western
Australia, Australia. allisonm@psy.uwa.edu.au

PURPOSE: To determine whether perimetric performance is worse the day after a
migraine than prior interictal measurements, and if so, to determine whether
differences have resolved by 1 week after migraine. METHODS: Twenty-two
nonheadache control subjects (aged 18-45 years) and 22 migraineurs (aged 18-45
years: 10 migraine with visual aura, 12 migraine without aura) participated.
Standard automated perimetry (SAP) and temporal modulation perimetry (TMP) were
measured by perimeter (model M-700; Medmont, Pty Ltd., Camberwell, Victoria,
Australia). Control subjects attended two test visits: baseline and retest.
Migraineurs attended three times: baseline (>or=4 days after migraine), the day
after the offset of the next migraine, and 7 days later. Groups were compared
using the global indices of the perimeter: Average Defect (AD) and Pattern Defect
(PD), in addition to point-wise comparisons. RESULTS: Group migraineur TMP
performance was significantly worse the day after a migraine, showing decreased
general sensitivity and increased localized loss. Performance measured 7 days
later was not significantly different from that measured the day after a
migraine. Group migraineur SAP performance was not significantly worse after
migraine; however, a subgroup of six eyes from five patients had 10 or more
visual field locations with decreases in sensitivity greater than control
test-retest 95% confidence limits. CONCLUSIONS: Decreased visual field
performance was present after migraine, as well as greater test-retest
variability in the migraine group compared with control subjects. As migraineurs 
constitute 10% to 15% of the general population, the presence of this subgroup of
patients with periodic prolonged decreased visual field sensitivity after
migraine has implications for differential clinical diagnosis, and for clinical
research using perimetry.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 15037569 [PubMed - indexed for MEDLINE]

2295: Pain. 2004 Apr;108(3):267-75.

Pattern-reversal visual-evoked potentials in children with migraine and other
primary headache: evidence for maturation disorder?

Oelkers-Ax R, Bender S, Just U, Pfüller U, Parzer P, Resch F, Weisbrod M.

Department of Child and Adolescent Psychiatry, University of Heidelberg,
Blumenstrasse 8, D-69115 Heidelberg, Germany. rieke_oelkers@med.uni-heidelberg.de

Recently, evidence for a disturbed maturation of cerebral information processing 
in migraine came from studies investigating the auditory-evoked contingent
negative variation and the auditory-evoked potential from childhood to adulthood.
This study is to clarify whether age-dependent development is altered also for
the processing of visual stimuli in migraine. Components of pattern-reversal
visual-evoked potentials at four different spatial frequencies (which can
preferentially activate the magno- and the parvocellular visual system) were
compared between children aged 6 and 18 years with primary headache (N = 123; 67 
migraine without aura, MO; 32 migraine with aura, MA; 24 tension-type headache,
TH) in the headache-free interval and healthy controls (N = 82). Children were
divided into two age groups: 6-11 years (pre- and early puberty) and 12-18 years 
(late and post-puberty). Age-dependent development was normal for N80 and P100
latency in children with primary headache, but altered for N135 latency as
indicated by a significant interaction among the factors diagnosis, spatial
frequency and age group (P < 0.01). In headache-free controls, N135 latency
reduction between pre- and post-puberty age was most pronounced at high spatial
frequency. The main 'decline' of N135 latency with increasing age was shifted to 
lower spatial frequencies in the headache subgroups. The results give evidence
that maturation of visual processing is partly disturbed in migraineurs.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 15030946 [PubMed - indexed for MEDLINE]

2296: Cephalalgia. 2004 Apr;24(4):298-304.

Triptans and chest symptoms: the role of pulmonary vasoconstriction.

Dodick DW.

Department of Neurology, Mayo Clinic, Scottsdale, AZ, USA. dodick.david@mayo.edu

Triptans are effective and well tolerated in the treatment of acute migraine.
Chest symptoms are a common adverse effect unrelated to coronary vasoconstriction
in most patients. Although the aetiology of chest symptoms remains to be fully
defined, pulmonary vasoconstriction is a possible underlying mechanism.
Pre-clinical studies of isolated human blood vessels were used to identify the
cerebral selectivity of triptans and ascertain if selectivity vs the pulmonary
vasculature predicts a lower rate of chest symptoms. Controlled clinical trials
and post-marketing surveillance studies were reviewed to document the incidence
of chest symptoms after triptan therapy. In clinical trials, the incidence of
chest symptoms at usual therapeutic doses ranged from 1 to 4% depending on the
triptan and study design, whereas in post-marketing surveillance studies, up to
41% of patients specifically asked about chest symptoms reported them. A
comparative clinical trial showed that almotriptan was associated with lower
incidence of chest symptoms than sumatriptan (0.3 vs 2.2%). The intrinsic
activity of almotriptan, a second-generation triptan, on human pulmonary arteries
and veins was lower than that of sumatriptan. Pre-clinical studies of isolated
pulmonary blood vessels may predict the clinical likelihood of chest symptoms;
however, additional comparisons are needed.

Publication Types: 
    Review

PMID: 15030540 [PubMed - indexed for MEDLINE]

2297: Cephalalgia. 2004 Apr;24(4):293-7.

Prevalence and clinical characteristics of an experimental model of 'ice-cream
headache' in migraine and episodic tension-type headache patients.

Selekler HM, Erdogan MS, Budak F.

Department of Neurology, Kocaeli University, Faculty of Medicine, Kocaeli,
Turkey. macitselekler@hotmail.com

This study was designed to compare the prevalence and clinical characteristics of
'cold-induced headache' between migraine and episodic tension-type headache
patients. Seventy-six migraine and 38 episodic tension-type headache patients
were included in the study. An experimental model of an 'ice-cream headache' was 
developed for the study. The pain occurrence period, its location and quality
were recorded for each patient who felt pain in their head during the test
procedure. Pain in the head occurred in 74% of migraine and 32% of 'tension-type 
headache' patients. Although the most frequent pain location was the temple in
both groups of patients, this rate was greater than twofold in migraine patients 
when compared with episodic tension-type headache patients. While headache
quality was throbbing in 71% of migraine patients, it was so in only 8% of the
episodic tension-type headache patients. Considering all the results, it seems
that 'cold-stimulus headache' is not only more frequent in migraine patients, but
also its location and quality differ from 'tension-type headache'.

Publication Types: 
    Comparative Study

PMID: 15030539 [PubMed - indexed for MEDLINE]

2298: Cephalalgia. 2004 Apr;24(4):271-9.

Interictal daily functioning in migraine.

Stronks DL, Tulen JH, Bussmann JB, Mulder LJ, Passchier J.

Department of Medical Psychology and Psychotherapy, Erasmus Medical Center,
Rotterdam, the Netherlands.

Migraine induces disability and an impaired quality of life, even between
attacks. As most studies are based on subjective reports only, this study was set
up to objectively quantify the interictal daily activities and heart rate of
migraine patients, in relation to their subjectively reported highest realizable 
level of activity and of symptoms of mood in their habitual environment.
Measurements were obtained during a migraine-free 2-day period of 24 patients
(age range: 21-57 years) and 24 controls (age range: 18-59 years). Accelerometry 
was used to quantify the time spent in different postures and movements. The
subjective parameters were documented by daily log. Whereas heart rate was
similar for patients and controls, migraineurs were found to be significantly
less physically active than controls and reported a significantly lower
realizable level of activity. In addition, when active, their body motility was
less than that of controls. Migraine patients also showed a higher level of
sleepiness and lower level of vigour. These interictal behavioural and subjective
phenomena objectively illustrate the individual and societal burden of migraine
and its chronic impact on both domains.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 15030535 [PubMed - indexed for MEDLINE]

2299: Cephalalgia. 2004 Apr;24(4):262-70.

Assessment of migraine severity using the MIGSEV scale: relationship to migraine 
features and quality of life.

El Hasnaoui A, Vray M, Blin P, Nachit-Ouinekh F, Boureau F; HEMISHERE study
group.

Epidemiology Department, GSK Laboratory, Marly le-Roi, France. aeh82790@gsk.com

We have recently developed an instrument to describe and categorize severity of
migraine attacks from patient self-report, the MIGSEV questionnaire. We have now 
performed a large prospective survey using this tool to evaluate migraine
severity in 2979 patients consulting for headache in France, included by 1164
general practitioners, 174 neurologists and 82 gynaecologists. The objective of
the study was to determine the prevalence of severity grades in a large
population who consults for migraine, to test the concordance between severity
calculated from physician-derived and patient-derived data, and to test the
relevance of the concept of severity as applied to diagnosis, other measures of
the burden of migraine, and to health-related quality of life. Severe attacks
were reported in around one-fifth of the sample. Physician- and patient-derived
data provided concordant estimates of severity in 71% of cases, the discordant
cases representing principally an underestimate by the physician of headache
severity. Migraine severity was associated with frequent, long-lasting and
treatment-resistant attacks, and with poor quality of life. The MIGSEV
questionnaire is proposed as a simple measure of severity for the diagnosis and
management of migraineurs, suitable for use both by physicians and patients.

Publication Types: 
    Comparative Study

PMID: 15030534 [PubMed - indexed for MEDLINE]

2300: J Biopharm Stat. 2004 Feb;14(1):31-51.

Planning analyses of quality-of-life studies: a case example with migraine
prophylaxis.

Fairclough DL, Gagnon D, Papadopoulos G.

Colorado Health Outcomes Program and Department of Preventive Medicine and
Biometry, University of Colorado Health Sciences Center, Denver, Colorado 80210, 
USA. dianefairclough@earthlink.net

Assessment of health-related quality of life (QOL) has become increasingly common
in clinical trials. Because QOL has multiple dimensions and is assessed
repeatedly over time, multiple comparisons and missing data must be addressed in 
the design and analysis of these trials. While the development of an analysis
plan will be a continuous process, described here are three critical phases in
the ideal development of a statistical analysis plan for the QOL component of a
clinical trial: concept, initial design, and final analysis plans. A clinical
trial designed to evaluate a new therapy for the prevention of migraines was used
to illustrate the critical decisions that are made during the design and analysis
phases of a trial that incorporates QOL in the assessment procedure. Specifically
addressed are clearly defining goals and objectives, endpoints, multiple
comparisons, analysis of longitudinal data with dropout, and estimation of power.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 15027499 [PubMed - indexed for MEDLINE]

2301: Curr Med Res Opin. 2004 Mar;20(3):269-77.

Eletriptan for the acute treatment of migraine: results of bridging a Japanese
study to Western clinical trials.

Sakai F, Diener HC, Ryan R, Poole P.

Department of Medicine, Kitasato University Hospital, Sagamihara City, Kanagawa
Prefecture, Japan. fsakai@kitasato-u.ac.jp

OBJECTIVE: To compare the efficacy, safety and tolerability of eletriptan (20, 40
and 80 mg) to placebo when given to Japanese and Western patients for the acute
treatment of migraine. METHODS: A double-blind, randomized, parallel-group trial 
with the aforementioned therapeutic objectives was conducted in Japan (N = 321). 
By bridging analysis, data from this study were compared to two migraine trials
previously conducted in the US (N = 1190) and Europe (N = 563). RESULTS: The 2-h 
post-dose headache response rates (i.e., the primary efficacy endpoint) of
Japanese migraineurs to eletriptan 20, 40 and 80 mg were 64, 67 and 76%,
respectively; European and American migraineurs showed similar trends and, in
these studies, eletriptan was significantly superior to placebo (p < 0.05).
Japanese patients did demonstrate a higher placebo response than Westerners,
possibly due to differences in previous triptan exposure or expectation. Adverse 
events were generally mild to moderate, were comparable in all three studies, and
showed a modest dose-response effect. CONCLUSION: The efficacy and tolerability
of eletriptan for the acute treatment of migraine is comparable in Japan, Europe 
and the US.

Publication Types: 
    Clinical Trial
    Clinical Trial, Phase II
    Clinical Trial, Phase III
    Comparative Study
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 15025836 [PubMed - indexed for MEDLINE]

2302: Otolaryngol Clin North Am. 2003 Dec;36(6):1063-78, v-vi.

Migraine mechanism and management.

Spierings EL.

Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, 75
Francis Street, Boston, MA 02115, USA.

Migraine affects an estimated 10% to 15% of the population with greater or lesser
regularity and throughout much of their lifetime. It causes disability, be it
often temporary, and strains personal relationships and professional development.
Little is known about it scientifically, and its treatment remains mostly
empirical. This article describes the pathogenesis of migraine, as well as its
management in terms of abortive and preventive treatment.

Publication Types: 
    Review

PMID: 15025007 [PubMed - indexed for MEDLINE]

2303: Genet Epidemiol. 2004 Apr;26(3):231-44.

Latent class and genetic analysis does not support migraine with aura and
migraine without aura as separate entities.

Nyholt DR, Gillespie NG, Heath AC, Merikangas KR, Duffy DL, Martin NG.

Queensland Institute of Medical Research, Brisbane, Queensland, Australia.
daleN@qimr.edu.au

Latent class and genetic analyses were used to identify subgroups of migraine
sufferers in a community sample of 6,265 Australian twins (55% female) aged 25-36
who had completed an interview based on International Headache Society (IHS)
criteria. Consistent with prevalence rates from other population-based studies,
703 (20%) female and 250 (9%) male twins satisfied the IHS criteria for migraine 
without aura (MO), and of these, 432 (13%) female and 166 (6%) male twins
satisfied the criteria for migraine with aura (MA) as indicated by visual
symptoms. Latent class analysis (LCA) of IHS symptoms identified three major
symptomatic classes, representing 1) a mild form of recurrent nonmigrainous
headache, 2) a moderately severe form of migraine, typically without visual aura 
symptoms (although 40% of individuals in this class were positive for aura), and 
3) a severe form of migraine typically with visual aura symptoms (although 24% of
individuals were negative for aura). Using the LCA classification, many more
individuals were considered affected to some degree than when using IHS criteria 
(35% vs. 13%). Furthermore, genetic model fitting indicated a greater genetic
contribution to migraine using the LCA classification (heritability, h(2)=0.40;
95% CI, 0.29-0.46) compared with the IHS classification (h(2)=0.36; 95% CI,
0.22-0.42). Exploratory latent class modeling, fitting up to 10 classes, did not 
identify classes corresponding to either the IHS MO or MA classification. Our
data indicate the existence of a continuum of severity, with MA more severe but
not etiologically distinct from MO. In searching for predisposing genes, we
should therefore expect to find some genes that may underlie all major recurrent 
headache subtypes, with modifying genetic or environmental factors that may lead 
to differential expression of the liability for migraine. Copyright 2004
Wiley-Liss, Inc.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 15022209 [PubMed - indexed for MEDLINE]

2304: Psychopharmacol Bull. 2003;37 Suppl 2:98-115.

Divalproex in the treatment of migraine.

Freitag FG.

Diamond Headache Clinic, Suite 500, 467 W. Deming Place, Chicago, IL 60614, USA. 
dhcdoc@aol.com

Valproic acid has been used in the treatment of migraine headache for nearly 20
years. During this period of use several additional delivery modes have been
developed to either improve tolerability or patient compliance with the
divalproex sodium formulation and the extended-release formulation of divalproex 
sodium. Additionally, an intravenous formulation has become available which
permits rapid achievement of therapeutic levels of the drug. There have been a
number of reports on the use of valproic acid in migraine and other headache
disorders, suggesting it to be an efficacious treatment. This paper reviews the
results of the published reports of valproic acid in migraine and other headache 
disorders, including open-label studies, comparator trials, and double-blind,
placebo-controlled trials. These studies have been conducted with the various
formulations of valproic acid that have been on the market. The papers utilized
in this study were obtained though Medline searches on valproic acid and
divalproex sodium coupled with the various headache disorders. Additionally, the 
CD-ROM of past issues of Headache and Cephalalgia was reviewed for similar
keywords. Lastly, the indices of the journal Headache Quarterly were reviewed for
additional articles on valproic acid and divalproex sodium. Valproic acid in its 
various formulations has been demonstrated to be an efficacious and
well-tolerated agent for the preventive treatment of migraine, chronic daily
headache, and cluster headache. Additionally, it has been demonstrated to be
efficacious and well tolerated in treating acute migraine attacks when given as
an intravenous solution.

Publication Types: 
    Review

PMID: 15021865 [PubMed - indexed for MEDLINE]

2305: Otol Neurotol. 2004 Mar;25(2):135-8.

Characterizing and treating dizziness after mild head trauma.

Hoffer ME, Gottshall KR, Moore R, Balough BJ, Wester D.

Department of Defense Spatial Orientation Center, Department of Otolaryngology,
Naval Medical Center San Diego, San Diego, California 92134-2200, USA.
mehoffer@nmcsd.med.navy.mil

OBJECTIVE: The objectives of this study were to characterize patterns of
dizziness seen after mild head trauma and to examine the diagnosis and treatment 
of this disorder. STUDY DESIGN: Prospective patient registry. SETTING: Tertiary
referral center. PATIENTS: Fifty-eight cases of active duty and retired military 
personnel who sustained mild head trauma and had resultant dizziness.
INTERVENTIONS: Vestibular evaluation, characterization by group, and treatment.
MAIN OUTCOME MEASURES: Outcome measures include characterization of diagnosis
types, patient distribution by diagnosis type, and patient outcome. RESULTS:
Individuals suffering from dizziness after mild head injury were divided into
three diagnostic groups. Forty-one percent of the individuals suffered from
posttraumatic vestibular migraines, 28% of the individuals had posttraumatic
positional vertigo, and 19% of the individuals were classified as posttraumatic
spatial disorientation. The remaining 12% of the patients could not be
characterized. The positional group had objective physical examination findings, 
which cleared with treatment in all cases. The migraine group of patients and the
disorientation group of patients had distinct abnormalities of the
vestibulo-ocular reflex (VOR) and the vestibulo-spinal reflex (VSR). Eighty-four 
percent of the migraine group demonstrated an improvement of these test results
as compared with 27% of the disorientation group. Mean time to return to work was
less than 1 week for the positional group, 3.8 weeks for the migraine group, and 
greater than 3 months for the disorientation group. CONCLUSIONS: Using our
patient registry of individuals suffering from dizziness after mild head trauma, 
we were able to characterize the majority of these cases into one of three more
specific diagnostic groups. We present diagnostic criteria, suggested treatment
guidelines, and our prognostic data.

PMID: 15021772 [PubMed - indexed for MEDLINE]

2306: Proc Natl Acad Sci U S A. 2004 Mar 23;101(12):4274-9. Epub 2004 Mar 11.

Disruption of communication between peripheral and central trigeminovascular
neurons mediates the antimigraine action of 5HT 1B/1D receptor agonists.

Levy D, Jakubowski M, Burstein R.

Departments of Anesthesia and Critical Care, Beth Israel Deaconess Medical
Center, Boston, MA 02115, USA.

Triptans are 5HT(1B/1D) receptor agonists commonly prescribed for migraine
headache. Although originally designed to constrict dilated intracranial blood
vessels, the mechanism and site of action by which triptans abort the migraine
pain remain unknown. We showed recently that sensitization of peripheral and
central trigeminovascular neurons plays an important role in the pathophysiology 
of migraine pain. Here we examined whether the drug sumatriptan can prevent
and/or suppress peripheral and central sensitization by using single-unit
recording in our animal model of intracranial pain. We found that sumatriptan
effectively prevented the induction of sensitization (i.e., increased spontaneous
firing; increased neuronal sensitivity to intracranial mechanical stimuli) in
central trigeminovascular neurons (recorded in the dorsal horn), but not in
peripheral trigeminovascular neurons (recorded in the trigeminal ganglion). After
sensitization was established in both types of neuron, sumatriptan effectively
normalized intracranial mechanical sensitivity of central neurons, but failed to 
reverse such hypersensitivity in peripheral neurons. In both the peripheral and
central neurons, the drug failed to attenuate the increased spontaneous activity 
established during sensitization. These results suggest that neither peripheral
nor central trigeminovascular neurons are directly inhibited by sumatriptan.
Rather, triptan action appears to be exerted through presynaptic 5HT(1B/1D)
receptors in the dorsal horn to block synaptic transmission between axon
terminals of the peripheral trigeminovascular neurons and cell bodies of their
central counterparts. We therefore suggest that the analgesic action of triptan
can be attained specifically in the absence, but not in the presence, of central 
sensitization.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 15016917 [PubMed - indexed for MEDLINE]

2307: N Engl J Med. 2004 Mar 11;350(11):1104-10.

Comment in:
    Expert Opin Pharmacother. 2004 Aug;5(8):1837-40.    N Engl J Med. 2004 Mar 11;350(11):1073-5.

Calcitonin gene-related peptide receptor antagonist BIBN 4096 BS for the acute
treatment of migraine.

Olesen J, Diener HC, Husstedt IW, Goadsby PJ, Hall D, Meier U, Pollentier S,
Lesko LM; BIBN 4096 BS Clinical Proof of Concept Study Group.

Department of Neurology, Glostrup Hospital, University of Copenhagen, Copenhagen,
Denmark. jeol@glostruphosp.kbhamt.dk

BACKGROUND: Calcitonin gene-related peptide (CGRP) may have a causative role in
migraine. We therefore hypothesized that a CGRP-receptor antagonist might be
effective in the treatment of migraine attacks. METHODS: In an international,
multicenter, double-blind, randomized clinical trial of BIBN 4096 BS, a highly
specific and potent nonpeptide CGRP-receptor antagonist, 126 patients with
migraine received one of the following: placebo or 0.25, 0.5, 1, 2.5, 5, or 10 mg
of BIBN 4096 BS intravenously over a period of 10 minutes. A group-sequential
adaptive treatment-assignment design was used to minimize the number of patients 
exposed. RESULTS: The 2.5-mg dose was selected, with a response rate of 66
percent, as compared with 27 percent for placebo (P=0.001). The BIBN 4096 BS
group as a whole had a response rate of 60 percent. Significant superiority over 
placebo was also observed with respect to most secondary end points: the
pain-free rate at 2 hours; the rate of sustained response over a period of 24
hours; the rate of recurrence of headache; improvement in nausea, photophobia,
phonophobia, and functional capacity; and the time to meaningful relief. An
effect was apparent after 30 minutes and increased over the next few hours. The
overall rate of adverse events was 25 percent after the 2.5-mg dose of the drug
and 20 percent for the BIBN 4096 BS group as a whole, as compared with 12 percent
for placebo. The most frequent side effect was paresthesia. There were no serious
adverse events. CONCLUSIONS: The CGRP antagonist BIBN 4096 BS was effective in
treating acute attacks of migraine. Copyright 2004 Massachusetts Medical Society

Publication Types: 
    Clinical Trial
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 15014183 [PubMed - indexed for MEDLINE]

2308: Expert Opin Pharmacother. 2004 Mar;5(3):669-77.

A review of rizatriptan, a quick and consistent 5-HT1B/1D agonist for the acute
treatment of migraine.

Pascual J.

Service of Neurology, University Hospital Marqués de Valdecilla (UC), Spain.
juliopascual@telefonica.net

Rizatriptan is a second-generation triptan marketed as 5 and 10 mg tablets and
rapidly disintegrating wafer formulations. In > 5000 acute migraine patients
enrolled in short-term trials and almost 1800 patients in long-term, open-label
trials treating approximately 47000 attacks, rizatriptan was effective and
well-tolerated. Controlled head-to-head data and a meta-analysis of 53
randomised, placebo-controlled trials of oral triptans in > 24000 patients have
shown that rizatriptan 10 mg offers efficacy advantages over oral sumatriptan 50 
and 100 mg and other oral triptans, both in terms of speed of onset of action and
consistency. These advantages may reflect its improved pharmacological profile
over sumatriptan in terms of higher oral bioavailability and a shorter time to
maximum concentration. The wafer formulation offers the convenience of being
administered without water. As a result of its superior efficacy profile and
generally good tolerability, rizatriptan can be considered as a first-line
treatment for acute migraine.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 15013934 [PubMed - indexed for MEDLINE]

2309: Headache. 2004 Mar;44(3):271-85.

Cost considerations of acute migraine treatment.

Adelman JU, Adelman LC, Freeman MC, Von Seggern RL, Drake J.

Headache Wellness Center, Greensboro, NC 27401, USA.

OBJECTIVE: To provide medication price data and cost-reducing strategies for the 
acute treatment of migraine. METHODS: Retail prices for common acute care
medications were found at http://www.drugstore.com. Cost-reduction tactics were
obtained from literature searches and clinical experience. RESULTS: Several
strategies can reduce cost without sacrificing treatment outcome. In mild to
moderate migraine, low-priced nonsteroidal anti-inflammatory drugs can be used as
first-line medications due to their proven efficacy and favorable tolerability.
For patients with more severe migraine, implementing a stratified care
approach-using migraine-specific medications early in acute treatment-is
cost-effective for most patients. Stratified care not only improves outcome and
decreases disability, but also reduces cost. Pill splitting and early
administration of triptans within an attack enhance their value. Supplying rescue
medications, such as opioids, sedatives, and phenothiazines, can prevent
emergency department visits. Minimizing multiple dosing of triptans and reducing 
utilization of expensive health care resources are key factors in reducing the
cost of effective migraine treatment. An important affordability factor for
patients with co-payments is the number of triptan pills per package.
Sumatriptan, naratriptan, and frovatriptan each contain 9 tablets per package,
while most other triptan packages contain 6. Current triptan retail prices (per
unit) include: Amerge 1 and 2.5 mg, 17.78 dollars; Axert 6.25 and 12.5 mg, 16.31 
dollars; Frova 2.5 mg, 13.89 dollars; Imitrex 50 mg, 14.96 dollars; Imitrex 100
mg, 14.41 dollars; Imitrex Nasal Spray 20 mg, 21.61 dollars; Imitrex SQ 6 mg,
50.26 dollars; Maxalt 5 and 10 mg, 15 dollars; Maxalt-MLT 5 and 10 mg, 15
dollars; Relpax 40 mg, 13.58 dollars; Zomig 2.5 mg, 13.67 dollars; Zomig 5 mg,
15.89 dollars; Zomig-ZMT 2.5 mg, 13.67 dollars; and Zomig-ZMT 5 mg, 15.89
dollars. CONCLUSIONS: Practitioners can optimize the use of health care dollars
without compromising quality of care through awareness of cost-saving treatment
strategies, as well as price variations among medications.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 15012668 [PubMed - indexed for MEDLINE]

2310: Headache. 2004 Mar;44(3):265-70.

Comment in:
    Headache. 2005 Jan;45(1):89-90.    Headache. 2005 Jan;45(1):89; author reply 89-90.

Migraine-associated seizures with recurrent and reversible magnetic resonance
imaging abnormalities.

Mateo I, Foncea N, Vicente I, Gómez Beldarrain M, Garcia-Monco JC.

Neurology Service, Galdakao Hospital, Vizcaya, Spain.

Migraine and epilepsy are highly comorbid, but the nature of their association
remains unclear. Exceptionally, reversible brain magnetic resonance imaging (MRI)
abnormalities following migraine and seizures have been reported. There are no
descriptions, however, of patients with recurrent brain MRI changes. We report a 
patient with repeated episodes of migraine-with-aura-associated seizures
(migralepsy) and recurrent and reversible brain MRI abnormalities. Location of
the abnormalities was always consistent with the neurologic deficits. The
possibility that transient brain MRI abnormalities in a patient with migraine
with aura followed by seizures may be due to migralepsy should be borne in mind
to avoid misdiagnosis and potentially aggressive procedures.

Publication Types: 
    Case Reports

PMID: 15012667 [PubMed - indexed for MEDLINE]

2311: Headache. 2004 Mar;44(3):262-4.

Hourglass deformity after botulinum toxin type A injection.

Guyuron B, Rose K, Kriegler JS, Tucker T.

Case Western Reserve University, Cleveland, Ohio, USA.

BACKGROUND: Complications, such as eyelid ptosis, have been attributed to
botulinum toxin type A. An "hourglass" deformity, which is the consequence of
temporalis muscle atrophy, has not been reported previously. OBJECTIVE: To report
a transient muscle deformity of the temporalis muscle caused by botulinum toxin
type A. METHODS: Patients who underwent injection of 25 units of botulinum toxin 
type A into the temporal muscle, in a fan-shaped fashion, during an ongoing study
for treatment of migraine were noted to develop temporary depression of the
temples. Preinjection and postinjection photographs were taken. Patients were
also sent questionnaires to verify the observed information. RESULTS: Only 26 of 
92 patients who underwent injection of botulinum toxin type A into the temporalis
muscle subsequently reported depression of the muscle. When examined, all 92
patients exhibited this deformity ranging from minimal to significant. Patients
who seemed to have less deformity were those who had excessive soft tissue
overlying the muscle due to excess weight. CONCLUSION: A newly recognized
deformity is reported subsequent to the injection of botulinum toxin type A into 
the temporalis muscle. Informing patients of this transient deformity may
minimize concern following treatment.

PMID: 15012666 [PubMed - indexed for MEDLINE]

2312: Headache. 2004 Mar;44(3):238-43.

Efficacy and safety of levetiracetam in pediatric migraine.

Miller GS.

Pediatric Neurology Department, Hillcrest Healthcare System, Children's Medical
Center, Tulsa, Okla. 74104, USA.

BACKGROUND: Headache is a frequent occurrence among children and adolescents.
Chronic headaches can be severe and disabling, and require prophylactic
treatment; however, additional data on the use of prophylactic medications for
migraine in children are needed. OBJECTIVE: To review the efficacy and safety of 
levetiracetam (Keppra) in pediatric patients with a history of recurrent
headache. DESIGN/METHODS: Data from 19 pediatric patients were retrospectively
reviewed. The initial dose of levetiracetam was usually 125 or 250 mg twice
daily, but varied depending upon clinical judgment. RESULTS: Charts of 9 girls
and 10 boys (mean age, 11.9 years) were reviewed. A variety of medications,
including triptans, had been used before initiating treatment with levetiracetam.
Mean headache frequency before treatment was 6.3 per month (standard deviation
[SD], 3.8; confidence interval [CI], 4.4 to 8.1). Duration of headaches ranged
from 0.25 to 8 years. Migraine (63.2%) and migraine with aura (15.8%) were the
most common types of headache reported. Most patients (89.5%) had headaches that 
were severe. After treatment, the mean headache frequency decreased to 1.7 per
month (SD, 2.7; CI, 0.4 to 3.0), representing a reduction compared with baseline 
(P <.0001). Levetiracetam eliminated headaches in 10 patients (52.6%), and 7
patients (36.8%) had less severe and less frequent headaches. Levetiracetam did
not have an effect on headaches in 2 patients (10.5%). Mean duration of treatment
with levetiracetam was 4.1 months. Doses ranged from 125 to 750 mg twice daily.
Sixteen patients (84.2%) reported no side effects on levetiracetam. One patient
experienced asthenia/somnolence and dizziness, and irritable, hyperactive, and
hostile behavior led to discontinuation of levetiracetam in another patient. A
third patient experienced irritability and moodiness that attenuated after 1
month of treatment and did not require discontinuation. CONCLUSIONS: In this
small retrospective review, levetiracetam was found to be generally well
tolerated and appears to be a promising candidate for additional evaluation in
well-controlled clinical trials of pediatric patients with migraine.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 15012661 [PubMed - indexed for MEDLINE]

2313: Headache. 2004 Mar;44(3):230-7.

Comment in:
    Headache. 2004 Oct;44(9):935.

Prophylactic treatment of pediatric migraine.

Lewis DW, Diamond S, Scott D, Jones V.

Department of Pediatrics, Division of Pediatric Neurology, Children's Hospital of
the King's Daughters, Norfolk, Va 23510, USA.

BACKGROUND: Migraine occurs in 3% to 5% of young children and up to 18% of
adolescents. Management requires a tailored regimen of pharmacological and
behavioral measures that consider the headache burden and disability. Patients
with frequent or disabling attacks (or both) may warrant preventive agents.
OBJECTIVE: To investigate the patterns of prophylactic treatment of pediatric
migraine within one pediatric neurology practice. METHODS: All charts of patients
diagnosed with headache (International Classification of Diseases [ICD] code
784.0) and migraine (codes 346.0, 346.1, and 346.2) during January 2001 July 2001
were retrospectively reviewed to identify diagnosis, demographics, medical
decision making, rationale for treatment selections, and outcome assessments.
Migraine was diagnosed according to the 1997 proposed pediatric migraine
revisions to the International Headache Society. RESULTS: Charts of 250 children 
and adolescents, aged 3.2 to 18 years (mean, 12), were reviewed. One hundred
twenty-six (50%) were prescribed prophylaxis, along with intermittent analgesic
agents. Mean age of those provided with daily prophylaxis was 12.4 years (range, 
3.9 to 18), and the mean age of those managed with intermittent therapies was
11.5 years. Preventive agents included amitriptyline (n = 73), cyproheptadine (n 
= 30), propranolol (n = 8), valproic acid (n = 3), naproxen (n = 3), nimodipine
(n = 3), imipramine (n = 3), and topiramate (n = 3). Amitriptyline was the most
commonly prescribed agent (58%). Ten patients initially treated with other agents
were changed to amitriptyline. Fifteen patients required dosing adjustments, 2
stopped treatment, and 7 changed to other agents for lack of efficacy. Mean
headache frequency before treatment was 10.9 per month (range, 4 to 15). After
treatment, the mean headache frequency decreased to 4.1 per month (range, 0 to
12), a decrease of 62.4% (n = 54). The overall positive response rate was 89%.
Cyproheptadine was the second most commonly prescribed agent (mean age, 8.8
years). Thirty patients were initially treated, 5 later changed to
cyproheptadine, 6 required dosage changes, 5 changed to other agents for lack of 
efficacy, and 1 stopped treatment. Mean headache frequency before treatment was
8.4 per month (range, 4 to 15) and following treatment decreased to 3.75 per
month (range, 0 to 12), a decrease of 55.3%. The overall positive response rate
was 83%. CONCLUSIONS: Fifty percent of patients with migraine were prescribed
daily prophylactic medicines, reflecting a referral bias. The most commonly
prescribed agents were amitriptyline (preferred for the older patients) and
cyproheptadine (preferred for the younger patients). The overall positive
response rates were 89% for amitriptyline and 83% for cyproheptadine during a
6-month follow-up. Headache frequencies were reduced with amitriptyline by 62%
and with cyproheptadine by 55%. Long-term follow-up of this population is
ongoing, and prospective studies are needed.

PMID: 15012660 [PubMed - indexed for MEDLINE]

2314: Headache. 2004 Mar;44(3):209-16.

Effectiveness of eletriptan in acute migraine: primary care for Excedrin
nonresponders.

Diamond ML, Hettiarachchi J, Hilliard B, Sands G, Nett R.

Diamond Headache Clinic, Chicago, Ill 60614, USA.

OBJECTIVE: To evaluate the effectiveness of eletriptan as a treatment for acute
migraine in patients who were poor responders to Excedrin and had not yet been
exposed to a triptan. BACKGROUND: Self-medication with over-the-counter drugs,
such as Excedrin, is the most common treatment for migraine. Guidelines, however,
recommend that triptans be used as first-line treatment of moderate to severe
migraine--the severity affecting approximately 80% of migraineurs. Since
over-the-counter medications, such as Excedrin, continue to be used in many
patients, it is important that clinicians have information on the efficacy of
triptans as first-line treatment and on treatment of migraineurs who have shown
poor response to over-the-counter medications. METHODS: One hundred ten patients 
meeting criteria for migraine who were poor responders to Excedrin received
open-label treatment with a 40-mg dose of eletriptan for one migraine attack.
Efficacy assessments were made at 1, 2, 4, and 24 hours postdose and consisted of
headache and pain-free response rates, absence of associated symptoms, and
functional response. RESULTS: At 1 hour, the headache response rate was 44%; at 2
hours, 81%. The pain-free response rate at 1 hour was 14% and at 2 hours, 48%. At
2 hours, relief of baseline-associated symptoms ranged from 74% to 80%.
Functional response was achieved by 82% of patients by 2 hours, and 68% of
patients achieved relief of migraine that was sustained across 24 hours with no
need for a second dose of eletriptan or for rescue medication. Eletriptan was
well tolerated with adverse events being transient and mild to moderate in
intensity. CONCLUSION: Previous studies have established the efficacy of
eletriptan as a first-line treatment for migraine. The results of this open-label
trial demonstrate that the 40-mg dose of eletriptan had a high degree of efficacy
and tolerability among patients who were poor responders to Excedrin.

Publication Types: 
    Clinical Trial
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 15012657 [PubMed - indexed for MEDLINE]

2315: Headache. 2004 Mar;44(3):204-8.

Comment in:
    Headache. 2005 Feb;45(2):177-8; author reply 178.

Spatio-temporal imaging of cortical desynchronization in migraine visual aura: a 
magnetoencephalography case study.

Hall SD, Barnes GR, Hillebrand A, Furlong PL, Singh KD, Holliday IE.

Wellcome Trust Laboratory for MEG Studies, Neurosciences Research Institute,
Aston University, Birmingham, UK.

OBJECTIVE: To determine cortical oscillatory changes involved in migraine visual 
aura using magnetoencephalography (MEG). BACKGROUND: Visual aura in the form of
scintillating scotoma precedes migraine in many cases. The involvement of
cortical spreading depression within striate and extra-striate cortical areas is 
implicated in the generation of the disturbance, but the details of its
progression, the effects on cortical oscillations, and the mechanisms of aura
generation are unclear. METHODS: We used MEG to directly image changes in
cortical oscillatory power during an episode of scintillating scotoma in a
patient who experiences aura without subsequent migraine headache. Using the
synthetic aperture magnetometry method of MEG source imaging, focal changes in
cortical oscillatory power were observed over a 20-minute period and visualized
in coregistration with the patient's magnetic resonance image. RESULTS: Alpha
band desynchronization in both the left extra-striate and temporal cortex
persisted for the duration of reported visual disturbance, terminating abruptly
upon disappearance of scintillations. Gamma frequency desynchronization in the
left temporal lobe continued for 8 to 10 minutes following the reported end of
aura. CONCLUSIONS: Observations implicate the extra-striate and temporal cortex
in migraine visual aura and suggest involvement of alpha desynchronization in
generation of phosphenes and gamma desynchronization in sustained inhibition of
visual function.

Publication Types: 
    Case Reports
    Research Support, Non-U.S. Gov't

PMID: 15012656 [PubMed - indexed for MEDLINE]

2316: Cephalalgia. 2004 Mar;24(3):197-205.

Use and misuse of triptans in France: data from the GRIM2000 population survey.

Lucas C, Auray JP, Gaudin AF, Dartigues JF, Duru G, Henry P, Lantéri-Minet M,
Pradalier A, Chazot G, El Hasnaoui A.

Hôpital Roger Salengro, Lille, Université Claude Bernard, Lyon, France.
clucas@chru-lille.fr

The extent and nature of triptan use for headache relief has been evaluated in a 
large epidemiological survey in the French general population. Over 25 000
individuals were screened for headache and for triptan use. Of this sample, 290
triptan users were identified from whom extensive data on headache
characteristics and healthcare resource consumption were obtained. The use of
triptans is relatively infrequent, 0.2% in the general population, with only 7.5%
of migraine sufferers using these drugs. The majority of triptan users were
female (80%) and presented headache characteristics typical of migraine (80%).
The remaining 20% of subjects were thus using triptans for headache types in
which the utility of these drugs has not been demonstrated. Among migraineurs,
triptan consumers reported more frequent and severe headaches than non-consumers,
and reported a higher incidence of nausea and vomiting. The principal determinant
of triptan prescription was consultation with a general practitioner (GP), which 
may itself have been triggered by the severity of the headaches. GPs, rather than
specialists, are the primary prescribers of triptans in France.

Publication Types: 
    Comparative Study

PMID: 15009013 [PubMed - indexed for MEDLINE]

2317: Dis Manag Advis. 2004 Jan;10(1):6-10, 1.

Alternative approach to IBS and migraine is winning over providers.

[No authors listed]

Many clinicians have long suspected that symptoms of IBS are somehow related to
diet. In fact, research conducted over many years in Europe suggests than many
cases of IBS are, in fact, the result of inflammatory reactions to specific foods
or ingredients. Further, some cases of migraine appear to be linked to food
intolerances as well. Now, a company in Florida has developed a DM program that
can pinpoint specific cases of food intolerance and create an individualized
program for eliminating symptoms.

PMID: 15007999 [PubMed - indexed for MEDLINE]

2318: Neurology. 2004 Mar 9;62(5 Suppl 2):S2-8.

Migraine throughout the life cycle: treatment through the ages.

Landy S.

Wesley Headache Clinic, Memphis, TN 38138, USA.

Migraine seriously impairs the quality of life in those who suffer from it and
exacts a high socioeconomic cost in lost productivity. About half of all persons 
with migraine go undiagnosed. To avoid misdiagnosis of migraine, clinicians must 
be prepared to recognize atypical presentations, including tension headache-like 
and "sinus" symptoms. Nonpharmacologic treatments, including relaxation training 
and thermal or EMG biofeedback training, may be appropriate for some patients.
Pharmacotherapy for migraine may be acute or preventive. In prescribing
treatment, the clinician should consider the characteristics of the patient's
headaches, the patient's medication history and preferences, and co-morbidities. 
For acute treatment in patients with more severe migraine and those whose
headaches respond poorly to nonsteroidal anti-inflammatory drugs or combination
analgesics, migraine-specific agents, such as triptans, dihydroergotamine, and
ergotamine, are recommended. Early intervention--identifying and treating the
headache during the mild phase--is often a key to successful management.
Preventive treatment of migraine may be appropriate to reduce the frequency,
severity, and duration of migraine attacks, to improve the response to acute
treatment, and to reduce disability. Clinicians who treat migraine must be aware 
of considerations specific to children, women, and the elderly.

Publication Types: 
    Review

PMID: 15007158 [PubMed - indexed for MEDLINE]

2319: Neurology. 2004 Mar 9;62(5):788-90.

Incidence and predictors for chronicity of headache in patients with episodic
migraine.

Katsarava Z, Schneeweiss S, Kurth T, Kroener U, Fritsche G, Eikermann A, Diener
HC, Limmroth V.

Department of Neurology, University Hospital Essen, Germany.

The authors followed 532 consecutive patients with episodic migraine (<15
days/month) for 1 year. Sixty-four patients (14%) developed chronic headache
(>/=15 days/month). The odds ratios for developing CH were 20.1 (95% CI 5.7 to
71.5) comparing patients with a "critical" (10 to 14 days/month) vs "low" (0 to 4
days/month) and 6.2 (95% CI 1.7 to 26.6) in patients with an "intermediate" (6 to
9 days/month) vs "low" headache frequency and 19.4 (95% CI 8.7 to 43.2) comparing
patients with and without medication overuse.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 15007133 [PubMed - indexed for MEDLINE]

2320: BMC Neurol. 2004 Jan 28;4:4.

Acute treatment of migraine. Breaking the paradigm of monotherapy.

Krymchantowski AV.

Department of Neurology, Universidade Federal Fluminense, Rio de Janeiro, Brazil.
abouchkrym@globo.com

BACKGROUND: Migraine is a highly prevalent disorder. The disability provoked by
its attacks results in suffering as well as considerable economic and social
losses. The objective of migraine acute treatment is to restore the patient to
normal function as quickly and consistently as possible. There are numerous drugs
available for this purpose and despite recent advances in the understanding of
the mechanisms and different biological systems involved in migraine attacks,
with the development of specific 5-HT agonists known as triptans, current options
for acute migraine still stand below the ideal. DISCUSSION: Monotherapeutic
approaches are the rule but up to one third of all patients discontinue their
medications due to lack of efficacy, headache recurrence, cost and/or side
effects. In addition, a rationale has been suggested for the development of
polytherapeutic approaches, simultaneously aiming at some of the biological
systems involved. This paper reviews the fundamentals for this changing approach 
as well as the evidence of its better efficacy. CONCLUSION: As a conclusion, most
of the patients with a past history of not responding (no pain-free at 2 hours
and/or no sustained pain-free at 24 hours) in at least 5 previous attacks should 
undergo a combination therapy suiting to their individual profile, which must
include analgesics or non-steroidal anti-inflammatory agents plus a triptan or a 
gastro kinetic drug. The three-drug regimen may also be considered. In addition, 
changing the right moment to take it and the choice for formulations other than
oral has also to be determined individually and clearly posted to the patient.

Publication Types: 
    Review

PMID: 15005810 [PubMed - indexed for MEDLINE]

2321: Neuron. 2004 Mar 4;41(5):701-10.

Comment in:
    Neuron. 2004 Mar 4;41(5):679-80.

A Cacna1a knockin migraine mouse model with increased susceptibility to cortical 
spreading depression.

van den Maagdenberg AM, Pietrobon D, Pizzorusso T, Kaja S, Broos LA, Cesetti T,
van de Ven RC, Tottene A, van der Kaa J, Plomp JJ, Frants RR, Ferrari MD.

Department of Biomedical Sciences, University of Padova, CNR Institute of
Neuroscience, Viale G. Colombo 3, 35121 Padova, Italy. dani@civ.bio.unipd.it

Migraine is a common, disabling, multifactorial, episodic neurovascular disorder 
of unknown etiology. Familial hemiplegic migraine type 1 (FHM-1) is a Mendelian
subtype of migraine with aura that is caused by missense mutations in the CACNA1A
gene that encodes the alpha(1) subunit of neuronal Ca(v)2.1 Ca(2+) channels. We
generated a knockin mouse model carrying the human pure FHM-1 R192Q mutation and 
found multiple gain-of-function effects. These include increased Ca(v)2.1 current
density in cerebellar neurons, enhanced neurotransmission at the neuromuscular
junction, and, in the intact animal, a reduced threshold and increased velocity
of cortical spreading depression (CSD; the likely mechanism for the migraine
aura). Our data show that the increased susceptibility for CSD and aura in
migraine may be due to cortical hyperexcitability. The R192Q FHM-1 mouse is a
promising animal model to study migraine mechanisms and treatments.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 15003170 [PubMed - indexed for MEDLINE]

2322: Neuron. 2004 Mar 4;41(5):679-80.

Comment on:
    Neuron. 2004 Mar 4;41(5):701-10.

Migraine aura: a knockin mouse with a knockout message.

Goadsby PJ.

Headache Group, Institute of Neurology and The National Hospital for Neurology
and Neurosurgery, Queen Square, London, United Kingdom.

Migraine aura is a sometimes disabling disorder of the brain that involves
significant neurological symptoms in about 30% of patients. In this issue of
Neuron, van den Maagdenberg et al. characterize a mouse with a knockin mutation
known to cause familial hemiplegic migraine and provide evidence that a lowered
threshold to the triggering of CSD may account for the devastating phenotype of
familial hemiplegic migraine.

Publication Types: 
    Comment
    Review

PMID: 15003166 [PubMed - indexed for MEDLINE]

2323: Am J Ther. 2004 Mar-Apr;11(2):130-40.

The medical management of migraine.

Bigal ME, Lipton RB, Krymchantowski AV.

Department of Neurology, Albert Einstein College of Medicine, Bronx, New York
10461, USA. mbigal@aecom.yu.edu

Migraine is a common, chronic neurologic disorder that affects 11% of the adult
population in Western countries. In this article, we review the current
approaches to the pharmacologic treatment of migraine. Once migraine is
diagnosed, and illness severity has been assessed, clinicians and patients should
work together to develop a treatment plan based on the patient needs and
preferences. The goals of the treatment plan usually include reducing attack
frequency, intensity, and duration; minimizing headache-related disability;
improving health-related quality of life; and avoiding headache escalation and
medication misuse. Medical treatments for migraine can be divided into preventive
drugs, which are taken on a daily basis regardless of whether headache is
present, and acute drugs taken to treat individual attacks as they arise. Acute
treatments are further divided into nonspecific and migraine-specific treatments.
The US Headache Consortium Guidelines recommend stratified care based on the
level of disability to help physicians individualize treatment. Simple analgesics
are appropriate as first-line acute treatments for less disabled patients; if
simple analgesics are unsuccessful, treatment is escalated. For those with high
disability levels, migraine-specific acute therapies, such as the triptans, are
recommended as the initial treatment, with preventive drugs in selected patients.
A variety of behavioral interventions are helpful. The clinicians have in their
armamentariums an ever-expanding variety of medications. With experience,
clinicians can match individual patient needs with the specific characteristics
of a drug to optimize therapeutic benefit.

Publication Types: 
    Review

PMID: 14999365 [PubMed - indexed for MEDLINE]

2324: Pharmacoepidemiol Drug Saf. 2004 Feb;13(2):73-82.

Naratriptan for the treatment of acute migraine: meta-analysis of randomised
controlled trials.

Ashcroft DM, Millson D.

School of Pharmacy and Pharmaceutical Sciences, University of Manchester, UK.
darren.ashcroft@man.ac.uk

OBJECTIVE: To evaluate the comparative efficacy and tolerability of naratriptan
in the treatment of acute attacks of migraine. DESIGN: Meta-analysis of
randomised controlled trials using a random effects model. SUBJECTS: A total of
4499 patients suffering from moderate or severe attacks of acute migraine
reported in ten trials. MAIN OUTCOME MEASURES: Response rate ratios for headache 
relief, pain-free response and sustained relief (4-24 hours). Adverse events were
estimated with the rate ratio (RR), risk difference and number needed to harm.
RESULTS: Pooled RRs relative to placebo for pain-free response at 2 and 4 hours
for naratriptan 2.5 mg were 2.52 (95% CI: 1.78-3.57) and 2.58 (1.99-3.35).
Naratriptan 2.5 mg was more effective than naratriptan 1 mg; the corresponding
RRs for pain-free response at 2 and 4 hours were 1.54 (95% CI: 1.28-1.86) and
1.35 (1.20-1.51). In contrast, naratriptan 2.5 mg was less effective in pain-free
response than either rizatriptan 10 mg at 4 hours (RR: 0.68; 95% CI: 0.55-0.85)
or sumatriptan 100 mg at 4 hours (RR: 0.79; 95% CI: 0.67-0.93). However,
significantly fewer patients experienced adverse effects with naratriptan 2.5 mg 
than with rizatriptan 10 mg (RR: 0.73; 95% CI: 0.56-0.97) or sumatriptan 100 mg
(RR: 0.68; 95% CI: 0.55-0.86). CONCLUSIONS: Naratriptan is an effective and
well-tolerated treatment for acute attacks of migraine. Head-to-head comparisons 
suggest that naratriptan 2.5 mg is significantly more effective than the 1 mg
dose. Rizatriptan 10 mg and sumatriptan 100 mg were superior to naratriptan in
terms of headache relief, while zolmitriptan 2.5 mg seemed to have comparable
efficacy. Randomised controlled trials have shown that at licensed doses (1 and
2.5 mg), naratriptan is associated with a lower incidence of adverse effects than
rizatriptan, sumatriptan and zolmitriptan. The incidence rates of adverse effects
were similar to placebo.

Publication Types: 
    Comparative Study
    Meta-Analysis
    Research Support, Non-U.S. Gov't

PMID: 14998068 [PubMed - indexed for MEDLINE]

2325: J Neurol. 2004 Feb;251 Suppl 1:I8-11.

Botulinum toxin in migraine prophylaxis.

Göbel H.

Neurologisch-verhaltensmedizinische Schmerzklinik Kiel, Heikendorfer Weg 9-27,
24149 Kiel, Germany. hg@schmerzklinik.de

Migraine is a chronic headache disorder manifesting in attacks lasting 4-72
hours. Characteristics of headache are unilateral location, pulsating quality,
moderate or severe intensity, aggravation by routine physical activity, and
association with nausea, photophobia and phonophobia. The migraine aura is a
complex of neurological symptoms, which occurs just before or at the onset of
migraine headache. Botulinum toxin A represents a completely new option for
patients with chronic pain conditions. Numerous retrospective open-label chart
reviews and 4 double-blind, placebo-controlled studies have demonstrated that
botulinum toxin type A is significantly effective in migraine prophylaxis and
reduces the frequency, severity, and disability associated with migraine
headaches. Studies have generally reported a good and consistent efficacy. The
differential therapeutic use of botulinum toxin appears to be worth attempting in
migraine patients with the following characteristic features: (1) Muscular stress
as migraine trigger, e. g., in craniocervical dystonia, pericranial painful
muscular trigger points or tender points, oromandibular dysfunction, (2)
concurrent chronic tension-type headache with the aggravating factors of muscular
stress or oromandibular dysfunction, (3) chronic migraine with frequent migraine 
attacks on more than 15 days per month for longer than 3 months and if other
therapeutic options have been either ineffective or have not been tolerated. The 
use of the agent does not cause CNS side effects. Migraine patients in
particular, often suffer greatly, as a result of the adverse effects of the drugs
used, from fatigue, dizziness, reduced concentration, loss of appetite, weight
gain, hair loss and changes in libido. These side effects are not known in
association with botulinum toxin A. To date, neither organic damage nor allergic 
complications have been reported. Thus, both the tolerability and the safety of
this therapeutic measure are high. The mode of action by which botulinum toxin is
effective in migraine prophylaxis is not fully understood and is under
investigation. Currently, a number of other randomized, placebo-controlled,
clinical trials are being conducted to evaluate the efficacy, optimal dosing, and
side-effect profile of botulinum toxin type A in the prophylaxis of migraine and 
other headache entities.

Publication Types: 
    Review

PMID: 14991336 [PubMed - indexed for MEDLINE]

2326: Curr Neurol Neurosci Rep. 2004 Mar;4(2):98-104.

The epidemiology and impact of migraine.

Bigal ME, Lipton RB, Stewart WF.

Department of Neurology, Albert Einstein College of Medicine, 1300 Morris Park
Avenue, Bronx, NY 10461, USA. mbigal@aecom.yu.edu

Migraine is a highly prevalent headache disorder that has a substantial impact on
the individual and society. In this article, we review the burden of migraine,
emphasizing the population-based studies that used standardized diagnostic
criteria. We highlight descriptive epidemiology, burden of disease, patterns of
diagnosis, and treatment. We focus on the epidemiology and burden of probable
migraine, a subtype of migraine where just one clinical feature is missing. We
finish by describing approaches to improving healthcare delivery for migraine and
probable migraine. Although migraine is a remarkably common cause of temporary
disability, many migraineurs, even those with disabling headache, have never
consulted a physician for the problem. Prevalence is highest in women, in persons
between the ages of 25 and 55 years, and, at least in the United States, in
individuals from low-income households. Nonetheless, prevalence is high in groups
other than these high-risk groups. Probable migraine is a prevalent form of
migraine, and like migraine with and without aura it produces decrements in
health-related quality of life and increments in disability relative to control
subjects.

Publication Types: 
    Review

PMID: 14984680 [PubMed - indexed for MEDLINE]

2327: Cephalalgia. 2003 Dec;23(10):982-93.

Out-patient detoxification in chronic migraine: comparison of strategies.

Krymchantowski AV, Moreira PF.

Department of Neurology, Universidade Federal Fluminense, Niterói, Rio de
Janeiro, Brazil. abouchkrym@globo.com

Chronic migraine (CM) patients frequently overuse symptomatic medications (SM).
These medications may create a cycle of rebound, worsening of headache and
withdrawal symptoms that perpetuate the headache itself. In addition, the overuse
of such substances is believed to counteract the efficacy of preventive
treatments. We conducted a prospective randomized open-label trial comparing
approaches to out-patient management in 150 CM patients (125 women, 25 men; ages 
18-80 years, mean 40.3 +/- 13.8) with overuse of SM. In each group, 50 patients
received education and orientation and were then abruptly withdrawn from all SM. 
Immediately following withdrawal, the first group took prednisone (60 mg/ day 2
days, 40 mg/day 2 days and 20 mg/day 2 days) for 6 days, the second group did not
have any regular medications to take and the third group took naratriptan (2.5 mg
twice a day) during this initial period. All patients had similar profiles of
headache characteristics and consumption (quality and quantity) of SM before
initiation of the treatment, but most were not severe headache sufferers, heavy
SM overusers or were overusing opioids. After 5 weeks the headache frequency and 
intensity, the prevalence and frequency of withdrawal symptoms and consumption of
rescue medications during the first 6 days were compared between groups. In
addition, adherence to treatment (who returned or not and for which reasons,
between groups) and headache frequency, week by week, among the groups of
patients were also compared. Forty-four (88%) patients from the prednisone group,
41 (82%) from the 'nothing' group and 35 (70%) from the naratriptan group adhered
to the treatment and returned. The were no differences between groups with regard
to treatment adherence (P = 0.072), headache frequency as well as intensity (P = 
0.311) and decreasing of days with headache after 5 weeks and weekly (P = 0.275).
However, the incidence of withdrawal symptoms and consumption of rescue drugs was
higher among the patients who did not take regular medications during the first 6
days (P = 0.0001 and P = 0.006). We concluded that CM patients with moderate
overuse of SM other than opioids may be detoxified on an out-patient basis
regardless of the strategy adopted with regard to the use of regular drugs during
the initial days of withdrawal, but prednisone and naratriptan may be useful for 
reducing withdrawal symptoms and rescue medication consumption. Further
controlled studies are necessary to confirm these observations.

Publication Types: 
    Clinical Trial
    Comparative Study
    Randomized Controlled Trial

PMID: 14984232 [PubMed - indexed for MEDLINE]

2328: Cephalalgia. 2003 Dec;23(10):972-6.

Aerobic exercise and plasma beta endorphin levels in patients with migrainous
headache without aura.

Köseoglu E, Akboyraz A, Soyuer A, Ersoy AO.

Department of Neurology, University of Erciyes, Kayseri, Turkey.
emelk@erciyes.edu.tr

This study aims to evaluate the effects of plasma beta endorphin level and
exercise on migrainous headache. Forty patients with migrainous headache without 
aura (MWOA), firstly exercised on a treadmill and afterwards were asked to
continue an aerobic home exercise program for six weeks. On evaluation, basal
plasma beta endorphin level was negatively correlated with total duration of
attacks in the last month period (P = 0.01). Exercise was found to have
beneficial effects on all migraine parameters (P < 0.0001) and to increase beta
endorphin levels after the treadmill practice (P < 0.0001) and after the home
exercise program except four patients not regularly attended to the program (P < 
0.0001). Any of the changes in headache parameters was not correlated with the
change in beta endorphin level. However, pre-exercise beta endorphin level was
found to be negatively correlated with the changes in the number of attacks (P < 
0.05) and total duration of attacks (P = 0.01) and also with the change in beta
endorphin level due to exercise (P < 0.0001). As a result, this study emphasizes 
the beneficial effect of exercise on migrainous headache, especially in patients 
with lower basal beta endorphin level.

Publication Types: 
    Comparative Study

PMID: 14984230 [PubMed - indexed for MEDLINE]

2329: Cephalalgia. 2003 Dec;23(10):961-2.

Combined therapy for migraine prevention? Clinical experience with a beta-blocker
plus sodium valproate in 52 resistant migraine patients.

Pascual J, Leira R, Láinez JM.

Service of Neurology, Department of Medicine (UC), University Hospital 'Marqués
de Valdecilla', Santander, Spain. juliopascual@telefonica.net

The aim was to explore whether combining a beta-blocker and sodium valproate
could lead to an advantage in efficacy in patients with migraine previously
resistant to the two medications in monotherapy. Fifty-two patients (43 women)
with a history of episodic migraine with or without aura, and previously
unresponsive to beta-blockers and sodium valproate in monotherapy, were treated
with a combination of propranolol or nadolol and sodium valproate in an
open-label fashion. Eight patients (15%) discontinued due to adverse events.
Fifteen (29%) did not respond. The remaining 29 cases (56%) showed response (>
50% reduction in migraine days). The response was excellent in nine (17%). From
this open trial, combination therapy with a beta-blocker and sodium valproate
appears to be a good migraine preventative in some previously resistant migraine 
cases. Controlled trials are now necessary to determine the true advantage in
efficacy of this combination in difficult to treat migraineurs.

Publication Types: 
    Clinical Trial

PMID: 14984228 [PubMed - indexed for MEDLINE]

2330: Cephalalgia. 2003 Dec;23(10):953-60.

Characteristics of migraine in an out-patient population over 60 years of age.

Mazzotta G, Gallai V, Alberti A, Billeci AM, Coppola F, Sarchielli P.

Department of Neuroscience, University of Perugia, Italy.

One hundred and sixty-three consecutive patients (129 females and 34 males) over 
60 years of age attending the Headache Centre of the University of Perugia in the
period January 2000-December 2001 were included in the study. One hundred and
fifty-two (93.3%) were affected by a primary headache disorder. According to the 
1988 IHS Criteria, their prevailing attacks could be diagnosed as migraine
without aura (MwoA) in 57.2% of cases (n = 87) and as migraine with aura (MwA) in
11.8% of cases (n = 18). Attacks both in MwoA and MwA were unilateral and of
severe-to-moderate intensity in 45% and 50% of cases. Head pain was referred as
pulsating by 56% and 38.9% of MwoA patients MwA patients, respectively.
Aggravation with routine daily activities was present in 72.4% and 61.1% in MwoA 
and MwA patient groups. The most frequent accompanying symptoms were photophobia 
and phonophobia. Headache attacks were of shorter duration in MwA patients, but
in 3.4% of MwoA patients attacks lasted between 2 and 4 h. Of patients affected
by MwA, 55% referred, together with the typical attacks, symptoms of aura not
followed by headache. A worsening of headache in the last 5 years was reported by
67.8% and 44.4% of MwoA and MwA patients, respectively. Of the patients with
MwoA, 86.2% (n = 75), and 83.3% (n = 15) of those with MwA used symptomatic drugs
for their attacks. In the majority of cases they took more than one analgesic or 
non steroidal anti-inflammatory drug. A total of 51.7% of patients with MwoA and 
55.5% of patients with MwA were under prophylactic treatment. Preventive drugs
included antidepressants, beta-blockers, calcium channel antagonists and
antiepileptic drugs. The choice of symptomatic or prophylactic drugs was made, in
the majority of cases, on the basis of concomitant diseases.

Publication Types: 
    Comparative Study

PMID: 14984227 [PubMed - indexed for MEDLINE]

2331: Cephalalgia. 2003 Dec;23(10):942-52.

Erratum in:
    Cephalalgia. 2004 Feb;24(2):158.

Comparative efficacy of eletriptan and zolmitriptan in the acute treatment of
migraine.

Steiner TJ, Diener HC, MacGregor EA, Schoenen J, Muirheads N, Sikes CR.

Division of Neuroscience, Imperial College London, London, UK. t.steiner@ic.ac.uk

Eletriptan 40 mg and 80 mg have shown greater efficacy in acute migraine than
oral sumatriptan 100 mg and naratriptan 2.5 mg. This study continues the
systematic series of active comparator trials in the eletriptan clinical
development programme. In a multicentre double-blind, double-dummy,
parallel-groups trial, 1587 outpatients with migraine by IHS criteria were
randomised in a 3: 3 : 3: 1 ratio to eletriptan 80 mg, eletriptan 40 mg,
zolmitriptan 2.5 mg or placebo. Of these, 1312 treated a single migraine attack
and recorded baseline and outcome data to be included in the intention-to-treat
population. The primary analysis was between eletriptan 80 mg and zolmitriptan.
For the primary efficacy end-point of 2-h headache response, rates were 74% on
eletriptan 80 mg, 64% on eletriptan 40 mg, 60% on zolmitriptan (P < 0.0001 vs.
eletriptan 80 mg) and 22% on placebo (P < 0.0001 vs. all active treatments).
Eletriptan 80 mg was superior to zolmitriptan on all secondary end-points at 1, 2
and 24 h, in most cases with statistical significance. Eletriptan 40 mg had
similar efficacy to zolmitriptan 2.5 mg in earlier end-points, and significantly 
(P < 0.05) lower recurrence rate and need for rescue medication over 24 h. All
treatments were well tolerated; 30-42% of patients on active treatments and 40%
on placebo reported all-causality adverse events that were mostly mild and
transient. On patients' global ratings of treatment, both eletriptan doses scored
significantly better than zolmitriptan.

Publication Types: 
    Clinical Trial
    Comparative Study
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 14984226 [PubMed - indexed for MEDLINE]

2332: J Am Acad Nurse Pract. 2003 Dec;15(12):536-8.

Migraine headaches.

Goolsby MJ.

Migraine headaches are the source of significant disability for many individuals 
and their management can present a considerable clinical challenge. The American 
Academy of Family Physicians (AAFP) and American College of Physicians--American 
Society of Internal Medicine (ACP-ASIM) "Pharmacologic Management of Acute
Attacks of Migraine and Prevention of Migraine Headaches," provides a succinct,
evidence-based resource for primary care nurse practitioners. In addition to
reviewing this clinical practice guideline, this column describes related
supporting documents.

PMID: 14983568 [PubMed - indexed for MEDLINE]

2333: JAMA. 2004 Feb 25;291(8):965-73.

Comment in:
    Expert Opin Pharmacother. 2004 Aug;5(8):1837-40.    J Pediatr. 2004 Sep;145(3):419-20.

Topiramate for migraine prevention: a randomized controlled trial.

Brandes JL, Saper JR, Diamond M, Couch JR, Lewis DW, Schmitt J, Neto W, Schwabe
S, Jacobs D; MIGR-002 Study Group.

Nashville Neuroscience Group, Nashville, Tenn 37203, USA.
jbrandes@nashvilleneuroscience.com

CONTEXT: Small open-label and controlled trials suggest that the antiepileptic
drug topiramate is effective for migraine prevention. OBJECTIVE: To assess the
efficacy and safety of topiramate for migraine prevention in a large controlled
trial. DESIGN, SETTING, AND PATIENTS: A 26-week, randomized, double-blind,
placebo-controlled study was conducted during outpatient treatment at 52 North
American clinical centers. Patients were aged 12 to 65 years and had a 6-month
history of migraine (International Headache Society criteria) and 3 to 12
migraines a month but no more than 15 headache days a month during a 28-day
prospective baseline phase. INTERVENTIONS: After a washout period, patients
meeting entry criteria were randomized to topiramate (50, 100, or 200 mg/d) or
placebo. Topiramate was titrated by 25 mg/wk for 8 weeks to the assigned or
maximum tolerated dose, whichever was less. Patients continued receiving that
dose for 18 weeks. MAIN OUTCOME MEASURES: The primary efficacy measure was change
from baseline in mean monthly migraine frequency. Secondary efficacy measures
included responder rate (proportion of patients with > or =50% reduction in
monthly migraine frequency), reductions in mean number of monthly migraine days, 
severity, duration, and days a month requiring rescue medication, and adverse
events. The month of onset of preventive treatment action was assessed. RESULTS: 
Of 483 patients randomized, 468 provided at least 1 postbaseline efficacy
assessment and comprised the intent-to-treat population. Mean monthly migraine
frequency decreased significantly for patients receiving topiramate at 100 mg/d
(-2.1, P =.008) and topiramate at 200 mg/d (-2.4, P<.001) vs placebo (-1.1).
Statistically significant reductions (P<.05) occurred within the first month with
topiramate at 100 and 200 mg/d. The responder rate was significantly greater with
topiramate at 50 mg/d (39%, P =.01), 100 mg/d (49%, P<.001), and 200 mg/d (47%,
P<.001) vs placebo (23%). Reductions in migraine days were significant for the
100-mg/d (P =.003) and 200-mg/d (P<.001) topiramate groups. Rescue medication use
was reduced in the 100-mg/d (P =.01) and 200-mg/d (P =.005) topiramate groups.
Adverse events resulting in discontinuation in the topiramate groups included
paresthesia, fatigue, and nausea. CONCLUSION: Topiramate showed significant
efficacy in migraine prevention within the first month of treatment, an effect
maintained for the duration of the double-blind phase.

Publication Types: 
    Clinical Trial
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 14982912 [PubMed - indexed for MEDLINE]

2334: Neurology. 2004 Feb 24;62(4):563-8.

Triptans in migraine: the risks of stroke, cardiovascular disease, and death in
practice.

Hall GC, Brown MM, Mo J, MacRae KD.

Institute of Neurology, University College London, UK.
gillian_hall@gchall.demon.co.uk

BACKGROUND: Triptans are widely used to treat migraine but have been associated
with stroke, myocardial infarction (MI), and ischemic heart disease (IHD) in case
reports. OBJECTIVE: To estimate the incidence of stroke, cardiovascular events,
and death in a migraine cohort, stratified by triptan prescription, and
investigate whether the risk of these events was increased in those treated with 
triptans. METHODS: Migraine patients and matched nonmigraine control subjects
were identified from the General Practice Research Database. Computerized records
were searched for triptan prescriptions, stroke, TIA, MI, IHD, death, arrhythmia,
and confounding variables. Incidence rates were calculated and migraine groups
compared with controls using a Cox model, adjusting for confounders. RESULTS: Of 
63,575 migraine patients, 13,664 were prescribed a triptan. There was no
association between triptan prescription and stroke (hazard ratio [HR] 1.13; 95% 
CI 0.78, 1.65), MI (HR 0.93; 95% CI 0.60, 1.43), or other outcomes studied. The
larger group of migraine patients not prescribed a triptan had an increased risk 
of stroke (HR 1.51; 95% CI 1.26, 1.82) and IHD (HR 1.35; 95% CI 1.18, 1.54) and a
decreased risk of all-cause mortality (HR 0.72; 95% CI 0.65, 0.80). CONCLUSIONS: 
In general practice, triptan treatment in migraine does not increase the risk of 
stroke, MI, cardiovascular death, IHD, or mortality. Triptans are prescribed to
those less at risk of these events.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 14981171 [PubMed - indexed for MEDLINE]

2335: Curr Pain Headache Rep. 2004 Apr;8(2):91-5.

Prophylactic migraine therapy: mechanisms and evidence.

Ramadan NM.

Clinical & External Affairs, Department of Neurology, Finch University of Health 
Sciences/The Chicago Medical School, 3333 Green Bay Road, North Chicago, IL
60064-3095, USA. ramadan@finchcms.edu

This article focuses on the scientific evidence for pharmacotherapy for migraine 
prevention. Non-pharmacologic approaches are not discussed. However, it is
important to remember the complementary value of some of these strategies (eg,
biofeedback) to migraine treatment.

Publication Types: 
    Review

PMID: 14980143 [PubMed - indexed for MEDLINE]

2336: Curr Pain Headache Rep. 2004 Apr;8(2):85-90.

The changing face of migraine.

Potrebic S.

Southern California Permanente Medical Group, Department of Neurology, 1505
Edgemont, 5th Floor, Los Angeles, CA 90027, USA. Sonja.X.Potrebic@kp.org

Migraine is a major source of pain-related disability. Despite the personal and
societal impact of this disorder, migraine continues to be misdiagnosed and
undertreated even though well-established diagnostic criteria and safe and
effective treatments are available. The recent revision of diagnostic criteria
for headache diagnosis and consensus guidelines for migraine treatment hopefully 
will promote better medical care for headache sufferers. Advancements in
understanding the neurobiology of migraine will guide the development of new
treatments.

Publication Types: 
    Review

PMID: 14980142 [PubMed - indexed for MEDLINE]

2337: Headache. 2004 Jan;44(1):95-101.

Changes of cerebrovascular response to visual stimulation in migraineurs after
repetitive sessions of somatosensory stimulation (acupuncture): a pilot study.

Bäcker M, Hammes M, Sander D, Funke D, Deppe M, Tölle TR, Dobos GJ.

Department of Internal Medicine V, Kliniken Essen Mitte, Germany.

OBJECTIVES: To evaluate the effect of repetitive somatosensory stimulation
(acupuncture) on cerebrovascular response in migraineurs by functional
transcranial Doppler. METHODS: Changes of cerebral blood flow velocity in the
right posterior and left middle cerebral arteries were measured by functional
transcranial Doppler during visual stimulation (flickering light over 57 seconds)
in 10 migraineurs before and after 10 acupuncture sessions. The same stimulation 
paradigm was performed in 10 control subjects. Cerebral blood flow velocity data 
were analyzed with a previously validated technique based on automated
stimulus-related averaging. To evaluate the clinical effect of the treatment, a
headache diary monitored the frequency and intensity of the migraine attacks. A
positive treatment effect was defined as a reduction of at least 50% in the
attack frequency or the mean headache intensity (or both). RESULTS: Before
treatment, migraineurs showed overshooting cerebral blood flow velocity changes
at the beginning and at the end of the stimulation and a delayed decline to
baseline compared with control subjects. After treatment, this response pattern
was significantly diminished (P</=.05) in those who benefited from treatment (n =
6). Those who did not benefit from treatment (n = 4) showed a significantly
(P</=.05) more marked alteration of the cerebral blood flow velocity pattern.
CONCLUSIONS: Data indicate that repetitive somatosensory stimulation
(acupuncture) might positively influence the abnormal cerebrovascular response in
migraineurs. In a subgroup of migraineurs, however, the dysfunction of the
cerebrovascular system might deteriorate under the treatment.

Publication Types: 
    Clinical Trial
    Comparative Study
    Controlled Clinical Trial
    Research Support, Non-U.S. Gov't

PMID: 14979891 [PubMed - indexed for MEDLINE]

2338: Headache. 2004 Jan;44(1):90-4.

Morbidity and medication preferences of individuals with headache presenting to a
community pharmacy.

Wenzel RG, Schommer JC, Marks TG.

Diamond Headache Clinic Inpatient Unit, St. Joseph Hospital, Resurrection Health 
Care, Chicago, Illinois, USA.

OBJECTIVE: To assess the degree of debilitation and the treatment views of
individuals with headache presenting to a community pharmacy. BACKGROUND:
Migraine and chronic daily headache are common poorly managed illnesses.
Pharmacists recommend an over-the-counter "headache product" to customers more
than 53 000 times daily, thus they are well positioned to help those with
headache. DESIGN: Pilot project of 22 self-administered surveys of individuals
presenting to a community pharmacy with a complaint of headache. RESULTS:
Thirteen persons had Migraine Disability Assessment scores of grade III or grade 
IV. Of the sample population, a substantial minority (41%) did not believe their 
headaches could be effectively managed with over-the-counter medications, 72% did
not feel over-the-counter agents were safer than prescription products, 96% did
not indicate that over-the-counter drugs were more effective than prescription
drugs, and 50% disagreed that a physician's evaluation was not necessary. Only
half of the population was satisfied with their current therapy, and individuals 
overwhelmingly (91%) wished they could prevent their headaches. CONCLUSIONS: The 
majority of individuals with headache presenting to a community pharmacy had high
levels of morbidity and were in need of education regarding the proper role of
over-the-counter medications, the advantages of prescription agents, and the
benefits of a physician's referral. These preliminary results indicate that
community pharmacies are potentially important locations for identification,
education, and referral of individuals with headache.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 14979890 [PubMed - indexed for MEDLINE]

2339: Headache. 2004 Jan;44(1):53-64.

Comment in:
    Headache. 2004 Sep;44(8):841-2.

Migraine: a chronic sympathetic nervous system disorder.

Peroutka SJ.

OBJECTIVES: To determine the degree of diagnostic and clinical similarity between
chronic sympathetic nervous system disorders and migraine. BACKGROUND: Migraine
is an episodic syndrome consisting of a variety of clinical features that result 
from dysfunction of the sympathetic nervous system. During headache-free periods,
migraineurs have a reduction in sympathetic function compared to nonmigraineurs. 
Sympathetic nervous system dysfunction is also the major feature of rare
neurological disorders such as pure autonomic failure and multiple system
atrophy. There are no known reports in the medical literature, however, comparing
sympathetic nervous system function in individuals with migraine, pure autonomic 
failure, and multiple system atrophy. METHODS: A detailed review of the
literature was performed to compare the results of a wide variety of diagnostic
tests and clinical signs that have been described in these 3 heretofore unrelated
disorders. RESULTS: The data indicate that migraine shares significant diagnostic
and clinical features with both pure autonomic failure and multiple system
atrophy, yet represents a distinct subtype of chronic sympathetic dysfunction.
Migraine is most similar to pure autonomic failure in terms of reduced supine
plasma norepinephrine levels, peripheral adrenergic receptor supersensitivity,
and clinical symptomatology directly related to sympathetic nervous system
dysfunction. The peripheral sympathetic nervous system dysfunction is much more
severe in pure autonomic failure than in migraine. Migraine differs from both
pure autonomic failure and multiple system atrophy in that migraineurs retain the
ability, although suboptimal, to increase plasma norepinephrine levels following 
physiological stressors. CONCLUSIONS: The major finding of the present study is
that migraine is a disorder of chronic sympathetic dysfunction, sharing many
diagnostic and clinical characteristics with pure autonomic failure and multiple 
system atrophy. However, the sympathetic nervous system dysfunction in migraine
differs from pure autonomic failure and multiple system atrophy in that occurs in
an anatomically intact system. It is proposed that the sympathetic dysfunction in
migraine relates to an imbalance of sympathetic co-transmitters. Specifically, it
is suggested that a migraine attack is characterized by a relative depletion of
sympathetic norepinephrine stores in conjunction with an increase in the release 
of other sympathetic cotransmitters such as dopamine, prostaglandins, adenosine
triphosphate, and adenosine. An enhanced understanding of the sympathetic
dysfunction in migraine may help to more effectively diagnose, prevent, and/or
treat migraine and other types of headache.

Publication Types: 
    Comparative Study
    Review

PMID: 14979884 [PubMed - indexed for MEDLINE]

2340: Headache. 2004 Jan;44(1):48-52.

Consequences of transforming measures of efficacy for acute therapies: 5-HT
agonists as a worked example.

Fox AW, Keywood C, Sheftell FD, Spierings EL.

EBD Group, Carlsbad, California, USA.

OBJECTIVES: To examine whether the distributions of active and placebo response
rates change after transformation into therapeutic gains, numbers needed to
treat, and therapeutic ratios for 51 published clinical trials of 5-HT(1B/1D)
agonists in the acute treatment of migraine. BACKGROUND: Acute migraine therapies
have been compared using meta-analysis. Before pooling the results of
noncontemporaneous clinical trials for meta-analysis, reconciliation of active
response rates with concurrent placebo controls is done because of fluctuations
in placebo response rates. The 3 common methods of reconciliation are to find for
each clinical trial the therapeutic gain, the number needed to treat, or the
therapeutic ratio. METHODS: Raw active and placebo response rates were tabulated 
and displayed as histograms. The distributions of the therapeutic gains, numbers 
needed to treat, and therapeutic ratios were similarly plotted. These
distributions were then compared with normal distributions using chi-squared
goodness-of-fit methodology. RESULTS: The distribution of active response rates
was consistent with a normal distribution (passing a goodness-of-fit test).
Placebo response rates were not normally distributed. The distribution of
therapeutic gains failed a test of normality (P=.018), as did the numbers needed 
to treat (P <.001); the skews of these distributions were toward opposite ends of
the scale for relative efficacy. The therapeutic ratios also failed a test for
normality, but passed a test for log-normal distribution. CONCLUSIONS: Choice of 
transformation is a potential source of bias in meta-analysis of acute migraine
therapies.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 14979883 [PubMed - indexed for MEDLINE]

2341: Headache. 2004 Jan;44(1):35-42; discussion 42-3.

Regulation of calcitonin gene-related peptide secretion from trigeminal nerve
cells by botulinum toxin type A: implications for migraine therapy.

Durham PL, Cady R, Cady R.

Department of Biology, Southwest Missouri State University, MO, USA.

OBJECTIVES: To determine the effect of botulinum toxin type A on calcitonin
gene-related peptide secretion from cultured trigeminal ganglia neurons.
BACKGROUND: The ability of botulinum toxins to cause muscle paralysis by blocking
acetylcholine release at the neuromuscular junction is well known. Previous
studies and clinical observations have failed to demonstrate sensory changes
related to botulinum toxins or the disease of botulism. Recent studies, however, 
have suggested that botulinum toxin type A injected into pericranial muscles may 
have a prophylactic benefit in migraine. This observation has renewed the debate 
of a mechanism of sensory inhibition mediated by botulinum toxin type A. METHODS:
Primary cultures of rat trigeminal ganglia were utilized to determine whether
botulinum toxin type A could directly decrease the release of calcitonin
gene-related peptide, a neuropeptide involved in the underlying pathophysiology
of migraine. Untreated cultures or cultures stimulated with a depolarizing
stimulus (potassium chloride) or capsaicin, an agent known to activate sensory C 
fibers, were treated for 3, 6, or 24 hours with clinically effective doses of
botulinum toxin type A or a control vehicle. The amount of calcitonin
gene-related peptide secreted into the culture media following the various
treatments was determined using a specific radioimmunoassay. RESULTS: A high
percentage (greater than 90%) of the trigeminal ganglia neurons present in 1- to 
3-day-old cultures was shown to express calcitonin gene-related peptide.
Treatment with depolarizing stimuli (potassium chloride), a mixture of
inflammatory agents, or capsaicin caused a marked increase (4- to 5-fold) in
calcitonin gene-related peptide released from the trigeminal neurons.
Interestingly, overnight treatment of trigeminal ganglia cultures with
therapeutic concentrations of botulinum toxin type A (1.6 or 3.1 units) did not
affect the amount of calcitonin gene-related peptide released from these neurons.
The stimulated release of calcitonin gene-related peptide following chemical
depolarization with potassium chloride or activation with capsaicin, however, was
greatly repressed by the botulinum toxin, but not by the control vehicle. A
similar inhibitory effect of overnight treatment with botulinum toxin type A was 
observed with 1.6 and 3.1 units. These concentrations of botulinum toxin type A
are well within or below the range of tissue concentration easily achieved with a
local injection. Incubation of the cultures with toxin for 24, 6, or even 3 hours
was very effective at repressing stimulated calcitonin gene-related peptide
secretion when compared to control values. CONCLUSIONS: These data provide the
first evidence that botulinum toxin type A can directly decrease the amount of
calcitonin gene-related peptide released from trigeminal neurons. The results
suggest that the effectiveness of botulinum toxin type A in the treatment of
migraine may be due, in part, to its ability to repress calcitonin gene-related
peptide release from activated sensory neurons.

Publication Types: 
    Research Support, U.S. Gov't, P.H.S.

PMID: 14979881 [PubMed - indexed for MEDLINE]

2342: Headache. 2004 Jan;44(1):29-34.

Basilar and middle cerebral artery reactivity in patients with migraine.

Silvestrini M, Baruffaldi R, Bartolini M, Vernieri F, Lanciotti C, Matteis M,
Troisi E, Provinciali L.

Neurological Clinic, University of Ancona, Torrette di Ancona, Italy.

BACKGROUND: Migraine has been reported as a possible risk factor for ischemic
stroke. The mechanisms underlying this association are unknown. OBJECTIVES: To
evaluate cerebrovascular reactivity to hypercapnia in the anterior and posterior 
circulation of patients with migraine, as reduced cerebrovascular reactivity is
associated with a predisposition to stroke in various clinical conditions.
METHODS: Using transcranial Doppler ultrasonography, changes in flow velocity
during apnea were measured in both middle cerebral arteries and in the basilar
artery of 15 control subjects and 30 patients with migraine (15 with aura and 15 
without aura) during an attack-free period. Cerebrovascular reactivity was
evaluated using the breath-holding index, which is calculated by dividing the
percent increase in mean flow velocity recorded during a breath-holding episode
by its duration (in seconds) after a normal inspiration. RESULTS: Vascular
reactivity in the middle cerebral arteries was similar in patients and controls
and significantly lower in the basilar artery of patients with migraine with aura
compared with the other 2 groups (P <.0001). CONCLUSIONS: These findings show
that in patients with migraine with aura, there is an impairment in the adaptive 
cerebral hemodynamic mechanisms in the posterior circulation. This fact could
have pathogenetic implications since the association between migraine and stroke 
frequently regards patients with migraine with aura, and cerebral infarcts occur 
more commonly in the vertebrobasilar district.

PMID: 14979880 [PubMed - indexed for MEDLINE]

2343: Headache. 2004 Jan;44(1):20-8.

Erratum in:
    Headache. 2004 Sep;44(8):following 852. Carson, April L Perry [corrected to
Carson, April Perry].    Headache. 2005 Jan;45(1):99.

Lifetime prevalence of migraine and other headaches lasting 4 or more hours: the 
Atherosclerosis Risk in Communities (ARIC) study.

Carson AP, Rose KM, Sanford CP, Ephross SA, Stang PE, Hunt KJ, Brown CA, Szklo M.

Department of Epidemiology, University of North Carolina at Chapel Hill, USA.

OBJECTIVES: To evaluate the lifetime prevalence of migraine and other headaches
lasting 4 or more hours in a population-based study of older adults. BACKGROUND: 
Migraine and other headaches not fulfilling migraine criteria are common
afflictions. Yet the health and social effects of these conditions have not been 
fully appreciated, particularly among older adults. METHODS: The study included
12 750 participants in the Atherosclerosis Risk in Communities (ARIC) Study from 
4 US communities. Prevalence estimates of a lifetime history of migraine and
other headaches lasting 4 or more hours were obtained for race and gender groups.
A cross-sectional analysis was done to assess the relationship between headache
type, by aura status, and various sociodemographic and health-related indices.
RESULTS: Compared to education beyond high school, having completed less than 12 
years of education was significantly associated with an increased occurrence of
migraine with aura (prevalence odds ratio [POR], 1.47; 95% confidence interval
[CI], 1.08 to 2.01). Family income less than $16 000, compared to family income
of $75 000 or greater, was significantly associated with migraine with aura (POR,
1.68; 95% CI, 1.07 to 2.64), migraine without aura (POR, 1.56; 95% CI, 1.14 to
2.14), and other headaches with aura (POR, 1.89; 95% CI, 1.14 to 3.13). The
prevalence odds ratio was higher in each headache category, particularly for
those with an aura, for those with hypertension versus normotension and for those
who perceived their general health as poor compared to those whose perception was
excellent. CONCLUSIONS: A lifetime history of migraine with aura and other
headaches with aura was more common among whites, women, and younger
participants. Further investigation of headaches lasting 4 or more hours,
particularly by aura status, is warranted.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 14979879 [PubMed - indexed for MEDLINE]

2344: Headache. 2004 Jan;44(1):8-19.

Population-based door-to-door survey of migraine in Japan: the Daisen study.

Takeshima T, Ishizaki K, Fukuhara Y, Ijiri T, Kusumi M, Wakutani Y, Mori M,
Kawashima M, Kowa H, Adachi Y, Urakami K, Nakashima K.

Department of Neurology, Institute of Neurological Sciences, Tottori University
Faculty of Medicine, Yonago, Japan.

OBJECTIVES: To determine prevalence and characteristics of migraine in Japan, and
to investigate use of medical care and whether food preference is associated with
risk of migraine. METHODS: Structured questionnaires were given to all adult
residents (N = 5758; 2681 men and 3077 women) in Daisen, a rural community in
western Japan. Second questionnaires, specific to headache, were given to 1628
residents with headache. A telephone survey was also carried out. Statistical
Packages for the Social Sciences analyzed the data. RESULTS: The 1-year
prevalence of migraine was 2.3% (migraine with aura, 0.4% and without aura, 1.9%)
in men and 9.1% (migraine with aura, 1.0% and migraine without aura, 8.1%) in
women. Overall prevalence of migraine in Daisen was 6.0% (95% confidence interval
[CI], 5.4% to 6.6%). Women observed a 5.9-fold higher risk of migraine than men
(odds ratio, 5.9; 95% CI, 4.5 to 8.0; P <.0001, after age adjustment, by logistic
analysis). Fatigue and loss of vigor were predominant premonitory symptoms of
migraine. Fatigue, mental stress, and lack of sleep were the main headache
triggers. Over a 3-month period, 20.3% of migraineurs experienced time or days
off work due to headache. Only 7.3% of those with migraine with aura and 5.3% of 
those with migraine without aura had consulted a physician, and of those with
migraine, 61.0% with aura and 71.8% without aura had never visited a medical
doctor for their headache. Consumption of alcohol and cigarette smoking did not
influence the risk for migraine or tension-type headache, after age and gender
adjustment (logistic analysis). Migraineurs consume significantly more fatty/oily
foods, coffee, and tea than nonheadache subjects of the same community.
Migraineurs consume significantly fewer fish than nonheadache residents.
CONCLUSIONS: Only a few Japanese migraineurs receive benefits of medical services
and recent advances of headache medicine. Public education concerning headaches
is one of the most urgent issues in Japan.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 14979878 [PubMed - indexed for MEDLINE]

2345: Headache. 2004 Jan;44(1):2-7.

Comment in:
    Headache. 2004 Oct;44(9):933-4.

Women's issues of migraine in tertiary care.

Kelman L.

Headache Center of Atlanta, GA, USA.

OBJECTIVES: To document the frequency and types of symptoms of migraine in a
large group of female migraineurs in tertiary care. Background.-Hormonal changes 
remain a significant accompaniment in the life cycle of the female migraineur.
Little is documented on the relationship of women's issues to other features of
migraine or to the lives of patients with migraine. Successful management of
migraine mandates attention to women's issues from menarche to beyond menopause. 
The more information available to this end, the more confidently the clinician
can prognosticate, guide, and treat the female patient. METHODS: Women's issues
were evaluated in 504 women with migraine diagnosed according to the criteria of 
the International Headache Society (codes 1.1 and 1.2). The variables graded on a
scale of 0 to 3 at the initial visit included premenstrual syndrome, menopausal
symptoms, use of birth control pills, use of hormone replacement therapy,
hormonal triggering of headaches, worsening of headaches with birth control pills
or hormone replacement therapy, headaches with menses only, headaches with menses
and at other times, headaches in pregnancy, headaches unchanged in pregnancy,
headaches worse in pregnancy, and headaches better in pregnancy. These variables 
were stratified by age and headache diagnosis. RESULTS: Premenstrual syndrome was
reported in 68.7% of patients, menopausal symptoms in 29.0%, and headaches
attributed to birth control pills or hormone replacement therapy in 24.4% of
patients. Sixty-four point nine percent of women had headaches with menses as
well as at other times, while 3.4% of women had headaches exclusively with
menses. A pregnancy was reported in 61.3% of the women; 20.4% did not experience 
headache in pregnancy. Of the 79.6% who did experience headache, 17.8% reported
that headaches improved in pregnancy, 27.8% reported headaches to be unchanged,
and 34% reported a worsening of headaches. Hormone replacement therapy or birth
control pills triggered headaches in 64% of the study group. Patients with 100%
aura were significantly different from patients with 0% aura, being less likely
to have headaches worsening with birth control pills or hormone replacement
therapy (P <.01) and more likely to have headaches occurring during pregnancy (P 
<.05). When patients with 100% aura were matched for age, headache frequency, use
of birth control pills or hormone replacement therapy, and use of prophylactic
medications with patients having 0% aura, the former were significantly less
likely to have menopausal symptoms (P <.05), less likely to have headaches
worsening with birth control pills or hormone replacement therapy (P <.01), and
more likely to have headaches occurring only during pregnancy (P <.05).
CONCLUSIONS: This study provides a documentation of women's issues in a large
cohort of patients. Stratification by headache type, presence of aura, and age
refine the study.

PMID: 14979877 [PubMed - indexed for MEDLINE]

2346: Behav Med. 2003 Spring;29(1):4-13.

Personality traits and stress sensitivity in migraine patients.

Huber D, Henrich G.

Institute under Poliklinik für Psychomatischie, Psychotherapie under Med.
Psychologie, Klinikum rechts der Isar der Technischen Universität München, Munich
Germany.

A review of the literature on migraine and personality yielded strong evidence
for secondary neuroticism and increased sensitivity to stress in patients with
migraine. This study focused on the identification of specific stressful
situations and coping strategies in such patients. We conducted a
psychodiagnostic study of 30 migraine patients in accordance with the criteria of
the Headache Classification Committee of the International Headache Society and
30 healthy control subjects matched for age, sex, and social status. All
participants completed the Minnesota Multiphasic Personality Inventory (MMPI) and
special questionnaires on stressful situations and coping strategies. The
migraine patients had higher neuroticism and introversion scores on the MMPI than
the healthy subjects. There was a positive correlation between the neuroticism
score and headache duration (number of hours per week). The patients used coping 
strategies characterized by the development of physical symptoms, social
isolation, and preoccupation with stress. They rated themselves as less calm,
less capable of relaxing, and more irritable than did the healthy controls
subjects, and they responded more often with internal tension, especially in work
and other achievement situations. Questionnaires that measure constructs dealing 
with stress yield information that is more relevant for the treatment of
migraines than do global personality tests.

PMID: 14977242 [PubMed - indexed for MEDLINE]

2347: Cochrane Database Syst Rev. 2004;(1):CD002286.

Update of:
    Cochrane Database Syst Rev. 2000;(3):CD002286.

Feverfew for preventing migraine.

Pittler MH, Ernst E.

Department of Complementary Medicine, Peninsula Medical School, Universities of
Exeter and Plymouth, 25 Victoria Park Road, Exeter, Devon, UK, EX2 4NT.

BACKGROUND: Feverfew (Tanacetum parthenium L.) extract is a herbal remedy used
for preventing attacks of migraine. OBJECTIVES: To systematically review the
evidence from double-blind randomised controlled trials (RCTs) assessing the
clinical efficacy and safety of feverfew versus placebo for preventing migraine. 
SEARCH STRATEGY: Publications describing (or which might describe) double-blind
RCTs of feverfew extract for migraine were sought through the Cochrane Central
Register of Controlled Trials (CENTRAL) (The Cochrane Library, Issue 2, 2003);
PREMEDLINE/MEDLINE (1966 to July 2003); EMBASE (1974 to July 2003); the trials
register of the Cochrane Pain, Palliative and Supportive care group (July 2003); 
and AMED (1985 to July 2003). Manufacturers of feverfew were contacted and the
bibliographies of identified articles checked for further trials. SELECTION
CRITERIA: Randomised, placebo-controlled, double-blind trials assessing the
efficacy of feverfew for preventing migraine were included. Trials using clinical
outcome measures were included. Trials focusing exclusively on physiological
parameters were excluded. There were no restrictions regarding the language of
publication. DATA COLLECTION AND ANALYSIS: Data on patients, interventions,
methods, outcome measures, results and adverse events were extracted
systematically. Methodological quality was evaluated using the scoring system
developed by Jadad and colleagues. Two reviewers independently selected studies, 
assessed methodological quality and extracted data. Disagreements concerning
evaluation of individual trials were resolved through discussion. MAIN RESULTS:
Five trials (343 patients) met the inclusion criteria. Results from these trials 
were mixed and did not convincingly establish that feverfew is efficacious for
preventing migraine. Only mild and transient adverse events were reported in the 
included trials. REVIEWER'S CONCLUSIONS: There is insufficient evidence from
randomised, double-blind trials to suggest an effect of feverfew over and above
placebo for preventing migraine. It appears from the data reviewed that feverfew 
presents no major safety problems.

Publication Types: 
    Review

PMID: 14973986 [PubMed - indexed for MEDLINE]

2348: Pharmacoepidemiol Drug Saf. 2004 Jan;13(1):41-7.

Reduction in the therapeutic intensity of abortive migraine drug use during ACE
inhibition therapy--a pilot study.

Rahimtoola H, Buurma H, Tijssen CC, Leufkens HG, Egberts AC.

Department of Pharmacoepidemiology and Pharmacotherapy, Utrecht Institute for
Pharmaceutical Sciences (UIPS), Sorbonnelaan 16, PO Box 80082, 3508 TB Utrecht,
The Netherlands. h.rahimtoola@pharm.uu.nl

INTRODUCTION: Since a few case reports have demonstrated some beneficial effects 
of angiotensin converting enzyme (ACE) inhibitors in migraine prevention, we were
interested in studying the impact of ACE inhibitors and angiotensin II receptor
antagonists (Ang II) on the consumption of specific abortive migraine drugs and, 
therefore, indirectly on the frequency of migraine attacks. METHODS: Data from a 
large prescription database involving 95 patients initiating a specific abortive 
migraine drug (ergotamine or a triptan) and subsequently treated with either an
ACE inhibitor or angiotensin receptor antagonist (index group: ACE/Ang II) or
diuretic (reference group) were analysed. The effects of ACE/Ang II inhibition as
well as diuretic therapy on reducing the frequency of migraine attacks were
assessed by measuring the mean consumption of abortive migraine drug use, in DDDs
per month ('therapeutic intensity'), before, during and after ACE/Ang II or
diuretic therapy. A 'therapeutic fluctuation intensity estimate' of abortive
migraine drug use for all patients was likewise calculated. RESULTS: On an
individual level, the therapeutic intensity (TI) fluctuation estimate, 'during'
relative to 'before' ACE diuretic therapy, was significantly larger for the
ACE/Ang II group (62% reduction) than for the diuretic group (24% reduction) (p =
0.02). For patients who continued abortive migraine drug use during and after
ACE/Ang II or diuretic therapy, a significantly larger reduction in this estimate
was observed during ACE/Ang II inhibition (68.9%) compared to during diuretic
therapy (10.5% increase) (p = 0.004). The TI fluctuation estimate, after relative
to 'during', had increased by 50.3% after ACE/Ang II inhibition and had reduced
by 22.2% after diuretic treatment (p = 0.1). CONCLUSIONS: A clear reduction in
the TI of abortive migraine drug use during the use of ACE inhibitors as compared
to diuretic treatment was observed. Our findings may indirectly support a
positive effect of ACE/Ang II inhibition on the frequency and severity of
migraine attacks, as observed in other studies and reports.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 14971122 [PubMed - indexed for MEDLINE]

2349: Neurology. 2004 Feb 10;62(3):469-72.

Migrainous vertigo presenting as episodic positional vertigo.

von Brevern M, Radtke A, Clarke AH, Lempert T.

Neurologische Klinik Charité, Campus Virchow, Klinikum Benjamin Franklin, Berlin,
Germany. michael.von_brevern@charite.de

Migraine can cause vestibular symptoms including positional vertigo. Of 362
consecutive patients presenting with positional vertigo, 10 with migrainous
vertigo mimicking benign paroxysmal positional vertigo (BPPV) were identified.
The following factors help to distinguish migrainous positional vertigo from
BPPV: short-duration symptomatic episodes and frequent recurrences, manifestation
early in life, migrainous symptoms during episodes with positional vertigo, and
atypical positional nystagmus.

Publication Types: 
    Review

PMID: 14872034 [PubMed - indexed for MEDLINE]

2350: Plast Reconstr Surg. 2004 Feb;113(2):693-7; discussion 698-700.

The anatomy of the greater occipital nerve: implications for the etiology of
migraine headaches.

Mosser SW, Guyuron B, Janis JE, Rohrich RJ.

Case Western Reserve University, Cleveland, Ohio, USA.

An interest in pursuing new theories of the underlying etiology of migraine
headaches has been sparked by previously published reports of an association
between amelioration of migraine headache symptoms and corrugator resection
during endoscopic brow lift. This theory has further been reinforced by recent
publications documenting improvement in migraine headaches following injection of
botulinum A toxin. There are thought to be four major "trigger points" along the 
course of several peripheral nerves that may cause migraine headaches. Among
these peripheral nerves is the greater occipital nerve. For this reason, the
authors have undertaken an anatomic study of this nerve to determine its usual
course, potential anatomic variations, and possible points of potential
entrapment or compression. The results of this anatomic study have enhanced
further development of techniques designed to address these points of
entrapment/compression and potentially lead to relief of migraine headaches
caused by this mechanism. Twenty cadaver heads from patients with an unknown
history of migraine headaches were dissected to trace the normal course of the
greater occipital nerve from the semispinalis muscle penetration to the superior 
nuchal line. Standardized measurements were performed on 14 specimens to
determine the location of the emergence of the nerve using the midline and
occipital protuberance as landmarks. On the basis of this information, the
location of emergence was determined to be at a point centered approximately 3 cm
below the occipital protuberance and 1.5 cm lateral to the midline. This location
can, in turn, be used to guide the practitioner performing chemodenervation of
the semispinalis capitis muscle in an attempt to provide migraine symptom relief.

PMID: 14758238 [PubMed - indexed for MEDLINE]

2351: Headache. 2004 Feb;44(2):178-82.

Frequent triptan use: observations on safety issues.

Robbins L.

Department of Neurology, Rush Medical College, Chicago, Ill. 60062, USA.

OBJECTIVE: To examine the safety of frequent triptan use over extended periods.
For a small group of patients with refractory migraine plus chronic daily
headache, triptans are effective. METHODS: This retrospective study primarily
evaluated the cardiac safety of daily triptan use in 118 patients and, in
addition, hematologic tests were assessed. Each patient had utilized a triptan
for a minimum of 4 days per week for at least 6 months. Patients with rebound
headache had been withdrawn from the triptans. Most patients (97 of 118) averaged
1 tablet daily; most would occasionally go for several days without a triptan.
Forty patients had taken a triptan for 6 months to 2 years, 37 patients from 2 to
4 years, and 41 for 4 or more years. RESULTS: Routine hematologic tests were
performed periodically on all patients, and no abnormalities were attributable to
triptans. Almost all patients had an electrocardiogram, and no abnormal
electrocardiograms were felt to be related to triptans. Cardiac echocardiography 
was performed in 57 patients. The 10 abnormal echocardiograms were not due to
triptans. All 20 cardiac stress tests revealed normal findings. Adverse events
were minimal; 9 patients described fatigue due to triptans, and 5 had mild chest 
tightness. CONCLUSION: This long-term study of 118 patients indicates that
frequent triptan use may be relatively safe.

PMID: 14756859 [PubMed - indexed for MEDLINE]

2352: Headache. 2004 Feb;44(2):174-6.

Efficacy of topiramate in migraine aura prophylaxis: preliminary results of 12
patients.

Lampl C, Bonelli S, Ransmayr G.

Pain and Headache Centre, Department of Neurology and Psychiatry, General
Hospital Linz, Austria.

OBJECTIVE: To evaluate the efficacy of topiramate in the treatment of migraine
aura. Antiepileptic drugs may be useful in migraine prevention through such
mechanisms as acting directly on the nociceptive system or by modulating the
biochemical phenomena of aura. Topiramate acts directly on N-methyl-d-aspartate
and amino-3-hydroxy-5-methylisoxazole-4-propionic acid/kainate glutamate
receptors and modulates calcium ion channel activity by inhibiting
high-voltage-activated L-type calcium ion channels. METHODS: Twelve patients with
migraine with aura were enrolled in an open-label study and treated with
topiramate for 6 months. The dose of topiramate was increased weekly by 25 mg up 
to a daily dose of 100 mg after 4 weeks. RESULTS: In all 12 patients after 6
months of treatment, topiramate did not statistically influence aura frequency
(P=.317) or duration (P=.480) compared with baseline. Mild to moderate side
effects were observed, but they did not interfere with treatment. Consistent with
previous observations, migraine frequency as well as headache intensity and
duration improved statistically significantly. CONCLUSION: Topiramate is not
effective in preventing migraine aura.

PMID: 14756858 [PubMed - indexed for MEDLINE]

2353: Headache. 2004 Feb;44(2):166-9.

Cranial magnetic resonance imaging findings in patients with migraine.

Gozke E, Ore O, Dortcan N, Unal Z, Cetinkaya M.

Departments of Neurology, PTT Teaching and Research Hospital, Istanbul, Turkey.

OBJECTIVE: To investigate the frequency of cranial magnetic resonance imaging
abnormalities in patients with migraine and their relationship to type, duration,
and frequency of migraine attacks. METHODS: Forty-five patients (43 women, 2 men)
with migraine whose ages ranged between 19 and 53 years (mean, 40.91 [SD, 7.69]) 
were evaluated. Of the 45 patients, 20 had migraine with aura and 25 had migraine
without aura, according to the diagnostic criteria of the International Headache 
Society. RESULTS: In 13 (28.8%) of 45 patients, white matter foci were present on
magnetic resonance imaging. Eight of these patients (61.5%) had migraine with
aura, and 5 patients (38.4%) had migraine without aura. The presence of white
matter foci was significantly higher in the patients with aura (8 [40%] of 20)
than in those without aura (5 [20%] of 25). It was found that as the frequency of
attacks per month increased, the number of patients with white matter foci also
increased. Although the mean duration of migraine was longer in patients with
white matter foci (149.5 months [SD, 87.9]) than in those without white matter
foci (134.1 months [SD, 88.3]), there was no significant difference (P >.05).
CONCLUSION: Although there are no specific magnetic resonance imaging findings
peculiar to migraine, detection of white matter foci should be taken into
consideration in patients with migraine (especially migraine with aura).
Frequency of attacks is an important indicator of existence of white matter foci.

PMID: 14756856 [PubMed - indexed for MEDLINE]

2354: Headache. 2004 Feb;44(2):160-5.

Rofecoxib in the prevention of perimenstrual migraine: an open-label pilot trial.

Von Seggern RL, Mannix LK, Adelman JU.

Headache Wellness Center, Greensboro, NC 27401, USA.

OBJECTIVE: To investigate the effectiveness of rofecoxib in the prevention of
perimenstrual migraine. BACKGROUND: Nonsteroidal anti-inflammatory drugs have
demonstrated benefit in reducing the frequency and intensity of menstrual
migraine when administered perimenstrually. Anti-inflammatory drugs, however, may
not be well tolerated and can produce gastrointestinal irritation. Rofecoxib, a
selective cyclooxygenase-2 inhibitor, has anti-inflammatory and analgesic
properties, and a significantly improved gastrointestinal tolerability profile.
METHODS: A pilot study was conducted in which patients with a history of
menstrually associated migraine and experiencing at least one migraine monthly
during the perimenstrual period were enrolled. Patients who completed a baseline 
diary for the first month were randomized to receive either rofecoxib 25 mg or 50
mg daily for 10 days, starting 5 days before menstrual flow. Headaches
experienced during this 10-day period were recorded in the patient's diary.
Patients continued rofecoxib for 2 consecutive menstrual cycles. Mean migraine
frequency, intensity, and duration as well as patient's level of functioning
during the 2 cycles were compared with baseline. RESULTS: Fourteen patients
completed baseline and rofecoxib dosing for 2 menstrual cycles. Mean migraine
frequency decreased from 5.6 to 2.6 migraines per menstrual cycle (P=.005). Eight
(57%) of 14 patients had a > or = 50% reduction in headache frequency. No
significant improvement in headache intensity, duration, and functional
impairment were observed. Both doses of rofecoxib were well tolerated with no
statistical difference in patient response between the doses. CONCLUSION:
Rofecoxib at a perimenstrual daily dose of 25 or 50 mg demonstrated a significant
reduction in frequency of perimenstrual migraine. A double-blind,
placebo-controlled trial of rofecoxib in the prevention of perimenstrual migraine
is warranted.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 14756855 [PubMed - indexed for MEDLINE]

2355: Headache. 2004 Feb;44(2):148-53.

Headache induced by chronic substance use: analysis of medication overused and
minimum dose required to induce headache.

Relja G, Granato A, Maria Antonello R, Zorzon M.

Headache Center, Department of Clinical Medicine and Neurology, University of
Trieste, Italy.

BACKGROUND: The International Headache Society has defined the diagnostic
criteria for headache induced by substance use. Recently, a revision to these
criteria has been proposed. OBJECTIVE: To consider whether the International
Headache Society criteria for headache induced by substance use and the proposed 
revisions for the classification of daily and near-daily headache with medication
abuse permit classification of patients commonly seen in a headache center.
METHODS: One hundred fourteen consecutive patients (96 women [84.2%] and 18 men
[15.8%]; mean age, 54.2 years [SD, 14]) with headache and chronic overuse of
medications, admitted for detoxification to the inpatient unit of a headache
center, participated in the study. The initial headache, medications and doses
used, duration of daily medication use, and means of medication administration
were studied. RESULTS: Eighty-one patients (71%) had an initial headache of
migraine without aura, 13 patients (11.4%) had migraine without aura and
coexistent tension-type headache, 11 (9.7%) patients had migraine with and
without aura, and 9 patients (7.9%) had episodic tension-type headache.
Medications overused by patients included analgesics combined with barbiturates
or other nonnarcotic substances in 39.5%, simple analgesics in 38.6%, triptans in
11.4%, and ergotamine in 10.5%. Using the International Headache Society
diagnostic criteria, we were able to classify only 28.1% of our patients; the
proposed revised criteria for daily and near-daily headaches with medication
abuse permitted the classification of 46.4% of patients. CONCLUSION: The minimum 
dose of medication required to induce chronic headache should be revised because 
a high proportion of patients are not classifiable using either the International
Headache Society diagnostic criteria or the revised criteria recently proposed. A
more comprehensive definition for the required minimum dose might be used.
Triptan abuse can cause chronic headache and should be included in the
International Headache Society classification.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 14756853 [PubMed - indexed for MEDLINE]

2356: Headache. 2004 Feb;44(2):142-7.

Onset of effect of 5-HT1B/1D agonists: a model with pharmacokinetic validation.

Fox AW.

EBD Group, Carlsbad, Calif 92009, USA.

OBJECTIVE: To quantitate onset of effect of all formulations of sumatriptan, and 
to investigate whether this is related to rate, not extent, of drug absorption.
METHODS: From published literature, for 4 formulations of sumatriptan and
matching placebos, response rates were modeled using a simple logarithmic
equation, with a being a parameter of curve convexity and B, a location parameter
(equal to response rate at 2 hours [the standard regulatory parameter]). The
average rate of drug absorption (A) was estimated by dividing the maximal drug
concentration by the time needed to achieve it (Cmax/Tmax). Least mean square
correlation was then performed between the therapeutic gains and therapeutic
ratios of curve convexity and rate of drug absorption. RESULTS:-Models closely
fitted observed response rates (2 hours or less). Curve convexity correlated with
rate of drug absorption. Sumatriptan response rates (0 to 2 hours) for
formulations correlated with rate, not extent, of drug absorption. The range of
rates of onset of effect among different routes of administration was greater
than that for tablets with 4-fold differences in dose size. CONCLUSION: Onset of 
effect is related to rate of absorption of sumatriptan. There is greater scope
for improving onset of effect using an alternative route of administration than
by increasing the oral dose.

Publication Types: 
    Clinical Trial
    Comparative Study
    Controlled Clinical Trial

PMID: 14756852 [PubMed - indexed for MEDLINE]

2357: Headache. 2004 Feb;44(2):136-41.

Efficacy of diclofenac sodium softgel 100 mg with or without caffeine 100 mg in
migraine without aura: a randomized, double-blind, crossover study.

Peroutka SJ, Lyon JA, Swarbrick J, Lipton RB, Kolodner K, Goldstein J.

Burlingame, Calif. 94010, USA.

OBJECTIVE: A phase II, randomized, double-blind, crossover study was designed to 
evaluate the efficacy of 100-mg diclofenac sodium softgel (formulated using
ProSorb technology) with or without 100-mg caffeine versus placebo in migraineurs
during migraine attacks. BACKGROUND: Diclofenac has been demonstrated to be an
effective migraine treatment in several placebo-controlled studies. A rapidly
absorbed softgel of diclofenac has been shown to be effective in the rapid relief
of acute pain, and may have advantages in migraine treatment. In addition,
caffeine has consistently been shown to increase both the efficacy and speed of
onset of concurrently administered analgesics. The ability of caffeine to both
enhance and accelerate analgesic effects has been documented with a variety of
different medications (ie, aspirin, acetaminophen, ibuprofen, and ergotamine).
METHODS: The 3-period crossover study was designed to compare diclofenac softgel 
100 mg, diclofenac softgel 100 mg plus caffeine 100 mg, and placebo in the acute 
treatment of migraine. Subjects treated one moderate or severe attack with each
study medication. The primary efficacy parameter was the percentage of subjects
with headache relief at 60 minutes as defined by a reduction of headache severity
from moderate or severe at baseline to absent or mild compared with placebo.
Though the sample size estimate required that 72 subjects treat 3 separate
attacks, 51 subjects treated 1 migraine attack, 44 treated 2 attacks, and 39
treated 3 attacks. Results.-In the placebo group, 6 (14%) of 43 subjects reported
headache relief at 60 minutes versus 12 (27%) of 45 subjects in the diclofenac
softgel group, and 19 (41%) of 46 subjects in the diclofenac softgel plus
caffeine group. Differences were statistically significant for the diclofenac
softgel plus caffeine group versus placebo (odds ratio, 4.2; 95% confidence
interval, 1.3 to 13.7). Rescue medication was used by 27 (63%) of 43 subjects
treated with placebo, 15 (33%) of 45 subjects treated with diclofenac softgel,
and 14 (30%) of 46 subjects treated with diclofenac softgel plus caffeine. This
result is highly statistically significant (chi22= 11.56, P=.003). Both the
diclofenac plus caffeine (P <.03) and diclofenac only (P <.03) groups were
significantly different from the placebo group in terms of the visual analog
scale score at 60 minutes. CONCLUSIONS: The major finding of the present study is
that diclofenac softgel plus caffeine produces statistically significant benefits
relative to placebo at 60 minutes. Diclofenac softgel alone did not differ
significantly from placebo, perhaps due to limits in sample size. Nonsignificant 
trends support the analgesic adjuvant benefit of caffeine when added to
diclofenac softgels.

Publication Types: 
    Clinical Trial
    Comparative Study
    Randomized Controlled Trial

PMID: 14756851 [PubMed - indexed for MEDLINE]

2358: Headache. 2004 Feb;44(2):131-5.

Consecutive transcranial magnetic stimulation: phosphene thresholds in
migraineurs and controls.

Young WB, Oshinsky ML, Shechter AL, Gebeline-Myers C, Bradley KC, Wassermann EM.

Jefferson Headache Center, Department of Neurology, Thomas Jefferson University
Hospital, Philadelphia, PA 19107, USA.

OBJECTIVE: To characterize the temporal course of transcranial magnetic
stimulation-induced phosphene thresholds in subjects with migraine and in
controls. METHODS: Eleven subjects with migraine with aura, 10 subjects with
migraine without aura, 9 subjects with menstrual migraine, and 15 controls (no
history of migraine and without migraine during the study) were studied. Subjects
were not on preventive medication. Transcranial magnetic stimulation was
performed, and a phosphene threshold was measured 3 times a week over 3 weeks in 
a manner timed to incorporate the menstrual period in females. A headache
calendar was kept during the study. RESULTS: Mean transcranial magnetic
stimulation thresholds were lower for each migraine group compared with controls 
(P <.001) for each comparison. There was a trend for lower thresholds among
subjects with migraine with aura compared with subjects with migraine without
aura (P <.10), but not subjects with menstrual migraine. There was consistent
lowering of thresholds from the first to the last stimulation in all migraine
groups and in the controls. Maximum and minimum thresholds did not predict
headache occurrence, nor did the occurrence of headache predict an ensuing
maximum or minimum phosphene threshold. CONCLUSIONS: Transcranial magnetic
stimulation thresholds are lower in subjects with migraine compared with
controls. The reported phosphene threshold is lowered with repeated measurement. 
Neither high nor low phosphene thresholds predict a subsequent headache, nor do
migraines predict a subsequent high or low threshold.

Publication Types: 
    Comparative Study

PMID: 14756850 [PubMed - indexed for MEDLINE]

2359: Headache. 2004 Feb;44(2):120-30.

Efficacy and tolerability of oral zolmitriptan in menstrually associated
migraine: a randomized, prospective, parallel-group, double-blind,
placebo-controlled study.

Loder E, Silberstein SD, Abu-Shakra S, Mueller L, Smith T.

Spaulding Rehabilitation Hospital, Boston, Mass 02114, USA.

BACKGROUND: Approximately 60% of female migraineurs report experiencing migraine 
in association with menstruation, while 7% to 25% experience attacks almost
exclusively with menstruation. OBJECTIVE: To examine the efficacy and
tolerability of oral zolmitriptan in the acute treatment of menstrually
associated migraine. In this study, menstrually associated migraine was defined
as migraine that consistently occurred from 72 hours before to 5 days after onset
of menses. Methods.-Participants were women with regular menstrual cycles, aged
18 to 55 years, who had experienced migraine with at least two thirds of prior
menstrual cycles. Subjects were randomized to treat one attack per menstrual
cycle for 3 months with either zolmitriptan or placebo. Treatment was intensity
based: mild migraines were treated with half of a 2.5-mg zolmitriptan tablet,
moderate migraines were treated with zolmitriptan 2.5 mg, and severe migraines
were treated with 5 mg (two 2.5-mg tablets) of zolmitriptan, or placebo. RESULTS:
Of the 579 women enrolled in the study, 260 were treated with zolmitriptan and
251 were assigned placebo. Twelve hundred thirty-two attacks were treated, and a 
2-hour headache response was achieved in 48% of zolmitriptan-treated attacks as
compared with 27% of placebo-assigned attacks (P <.0001). Zolmitriptan was
superior to placebo in achieving a headache response as early as 30 minutes (18% 
versus 14%, P=.03) and at 1 hour (33% versus 23%, P <.001). Drug-related adverse 
events were reported in 16% of subjects receiving zolmitriptan and 9% of subjects
receiving placebo. CONCLUSION: Oral zolmitriptan exhibits efficacy and good
tolerability in the treatment of menstrually associated migraine. Improvement
over placebo was observed as early as 30 minutes following treatment.

Publication Types: 
    Clinical Trial
    Comparative Study
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 14756849 [PubMed - indexed for MEDLINE]

2360: Eur Neurol. 2004;51(2):89-97. Epub 2004 Jan 28.

The first placebo-controlled trial of a special butterbur root extract for the
prevention of migraine: reanalysis of efficacy criteria.

Diener HC, Rahlfs VW, Danesch U.

Department of Neurology, University of Essen, Hufelandstrasse 55, DE-45122 Essen,
Germany. h.diener@uni-essen.de

This is an independent reanalysis of a randomised, placebo-controlled
parallel-group study on the efficacy and tolerability of a special butterbur root
extract (Petadolex) for the prophylaxis of migraine. The original protocol and
analysis had a number of major shortcomings. In order to follow regulatory
requirements, an independent reanalysis of the original data was performed.
Following a 4-week baseline phase, 33 patients were randomised to treatment with 
two capsules 25 mg butterbur twice a day and 27 to placebo. The mean attack
frequency per month decreased from 3.4 at baseline to 1.8 after 3 months (p =
0.0024) in the verum group and from 2.9 to 2.6 in the placebo group (n.s.). The
responder rate (improvement of migraine frequency > or =50%) was 45% in the verum
group and 15% in the placebo group. Butterbur was well tolerated. This small
trial indicates that butterbur may be effective in the prophylaxis of migraine.
Copyright 2004 S. Karger AG, Basel

Publication Types: 
    Clinical Trial
    Comparative Study
    Randomized Controlled Trial

PMID: 14752215 [PubMed - indexed for MEDLINE]

2361: Pain Med. 2003 Dec;4(4):366-72.

A placebo for the pain: a medico-legal case analysis.

Rich BA.

University of California, Davis School of Medicine, Sacramento, California 95817,
USA. barich@ucdavis.edu

OBJECTIVES: The objectives of this medico-legal case report are to consider the
current status of the use of placebos in pain medicine from clinical, ethical,
and legal perspectives. The focus of the analysis is a particular case in which
the deceptive use of placebo pain therapy on an adolescent gave rise to
professional grievances filed by the patient's mother against the physician who
ordered and several nurses who administered the placebo. The medical board
declined to take disciplinary action against the physician, and disciplinary
action by the board of registered nursing against the nurses was successfully
challenged by two of the charged nurses in an administrative review. While there 
is a growing literature that challenges the need for or justification of the
deceptive use of placebos, the practice continues and, as the case under
consideration indicates, retains some influential supporters. DESIGN: This is a
case report from a community hospital. The patient, referred to here as KC, was
an adolescent with migraine headaches. The substitution of a placebo (saline
solution) for an opioid analgesic (morphine) was made during KC's treatment.
RESULTS: The patient's pain subsided sufficiently following the administration of
a placebo to permit his discharge from the hospital. The subsequent discovery by 
the patient's mother of the deceptive use of a placebo prompted her to file
charges of professional misconduct against the treating physician and three
nurses with their respective professional licensing boards. The medical board
declined to take disciplinary action against the physician, and the disciplinary 
action by the board of registered nursing was successfully challenged in a ruling
by an administrative law judge following a hearing in which expert witnesses took
conflicting positions on the acceptability of the deceptive use of a placebo.
CONCLUSION: While there is a developing literature that challenges the ethical
legitimacy of the deceptive use of placebos in pain medicine, that literature has
yet to be recognized as unqualifiedly setting the standard of care or of
professionalism in medicine and nursing.

Publication Types: 
    Case Reports
    Legal Cases

PMID: 14750916 [PubMed - indexed for MEDLINE]

2362: Brain. 2004 Mar;127(Pt 3):526-34. Epub 2004 Jan 28.

Comment in:
    Brain. 2004 Nov;127(Pt 11):E18; author reply E19.

Facial pain increases nausea and headache during motion sickness in migraine
sufferers.

Drummond PD, Granston A.

School of Psychology, Murdoch University, 6150 Western Australia, Australia.
drummond@central.murdoch.edu.au

The aim of this study was to determine whether trigeminal nerve discharge
associated with painful stimulation of the temple would intensify symptoms of
motion sickness in migraine sufferers. If so, this would support the notion that 
symptoms such as nausea and headache interact with each other during attacks of
migraine. Symptoms of motion sickness were rated at 2 min intervals during 15 min
of optokinetic stimulation in 27 migraine sufferers and 23 age- and sex-matched
controls. To document changes in frontotemporal blood flow, pulse amplitude was
monitored with photoelectric pulse transducers. To induce facial pain, ice was
applied to the temple for 30 s, three times at 4 min intervals during optokinetic
stimulation. On another occasion, pain was induced during optokinetic stimulation
by immersing the non-dominant hand in 2 degrees C ice water for 30 s, three times
at 4 min intervals. On a third occasion, measures were obtained during
optokinetic stimulation alone. Migraine sufferers rated themselves as being
generally more susceptible to motion sickness than controls. In addition,
symptoms of motion sickness provoked by optokinetic stimulation were greater in
migraine sufferers than in controls. Painful stimulation of the temple
intensified nausea and headache during optokinetic stimulation, whereas painful
stimulation of the hand did not. Since nausea also intensifies facial pain during
motion sickness, nausea and headache may reinforce each other in a vicious
circle. In the absence of painful stimulation, increases in pulse amplitude
during optokinetic stimulation were greater in migraine sufferers than controls, 
possibly because the discomfort associated with motion sickness triggered
extracranial vasodilatation in migraine sufferers as part of a fight-or-flight
(defense) response. Extracranial vasodilatation did not differ between migraine
sufferers and controls when ice was applied to the temple or hand during
optokinetic stimulation, implying that the additional discomfort associated with 
painful stimulation of the head and hand evoked a defense response in controls.
These findings suggest that a mechanism which boosts extracranial neurovascular
reflexes to stress and which heightens symptoms of motion sickness, increases
susceptibility to migraine.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 14749288 [PubMed - indexed for MEDLINE]

2363: Eur J Neurol. 2004 Feb;11(2):125-34.

The 40-mg dose of eletriptan: comparative efficacy and tolerability versus
sumatriptan 100 mg.

Diener HC, Ryan R, Sun W, Hettiarachchi J.

Department of Neurology, University of Essen, Essen, Germany.
h.diener@uni-essen.de

Meta-analysis provides valuable information regarding relative efficacies of
triptans, but head-to-head comparator studies remain the gold standard. Three
similar head-to-head trials comparing eletriptan 40 mg (E40) with sumatriptan 100
mg (S100) provide a rare opportunity and sufficient power, for robust comparisons
of efficacy. Data were combined from three double-blind, placebo-controlled,
first-dose, first-attack acute migraine treatment studies comparing E40 (n=1132),
S100 (n=1129), and placebo (n=645). The primary outcome was headache response at 
2 h. Secondary outcomes included headache response at 1 h, pain-free and
functional responses, and sustained headache and pain-free responses. Odds ratios
were calculated for summary estimates of probability of response. There were
higher headache response rates with eletriptan versus sumatriptan at 2 h (67% vs.
57%; P<0.0001) and 1 h (34% vs. 26%; P<0.0001). Eletriptan also had higher 2 h
pain-free (35% vs. 25%; P<0.0001) and functional responses (67% vs. 58%;
P<0.0001). Sustained headache (42%) and pain-free (22%) response rates were
higher for eletriptan versus sumatriptan (34%, P<0.0001; 15%, P<0.0001). The
probability of response for eletriptan versus sumatriptan ranged from 36% higher 
(relief of nausea) to 64% higher (sustained pain-free rate). Combined analysis
demonstrates that E40 has superior efficacy versus S100 across all clinically
relevant outcomes.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 14748774 [PubMed - indexed for MEDLINE]

2364: Ann Emerg Med. 2004 Feb;43(2):256-62.

Comment in:
    J Fam Pract. 2004 Jun;53(6):444.

Treatment of pediatric migraine headaches: a randomized, double-blind trial of
prochlorperazine versus ketorolac.

Brousseau DC, Duffy SJ, Anderson AC, Linakis JG.

Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI, USA.
dbrousse@mail.mcw.edu

STUDY OBJECTIVE: We compare the effectiveness of intravenous ketorolac and
intravenous prochlorperazine in the treatment of pediatric migraine headaches.
METHODS: We performed a prospective, randomized, double-blind clinical trial in 2
pediatric emergency departments (EDs) within children's hospitals. Children aged 
5 to 18 years presenting to the ED with migraine headaches were eligible for the 
study. Contraindications to either medication or the inability to complete the
pain score resulted in exclusion. Children were randomized to receive intravenous
ketorolac (0.5 mg/kg; maximum 30 mg) or intravenous prochlorperazine (0.15 mg/kg;
maximum 10 mg). All children also received a normal saline solution bolus.
Successful treatment was defined as a 50% or greater reduction in the Nine Faces 
Pain Scale score at 60 minutes. If a less than 50% improvement occurred by 60
minutes, the child received the other medication. Forty-eight-hour follow-up
telephone calls were made to each family to assess recurrence and late side
effects. RESULTS: Sixty-two children were enrolled: 33 initially received
prochlorperazine, and 29 initially received ketorolac. By 60 minutes, 16 (55.2%) 
of 29 of those who received ketorolac and 28 (84.8%) of 33 of those who received 
prochlorperazine were successfully treated (difference=30%; 95% confidence
interval [CI] 8% to 52%). Fifty-six (93.3%) of the 60 children who completed the 
study were successfully treated by the study's conclusion. Approximately 30% of
each group had a recurrence of some headache symptoms. Only 2 children reported
side effects, both mild and self-limited. CONCLUSION: In children, intravenous
prochlorperazine is superior to intravenous ketorolac in the acute treatment of
migraine headaches.

Publication Types: 
    Clinical Trial
    Comparative Study
    Randomized Controlled Trial

PMID: 14747817 [PubMed - indexed for MEDLINE]

2365: Ann Emerg Med. 2004 Feb;43(2):238-42.

Chronic migraineurs: an important subgroup of patients who visit emergency
departments frequently.

Chan BT, Ovens HJ.

Institute for Clinical Evaluative Sciences, Faculty of Medicine, Department of
Health Policy, Evaluation and Management, University of Toronto, Toronto,
Ontario, Canada. ben@ices.on.ca

STUDY OBJECTIVE: We examine whether patients with frequent migraines represent a 
distinct subgroup of patients who visit emergency departments (EDs) frequently.
METHODS: This population-based, cross-sectional study used fiscal year 1998
physician billing data from Ontario, Canada. "Frequent ED visitors" were
individuals with at least 12 ED visits per year and were classified as either
"frequent migraineurs" (> or =50% of ED visits for migraine) and "other frequent 
ED visitors." RESULTS: There were 2,158,291 ED visitors, of whom 6,839 were
frequent ED visitors. These individuals accounted for 3.5% of all ED visits.
Among frequent ED visitors, 478 were frequent migraineurs. The proportion of
patients who were female was 79% among frequent migraineurs, 53% among other
frequent ED visitors, and 50% among patients who were not frequent ED visitors.
The proportions between ages 30 and 54 years for these 3 groups were 79%, 43%,
and 31%, respectively. Average annual visits to EDs were 26, 18, and 1.7,
respectively, and average visits to family physicians were 40, 20, and 5.9,
respectively. Despite heavy health care use, frequent migraineurs sought 83% of
their ED care from their most frequently visited ED and 71% of their primary care
from their main family physician. CONCLUSION: Frequent migraineurs are
predominantly women aged 30 to 54 years and with a particularly intense use of
health care services. Management strategies may require targeted interventions
for these individuals. Because these patients seek most of their care from 1 main
ED and 1 principal primary care physician, coordination of care may be easier
than expected.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 14747814 [PubMed - indexed for MEDLINE]

2366: JAMA. 2004 Jan 28;291(4):427-34.

Comment in:
    JAMA. 2004 Jan 28;291(4):493-4.    JAMA. 2004 May 5;291(17):2072; author reply 2072-3.

Migraine as a risk factor for subclinical brain lesions.

Kruit MC, van Buchem MA, Hofman PA, Bakkers JT, Terwindt GM, Ferrari MD, Launer
LJ.

Department of Radiology, Leiden University Medical Center, Leiden, The
Netherlands. m.c.kruit@lumc.nl

CONTEXT: Clinical series have suggested an increased prevalence of cerebral
infarction and white matter lesions (WMLs) in migraine patients. It is not known 
whether these lesions are prevalent in the general migraine population.
OBJECTIVES: To compare the prevalence of brain infarcts and WMLs in migraine
cases and controls from the general population and to identify migraine
characteristics associated with these lesions. DESIGN: Cross-sectional,
prevalence study of population-based sample of Dutch adults aged 30 to 60 years. 
PARTICIPANTS: Randomly selected patients with migraine with aura (n = 161),
patients with migraine without aura (n = 134), and controls (n = 140), who were
frequency matched to cases for age, sex, and place of residence. Nearly 50% of
the cases had not been previously diagnosed by a physician. MAIN OUTCOME
MEASURES: Brain magnetic resonance images were evaluated for infarcts, by
location and vascular supply territory, and for periventricular WMLs (PVWMLs) and
deep WMLs (DWMLs). The odds ratios (ORs) and 95% confidence intervals (CIs) of
these brain lesions compared with controls were examined by migraine subtype
(with or without aura) and monthly attack frequency (<1 attack, > or =1 attack), 
controlling for cardiovascular risk factors and use of vasoconstrictor migraine
agents. All participants underwent a standard neurological examination. RESULTS: 
No participants reported a history of stroke or transient ischemic attack or had 
relevant abnormalities at standard neurological examination. We found no
significant difference between patients with migraine and controls in overall
infarct prevalence (8.1% vs 5.0%). However, in the cerebellar region of the
posterior circulation territory, patients with migraine had a higher prevalence
of infarct than controls (5.4% vs 0.7%; P =.02; adjusted OR, 7.1; 95% CI,
0.9-55). The adjusted OR for posterior infarct varied by migraine subtype and
attack frequency. The adjusted OR was 13.7 (95% CI, 1.7-112) for patients with
migraine with aura compared with controls. In patients with migraine with a
frequency of attacks of 1 or more per month, the adjusted OR was 9.3 (95% CI,
1.1-76). The highest risk was in patients with migraine with aura with 1 attack
or more per month (OR, 15.8; 95% CI, 1.8-140). Among women, the risk for high
DWML load (top 20th percentile of the distribution of DWML load vs lower 80th
percentile) was increased in patients with migraine compared with controls (OR,
2.1; 95% CI, 1.0-4.1); this risk increased with attack frequency (highest in
those with > or =1 attack per month: OR, 2.6; 95% CI, 1.2-5.7) but was similar in
patients with migraine with or without aura. In men, controls and patients with
migraine did not differ in the prevalence of DWMLs. There was no association
between severity of PVWMLs and migraine, irrespective of sex or migraine
frequency or subtype. CONCLUSIONS: These population-based findings suggest that
some patients with migraine with and without aura are at increased risk for
subclinical lesions in certain brain areas.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 14747499 [PubMed - indexed for MEDLINE]

2367: Annu Rev Med. 2004;55:505-18.

Botulinum toxin and other new approaches to migraine therapy.

Ashkenazi A, Silberstein SD.

Jefferson Headache Center, Thomas Jefferson University Hospital, Philadelphia,
Pennsylvania 19107, USA.

The number of migraine treatments and our understanding of migraine
pathophysiology are both increasing. Newer treatments focus on migraine
prevention. Botulinum toxin (BTX) is a potent neurotoxin used primarily to treat 
diseases associated with increased muscle activity. Recently, BTX was found to
have antinociceptive effects that are probably independent of its muscle-relaxant
action. Clinical trials support the efficacy of BTX type A (and possibly also
type B) in the treatment of migraine. The anticonvulsant topiramate was recently 
shown to be effective for migraine prevention. At the low doses used for this
indication, cognitive side effects are not a major concern. Another new approach 
to migraine prevention is angiotensin type 1 (AT1) receptor blockade. The high
tolerability of the AT1 receptor blocker candesartan warrants further studies to 
assess its role in migraine prevention.

Publication Types: 
    Review

PMID: 14746533 [PubMed - indexed for MEDLINE]

2368: Curr Med Res Opin. 2004 Jan;20(1):49-53.

Effect of preventive treatment with botulinum toxin type A on acute headache
medication usage in migraine patients.

Schim J.

North County Neurology Associates, 320 Santa Fe Drive, Encinitas, CA 92024, USA. 
jschim@neurocenter.com

OBJECTIVE: To evaluate the impact of preventive treatment of migraine with
botulinum toxin type A (BoNT-A as BOTOX) on the amount of acute headache
medications used. RESEARCH DESIGN AND METHODS: Data from four studies of BoNT-A
treatment for migraine were pooled for an aggregate analysis. All studies were at
least 12 weeks in duration. For each study, the amounts of headache medications
used at weeks 8-12 following BoNT-A treatment were compared with pretreatment
baseline amounts and expressed preventive headache care considering acute as a
percentage change. MAIN OUTCOME MEASURES: The mean value for the reduction in
medication usage was calculated by pooling data from the individual studies and
weighting the data according to the sample size of each study. RESULTS: Four
studies (one published, and three presented as recent meeting abstracts) with a
total of 167 patients quantified acute headache medication use before and after
BoNT-A treatment. The weighted average reduction in medication usage (primarily
triptans) was 57% (range 38-75%). CONCLUSIONS: The results of this pooled
analysis indicated a 57% reduction in acute headache medication use in the 8- to 
12-week period following injection of BoNT-A. A reduction of this magnitude could
represent substantial savings in the costs of acute medications. This could help 
to offset the total cost of treatment and suggests BoNT-A may be a
cost-reasonable option for medication offsets alone especially in patients with
chronic headache with higher acute medication use. Additional larger controlled
efficacy and safety studies must be done to confirm these results since three of 
the four studies were preliminary research and of different study types. Further 
prospective studies of direct and indirect costs, including those for disability 
and lost productivity, are needed to evaluate the overall impact of BoNT-A
therapy on the economic, societal, and individual burden of migraine headache.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 14741072 [PubMed - indexed for MEDLINE]

2369: Pediatr Neurol. 2004 Jan;30(1):64-6.

Ophthalmoplegic migraine.

Weiss AH, Phillips JO.

Division of Ophthalmology, Children's Hospital & Regional Medical Center,
Seattle, Washington 98105, USA.

Ophthalmoplegic migraine is a rare presentation of migraine complicated by an
isolated oculomotor paresis. Vasodilation of extracranial vessels is believed to 
underlie the headache, and vasoconstriction to account for the ophthalmoplegia.
Whether the vascular insult involves the central or peripheral portions of the
oculomotor nerve is still uncertain. We describe a child who presented with
ophthalmoplegic migraine and was demonstrated to have a deficiency of the near
triad documented by eye movement and pupillary recordings. Voluntary conjugate
eye movements--saccades, smooth pursuit, and optokinetic nystagmus--were normal. 
Vergence amplitudes appropriate to fixation distance were elicited for Snellen
optotypes but not to a point source of light. Concurrent measures of pupillary
diameter failed to reveal significant modulation to either stimulus. Brain
magnetic resonance imaging scan was normal, and there was no contrast enhancement
of the oculomotor nerve at its exit from the midbrain. Both the oculomotor
paresis and concurrent presence of a deficiency of the near triad localized the
vascular insult to the oculomotor nerve complex in the brainstem.

Publication Types: 
    Case Reports

PMID: 14738955 [PubMed - indexed for MEDLINE]

2370: Rocz Akad Med Bialymst. 2003;48:154-7.

The pattern--reversal visual evoked potentials in children with migraine with
aura and without aura.

Boćkowski L, Sobaniec W, Smigielska-Kuzia J, Kułak W, Sołowiej E.

Department of Pediatric Neurology, Medical University of Białystok, SP DSK, ul.
Waszyngtona 17, 15-274 Białystok, Poland. bockow@kki.pl

PURPOSE: Studies of the visual evoked potentials (VEP) in migraine have yielded
contradictory results. Several investigators suggested that VEP may be helpful
test in diagnosis of a child with headache. The aim of our study was to compare
interictal pattern-reversal visual evoked potentials (PR-VEP) in children and
adolescents with migraine and tension-type headaches and to evaluate VEP
parameters in migraine with and without aura. MATERIAL AND METHODS: The study was
carried out in 93 children and adolescents aged 7-18 years with attack headaches.
RESULTS: 51 children had diagnosed migraine. In this group 30 children (59%) had 
migraine without aura (MO), 12 children (23.5%) migraine with aura (MA) and 9
(17.5%) patients other variants of migraine (MV): hemiplegic, ophthalmoplegic,
basilar. In control group 42 children were classified as tension-type headaches. 
All children had PR-VEP performed in headache-free period, without prophylactic
treatment. The P100 mean latency was significantly longer in migraine than in
tension-type headache. Amplitudes N1-P100 and P100-N2 were significantly larger
in migraneurs compared with tension-type headache. The mean amplitudes of N1-P100
and P100-N2 were significantly lower in MA compared with group MO. There were no 
statistically significant differences of other PR-VEP parameters between MA, MO, 
MV. If we compare individual results of each patient with migraine with mean
value +/- 2 standard deviations (SD) of tension-type headaches group, only 25%
have VEP abnormalities of latency or amplitude above 2SD value in tension-type
headache group. CONCLUSIONS: The diagnosis of migraine in children actually
remains predominantly based on medical history, due to low sensitivity and
specificity of electrodiagnostic tests in headaches. However PR-VEP may support
the diagnosis of migraine in some cases. VEP could be also helpful method in
studying the pathogenesis of different forms of migraine. VEP abnormalities in
migraine can be related to a cortical spreading depression and a central
neurotransmitter alterations.

PMID: 14737964 [PubMed - indexed for MEDLINE]

2371: Cephalalgia. 2004 Feb;24(2):134-9.

Sleep and migraine: an actigraphic study.

Bruni O, Russo PM, Violani C, Guidetti V.

Department of Developmental Neurology and Psychiatry, University of Rome La
Sapienza, Rome, Italy. oliviero.bruni@uniroma1.it

The aim of the study was to evaluate sleep of children with migraine during the
interictal period and the modifications of sleep which precede, are concomitant
with, or follow migraine attacks. Eighteen patients with migraine without aura
were compared with a group of 17 healthy age-matched children. Sleep parameters
were monitored for two full weeks by means of actigraphs and self-report diaries.
Headache diaries were also filled out in order to evaluate the occurrence and the
characteristics of migraine attacks. Fifty-seven attacks were recorded during the
monitoring period. During the interictal period, sleep parameters of children
suffering from migraine did not differ from those of controls; only sleep onset
latency was slightly prolonged in the migraine group. Timing of the attack
affected nocturnal motor activity which presented the lowest values on the night 
preceding the attack, indicating a decrease in cortical activation during sleep
preceding migraine attacks. Further studies should clarify if the observed
reduction in nocturnal motor activity close to the attack is related to
neurotransmitter imbalance.

PMID: 14728709 [PubMed - indexed for MEDLINE]

2372: Cephalalgia. 2004 Feb;24(2):128-33.

Melatonin secretion is supersensitive to light in migraine.

Claustrat B, Brun J, Chiquet C, Chazot G, Borson-Chazot F.

Service de Radioanalyse, Hôpital Neuro-Cardiologique, Institut Fédératif de
Neurosciences, Lyon, France. bruno.claustrat@chu-lyon.fr

The present study examined the sensitivity to light of melatonin (MLT) secretion 
in familial migraine during a headache-free interval. Twelve female patients and 
12 healthy controls were included in the trial. All subjects were studied twice. 
In each session, light exposure (300 lx) or placebo was randomly administered for
30 min between 00.30 and 01.00 h. Blood was sampled hourly between 20.00 and
24.00 h, and 02.00 and 04.00 h and every 15 min between 00.30 and 01.30 h. Plasma
MLT levels were determined by radioimmunoassay. MLT suppression was more marked
in the migraine group than in the control group [difference of area under curve
(DeltaAUC)=-53.8 +/- 16.2 vs. 18.5 +/- 12.7 pg/h/ml, P<0.005; maximum of MLT
suppression (Delta)=-35.7 +/- 10.2 vs. - 6.7 +/- 5.8 pg/ml, P<0.05]. These
findings show a clear hypersensitivity to light in young female migraineurs
during the headache-free period.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 14728708 [PubMed - indexed for MEDLINE]

2373: Cephalalgia. 2004 Feb;24(2):120-7.

Quality of life in paediatric migraine: characterization of age-related effects
using PedsQL 4.0.

Powers SW, Patton SR, Hommel KA, Hershey AD.

Division of Psychology, Cincinnati Children's Hospital Medical Center, University
of Cincinnati College of Medicine, Cincinnati, OH 45229-3039, USA.

The aim of this study was to measure quality of life (QOL) across a broad age
range of paediatric migraine patients. Children and adolescents (n=686) with
migraine completed the Pediatric Quality of Life Inventory, version 4.0 (PedsQL
4.0) and a standardized headache assessment at an initial clinic visit. The
sample size for each PedsQL age group was: age 2-4=21, age 5-7=86, age 8-12=298, 
and age 13-18=281. Mean total score was 72.7 +/- 14.8, significantly less than
healthy norms (P<0.01). Teens reported lower School Functioning than older and
young children (P<0.05) and young children reported lower Social Functioning than
older children and teens (P<0.001). A moderate relation was found between self
and parent report. Age-related effects on QOL have implications for the
evaluation and management of migraine in paediatric practice. The self and parent
report forms of the PedsQL can be used in a practice setting.

Publication Types: 
    Comparative Study

PMID: 14728707 [PubMed - indexed for MEDLINE]

2374: Cephalalgia. 2004 Feb;24(2):110-9.

Comment in:
    Cephalalgia. 2005 Aug;25(8):636-7; author reply 637-9.

Reliability of the nitroglycerin provocative test in the diagnosis of
neurovascular headaches.

Sances G, Tassorelli C, Pucci E, Ghiotto N, Sandrini G, Nappi G.

Headache Unit, University Centre for Adaptive Disorders and Headache, IRCCS C
Mondino Foundation Institute of Neurology, Pavia, Italy. grazia.sances@mondino.it

Nitroglycerin administration provokes spontaneous-like migraine attacks in
migraine and cluster headache (CH) patients. Nitroglycerin-induced migraine-like 
headache has been used as an experimental model of migraine. In this paper, we
evaluate the possibility of using the nitroglycerin provocative test (NPT) as a
supportive measure in the diagnosis of primary neurovascular headaches by
assessing its reliability on a large population and adopting strict criteria for 
rating the response as positive or negative. Our population consisted of 197
migraineurs, 42 subjects suffering from cluster headache and 53 healthy controls.
In migraine without aura, the test sensitivity was 82.1%, specificity 96.2% and
accuracy 85.5%, while in subjects suffering from migraine with aura, the
reliability of the NPT was less satisfactory (sensitivity 13.6%, specificity
96.2% and accuracy 72%). In CH patients tested during the active phase of the
disease the sensitivity was 80.6%, specificity 100% and accuracy 92.9%. NPT is an
easy, low-cost and reliable method for supporting the diagnosis of migraine
without aura and cluster headache.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 14728706 [PubMed - indexed for MEDLINE]

2375: Cephalalgia. 2004 Feb;24(2):99-109.

Naratriptan has a selective inhibitory effect on trigeminovascular neurones at
central 5-HT1A and 5-HT(1B/1D) receptors in the cat: implications for migraine
therapy.

Boers PM, Donaldson C, Zagami AS, Lambert GA.

Faculty of Medicine, The University of New South Wales and Institute of
Neurological Sciences, The Prince Henry and Prince of Wales Hospitals, Sydney,
Australia. BoersP@sesahs.nsw.gov.au

The triptans are agonists at serotonin (5-HT)1B/1D receptors; however, they are
also active at 5-HT1A and 5-HT1F receptors. We conducted this series of
experiments to further elucidate the site of action of naratriptan using a
well-established animal model of trigeminovascular stimulation. Following
electrical stimulation of the superior sagittal sinus of the cat, single cell
responses (n=83) were recorded in the trigeminal nucleus caudalis. Most cells
(91%) also responded to electrical and mechanical stimulation of cutaneous or
mucosal facial receptive fields. The microiontophoretic application of
naratriptan resulted in a significant suppression of the response to sagittal
sinus stimulation (response suppressed by 47 +/- 4%, P<0.001). The effect of
naratriptan was significantly attenuated by application of either the 5-HT(1B/1D)
receptor antagonist GR-127935 (P<0.001) or the 5-HT1A antagonist WAY-100635
(P<0.05). The response of single cells to receptive field stimulation was also
suppressed by microiontophoretic application of naratriptan, but by only 20 +/-
3%. Intravenous administration of naratriptan resulted in a similar selective
suppression of sagittal sinus vs. receptive field responses in trigeminal
neurones. These results indicate that naratriptan has a central effect in the
trigeminovascular system, selectively inhibiting afferent activity in
craniovascular neurones, via both 5-HT(1B/1D) and 5-HT1A receptors.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 14728705 [PubMed - indexed for MEDLINE]

2376: Cephalalgia. 2004 Feb;24(2):83-91.

Comment in:
    Cephalalgia. 2004 Feb;24(2):81-2.    Cephalalgia. 2005 Sep;25(9):761-2; author reply 762-3.

Vertigo and dizziness related to migraine: a diagnostic challenge.

Neuhauser H, Lempert T.

Neurologische Klinik, Charité, Humboldt-Universität, Germany. neuhauserh@rki.de

Vertigo and dizziness can be related to migraine in various ways: causally,
statistically or, quite frequently, just by chance. Migrainous vertigo (MV) is a 
vestibular syndrome caused by migraine and presents with attacks of spontaneous
or positional vertigo lasting seconds to days and migrainous symptoms during the 
attack. MV is the most common cause of spontaneous recurrent vertigo and is
presently not included in the International Headache Society classification of
migraine. Benign paroxysmal positional vertigo (BPPV) and Ménière's disease (MD) 
are statistically related to migraine, but the possible pathogenetic links have
not been established. Moreover, migraineurs suffer from motion sickness more
often than controls. Persistent cerebellar symptoms may develop in the course of 
familial hemiplegic migraine. Dizziness may also be due to orthostatic
hypotension, anxiety disorders or major depression which all have an increased
prevalence in patients with migraine.

Publication Types: 
    Review

PMID: 14728703 [PubMed - indexed for MEDLINE]

2377: Magn Reson Imaging. 2003 Dec;21(10):1201-6.

Cerebellar metabolite alterations detected in vivo by proton MR spectroscopy.

Macrì MA, Garreffa G, Giove F, Ambrosini A, Guardati M, Pierelli F, Schoenen J,
Colonnese C, Maraviglia B.

Dipartimento di Medicina Sperimentale e Patologia, Università, La Sapienza, di
Roma, Rome, Italy.

The aim of our work was to evaluate the feasibility of in vivo single-voxel
quantitative proton MR spectroscopy in order to identify possible alterations in 
the main metabolite concentrations due to some metabolic dysfunctions in the
cerebellum of patients suffering from a particular form of migraine called "with 
aura." Measurements of metabolite levels in the cerebellum disclosed reduced
choline values (normalized both to N-acetyl-aspartate and creatine) in the
patient group with respect to the age-matched control group. Our interest in this
pathology is motivated by the fact that there are no available specific
biochemical markers for migraine characterization, and the current diagnostic
only takes advantage of the medical history and the clinical examination.

PMID: 14725927 [PubMed - indexed for MEDLINE]

2378: J Occup Environ Med. 2004 Jan;46(1):48-54.

Productivity cost benefit to employers of treating migraine with rizatriptan: a
specific worksite analysis and model.

Gerth WC, Sarma S, Hu XH, Silberstein SD.

Worldwide Outcomes Research, Merck & Co., Inc., Whitehouse Station, New Jersey
08889, USA. william_gerth@merck.com

Employers in the United States might not be aware of the productivity costs of
migraine or the extent to which those costs can be reduced by optimal treatment. 
An economic model was developed to enable employers to estimate the productivity 
costs of migraine to their company and the savings that will accrue if those
patients who suffer from migraine are treated with rizatriptan. Analyses were run
for both a major financial services corporation and a representative U.S.
company. The major financial services corporation, with 87,821 employees, is
projected to lose 538 person-years annually, at an estimated cost of 23.8 million
dollars. A representative U.S. company with 10,000 employees is projected to lose
46.0 person-years of productive effort annually as a result of migraine, valued
at approximately 1.94 million dollars. The value of the annual work loss avoided 
if migraine is treated with rizatriptan is projected at 10.3 million dollars for 
the financial services corporation and 841,000 dollars for the representative
U.S. company. There is a substantial productivity cost burden of migraine from a 
U.S. employer perspective. These productivity costs can be reduced significantly 
by treating migraine headaches with rizatriptan.

PMID: 14724478 [PubMed - indexed for MEDLINE]

2379: Neurology. 2004 Jan 13;62(1):141-3.

Association between the tumor necrosis factor-alpha -308 G/A gene polymorphism
and migraine.

Rainero I, Grimaldi LM, Salani G, Valfrè W, Rivoiro C, Savi L, Pinessi L.

Neurology III Headache Center, Department of Neuroscience, University of Torino, 
Italy. irainero@molinette.piemonte.it

In a group of 299 migraine patients and 306 control subjects, the association of 
the -308 G/A polymorphism in the tumor necrosis factor-alpha gene (TNFalpha) with
the occurrence and clinical characteristics of migraine was tested. Homozygosity 
for the G allele was associated with an increased risk of migraine (odds ratio
[OR] = 2.85, p < 0.001). When the patients were divided into subgroups, the
association was confirmed in patients affected by migraine without aura (OR =
3.30, p < 0.001) but not in migraine with aura. These data suggest that the
TNFalpha gene or a linked locus significantly modulates the risk for migraine.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 14718719 [PubMed - indexed for MEDLINE]

2380: J Womens Health (Larchmt). 2003 Dec;12(10):1027-36.

Postmenopausal hormone therapy and migraine headache.

Misakian AL, Langer RD, Bensenor IM, Cook NR, Manson JE, Buring JE, Rexrode KM.

University of California-San Diego School of Medicine, San Diego, California,
USA.

BACKGROUND: Estrogen withdrawal has been described as a trigger for migraine
headache, and some studies suggest that estrogen and progestin may exacerbate
migraine. No population-based studies have examined the association between
hormone therapy (HT) and migraine among postmenopausal women. METHODS: To examine
the association between HT and migraine headache in postmenopausal women, we used
self-report of HT use, HT characteristics, and migraine headache within the past 
year among 17,107 postmenopausal female health professionals enrolled in the
Women's Health Study. RESULTS: Analyses were restricted to the 17,107 of 21,788
postmenopausal women who were postmenopausal at baseline and who were never
(38.5%) or current (61.5%) users of HT. Of these, 1,909 (11.2%) experienced
migraine headache within the last year. Women with migraine headache were
significantly younger, had a younger age at menopause, were more likely to have
had a surgical menopause, and were more likely to be current users of HT. After
adjusting for age, race, smoking, alcohol use, ever use of oral contraception,
age at menopause, and menopause type, the odds ratio (OR) for migraine headache
was 1.42 (95% CI 1.24-1.62) for women who were current users of HT compared with 
never users. ORs were similar for users of estrogen alone (OR 1.39, 95% CI
1.14-1.69) and users of both estrogen and progestin (OR 1.41, 95% CI 1.22-1.63). 
CONCLUSIONS: In this cross-sectional study, current HT use was associated with
higher rates of migraine headache than nonuse. Clinical trials are needed to
determine if HT increases the incidence of migraine in postmenopausal women.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 14709191 [PubMed - indexed for MEDLINE]

2381: Ann Neurol. 2004 Jan;55(1):27-36.

Analgesic triptan action in an animal model of intracranial pain: a race against 
the development of central sensitization.

Burstein R, Jakubowski M.

Departments of Anesthesia and Critical Care, Beth Israel Deaconess Medical
Center, Boston, MA, USA. rburstei@caregroup.harvard.edu

We have shown that the development of cutaneous allodynia (exaggerated skin
sensitivity) during migraine is detrimental to the anti-migraine action of the
5HT(IB/ID) receptor agonists known is triptans. Because cutaneous allodynia is a 
manifestation of sensitization of central trigeminovascular neurons, we examined 
whether triptan treatment can intercept such sensitization before its initiation 
or after its establishment in our rat model for cutaneous allodynia induced by
intracranial pain. Single-unit recordings were obtained from spinal trigeminal
neurons that proved to received convergent inputs from the dura and facial skin. 
The effects of sumatriptan (300 microg/kg i.v.) on central sensitization induced 
by topical application of inflammatory soup (IS) on the dura were determined when
the drug was administered either 2 h after IS (late intervention) or at the same 
time as IS (early intervention). Late sumatriptan intervention counteracted two
aspects of central sensitization: dural receptive fields, which initially
expanded by IS, shrunk back after treatment; neuronal response threshold to dural
indentation, which initially decreased after IS, increased after sumatriptan. On 
the other hand, late sumatriptan intervention did not reverse other aspects of
central sensitization: spontaneous firing rate and neuronal response magnitude to
skin brushing which initially increased after IS, remained elevated after
sumatriptan; response threshold to heating of the skin, which initially dropped
after IS, remained low after sumatriptan. Early sumatriptan intervention
effectively blocked the development of all aspects of central sensitization
expected to be induced 2 h after IS application: dural receptive fields did not
expand; neuronal response threshold to dural indentation and skin stimulation did
not decrease; spontaneous firing rate did not increase. The early treatment
results suggest that triptan action provides a powerful means of preventing the
initiation of central sensitization triggered by chemical stimulation of
meningeal nociceptors. The late treatment results suggest that triptan action is 
insufficient to counteract an already established central sensitization. Thus,
triptan action appears to be exerted directly on peripheral rather than central
trigeminovascular neurons.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 14705109 [PubMed - indexed for MEDLINE]

2382: Ann Neurol. 2004 Jan;55(1):19-26.

Defeating migraine pain with triptans: a race against the development of
cutaneous allodynia.

Burstein R, Collins B, Jakubowski M.

Departments of Anesthesia and Critical Care, Beth Israel Deaconess Medical
Center, Boston, MA, USA. rburstei@caregroup.harvard.edu

For many migraine patients, triptan therapy provides complete pain relief in some
attacks but not in others. Here, we tested whether the success of triptan therapy
is hindered in the presence of cutaneous allodynia (pain resulting from a
nonnoxious stimulus to normal skin), a phenomenon we previously described develop
gradually during the course of the migraine attack in more than 70% of patients. 
We studied migraine patients repeatedly on three visits to the clinic: in the
absence of migraine (baseline), within the first hour of one attack, or at 4
hours from onset of another attack. Presence or absence of allodynia was
determined based on differences between migraine and baseline pain thresholds to 
mechanical and thermal stimulation of periorbital skin. In 31 patients, we
studied 34 migraine attacks that were associated with allodynia at the time of
triptan treatment and 27 attacks that were not. Within 2 hours of triptan
treatment, patients were rendered pain-free in 5 of 34 (15%) of allodynic attacks
versus 25 of 27 (93%) of nonallodynic attacks. Treating migraine attacks 1 hour
(early) or 4 hours (late) after the onset of pain was equally ineffective in
inducing a pain-free state in the presence of allodynia, and equally effective in
the absence of allodynia. For patients susceptible to allodynia during the
attack, triptan therapy was by far more likely to provide complete pain relief if
administered before rather than after the establishment of cutaneous allodynia.
Patients who never developed allodynia were highly likely to be rendered
pain-free by triptan therapy anytime after the onset of pain. We conclude that
the probability of consistent pain-free outcome increases drastically if triptan 
therapy is vigilantly timed to precede any signs of cutaneous allodynia.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 14705108 [PubMed - indexed for MEDLINE]

2383: Funct Neurol. 2003 Jul-Sep;18(3):155-9.

Cinnarizine in migraine prophylaxis: efficacy, tolerability and predictive
factors for therapeutic responsiveness. An open-label pilot trial.

Rossi P, Fiermonte G, Pierelli F.

Department of Neurology and Otolaryngology, University "La Sapienza", Rome,
Italy. paolo.rossi90@tin.it

The efficacy and tolerability of cinnarizine (75 mg, at bedtime) in migraine
prophylaxis and the presence of possible predictive factors for therapeutic
responsiveness were evaluated in an open-label pilot trial. Eighty consecutive
outpatients suffering from migraine with or without aura participated in the
study. After 12 weeks of therapy, 55 patients experienced a greater than 66%
reduction in headache frequency and were considered responders. A significant
reduction in the number of migraine days (mean reduction 58 +/- 8%) and in intake
of medication to treat acute attacks (mean reduction 55 +/- 11%) was also
observed. Cinnarizine was well tolerated, as documented by the low number of
adverse effects. Failure to respond to previous prophylactic treatments was a
negative predictive factor correlated with a poor prognosis. This study, even
bearing in mind its limitations as an open-label trial, suggests that cinnarizine
might be an effective prophylactic anti-migraine agent. The clinical
characteristics of migraine patients do not help to predict response to
treatment.

Publication Types: 
    Clinical Trial

PMID: 14703897 [PubMed - indexed for MEDLINE]

2384: Funct Neurol. 2003 Jul-Sep;18(3):121-6.

Stroke and migraine--the spectrum of cause and effect.

Welch KM.

Finch University of Health Sciences, The Chicago Medical School, 3333 Green Bay
Road, North Chicago, IL 60064, USA. welch@finchcms.edu

The relationship of migraine and stroke is complex. Stroke may be coincidental
with migraine but migraine may confer an increased risk of stroke in women under 
45 years of age and possibly in men who have migraine with aura. Stroke may mimic
migraine but migraine syndromes may be symptomatic of underlying cerebrovascular 
disorders. True migraine-induced stroke is rare. The mechanisms of stroke induced
during a migraine attack remain to be determined but probably involve an
interaction between the dynamic shifts in cerebral blood flow and stroke risk
factors.

Publication Types: 
    Lectures

PMID: 14703893 [PubMed - indexed for MEDLINE]

2385: J Child Neurol. 2003 Nov;18(11):772-5.

Parental satisfaction with sumatriptan nasal spray in childhood migraine.

Pakalnis A, Kring D, Paolicchi J.

Department of Neurology, Ohio State University College of Medicine, Columbus, OH,
USA. pakalnisa@pediatrics.ohio-state.edu

Migraine headaches are a frequently encountered neurologic problem in children.
The utility of the triptans has not been as clearly documented in this
population, although it is well delineated in acute migraine attacks in adults.
We conducted a retrospective chart review of our experience with using
sumatriptan nasal spray in children aged 5 to 12 years from our headache clinic
population with migraine headaches. The nasal spray formulation is used
frequently in our clinic population with patients who have failed
over-the-counter therapy with ibuprofen or acetaminophen. None of the triptans
are approved by the US Food and Drug Administration for use in children or
adolescents (12 years and older). One hundred of these patients were identified, 
and their parents or guardians completed a standardized questionnaire regarding
their child's response to sumatriptan nasal spray in acute migraine. Fifty-seven 
of 100 families completed the questionnaire, and 44 of 57 families (77%) reported
good to excellent relief of their child's migraine attacks with sumatriptan nasal
spray. In our cohort of pediatric patients, sumatriptan nasal spray was effective
and well tolerated when used for abortive therapy of acute migraine attacks.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 14696905 [PubMed - indexed for MEDLINE]

2386: Neurology. 2003 Dec 23;61(12):1748-52.

Subclinical vestibulocerebellar dysfunction in migraine with and without aura.

Harno H, Hirvonen T, Kaunisto MA, Aalto H, Levo H, Isotalo E, Kallela M, Kaprio
J, Palotie A, Wessman M, Färkkilä M.

Department of Neurology, Helsinki University Central Hospital, Finland.
hanna.harno@hus.fi

OBJECTIVE: In patients with migraine, neurotologic symptoms and signs occur
commonly. The authors' aim was to determine whether neurotologic findings are in 
accordance with the type of migraine and whether test findings differ from those 
of healthy controls. METHODS: The authors examined 36 patients with various types
of migraine classified by International Headache Society criteria. Comprehensive 
neurotologic tests were performed between attacks: video-oculography (VOG),
electronystagmography, static posturography, and audiometry on 12 patients with
migraine with aura (MA) and 24 patients with migraine without aura (MO). Results 
were compared to those of test-specific nonmigrainous control groups. Only eight 
migraineurs (six with MA and two with MO) had vertigo or dizziness. RESULTS:
Despite the absence of clinical neurotologic symptoms, most of the patients with 
migraine (83%) showed abnormalities in at least one of these tests. Both migraine
types differed significantly from the control group (in VOG, in saccadic
accuracy, and in static posturography). Vestibular findings tended to be more
severe in MA than in MO. CONCLUSIONS: These data suggest that interictal
neurotologic dysfunction in MA and MO share similar features and that the
defective oculomotor function is mostly of vestibulocerebellar origin.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 14694041 [PubMed - indexed for MEDLINE]

2387: Clin Ther. 2003 Nov;25(11):2920-35.

Measuring satisfaction with migraine treatment: expectations, importance,
outcomes, and global ratings.

Patrick DL, Martin ML, Bushnell DM, Pesa J.

Departent of Health Services, University of Washington, School of Public Health
and Community Medicine, Seattle 98195-7660, USA. donald@u.washington.edu

BACKGROUND: Patients tend to express high satisfaction with treatment using
global rating scales. Previous work in health services, marketing, and operations
research suggested that global ratings of satisfaction need to account for
multiple influences and differing patient values. Prior qualitative work with
patients and clinicians supported a 4-part model that incorporates the gap
between expectations and outcomes of treatment and accounts for the relative
importance of different treatment attributes. OBJECTIVE: The aim of this work ws 
to generate a small experimental data set to develop and evaluate the potential
usefulness of the conceptual model and scoring algorithm for the application of
this new measurement strategy, the Migraine Treatment Satisfaction Measure
(MTSM). METHODS: Before treatment, migraine patients who were beginning a new
prescription for headache rated their expectations and the importance of 9
attributes of treatment: pain relief, speed of relied, freedom from pain,
additional symptoms, confidence in treatment, disruption in life, dosing, freedom
from relapse, and ease of use. After treatment, patients rates outcomes on these 
9 attributes and provided global satisfaction ratings. Weights reflecting the gap
between expectations and outcomes and the importance ratings were applied to
these global ratings after treatment to produce the MTSM score. The weighted
rating scales were then tested for internal consistency, reliability, and
construct validity using the Short-Form 36-item Health Survey (SF-36), 24-hour
Migraine Quality of Life Questionnaire (MQoLQ), a measure of symptom
bothersomeness, and a measure of migraine intensity. RESULTS: Forty-eight
patients were screened and 29 patients completed this pilot study. Internal
consistency of coefficients exceeded 0.90 for all 4 components of the MTSM
(patients' expectations of treatment, ratings of the importance of individual
attributes of treatment, assessments of outcome on each attribute, and global
treatment satisfaction ratings). Derived or weighted scores expanded the
distribution of unweighted global satisfaction ratings and improved statistical
performance by reducing variability (from 20.5 to 14.8) for overall score).
Hypothesized associations were confirmed between the MTSM, SF-36, MQoLQ, symptom 
bothersomeness, and migraine intensity. CONCLUSION: The 4-part conceptual model
reflecting multiple attributes of treatment and preliminary scoring system for
the MTSM generated satisfaction scores that improved discrimination among
patients. Further validation is warranted.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 14693316 [PubMed - indexed for MEDLINE]

2388: Clin Ther. 2003 Nov;25(11):2903-19.

Cost-effectiveness of almotriptan and rizatriptan in the treatment of acute
migraine.

Williams P, Reeder CE.

PAREXEL International, Uxbridge, Middlesex, United Kingdom.
paul.williams@parexel.com

BACKGROUND: Migraine is a common disorder that costs US employers billions of
dollars each year in missed workdays and reduced productivity. Seven triptans,
including almotriptan and rizatriptan, are recommended as first-line therapy for 
acute migraine. OBJECTIVE: The aim of this study was to assess the relative
cost-effectiveness of almotriptan and rizatriptan in the treatment of acute
migraine. METHODS: A model was built to compare almotriptan 12.5 mg and
rizatriptan 10 mg for the treatment of a single, acute migraine attack.
Cost-effectiveness (in year-1999 US dollars) was evaluated from the perspective
of a US health care payer. Mean and incremental cost-effectiveness ratios (CERs) 
were calculated. The effectiveness measure was the proportion of patients who
achieved sustained freedom from pain with no adverse events (SNAE). Data on
sustained pain-free outcomes and adverse-event rates were obtained from a
meta-analysis of oral triptan trials. Efficacy and tolerability were assumed to
be independent in the base-case scenario, so the total direct cost of treating a 
single migraine attack was calculated, adding drug costs to health service costs 
per attack. RESULTS: In the base-case analysis, the mean CERs for almotriptan
12.5 mg and rizatriptan 10 mg were 91.12 dollars and 131.26 dollars,
respectively, per attack at which SNAE was achieved after treatment. The
incremental CER for almotriptan (compared with rizatriptan 10 mg) was 6.94
dollars per additional SNAE achieved. The economic benefit of almotriptan 12.5 mg
was robust in a range of sensitivity analyses. CONCLUSION: Almotriptan 12.5 mg
was more cost-effective than rizatriptan 10 mg for the treatment of acute
migraine in this analysis based on published data.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 14693315 [PubMed - indexed for MEDLINE]

2389: Cephalalgia. 2004 Jan;24(1):37-43.

Neutrophil-free radical generation and enzymatic antioxidants in migraine
patients.

Shukla R, Barthwal MK, Srivastava N, Sharma P, Raghavan SA, Nag D, Srimal RC,
Seth PK, Dikshit M.

Department of Neurology, Chhatrapati Shahuji Maharaj Medical University (Upgraded
King George's Medical College), Lucknow, India.
raheshshukla_rakesh@rediffmail.com

The present study was undertaken to elucidate the role of circulating neutrophils
if any in oxidative stress in migraine by evaluating free radical generation and 
activities of enzymatic antioxidants in the blood in 55 patients with migraine
and 60 healthy controls. Free radical generation was assessed by flow cytometry, 
while activity of catalase, superoxide dismutase (SOD) and glutathione peroxidase
(GPx) was estimated in blood polymorphonuclear neutrophils (PMNs) by standard
procedures. Platelet SOD was also measured. No significant change was found in
free radical generation and in the activity of catalase, SOD and GPx in migraine 
patients. Univariate analysis of PMN catalase level revealed that migraineurs
with a positive family history had significantly lower catalase activity compared
with those with a negative family history. No correlation was found in the
activity of antioxidant enzymes with age, duration of disease, time since last
attack and headache index. The platelet SOD also did not show any significant
change in patients of migraine without aura. Platelet aggregation in the presence
or absence of PMNs was also not altered significantly. Thus the findings of the
present study suggest that neutrophils are not the cause of oxidative stress
observed in migraine patients.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 14687011 [PubMed - indexed for MEDLINE]

2390: Cephalalgia. 2004 Jan;24(1):23-8.

Characteristics of postictal headache in patients with partial epilepsy.

Ito M, Adachi N, Nakamura F, Koyama T, Okamura T, Kato M, Kanemoto K, Nakano T,
Matsuura M, Hara S.

Tenshi Hospital, Kita-12, Higashi-3. Higashi-ku, Sapporo 065-8611, Japan.
mitou-psy@umin.ac.jp

Migraine-like features sometimes characterize the headache that follows epileptic
seizure (postictal headache, PIH). We compared patients with different types of
epilepsy to investigate the association between migraine-like PIH and seizure
type. Subjects comprised 364 patients with partial epilepsy. Epilepsy types were 
temporal lobe epilepsy (TLE, n = 177), frontal lobe epilepsy (FLE, n = 116), and 
occipital lobe epilepsy (OLE, n = 71). Patients participated in a structured
interview pertaining to PIH as well as interictal headache and family history of 
migraine. Headaches were classified according to the International Headache
Society criteria, which was modified for this study. Forty percent had PIH and
26% of these patients had migraine-like PIH. Migraine-like PIH occurred
significantly more often in cases of TLE and OLE than in cases of FLE. In
addition, the incidence of interictal migraine headache was significantly higher 
in patients with migraine-like PIH. These results suggest that migraine-like PIH 
is related to particular regions of epileptogenic focus and that susceptibility
to migraine headache predisposes to migraine-like PIH.

Publication Types: 
    Clinical Trial
    Multicenter Study

PMID: 14687009 [PubMed - indexed for MEDLINE]

2391: Cephalalgia. 2004 Jan;24(1):18-22.

Prognosis of migraine with aura.

Eriksen MK, Thomsen LL, Russell MB.

Danish Headache Centre, Department of Neurology, University of Copenhagen,
Glostrup Hospital, Nordre Ringvej 57, DK-2600 Glostrup, Denmark.
kirchmann@dadlnet.dk

The present study is a 16-year follow-up study assessing the long-term outcome of
migraine with aura (MA). Additionally possible predictive factors in the
prognosis of MA were evaluated. Patients were recruited from the files of Danish 
headache clinics. A total of 53 patients (11M:42F) with MA (IHS criteria)
participated in a follow-up interview. At follow-up attacks had ceased (no MA for
2 years) in 36% of patients. Attacks had ceased in 55% of males and 31% of
females (P = 0.17). Attacks had ceased in 41% of patients with visual aura
without other aura symptoms and in 25% of those with sensory or aphasic aura
besides their visual aura (P = 0.36). Among those with attacks of MA at follow-up
frequency of attacks and headache intensity was improved in 44% and 41% of the
patients, respectively. The results point to a favourable evolution of MA and
suggest possible predictive factors.

Publication Types: 
    Multicenter Study

PMID: 14687008 [PubMed - indexed for MEDLINE]

2392: Cephalalgia. 2004 Jan;24(1):12-7.

Clinical features of migraine: a cross-sectional study in patients aged three to 
sixty-nine.

Wöber-Bingöl C, Wöber C, Karwautz A, Auterith A, Serim M, Zebenholzer K, Aydinkoc
K, Kienbacher C, Wanner C, Wessely P.

Department of Neuropsychiatry of Childhood and Adolescence, University of Vienna,
Währinger Gürtel 18-20, A-1090 Vienna, Austria. yasar.woeber-bingoel@univie.ac.at

We investigated 260 consecutive patients classified as migraine cases aged 3-69
at two tertiary headache centres, one for children and adolescents and the other 
for adults to evaluate the relationship between age and clinical features of
migraine cross-sectionally. We only included subjects with definite migraine
without or with aura and we excluded subjects with coexisting tension-type
headache, medication overuse and/or other clinically relevant disorders. The
percentage of males decreased markedly from childhood to adulthood and this
affected the evaluation of age-related changes in male patients, as only large
differences reached the level of statistical significance. In females, the
headache duration and the prevalence of unilateral, pulsating pain, photophobia
and phonophobia increased, whereas the prevalence of aggravation by physical
activity decreased with age. In conclusion, this cross-sectional, clinic-based
study on a strictly defined sample of 260 consecutive patients with definite
migraine covering a wide range of age from the very young to the old suggests
marked age-related differences of the clinical features of migraine in females
and failed to demonstrate similar differences in males due to the small number of
adult male migraineurs.

Publication Types: 
    Clinical Trial
    Comparative Study
    Multicenter Study

PMID: 14687007 [PubMed - indexed for MEDLINE]

2393: Int J Clin Pract. 2003 Nov;57(9):761-8.

Patient-reported benefits of rizatriptan compared with usual non-triptan therapy 
for migraine in a primary care setting.

Baos V, Serrano A, Torrecilla M, Bertral C, Caloto MT, Nocea G, Gerth WC; I-MAX
Study Group.

Healthcare Clinic, Collado Villalba, Madrid, Spain.

The purpose of this open-label study was to compare rizatriptan with usual
non-triptan therapy for migraine in patients who had never received a triptan.
Patient-reported outcomes were examined for a prestudy migraine attack and after 
three consecutive study attacks, the first and third treated with rizatriptan 10 
mg wafer and the second with usual non-triptan therapy. A total of 97 patients
(83% women; mean age 39 years) completed the study. Two-thirds of patients
reported severe or total disability during migraine attacks. All comparisons
between rizatriptan therapy and usual non-triptan therapy significantly favoured 
rizatriptan (p < or = 0.01). Headache relief by 2 hours was reported by 78-83% of
patients after rizatriptan and by 46-48% of patients after usual therapy; 41-47% 
and 12-18%, respectively, were pain free at 2 hours. Patient satisfaction and
migraine-specific quality-of-life scores were also significantly better for
attacks treated with rizatriptan. At study end, 62% and 17% of patients were very
or completely satisfied with rizatriptan and usual non-triptan therapy,
respectively. Among those patients who worked for pay, therapy with rizatriptan
significantly reduced absenteeism and improved the amount and quality of time at 
work compared with usual non-triptan therapy. Allowing patients to have
experience with rizatriptan may improve the level of medical care for migraine
attacks.

Publication Types: 
    Clinical Trial
    Comparative Study
    Multicenter Study
    Research Support, Non-U.S. Gov't

PMID: 14686564 [PubMed - indexed for MEDLINE]

2394: Appl Psychophysiol Biofeedback. 2003 Dec;28(4):255-65.

EMG reactivity and oral habits among young adult headache sufferers and painfree 
controls in a scheduled-waiting task.

Ong JC, Nicholson RA, Gramling SE.

Virginia Commonwealth University, Richmond, Virginia 23284-2018, USA.

Previous research has shown that patients with facial pain exhibit a pattern of
physiological and behavioral reactivity to scheduled-waiting tasks that may help 
account for the development of facial pain. The present study extended this line 
of research by examining the psychophysiological reactivity of headache sufferers
in a similar task. A total of 34 frequent headache sufferers screened by
International Headache Society (IHS) criteria and 13 painfree controls completed 
a psychophysiological assessment consisting of 4 phases (adaptation, free-play,
scheduled-play, and recovery) that included a scheduled-waiting condition
(scheduled-play) designed to produce adjunctive behavior. Masseter and frontalis 
EMG were measured continuously during each phase and self-reported oral habits
and pain ratings were collected following each phase. A significant interaction
and group effect was found on frontalis EMG, with the headache group exhibiting
elevated EMG levels across the phases, whereas the control group exhibited
increasing EMG levels that peaked during the scheduled-play phase. Only a
significant phase effect was found on masseter EMG, with the highest EMG levels
recorded during the scheduled-play phase for both groups. In addition, a
significant phase effect was found on self-reported oral habits data. Overall,
these results provide general support for the adjunctive behavior effect, but the
predicted difference in magnitude between the groups was not found.

PMID: 14686079 [PubMed - indexed for MEDLINE]

2395: Pediatr Neurol. 2003 Nov;29(5):425-9.

Triptans for treatment of acute pediatric migraine: a systematic literature
review.

Major PW, Grubisa HS, Thie NM.

Orthodontic Graduate Program, Faculty of Medicine and Dentistry, University of
Alberta, Edmonton, Alberta, Canada.

The purpose of this article is to evaluate the effectiveness and safety of
triptans for the treatment of acute migraine in children and adolescents.
Randomized and open label trials of triptans in acute pediatric patients (ages
6-18 years) were identified by Medline (1966-2002) and PubMed (1991-2002).
Additional reports were identified from the reference list of the retrieved
studies. To study effectiveness, only randomized controlled trials were included,
but open label studies were also included to study adverse effects.
Pharmacokinetic studies of triptans in pediatric patients were also searched.
Four randomized controlled trials were identified. One study reported oral
sumatriptan, another oral rizatriptan, and two studies reported nasal spray
sumatriptan. Rizatriptan is well tolerated but not clearly beneficial when used
in adolescents. Effectiveness of nasal spray sumatriptan in acute pediatric
migraine where other medications had failed was supported. Effectiveness of oral 
sumatriptan was not established. Adverse effects were minor for oral sumatriptan 
and rizatriptan and nasal sumatriptan. Pharmacokinetics of sumatriptan in
pediatric patients has not been established. In conclusion, nasal spray
sumatriptan should be considered in acute pediatric migraine in patients not
experiencing adequate relief with other interventions.

Publication Types: 
    Review

PMID: 14684238 [PubMed - indexed for MEDLINE]

2396: Dis Manag Advis. 2003 Oct;9(10):137-9, 129.

Simple three-item screen offers efficient way to identify migraine in primary
care.

[No authors listed]

It's a problem that is commonly overlooked by PCPs--despite the fact that
migraine costs employers billions each year in absenteeism and lost productivity.
Additionally, migraine sufferers often must deal with substantial pain and
disability even though there are highly effective treatments available. Now, a
new self-administered tool has been validated that can identify migraine with
just three simple questions. Get the details.

PMID: 14679873 [PubMed - indexed for MEDLINE]

2397: J Neurogenet. 2003 Apr-Sep;17(2-3):231-40.

Association analysis of 5-HTTLPR variants, 5-HT2a receptor gene 102T/C
polymorphism and migraine.

Juhasz G, Zsombok T, Laszik A, Gonda X, Sotonyi P, Faludi G, Bagdy G.

Laboratory of Neurochemistry and Experimental Medicine, and Department of
Vascular Neurology, Faculty of Medicine, Semmelweis University, National
Institute of Psychiatry and Neurology, Budapest, Hungary.

It is well known that migraine has a strong genetic component, although the type 
and number of genes involved is not yet clear. There is evidence to suggest that 
serotonin-related genes participate in the pathogenesis of migraine. Previous
studies have shown that gender differences influence the serotonergic
neurotransmission and, in addition, the migraine prevalence is higher in females 
than males. Therefore, we investigated the functional polymorphism in the
upstream regulatory region of the serotonin transporter gene (5-HTTLPR) and the
102T/C polymorphism of the 5-HT2A receptor gene in the Hungarian female
population. These genes were analysed in 126 migraine sufferers (with or without 
aura)and 101 unrelated healthy controls using case control design. A borderline
association (chi2 = 3.84, df = 1, p = 0.049; OR = 1.45, 95% CI = 1.00-2.12)
between 5-HTTLPR short (S) allele and migraine was found. No significant
difference between migraine sufferers and controls was observed for the 102T/C
polymorphism of 5-HT2A receptor gene. Furthermore, there was no significant
interaction between5-HTTLPR and 102T/C polymorphisms in our study population. In 
conclusion, our results support that the genetic susceptibility of migraine may
be associated with a locus at or near the 5-HT transporter gene.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 14668201 [PubMed - indexed for MEDLINE]

2398: Clin Ther. 2003 Oct;25(10):2506-38.

Newer antiepileptic drugs: possible uses in the treatment of neuropathic pain and
migraine.

Pappagallo M.

Division of Chronic Pain, Department of Pain and Palliative Medicine, Beth Israel
Medical Center, 1st Avenue at 16th Street, New York, NY 10003, USA.
mpappaga@chpnet.org

BACKGROUND: Both neuropathic pain and migraine are now being treated with a
variety of newer antiepileptic drugs (AEDs). The proven efficacy of gabapentin in
postherpetic neuralgia (PHN) and painful diabetic neuropathy (PDN), and of
divalproex sodium in the prevention of migraine has led to increased clinical
investigation of the newer AEDs for these conditions. While basic and clinical
research are expanding the knowledge base concerning the fundamental mechanisms
of neuropathic pain and migraine, growing recognition of the similarities in the 
pathophysiology of epilepsy, migraine, and various chronic pain disorders has
further heightened interest in exploring the newer AEDs in the treatment of these
conditions.OBJECTIVE: The goals of this article were to review the empiric basis 
and scientific rationale for the use of AEDs in the treatment of neuropathic pain
and migraine; summarize available clinical research on the use of 5 newer AEDs
(gabapentin, lamotrigine, oxcarbazepine, topiramate, and zonisamide) in these
conditions; and provide a summary comparison of the dosing, tolerability, and
drug-interaction potential of these agents.METHODS: Relevant English-language
articles were identified through searches of MEDLINE (1990-March 2003), American 
Academy of Neurology abstracts (1999-2003), and American Epilepsy Society
abstracts (2000-2002). The search terms were antiepileptic medication or drug,
migraine headache, neuropathic pain, pathophysiology, treatment, mechanism of
action, gabapentin, lamotrigine, oxcarbazepine, topiramate, and
zonisamide.CONCLUSIONS: The newer AEDs possess the potential advantages of better
tolerability and fewer drug-drug interactions compared with standard treatments
such as tricyclic antidepressants or established AEDs. However, with the
exception of data supporting the efficacy of gabapentin in PHS and PDN, there is 
currently insufficient evidence to determine whether the newer AEDs have equal or
superior efficacy relative to proven pharmacotherapies.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't
    Review

PMID: 14667954 [PubMed - indexed for MEDLINE]

2399: Control Clin Trials. 2003 Dec;24(6):731-5.

Use of a single global assessment to reduce missing data in a clinical trial with
follow-up at one year.

Vickers AJ, McCarney R.

Integrative Medicine Service, Biostatistics Service, Memorial Sloan-Kettering
Cancer Center, New York, New York 10021, USA. vickersa@mskcc.org

We conducted a randomized controlled trial (ISRCTN96537534) to assess the effects
of acupuncture on migraine and chronic tension headache. Patients (n=401)
completed a diary of headache severity four times a day for 4 weeks at baseline, 
immediately following a 3-month treatment period and 1 year after randomization. 
During the trial, it appeared that dropout might be higher than expected. We
therefore obtained a rapid global assessment of headache from participants to aid
imputation of missing data. Patients were contacted by telephone and asked to
rate current and baseline headache on a 0-10 scale. Use of global assessment
reduced the number of patients from whom we obtained no follow-up headache data
from 69 (17%) to 24 (6%). Analysis of patients who provided both a diary and a
global assessment demonstrated excellent properties of global assessment, with
very similar results to the full diary. We therefore used the global assessment
to help impute missing 1-year diary scores. Rapid global assessment can be easily
implemented in any trial and aids imputation of missing data, though it should
not be used instead of more intensive methods of assessment. Further research
might usefully examine the value of global assessment for imputation of missing
data in a variety of different settings.

Publication Types: 
    Clinical Trial
    Comparative Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 14662279 [PubMed - indexed for MEDLINE]

2400: Expert Opin Emerg Drugs. 2003 Nov;8(2):437-56.

Emerging drugs in migraine treatment.

Waeber C.

Department of Radiology, Massachusetts General Hospital/Harvard Medical School,
CNY149 Room 6403, 149 13th Street, Charlestown, Massachusetts, MA 02129, USA.

Ergot alkaloids have been the mainstay of acute migraine therapy for most of the 
20th century. They have been supplanted by sumatriptan-like drugs ('triptans'),
which, while keeping some of the ergotś mechanisms of action, show improved
safety profiles due to their increased receptor selectivity. However, triptans
are still far from being perfect drugs: they can constrict human coronary
arteries at therapeutic doses and, therefore, are contra-indicated in the
presence of cardiovascular disease. Another problem with these agents is
recurrence of moderate-to-severe pain within 24 h of initial headache relief.
While mechanism-driven drug design has led to the development of various novel,
albeit still imperfect, acute antimigraine medications, only a few new
prophylactic agents have been made available to migraine clinicians. The efficacy
of most, if not all of them has been discovered serendipitously. This is probably
due to the fact that, while the pathophysiology of a migraine attack is now
reasonably understood, the mechanisms leading to an attack are still mostly
unknown. This update analyses the profile of some antimigraine drugs in clinical 
trials, their mode of action and their potential advantages or drawbacks over
already available agents.

Publication Types: 
    Review

PMID: 14661998 [PubMed - indexed for MEDLINE]

2401: Laryngoscope. 2003 Dec;113(12):2151-6.

Endonasal surgery for contact point headaches: a 10-year longitudinal study.

Welge-Luessen A, Hauser R, Schmid N, Kappos L, Probst R.

Department of Otorhinolaryngology, University of Basel, Kantonsspital,
Petersgraben 4, CH-4031 Basel, Switzerland. awelge@uhbs.ch

OBJECTIVE: Some migraine and cluster headaches may be triggered by stimulation of
intranasal contact points via the trigeminovascular system. Endonasal surgery is 
successful in some patients, but long-term outcomes have not been reported. STUDY
DESIGN: Prospective. METHODS: This investigation included 20 patients with a mean
18-year history of refractory cluster or migraine headaches who were selected for
surgery. All had endoscopically visible endonasal contact as well as a positive
preoperative cocaine test result. Changes in pain severity and frequency and
duration of headache attacks were statistically rated using a MANOVA. Follow-up
averaged 112 months. RESULTS: Almost 10 years after surgery, six patients
remained completely free of pain, seven had significant symptom improvement, and 
seven received no benefit from surgery (65% improvement). Two patients had been
free of all symptoms for 7 and 8 years, respectively, before complaints returned.
CONCLUSION: Our data suggest that some patients with refractory headaches and
endonasal contact areas benefit from surgery, thereby supporting the existence of
a connection between the two. Even though it is clear that surgery should be
considered only if all other treatments have failed, a success rate of 65% over
almost 10 years justifies evaluation of this option. Preoperative patient
selection remains crucial and warrants further investigation.

PMID: 14660919 [PubMed - indexed for MEDLINE]

2402: Pain. 2003 Dec;106(3):461-70.

NO-induced migraine attack: strong increase in plasma calcitonin gene-related
peptide (CGRP) concentration and negative correlation with platelet serotonin
release.

Juhasz G, Zsombok T, Modos EA, Olajos S, Jakab B, Nemeth J, Szolcsanyi J, Vitrai 
J, Bagdy G.

Laboratory of Neurochemistry and Experimental Medicine, Department of Vascular
Neurology, Faculty of Medicine, Semmelweis University, National Institute of
Psychiatry and Neurology, Huvosvolgyi ut 116, Budapest, H-1021, Hungary.

The aim of the present study was to investigate changes in the plasma calcitonin 
gene-related peptide (CGRP) concentration and platelet serotonin
(5-hydroxytriptamine, 5-HT) content during the immediate headache and the delayed
genuine migraine attack provoked by nitroglycerin. Fifteen female migraineurs
(without aura) and eight controls participated in the study. Sublingual
nitroglycerin (0.5 mg) was administered. Blood was collected from the antecubital
vein four times: 60 min before and after the nitroglycerin application, and 60
and 120 min after the beginning of the migraine attack (mean 344 and 404 min; 12 
subjects). In those subjects who had no migraine attack (11 subjects) a similar
time schedule was used. Plasma CGRP concentration increased significantly
(P<0.01) during the migraine attack and returned to baseline after the cessation 
of the migraine. In addition, both change and peak, showed significant positive
correlations with migraine headache intensity (P<0.001). However, plasma CGRP
concentrations failed to change during immediate headache and in the subjects
with no migraine attack. Basal CGRP concentration was significantly higher and
platelet 5-HT content tended to be lower in subjects who experienced a migraine
attack. Platelet serotonin content decreased significantly (P<0.01) after
nitroglycerin in subjects with no migraine attack but no consistent change was
observed in patients with migraine attack. In conclusion, the fact that plasma
CGRP concentration correlates with the timing and severity of a migraine headache
suggests a direct relationship between CGRP and migraine. In contrast, serotonin 
release from platelets does not provoke migraine, it may even counteract the
headache and the concomitant CGRP release in this model.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 14659530 [PubMed - indexed for MEDLINE]

2403: J Pediatr. 2003 Dec;143(6):776-9.

Brain imaging and prophylactic therapy in children with migraine: recommendations
versus reality.

Schor NF.

Division of Child Neurology, Children's Hospital of Pittsburgh of the University 
of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA. nfschor@pitt.edu

OBJECTIVES: To determine the concordance between referring physician behavior and
published criteria for performance of imaging studies and institution of
prophylactic therapy, respectively, in children referred to an academic
children's hospital headache clinic.Study design A retrospective review of the
records of 106 consecutive patients referred to an academic children's hospital
headache clinic. RESULTS: Approximately half of patients referred to the clinic
had already had head computed tomography or magnetic resonance imaging ordered by
the referring doctor and performed before their clinic appointment. However,
using published criteria, only 10% of patients seen in the clinic would have
required an imaging procedure before institution of therapy. The referring
physician had initiated treatment with daily prophylactic medications for
headache in more than 30% of patients before their clinic appointments, of whom
89% were on appropriate medications at age-appropriate and weight-appropriate
doses. Half of these children exhibited a positive response to this medication
before being seen by the consulting neurologist. However, more than 60% of the
children actually met the criteria for recommending prophylactic therapy.
CONCLUSIONS: Imaging is more frequently obtained and prophylactic therapy less
frequently implemented by the referring physician than would be indicated by
published recommendations.

Publication Types: 
    Comparative Study

PMID: 14657827 [PubMed - indexed for MEDLINE]

2404: Semin Pediatr Surg. 2003 Nov;12(4):254-8.

Abdominal migraine and cyclical vomiting.

Catto-Smith AG, Ranuh R.

Department of Gastroenterology and Clinical Nutrition, Royal Children's Hospital,
Parkville, Vic, Australia.

Vomiting and abdominal pain are symptoms that may arise from a number of
different causes. Cyclical vomiting and abdominal migraine are terms that have
been applied to a presentation characterized by its episodic pattern and
intervals of complete health. The 2 share many clinical features, but it is
important to distinguish them as they have different responses to therapies such 
as prophylactic antimigraine medications. Both are noted for the absence of
pathognomonic clinical features but also for the large number of other conditions
to be considered in their differential diagnoses. Definitive diagnosis is
frequently delayed. It is important to carefully evaluate these patients as
well-being between vomiting episodes does not guarantee the absence of organic
disease. While there is a role for a basic set of diagnostic tests, there is
evidence to suggest that a trial of empiric therapy with upper gastrointestinal
and small-bowel radiological studies is cost-effective.

Publication Types: 
    Review

PMID: 14655164 [PubMed - indexed for MEDLINE]

2405: Qual Life Res. 2003 Dec;12(8):1003-12.

Usefulness of the SF-8 Health Survey for comparing the impact of migraine and
other conditions.

Turner-Bowker DM, Bayliss MS, Ware JE Jr, Kosinski M.

QualityMetric Incorporated, Lincoln, RI, USA. dtbowker@qualitymetric.com

BACKGROUND: Migraine headaches have been shown to have substantial personal and
societal implications. Health-related quality of life (HRQOL) assessments of
migraineurs have been used to monitor and evaluate patient- and population-based 
outcomes, and to evaluate effectiveness and responsiveness to treatment. In this 
paper, we test a new, even shorter generic health survey, the SF-8 Health Survey 
(SF-8), an alternate form that uses one question to measure each of the eight
SF-36 Health Survey (SF-36) domains, in a sub-sample of migraine sufferers.
METHODS: Data from 7557 participants surveyed via the Internet and mail were used
to document the burden of migraine on HRQOL and to compare the relative burden of
migraine with other chronic conditions using the SF-8. RESULTS: Migraineurs'
HRQOL is similar to those with congestive heart failure, hypertension and
diabetes, and is better than those with depression. Migraine sufferers experience
better physical health and worse mental health (MH) than those with
osteoarthritis. Results support prior research indicating that the burden of
migraine on functional health and well-being is considerable and comparable to
other chronic conditions known to have substantial impact on HRQOL. CONCLUSIONS: 
The SF-8 may provide a more practical and efficient method to describe the burden
of migraine in population studies.

Publication Types: 
    Comparative Study

PMID: 14651418 [PubMed - indexed for MEDLINE]

2406: Qual Life Res. 2003 Dec;12(8):903-12.

The responsiveness of headache impact scales scored using 'classical' and
'modern' psychometric methods: a re-analysis of three clinical trials.

Kosinski M, Bjorner JB, Ware JE Jr, Batenhorst A, Cady RK.

QualityMetric Incorporated, Lincoln, RI, USA. mkosinski@qualitymetric.com

BACKGROUND: While item response theory (IRT) offers many theoretical advantages
over classical test theory in the construction and scoring of patient based
measures of health few studies compare scales constructed from both methodologies
head to head. OBJECTIVE: Compare the responsiveness to treatment of migraine
specific scales scored using summated rating scale methods vs. IRT methods.
METHODS: The data came from three clinical studies of migraine treatment that
used the Migraine Specific Quality of Life Questionnaire (MSQ). Five methods of
quantifying responsiveness were used to evaluate and compare changes from pre- to
post-treatment in MSQ scales scored using Likert and IRT scaling methods.
RESULTS: Changes in all MSQ scale scores from pre- to post-treatment were highly 
significant in all three studies. A single index scored from the MSQ using IRT
methods was determined to be more responsive than any one of the MSQ subscales
across the five methods used to quantify responsiveness. Across 13 of the 15
tests (5 responsiveness methods * 3 studies) conducted, the single index scored
from the MSQ using IRT methods was the most responsive measure. CONCLUSIONS: IRT 
methods increased the responsiveness of the MSQ to the treatment of migraine. The
results agree with the psychometric evidence that suggest that it is feasible to 
score a single index from the MSQ using IRT methods. This approach warrants
further testing with other measures of migraine impact.

PMID: 14651411 [PubMed - indexed for MEDLINE]

2407: Qual Life Res. 2003 Dec;12(8):887-902.

The feasibility of applying item response theory to measures of migraine impact: 
a re-analysis of three clinical studies.

Bjorner JB, Kosinski M, Ware JE Jr.

QualityMetric Incorporated, Lincoln, RI 02895, USA. jbjorner@qualitymetric.com

BACKGROUND: Item response theory (IRT) is a powerful framework for analyzing
multiitem scales and is central to the implementation of computerized adaptive
testing. OBJECTIVES: To explain the use of IRT to examine measurement properties 
and to apply IRT to a questionnaire for measuring migraine impact--the Migraine
Specific Questionnaire (MSQ). METHODS: Data from three clinical studies that
employed the MSQ-version 1 were analyzed by confirmatory factor analysis for
categorical data and by IRT modeling. RESULTS: Confirmatory factor analyses
showed very high correlations between the factors hypothesized by the original
test constructions. Further, high item loadings on one common factor suggest that
migraine impact may be adequately assessed by only one score. IRT analyses of the
MSQ were feasible and provided several suggestions as to how to improve the items
and in particular the response choices. Out of 15 items, 13 showed adequate fit
to the IRT model. In general, IRT scores were strongly associated with the scores
proposed by the original test developers and with the total item sum score.
Analysis of response consistency showed that more than 90% of the patients
answered consistently according to a unidimensional IRT model. For the remaining 
patients, scores on the dimension of emotional function were less strongly
related to the overall IRT scores that mainly reflected role limitations. Such
response patterns can be detected easily using response consistency indices.
Analysis of test precision across score levels revealed that the MSQ was most
precise at one standard deviation worse than the mean impact level for migraine
patients that are not in treatment. Thus, gains in test precision can be achieved
by developing items aimed at less severe levels of migraine impact. CONCLUSIONS: 
IRT proved useful for analyzing the MSQ. The approach warrants further testing in
a more comprehensive item pool for headache impact that would enable computerized
adaptive testing.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 14651410 [PubMed - indexed for MEDLINE]

2408: Prog Brain Res. 2004;144:305-20.

Auras and other hallucinations: windows on the visual brain.

Wilkinson F.

Centre for Vision Research, Toronto Western Research Institute, and York
University, 4700 Keele St, Toronto, ON M3J 1P3, Canada. franw@yorku.ca

Hallucinations in psychologically normal individuals provide a valuable route to 
studying the neural mechanisms of visual awareness. Migraine auras, epileptic
auras and the hallucinations of Charles Bonnet Syndrome are examined in this
context. Both similarities and striking differences in content are noted and the 
extent to which we are currently able to localize the source of these forms of
endogenously driven visual awareness is discussed.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 14650857 [PubMed - indexed for MEDLINE]

2409: J Neurosci. 2003 Nov 26;23(34):10988-97.

Peptidergic nociceptors of both trigeminal and dorsal root ganglia express
serotonin 1D receptors: implications for the selective antimigraine action of
triptans.

Potrebic S, Ahn AH, Skinner K, Fields HL, Basbaum AI.

Department of Neurology, University of California, San Francisco, San Francisco, 
California 94143-0452, USA.

Agonists at serotonin 1D (5-HT1D) receptors relieve migraine headache but are not
clinically used as general analgesics. One possible explanation for this
difference is that 5-HT1D receptors are preferentially expressed by cranial
afferents of the trigeminal system. We compared the distribution of 5-HT1D
receptor-immunoreactive (5-HT1D-IR) peripheral afferents within the trigeminal
ganglion (TRG) and lumbar dorsal root ganglion (DRG) of the rat. We also examined
the neurochemical identity of 5-HT1D-IR neurons with markers of primary afferent 
nociceptors, peripherin, isolectin B4, and substance P, and markers of myelinated
afferents, N52 and SSEA3. We observed a striking similarity in the size,
distribution, and neurochemical identity of 5-HT1D-IR neurons in TRG and lumbar
DRG afferents. Furthermore, the vast majority of 5-HT1D-IR neurons are
unmyelinated peptidergic afferents that distribute peripherally, including the
dura, cornea, and the sciatic nerve. In the central projections of these
afferents within the trigeminal nucleus caudalis and the spinal cord dorsal horn,
5-HT1D-IR fibers are concentrated in laminas I and outer II; a few axons
penetrate to lamina V. At the ultrastructural level, 5-HT1D receptors in the
spinal cord dorsal horn are localized exclusively within dense core vesicles of
synaptic terminals. We observed scattered 5-HT1D-IR neurons in the nodose
ganglia, and there was sparse terminal immunoreactivity in the solitary nucleus. 
The visceral efferents of the superior cervical ganglia did not contain 5-HT1D
immunoreactivity. Our finding, that 5-HT1D receptors are distributed in
nociceptors throughout the body, raises the possibility that triptans can
regulate not only headache-associated pain but also nociceptive responses in
extracranial tissues.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 14645495 [PubMed - indexed for MEDLINE]

2410: J Clin Neurosci. 2004 Jan;11(1):4-7.

Ergot of rye-the first specific for migraine.

Eadie MJ.

Department of Medicine, University of Queensland, Brisbane, Australia.
M.Eadie@mailbox.uq.edu.au

Over the past decade the various triptan derivatives have been accepted as the
most effective available agents for relieving migraine attacks. Prior to that,
for a period of half a century, ergotamine was the only 'specific' available for 
this purpose. In 1918, Stoll had isolated it from the various alkaloids present
in extracts of the sclerotia of the fungus Claviceps purpurea (ergot), which grow
on rye and, to a lesser extent, on other grasses. By 1925 ergotamine was
beginning to be used to treat migraine attacks. However, as ergotamine was
present in extracts of ergot, which had been used to treat migraine first in
Italy in 1862, and then by Edward Woakes (1868) in England, and after him by
Albert Eulenburg in Germany (1883), the drug had actually come into unrecognised 
use for the disorder more than half a century before ergotamine itself was known 
to exist. Unfortunately, because of ergotamine's chemical and pharmacokinetic
properties, extracts of ergot of rye were incapable of producing consistent
therapeutic results, so that general acceptance that the first specific substance
for migraine treatment existed had to wait until pure ergotamine was available
for administration.

Publication Types: 
    Historical Article
    Review

PMID: 14642357 [PubMed - indexed for MEDLINE]

2411: Neurology. 2003 Nov 25;61(10):1446-8.

1 Hz rTMS enhances extrastriate cortex activity in migraine: evidence of a
reduced inhibition?

Fierro B, Ricci R, Piazza A, Scalia S, Giglia G, Vitello G, Brighina F.

Neurophysiological Unit, University of Palermo, Italy. fierro@unipa.it

We recently reported a paradoxical facilitatory effect of 1 Hz repetitive TMS
(rTMS) on the primary visual cortex in migraine possibly due to the failure of
inhibitory circuits, unable to be upregulated by low frequency rTMS. To
investigate if inhibitory circuit dysfunction extends beyond striate cortex in
migraine with aura, we studied the effects of 1 Hz rTMS over the right
extrastriate cortex on perception of illusory contours in these patients.
Low-frequency rTMS enhanced activity of extrastriate cortex in migraineurs,
speeding up reaction times on illusory contour perception. This finding supports 
the view of a failure of inhibitory circuits also involving the extrastriate
cortex in migraine with aura.

PMID: 14638977 [PubMed - indexed for MEDLINE]

2412: J Pain. 2003 Nov;4(9):530-4.

Comment in:
    J Pain. 2004 Mar;5(2):139; author reply 140.

The effect of vagus nerve stimulation on migraines.

Hord ED, Evans MS, Mueed S, Adamolekun B, Naritoku DK.

Department of Neurology, Southern Illinois University, Springfield, Illinois
62794-9637, USA.

Vagus nerve stimulation (VNS) inhibits nociceptive behavior in animals. VNS might
reduce pain in patients with VNS device implanted for intractable seizures. One
case report described possible benefits on migraines. We contacted all patients
who received VNS therapy for intractable epilepsy between 1993 and 1999 at
Southern Illinois University, Springfield, Illinois. Patients who had concomitant
chronic pain were subsequently interviewed. Pain intensity before and after VNS
implantation was rated by the patient as average, worst, and least and on numeric
rating scale from 1 to 10. Current pain measurements were compared to
preimplantation by using Global Pain Relief Rating Scale. Of 62 patients who
received VNS, 27 patients were interviewed; 4 patients had common migraine, and
no other chronic pain syndromes were identified. All patients with migraine
reported reductions in headache frequency and numeric rating scale score for
average and least headache intensity. One patient reported complete relief of
headaches. Improvement was reported to start 1 to 3 months after initiation of
therapy. On Global Pain Relief Rating Scale, 1 patient reported complete pain
relief, 2 reported a lot of pain relief, and 1 reported slight pain relief.
Concomitant antiepileptic drugs were decreased in 3 patients and slightly
increased in 1. VNS might be beneficial for prophylactic therapy of migraine.

Publication Types: 
    Case Reports

PMID: 14636821 [PubMed - indexed for MEDLINE]

2413: J Ky Med Assoc. 2003 Nov;101(11):498-504.

Pediatric migraines: a case report.

Greenlee CR, Puri V.

University of Louisville, Louisville, Kentucky, USA.

Migraines are a common problem faced by the pediatrician. It can be difficult to 
determine the difference between a common headache and a migraine in young
children. This case report will review a case that presented to the neurologist's
office, then discuss the epidemiology, pathophysiology, classification of
migraine, migraine variants, clinical evaluation, differential diagnosis, and
treatment of migraines in a pediatric population.

Publication Types: 
    Case Reports

PMID: 14635578 [PubMed - indexed for MEDLINE]

2414: Eur Neurol. 2003;50(4):195-9.

An epidemiological study of migraine with aura in the San Severo general
population: a pilot research project of cooperation between neurologists and
general practitioners.

Cologno D, Manzoni GC; Drion Medical Association.

I.R.C.C.S. Santa Lucia, Rome, Italy. danielacologno@virgilio.it

OBJECTIVES: (A) To define the lifetime prevalence of migraine with aura (MA) in
patients recruited in general practices for an epidemiologic study by the
University of Parma Headache Centre from the general population of San Severo,
Italy, and (B) to assess the recognition of MA in general practice. METHODS: The 
study was conducted over a period of 5 consecutive months (January to May 2001)
on patients aged 18-65, taken from the following general practice populations:
(a) from the patient population of 4 general practitioners (GPs; 3,616 patients) 
and (b) from the patient population of 12 GPs (12,996 patients). The clinical
diagnosis of MA was subsequently confirmed by a headache specialist. RESULTS: For
objective A, 648 patients (420 women and 228 men) were interviewed; MA diagnosis 
was confirmed in 10 patients (7 women and 3 men), lifetime MA prevalence being
1.5%. For objective B, 150 'suspected' MA cases (96 women and 54 men) were
reported by the 12 GPs; however, the diagnosis of MA was confirmed in only 3
cases (2 women and 1 man). CONCLUSION: The prevalence of MA observed in our small
sample of the general practice patient population was comparable with that
observed in the general population of San Severo, Italy. The results also suggest
that GPs may be overestimating the number of cases of MA in their patient
population. Copyright 2003 S. Karger AG, Basel

Publication Types: 
    Comparative Study

PMID: 14634262 [PubMed - indexed for MEDLINE]

2415: Eur Neurol. 2003;50(4):191-4.

Comment in:
    Eur Neurol. 2003;50(4):189-90.    Eur Neurol. 2004;51(3):186; author reply 186-7.

The metaphysical art of Giorgio de Chirico. Migraine or epilepsy?

Blanke O, Landis T.

Department of Neurology, Geneva University Hospital, Geneva, Switzerland.
olaf.blanke@hcuge.ch

It has been suggested that the great Italian painter Giorgio de Chirico
(1888-1978), who developed the unique style of 'metaphysical art', suffered from 
migraine and used some of his morbid manifestations as a source of inspiration
for his paintings. Yet, whereas many of the symptoms that de Chirico described
are rare in migraine, they are frequently encountered in patients with temporal
lobe epilepsy. Here we rediscuss de Chirico's symptoms critically and suggest
that, if his symptoms were of neurological origin, they rather relate to temporal
lobe epilepsy than migraine. Copyright 2003 S. Karger AG, Basel

Publication Types: 
    Biography
    Historical Article

Personal Name as Subject: 
    de Chirico G

PMID: 14634261 [PubMed - indexed for MEDLINE]

2416: Headache. 2003 Nov-Dec;43(10):1102-8.

Impact of antimigraine compounds on cognitive processing: a placebo-controlled
crossover study.

Evers S, Rüschenschmidt J, Frese A, Rahmann A, Husstedt IW.

Department of Neurology, University of Münster, Germany.

OBJECTIVE: To evaluate potential cognitive impairment caused by acute
antimigraine drugs. METHODS: We conducted a placebo-controlled, double-blind,
crossover study to detect the short-term impact of sumatriptan, zolmitriptan, and
ergotamine tartrate on cognitive processing as measured by event-related
potentials and a d2 test. Sixteen healthy subjects were enrolled in the study and
given placebo, sumatriptan 100 mg, zolmitriptan 2.5 mg, and ergotamine tartrate 2
mg on different days and in random order. Before and 2 hours after drug
administration, visually evoked event-related potentials and a d2 test were
measured. RESULTS: The N2 latency was significantly increased after ergotamine
intake. No other significant differences could be observed in all other
event-related potential parameters. In the d2 test, the GZ value was unchanged
after ingestion of zolmitriptan and ergotamine, but improved significantly after 
taking placebo and sumatriptan. The number of relative errors and the
concentration value did not change significantly. All results fell within the
reference values for the d2 test in all examinations. CONCLUSION: Our data
suggest that there may be a slight cognitive decline 2 hours after ingestion of
ergotamine tartrate and, to an even lesser extent, zolmitriptan, but not after
ingestion of sumatriptan or placebo. All changes recorded were very mild and
unlikely to be clinically relevant.

Publication Types: 
    Clinical Trial
    Comparative Study
    Randomized Controlled Trial

PMID: 14629247 [PubMed - indexed for MEDLINE]

2417: Headache. 2003 Nov-Dec;43(10):1085-9.

Single-site botulinum toxin type a injection for elimination of migraine trigger 
points.

Behmand RA, Tucker T, Guyuron B.

American Migraine Center, Cleveland, Ohio, USA.

BACKGROUND: Botulinum toxin may be effective in suppressing migraine. Most
injection regimens utilized have involved multiple sites. PURPOSE: To evaluate
prospectively the effect of botulinum toxin type A injections into the corrugator
supercilii muscles alone on the frequency and severity of migraine. METHODS:
Twenty-nine patients (24 women, 5 men) with migraine were enrolled in the study. 
Average age was 45 years (range, 24 to 63). The frequency (number of migraines
per month) and intensity (recorded on an analog scale of 1 to 10, 10 being most
severe) of headache were recorded before and after treatment. Twenty-five units
of botulinum toxin type A was injected into each corrugator supercilii muscle,
for a total of 50 units. RESULTS: At 2 months, 24 (83%) of 29 patients reported a
positive response to the injection of botulinum toxin type A (P <.001). Sixteen
patients (55%) reported complete elimination of headache (P <.001), 8 (28%)
experienced significant improvement (at least 50% reduction in frequency or
intensity) (P <.04), and 5 (17%) did not notice a change in headache. The
duration of efficacy of the botulinum toxin type A injections ranged from 6 to 12
weeks, with an average of 8 weeks. In patients who had improvement in migraine
but not complete elimination, the headache frequency decreased from 6.4 to 2.1
per month on average (P <.04), and the intensity decreased from 8.6 to 6.1 (P
<.04). CONCLUSION: These results support the hypothesis that focal injection of
botulinum toxin type A may be an effective therapy for migraine.

Publication Types: 
    Clinical Trial

PMID: 14629244 [PubMed - indexed for MEDLINE]

2418: Headache. 2003 Nov-Dec;43(10):1080-4.

Topiramate as an adjunctive treatment in migraine prophylaxis.

Martínez HR, Londoño O, Cantú-Martínez L, del Carmen Tarín L, Castillo CD.

Neurology Service, Hospital Universitario, Monterrey, NL, Mexico.

BACKGROUND: Anticonvulsants now are commonly used for headache prevention.
Topiramate, one of the newer anticonvulsants, recently has been demonstrated to
be effective as monotherapy for migraine prophylaxis. OBJECTIVE: To assess the
efficacy, safety, and tolerability of topiramate as adjunctive prophylactic
therapy for migraine. MATERIAL AND METHODS: A prospective trial involving
patients with more than 3 migraine attacks per month was performed. Patients
continued their usual prophylactic treatment. Baseline analgesic use and
frequency and duration of migraine attacks were recorded. A 4-point visual analog
scale evaluated severity. Laboratory tests, electrocardiogram, and computed
tomography or magnetic resonance imaging were performed before study entry. After
informed consent was obtained, patients were instructed to take 25 mg of
topiramate per day, with 25- to 50-mg weekly increments to a maximum of 100 mg
per day. Safety was assessed at the first month; tolerability and efficacy were
assessed every week for the first month and then every month for 3 months.
Effectiveness was assessed by comparing baseline and on-treatment migraine
status, and data were analyzed by the Fisher exact test. RESULTS: Twenty-five
women and 11 men (mean age, 44 years) were evaluated. Existing prophylactic
treatment was either propranolol or flunarizine (or both) in 80% of the patients.
At 3 months of therapy with topiramate, headache frequency decreased from 17 to 3
episodes per month, headache duration from 559 to 32 minutes, and intensity from 
9 to 1 by visual analog scale (P <.001). Improvement in frequency and severity of
migraine was observed in 83% of patients. Slight or no changes in headache were
observed in 6 patients. Tolerability was good in 30 patients. The most common
side effects were acroparesthesias, weight loss, sleepiness, and headache
worsening. No adverse interaction with propranolol or flunarizine was observed.
CONCLUSIONS: These results suggest that topiramate is efficacious and safe as an 
adjunctive treatment in patients with migraine whose prior response to
prophylactic management has been less than satisfactory.

Publication Types: 
    Clinical Trial

PMID: 14629243 [PubMed - indexed for MEDLINE]

2419: Headache. 2003 Nov-Dec;43(10):1075-9.

Early intervention with almotriptan improves sustained pain-free response in
acute migraine.

Mathew NT.

Houston (Tex) Headache Clinic, TX 77004, USA.

OBJECTIVE: To determine whether treatment of migraine with almotriptan, when pain
intensity is mild, improves 1- and 2-hour pain-free and sustained pain-free rates
compared with treatment when pain intensity is moderate or severe. METHODS: This 
was a post hoc analysis derived from an open-label, multicenter, long-term study 
of the safety, tolerability, and efficacy of almotriptan 12.5 mg. Patients who
met International Headache Society criteria for migraine with or without aura
were eligible. Patients were instructed to take a single dose of almotriptan 12.5
mg at the onset of a migraine attack. Rescue medication could be taken if
migraine pain had not disappeared at 2 hours. A second dose of almotriptan 12.5
mg could be taken if head pain recurred within 24 hours of the initial dose.
Patients reported the intensity of pain at baseline and at 1 and 2 hours
postmedication using a 4-point scale: no pain, mild, moderate, or severe pain.
They also reported recurrence of pain (return of moderate or severe pain within 2
to 24 hours of taking the study medication) and use of rescue medication. Rescue 
medication consisted of supplemental analgesics taken for pain relief at 2 to 24 
hours postdose. Ergotamines and other 5-HT1B/1D agonists were excluded as rescue 
medications. Based on these patient-reported end points, sustained pain-free
rates, defined as pain-free at 2 hours with no recurrence from 2 to 24 hours and 
no use of rescue medication, were calculated. RESULTS: A higher proportion of
migraine attacks of mild intensity were pain-free at 1 hour (35.3%) compared with
attacks of moderate or severe intensity (7.5%) (P <.001). Two-hour pain-free
rates also were significantly higher with mild intensity pain (76.9%) compared to
moderate or severe intensity (43.9%) (P <.001). In addition, recurrence rates and
use of rescue medication were reduced when attacks were treated during mild pain.
Recurrence was 12.9% for mild pain versus 25.0% for moderate or severe pain (P
<.001), and use of rescue medication was 9.4% for mild pain versus 17.2% for
moderate or severe pain (P <.001). Sustained pain-free rates were nearly twice as
high when attacks were treated during mild intensity pain (66.6%) compared with
attacks treated during moderate or severe pain (36.6%) (P <.001). CONCLUSION:
Treatment with almotriptan 12.5 mg during migraine attacks of mild pain intensity
improves 1- and 2-hour pain-free and sustained pain-free responses.

Publication Types: 
    Comparative Study

PMID: 14629242 [PubMed - indexed for MEDLINE]

2420: Headache. 2003 Nov-Dec;43(10):1049-59.

Migraine frequency and intensity: relationship with disability and psychological 
factors.

Magnusson JE, Becker WJ.

Department of Clinical Neurosciences, University of Calgary and the Calgary
Health Region, Alberta, Canada.

BACKGROUND: Migraine can be disabling, but it varies greatly in frequency and
intensity between individuals. It is not clear which clinical features have the
greatest impact on a migraineur's quality of life. OBJECTIVE: To determine the
influence of headache intensity and frequency on headache-related disability.
METHODS: Patients who were referred to a headache clinic and given a diagnosis of
migraine with or without aura or transformed migraine (n = 115) were divided into
different groups based on headache frequency and mean headache intensity.
Headache frequency was determined from patient diaries. Headache intensity also
was assessed from patient diaries and from scores on the pain severity scale of
the Multidimensional Pain Inventory (MPI). Headache-related disability was
assessed with the Headache Disability Inventory and by scores on the activity
interference scale of the MPI. The degree of depression present was assessed with
the Beck Depression Inventory, and emotional distress was measured by scores on
the affective distress scale of the MPI. RESULTS: In our patient population,
higher mean headache intensity levels were associated with higher levels of
headache-related disability. Our results also suggested that increased headache
intensity is associated with higher levels of depression and emotional distress, 
although this correlation was statistically significant in only 1 of 4
comparisons. Headache frequency did not correlate with disability, depression, or
emotional distress. CONCLUSIONS: For a headache referral population, headache
intensity appears to be a major determinant of headache-related disability, and
it also correlates, to some extent, with the degree of depression and emotional
distress present. Headache frequency was not clearly related to disability or
psychological factors.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 14629240 [PubMed - indexed for MEDLINE]

2421: Headache. 2003 Nov-Dec;43(10):1042-8.

Exploring the relationship between maternal migraine and child functioning.

Fagan MA.

Department of Human Development and Applied Psychology, University of Toronto,
Ontario, Canada.

OBJECTIVE: To investigate the relationship between mothers' migraines and the
roles and expectations of their children. METHODS: Twenty-five mothers diagnosed 
with migraine completed questionnaires concerning their levels of
migraine-related disability and their parenting and child-rearing attitudes.
Migraine-related disability was assessed using the Migraine-Specific Quality of
Life Questionnaire (version 2.1). Parenting and child-rearing attitudes were
assessed using the Adult-Adolescent Parenting Inventory. RESULTS: Significant
positive relationships were found between the mothers' migraine-related
disability and both inappropriate expectations of their children and parent-child
role reversal; ie, the more migraine-related disability reported by the mothers, 
the more they reported having inappropriate expectations of their children and
favoring parent-child role reversal. CONCLUSIONS: This study suggests that
migraine may be associated with dysfunctional parenting patterns. More
specifically, it suggests that in families wherein the mother has migraine,
children may be at risk of inappropriately or prematurely assuming roles for
which they are developmentally unready. Clinical implications are that mothers
with migraine may benefit from some type of family-focused intervention, in
addition to headache treatment.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 14629239 [PubMed - indexed for MEDLINE]

2422: Headache. 2003 Nov-Dec;43(10):1034-41.

Quality of life of patients with cervicogenic headache: a comparison with control
subjects and patients with migraine or tension-type headache.

van Suijlekom HA, Lamé I, Stomp-van den Berg SG, Kessels AG, Weber WE.

Department of Anesthesiology, Intensive Care, and Pain Management, Catharina
Hospital, Eindhoven, The Netherlands.

OBJECTIVE: To establish the health-related quality of life of patients with
cervicogenic headache and to compare it with a random Dutch sample of control
subjects and with patients with migraine without aura or with episodic
tension-type headache. METHODS: Thirty-seven patients with cervicogenic headache,
42 patients with episodic tension-type headache, and 39 patients with migraine
without aura completed a Medical Outcomes Study 36-Item Short Form questionnaire.
RESULTS: Domain scores for "physical functioning" of patients with cervicogenic
headache were worse than those of patients with migraine or tension-type
headache. Physical functioning scores were lower for patients with tension-type
headache than for those with migraine. Migraineurs reported a diminished score
for "social functioning" compared to patients with tension-type headache. All
Medical Outcomes Study 36-Item Short Form domain scores were significantly lower 
for patients with cervicogenic headache relative to the control group.
CONCLUSIONS: Patients with cervicogenic headache have a quality of life burden
that is substantial. Although impairment in the quality of life of patients with 
cervicogenic headache is comparable to patients with migraine without aura and
those with episodic tension-type headache, there are some specific differences.

Publication Types: 
    Comparative Study

PMID: 14629238 [PubMed - indexed for MEDLINE]

2423: Headache. 2003 Nov-Dec;43(10):1026-31.

Comment in:
    Headache. 2003 Nov-Dec;43(10):1032-3.    Headache. 2004 Jul-Aug;44(7):728-30; author reply 730.    Headache. 2004 Sep;44(8):840-1.

Treatment of primary headache in the emergency department.

Blumenthal HJ, Weisz MA, Kelly KM, Mayer RL, Blonsky J.

Neurological Associates of Tulsa, Inc, Tulsa, OK 74136, USA.

BACKGROUND: Each year many patients present to an emergency department for
treatment of acute primary headache. We investigated the diagnosis and clinical
outcome of patients treated for primary headache in the emergency department.
METHODS: Patients treated for acute primary headache in the emergency department 
completed a questionnaire related to their headache symptoms, response to
treatment, and ability to return to normal function. These responses were
compared to the treating physicians' observations of the patient's condition at
the time of discharge from the emergency department. RESULTS: Based on the
questionnaire, 95% of the 57 respondents met International Headache Society
diagnostic criteria for migraine. Emergency department physicians, however,
diagnosed only 32% of the respondents with migraine, while 59% were diagnosed as 
having "cephalgia" or "headache NOS" (not otherwise specified). All patients
previously had taken nonprescription medication, and 49% had never taken a
triptan. In the emergency department, only 7% of the patients received a drug
"specific" for migraine (ie, a triptan or dihydroergotamine). Sixty-five percent 
of the patients were treated with a "migraine cocktail" comprised of a variable
mixture of a nonsteroidal anti-inflammatory agent, a dopamine antagonist, and/or 
an antihistamine; 24% were treated with opioids. All 57 patients reported that
after discharge they had to rest or sleep and were unable to return to normal
function. Sixty percent of patients still had headache 24 hours after discharge
from the emergency department. CONCLUSION: The overwhelming majority of patients 
who present to an emergency department with acute primary headache have migraine,
but the majority of patients receive a less specific diagnosis and a treatment
that is correspondingly nonspecific.

Publication Types: 
    Case Reports
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 14629236 [PubMed - indexed for MEDLINE]

2424: Acta Neurol Belg. 2003 Sep;103(3):144-54.

Transcranial magnetic stimulation in migraine: a review of facts and
controversies.

Fumal A, Bohotin V, Vandenheede M, Schoenen J.

Departments of Neurology and Neuroanatomy, University of Liège, B-4000 Liège,
Belgium.

There is compelling evidence that cortical excitability is modified in migraine
patients between attacks. Transcranial magnetic stimulation (TMS) is a
non-invasive tool to investigate this abnormality. Repetitive transcranial
magnetic stimulation (rTMS) activates the underlying cortex at high, but inhibits
it at low stimulation frequencies. This is a review of published results obtained
in migraineurs with TMS and rTMS over motor or visual cortices. Prevalence and/or
threshold data of phosphenes induced by single pulse TMS of the visual cortex are
contradictory, some favouring increased, others decreased interictal
excitability. The discrepancies may be due to differences in methodology and poor
reliability of phosphene reporting. In a recent rTMS study of the occipital
cortex we have found evidence in favour of an interictal decrease of the
preactivation excitability level by using amplitude of visual evoked potentials
and its habituation during sustained stimulation as indices of cortical
excitability. The hypothesis of increased cortical excitability, taken in its
strict physiological sense of a decreased response threshold and/or an increased 
response to a single suprathreshold stimulus, may thus not be any longer tenable.
The long lasting effects of rTMS allow in future studies to assess metabolic
changes of the cortex and subcortical structures with functional imaging methods 
and to explore novel therapeutic strategies for migraine.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 14626694 [PubMed - indexed for MEDLINE]

2425: Twin Res. 2003 Oct;6(5):422-31.

Genetic and environmental influences on migraine: a twin study across six
countries.

Mulder EJ, Van Baal C, Gaist D, Kallela M, Kaprio J, Svensson DA, Nyholt DR,
Martin NG, MacGregor AJ, Cherkas LF, Boomsma DI, Palotie A.

Dept of Biological Psychology, Vrije Universiteit, Amsterdam, The Netherlands.
ejcm.mulder@psy.vu.nl

Migraine is a common neurovascular brain disorder that is manifested in recurrent
episodes of disabling headache. The aim of the present study was to compare the
prevalence and heritability of migraine across six of the countries that
participate in GenomEUtwin project including a total number of 29,717 twin pairs.
Migraine was assessed by questionnaires that differed between most countries. It 
was most prevalent in Danish and Dutch females (32% and 34%, respectively),
whereas the lowest prevalence was found in the younger and older Finnish cohorts 
(13% and 10%, respectively). The estimated genetic variance (heritability) was
significant and the same between sexes in all countries. Heritability ranged from
34% to 57%, with lowest estimates in Australia, and highest estimates in the
older cohort of Finland, the Netherlands, and Denmark. There was some indication 
that part of the genetic variance was non-additive, but this was significant in
Sweden only. In addition to genetic factors, environmental effects that are
non-shared between members of a twin pair contributed to the liability of
migraine. After migraine definitions are homogenized among the participating
countries, the GenomEUtwin project will provide a powerful resource to identify
the genes involved in migraine.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't
    Twin Study

PMID: 14624726 [PubMed - indexed for MEDLINE]

2426: Catheter Cardiovasc Interv. 2003 Dec;60(4):540-2.

Comment in:
    Catheter Cardiovasc Interv. 2004 Oct;63(2):255.

Migraine with aura related to the percutaneous closure of an atrial septal
defect.

Rodés-Cabau J, Molina C, Serrano-Munuera C, Casaldáliga J, Alvarez-Sabin J,
Evangelista A, Soler-Soler J.

Department of Cardiology, Hospital Universitari Vall d'Hebron, Barcelona, Spain. 
joseprodes@hotmail.com

We report a case of a 31-year-old woman who presented migraine attacks with aura 
within the 48 hr after transcatheter closure of an atrial septal defect with the 
Amplatzer septal occluder device. The migraine attacks persisted for 3 months,
and all examinations performed to rule out a thromboembolic origin of migraine
were negative. Copyright 2003 Wiley-Liss, Inc.

Publication Types: 
    Case Reports

PMID: 14624438 [PubMed - indexed for MEDLINE]

2427: Hum Genet. 2004 Feb;114(3):225-35. Epub 2003 Nov 18.

Update on the genetics of migraine.

Estevez M, Gardner KL.

Department of Neurology, Veterans Administration Hospital and University of
Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA. m_estevez@yahoo.com

The field of migraine genetics has seen an explosion of information over the last
year. In a recent breakthrough, missense mutations in a chromosome 1q23 gene,
ATP1A2, encoding a Na+, K+-ATPase, have been identified in four distinct
pedigrees with a rare form of familial hemiplegic migraine (FHM). ATP1A2 is
expressed in the brain, like the voltage gated calcium channel gene, CACNA1A,
previously identified as the first hemiplegic migraine gene (FHM1). The shared
hemiplegic migraine phenotype of mutations in ATP1A2 and CACNA1A raises the
possibility that they coordinately regulate ion homeostasis that determines
susceptibility to the initiation of both migraine aura and the pain phase of
migraine. For the more common and genetically complex forms of migraine,
genome-wide screens have identified several new loci on 4q24, 6p12.2-21.1, 11q24,
and 14q21.2-q22.3, suggesting additional migraine genes in these regions. In
addition, a recent large case-control association study has linked single
nucleotide polymorphisms in the insulin receptor/INSR gene with migraine.
However, these polymorphisms do not result in detectable changes in receptor
function. The continuing genetic identification of key proteins involved in
migraine will refine our understanding of this common and sometimes debilitating 
disorder, which can strike during the most productive years of a person's life.
Given the co-morbidity of migraine with depression and bipolar disorder, our
knowledge of the causes of migraine may also contribute to our understanding of
these disorders.

Publication Types: 
    Review

PMID: 14624354 [PubMed - indexed for MEDLINE]

2428: Arch Neurol. 2003 Nov;60(11):1595-8.

Comment in:
    Arch Neurol. 2004 Apr;61(4):606-7; author reply 607.

Migraine headache in patients with Tourette syndrome.

Kwak C, Vuong KD, Jankovic J.

Parkinson's Disease Center and Movement Disorders Clinic, Baylor College of
Medicine, Houston, TX 77030, USA.

BACKGROUND: Tourette syndrome (TS) is recognized as one of the most common
childhood movement disorders, characterized by motor and phonic tics often
associated with neurobehavioral comorbidities, such as obsessive-compulsive
disorder. Neurotransmitter dysregulation, particularly involving the serotonin
system, has been implicated in the pathogenesis of TS, obsessive-compulsive
disorder, and migraine headache. OBJECTIVES: To investigate the possible
association between migraine headache and TS and to report preliminary findings
of family history of migraine headache in patients with TS. METHODS: Subjects
diagnosed as having TS at the Baylor College of Medicine Parkinson's Disease
Center and Movement Disorders Clinic were administered a migraine headache
questionnaire based on the migraine criteria established by the Headache
Classification Committee of the International Headache Society. RESULTS: Of 100
patients with TS, 25 (25.0%) satisfied the diagnostic criteria for migraine
headache, significantly greater than the estimated 10% to 13% in the general
adult population (P<.001) and the estimated 2% to 10% in the general pediatric
population (P<.04). There was no significant (P =.44) difference in the presence 
of comorbid obsessive-compulsive traits in the TS migraine and TS nonmigraine
sample groups. Furthermore, our TS group with migraines was not more likely to
have features of obsessive-compulsive disorder compared with
attention-deficit/hyperactivity disorder. Of patients with TS, 56.0% reported a
family history of migraines, 44.0% of whom were first-degree relatives.
CONCLUSIONS: The frequency of migraine headache in a clinic sample of TS subjects
was nearly 4-fold more than the frequency of migraines reported in the general
population. Contrary to previous reports, the co-occurrence of migraines and TS
in our sample group may possibly be attributed to another TS comorbidity, other
than obsessive-compulsive traits.

PMID: 14623732 [PubMed - indexed for MEDLINE]

2429: Hippocampus. 2003;13(7):835-44.

Hippocampal spreading depression bilaterally activates the caudal trigeminal
nucleus in rodents.

Kunkler PE, Kraig RP.

Department of Neurology, University of Chicago, Chicago, Illinois 60637, USA.

Spreading depression (SD) and migraine aura involve transiently altered (i.e.,
increased followed by decreased) electrophysiological activity that propagates at
the distinctive rate of millimeters per minute (mm/min), leading to the
suggestion that they (and perhaps pain from migraine) are causally related via
changes in the same brain structure. Neocortex is considered the anatomical zone 
associated with migraine aura and is the sole area known to induce caudal
trigeminal nucleus (TNC) activation from SD in rodents. However, classical
evidence of SD in human neocortex is reported only with severe brain disease,
while migraine is a common and comparatively benign disorder. Because SD occurs
in human hippocampus, and memory dysfunction referable to hippocampus is seen in 
migraineurs, we determined whether recurrent SD confined to hippocampus in rat
could induce TNC activation. Our work shows that recurrent hippocampal SD evoked 
a significant (P < 0.05-0.001) increase in bilateral c-fos immunostaining within 
TNC superficial laminae compared with sham controls. Furthermore, hippocampal SD 
occurred with a correlated and transient change in spontaneous activity and blood
flow in the ipsilateral neocortex without spread of SD to that area. Thus,
hippocampal SD may be a previously unrecognized, potential trigger for
nociceptive activation of TNC perhaps associated with migraine.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 14620879 [PubMed - indexed for MEDLINE]

2430: Cephalalgia. 2003 Nov;23(9):921-8.

Sporadic hemiplegic migraine is an aetiologically heterogeneous disorder.

Thomsen LL, Ostergaard E, Romer SF, Andersen I, Eriksen MK, Olesen J, Russell MB.

The Danish Headache Centre, University of Copenhagen, Department of Neurology,
Glostrup Hospital, Denmark. LLT@dadlnet.dk

In order to better understand sporadic hemiplegic migraine (SHM) and particularly
its relation to familial hemiplegic migraine (FHM), migraine without aura (MO)
and typical migraine with aura (typical MA), we investigated the occurrence of MO
and typical MA among probands with SHM and their first-degree relatives. The
pattern of familial aggregation of MO and typical MA was assessed by population
relative risk calculations. A total of 105 SHM probands and 483 first-degree
relatives were identified in the Danish population. Compared with the general
population, SHM probands had no increased risk of MO, but a highly increased risk
of typical MA. First-degree relatives of all SHM probands had an increased risk
of both MO and typical MA, whereas first-degree relatives of probands with
exclusively SHM had no increased risk of MO but an increased risk of typical MA. 
Our data suggest that SHM is a genetically heterogeneous disorder.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 14616935 [PubMed - indexed for MEDLINE]

2431: Cephalalgia. 2003 Nov;23(9):914-20.

Relationship between migraine, blood pressure and carotid thickness. A
population-based study in the elderly.

Tzourio C, Gagnière B, El Amrani M, Alpérovitch A, Bousser MG.

INSERM U 360, Hôpital Salpêtrière, and Department of Neurology, Hôpital
Lariboisière, Paris, France. tzourio@chups.jussieu.fr

The relationship between migraine and blood pressure is controversial. We studied
the association between migraine and blood pressure in a population-based sample 
of elderly patients. Participants were 1373 subjects 59-71 years of age. Lifetime
migraine was diagnosed according to the International Headache Society criteria
by a headache specialist. Blood pressure was measured as well as the carotid
intima-media thickness (IMT) which is a good marker of the long-term exposure to 
high blood pressure. Migraine during life was diagnosed in 140 participants. Mean
systolic blood pressure was lower in subjects with migraine than in those without
headache (128 mmHg vs. 137 mmHg). There was a significant trend of decreasing
frequency of migraine with increasing blood pressure and also with increasing
IMT. In this study, migraine was associated with lower levels of blood pressure
and with smaller values of carotid wall thickness.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 14616934 [PubMed - indexed for MEDLINE]

2432: Cephalalgia. 2003 Nov;23(9):907-13.

Perfusion changes with photic stimulation during two phases of the menstrual
cycle: a pilot study comparing controls and true menstrual migraine patients.

Ances BM, Detre JA.

Department of Neurology University of Pennsylvania, Philadelphia 19104, USA.

This pilot study investigated the effect of menstrual cycle phase (late luteal
and mid-follicular) on cerebral perfusion changes during photic stimulation in
both controls (n = 5) and true menstrual migraine patients (n = 5). No
significant differences in resting baseline perfusion were observed between the
two groups during either phase of the menstrual cycle. During the late luteal
phase, changes in perfusion within the occipital lobe due to photic stimulation
were similar for both groups. However, during the mid-follicular phase, occipital
perfusion during visual stimulation decreased for controls but significantly
increased for true menstrual migraine patients (P < 0.05). A two way repeated
measures anova also demonstrated a significant difference between menstrual
migraine patients and controls for photic activation (P < 0.05).

Publication Types: 
    Comparative Study

PMID: 14616933 [PubMed - indexed for MEDLINE]

2433: Cephalalgia. 2003 Nov;23(9):892-900.

Quality of life in migraine patients: a qualitative study.

Ruiz de Velasco I, González N, Etxeberria Y, Garcia-Monco JC.

Servicio de Neurología, Hospital de Galdacano, Vizcaya, Spain.

The impact of migraine on quality of life has been traditionally evaluated by
quantitative analysis, but diverse aspects remain insufficiently assessed, so a
complementary qualitative approach may have advantages. The aim of this study was
to assess the impact of migraine on the quality of life of migraineurs through
the perception of patients and their relatives, and healthcare professionals.
Qualitative methods were used, including six focus groups and nine personal
interviews with 33 migraine patients under physician-directed treatment, five
self-medicated patients, five relatives of migraine patients and seven healthcare
professionals. Migraine has a negative affect on the quality of life, including
physical, emotional and social aspects of daily life such as family, work and
social relationships. Family environment and psychological well-being of patients
were the aspects most affected according to patients and relatives. Health
professionals emphasized work impairment and focused on pharmacological
management and on the need for adequate information about migraine for
non-medicated patients and patients' relatives. Qualitative methods, such as
focus groups and interviews, are a valuable resource for assessing quality of
life and well-being of migraine patients. These techniques open up new areas for 
further research.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 14616931 [PubMed - indexed for MEDLINE]

2434: Cephalalgia. 2003 Nov;23(9):887-91.

Are vascular disorders more prevalent in the relatives of children and
adolescents with migraine?

Lanzi G, Termine C, Rossi M, Ferrari Ginevra O, D'Arrigo S, Amica I, Mongelli A, 
Avantaggiato P, Beghi E.

Department of Child Neurology and Psychiatry, IRCCS Casimiro Mondino Foundation, 
University of Pavia, Pavia, Italy. glanzi@unipv.it

The objective of the study was to assess whether a family history of vascular
disorders is more common in children and adolescents with migraine than in the
general population. Family history of stroke, arterial hypertension, myocardial
infarction and diabetes was investigated by history taking in relatives of
ambulatory children and young adults with migraine and in a control group. The
odds ratios (ORs) with 95% confidence intervals (95% CI) were used as a risk
measure. Using univariate and multivariate (logistic regression) analysis, family
history was assessed in the whole sample and in subgroups by sex and age, degree 
of relationship (parents and grandparents vs. relatives), disease type (migraine 
with and without aura), and type of vascular disorder. The sample included 143
cases (migraine with aura 35, migraine without aura 108) and 164 controls aged
3-24 years (mean 12 +/- 3.8 years). Patients with migraine were at increased risk
of vascular disorders in parents and grandparents but not in all relatives.
Multivariate analysis indicated family history of stroke as most common only in
boys. In conclusion, our study provides some clues to the assumption that
migraine and vascular disorders have common pathogenic mechanisms and that
genetic susceptibility plays a role in increasing the risk of migraine in the
offspring of families with one or more cerebrovascular or cardiovascular
conditions.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 14616930 [PubMed - indexed for MEDLINE]

2435: Cephalalgia. 2003 Nov;23(9):877-86.

The effect of nitric oxide synthase inhibition on histamine induced headache and 
arterial dilatation in migraineurs.

Lassen LH, Christiansen I, Iversen HK, Jansen-Olesen I, Olesen J.

Department of Neurology, Glostrup Hospital, University of Copenhagen, DK-2600
Glostrup, Denmark. l.h.lassen@dadlnet.dk

We have previously proposed that histamine causes migraine via increased NO
production. To test this hypothesis, we here examined if the NOS inhibitor, L-NG 
methylarginine hydrochloride (L-NMMA:546C88), could block or attenuate histamine 
induced migraine attacks and responses of the middle cerebral, temporal and
radial arteries. In a double blind crossover design 12 patients were randomized
to receive pretreatment with L-NMMA (6 mg/kg) or placebo i.v. over 15 min
followed on both study days by histamine (0.5 microg/kg/min) i.v. for 20 min.
Headache scores, mean maximal blood velocity (Vmean) in the middle cerebral
artery (MCA) (transcranial doppler) and diameters of temporal and radial arteries
(high resolution ultrasound) were repeatedly measured. Pre-treatment with L-NMMA,
had no effect on histamine induced headache or migraine, but also had no effect
on the magnitude of histamine induced-decrease in MCA blood velocity, or
dilatation of neither the temporal nor the radial artery. L-NMMA constricted the 
temporal artery by 8% before histamine infusion, whereas the radial artery was
unaffected. The temporal artery dilated 4-5 times more than the radial artery
during histamine infusion. In conclusion the use of a NOS inhibitor in the
highest possible dose did not block the histamine-induced headache response or
arterial dilatation. Either the concentration of L-NMMA reaching the smooth
muscle cell was insufficient or, histamine dilates arteries and causes headache
via NO independent mechanisms. Our results showed for the first time a
craniospecificity for the vasodilating effect of histamine and for the arterial
effects of NOS inhibition.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 14616929 [PubMed - indexed for MEDLINE]

2436: Cephalalgia. 2003 Nov;23(9):869-76.

Comparative efficacy of eletriptan vs. naratriptan in the acute treatment of
migraine.

Garcia-Ramos G, MacGregor EA, Hilliard B, Bordini CA, Leston J, Hettiarachchi J.

Hospital Médica Sur, Colonia Toriello Guerra, México.

This was a randomized, double-blind study designed to evaluate the comparative
efficacy and tolerability of the 40-mg dose of eletriptan and the 2.5-mg dose of 
naratriptan. Patients (n = 548) meeting International Headache Society (IHS)
criteria for migraine were randomized to treat a single migraine attack with
either eletriptan 40 mg, naratriptan 2.5 mg, or placebo. Headache response rates 
at 2 h and 4 h, respectively, were 56% and 80% for eletriptan, 42% and 67% for
naratriptan (P < 0.01 for both time-points vs. eletriptan), and 31% and 44% for
placebo (P < 0.0001 vs. both active drugs at both time-points). Eletriptan also
showed a significantly greater pain-free response at 2 h (35% vs. 18%; P < 0.001)
as well as lower use of rescue medication (15% vs. 27%; P < 0.01) and higher
sustained headache response at 24 h (38%) compared with naratriptan (27%; P <
0.05) and placebo (19%; P < 0.01). Both eletriptan and naratriptan were well
tolerated. The results confirm previous meta-analyses that have suggested the
superiority of eletriptan vs. naratriptan in the acute treatment of migraine.

Publication Types: 
    Clinical Trial
    Comparative Study
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 14616928 [PubMed - indexed for MEDLINE]

2437: Cephalalgia. 2003 Nov;23(9):860-8.

Enhanced interictal responsiveness of the migraineous visual cortex to
incongruent bar stimulation: a functional MRI visual activation study.

Vincent M, Pedra E, Mourão-Miranda J, Bramati IE, Henrique AR, Moll J.

Department of Neurology, Hospital Universitário Clementino Fraga Filho,
Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil. vincent@ufrj.br

Since visual aura is usually described as expanding zigzag lines, neurones
involved with the perception of line orientation may initiate this phenomenon. A 
visual incongruent line stimulation protocol was developed to obtain functional
magnetic resonance images (fMRI) interictally in 5 female migraine patients with 
typical fortification spectra and in 5 normal matched controls. Activation in the
visual cortex was present contralateral to the side of stimulation in 4 of 5
patients, notably in the extrastriate visual cortex. In 4 of 5 controls
activation was observed in the medial and anterior orbitofrontal cortex. In one
of them additional activation at the right nucleus accumbens/ventral striatum and
right ventral pallidum was present. In the remaining control subject activation
was present in the left primary visual cortex. The enhanced interictal reactivity
of the visual cortex in migraineurs supports the hypothesis of abnormal cortical 
excitability as an important pathophysiological mechanism in migraine aura,
though the role of specific regions of the visual cortex remains to be explored.

PMID: 14616927 [PubMed - indexed for MEDLINE]

2438: Curr Opin Ophthalmol. 2003 Dec;14(6):344-52.

Migraine: an ophthalmologist's perspective.

Arunagiri G, Santhi S.

Neuro-Ophthalmology Service, Department of Ophthalmology, Geisinger Medical
Center, Danville, Pennsylvania 17822, USA. eye@usa.com

PURPOSE OF REVIEW: Migraine is a common disorder with visual and neurologic
manifestations. Many patients present to ophthalmologists without a previous
diagnosis of migraine. It is therefore essential for the ophthalmologist to have 
a good understanding of migraine to appropriately help these patients. Neurologic
syndromes with migraine and retinopathy are well known. Here again, the
ophthalmologist may play a role in establishing the correct diagnosis. RECENT
FINDINGS: For long the initial changes during a migraine attack have been shown
to occur in the occipital cortex. In the recent years, the understanding of
migraine has advanced with the availability of functional neuroimaging. A
possible role of brainstem structures in the initiation of migraine attacks has
been proposed based on functional magnetic resonance imaging blood oxygenation
level-dependent signals. Activation of brainstem structures preceded activation
of occipital cortex. Our understanding of cortical spreading depression is also
advancing. Using multiwavelength optical intrinsic imaging, cortical spreading
depression has been shown to have a triphasic response in rats. For the first
time it has been shown that the cortical spreading depression activated the
trigeminovascular system, which is followed by a series of cortical meningeal and
brainstem events that cause the migraine headache. Sildenafil has been shown to
induce migraine attack without dilation of cerebral blood vessels, further
confirming that Wolf's vasogenic theory may not be true. Several loci for
migraine have been identified in recent years. A new locus for migraine with and 
without aura has been identified on chromosome 6, a locus for migraine without
aura to chromosome 14, and a locus for migraine with aura on chromosome 4.
SUMMARY: Our understanding of migraine is rapidly evolving with functional
neuroimaging. There are several unanswered questions. In this article, we will
review the epidemiology, genetics, and clinical features of various forms of
migraine with emphasis on ocular migraine, pathogenesis, and briefly the
management of migraine.

Publication Types: 
    Review

PMID: 14615638 [PubMed - indexed for MEDLINE]

2439: J Manag Care Pharm. 2003 Jul-Aug;9(4):335-45.

Comment in:
    J Manag Care Pharm. 2003 Jul-Aug;9(4):368-9, 371.

Evaluation of a monthly coverage maximum (drug-specific quantity limit) on the
5-HT1 agonists (triptans) and dihydroergotamine nasal spray.

Hoffman L, Mayzell G, Pedan A, Farrell M, Gilbert T.

Blue Cross and Blue Shield of Florida Inc, Jacksonville, FL 32246, USA.
Lauren.hoffman@bcbsfl.com

BACKGROUND: Ensuring the appropriate use of migraine therapies is an important
consideration for care providers, patients, employers, and managed care
organizations (MCOs) because of the high cost of treatment for this fairly
prevalent disabling disease. A review of utilization of serotonin 5-HT1 receptor 
agonists (triptans) in an MCO determined that about 24% of the patients who
received triptan therapy exceeded the manufacturers. recommendations regarding
the maximum daily dose and safe treatment guidelines in a 30-day period. An
initiative was designed to manage the coverage of migraine abortive therapies
with the anticipated outcome of decreasing potential misuse or overuse of the
medications. OBJECTIVE: The objective of this retrospective, observational study 
was to determine the impact of a monthly drug-specific milligram coverage maximum
(quantity limit) on serotonin 5-HT1 receptor agonists (triptans) and
dihydroergotamine (DHE) nasal spray on the utilization and costs of migraine care
in an MCO with approximately 600000 covered members. METHODS: A longitudinal,
retrospective cohort analysis was conducted. All migraine-related services were
analyzed, including outpatient medical visits, emergency department utilization, 
inpatient hospitalizations, and outpatient prescription drug use. The analysis
was conducted using medical and pharmacy administrative claims. Analysis of data 
was performed for the period 12 months prior (October 1999 to September 2000) and
18 months postimplementation of the monthly drug-specific milligram coverage
maximum (October 2000 through March 2002). RESULTS: Imposition of a monthly
coverage maximum for migraine-abortive therapies was associated with a 26.1%
reduction in overall per- patient-per-month (PPPM) medical costs for migraine
care, from US dollars 55.52 PPPM to US dollars 41.02 PPPM (P<0.01). Utilization
of serotonin 5-HT1 receptor agonists and DHE nasal spray declined by 16.7%, from 
0.18 prescriptions PPPM to 0.15 prescriptions PPPM (P=0.039), and direct drug
costs declined by 28.8%, from US dollars 29.18 PPPM to US dollars 20.78 PPPM
(P<0.001). Utilization and costs of outpatient and inpatient migraine-related
medical services declined by 40% from US dollars 16.58 PPPM in the preperiod to
US dollars 9.94 PPPM in the postperiod (P<0.001). CONCLUSION: A monthly
drug-specific milligram coverage maximum was associated with significant
reduction in drug costs and utilization of serotonin 5-HT1 receptor agonists
(triptans) and DHE nasal spray. Utilization and costs of migraine-related medical
services also declined after implementation of the coverage maximum for triptans 
and DHE nasal spray. The monthly drug-specific milligram coverage maximum
appeared to have been successful in managing utilization of triptans and DHE
nasal spray, including reduction of overall costs of migraine-related medical
services and direct drug costs.

PMID: 14613452 [PubMed - indexed for MEDLINE]

2440: J Manag Care Pharm. 2003 Jan-Feb;9(1):45-52.

Comment in:
    J Manag Care Pharm. 2003 Jan-Feb;9(1):89-90.    J Manag Care Pharm. 2003 May-Jun;9(3):279-80; author reply 280-1.

Meta-analysis of oral triptan therapy for migraine: number needed to treat and
relative cost to achieve relief within 2 hours.

Adelman JU, Belsey J.

Headache Wellness Center, 301 E. Wendover Ave., Greensboro, NC 27401, USA.
jadelman@triad.rr.com

OBJECTIVE: To determine the cost-effectiveness of the 5-HT1B/1D agonists, or
triptans, in the acute treatment of migraine. METHODS: To determine the
cost-effectiveness of the triptans, a meta-analysis was conducted of the efficacy
data from 27 oral triptan trials, using the endpoint of "pain-free" status within
2 hours after initial dosing as the indicator of efficacy. Efficacy data were
used to determine the number needed to treat (NNT) to achieve pain-free status in
1 patient within 2 hours postdose and then applied the per-dose costs for each
triptan to the NNT values. RESULTS: Rizatriptan 10 mg and almotriptan 12.5 mg
were the most cost-effective of the triptans, costing $48.34 and $48.57 US
dollars, respectively, to achieve pain-free status in 1 patient within 2 hours
postdose. Frovatriptan 2.5 mg was the most costly, with a cost-effective ratio of
$162.49 US dollars. All other triptans fell between these extremes: zolmitriptan 
5 mg ($65.18 US dollars), sumatriptan 100 mg ($70.83 US dollars), sumatriptan 50 
mg ($75.67 US dollars), zolmitriptan 2.5 mg ($78.74 US dollars), and naratriptan 
2.5 mg ($141.43 US dollars), in decreasing order of cost-effectiveness.
CONCLUSION: Using an NNT analysis, the least-costly drugs to achieve migraine
cure within 2 hours are rizatriptan 10 mg and almotriptan 12.5 mg. From a
population health perspective, the lower acquisition cost of almotriptan 12.5 mg 
allows for effective treatment of more patients than rizatriptan 10 mg for no
additional medication cost.

Publication Types: 
    Meta-Analysis
    Research Support, Non-U.S. Gov't

PMID: 14613361 [PubMed - indexed for MEDLINE]

2441: Neurology. 2003 Nov 11;61(9):1271-2.

Comment in:
    Neurology. 2004 Jan 27;62(2):342; author reply 342.

The prevalence of migraine in neurologists.

Evans RW, Lipton RB, Silberstein SD.

Baylor College of Medicine, Houston, TX, USA. rwevans@pol.net

To assess the prevalence of migraine among neurologists and neurologist headache 
specialists, the authors performed a survey of neurologists who attended a
headache review course. The 1-year and lifetime prevalences of migraine in the
220 respondents were as follows: male neurologists, 34.7%, 46.6%; male headache
specialists, 59.3%, 71.9%; female neurologists, 58.1%, 62.8%; and female headache
specialists, 74.1%, 81.5%. Migraine is much more prevalent among neurologists
than in the general population.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 14610136 [PubMed - indexed for MEDLINE]

2442: Brain. 2004 Jan;127(Pt 1):220-30. Epub 2003 Nov 7.

Central neuromodulation in chronic migraine patients with suboccipital
stimulators: a PET study.

Matharu MS, Bartsch T, Ward N, Frackowiak RS, Weiner R, Goadsby PJ.

Headache Group, Institute of Neurology and National Hospital for Neurology and
Neurosurgery, Queen Square, London WC1N 3BG, UK.

Electrical stimulation of primary sensory afferents is known to have an
antinociceptive effect. Animal and functional imaging studies suggest a role for 
supraspinal structures in this response. Eight patients with chronic migraine (> 
or =15 days per month of attacks of migraine without aura), who had shown a
marked beneficial response to implanted bilateral suboccipital stimulators, were 
studied. Stimulation evoked local paraesthesia, the presence of which was a
criterion of pain relief. On stimulation, the headache began to improve
instantaneously and was completely suppressed within 30 min. On switching off the
stimulation, the headache recurred instantly and peaked within 20 min. PET scans 
were performed using regional cerebral blood flow (rCBF) as a marker of neuronal 
activity. Each patient was scanned in the following three states: (1) stimulator 
at optimum settings: patient pain-free but with paraesthesia; (2) stimulator off:
patient in pain and no paraesthesia; (3) stimulator partially activated: patient 
with intermediate levels of pain and paraesthesia. All scans were processed and
analysed using Statistical Parametric Mapping (SPM) 99. There were significant
changes in rCBF in the dorsal rostral pons, anterior cingulate cortex (ACC) and
cuneus, correlated to pain scores, and in the ACC and left pulvinar, correlated
to stimulation-induced paraesthesia scores. The activation pattern in the dorsal 
rostral pons is highly suggestive of a role for this structure in the
pathophysiology of chronic migraine. The localization and persistence of activity
during stimulation is exactly consistent with a region activated in episodic
migraine, and with the persistence of activation of that area after successful
treatment. The dorsal rostral pons may be a locus of neuromodulation by
suboccipital stimulation. In addition, suboccipital stimulation modulated
activity in the left pulvinar.

Publication Types: 
    Case Reports
    Research Support, Non-U.S. Gov't

PMID: 14607792 [PubMed - indexed for MEDLINE]

2443: J Neurol Sci. 2003 Dec 15;216(1):17-21.

Fingertip photoplethysmography and migraine.

Komatsu K, Fukutake T, Hattori T.

Department of Neurology (D3), Chiba University Graduate School of Medicine, 1-8-1
Inohana, Chuo, Chiba 260-8670, Japan. komakan@nifty.com

Whether migraine is accompanied by generalized disturbance of arteries throughout
the body remains unclear. The second derivative of the fingertip
photoplethysmography waveform (SDPTG) is now considered a useful tool for
evaluating peripheral circulation. SDPTGs were obtained for 101 migraine patients
during headache-free periods and for the same number of headache-free normal
controls. ANOVAs showed significant effects of migraine on SDPTG waveform
parameters as well as aging effects. Absolute values of these parameters were
significantly higher in the migraine patients than in the normal controls in most
age subgroups. These results indicate that migraine is complicated by peripheral 
circulation disorder of vasoconstrictive nature that exists even during
headache-free periods.

PMID: 14607298 [PubMed - indexed for MEDLINE]

2444: Soc Sci Med. 2004 Jan;58(2):305-14.

A direct method for estimating the compensating income variation for severe
headache and migraine.

Groot W, Maassen van den Brink H.

Department of Health Sciences, Maastricht University, P.O. Box 616, 6200 MD
Maastricht, The Netherlands. wim.groot@beoz.unimaas.nl

A subjective quality of life measurement method is introduced to calculate the
compensating income variation for diseases and handicaps. This approach avoids
some of the limitations of existing methods. The method is based on the direct
measurement of life satisfaction of individuals. We apply the method to severe
headache and migraine. It is found that severe headache and migraine have a large
effect on well being and that the compensating income variation for severe
headache and migraine is substantial.

PMID: 14604616 [PubMed - indexed for MEDLINE]

2445: Arq Neuropsiquiatr. 2003 Sep;61(3B):848-50. Epub 2003 Oct 28.

Oscillucusis and sudden deafness in a migraine patient.

Piovesan EJ, Kowacs PA, Werneck LC, Siow C.

Departamento de Clinica Médica, Hospital de Clinicas, Universidade Federal do
Paraná, Curitiba, PR, Brazil. Piovesan@avalon.sul.com.br

Migraine is a complex disease that includes neurologic, gastrointestinal and
autonomic symptoms, although headache is most common feature. In a portion of
cases headache is preceded by focal neurologic symptoms termed auras. Auditory
symptoms only rarely occur as part of an aura. We describe a patient whose
13-year migraine history that included the abnormal perception an oscillation of 
the intensity of ambient sounds (oscillucusis). During a migraine attack
immediately after oscillucusis, the patient developed acute and permanent sudden 
deafness. Clinical and neurologic examinations revealed only profound hearing
loss in her left ear. Audiometric testing confirmed the sensorineural nature of
the hearing loss. The clinical aspects and physiopathology of auditory symptoms
in this case and in patients with migraine is reviewed.

Publication Types: 
    Case Reports
    Review

PMID: 14595494 [PubMed - indexed for MEDLINE]

2446: J Otolaryngol. 2003 Aug;32(4):234-8.

Migraine patients with or without vertigo: comparison of clinical and
electronystagmographic findings.

Bir LS, Ardiç FN, Kara CO, Akalin O, Pinar HS, Celiker A.

Department of Neurology, Pamukkale University, School of Medicine, Denizli,
Turkey.

OBJECTIVE: To find the differences between patients with migraine with and
without vertigo. STUDY DESIGN: A prospective study. SETTING: Ambulatory dizziness
centre of a tertiary referral hospital. METHODS: Eighty-four patients with
migraine (31 with headache, 53 with headache and vertigo) according to the
diagnostic criteria of migraine published by the International Headache Society
in 1988 were included in the study. Patient history, vestibular tests,
electronystagmography (ENG), and imaging studies were performed for differential 
diagnosis. MAIN OUTCOME MEASURES: Clinical findings and ENG parameters. RESULTS: 
Fifty-three of 84 patients (63%) had episodic vertigo attacks. Vertigo was
independent from headache in 24 patients (45%). Vertigo symptoms always appeared 
later in the history of migraine headache. Headache started at age 27 +/- 8.3
years and vertigo symptoms began 7.7 +/- 8.7 years later. The beginning age of
the migraine and female-to-male ratio were significantly greater in the vertigo
group. Fifty-eight of the 84 patients had ENG testing. Fifty-eight percent of the
patients with migraine and 55% of the patients with migraine + vertigo had
abnormal ENG findings. None of the tests except the Dix-Hallpike manoeuvre had a 
statistically significant difference between the two groups. CONCLUSION: The
presence of the same ENG abnormalities in patients with pure headache shows that 
the vestibular pathways are also affected in these patients, even when there are 
no vestibular symptoms.

Publication Types: 
    Comparative Study

PMID: 14587563 [PubMed - indexed for MEDLINE]

2447: J Emerg Med. 2003 Oct;25(3):245-9.

Rizatriptan RPD for severe migraine in the emergency department--a multicenter
study.

Hay E, Rodrig J, Hussain A, Derazon H, Kopelovitch G, Dashkovsky E, Bokish N,
Kafka M, Shtibelman I, Nassimyan S.

Department of Emergency Medicine, Barzilai Medical Center, Ashkelon 78306,
Israel.

Many patients with severe migraine come to the Emergency Department (ED) due to
failure of different drug regimens to stop their headache. We treated 98 patients
with severe migraine who were seen in three different EDs. We used rizatriptan
RPD wafers 10 mg and observed the patients for 2 h. We found that at 2 h, 92.9%
(91/98) of the patients had pain relief, and 73.5% were pain free. The mean time 
to pain relief was 26.9 +/- 29.6 min with a median of 15 min, and the time to
pain free was 70.2 +/- 47.3 min with a median of 75 min. Eighty-five percent of
the patients were free of associated symptoms, such as nausea and vomiting, at 2 
h with a mean time to symptom free of 55 +/- 47.5 min and a median of 45 min.
Rizatriptan was reported to be much better than other drugs by 74.4% of the
patients. Side effects were minor and transient. Recurrence of migraine occurred 
part of the day in 17.1% of the patients and all day or almost all day in 8.6% of
the patients only. The results were consistent in all three EDs. We conclude that
rizatriptan RPD is very effective and reliable as a first-line therapy for acute 
migraine in the ED. It dissolves immediately in the mouth without the
inconvenience of an injection. It works fast and has few side effects and low
headache recurrence.

Publication Types: 
    Clinical Trial
    Multicenter Study

PMID: 14585450 [PubMed - indexed for MEDLINE]

2448: Cochrane Database Syst Rev. 2003;(4):CD002761.

Drugs for preventing migraine headaches in children.

Victor S, Ryan SW.

BACKGROUND: It has been estimated that about ten per cent of children between six
and 20 years of age suffer from migraine. It is estimated that children with
migraine lose one and a half weeks more schooling per year than their peers.
Prophylactic drugs can be prescribed when children suffer from frequent or
disabling headaches. OBJECTIVES: We aimed to describe and assess the evidence
from controlled trials on the efficacy and tolerability of pharmacological agents
taken on a regular basis to prevent the occurrence of migraine attacks and/or
reduce the intensity of such attacks in children with migraine. SEARCH STRATEGY: 
The Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, and EMBASE
were searched from 1966 through 2002. Additional strategies for identifying
trials included searching the reference lists of review articles and included
studies and searching books related to headache. SELECTION CRITERIA: Prospective 
randomised controlled trials (RCTs) of self- or parent-administered drug
treatments in children (under 18 years of age) who had received a diagnosis of
migraine were included. DATA COLLECTION AND ANALYSIS: Two investigators
extracted, assessed, and coded separately all data for each study, using a form
that was designed specifically for the review. Any disagreement was resolved by
discussion. Headache frequency standardised over 28 days was used as the primary 
outcome measure. Headache intensity, headache duration, amount of symptomatic
treatment used, and headache indices were used as secondary outcome measures.
Data were extracted from both parallel-group and crossover trials. Continuous and
dichotomous data were used to calculate standardised mean differences (SMDs) and 
odds ratios (ORs), respectively. Numbers-needed-to-treat (NNTs) and
numbers-needed-to-harm (NNHs) were also calculated. MAIN RESULTS: Thirty-eight
studies were selected. Eighteen were excluded. Eleven preventive drugs were
compared with placebo in a total of 15 studies. Drug-drug comparisons were made
in just six studies. For only four drugs (L-5-hydroxytryptophan [L-5HTP],
flunarizine, clonidine, and propranolol) were two or more studies selected. For
only six drugs (trazodone, L-5HTP, propranolol, flunarizine, papaverine, and
nimodipine) were data reported for effect on frequency. For no individual drug
were comparable data reported in more than one study, thus meta-analysis was not 
possible.Two placebo-controlled studies showed a beneficial effect on the primary
outcome measure, headache frequency. They were for the drugs propranolol and
flunarizine. The propranolol study reported a dichotomous outcome (proportion of 
children responding), and it was possible to calculate a number-needed-to-treat
to produce a two-thirds reduction in headache frequency (NNT = 1.5, 95%CI 1.15 to
2.1). The flunarizine study produced a SMD of 1.51 (95% confidence interval,
-2.21 to -0.82), which was statistically significant in favour of flunarizine (p 
< 0.001). Nimodipine, timolol, papaverine, pizotifen, trazodone, L-5HTP,
clonidine, metoclopramide, and domperidone showed no efficacy in reduction of
frequency of attacks. The available studies on cyproheptadine, phenobarbitone,
phenytoin, amitriptyline, carbamazepine, metoprolol, and piracetam were excluded 
for various reasons. REVIEWER'S CONCLUSIONS: Only one study each for propranolol 
and flunarizine were identified showing efficacy of these drugs as prophylactics 
of paediatric migraine. Nimodipine, timolol, papaverine, pizotifen, trazodone,
L-5HTP, clonidine, metoclopramide, and domperidone showed no efficacy in
reduction of frequency of attacks. Available studies on other commonly used drugs
failed to meet our inclusion criteria. The quality of evidence available for the 
use of drug prophylaxis in paediatric migraine was poor. Studies were generally
small, with no planning of sample size, so that for many drugs, despite the
negative findings of this review, we do not have conclusive evidence of 'no
effect'. There is a clear and urgent need for methodologically sound RCTs for the
use of pings of this review, we do not have conclusive evidence of 'no effect'.
There is a clear and urgent need for methodologically sound RCTs for the use of
prophylactic drugs in paediatric migraine, starting with propranolol. These
studies need to be adequately powered to investigate meaningful reductions in
pain and suffering from a patient's perspective.

Publication Types: 
    Review

PMID: 14583952 [PubMed - indexed for MEDLINE]

2449: Neurology. 2003 Oct 28;61(8 Suppl 4):S31-4.

Clinical applications of new therapeutic deliveries in migraine.

Dahlöf C.

Gothenburg Migraine Clinic, Sociala Huset, Gothenburg, Sweden.

A number of serotonin (5-HT)1B/1D agonists (triptans) are available worldwide for
the treatment of migraine. The first-generation triptan, sumatriptan, was
initially launched as an SC injection, which is fast-acting and consistently
effective but relatively expensive and can be associated with adverse events in
some patients. Sumatriptan was then launched as an oral tablet, shortly followed 
by the development of second-generation triptans that are now available in
several formulations. Tablets are highly effective and convenient but may not be 
suitable in all migraine situations, e.g., migraine-associated nausea or vomiting
and gastric disturbances. An intranasal route of administration appears to be an 
obvious way to deliver a migraine treatment and two triptans, sumatriptan and
zolmitriptan, are available in nasal spray formulations. Sumatriptan offered the 
first nasal spray and has similar efficacy to the sumatriptan tablet, but the
response is inconsistent and many patients cannot tolerate the unpleasant taste. 
The latest nasal spray, zolmitriptan, has produced exciting results in clinical
studies and combines a rapid onset of action and consistently high response rates
with a good tolerability profile. Early results from the author's clinic suggest 
that this promise is realized in clinical practice and that this combination of
patient benefits makes zolmitriptan nasal spray an ideal way for patients to
treat their migraine. With the introduction of zolmitriptan nasal spray,
zolmitriptan is now available in three different formulations, enabling patients 
to tailor their treatment to the circumstances of the individual attack.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 14581656 [PubMed - indexed for MEDLINE]

2450: Neurology. 2003 Oct 28;61(8 Suppl 4):S27-30.

Zolmitriptan nasal spray: advances in migraine treatment.

Syrett N, Abu-Shakra S, Yates R.

AstraZeneca, Macclesfield, United Kingdom.

Zolmitriptan nasal spray was developed specifically to achieve fast, high
effectiveness and to overcome many of the limitations associated with oral and sc
migraine therapies. Pharmacokinetic studies have demonstrated a very rapid
appearance of zolmitriptan in plasma as early as 5 minutes after intranasal
dosing, with about 40% of peak plasma concentration (C(max)) being achieved
within 10 to 15 minutes of dosing. Comparison of plasma concentration-time
profiles of zolmitriptan and its active metabolite after oral and intranasal
administration, together with PET scanning, clearly indicate direct absorption of
zolmitriptan across the nasal mucosa after intranasal administration. The
remainder of the dose is then swallowed and is absorbed through the
gastrointestinal tract. In one blinded, randomized, placebo-controlled,
multiple-attack study of zolmitriptan nasal spray, headache response was superior
to placebo as early as 15 minutes after dosing (p < 0.05). In the zolmitriptan 5 
mg treatment group, the primary end point of 2-hour headache response was
achieved in 70% (300/427) of attacks versus 31% of attacks (119/389 attacks) in
the placebo group (p < 0.001). Patients achieved a 2-hour headache response, had 
no recurrence, and used no additional or escape medications for up to 24 hours in
49% of attacks versus 14% of attacks in the placebo group (p < 0.001).
Zolmitriptan 5 mg nasal spray was well tolerated. These data and those from other
similar studies demonstrate that zolmitriptan nasal spray combines early,
sustained efficacy and good tolerability, making it an optimal acute treatment
for migraine.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 14581655 [PubMed - indexed for MEDLINE]

2451: Neurology. 2003 Oct 28;61(8 Suppl 4):S21-6.

Treatment approaches to maximizing therapeutic response in migraine.

Brandes JL.

Department of Neurology, Vanderbilt University School of Medicine, Nashville, TN,
USA.

Migraine is a chronic condition that presents with episodic disabling attacks,
which can respond unpredictably to therapies. Studies support early treatment
intervention strategies as part of the routine clinical care of migraine
patients. Identifying illness severity and stratifying treatment accordingly (as 
in other diseases such as asthma, diabetes, or hypertension) improves patient
outcome. Assessing the presence of any coexisting conditions, such as depression 
or anxiety, is another essential part of managing migraine.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 14581654 [PubMed - indexed for MEDLINE]

2452: Neurology. 2003 Oct 28;61(8 Suppl 4):S2-8.

Contemporary concepts of migraine pathogenesis.

Welch KM.

Department of Neurology, Finch University of the Health Sciences and the Chicago 
Medical School, Chicago, Illinois, USA.

The pathogenesis of migraine is incompletely understood. Recent discoveries have 
shed light on the neuronal events mediating both the aura and the headache phases
of migraine, identifying a cerebral cortical origin of migraine aura,
susceptibility to attacks based on cortical hyperexcitability, and headache
originating in the trigeminovascular system and its central projections. Abnormal
modulation of brain nociceptive systems, at first transient but becoming
permanent with continuing illness and, predisposing to central sensitization, may
explain the prolonged headache of the migraine attack and the shift of the
migraine phenotype from episodic to chronic headache. Migraine attacks might also
originate in abnormal nociceptive neuromodulator centers in the brainstem.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 14581652 [PubMed - indexed for MEDLINE]

2453: Clin Neurophysiol. 2003 Nov;114(11):2132-7.

Vector analysis of visual evoked potentials in migraineurs with visual aura.

Coutin-Churchman P, Padrón de Freytez A.

Hospital Universitario de Los Andes, Unidad de Neurología, 5101 Mérida,
Venezuela. coutinpe@hotmail.com

OBJECTIVE: To assess the capability of vector analysis of visual evoked
potentials (VEPs) for revealing alterations in posterior visual pathways in
migraineurs with visual aura. METHODS: VEPs to pattern reversal (PR) and LED
goggle stimulation were obtained in 23 patients suffering from migraine with
visual aura, in an orthogonal Fpz-Oz and T3-T4 montage and displayed as a
two-channel Lissajous' trajectory. VEP latency and amplitude at Fpz-Oz, bc
segment amplitude (V) and bc vector orientation angle (theta) were compared with 
a previously collected normative database for individual assessment, and group
comparisons with the previously collected normal sample were made.
Electrophysiological measures were also correlated with time from onset of
disease and from the last crisis, and with the side of symptoms. RESULTS: No
individual alterations in VEP latency or amplitude were observed. However, 36.4% 
of patients showed alterations in vector orientation to PR and 78% to LED
goggles. Group differences with respect to normal subjects were found not only in
vector orientation but also in midline VEP and V, only for PR stimulation. A
significant relationship was found between the laterality of vector deviation and
the laterality of symptoms. CONCLUSIONS: Vector analysis of VEP revealed
alterations possibly corresponding to asymmetrical visual cortex activation in
migraineurs with visual aura, mainly to diffuse light stimulation. SIGNIFICANCE: 
An electrophysiological parameter of individual value for revealing asymmetric
activation of visual cortex in migraineurs is proposed.

PMID: 14580611 [PubMed - indexed for MEDLINE]

2454: Phys Med Rehabil Clin N Am. 2003 Nov;14(4):885-99.

Botulinum toxins in the treatment of migraine and tension-type headaches.

Winner P.

Palm Beach Headache Center, Premiere Research Institute, 5205 Greenwood Avenue,
Suite 200, West Palm Beach, FL 33407, USA.

Botulinum toxins are promising preventive treatments for patients with moderate
to severe episodic and chronic migraine and chronic daily headache. The
recommended indications for botulinum toxins as preventive therapy lend
themselves to the following patient types: those who demonstrate a lack of
improvement from preventive (prophylactic) pharmacotherapy; those who experience 
severe and intolerable adverse events from preventive medications; those who
refuse to use daily medications; those who have contraindications to acute
migraine therapy, and elderly patients with chronic migraine. Both open-label and
double-blind placebo-controlled studies using fixed-site, "follow the pain." or a
combination approach have demonstrated significant reduction in migraine
frequency, severity, and duration, as well as decreased use of acute medications.
The most prominent reductions have been noted in those with reportedly the most
severe migraine headaches. Large, well-designed, double-blind, placebo-controlled
studies are recommended to further clarify optimum dosage and location of
injection, reduce treatment frequency and duration, and address other primary
headache disorders that may benefit from this therapy.

Publication Types: 
    Review

PMID: 14580043 [PubMed - indexed for MEDLINE]

2455: Nucleic Acids Res. 2003 Nov 1;31(21):e130.

Short bioactive Spiegelmers to migraine-associated calcitonin gene-related
peptide rapidly identified by a novel approach: tailored-SELEX.

Vater A, Jarosch F, Buchner K, Klussmann S.

NOXXON Pharma AG, Max-Dohrn-Strasse 8-10, D-10589 Berlin, Germany.

We developed an integrated method to identify aptamers with only 10 fixed
nucleotides through ligation and removal of primer binding sites within the
systematic evolution of ligands by exponential enrichment (SELEX) process. This
Tailored-SELEX approach was validated by identifying a Spiegelmer ('mirror-image 
aptamer') that inhibits the action of the migraine-associated target calcitonin
gene-related peptide 1 (alpha-CGRP) with an IC50 of 3 nM at 37 degrees C in cell 
culture. Aptamers are oligonucleotide ligands that can be generated to bind to
targets with high affinity and specificity. Stabilized aptamers and Spiegelmers
have shown activity in vivo and may be used as therapeutics. Aptamers are
isolated by in vitro selection from combinatorial nucleic acid libraries that are
composed of a central randomized region and additional fixed primer binding sites
with approximately 30-40 nt. The identified sequences are usually not short
enough for efficient chemical Spiegelmer synthesis, post-SELEX stabilization of
aptamers and economical production. If the terminal primer binding sites are part
of the target recognizing domain, truncation of aptamers has proven difficult and
laborious. Tailored-SELEX results in short sequences that can be tested more
rapidly in biological systems. Currently, our identified CGRP binding Spiegelmer 
serves as a lead compound for in vivo studies.

PMID: 14576330 [PubMed - indexed for MEDLINE]

2456: Am J Pharmacogenomics. 2003;3(5):329-43.

Molecular mechanisms of migraine: prospects for pharmacogenomics.

Rogers KL, Lea RA, Griffiths LR.

Genomics Research Centre, Griffith University Gold Coast, Gold Coast Mail Centre,
Southport, Queensland 9726, Australia.

Migraine is a common complex disorder that affects a large portion of the
population and thus incurs a substantial economic burden on society. The disorder
is characterized by recurrent headaches that are unilateral and usually
accompanied by nausea, vomiting, photophobia, and phonophobia. The range of
clinical characteristics is broad and there is evidence of comorbidity with other
neurological diseases, complicating both the diagnosis and management of the
disorder. Although the class of drugs known as the triptans (serotonin
5-HT(1B/1D) agonists) has been shown to be effective in treating a significant
number of patients with migraine, treatment may in the future be further enhanced
by identifying drugs that selectively target molecular mechanisms causing
susceptibility to the disease.Genetically, migraine is a complex familial
disorder in which the severity and susceptibility of individuals is most likely
governed by several genes that may be different among families. Identification of
the genomic variants involved in genetic predisposition to migraine should
facilitate the development of more effective diagnostic and therapeutic
applications. Genetic profiling, combined with our knowledge of therapeutic
response to drugs, should enable the development of specific,
individually-tailored treatment.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 14575521 [PubMed - indexed for MEDLINE]

2457: Int Clin Psychopharmacol. 2003 Nov;18(6):331-9.

Incidence and determinants of antidepressant drug use in migraine patients.

Rahimtoola H, Buurma H, Tijssen CC, Leufkens HG, Egberts AC.

Department. of Pharmacoepidemiology and Pharmacotherapy, Utrecht Institute for
Pharmaceutical Sciences, Utrecht, The Netherlands.
apo.notekraker@zorggroep-almere.nl

The purpose of this retrospective, follow-up study was to characterise the use of
antidepressant medication in a defined migraine population and evaluate the
determinants thereof. Data was obtained from the PHARMO-RLS prescription
database. Our migraine population (2,517 people) included patients having
commenced specific migraine drugs, ergotamine or sumatriptan, for the first time 
from January 1 1992 to December 31 1998. The corresponding date was termed the
'index date'. Non-migraine patients, those not having used any medication
specific for migraine, were selected and equally matched (n=2,517). The
cumulative incidence of initiating antidepressant treatment was estimated during 
two-year observation periods prior to and after the index date. Several
demographic and comedication characteristics were assessed as potential
determinants of antidepressant drug use within the migraine population. Other
determinants included usage patterns ("therapeutic intensity") of ergotamine and 
sumatriptan, defined as the absolute number of Defined Daily Doses (DDDs)
dispensed per patient during one year prior to initiation of antidepressant
therapy. A total of 300 migraine patients (11.9%) and 213 non-migraine patients
(8.5%) had initiated antidepressant treatment in the two-year period prior to or 
in the two-year period after the index date (RR adj 1.4; 95% CI 1.2-1.7). The
cumulative incidence of initiation of antidepressant treatment for the migraine
population was 3.0% per year prior to and 3.2% per year after the initiation of
specific migraine analgesia. The concomitant use of benzodiazepines (RR adj 4.7; 
95% CI 3.5-6.3), migraine prophylactic medication (RR adj 2.1; 95% CI 1.6-2.8)
and heavy therapeutic intensity use of specific migraine analgesia, defined as
>/=150 DDDs per year were highly predictive of antidepressant drug use within the
migraine population.In conclusion, compared to the non-migraine population, the
initiation of antidepressant treatment was only slightly higher in the migraine
population. A number of determinants within the latter were found to be strongly 
associated with antidepressant drug use, the nature of which most likely reflects
an increased severity of migraine whereby therapeutic needs are higher.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 14571153 [PubMed - indexed for MEDLINE]

2458: Psychiatr Clin North Am. 2003 Sep;26(3):725-40.

Chronic episodic disorders in women.

Warnock JK, Clayton AH.

Department of Psychiatry, University of Oklahoma Health Sciences Center-Tulsa,
4502 East 41st Street, Tulsa, OK 74135-2553, USA. faye-biggs@ouhsc.edu

Chronic episodic disorders, such as depressive disorders, IBS, migraine, and FMS,
have important commonalities, including cormorbidities, an absence of classic
anatomic pathology in the tissues, a lack of objective findings on physical
examination, and a lack of abnormal findings by routine laboratory and radiologic
tests. These CED are more prevalent in women (perhaps due to changes in estrogen 
levels), are generally worsened by stress (with resultant hyperactivity of the
HPA axis), and often improve with aerobic exercise and common classes of
medications affecting serotonin function, such as antidepressants. Thus, an
increased understanding of the CED may result in improved treatment and
functioning of many patients.

Publication Types: 
    Review

PMID: 14563106 [PubMed - indexed for MEDLINE]

2459: Gastroenterol Clin North Am. 2003 Sep;32(3):997-1019.

Cyclic vomiting syndrome: a brain-gut disorder.

Li BU, Misiewicz L.

Department of Pediatrics, Feinberg School of Medicine, Northwestern University
and Children's Memorial Hospital Chicago, IL 60614, USA.
bli@childrensmemorial.org

Despite the "black box" surrounding CVS, the authors' understanding of this
clinical entity has advanced substantially in the last decade as a result of an
international interdisciplinary clinical and research effort. Although CVS is now
recognized as a unique clinical entity, patients still undergo innumerable
hospitalizations and diagnostic tests. Although controlled therapeutic studies
are lacking, reasonably effective empiric approaches have been developed by trial
and error using anti-migraine, anti-emetic, and anti-epileptic regimens. The
ongoing investigations of migraine mechanisms through NMR spectroscopy,
mitochondrial DNA mutations and cellular energetics, corticotropin-releasing
factor and gastric motility, and brainstem regulation of autonomic function may
lead to breakthroughs in the understanding of and new therapies for CVS in the
next decade.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.
    Review

PMID: 14562585 [PubMed - indexed for MEDLINE]

2460: Obstet Gynecol. 2003 Oct;102(4):835-42.

Pain-free efficacy after treatment with sumatriptan in the mild pain phase of
menstrually associated migraine.

Nett R, Landy S, Shackelford S, Richardson MS, Ames M, Lener M.

Texas Headache Associates, San Antonio, Texas, USA.

OBJECTIVE: To estimate the efficacy of sumatriptan 50-mg and 100-mg tablets in
menstrually associated migraine when treatment is administered during the mild
pain phase. METHODS: A randomized, double-blind, placebo-controlled,
single-attack study was conducted. Menstrually associated migraine was defined as
any migraine beginning on or between day -2 and day 4, with day 1 = first day of 
flow. Patients had at least a 1-year history of migraine as defined by
International Headache Society criteria and reported regularly occurring
menstrually associated migraines typically having a mild pain phase. Patients
treated attacks within 1 hour of the onset of pain but only if the pain was mild 
at onset and while the pain was still mild. RESULTS: In the 349 women with
menstrually associated migraine, sumatriptan was significantly more effective
than placebo: 61% and 51% of patients who used sumatriptan 100 mg and 50 mg,
respectively, were pain-free 2 hours after treatment compared with 29% of
patients who used placebo (P <.001 for both comparisons). At 2 hours, 51% and 45%
of patients who used sumatriptan 100 mg and 50 mg were free of pain and
associated symptoms (photophobia, phonophobia, nausea, vomiting) compared with
25% of placebo patients (P <.001 for both comparisons). Adverse events were low
for sumatriptan 100 and 50 mg, and both doses were generally well tolerated.
CONCLUSION: Sumatriptan 50-mg and 100-mg tablets are generally well tolerated and
effective in providing pain-free relief and relief of the associated symptoms of 
menstrually associated migraine when administered in the mild pain phase.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 14551015 [PubMed - indexed for MEDLINE]

2461: Mayo Clin Proc. 2003 Oct;78(10):1214-22.

Pain-free results with sumatriptan taken at the first sign of migraine pain: 2
randomized, double-blind, placebo-controlled studies.

Winner P, Mannix LK, Putnam DG, McNeal S, Kwong J, O'Quinn S, Richardson MS.

Palm Beach Headache Center, West Palm Beach, Fla, USA.

OBJECTIVE: To evaluate the efficacy and tolerability of sumatriptan, 50-mg and
100-mg tablets, compared with placebo for treatment of migraine at the first sign
of pain. PATIENTS AND METHODS: Two identical multicenter randomized,
double-blind, placebo-controlled, single-attack studies were conducted from May
through November 2000 in adults (aged 18-65 years). Patients treated migraine at 
the first sign of pain, while pain was mild, but not more than 2 hours after
onset with oral sumatriptan, 50 mg or 100 mg, or matching placebo. The primary
end point was pain-free relief at 2 hours after treatment with 50 mg of
sumatriptan compared with placebo. RESULTS: There were 354 patients in study 1
and 337 patients in study 2. Significantly more patients treated with
sumatriptan, 50 mg and 100 mg, were completely free from pain 2 and 4 hours after
treatment vs patients treated with placebo (at 2 hours, 50% and 57% vs 29%; at 4 
hours, 61% and 68% vs 30%; for both, P < .001). Also, significantly more patients
treated with sumatriptan, 50 mg and 100 mg, were migraine-free (no pain or
associated symptoms) vs those treated with placebo at 2 and 4 hours after
treatment (at 2 hours, 43% and 49% vs 24%; at 4 hours, 54% and 63% vs 28%; for
both, P < .001). The incidence of overall adverse events was low with the 50- and
100-mg dose of sumatriptan (placebo, 7%; sumatriptan at 50 mg, 14%; sumatriptan
at 100 mg, 16%). CONCLUSIONS: Treatment of migraine at the first sign of pain
with sumatriptan, 50-mg and 100-mg tablets, provides superior pain-free relief at
2 and 4 hours after treatment compared with placebo. Results of these studies
suggest that sumatriptan at 100 mg may be more efficacious than at 50 mg when
used in the early treatment paradigm. Because these studies were not powered to
detect statistical differences between active doses, studies to investigate this 
finding are warranted.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 14531480 [PubMed - indexed for MEDLINE]

2462: Int J Clin Pract. 2003 Sep;57(7):573-6.

Comment in:
    Int J Clin Pract. 2004 Mar;58(3):322; author reply 322-3.

Patients with migraine prefer zolmitriptan orally disintegrating tablet to
sumatriptan conventional oral tablet.

Dowson AJ, Charlesworth BR.

King 's Headache Services, King's College Hospital, London, UK.

The Zolmitriptan Evaluation versus Sumatriptan Trial (ZEST) assessed patient
preference for 2.5 mg zolmitriptan orally disintegrating tablet (ODT) or 50 mg
sumatriptan conventional tablet in 218 patients with significant migraine
disability. Significantly more patients preferred zolmitriptan ODT to sumatriptan
conventional tablet (60.1% vs 39.9%; p = 0.0130). In terms of efficacy,
significantly more patients considered zolmitriptan ODT to be an effective
migraine treatment than sumatriptan conventional tablet (77% vs 63%; p = 0.0063).
When asked about specific formulation attributes, significantly more patients
selected zolmitriptan ODT as the least disruptive therapy (83.6% vs 16.4%), the
easiest to take (85.5% vs 14.5%), the most convenient to take (86.1% vs 13.9%),
and the one which enabled them to maintain an active lifestyle (65.5% vs 34.5%), 
compared with the sumatriptan conventional tablet (all comparisons p < 0.001).
Zolmitriptan ODT is a convenient and beneficial alternative to conventional
tablets and is preferred to sumatriptan conventional tablets by migraineurs.

Publication Types: 
    Clinical Trial
    Multicenter Study
    Randomized Controlled Trial

PMID: 14529055 [PubMed - indexed for MEDLINE]

2463: Epilepsy Behav. 2003 Oct;4 Suppl 2:S13-24.

Epilepsy and migraine.

Bigal ME, Lipton RB, Cohen J, Silberstein SD.

Department of Neurology, Albert Einstein College of Medicine, 1300 Morris Park
Avenue, Bronx, NY 10461, USA. mbigal@aecom.yu.edu

Migraine and epilepsy are both chronic disorders characterized by recurrent
neurologic attacks variously accompanied by headache as well as by
gastrointestinal, autonomic, and psychologic features. Migraine and epilepsy are 
linked by their symptom profiles, comorbidity, and treatment. The presence of one
disorder increases the likelihood that the other is also present. In addition, a 
number of migraine syndromes can be confused with epilepsy. The diagnosis and
treatment of each disorder must take into account the potential presence of the
other. Herein, we review the relationship between migraine and epilepsy. We
discuss the diagnosis of migraine using the International Headache Society
criteria, emphasizing the variants of migraine most frequently mistaken for
epilepsy. We summarize the epidemiologic evidence that migraine and epilepsy are 
associated and discuss specific interrelationships between migraine and epilepsy.

Publication Types: 
    Review

PMID: 14527480 [PubMed - indexed for MEDLINE]

2464: Drugs. 2003;63(21):2285-305.

Newer formulations of the triptans: advances in migraine management.

Gladstone JP, Gawel M.

Sunnybrook & Women's College Health Sciences Centre, University of Toronto,
Toronto, Ontario, Canada. jon.gladstone@utoronto.ca

Migraine is a common, frequently incapacitating, headache disorder that imposes a
substantial burden on both the individual patient and society. The last two
decades have witnessed an explosion in our understanding of the pathophysiology
of migraine, and in our development of an efficacious and diverse therapeutic
armamentarium. There are several routes of drug administration available to
patients with migraine. All the serotonin 5-HT(1B/1D) receptor agonists
(triptans) are available as oral tablets (sumatriptan, rizatriptan, zolmitriptan,
naratriptan, almotriptan, frovatriptan and eletriptan). Only sumatriptan is
available as a subcutaneous injection. Some triptans are also available via newer
routes of administration, including orally disintegrating tablets (rizatriptan
and zolmitriptan), rectal suppositories (sumatriptan) and intranasal sprays
(sumatriptan and zolmitriptan). Oral disintegrating tablets and other non-oral
triptan routes (subcutaneous, intranasal, rectal) are a useful alternative to
conventional oral tablets for patients who have difficulty swallowing pills or
prefer not to do so, and for patients whose nausea and/or vomiting precludes
swallowing tablets and/or makes the likelihood of complete absorption
unpredictable. This is important because epidemiological studies in migraine
reveal that the vast majority of patients (>90%) have experienced nausea during a
migraine attack and more than 50% have nausea with the majority of attacks.
Similarly, most (almost 70%) have vomited at some time during an attack and of
these patients, almost one-third vomit in the majority of attacks. The newer
formulations, rapidly dissolving tablets and intranasal sprays, afford patients
the opportunity to use abortive therapy without the need for liquids, at anytime 
and anywhere, at the onset of a migraine attack. Furthermore, the intranasal
sprays are absorbed rapidly and have a prompt onset of action allowing for
significant pain free rates versus placebo as early as 15 minutes post
administration. The ability to administer treatment early in a migraine attack
and have a rapid onset of action is particularly important in acute migraine
treatment in order to prevent the development of central sensitisation. While
many patients and physicians choose conventional oral tablets because of
familiarity and ease of administration, the newer formulations, oral
disintegrating tablets and intranasal sprays, should be given consideration as
first-line agents in selected patients.

Publication Types: 
    Review

PMID: 14524731 [PubMed - indexed for MEDLINE]

2465: Expert Opin Pharmacother. 2003 Oct;4(10):1709-15.

Central nervous system abnormalities in migraine.

Marcus DA.

Pain Evaluation & Treatment Institute, 5750 Centre Avenue, Pittsburgh, PA 15206, 
USA. dawnpainmd@yahoo.com

Migraine is associated with structural and functional CNS changes, for example,
ictal hyperalgesia and allodynia and interictal neural excitation. Structural
abnormalities, most notably white matter changes, occur in greater prevalence in 
migraineurs (16 - 40%). Several studies have examined the neuropsychological
correlates of migraine and/or white matter abnormalities. These studies suggest
mild, interictal dysfunction in migraineurs. More research is needed to correlate
migraine severity, frequency and/or treatment with neuropsychological testing.
Additional studies should: identify interictal cognitive changes; clarify the
contribution to long-term cognitive changes from migraine genotype, sequelae of
repeated pain episodes or their treatment and the consequences of co-morbid
vascular disease; and include cognitive measures as secondary end points in
clinical trials.

Publication Types: 
    Review

PMID: 14521481 [PubMed - indexed for MEDLINE]

2466: Am J Hum Genet. 2003 Nov;73(5):986-93. Epub 2003 Sep 25.

Erratum in:
    Am J Hum Genet. 2005 Apr;76(4):715.

Localization of a gene for migraine without aura to chromosome 4q21.

Björnsson A, Gudmundsson G, Gudfinnsson E, Hrafnsdóttir M, Benedikz J,
Skúladóttir S, Kristjánsson K, Frigge ML, Kong A, Stefánsson K, Gulcher JR.

deCODE Genetics, Reykjavik, Iceland. asgeir.bjornsson@decode.is

Migraine is a common form of headache and has a significant genetic component.
Here, we report linkage results from a study in Iceland of migraine without aura 
(MO). The study group comprised patients with migraine recruited by neurologists 
and from the registry of the Icelandic Migraine Society, as well as through the
use of a questionnaire sent to a random sample of 20,000 Icelanders. Migraine
diagnoses were made and confirmed using diagnostic criteria established by the
International Headache Society. A genome-wide scan with multipoint allele-sharing
methods was performed on 289 patients suffering from MO. Linkage was observed to 
a locus on chromosome 4q21 (LOD=2.05; P=.001). The locus reported here overlaps a
locus (MGR1) reported elsewhere for patients with migraine with aura (MA) in the 
Finnish population. This replication of the MGR1 locus in families with MO
indicates that the gene we have mapped may contribute to both MA and MO. Further 
analysis indicates that the linkage evidence improves for affected females and,
especially, with a slightly relaxed definition of MO (LOD=4.08; P=7.2 x 10(-6)).

PMID: 14513409 [PubMed - indexed for MEDLINE]

2467: Headache. 2003 Oct;43(9):991-3.

Managing intractable migraine with naratriptan.

Gallagher RM, Mueller L.

University Headache Center, Moorestown, NJ 08057, USA.

BACKGROUND: Intractable migraine presents a significant treatment challenge to
both patient and physician. Most attacks are treatable or self-limiting, but
occasionally they may continue for extended periods regardless of treatment.
OBJECTIVE: To determine the efficacy of naratriptan 2.5 mg twice daily for the
treatment of intractable migraine. METHODS: We reviewed 24 patients treated with 
naratriptan twice daily for an intractable migraine attack. Patients were
permitted to take prophylactic medication if such treatment had been effective in
the past. RESULTS: Nineteen patients (79%) improved. Twelve patients showed
excellent response with cessation of pain and associated symptoms, 7 patients
partially responded with lessening of pain and cessation of associated symptoms, 
and 5 patients were nonresponsive. CONCLUSION: Short-term daily administration of
naratriptan may be effective in terminating status migrainosus.

PMID: 14511276 [PubMed - indexed for MEDLINE]

2468: Headache. 2003 Oct;43(9):984-90.

Efficacy of eletriptan in migraineurs with persistent poor response to
nonsteroidal anti-inflammatory drugs.

Chia YC, Lim SH, Wang SJ, Cheong YM, Denaro J, Hettiarachchi J.

University Malaya Medical Centre, Kuala Lumpur, Malaysia.

BACKGROUND/OBJECTIVE: Nonsteroidal anti-inflammatory drugs continue to be one of 
the most widely used therapies for migraine, but their efficacy in treating
moderate to severe migraine headache has not been well documented. In contrast,
the efficacy of triptans in this group of patients is well documented, although
no systematic research is available that evaluates the effectiveness of switching
to a triptan in patients who respond poorly to nonsteroidal anti-inflammatory
drugs. METHODS: One hundred thirteen patients who met International Headache
Society criteria for migraine and who did not experience satisfactory response to
nonsteroidal anti-inflammatory drugs, received open-label treatment with a 40-mg 
dose of eletriptan for one migraine attack. Efficacy assessments were made at 1, 
2, 4, and 24 hours postdose and consisted of headache and pain-free response
rates, absence of associated symptoms, and functional response. Global ratings of
treatment effectiveness and preference were obtained at 24 hours. RESULTS: The
pain-free response rate at 2 hours postdose was 25% and at 4 hours postdose, 55%;
the headache response rate at 2 hours was 66% and at 4 hours, 87%. At 2 hours
postdose, relief of baseline associated symptoms was achieved by 41% of patients 
with nausea compared to 82% of patients at 4 hours; for patients with
phonophobia, 67% were relieved at 2 hours and 93% at 4 hours, and for patients
with photophobia, 70% were relieved at 2 hours and 91% at 4 hours. Functional
response was achieved by 70% of patients by 2 hours postdose. The high level of
acute response was maintained over 24 hours, with only 24% of patients
experiencing a headache recurrence and only 10% using rescue medication. At 24
hours postdose, 74% of patients rated eletriptan as preferable to any previous
treatment for migraine. The most frequent reasons cited for this treatment
preference were faster headache improvement (83%) and functional response (78%). 
Overall, eletriptan was well tolerated; most adverse events were transient and
mild to moderate in severity. No serious adverse events were reported.
CONCLUSION: Results of this open-label trial found the 40-mg dose of eletriptan
to have a high degree of efficacy and tolerability among patients who responded
poorly to nonsteroidal anti-inflammatory drugs.

Publication Types: 
    Clinical Trial
    Research Support, Non-U.S. Gov't

PMID: 14511275 [PubMed - indexed for MEDLINE]

2469: Headache. 2003 Oct;43(9):962-74.

Tolerability and safety of eletriptan in the treatment of migraine: a
comprehensive review.

Mathew NT, Hettiarachchi J, Alderman J.

Houston Headache Clinic, Houston, TX 77004, USA.

OBJECTIVE: To provide a comprehensive review of the tolerability and safety of
eletriptan. Background.-Eletriptan is a potent and selective 5-HT1B/1D agonist
that has demonstrated significant efficacy in the acute treatment of migraine in 
doses of 20 mg, 40 mg, and 80 mg. DESIGN: This review reports the tolerability
and safety of eletriptan across a broad spectrum of preclinical studies and
clinical trials that collectively included treatment of more than 11 000 subjects
and more than 74 000 migraine attacks. RESULTS: In clinical trials, eletriptan
was well tolerated and safe across its dosing range of 20 mg to 80 mg. The
adverse event profile of eletriptan 20 mg was similar to placebo, while the most 
commonly used dose, eletriptan 40 mg, has an adverse event profile that is only
marginally higher than placebo. Eletriptan was safe and well tolerated regardless
of age or gender, and for both short- and long-term treatment. Eletriptan is
metabolized primarily by the CYP3A4 enzyme. Coadministration of potent CYP3A4
inhibitors was not associated with clinically meaningful change in eletriptan
tolerability or safety in the population included in these clinical trials. The
margin of cardiovascular safety for eletriptan was also confirmed by a
well-controlled clinical study in which intravenous eletriptan in excess of an
80-mg dose was rapidly infused in patients undergoing coronary angiography;
nonetheless, it is recommended that eletriptan not be coadministered with a
limited list of 7 potent CYP3A4 inhibitors; in addition, the triptan class in
general (including eletriptan) is contraindicated in patients with symptoms or
findings consistent with ischemic heart disease or other significant underlying
cardiovascular disease. CONCLUSIONS: This comprehensive review found that
eletriptan is safe and well tolerated, and that relatively large changes in dose 
and plasma concentration result in minimal changes in tolerability.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 14511273 [PubMed - indexed for MEDLINE]

2470: Headache. 2003 Oct;43(9):950-5.

Factors associated with migraine-related quality of life and disability in
adolescents: a preliminary investigation.

Tkachuk GA, Cottrell CK, Gibson JS, O'Donnell FJ, Holroyd KA.

Department of Psychology, Ohio University, Athens, OH, USA.

OBJECTIVES: This study examined factors associated with impaired quality of life 
and functioning in a sample of treatment-seeking adolescent migraineurs.
Subjects.-The 37 participants were 51.4% female, and averaged 14.3 years of age
and 4.1 migraines per month for the previous 36 months. PROCEDURE: The
Migraine-Specific Quality of Life Questionnaire, questionnaire items inquiring
about missed activities, and headache diary recordings of missed and impaired
activity time served as dependent measures. Variables studied were age; gender;
migraine frequency, duration, and severity; presence of nausea, photophobia, or
phonophobia; and number of visits to an emergency department in the previous
year. RESULTS: Three hierarchical forward regressions and one logistic
regression, controlling for age and gender, revealed that the presence of nausea 
and at least one emergency department visit predicted poorer quality of life and 
a greater number of missed activities in these adolescent migraineurs. The
presence of migraine-related missed activity hours from headache diaries was
predicted by being male, having higher combined photophobia and phonophobia
sensitivity scores, as well as more frequent and severe migraines. Greater
impairment was predicted by having longer average duration attacks. CONCLUSIONS: 
These preliminary findings suggest that the continued development of effective
treatment approaches to alleviate pain, suffering, and disability in adolescent
migraineurs is required. In particular, evidence for the impact of nausea and
sensitivities suggests that they may be important targets for treatment. As well,
adolescent migraineurs with a history of a visit to an emergency department in
the previous year likely experience greater individual and family distress, more 
disability, and poorer quality of life that require thoughtful, comprehensive
treatment to prevent the development of more severe headache difficulties.

PMID: 14511271 [PubMed - indexed for MEDLINE]

2471: Headache. 2003 Oct;43(9):940-9.

Prevalence, clinical correlates, and treatment of migraine in bipolar disorder.

Low NC, Du Fort GG, Cervantes P.

Mood and Anxiety Disorders Program, National Institute of Mental Health, National
Institutes of Health, Bethesda, MD 20892, USA.

OBJECTIVE: To investigate the prevalence, clinical correlates, and treatment of
migraine in bipolar disorder. BACKGROUND: The relationship between migraine and
mood disorders has been of long-standing interest to researchers and clinicians. 
Although a strong association has been demonstrated consistently for migraine and
major depression, there has been less systematic research on the links between
migraine and bipolar disorder. METHODS: A migraine questionnaire (based on
International Headache Society criteria) was administered to 108 outpatients with
bipolar disorder. Information on the clinical course of bipolar illness was also 
collected. RESULTS: The overall lifetime prevalence of migraine was 39.8% (43.8% 
among women and 31.4% among men). In the subgroup of patients with bipolar II
disorder, the lifetime prevalence of migraine was 64.7%. The bipolar with
migraine group was younger, tended to be more educated, was more likely to be
employed or studying, and had fewer psychiatric hospitalizations. Their initial
presentation for psychiatric treatment was more often for symptoms of depression,
rather than hypomania or mania. They were more likely to have a family history of
migraine and psychiatric disorders, and a greater number of affected relatives.
They were less likely to use mood stabilizers, and more likely to use atypical
antidepressants. Migraine was assessed by a neurologist in only 16% of affected
patients. The prevalence of the use of specific antimigraine medications
(triptans) was 27.9%. CONCLUSIONS: This study confirms the higher prevalence of
migraine among those with bipolar disorder compared to the general population.
Migraine in patients with bipolar disorder is underdiagnosed and undertreated.
Bipolar disorder with migraine is associated with differences in the clinical
course of bipolar disorder, and may represent a subtype of bipolar disorder.

Publication Types: 
    Comparative Study

PMID: 14511270 [PubMed - indexed for MEDLINE]

2472: Intern Med J. 2003 Sep-Oct;33(9-10):436-42.

Comment in:
    Intern Med J. 2004 Jun;34(6):372-3; author reply 373.

Migraine: diagnosis and management.

Goadsby PJ.

Institute of Neurology, The National Hospital for Neurology and Neurosurgery,
London, United Kingdom. peterg@ion.ucl.ac.uk

Migraine is the most common form of disabling primary headache and affects
approximately 12% of studied Caucasian populations. Non-pharmacological
management of migraine largely consists of lifestyle advice to help sufferers
avoid situations in which attacks will be triggered. Preventive treatments for
migraine should usually be considered on the basis of attack frequency,
particularly its trend to change with time, and tract-ability to acute care.
Acute care treatments for migraine can be divided into non-specific treatments
(general analgesics, such as aspirin or non-steroidal anti--inflammatory drugs)
and treatments relatively specific to migraine (ergotamine and the triptans). The
triptans--sumatriptan, naratriptan, rizatriptan, zolmitriptan, almotriptan,
eletriptan and frovatriptan--are potent serotonin, 5-HT1B/1D, receptor agonists
which represent a major advance in the treatment of acute migraine. Chronic daily
headache in association with analgesic overuse is probably the major avoidable
cause of headache disability in the developed world.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 14511196 [PubMed - indexed for MEDLINE]

2473: Cephalalgia. 2003 Oct;23(8):833-41.

Patients' decision-making for migraine and chronic daily headache management. A
qualitative study.

Peters M, Abu-Saad HH, Vydelingum V, Dowson A, Murphy M.

European Institute of Health and Medical Sciences, University of Surrey, UK.
M.Peters@surrey.ac.uk

The objective of this study was to gain insight into the patients'
decision-making for migraine and chronic daily headache management. Patients were
recruited by theoretical sampling in Surrey (UK). Semi-structured and
tape-recorded interviews (n = 13) were conducted, transcribed verbatim, coded and
analysed according to the grounded theory methodology. Thirteen patients (8
migraine and 5 chronic daily headache) described their management. All patients
employed multiple behaviours to manage their headaches. From the patients'
descriptions emerged their decision-making. Based on experience, perceptions and 
new information, the decision-making process involved four stages: headache
severity, evaluation, decision making and behaviours. Although the participants
were passive with regards to certain management strategies, overall they were
actively involved in treating and preventing their headaches. Furthermore, they
were active decision-makers in choosing appropriate management. Migraine and
chronic daily headache patients are actively involved in managing their
headaches. They are key decision-makers and should not be overlooked as a
resource for effective management.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 14510931 [PubMed - indexed for MEDLINE]

2474: Cephalalgia. 2003 Oct;23(8):820-4.

Topiramate in the treatment of chronic migraine.

Silvestrini M, Bartolini M, Coccia M, Baruffaldi R, Taffi R, Provinciali L.

Department of Neurological Sciences, University of Ancona, Ancona, Italy, IRCCS, 
S. Lucia, Rome, Italy. masilvestrini@libero.it

The purpose of this study was to evaluate the efficacy of topiramate in the
treatment of chronic migraine. This was a double-blind, randomized, placebo
controlled, parallel-group study. Patients suffering from chronic migraine with
analgesic overuse were randomly assigned in a 1 : 1 ratio to receive topiramate
or placebo. Following a baseline phase of eight weeks, the study drug was
titrated in 25-mg increments over one week to 50 mg daily. Titration phase was
followed by a 8-week maintenance phase. Number of days with headache during a
28-day period was the efficacy variable. At baseline, there was no difference in 
the number of days with headache between patients treated with topiramate and
those treated with placebo (mean +/- SD: 20.9 +/- 3.2 and 20.8 +/- 3.2,
respectively). During the last 4 week-maintenance phase, topiramate-treated
patients experienced a significantly lower 28-day headache frequency in
comparison to those treated with placebo (mean number of days with headache +/-
SD: 8.1 +/- 8.1 vs. 20.6 +/- 3.4, P < 0.0007). Topiramate at low doses proved to 
be an effective therapeutic approach to reduce headache frequency in patients
with chronic migraine and analgesic overuse.

Publication Types: 
    Clinical Trial
    Comparative Study
    Randomized Controlled Trial

PMID: 14510929 [PubMed - indexed for MEDLINE]

2475: Cephalalgia. 2003 Oct;23(8):814-9.

Abnormal habituation of 'nociceptive' blink reflex in migraine--evidence for
increased excitability of trigeminal nociception.

Katsarava Z, Giffin N, Diener HC, Kaube H.

Department of Neurology, University of Essen, Germany.

We studied the habituation of the 'nociceptive' blink reflex (nBR) in 15 healthy 
subjects and 17 migraine patients interictally as well as during unilateral
migraine headache within six hours of onset and after treatment. In healthy
volunteers the mean regression coefficient (MRC) was - 3.9 following right sided 
and - 4.9 left sided stimulation. This equals an amplitude loss of 19.5% (5 x
-3.9) and 24.5% (5 x -4.9), respectively, across five consecutive sweeps. An
augmentation of nBR responses was found in migraine patients interictally: MRC = 
3.3 following stimulation of the headache side (HA) and MRC = 4.0 of the
non-headache side (non-HA). The differences were statistically significant
(anova: d.f. = 1, F = 25.8, P < 0.001). During the migraine attack MRCs were
negative both before (-5.0, HA and - 4.0, non-HA) and after treatment (-2.6, HA
and - 1.9 non-HA) and significantly differed from those outside the migraine
attack (anova: d.f. = 2, F = 12.4, P < 0.001). The demonstrated lack of
habituation of the nBR responses indicates an abnormal trigeminal nociceptive
processing in migraine patients outside the migraine attack.

Publication Types: 
    Comparative Study

PMID: 14510928 [PubMed - indexed for MEDLINE]

2476: Cephalalgia. 2003 Oct;23(8):808-13.

An analysis of clinical characteristics in genetically linked migraine-affected
pedigrees.

Lea RA, Hilton DA, MacMillian JC, Griffiths LR.

Genomics Research Centre, School of Health Science, Griffith University,
Queensland, Australia.

Migraine is a common complex disorder characterized by severe recurrent headache 
and usually accompanied by nausea and vomiting. Previous studies in our
laboratory have utilized three large multigenerational Australian pedigrees
affected with migraine to indicate that the disease is genetically heterogeneous,
with linkage results implicating genomic susceptibility regions on both
chromosomes 19p and Xq. The present study explores the possibility of a
correlation between genetic and clinical heterogeneity in these affected
pedigrees. Specifically, the clinical characteristics of migraine including
subtype, age of onset, frequency, duration, and disease symptoms were compared
between the migraine pedigrees, and gender differences were also assessed. Our
exploratory analyses revealed no significant differences in any of the clinical
characteristics tested between the chromosome 19-linked family and the two
X-linked families. Also, we did not detect any differences in male vs. female
clinical features for these pedigrees. In conclusion, migraine is considered to
be a clinically and genetically heterogeneous disorder; however, our study
provided no conclusive evidence that variation in genomic susceptibility region
is related to heterogeneity at the clinical level in these migraine-affected
pedigrees.

Publication Types: 
    Comparative Study

PMID: 14510927 [PubMed - indexed for MEDLINE]

2477: Cephalalgia. 2003 Oct;23(8):790-802.

Migraine and asthma in childhood: evidence for specific asymmetric parent-child
interactions in migraine and asthma families.

Siniatchkin M, Kirsch E, Arslan S, Stegemann S, Gerber WD, Stephani U.

Institute of Medical Psychology, Christian-Albrechts-University of Kiel, Kiel,
Germany. m.siniatchkin@pedneuro.uni_kiel.de

In spite of the fact that migraine often manifests as a familial disorder, the
role of the family in migraine has not been adequately explored. In this study
parent-child interactions in 20 families with a child suffering from migraine
were analysed and compared with 20 healthy families and 20 families with an
asthma child. The families had to solve a puzzle within a limited time.
Parent-child interactions within migraine and asthma families were asymmetric,
revealing a disease-specific interpersonal context in the family. Communication
with the affected child in migraine families was significantly more directive,
with more specific instructions and less help, towards migraineurs than with the 
healthy siblings. Dominance of parents and submissive behaviour of children were 
the main features of interactions. In asthma families interactions were more
conflicting and less cooperative. This study demonstrated a specific, asymmetric,
pattern of family interactions predisposing children either to migraine or
asthma.

Publication Types: 
    Comparative Study

PMID: 14510925 [PubMed - indexed for MEDLINE]

2478: Cephalalgia. 2003 Oct;23(8):786-9.

Comment in:
    Cephalalgia. 2003 Oct;23(8):775.

Migraine and idiopathic narcolepsy--a case-control study.

The DMKG Study Group.

German Migraine and Headache Society, Department of Neurology, University of
Regensburg, Regensburg, Germany.

In order to evaluate a possible association between migraine and idiopathic
narcolepsy, we performed a multicentre case-control study on the comorbidity of
narcolepsy and different headaches. In total, 96 patients with idiopathic
narcolepsy were enrolled. The migraine frequency in the patients and in the
control group was 21.9% and 19.8%, respectively (P = 0.722). The migraine
features did not differ significantly between both groups. However, headache
fulfilling the criteria for tension-type headache was significantly more often
reported by narcolepsy patients than by the control group (60.3% vs. 40.7%, P=
0.006). We conclude that there is no association between migraine and narcolepsy 
but that patients with narcolepsy show more unspecific headache, probably due to 
sleep disturbances.

Publication Types: 
    Comparative Study

PMID: 14510924 [PubMed - indexed for MEDLINE]

2479: Cephalalgia. 2003 Oct;23(8):776-85.

5-HT1F receptor agonists in acute migraine treatment: a hypothesis.

Ramadan NM, Skljarevski V, Phebus LA, Johnson KW.

Eli Lilly and Co., Indiana, USA. ramadan@finchcms.edu

Serotonin-1F receptor (5-HT1F) agonists may relieve acute migraine without
vasoconstriction. We conducted a review of preclinical and clinical data that
assessed the potential link between migraine and 5-HT1F activation. (i) A high
correlation exists between the potency of various 5-HT1 receptor agonists in the 
guinea pig dural plasma protein extravasation assay and their 5-HT1F receptor
binding affinity. (ii) 5-HT1F receptors are on the trigeminal system, and may
participate in blocking migraine pain transmission through the trigeminal
ganglion and nucleus caudalis. (iii) 5-HT1F receptors are located on
glutamate-containing neurones and their activation might inhibit glutamate
release; glutamate excess may play a role in migraine. (iv) Selective 5-HT1F
receptor agonists (LY334370; LY344864) are effective in preclinical migraine
models and are non-vasoconstrictive. (v) LY334370 is effective in acute migraine,
and does not cause any symptoms/signs of coronary vasoconstriction. Preclinical
experiments and clinical observations argue for a role of selective 5-HT1F
agonists in migraine.

Publication Types: 
    Review

PMID: 14510923 [PubMed - indexed for MEDLINE]

2480: Neurologia. 2003 Sep;18(7):364-7.

Topiramate for patients with refractory migraine: an observational, multicenter
study in Spain.

Pascual J, Sánchez del Rio M, Mateos V, Láinez JM, Hernández-Gallego J, Leira R, 
Jiménez MD.

University Hospital Marqués de Valdecilla (UC), Santander.
juliopascual@telefonica.net

INTRODUCTION: The efficacy of current preventive migraine treatments is limited. 
In addition, tolerability problems are not infrequent. OBJECTIVES: To check our
experience with topiramate in the treatment of patients with refractory migraine.
PATIENTS AND METHODS: We offered treatment with topiramate to patients with the
diagnosis of International Headache Society (IHS) migraine who had not responded 
to or tolerated beta-blockers, amitriptyline, flunarizine and/or valproate. This 
series is made up of 115 patients (88 women), between 16 and 81 years. Most of
them (n=79) fulfilled the Silberstein et al. criteria for transformed migraine.
The parameters analyzed were "response" (reduction in migraine frequency>50%),
excellent response (>75%) and tolerability. RESULTS: After 3 months, the
maintenance doses of topiramate ranged from 25 to 400 mg, though most patients
took 100 mg. Twenty-four (21%) patients withdrew due to adverse events, mostly
cognitive difficulties, that had already occurred with doses as low as 25-50 mg, 
while 26 (23%) found topiramate ineffective. The remaining 65 (56%) patients
responded, 34 with excellent response. Sixteen patients (10 obese) lost weight
(3-13 kg). CONCLUSIONS: Topiramate seems to be a good therapeutic option for
about half of the patients with refractory migraine. In these patients response
is usually excellent. Intolerance due to adverse events appears in one-fifth of
the cases early and at low doses.

Publication Types: 
    Clinical Trial
    Multicenter Study

PMID: 14505244 [PubMed - indexed for MEDLINE]

2481: Arch Intern Med. 2003 Sep 22;163(17):2041-50.

Prevalence and correlates of panic attacks in postmenopausal women: results from 
an ancillary study to the Women's Health Initiative.

Smoller JW, Pollack MH, Wassertheil-Smoller S, Barton B, Hendrix SL, Jackson RD, 
Dicken T, Oberman A, Sheps DS; Women's Health Initiative Investigators.

Department of Psychiatry, Massachusetts General Hospital, Boston, MA 02114, USA. 
jsmoller@hms.harvard.edu

BACKGROUND: Panic attacks are known to be more common in women than in men, but
the prevalence and correlates of panic in the postmenopausal period have not been
well defined. METHODS: Cross-sectional survey of 3369 community-dwelling
postmenopausal women enrolled between December 1, 1997, and November 30, 2000, in
the Myocardial Ischemia and Migraine Study, a 10-center ancillary study of the
40-center Women's Health Initiative. Participants, aged 50 to 79 years and
predominantly white (73%), completed questionnaires about the occurrence of panic
attacks in the previous 6 months and about migraine headaches and underwent
24-hour ambulatory electrocardiographic monitoring. The 6-month prevalences of
full-blown and limited-symptom panic attacks were calculated, and their
associations with other sociodemographic and clinical variables were examined in 
multivariate analyses. RESULTS: One of the panic attack types was reported by
17.9% (95% confidence interval, 16.6%-19.2%) of women (full-blown attacks, 9.8%; 
limited-symptom attacks, 8.1%). Adjusting for age and race or ethnicity,
full-blown panic attacks were more common in women with a history of migraine,
emphysema, cardiovascular disease, chest pain during ambulatory
electrocardiography, and symptoms of depression. Full-blown panic attacks were
associated in a dose-response manner with negative life events during the past
year. Panic attacks were associated with functional impairment even after
adjusting for comorbid medical conditions and depression. There was no
significant association with self-reported use of hormone replacement therapy.
CONCLUSIONS: Panic attacks may be relatively common among postmenopausal women
and seem to be associated with stressful life events, medical comorbidity, and
functional impairment.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 14504117 [PubMed - indexed for MEDLINE]

2482: Pain. 2003 Sep;105(1-2):381-4.

Symptomatic migraine and sensitization of trigeminal nociception associated with 
contralateral pontine cavernoma.

Katsarava Z, Egelhof T, Kaube H, Diener HC, Limmroth V.

Department of Neurology, University Hospital Essen, Hufelandstrasse 55, 45122
Essen, Germany.

A 38-year-old woman is described with symptomatic strictly right-sided migraine
associated with a pontine cavernoma affecting the contralateral (left) nucleus
raphe magnus. A persistent facilitation of the right-sided trigeminal nociception
was detected interictally using the 'nociception specific' blink reflex, which
was more pronounced during the acute attack. This case shows for the first time, 
an impairment of the anti-nociceptive brainstem nuclei and the facilitation of
the trigeminal nociception in the same subject, thus providing further evidence
for the key role of the brainstem raphe nuclei in the pathophysiology of
migraine.

Publication Types: 
    Case Reports

PMID: 14499457 [PubMed - indexed for MEDLINE]

2483: Pain. 2003 Sep;105(1-2):57-64.

Reduced habituation to experimental pain in migraine patients: a CO(2) laser
evoked potential study.

Valeriani M, de Tommaso M, Restuccia D, Le Pera D, Guido M, Iannetti GD, Libro G,
Truini A, Di Trapani G, Puca F, Tonali P, Cruccu G.

Department of Neurology, Università Cattolica del Sacro Cuore, L go A Gemelli 8, 
00168, Rome, Italy. m.valeriani@tiscali.it

The habituation to sensory stimuli of different modalities is reduced in migraine
patients. However, the habituation to pain has never been evaluated. Our aim was 
to assess the nociceptive pathway function and the habituation to experimental
pain in patients with migraine. Scalp potentials were evoked by CO(2) laser
stimulation (laser evoked potentials, LEPs) of the hand and facial skin in 24
patients with migraine without aura (MO), 19 patients with chronic tension-type
headache (CTTH), and 28 control subjects (CS). The habituation was studied by
measuring the changes of LEP amplitudes across three consecutive repetitions of
30 trials each (the repetitions lasted 5 min and were separated by 5-min
intervals). The slope of the regression line between LEP amplitude and number of 
repetitions was taken as an index of habituation. The LEPs consisted of
middle-latency, low-amplitude responses (N1, contralateral temporal region, and
P1, frontal region) followed by a late, high-amplitude, negative-positive complex
(N2/P2, vertex). The latency and amplitude of these responses were similar in
both patients and controls. While CS and CTTH patients showed a significant
habituation of the N2/P2 response, in MO patients this LEP component did not
develop any habituation at all after face stimulation and showed a significantly 
lower habituation than in CS after hand stimulation. The habituation index of the
vertex N2/P2 complex exceeded the normal limits in 13 out of the 24 MO patients
and in none of the 19 CTTH patients (P<0.0001; Fisher's exact test). Moreover,
while the N1-P1 amplitude showed a significant habituation in CS after hand
stimulation, it did not change across repetitions in MO patients. In conclusion, 
no functional impairment of the nociceptive pathways, including the trigeminal
pathways, was found in either MO or CTTH patients. But patients with migraine had
a reduced habituation, which probably reflects an abnormal excitability of the
cortical areas involved in pain processing.

PMID: 14499420 [PubMed - indexed for MEDLINE]

2484: Pain Med. 2003 Sep;4(3):215-22.

Comment in:
    Pain Med. 2003 Sep;4(3):211-2.

Multidimensional subgroups in migraine: differential treatment outcome to a pain 
medicine program.

Davis PJ, Reeves JL 2nd, Graff-Radford SB, Hastie BA, Naliboff BD.

UCLA Department of Psychiatry and Biobehavioral Sciences, Los Angeles,
California, USA.

OBJECTIVE: The present study compared two different approaches for deriving
patient profiles on their ability to predict treatment outcome to a pain medicine
program for migraine headache. DESIGN/METHODS: Using visual analog scale measures
of pain intensity and functional limitations and the Beck Depression Inventory
(BDI), as a measure of depression, 235 migraine patients were classified into
statistical clusters. The same patients were also classified using the
Multidimensional Pain Inventory (MPI) algorithm into three subgroups: Adaptive
copers (AC), characterized by lower reported levels of pain intensity, life
interference, and distress, as well as higher levels of perceived life control;
interpersonally distressed (ID), characterized by more intermediate levels of
pain, distress, and interference, with a predominant perception of inadequate
support and punishing responses from significant others; and dysfunctional (Dys),
characterized by high levels of pain severity, life interference, and distress
and low levels of perceived life control and activity. RESULTS: The results of
the K-cluster analysis yielded a three-cluster solution: The low impact cluster, 
was characterized by low pain, low functional limitations and low depression and 
showed significant reductions in pre-to-posttreatment pain; the moderate impact
cluster displayed higher levels of pain and functional limitations and low
depression and showed only slight pre-to-posttreatment pain reduction; and the
high impact cluster displayed the highest levels of pain, functional limitations,
and depression and showed significant increases in pre-to-posttreatment pain.
Unlike the K-clustered groups, MPI subgroups failed to differentially predict
treatment outcome. When the K-clustered groups were crosstabulated with the MPI
subgroups, the predictive validity of the MPI subgroups was enhanced. CONCLUSION:
This study questions the validity of the MPI subgroup classification algorithm.
The results indicate that the K-clustering approach is more useful than the MPI
in deriving meaningful patient clusters that differentially predict treatment
outcome in a migraine population.

PMID: 12974820 [PubMed - indexed for MEDLINE]

2485: Forsch Komplementarmed Klass Naturheilkd. 2003 Aug;10(4):179-84.

Acupuncture Randomized Trials (ART) in patients with migraine or tension-type
headache--design and protocols.

Melchart D, Linde K, Streng A, Reitmayr S, Hoppe A, Brinkhaus B, Becker-Witt C,
Wagenpfeil S, Pfaffenrath V, Hammes M, Willich SN, Weidenhammer W.

Zentrum für naturheilkundliche Forschung, II. Medizinische Klinik und Poliklinik,
TU München, Germany.

BACKGROUND AND OBJECTIVE: We report the design and essentials of the protocols of
two Acupuncture Randomized Trials (ART) investigating whether acupuncture is more
efficacious than no treatment and minimal acupuncture in the interval treatment
of migraine and tension-type headache. DESIGN: Randomized controlled multicenter 
trials with three treatment arms and a total observation period of 28 weeks.
SETTING: 30 practitioners and outpatient units in Germany specialized in
acupuncture treatment. PATIENTS: Per study 300 patients with migraine and
episodic or chronic tension-type headache, respectively (diagnosis according to
the criteria of the International Headache Society). INTERVENTIONS: Patients are 
randomly assigned to receive either (1) semi-standardized acupuncture (150
patients), (2) standardized minimal acupuncture (75 patients), or (3) no interval
treatment for 12 weeks followed by semi-standardized acupuncture (75 patients,
waiting list control). Acupuncture treatment consists of 12 sessions per patient 
over a period of 8 weeks. MAIN OUTCOME MEASURE: Main outcome measure in the
migraine trial is the difference between the number of days with headache of
moderate or severe intensity during the 4 weeks before randomization and weeks 9 
to 12 after randomization. In the study on tension-type headache the main outcome
measure is similar to that described above, but for the number of headache days
regardless of intensity. OUTLOOK: The results of these two studies (available in 
2004) will provide health care providers and policy makers with the information
needed to make scientifically sound assessments of acupuncture therapy. Copyright
2003 S. Karger GmbH, Freiburg

Publication Types: 
    Clinical Trial
    Multicenter Study
    Randomized Controlled Trial

PMID: 12972722 [PubMed - indexed for MEDLINE]

2486: Clin Rehabil. 2003 Sep;17(6):624-30.

The effects of exercise and exercise-related changes in blood nitric oxide level 
on migraine headache.

Narin SO, Pinar L, Erbas D, Oztürk V, Idiman F.

School of Physical Therapy and Rehabilitation, Dokuz Eylül University, Izmir,
Turkey. selnur62@hotmail.com

OBJECTIVE: To observe the effects of moderate aerobic exercise on migraine
headache, to assess exercise-related changes in blood nitric oxide (NO) levels,
and to examine the impact of such changes on migraine attacks. DESIGN: Controlled
clinical trial. SETTING: School of Physical Therapy and Rehabilitation. SUBJECTS:
Forty women with general migraine attending the Neurology Department of the
Faculty of Medicine Faculty of Dokuz Eylül University. INTERVENTION: Patients
were assigned alternately into two groups: exercise group undertaking 1 hour
aerobic exercise three times weekly, and a control group. MAIN OUTCOME MEASURES: 
Patients were assessed before and after treatment using three clinical
scales--visual analogue scale for headache, Pain Disability Index and Quality of 
Life Scale--and chemiluminescence analysis for plasma nitric oxide. RESULTS:
After the eight-week therapy period, patient complaints concerning the intensity,
frequency and duration of pain had decreased significantly in both groups;
however, visual analogue scale scoring showed better pain relief in the exercised
group than in the controls (from 8.8 +/- 1.7 to 4.0 +/- 1.4 and from 8.5 +/- 0.8 
to 7.0 +/- 0.9 respectively). Quality of life measures also revealed better
migraine relief in the exercised women than in those who received medical
treatment only. Blood NO rose significantly from pre- to post-therapy in the
exercised group, but the change was not significant in the control group.
CONCLUSION: The study showed that regular long-term aerobic exercise reduced
migraine pain severity, frequency and duration possibly due to increased nitric
oxide production.

Publication Types: 
    Clinical Trial
    Controlled Clinical Trial

PMID: 12971707 [PubMed - indexed for MEDLINE]

2487: Br J Pharmacol. 2003 Sep;140(2):277-84. Epub 2003 Aug 11.

Agonist actions of dihydroergotamine at 5-HT2B and 5-HT2C receptors and their
possible relevance to antimigraine efficacy.

Schaerlinger B, Hickel P, Etienne N, Guesnier L, Maroteaux L.

Institut de Génétique et de Biologie Moléculaire et Cellulaire, UMR 7104 CNRS,
US184 INSERM, Université L. Pasteur de Strasbourg, BP 10142-67404 Illkirch,
Cedex, France.

1. The pharmaceutical compound, dihydroergotamine (DHE) is dispensed to prevent
and reduce the occurrence of migraine attacks. Although still controversial, the 
prophylactic effect of this drug is believed to be caused through blockade and/or
activation of numerous receptors including serotonin (5-HT) receptors of the
5-HT2 subtype. 2. To elucidate if 5-HT2 receptors (5-HT2Rs) may be involved in
DHE prophylactic effect, we performed investigations aimed to determine the
respective pharmacological profile of DHE and of its major metabolite
8'-hydroxy-DHE (8'-OH-DHE) at the 5-HT2B and 5-HT2CRs by binding, inositol
triphosphate (IP3) or cyclic GMP (cGMP) coupling studies in transfected
fibroblasts. 3. DHE and 8'-OH-DHE are competitive compounds at 5-HT2B and
5-HT2CRs. 8'-OH-DHE interaction at (5-HT2BRs) was best fitted by a biphasic
competition curve and displayed the highest affinity with a Ki of 5 nm. These two
compounds acted as agonists for both receptors in respect to cGMP production with
pEC50 of 8.32+/-0.09 for 8'-OH-DHE at 5-HT2B and 7.83+/-0.06 at 5-HT2CRs. 4.
Knowing that the antimigraine prophylactic effect of DHE is only observed after
long-term treatment, we chronically exposed the recombinant cells to DHE and
8'-OH-DHE. The number of 5-HT2BR-binding sites was always more affected than
5-HT2CRs. At 5-HT2BRs, 8'-OH-DHE was more effective than DHE, with an uncoupling 
that persisted for more than 40 h for IP3 or cGMP. By contrast, the 5-HT2CR
coupling was reversible after either treatment. 5. Chronic exposure to 8'-OH-DHE 
caused a persistent agonist-mediated desensitisation of 5-HT2B, but not 5-HT2CRs.
This may be of relevance to therapeutic actions of the compound.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 12970106 [PubMed - indexed for MEDLINE]

2488: Pharmacol Res. 2003 Nov;48(5):531-4.

Association study between the phenotype migraine without aura-panic disorder and 
dopaminergic receptor genes.

Stochino ME, Asuni C, Congiu D, Del Zompo M, Severino G.

Section of Clinical Pharmacology, Department of Neurosciences "B.B. Brodie",
Headache Center, Section of Clinical Pharmacology, University of Cagliari,
Cagliari, Italy.

Clinical and epidemiological evidence suggests that migraine often co-occurs with
psychopathological conditions. Several longitudinal and population-based studies 
have suggested that migraine and panic disorder might share a common
predisposition. An abnormal dopaminergic function has been hypothesized to be
involved as etiological factor in panic disorder as well as in migraine.
Epidemiological and molecular data suggest the role of genetic factors in the
pathogenesis of both migraine and panic attack disorder. We assessed the presence
of panic disorder in 100 probands suffering from migraine without aura and the
present study was designed to analyse the possible association of the
migraine-panic phenotype with dopaminergic genes. In our sample, 17 out of 100
migraineurs were affected by panic disorder and were thus considered for the
genetic association study. The allele frequencies of DRD1, DRD3, DRD5, DRD2 in
probands did not differ from that of parental non-transmitted chromosomes.This
result does not seem to support, in our limited sample, a common pathological
basis, with regard to the dopaminergic system, between migraine and panic. Should
migraine and panic disorder share some common mechanisms, these could be sought
in neuro-chemical systems other than the dopaminergic one.

PMID: 12967601 [PubMed - indexed for MEDLINE]

2489: Neurosci Lett. 2003 Oct 16;350(1):56-60.

Despite the general correlation of the serotonin transporter gene regulatory
region polymorphism (5-HTTLPR) and platelet serotonin concentration, lower
platelet serotonin concentration in migraine patients is independent of the
5-HTTLPR variants.

Juhasz G, Zsombok T, Laszik A, Jakus R, Faludi G, Sotonyi P, Bagdy G.

Laboratory of Neurochemistry and Experimental Medicine, and Department of
Vascular Neurology, Faculty of Medicine, Semmelweis University, National
Institute of Psychiatry and Neurology, Budapest, Huvosvolgyi ut 116, H-1021,
Hungary.

Platelet serotonin (5-HT) concentrations in a headache-free period during the
mid-follicular phase and the serotonin transporter gene regulatory region
polymorphism (5-HTTLPR) were measured in female migraine patients without aura (n
= 64) and healthy controls (n = 42). High-pressure liquid chromatography (HPLC)
was used to determine the platelet 5-HT concentration and genetic polymorphism
was determined by polymerase chain reaction. Significantly lower platelet 5-HT
concentrations were found in migraine patients compared to controls. Concerning
the 5-HTTLPR polymorphism, the S/S genotype was associated with a significantly
higher platelet 5-HT concentration (P = 0.027) in the whole study population.
This association between the 5-HTTLPR genotypes and platelet 5-HT concentrations 
was independent of the diagnosis. In addition, the platelet 5-HT concentration
was lower in migraineurs in all genotypes (S/S, S/L, L/L). In conclusion,
5-HTTLPR variants may have an effect on the platelet 5-HT concentrations, but the
lower 5-HT concentrations in migraine patients seem to be determined by other
factors.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 12962916 [PubMed - indexed for MEDLINE]

2490: Ann Neurol. 2003 Sep;54(3):360-6.

Novel mutations in the Na+, K+-ATPase pump gene ATP1A2 associated with familial
hemiplegic migraine and benign familial infantile convulsions.

Vanmolkot KR, Kors EE, Hottenga JJ, Terwindt GM, Haan J, Hoefnagels WA, Black DF,
Sandkuijl LA, Frants RR, Ferrari MD, van den Maagdenberg AM.

Department of Human Genetics, Leiden University Medical Centre, Wassenaarseweg
72, 2333 AL Leiden, The Netherlands.

Familial hemiplegic migraine (FHM) is a rare, severe, autosomal dominant subtype 
of migraine with aura. Up to 75% of FHM families have a mutation in the P/Q-type 
calcium channel Ca(v)2.1 subunit CACNA1A gene on chromosome 19p13. Some CACNA1A
mutations also may cause epilepsy. Here, we describe novel missense mutations in 
the ATP1A2 Na(+),K(+)-ATPase pump gene on chromosome 1q23 in two families with
FHM. The M731T mutation was found in a family with pure FHM. The R689Q mutation
was identified in a family in which FHM and benign familial infantile convulsions
partially cosegregate. In this family, all available affected family members with
FHM, benign familial infantile convulsions, or both, carry the ATP1A2 mutation.
Like FHM linked to 19p13, FHM linked to 1q23 also involves dysfunction of ion
transportation and epilepsy is part of its phenotypic spectrum.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 12953268 [PubMed - indexed for MEDLINE]

2491: Cephalalgia. 2003 Sep;23(7):519-27.

The prevalence and disability burden of adult migraine in England and their
relationships to age, gender and ethnicity.

Steiner TJ, Scher AI, Stewart WF, Kolodner K, Liberman J, Lipton RB.

Division of Neuroscience, Imperial College London, London, UK, Neuroepidemiology 
Branch, NINDS/NIH, Bethesda, MD, USA. t.steiner@ic.ac.uk

This study estimates the 1-year prevalence of migraine in adults in England in
relation to the major demographic variables of age, gender and ethnicity, and
describes some of its features, including aspects of consequential disability. A 
telephone survey was conducted of a random sample (n = 4007) of the population
aged 16-65 years of mainland England using a previously validated diagnostic
interview. The response rate was 76.5%. Overall, 7.6% of males and 18.3% of
females reported migraine with or without aura within the last year meeting
diagnostic criteria closely approximate to those of the International Headache
Society. Prevalence of migraine varied with age, rising through early adult life 
and declining in the late 40s and early 50s. Prevalence was higher in Caucasians 
than in other races. Attack rates were > or = 1/month in most migraineurs, and
most experienced interference with daily activities in > or = 50% of their
attacks. On average, an estimated 5.7 working days were lost per year for every
working or student migraineur, although the most disabled 10% accounted for 85%
of the total. Results were in keeping with those from surveys in other countries.
If these findings in mainland England are projected to the entire UK population, 
we estimate that 5.85 million people aged 16-65 years experience 190 000 migraine
attacks every day and lose 25 million days from work or school each year because 
of them. Migraine is an important public health problem in the UK, associated
with very substantial costs.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 12950377 [PubMed - indexed for MEDLINE]

2492: Cephalalgia. 2003 Sep;23(7):511-8.

What kind of habituation is impaired in migraine patients?

Siniatchkin M, Kropp P, Gerber WD.

Institute of Medical Psychology, Christian-Albrechts-University of Kiel, Kiel,
Germany. m.siniatchkin@pedneuro.uni-kiel.de

The acoustically evoked cortical potentials of 20 migraine patients were
investigated using a combined conditioning-testing and oddball paradigm. The
short- and long-term habituation results of the P50 and P300 waves were compared 
with 16 healthy subjects. Migraineurs were characterized by a sensory gating
deficit of the P50 wave (reduced short-term habituation) in the non-target
condition and a reduced long-term habituation of the P300 wave in the target
condition. The study describes disturbances of information processing on the
automatic and cognitive levels in migraine patients and emphasizes the role of
sensory gating and orienting response in migraine pathogenesis.

PMID: 12950376 [PubMed - indexed for MEDLINE]

2493: Cephalalgia. 2003 Sep;23(7):491-5.

Ethical aspects of placebo in migraine research.

Linde M, May A, Limmroth V, Dahlöf C; Headache Masters Programme.

Gothenburg Migraine Clinic and Institute of Clinical Neuroscience, Sahlgrenska
University Hospital, Göteborg, Sweden.

Randomized placebo-controlled clinical trials have been the 'golden standard'
during the last decades in the development of new drug therapies. This
scientifically valid approach has recently been questioned in the fifth revised
version of the Declaration of Helsinki, which states that the use of
placebo-controlled clinical trials is only acceptable when no proven treatment
exists for the studied disease. The World Medical Association further claims that
no national ethical, legal or regulatory requirements should be allowed to reduce
or eliminate any of the statements in the declaration. In spite of this, the
document is not generally accepted as the world ethical standard, as demonstrated
by its lack of adoption by many professional associations. In the evaluation
process for a drug to be approved in many countries today, clinical investigators
at the hospitals and researchers at the pharmaceutical companies are obliged to
use study protocols that would be rejected if the new declaration were to be
fully adopted. Adherence to the clinical trial guidelines of the International
Headache Society could also mean violation of the new Helsinki declaration of
ethics. Some ethics committees have already adopted the new declaration, which
has caused concern among clinical investigators, who find this document to be
vastly out of the line with common practice. At the moment, the situation is
unclear and debated with increasing polarity concerning the scientific and
ethical issues regarding the use of placebo in clinical trials.

Publication Types: 
    Review

PMID: 12950373 [PubMed - indexed for MEDLINE]

2494: Cephalalgia. 2003 Sep;23(7):487-90.

Placebo response in clinical randomized trials of analgesics in migraine.

Bendtsen L, Mattsson P, Zwart JA, Lipton RB.

Copenhagen Headache Research Centre, Department of Neurology, Glostrup Hospital, 
University of Copenhagen, Copenhagen, Denmark.

The objective was to assess the placebo response in randomized clinical trials of
analgesics in the treatment of migraine attacks. We included placebo-controlled
studies that used the criteria of the International Headache Society for the
diagnosis of migraine and headache response as the primary efficacy parameter. In
the 11 studies that qualified for inclusion, headache response occurred after
placebo treatment in 7-50% of the migraineurs with an average placebo response
rate of 30% (95% confidence interval (CI) 23-36). Two hours after treatment with 
placebo an average of 9% (95% CI 7-12, range 7-17%) of the patients were found to
be pain free. In conclusion, the average headache response rate to placebo was
30% in randomized clinical trials of analgesics in migraine with a tremendous
variation among studies. Placebo response rates vary with the choice of primary
efficacy measure as well as patient characteristics and study design.

Publication Types: 
    Review

PMID: 12950372 [PubMed - indexed for MEDLINE]

2495: Clin Ther. 2003 Jul;25(7):2053-69.

Migraine treatment patterns and patient satisfaction with prior therapy: a
substudy of a multicenter trial of rizatriptan effectiveness.

Ceballos Hernansanz MA, Sanchez Roy R, Cano Orgaz A, López-Gil A; START 10 Study 
Group.

12 de Octubre Hospital, Madrid, Spain.

BACKGROUND: Migraine is a common, chronic, often disabling neurologic condition
that is underdiagnosed and undertreated. OBJECTIVE: We undertook this
questionnaire-based study as a substudy of a multicenter trial of rizatriptan
effectiveness. Our goal was to assess the history of acute migraine medication
use and the relationship between different migraine medication regimens and
patient satisfaction with prior therapy. METHODS: This study was conducted at 85 
neurology clinics throughout Spain from March Lo December 2001. It was planned
prospectively as part of the screening visit for a multicenter trial of the
effectiveness of rizatriptan therapy for migraine. Male and female patients >/=18
years of age were eligible for the primary trial, and hence for this study, if
they had a history of migraine attacks and did not have a contraindication for
triptan use. At the screening visit for the primary trial, a questionnaire was
used by clinicians to record past and current use, and duration and order of use,
of analgesics, nonsteroidal anti-inflammatory drugs (NSAIDs), ergot derivatives, 
and triptans; satisfaction with treatment was scored on a 5-point scale ranging
from "very dissatisfied" to "very satisfied." RESULTS: Of 712 patients completing
the questionnaire (mean [SD] age, 34 [10] years; range, 18-69 years), 75% were
women and 94% experienced moderate or severe functional disability during
migraine attacks. Analgesics were used by the majority of patients (81%) and for 
the longest mean [SD] duration (8.8 [7.6] years) but were associated with the
least satisfaction (10% of patients "very satisfied" or "somewhat satisfied").
Triptans were used by the fewest patients (32%) and for the shortest mean
duration (18 [1.6] years) but were associated with the highest rate of
satisfaction (66%) compared with NSAIDs (27%) and ergot derivatives (31%).
Regardless of duration or order of drug use, or sex or age of the patient, the
likelihood of satisfaction with triptans was significantly greater (P < 0.001)
than with nontriptan regimens, with an adjusted odds ratio (95% CI) of 16.8
(11.4-24.9) versus analgesics, 5.1 (3.6-7.1) versus NSAIDs, and 4.1 (2.8-6.0)
versus ergot derivatives. CONCLUSIONS: Our results showed that analgesics,
NSAIDs, and ergot derivatives were used for long durations but provided low
satisfaction among patients. Triptans were rarely used as a first treatment
choice; however, patients reported the highest treatment satisfaction scores
after triptan therapy compared with ergot derivatives, NSAIDs, or analgesics.

Publication Types: 
    Clinical Trial
    Multicenter Study

PMID: 12946550 [PubMed - indexed for MEDLINE]

2496: Curr Pain Headache Rep. 2003 Oct;7(5):387-94.

Do the proposed cervicogenic headache diagnostic criteria demonstrate specificity
in terms of separating cervicogenic headache from migraine?

Fishbain DA, Lewis J, Cole B, Cutler RB, Rosomoff RS, Rosomoff HL.

University of Miami, Comprehensive Pain & Rehabilitation Center, 600 Alton Road, 
Miami Beach, FL 33139, USA. d.fishbain@miami.edu

Diagnostic criteria for cervicogenic headache (CH) have been proposed. These
criteria are controversial in that they appear to overlap or include
characteristics that usually are attributed to migraine headache (MH). Whether
these criteria are specific enough to separate CH patients from MH patients
remains to be controversial. The literature on this issue is reviewed. In
addition, the authors report the results of a study attempting to build a model
of variables typically associated with CH or MH, which would identify patients
with CH. A significant model could not be built that did not include MH symptoms.
As such, it has been concluded that it is unlikely that the criteria for CH will 
have the specificity required to separate CH patients from MH patients.

Publication Types: 
    Comparative Study

PMID: 12946293 [PubMed - indexed for MEDLINE]

2497: Curr Pain Headache Rep. 2003 Oct;7(5):371-6.

The trigeminocervical complex and migraine: current concepts and synthesis.

Bartsch T, Goadsby PJ.

Institute of Neurology, Queen Square, London WC1N 3BG, UK.

Neurones in the trigeminocervical complex are the major relay neurones for
nociceptive afferent input from the meninges and cervical structures; therefore, 
they are the neural substrates of head pain. This review highlights the
importance of two basic mechanisms in headache physiology: convergence of
nociceptive afferents and sensitization of trigeminocervical neurones. These
physiologic findings have clinical correlates such as hypersensitivity and spread
and referral of pain frequently seen in patients with primary headache, such as
migraine. Special reference is made to the influence of structures from the upper
cervical spine in generating and contributing to migraine headaches. The
pathophysiology and functional relevance of these basic mechanisms to headaches
is discussed in the context of recent experimental findings with regard to pain
processing.

Publication Types: 
    Review

PMID: 12946290 [PubMed - indexed for MEDLINE]

2498: Expert Opin Pharmacother. 2003 Sep;4(9):1609-14.

45(th) Annual Scientific Meeting of the American Headache Society June 19 -22,
2003, Chicago, IL, USA.

Marcus DA.

Pain Evaluation & Treatment Institute, 5750 Center Avenue, Pittsburgh, PA 15206, 
USA. MarcusD@anes.upmc.edu

The 45(th) Annual Scientific Meeting of the American Headache Society focused on 
new areas of headache research: revised diagnostic criteria, increased the
understanding of the pathogenesis of migraine and expansion of identified
physiological changes in migraine beyond head pain to include cognitive, sleep
and vestibular disturbances. A preview of the new International Headache Society 
criteria described changes in diagnostic categories, including special criteria
for research. New definitions to categorise chronic daily headache, menstrual
migraine and secondary headaches were the main highlights of the modified
criteria. In addition, novel data on activation within trigeminovascular pathways
expand the understanding of the pathogenesis of migraine. Identification of the
ability of treatment to impact activation and sensitisation of peripheral and
central neurons results in: an explanation for initial headache worsening and
neck/chest tightness that commonly occur with triptans, a better understanding of
the mechanisms of triptans, and a strong recommendation for early triptan
intervention (within 20 min of headache onset). Application of matrix
metalloproteinase models to migraine helps explain the ability of medications to 
cross the blood-brain barrier during a migraine episode, as well as describe
possible ischaemia with repeated migraine (e.g., white matter abnormalities seen 
on magnetic resonance scanning). Improved classification of headache disorders,
along with increased understanding of the physiology of migraine and mechanism of
action of common treatments, should enhance future development and evaluation of 
effective headache therapy.

Publication Types: 
    Congresses

PMID: 12943491 [PubMed - indexed for MEDLINE]

2499: Expert Opin Pharmacother. 2003 Sep;4(9):1573-8.

Divalproex sodium extended-release for the prophylaxis of migraine headache.

Freitag FG.

Diamond Headache Clinic, Suite 500, 467 W Deming Place, Chicago, IL 60614, USA.
dhcdoc@aol.com

The Diamond Headache Clinic first began using valproic acid in 1984.
Subsequently, a variety of open-label and then placebo-controlled trials were
carried out with valproic acid, followed by an enteric-coated formulation known
as divalproex sodium delayed-release. These trials demonstrated a consistent
pattern of efficacy and the delayed-release form improved tolerability while
offering a twice-daily dosing schedule. This led to the development of an
extended-release formulation. This formulation further improved tolerability and 
led to a once-daily dosing. The pivotal trial conducted in patients with migraine
with the extended-release formulation demonstrated efficacy similar to that seen 
with the delayed-release form.

Publication Types: 
    Review

PMID: 12943487 [PubMed - indexed for MEDLINE]

2500: Headache. 2003 Sep;43(8):892-5.

Pseudomigraine with lymphocytic pleocytosis: a calcium channelopathy? Clinical
description of 10 cases and genetic analysis of the familial hemiplegic migraine 
gene CACNA1A.

Chapman KM, Szczygielski BI, Toth C, Woolfenden A, Robinson G, Snutch TP, Spacey 
SD.

Division of Neurology, University of British Columbia, Vancouver, BC, Canada.

OBJECTIVE: To report the clinical findings of 10 patients diagnosed with
pseudomigraine with lymphocytic pleocytosis and the results of mutational
analysis of the CACNA1A gene in 8 of these patients. BACKGROUND: Pseudomigraine
with lymphocytic pleocytosis, also referred to as headache with neurologic
deficits and cerebrospinal fluid lymphocytosis (HaNDL), is characterized by
episodic transient neurologic dysfunction associated with moderate to severe
headache and cerebrospinal fluid lymphocytic pleocytosis. Episodes are recurrent 
and the condition is self-limiting. The etiology of this sporadic condition
remains unknown, but the episodic nature and its ability to be triggered by
angiography is somewhat reminiscent of the phenotypic features of familial
hemiplegic migraine, a condition caused by mutations in the CACNA1A gene.
DESIGN/METHODS: Utilizing retrospective chart review, we describe the clinical
features of pseudomigraine with lymphocytic pleocytosis in 10 patients. Whole
blood was taken from 8 patients (2 were lost to follow-up) and used for DNA
testing. The CACNA1A gene was screened for mutations using heteroduplex analysis 
and direct DNA sequencing. RESULTS: Clinical features of pseudomigraine with
lymphocytic pleocytosis included transient episodes of weakness, sensory and
visual symptoms, aphasia, and confusion lasting minutes up to 4 hours. Sensory
symptoms, typically affecting the face and arm, were the most common
presentation. Localization of symptoms did not conform to vascular territories.
Headache was typically throbbing and most often bilateral. Genetic analysis did
not identify any mutations in the CACNA1A gene. CONCLUSIONS: Similarities between
familial hemiplegic migraine and pseudomigraine with lymphocytic pleocytosis
include recurrent headache with reversible neurologic deficit, cerebrospinal
fluid lymphocytic pleocytosis, and triggers such as angiography. Even so,
heteroduplex analysis and DNA sequencing failed to identify any sporadic
mutations or shared polymorphisms in the exons or the intron/exon boundaries of
the CACNA1A gene. These results do not support a role of the CACNA1A gene in the 
etiology of pseudomigraine with lymphocytic pleocytosis.

Publication Types: 
    Case Reports
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 12940811 [PubMed - indexed for MEDLINE]

2501: Headache. 2003 Sep;43(8):878-83.

Relationship of locus of control in women with migraine and healthy volunteers.

Lampl C, Heuberger B, Haas S, Yazdi K, Buzath A, Kemetzhofer P.

Department of Neurology, Pain and Headache Center, General Hospital, Linz,
Austria.

OBJECTIVE: To investigate potential differences in various aspects of personality
in women with migraine with aura, without aura, and in healthy volunteers.
METHODS: The following instruments were used to evaluate a sample of 35 women
with migraine with aura, 35 women with migraine without aura, and 35 healthy
women: Locus of Control and Competence Questionnaire, Health Locus of Control
Questionnaire, Trait scale of the State-Trait Anxiety Inventory, and the
depression scale by von Zerssen. RESULTS: There were no significant differences
in generalized locus of control beliefs among the 3 groups. Migraineurs with aura
were found to score very low on the social locus of control scale. Statistically 
significant differences were found regarding anxiety in migraineurs with aura as 
opposed to migraineurs without aura and healthy control subjects. As for
depression, migraineurs with aura were significantly more likely to indicate
feelings of worthlessness and lack of self-confidence. CONCLUSIONS: Our results
suggest that migraineurs with aura differ from migraineurs without aura and
healthy control subjects in terms of anxiety and depression. With regard to
health-related locus of control, there was no correlation among mean number of
migraine attacks per year, duration of disease, time of last migraine attack, and
number of aura symptoms.

Publication Types: 
    Comparative Study

PMID: 12940809 [PubMed - indexed for MEDLINE]

2502: Headache. 2003 Sep;43(8):867-77.

Confirmation of the distinction between chronic migraine and chronic tension-type
headache by the McGill Pain Questionnaire.

Mongini F, Deregibus A, Raviola F, Mongini T.

Headache and Facial Pain Unit, Department of Clinical Pathophysiology, University
of Turin, Italy.

OBJECTIVE: To investigate if the McGill Pain Questionnaire confirms the
distinction between chronic migraine and chronic tension-type headache.
BACKGROUND: It has been suggested that different categories of chronic daily
headache should be distinguished; in particular, chronic migraine and chronic
tension-type headache. METHODS: The McGill Pain Questionnaire and a visual analog
scale were administered to 40 patients with chronic daily headache, 85 patients
with migraine, and 47 patients with episodic tension-type headache. The patients 
with chronic daily headache were subdivided, according to criteria described by
other authors, into those with chronic migraine (n=29) and those with chronic
tension-type headache (n=11). Weighted McGill Pain Questionnaire item scores,
subscales, total pain rating indexes, and choice frequency of the descriptors
were calculated. The data of chronic migraine and chronic tension-type headache
were compared and tested for significant differences (Student t test). The same
was done for migraine and episodic tension-type headache. Data were also
processed through the Self-organizing Map, a system based on a
counter-propagation neural network. RESULTS: In the chronic migraine group,
compared with the chronic tension-type headache group, scores were higher in 17
of 20 McGill Pain Questionnaire items (significantly in 5) and for the sensory
and affective subscales (significantly). In the migraine group, compared with the
episodic tension-type headache group, scores were higher for 18 McGill Pain
Questionnaire items (significantly in 7), and for the sensory, affective, and
mixed affective-evaluative subscales, total pain-rating index, and visual analog 
scale (all significantly). The coincidence of descriptors of first choice was low
between chronic migraine and chronic tension-type headache, but it was high
between chronic migraine and migraine and between chronic tension-type headache
and episodic tension-type headache. After Self-organizing Map analysis, chronic
migraine and chronic tension-type headache were prevalently distributed in 2
different areas of the map. CONCLUSIONS: In the disorders characterized by a
daily and near-daily headache, the McGill Pain Questionnaire consistently can
discriminate between those evolving from migraine and those evolving from
tension-type headache, indirectly confirming the validity of a distinction
between these 2 clinical conditions. The differences are similar to those
observed between patients with migraine and patients with episodic tension-type
headache. This seems to be independent of the pain level since the difference of 
the total pain-rating index and the visual analog scale between chronic migraine 
and chronic tension-type headache was not statistically significant.

Publication Types: 
    Comparative Study

PMID: 12940808 [PubMed - indexed for MEDLINE]

2503: Headache. 2003 Sep;43(8):861-6.

Comment in:
    Headache. 2004 Jul-Aug;44(7):730-1.

Electrocardiographic changes during migraine attacks.

Aygun D, Altintop L, Doganay Z, Guven H, Baydin A.

Department of Emergency Medicine, Ondokuz Mayis University, Samsun, Turkey.

OBJECTIVES: To clarify whether electrocardiographic (ECG) changes can be
identified during a migraine attack and to determine whether there are ECG
differences between periods with and without headache. BACKGROUND: The clinical
signs and symptoms of migraine point to involvement of the autonomic nervous
system, and especially to disrupted regulation of the circulatory system and
autonomic balance. This disruption may be more marked during a migraine attack.
During a migraine attack, autonomic imbalance within the heart and its vessels
conceivably may result in ECG abnormalities. METHODS: In 30 patients with
migraine, the ECG variables of heart rate, abnormalities of rhythm, PR interval, 
QRS duration, corrected QT interval, T inversion, and ST-segment changes were
recorded during migraine attacks and pain-free periods. RESULTS: Of the 30
patients studied during a migraine attack, 9 (30%) had one or more abnormalities 
of rhythm (including sinus arrhythmia, atrial premature contraction, and
ventricular premature contraction), 20% had PR intervals greater than 0.20
seconds, 40% had corrected QT intervals greater than 0.44 seconds, 66% had T
inversion, and 40% had ST-segment abnormalities. No patient had arrhythmia, PR
intervals greater than 0.20 seconds, or corrected QT intervals greater than 0.44 
seconds during a pain-free period. No differences were noted for ST-segment
changes, T inversion, and total ECG changes between periods with and without
headache, but both PR and corrected QT intervals were significantly longer during
migraine attacks than during pain-free periods. CONCLUSIONS: We conclude that ECG
abnormalities often are present during a migraine attack, and for most of these, 
particularly PR and corrected QT interval lengthening, these abnormalities will
be absent or less prominent during pain-free intervals.

Publication Types: 
    Comparative Study

PMID: 12940807 [PubMed - indexed for MEDLINE]

2504: Headache. 2003 Sep;43(8):845-52.

Effects of naratriptan versus naproxen on daily functioning in the acute
treatment of migraine: a randomized, double-blind, double-dummy, crossover study.

Stronks DL, Tulen JH, Bussmann HB, Mulder LJ, Passchier J.

Department of Medical Psychology, Erasmus MC, Rotterdam, The Netherlands.

OBJECTIVE: To evaluate the effect of acute treatment on ictal behavioral
functioning of patients with migraine via ambulatory accelerometry. BACKGROUND:
The inability to carry out daily activities often complicates migraine attacks.
Research into the effects of pharmacological drugs on this outcome parameter in
the acute treatment of migraine has been based on subjective reports only.
METHODS: In a double-blind, double-dummy, crossover study, 12 patients with
migraine treated 2 migraine attacks with the nonspecific antimigraine drug,
naproxen (500-mg capsule) or the more specific antimigraine drug, naratriptan
(2.5-mg tablet). The clinical symptoms of headache, nausea, vomiting,
photophobia, and phonophobia, and the subjective symptoms reflecting mood,
sleepiness, and level of functioning were measured by use of a daily log.
RESULTS: During the first 6 hours after intake of the study medication, the
objective behavioral parameters showed no significant effect of time and no
significant differences between naproxen and naratriptan, but naratriptan was
significantly more efficacious than naproxen in relieving headache, nausea, and
vomiting; the interval between treatment and relief was significantly shorter
after intake of naratriptan. CONCLUSIONS: Consciously perceived clinical and
subjective symptoms do not necessarily run in parallel with their behavioral
equivalents. It, thus, may be important to assess the effects of treatment on
behavioral functioning in the evaluation of the general efficacy of antimigraine 
drugs in the acute treatment of a migraine attack.

Publication Types: 
    Clinical Trial
    Comparative Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 12940805 [PubMed - indexed for MEDLINE]

2505: Headache. 2003 Sep;43(8):835-44.

Efficacy of a fixed combination of indomethacin, prochlorperazine, and caffeine
versus sumatriptan in acute treatment of multiple migraine attacks: a
multicenter, randomized, crossover trial.

Di Monda V, Nicolodi M, Aloisio A, Del Bianco P, Fonzari M, Grazioli I, Uslenghi 
C, Vecchiet L, Sicuteri F.

Neurology Division I, Spedali Civili di Brescia, Italy.

OBJECTIVE: To compare the efficacy of a fixed combination of indomethacin,
prochlorperazine, and caffeine suppositories with sumatriptan suppositories in
the treatment of 2 consecutive migraine attacks of moderate or severe intensity
in a multicenter, randomized, crossover study. BACKGROUND: A fixed combination of
indomethacin, prochlorperazine, and caffeine is the most commonly used drug for
the acute treatment of migraine in Italy. No studies have been published
comparing the efficacy of this combination with sumatriptan, the most widely
prescribed of the triptans. METHODS: One hundred twelve patients with migraine
with or without aura according to the diagnostic criteria of the International
Headache Society were randomized to treat 2 migraine attacks with a fixed
combination of indomethacin, prochlorperazine, and caffeine and 2 migraine
attacks with sumatriptan. Both drugs were rectally administered in a single dose 
for each attack. Patients were asked to take study medication as soon as possible
at the onset of a headache. RESULTS: Of the 112 patients, 88 were compliant to
the protocol. More attacks became pain-free at 2 hours postdose (primary end
point) on the combination than on sumatriptan (49% versus 34%; P<.01), while
there was no difference in the relief of headache at 2 hours postdose (71% versus
65%). The combination was statistically superior to sumatriptan in the time to a 
pain-free response (a higher percentage of attacks became pain-free from 0.5
hours postdose to 5 hours postdose), in alleviation of nausea, and in a sustained
pain-free response (pain-free at 2 hours postdose with no use of rescue
medication or relapses within 48 hours). Moreover, a significant consistent
response was achieved for the combination compared with sumatriptan across
(higher percentage of patients pain-free at 2 hours postdose in the first,
second, third, and fourth treated attack) and within patients (pain-free in 2 of 
2 treated attacks in 35% of patients taking the combination and 20% of patients
on sumatriptan). Both drugs were well-tolerated. CONCLUSIONS: This study,
analyzed according to the more recent guidelines for controlled trials in
migraine, showed that a fixed combination of indomethacin, prochlorperazine, and 
caffeine is significantly more effective than sumatriptan in the acute treatment 
of migraine attacks. It is notable that the combination is less expensive than
sumatriptan per unit dose.

Publication Types: 
    Clinical Trial
    Comparative Study
    Multicenter Study
    Randomized Controlled Trial

PMID: 12940804 [PubMed - indexed for MEDLINE]

2506: Mayo Clin Proc. 2003 Jun;78(6):770-1.

Sustained-release niacin for prevention of migraine headache.

Velling DA, Dodick DW, Muir JJ.

Division of Pain Management Mayo Clinic, Scottsdale, Ariz 85259, USA.

Considerable advances in the diagnosis and treatment of migraine headache have
occurred during the past decade, but treatment options for acute migraine attacks
have expanded at a faster rate than those for prophylaxis. We describe a patient 
whose migraine headaches responded dramatically to sustained-release niacin as
preventive treatment. Niacin is not generally considered to be effective for
migraine prevention. However, low plasma levels of serotonin have been implicated
in migraine pathogenesis, and niacin may act as a negative feedback regulator on 
the kynurenine pathway to shunt tryptophan into the serotonin pathway, thus
increasing plasma serotonin levels. Sustained-release niacin merits further study
as a potentially useful preventive therapy for migraine headache.

Publication Types: 
    Case Reports

PMID: 12934790 [PubMed - indexed for MEDLINE]

2507: Pain. 2003 Aug;104(3):693-700.

Repeated noxious stimulation of the skin enhances cutaneous pain perception of
migraine patients in-between attacks: clinical evidence for continuous
sub-threshold increase in membrane excitability of central trigeminovascular
neurons.

Weissman-Fogel I, Sprecher E, Granovsky Y, Yarnitsky D.

Department of Neurology, Rambam Medical Center and Technion Faculty of Medicine, 
Haifa, Israel.

Recent clinical studies showed that acute migraine attacks are accompanied by
increased periorbital and bodily skin sensitivity to touch, heat and cold.
Parallel pre-clinical studies showed that the underlying mechanism is
sensitization of primary nociceptors and central trigeminovascular neurons. The
present study investigates the sensory state of neuronal pathways that mediate
skin pain sensation in migraine patients in between attacks. The assessments of
sensory perception included (a) mechanical and thermal pain thresholds of the
periorbital area, electrical pain threshold of forearm skin, (b) pain scores to
phasic supra-threshold stimuli in the same modalities and areas as above, and (c)
temporal summation of pain induced by applying noxious tonic heat pain and brief 
trains of noxious mechanical and electrical pulses to the above skin areas.
Thirty-four pain-free migraine patients and 28 age- and gender-matched controls
were studied. Patients did not differ from controls in their pain thresholds for 
heat (44+/-2.6 vs. 44.6+/-1.9 degrees C), and electrical (4.8+/-1.6 vs. 4.3+/-1.6
mA) stimulation, and in their pain scores for supra-threshold phasic stimuli for 
all modalities. They did, however, differ in their pain threshold for mechanical 
stimulation, just by one von Frey filament (P=0.01) and in their pain scores of
the temporal summation tests. Increased summation of pain was found in
migraineurs for repeated mechanical stimuli (delta visual analog scale (VAS)
+2.32+/-0.73 in patients vs. +0.16+/-0.83 in controls, P=0.05) and repeated
electrical stimuli (delta VAS +3.83+/-1.91 vs -3.79+/-2.31, P=0.01). Increased
summation corresponded with more severe clinical parameters of migraine and
tended to depend on interval since last migraine attack. The absence of
clinically or overt laboratory expressed allodynia suggests that pain pathways
are not sensitized in the pain-free migraine patients. Nevertheless, the
increased temporal summation, and the slight decrease in mechanical pain
thresholds, suggest that central nociceptive neurons do express
activation-dependent plasticity. These findings may point to an important
pathophysiological change in membrane properties of nociceptive neurons of
migraine patients; a change that may hold a key to more effective prophylactic
treatment.

Publication Types: 
    Comparative Study

PMID: 12927642 [PubMed - indexed for MEDLINE]

2508: CNS Drugs. 2003;17(11):839-51.

Tolerability and consistency of effect of zolmitriptan nasal spray in a long-term
migraine treatment trial.

Dowson AJ, Charlesworth BR, Purdy A, Becker WJ, Boes-Hansen S, Färkkilä M.

The King's Headache Services, King's College Hospital, London, UK.
DrAndyDowson@dowsona.fsnet.co.uk

OBJECTIVES: To primarily assess the tolerability of zolmitriptan (Zomig) nasal
spray 5mg in the long-term treatment of migraine, as well as determine efficacy
and consistency of effect over time (up to 1 year). METHODS: This randomised,
double-blind-to-dose, parallel-group, multicentre study was designed as a
two-phase, crossover trial with a total duration of 1 year. In the pre-crossover 
phase, 1,093 patients aged 18-65 years with an established diagnosis of migraine 
with or without aura received intranasal zolmitriptan 5, 2.5, 1 or 0.5mg for the 
treatment of mild, moderate or severe migraine attacks. When a headache persisted
or recurred, a second dose of zolmitriptan nasal spray (or other approved escape 
medication) was permitted 2 hours post-administration but no later than 24 hours 
after the first dose. In the post-crossover phase, once a placebo-controlled,
dose-finding study had established 5mg as the dose with the optimal clinical
utility, all patients were crossed over under blinded conditions to receive this 
dose. As this was primarily a safety study, the primary endpoints for the study
were the incidence and nature of all serious adverse events (at any time before
or after administration) and nonserious adverse events (within 24 hours of
administration), as well as the incidence of clinically significant abnormalities
in either ECG or haematology and clinical chemistry parameters. Nose and throat
examinations were performed before and after the study at 30 predetermined trial 
centres.Other endpoint measures included headache response rate, pain-free
assessments, reduction in headache intensity, time to resumption of normal
activities and consistency of headache response. Efficacy rates were measured in 
90-day intervals up to a period of 360 days. RESULTS: Zolmitriptan nasal spray
5mg was well tolerated, with only 1.9% of patients withdrawing from the 12-month 
long-term trial because of adverse events. Adverse events occurred in 22.1% of
attacks treated with zolmitriptan nasal spray 5mg, and the majority were of short
duration and mild or moderate intensity. Serious adverse events occurred in 0.2% 
of attacks treated with zolmitriptan nasal spray 5mg. There was no evidence of
increased incidence of adverse events with increasing duration of treatment.
Nasopharyngeal adverse events were reported in 5.5% of attacks treated with
zolmitriptan nasal spray 5mg. Again, events were generally transient and of mild 
intensity. For the 1,093 patients who treated 13,806 attacks during the
pre-crossover phase, headache response rates at 2 hours over all attacks were
73.2%, 70.5%, 49.9% and 41.5% for zolmitriptan nasal spray 5, 2.5, 1 and 0.5mg,
respectively. Pain-free rates at 2 hours over all attacks were 51.5%, 48.1%,
24.7% and 21.8%, respectively. For the 783 patients receiving the 5mg dose in
either the pre- or post-crossover phases, the 2-hour headache response rates were
72.9%, 74.4%, 74.6% and 74.1% for the four 90-day periods between day 0 and day
360. Normal activities were resumed within 2 hours in 60.4% of attacks. Long-term
usage of zolmitriptan nasal spray 5mg was also associated with a consistently
effective response, with 57.8% of patients experiencing a 2-hour headache
response in over 75% of attacks. The majority of patients (70.3%) rated their
overall satisfaction with zolmitriptan nasal spray 5mg as good or excellent.
CONCLUSION: Zolmitriptan nasal spray 5mg provides good tolerability and efficacy 
in long-term use in a clinical setting, with consistently high 2-hour headache
and pain-free rates. This combination of benefits translates to high patient
satisfaction with this formulation of zolmitriptan.

Publication Types: 
    Clinical Trial
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 12921494 [PubMed - indexed for MEDLINE]

2509: Int Clin Psychopharmacol. 2003 Sep;18(5):301-3.

Migraine headache prophylaxis and treatment with low-dose mirtazapine.

Lévy E, Margolese HC.

Clinical Psychopharmacology Unit, Allan Memorial Institute, McGill University
Health Centre, 1025 Pine Avenue West, Montreal, Quebec H3A 1A1, Canada.

Other than amitriptyline, few antidepressants have shown consistent efficacy in
migraine treatment prophylaxis. Only one other case supporting the use of
mirtazapine for migraine prophylaxis has been reported. To our knowledge, there
are no reports suggesting dose dependence in mirtazapine effectiveness for
migraine treatment, nor proposals to explain the mechanism of this effect. A
25-year-old patient was followed in our outpatient department for DSM-IV
treatment-resistant recurrent major depression. Multiple antidepressants were
used and discontinued because of migraine exacerbation. Mirtazapine was then
initiated for residual depressive symptoms. Decreased frequency and intensity of 
migraines were observed with low-dose mirtazapine, which reoccurred with higher
doses. Migraine treatment with mirtazapine can be explained through two possible 
mechanisms. First, mirtazapine prevents migraine initiation through histamine and
5-HT(2) receptor family inhibition. Second, it treats migraines through 5-HT(1)
receptor family activation. However, at higher doses, histamine activation may
explain reoccurrence of migraines.

Publication Types: 
    Clinical Trial

PMID: 12920393 [PubMed - indexed for MEDLINE]

2510: Int J Psychophysiol. 2003 Aug;49(2):165-74.

Steady-state visual evoked potentials in the low frequency range in migraine: a
study of habituation and variability phenomena.

de Tommaso M, Stramaglia S, Schoffelen JM, Guido M, Libro G, Losito L,
Sciruicchio V, Sardaro M, Pellicoro M, Puca FM.

Department of Neurological and Psychiatric Sciences, University of Bari, Italy.
m.detommaso@neurol.uniba.it

Previous studies have revealed that migraine patients display an increased photic
driving to flash stimuli in the medium frequency range. The aim of this study was
to perform a topographic analysis of steady-state visual evoked potentials
(SVEPs) in the low frequency range (3-9 Hz), evaluating the temporal behaviour of
the F1 amplitude by investigating habituation and variability phenomena. The main
component of SVEPs, the F1, demonstrated an increased amplitude in several
channels at 3 Hz. Behaviour of F1 amplitude was rather variable over time, and
the wavelet-transform standard deviation was increased in migraine patients at a 
low stimulus rate. The discriminative value of the F1 mean amplitude and
variability index, tested by both an artificial neural network classifier and a
support vector machine, were high according to both methods. The increased photic
driving in migraine should be subtended by a more generic abnormality of visual
reactivity instead of a selective impairment of a visual subsystem. Temporal
behaviour of SVEPs is not influenced by a clear tendency to habituation, but the 
F1 amplitude seemed to change in a complex way, which is better described by
variability phenomena. An increased variability in response to flicker stimuli in
migraine patients could be interpreted as an overactive regulation mechanism,
prone to instability and consequently to headache attacks, whether spontaneous or
triggered.

Publication Types: 
    Comparative Study

PMID: 12919718 [PubMed - indexed for MEDLINE]

2511: Int J Clin Pract. 2003 Jul-Aug;57(6):493-507.

Establishing principles for migraine management in primary care.

Dowson AJ, Sender J, Lipscombe S, Cady RK, Tepper SJ, Smith R, Smith TR, Taylor
FR, Boudreau GP, van Duijn NP, Poole AC, Baos V, Wöber C.

King's Headache Service, King's College Hospital, London, UK.

Published guidelines for the management of migraine in primary care were
evaluated by an international advisory board of headache specialists, to
establish evidence-based principles of migraine management that could be
recommended for international use. Twelve principles of migraine management were 
identified, covering screening, diagnosis, management and treatments: Almost all 
headaches are benign/primary and can be managed by all practising clinicians. Use
questions/a questionnaire to assess the impact on daily living and everyday
activities, for diagnostic screening and to aid management decisions. Share
migraine management between the clinician and the patient. Provide individualised
care for migraine and encourage patients to manage their migraine. Follow up
patients, preferably with migraine calendars or diaries. Regularly re-evaluate
the success of therapy using specific outcome measures and monitor the use of
acute and prophylactic medications regularly. Adapt migraine management to
changes that occur in the illness and its presentation over the years. Provide
acute medication to all migraine patients and recommend it is taken at the
appropriate time, during the attack. Provide rescue medication/symptomatic
treatment for when the initial therapy fails. Offer to prescribe prophylactic
medications, as well as lifestyle changes, to patients who have four or more
migraine attacks per month or who are resistant to acute medications. Consider
concurrent co-morbidities in the choice of appropriate prophylactic medication.
Work with the patient to achieve comfort with mutually agreed upon treatment and 
ensure that it is practical for their lifestyle and headache presentation. Using 
these principles, practising clinicians can screen and diagnose their headache
patients effectively and manage their migraine patients over the long-term
natural history of the migraine process. In this way, the majority of migraine
patients can be well treated in primary care, ensuring a structured and
individualised approach to headache management, and conserving valuable
healthcare resources.

Publication Types: 
    Consensus Development Conference
    Research Support, Non-U.S. Gov't
    Review

PMID: 12918889 [PubMed - indexed for MEDLINE]

2512: Cochrane Database Syst Rev. 2003;(3):CD002915.

Oral sumatriptan for acute migraine.

McCrory DC, Gray RN.

Center for Clinical Health Policy Research, Duke University, 2200 W. Main Street,
Suite 220, Durham, NC 27705, USA.

BACKGROUND: Migraine is a common neurovascular disorder characterized by
recurrent episodes of disabling headache, autonomic nervous system dysfunction,
and, in some patients, neurological aura symptoms. Sumatriptan is one of a class 
of selective serotonin 5-hydroxytryptamine (5-HT1B/1D) agonists (triptans)
thought to relieve migraine attacks by several mechanisms, including cranial
vasoconstriction and peripheral and central neural inhibition. OBJECTIVES: To
describe and assess the evidence from randomized controlled trials (RCTs)
concerning the efficacy and tolerability of oral sumatriptan for the treatment of
a single acute attack of migraine in adults. SEARCH STRATEGY: We searched the
Cochrane Central Register of Controlled Trials (Cochrane Library, Issue 4, 2001),
MEDLINE (1966 through November 2001), and reference lists of articles and books. 
SELECTION CRITERIA: We included double-blind RCTs comparing oral sumatriptan (100
mg, 50 mg, 25 mg) with placebo, no intervention, other drug treatments,
behavioral therapy, or physical therapy for the treatment of an acute attack of
migraine in adults. Trials comparing different doses of sumatriptan or dosing
regimens were also included. Outcomes considered were: 2-hour pain-free response,
headache relief/headache intensity, and functional disability; headache
recurrence; and adverse events. DATA COLLECTION AND ANALYSIS: Data were
abstracted by one reviewer and over-read by the other. The two reviewers
independently assessed trial quality. Information on adverse events was collected
from trial reports. MAIN RESULTS: Twenty-five trials involving 16,200
participants were included. Methodological quality was generally good. Sixteen
trials were placebo comparisons and showed that sumatriptan in doses of 100 mg
(14 trials), 50 mg (five trials), and 25 mg (three trials) provided significantly
better pain-free response (100 mg and 25 mg only), headache relief, and relief of
disability at 2 hours. Numbers-needed-to-treat (NNTs) for pain-free response at 2
hours were 5.1 (3.9 to 7.1) for the 100-mg dose (n = 2221) and 7.5 (2.7 to 142)
for the 25-mg dose (n = 131); there was no significant difference between the
50-mg dose and placebo for this outcome (n = 127). For headache relief at 2
hours, NNTs were 3.4 (3.0 to 4.0), 3.2 (2.4 to 5.1), and 3.4 (2.3 to 6.6) for
sumatriptan 100 mg (n = 2940), 50 mg (n = 420), and 25 mg (n = 226),
respectively. Precise estimates of the efficacy of the 50- and 25-mg doses
relative to the 100-mg dose could not be obtained.Adverse events were more common
with sumatriptan 100 mg than with placebo (risk difference [RD] = 0.14 [0.09 to
0.20]; number-needed-to-harm [NNH] = 7.1 [5.0 to 11.1]; n = 3172). RDs for the
50- and 25-mg vs. placebo comparisons were not statistically significant.
REVIEWER'S CONCLUSIONS: Oral sumatriptan has been shown to be an effective drug
for the treatment of a single acute attack of migraine. It is well tolerated,
though minor adverse events were not uncommon in the included trials. Other
triptans were generally similar in efficacy and adverse events. Among non-triptan
drugs, ergotamine + caffeine was significantly less effective than sumatriptan,
and other drugs have been insufficiently studied to draw firm conclusions.

Publication Types: 
    Meta-Analysis
    Review

PMID: 12917936 [PubMed - indexed for MEDLINE]

2513: Hum Mol Genet. 2003 Oct 1;12(19):2511-7. Epub 2003 Jul 29.

Significant linkage to migraine with aura on chromosome 11q24.

Cader ZM, Noble-Topham S, Dyment DA, Cherny SS, Brown JD, Rice GP, Ebers GC.

Wellcome Trust Centre for Human Genetics, Oxford. UK.

Migraine with aura (MA) is a prevalent neurological condition with strong
evidence for a genetic basis. Familial hemiplegic migraine, a rare Mendelian form
of MA, can be caused by mutations in the calcium channel gene, CACNA1A or in the 
ATP1A2 gene, a Na+/K+ pump. Susceptibility genes for the more prevalent forms of 
migraine have yet to be identified despite several reports of linkage including
loci on 4q24, 1q31, 19p13 and Xq24-28. We have undertaken a genome-wide screen of
43 Canadian families, segregating MA with families chosen for an apparent
autosomal dominant pattern of transmission. Diagnosis was based upon
International Headache Society Criteria. Parametric linkage analysis revealed a
novel locus on 11q24 with a two-point LOD score of 4.2 and a multi-point
parametric LOD score of 5.6. We did not find any support for linkage at
previously reported loci. The lack of consensus amongst linkage studies,
including this study, is probably an indication of the heterogeneity that is
inherent for MA. Nevertheless, the finding of a highly significant locus with a
LOD score of 5.6 is powerful evidence that a gene increasing susceptibility to MA
resides on 11q24. Several candidate genes map to this region of the genome
including a number of ion channel genes such as GRIK4, SCNB2, KCNJ5 and KCNJ1.

PMID: 12915447 [PubMed - indexed for MEDLINE]

2514: Neurology. 2003 Aug 12;61(3):375-82.

A self-administered screener for migraine in primary care: The ID Migraine
validation study.

Lipton RB, Dodick D, Sadovsky R, Kolodner K, Endicott J, Hettiarachchi J,
Harrison W; ID Migraine validation study.

Department of Neurology, Albert Einstein College of Medicine, Bronx, NY 10461,
USA. rlipton@aecom.yu.edu

BACKGROUND: Migraine is a highly prevalent and disabling illness that remains
substantially undiagnosed in primary care. Because of the potential value of a
screening tool, the current study was designed to establish the validity and
reliability of a brief, self-administered migraine screener in patients with
headache complaints in the primary care setting. METHODS: A total of 563 patients
presenting for routine primary care appointments and reporting headaches in the
past 3 months completed a self-administered migraine screener. All patients were 
then referred for an independent diagnostic evaluation by a headache expert, of
whom 451 (80%) completed a full evaluation. Migraine diagnosis was assigned based
on International Headache Society criteria after completing a semi-structured
diagnostic interview. RESULTS: Of nine diagnostic screening questions, a
three-item subset of disability, nausea, and sensitivity to light provided
optimum performance, with a sensitivity of 0.81 (95% CI, 0.77 to 0.85), a
specificity of 0.75 (95% CI, 0.64 to 0.84), and positive predictive value of 0.93
(95% CI, 89.9 to 95.8). Test-retest reliability was good, with a kappa of 0.68
(95% CI, 0.54 to 0.82). The sensitivity and specificity of the three-item
migraine screener was similar regardless of sex, age, presence of other comorbid 
headaches, or previous diagnostic status. CONCLUSIONS: The three-item ID Migraine
migraine screener was found to be a valid and reliable screening instrument for
migraine headaches. Its ease of use and operating characteristics suggest that it
could significantly improve migraine recognition in primary care.

Publication Types: 
    Multicenter Study
    Research Support, Non-U.S. Gov't
    Validation Studies

PMID: 12913201 [PubMed - indexed for MEDLINE]

2515: Funct Neurol. 2003 Apr-Jun;18(2):97-101.

Dizziness and migraine: a causal relationship?

Versino M, Sances G, Anghileri E, Colnaghi S, Albizzati C, Bono G, Cosi V.

Department of Neurological Sciences, University of Pavia, Italy.
mversino@unipv.it

Both migraine and dizziness are very frequent complaints, but the comorbidity of 
the two disorders is higher than it might be expected to be on the basis of
chance alone. This implies a possible causal relationship, but definite
diagnostic criteria for migraine-related vertigo are still lacking. Very recent
attempts in this direction have shown that migraine may be the third leading
cause of vertigo and that migraine-related vertigo may be effectively treated. A 
review of the literature on this topic, which includes some preliminary data of
our own, demonstrates the difficulty in pinpointing migraine-associated vertigo
as a clearly-defined entity. However, there is a measure of agreement on a few
points: the spells of vertigo occur in patients who habitually suffer from motion
sickness, and who have a history of migraine, either without or with aura; the
delay between migraine and vertigo onset may be several years; migraine-related
vertigo may be described as rotatory and/or as a feeling of unsteadiness, and
single spells can occur without any other accompanying symptoms, however, when
spells do occur in association with headache, they usually precede it. The
vertigo duration may be shorter or longer than that of the migraine aura since it
ranges from a few seconds to a continuous condition of unsteadiness.

Publication Types: 
    Review

PMID: 12911141 [PubMed - indexed for MEDLINE]

2516: Expert Opin Drug Saf. 2002 Nov;1(4):331-8.

Medication overuse headaches -- what is new?

Fritsche G, Diener HC.

Department of Neurology, University Essen, Germany.
guenther.fritsche@uni-essen.de

Patients suffering from frequent migraine attacks or chronic tension-type
headache are at risk of developing drug-induced headache (now called 'medication 
overuse headache' [MOH]) as described by the new classification of the
International Headache Society. This headache entity is caused by frequent use of
antiheadache compounds (non-opioid analgesics, ergot alkaloids, 5-HT agonists,
combined preparations with caffeine or codeine) for more than 15 days/month. Most
patients, however, use the medication daily. The standard therapy of MOH is
withdrawal therapy (mostly under in-patient conditions) followed by prophylactic 
treatment of the primary headache. The relapse rate reaches up to 40% within 1
year after a previously successful withdrawal therapy. The pathophysiology of MOH
remains to be determined and, consequently, therapy has been driven by experience
rather than by scientific hypotheses. The identification of predictors for both
medication overuse and relapse after successful withdrawal should improve
prevention and therapy in the future. Several medical (e.g., class of overused
drugs) and psychological (e.g., standard of performance) predictors were recently
identified. Medication overuse in headache patients is based on multiple factors 
with physical, social and psychological impact. In view of the high prevalence
and relapse rate, it is necessary to establish a structured post-treatment
programme for patients after the acute withdrawal phase, which considers the
predictors for relapse.

Publication Types: 
    Review

PMID: 12904133 [PubMed - indexed for MEDLINE]

2517: Expert Opin Drug Saf. 2003 Mar;2(2):123-32.

Safety profile of the triptans.

Tepper SJ, Millson D.

The New England Center for Headache, 778 Long Ridge Rd, Stamford, CT 06902, USA. 
sjtepper@aol.com

The triptans are 5-HT(1B/1D) agonists used as migraine and cluster-specific
agents. Seven are in commercial use worldwide; in order of release these are
sumatriptan, zolmitriptan, rizatriptan, naratriptan, almotriptan, frovatriptan
and eletriptan. Sumatriptan has been in clinical use since 1991, and although
postmarketing studies have stimulated much debate of triptan strengths and
weaknesses, their overall safety profile appears excellent. The most serious
adverse events are cardiovascular, due to coronary artery narrowing as a
consequence of coronary artery 5-HT(1B) receptor activity. Triptans are
contraindicated in patients with vascular disease. Other events are even more
rare, and include the potential for drug-drug interactions, based on metabolic
elimination pathways. Serotonin syndrome has been a concern, but one large
prospective study failed to document a single case, and reports are sporadic and 
not clearly causative.

Publication Types: 
    Comparative Study
    Review

PMID: 12904112 [PubMed - indexed for MEDLINE]

2518: Headache. 2003 Jul-Aug;43(7):774-8.

Prevalence of headache in Puerto Rico.

Miranda H, Ortiz G, Figueroa S, Peña D, Guzmán J.

CEDOC Headache Management Center, San Francisco Hospital, Medical Sciences
Campus, University of Puerto Rico, 365 De Diego Avenue, San Juan, Puerto Rico
00923.

BACKGROUND: Headache is one of the most frequently reported disorders in the
general adult population. Despite the fact that this disorder is common, no
official estimate of the prevalence of headache exists in Puerto Rico. PURPOSE:
To examine the prevalence of headache and migraine, specifically, in Puerto Rico.
METHODS: A telephone survey of 1610 individuals was conducted. The telephone
calls were distributed using the 1990 census adjusted to the population of Puerto
Rico in 1998, and according to gender, geographical area, and age. RESULTS: The
prevalence of headache in Puerto Rico was 35.9% and migraine, in particular,
13.0%. When prevalence was fractionated by age, gender, and geographical areas,
the prevalence of headache was similar for all ages, with females exhibiting a
2:1 preponderance over males. In the younger population (between 20 and 50 years 
of age), the female-male ratio for migraine was 3:1, and the prevalence for
migraine was lower in the Metropolitan area. CONCLUSION: This study, the first of
its type in Puerto Rico, demonstrates that headache (and migraine specifically)
is a common disorder in this country.

PMID: 12890132 [PubMed - indexed for MEDLINE]

2519: Headache. 2003 Jul-Aug;43(7):767-73.

Use of the Migraine Disability Assessment Questionnaire in children and
adolescents with headache: an Italian pilot study.

D'Amico D, Grazzi L, Usai S, Andrasik F, Leone M, Rigamonti A, Bussone G.

Headache Center, C. Besta National Neurological Institute, Via Celoria 11, 20133 
Milan, Italy.

OBJECTIVES: To determine the suitability of the Migraine Disability Assessment
(MIDAS) Questionnaire for assessing disability in children and adolescents with
headache and to obtain preliminary information about disability in different
primary headaches. BACKGROUND: During the last decade, researchers have begun to 
employ standardized methodologies to investigate the global impact of primary
headaches. Disease-specific instruments have been developed to measure
headache-related disability. The MIDAS Questionnaire, which is the most
extensively studied of these instruments, was designed to assess the overall
impact of headaches over the 3 months before compilation. The MIDAS Questionnaire
is an optimal tool to assess headache-related disability in adults. METHODS:
Ninety-five patients aged 7 to 17 years with tension-type headache, migraine, or 
both completed the validated Italian form of the MIDAS questionnaire on 2
occasions. Test-retest reliability was assessed by the Spearman rank correlation 
test. The Cronbach alpha assessed internal consistency. The patients answered
questions about the adequacy of the questionnaire. RESULTS: The Cronbach alpha
was.8. Correlation coefficients were generally high for the overall MIDAS score
and for the items investigating disability in school and in family/leisure
activities; they were lower for the items about housework. Most patients thought 
that the MIDAS Questionnaire was useful (98.9%) and that it captured the impact
of their headaches (58.9%); 41% thought that questions about disability in
housework were useless, 44.2% suggested adding questions regarding inability to
do homework. All primary headaches had a considerable impact on daily activities,
but patients with migraine tended to have lower headache frequencies and lower
total disability time; those with tension-type headache suffered more days in
which activities, although performed, were substantially impaired. CONCLUSIONS:
The MIDAS Questionnaire is useful for assessing disability in children and
adolescents with different primary headaches. Minimal changes in the phrasing and
content of the items would be sufficient to render the MIDAS specific for the
younger population with headache.

Publication Types: 
    Evaluation Studies

PMID: 12890131 [PubMed - indexed for MEDLINE]

2520: Headache. 2003 Jul-Aug;43(7):742-54.

Burden of migraine in Brazil: estimate of cost of migraine to the public health
system and an analytical study of the cost-effectiveness of a stratified model of
care.

Bigal ME, Rapoport AM, Bordini CA, Tepper SJ, Sheftell FD, Speciali JG.

Department of Neurology, Albert Einstein College of Medicine, Bronx, NY, USA.

BACKGROUND: The search for rationality in health expenses in developing countries
collides with the lack of effectively conducted epidemiologic studies. PURPOSE:
To present an estimate of the impact and costs of migraine in the Brazilian
public health system and to estimate the impact on these costs and the
effectiveness of a model of stratified care in the management of migraine.
METHODS: An analytical model of utilization of the Brazilian public health system
was constructed. Data refer to 1999 and were obtained in accordance with the
following steps: (1) Brazilian demographic characteristics; (2) characteristics
of the public health system related to its 3 hierarchical levels-primary,
secondary, and tertiary care, the last being subdivided into emergency department
and hospital care; and (3) estimation of the number of migraine consultations at 
each complexity level. In Brazil, migraineurs seen in the public health system
are most often discharged with an acute treatment, usually a nonspecific
medication. We compared this treatment with a proposed stratified care model that
uses a triptan as an acute care medication. We have made the following
assumptions: (1) 15% of the patients would fall into the Migraine Disability
Assessment (MIDAS) grade I category, 25% would fall into the MIDAS grade II
category, 30% into the grade III category, and 30% into the MIDAS grade IV
category; (2) the mean number of migraine attacks per year are: MIDAS I, 7.49;
MIDAS II, 8.02; MIDAS III, 12.22; and MIDAS IV, 27.01. The annual costs of the
treatment were calculated according to the following equation: AC = P x N x C + P
x Cp + P x Cat x AMA, where P is the number of patients; N, the number of
consultations per patient; C, the cost of consultation per level; Cp, the cost of
preventive drugs; Cat, the cost of acute therapy drugs; and AMA is the number of 
migraine attacks per year. Results.-The public health system resources included
55 735 ambulatory units (primary and secondary) and 6453 emergency department and
public hospital units, with a corresponding budget of US $2 820 899 621.26. The
estimated cost of a consultation on the primary care level was US $11.53; on the 
secondary care level, US $22.18; in the emergency department, $34.82; and for
hospitalization, US $217.93. The total estimated public health system expenses
for migraine were US $140 388 469.60. The proposed model would imply a cost
reduction of 6.2% (US $7 514 604.40) with an improvement in the quality of the
public health system from the actual 18.2% to an estimated 84.5%. CONCLUSION:
Migraine seems to pose a huge burden on the Brazilian public health system. The
implementation of a stratified care model of treatment that would include
specific acute migraine therapies could result in a dramatic increase in the
quality of migraine care and a significant reduction in cost.

Publication Types: 
    Comparative Study

PMID: 12890129 [PubMed - indexed for MEDLINE]

2521: Headache. 2003 Jul-Aug;43(7):734-41.

Comment in:
    Headache. 2004 Feb;44(2):191-2.

Almotriptan versus rizatriptan in patients with migraine in Spain.

Leira R, Dualde E, del Barrio H, Machuca M, López-Gil A; Spanish Group for the
Study of Triptan Consumption in Community Pharmacies.

Servicio de Neurologia, Hospital Clínico Universitario, Santiago de Compostela,
La Coruña, Spain.

OBJECTIVES: To compare patient-reported use of rizatriptan 10 mg with that of
almotriptan 12.5 mg per migraine attack (24 hours) in a Spanish population.
METHODS: One hundred twenty Spanish community pharmacies recruited patients with 
migraine to whom they had dispensed almotriptan and rizatriptan. No other
selection criteria were used. Patients kept diaries for baseline pain intensity, 
the number of triptan tablets used, additional medication taken per attack, and
their degree of satisfaction with the medication 2 hours after the initial dose. 
Patients recorded details for a maximum of 3 attacks. Analysis of variance or the
Student t test and chi-squared or Fisher exact tests were used for univariate
comparisons. A generalized estimating equation method was used to correct for
within-subject variability. Adjusted odds ratios (ORs) and 95% confidence
intervals (CIs) were calculated. RESULTS: One hundred twenty-six patients (85%
women) recorded data for 318 migraine attacks. Rizatriptan was used to treat 122 
attacks, almotriptan was used to treat 110 attacks, and a nontriptan medication
was used in the initial treatment of 86 attacks. Triptan use (adjusted mean, 95% 
CI) per attack in this study was lower for rizatriptan (1.19 tablets; 95% CI,
1.06 to 1.32) than for almotriptan (1.43 tablets; 95% CI, 1.30 to 1.56; P=.003). 
The use of a triptan and additional medication per attack increased with baseline
pain severity. Rizatriptan was used to treat more attacks with only one tablet
(78%) than almotriptan (58%). Treatment of attacks with almotriptan was more than
twice as likely to involve the use of more than one tablet per attack (24 hours) 
than those treated with rizatriptan (adjusted OR, 2.42; 95% CI, 1.37 to 4.30;
P=.003). Patient satisfaction with treatment response at 2 hours was more than
2-fold greater for rizatriptan (85%) than for almotriptan (68%) (adjusted OR,
2.55; 95% CI, 1.11 to 5.87; P=.03). CONCLUSIONS: In this prescription-selected
Spanish population, a significantly lower number of rizatriptan tablets were
required to treat migraine attacks compared with almotriptan. Further, patients
were more than twice as likely to use more than one tablet or additional
medication (or both) for attacks treated with almotriptan than for those treated 
with rizatriptan. Although these data suggest that rizatriptan may be a more
effective treatment for migraine than almotriptan, further randomized studies are
required to confirm this conclusion.

Publication Types: 
    Comparative Study

PMID: 12890128 [PubMed - indexed for MEDLINE]

2522: Headache. 2003 Jul-Aug;43(7):729-33.

Comment in:
    Headache. 2004 May;44(5):446-7.

Sumatriptan plus metoclopramide in triptan-nonresponsive migraineurs.

Schulman EA, Dermott KF.

Center for Headache Management, Ambulatory Care Pavilion, Suite 533, One Medical 
Center Boulevard, Upland, PA 19013, USA.

OBJECTIVES: We evaluated the effectiveness of combination treatment using
sumatriptan plus metoclopramide versus sumatriptan alone for the treatment of
acute migraine. The patients who were treated had failed to respond to triptans
in the past despite adequate doses on at least 2 separate trials of the same
triptan or 2 trials involving different triptans. BACKGROUND: There is limited
evidence that dopaminergic antagonists may benefit the migraineur by relieving
migraine pain and associated symptoms. The exact mechanism of action in migraine 
is unknown. The postulated action is the inhibition of dopaminergic overactivity.
A dopaminergic antagonist, metoclopramide, may improve the efficacy of a
5-HT1B/1D agonist, sumatriptan. METHODS: In this double-blind, randomized,
crossover study, 16 adult migraineurs fulfilling International Headache Society
(IHS) criteria for migraine with or without aura who had failed to receive
adequate relief from triptans treated one migraine with each treatment:
sumatriptan 50 mg plus metoclopramide 10 mg or sumatriptan 50 mg plus placebo to 
match metoclopramide. Patients treated their migraines when they were moderate or
severe in intensity and recorded pain severity and symptoms prior to treatment
and 30, 60, 90, and 120 minutes and 24 hours after treatment. RESULTS: Thirteen
women and 3 men (mean age, 40 years) completed the study; ie, treated 2 migraines
(a total of 32 migraines), one attack with each treatment. Meaningful relief was 
attained in 10 (63%) of 16 migraines treated with the combination of sumatriptan 
50 mg plus metoclopramide 10 mg compared with 5 (31%) of 16 migraines treated
with sumatriptan 50 mg plus placebo. Headache response (moderate or severe to
mild or no pain at 2 hours) was achieved in 7 (44%) of 16 migraines with the
combination of sumatriptan 50 mg plus metoclopramide 10 mg compared with 5 (31%) 
of 16 migraines treated with sumatriptan 50 mg plus placebo. There did not appear
to be a difference between treatment groups with respect to associated symptoms. 
The combination of sumatriptan 50 mg plus metoclopramide 10 mg was well
tolerated. CONCLUSIONS: Combining sumatriptan with metoclopramide provided relief
in some migraineurs who failed to achieve adequate relief with a triptan alone.
It remains unknown whether initiating therapy when pain was mild or using a
higher dose of sumatriptan (ie, 100 mg) would have provided additional benefit.
Further studies are indicated.

Publication Types: 
    Clinical Trial
    Comparative Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 12890127 [PubMed - indexed for MEDLINE]

2523: Headache. 2003 Jul-Aug;43(7):725-8.

Prevalence of atrial septal aneurysm in patients with migraine: an
echocardiographic study.

Carerj S, Narbone MC, Zito C, Serra S, Coglitore S, Pugliatti P, Luzza F, Arrigo 
F, Oreto G.

Department of Cardiology, University of Messina, Via Campo delle Vettovaglie 10, 
98122 Messina, Italy.

OBJECTIVE: To evaluate the prevalence of atrial septal aneurysm in patients with 
migraine. BACKGROUND: Migraine has long been considered a risk factor for stroke.
Atrial septal aneurysm is often observed in young patients with ischemic stroke
and is frequently associated with other conditions potentially leading to
embolism. METHODS: We performed a transthoracic echocardiogram in 90 consecutive 
patients (65 women and 25 men; mean age, 35.3 years [standard deviation, 9]) with
migraine but free from cerebral and cardiovascular disease and in 53 control
subjects (37 women and 16 men; mean age, 34 years [standard deviation, 10]). The 
diagnosis of atrial septal aneurysm was performed according to Olivares-Reyes
criteria. A transesophageal echocardiogram also was performed in 75 patients with
migraine (83.3%). RESULTS: The prevalence of isolated atrial septal aneurysm was 
higher in patients with migraine with aura (28.5%) than in patients with migraine
without aura (3.6%) (P <.005) or in control subjects (1.9%) (P <.005).
CONCLUSIONS: Our data suggest a role of atrial septal aneurysm in the genesis of 
aura in patients with migraine.

PMID: 12890126 [PubMed - indexed for MEDLINE]

2524: Headache. 2003 Jul-Aug;43(7):715-24.

Headache management program improves outcome for chronic headache.

Harpole LH, Samsa GP, Jurgelski AE, Shipley JL, Bernstein A, Matchar DB.

Department of Medicine, Center for Clinical Health Policy Research, Duke
University Medical Center, First Union Tower, Suite 220, 2200 West Main Street,
Durham, NC 27705, USA.

OBJECTIVE: To determine the feasibility of developing a headache management
program and to assess the outcomes of patients referred to the program for
treatment of chronic headache. BACKGROUND: Effective headache treatment requires 
that the patient receives the correct headache diagnosis; that appropriate acute 
and, if indicated, preventive medications be prescribed; and that the patient
receives adequate education, including headache self-management skills.
DESIGN/METHODS: A headache management program was established at a northern
California staff-model health maintenance organization. Fifty-four patients were 
enrolled in the program and followed for 6 months. Patients participated in a
structured program of group and individual sessions with the program manager.
Data collection at baseline and 6 months included the Migraine Disability
Assessment (MIDAS), the Short Form-36 Health Survey (SF-36), a patient
satisfaction survey, and 2 additional short surveys--one that assessed patient
worries about their headaches and another that queried patients on their problems
with headache management. RESULTS: All enrolled patients participated in the
initial group visit; 74% had at least one additional visit. All but one patient
suffered from more than one headache type. Sixty-one percent of patients suffered
from migraine headache and 98% from tension-type headache. At baseline, patients 
were severely disabled, with a mean MIDAS score of 41. At 6 months, MIDAS scores 
decreased an average of 21.2 points (P <.005). Patients reported 14.5 fewer days 
with headache over the preceding 3 months (P <.0001) and experienced clinically
significant improvements in 6 of the SF-36 subscales. Patients were significantly
more satisfied with their headache care (P <.0001), reported less problems with
their headache management (P <.0001), and were less worried about their headaches
(P <.01). During the intervention, emergency department visits for headache
decreased (P <.02). CONCLUSIONS: A headache management program was successfully
established. Patients referred to the program experienced significant improvement
in headache-related disability and functional health status and reported greater 
satisfaction with care. Even so, these results were obtained at one site and in a
small sample that was not randomized. We currently are conducting a randomized
controlled trial to better evaluate the clinical and financial impact of a
headache management program for patients with chronic headache.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 12890125 [PubMed - indexed for MEDLINE]

2525: Headache. 2003 Jul-Aug;43(7):704-14.

Comment in:
    Headache. 2004 May;44(5):447.

2003 Wolff Award: Possible parasympathetic contributions to peripheral and
central sensitization during migraine.

Yarnitsky D, Goor-Aryeh I, Bajwa ZH, Ransil BI, Cutrer FM, Sottile A, Burstein R.

Departments of Anesthesia and Critical Care, Beth Israel Deaconess Medical
Center, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115, USA.

BACKGROUND: Neurologic signs of increased parasympathetic outflow to the head
often accompany migraine attacks. Because increased parasympathetic outflow to
the cranial cavity induces vasodilation of cerebral and meningeal blood vessels, 
it can enhance plasma protein extravasation and the release of proinflammatory
mediators that activate perivascular nociceptors. We recently showed that
activation of intracranial perivascular nociceptors induces peripheral and
central sensitization along the trigeminovascular pathway and proposed that these
sensitizations mediate the intracranial hypersensitivity and the cutaneous
allodynia of migraine. METHODS: The present study investigates possible
parasympathetic contributions to the generation of peripheral and central
sensitization during migraine by applying intranasal lidocaine to reduce cranial 
parasympathetic outflow through the sphenopalatine ganglion. RESULTS: In the
absence of migraine, patients were pain-free, and their skin sensitivity was
normal. Their mean baseline pain thresholds were less than 15 degrees C for cold,
more than 45 degrees C for heat, and more than 100 g for mechanical pressure.
Their mean pain score was 7.5 of 10 (standard deviation, 1.4) during untreated
migraine and 3.5 of 10 (standard deviation, 2.4) after the nasal
lidocaine-induced sphenopalatine ganglion block (P <.0001). Most patients
developed cutaneous allodynia during migraine, and their mean pain thresholds
changed to more than 25 degrees C for cold, less than 40 degrees C for heat, and 
less than 10 g for mechanical pressure. Following the nasal lidocaine
administration (sphenopalatine ganglion block), this allodynia remained unchanged
in spite of the pain relief. CONCLUSION: These findings suggest that cranial
parasympathetic outflow contributes to migraine pain by activating or sensitizing
(or both) intracranial nociceptors, and that these events induce
parasympathetically independent allodynia by sensitizing the central nociceptive 
neurons in the spinal trigeminal nucleus.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 12890124 [PubMed - indexed for MEDLINE]

2526: Headache. 2003 Jul-Aug;43 Suppl 1:S25-33.

Botulinum neurotoxin for the treatment of migraine and other primary headache
disorders: from bench to bedside.

Dodick DW.

Department of Neurology, Mayo Clinic, Scottsdale, AZ 85259, USA

Botulinum toxin type A, a neurotoxin, is effective for treating a variety of
disorders of involuntary muscle contraction including cervical dystonia,
blepharospasm, and hemifacial spasm. It inhibits neuromuscular signaling by
blocking the release of acetylcholine at the neuromuscular junction. The
biological effects of the toxin are transient, with normal neuronal signaling
returning within approximately 3 to 6 months postinjection. Recent clinical
findings suggest that botulinum toxin type A may inhibit pain associated with
migraine and other types of headache. However, the mechanism by which this toxin 
inhibits pain is not fully understood and is under investigation. Research
findings suggest that botulinum toxin type A inhibits the release of
neurotransmitters from nociceptive nerve terminals and, in this way, may possess 
an analgesic effect. A number of retrospective open-label chart reviews and 3
double-blind, placebo-controlled trials have demonstrated that localized
injections of botulinum toxin type A significantly reduce the frequency,
severity, and disability associated with migraine headaches. Although the
majority of patients in these studies experienced no botulinum toxin type
A-mediated side effects, a small percentage of patients did report transient
minor side effects including blepharoptosis, diplopia, and injection-site
weakness. Currently, 4 randomized, placebo-controlled, clinical trials are being 
conducted to evaluate the efficacy, optimal dosing, and side-effect profile of
botulinum toxin type A as a novel treatment for migraine and other types of
headache. These studies may provide further evidence that botulinum toxin type A 
is an effective option for the preventive treatment of migraine.

Publication Types: 
    Review

PMID: 12887391 [PubMed - indexed for MEDLINE]

2527: Headache. 2003 Jul-Aug;43 Suppl 1:S2-8.

Neurotoxins in the neurobiology of pain.

Silberstein SD.

Jefferson Headache Center, Thomas Jefferson University Hospital, Philadelphia, PA
19107, USA.

Migraine is a common, chronic, incapacitating, neurovascular disorder that
affects an estimated 12% of the population. Understanding the basic mechanisms of
pain is important when treating patients with chronic pain disorders. Pain, an
unpleasant sensory and emotional experience, is usually triggered by stimulation 
of peripheral nerves and often associated with actual or potential tissue damage.
Peripheral nerve fibers transmit pain signals from the periphery toward the
spinal cord or brain stem. The different diameter pain fibers (A and C) vary in
the speed of conduction and the type of pain transmitted (eg, sharp versus dull).
When stimulated, peripheral pain fibers carrying sensory input from the body
enter at different layers of the dorsal horn, which is then propagated toward the
thalamus via the spinothalamic tract within the spinal cord. Conversely, sensory 
input from the face does not enter the spinal cord but enters the brain stem via 
the trigeminal nerve. This review describes in detail the neurobiological
mechanisms and pathways for pain sensation, with a focus on migraine pain.

Publication Types: 
    Review

PMID: 12887388 [PubMed - indexed for MEDLINE]

2528: Indian Pediatr. 2003 Jul;40(7):665-9.

Prevalence and characteristics of migraine among adolescents: a questionnaire
survey.

Shivpuri D, Rajesh MS, Jain D.

Department of Pediatric Medicine, S.M.S. Medical College and Sir Padampat Mother 
Child Health Institute, Jaipur, India. dshivpuri@yahoo.com

A screening questionnaire was distributed to 1000 boys and 1000 girls, studying
in classes VI to X (11 to 15 years) in two public schools of Jaipur.
Questionnaire A consisted of a single question to parents. "Does your child
suffer from recurrent headache?" To those who responded in the affirmative, a
detailed questionnaire (B) was distributed Questionnaire B consisted of twenty
questions pertaining to characteristics and associations of headache. From
questionnaire B a diagnosis of common migraine was made according to IHS criteria
(1988). The prevalence of recurrent headache was found to be 18% in boys and 21% 
in girls, while the prevalence of migraine was 9% in boys and 14% in girls. Among
the other causes of recurrent headache tension type headache was seen in 3.6%,
eye problems in 0.389% sinusitis in 0.22%, and undetermined etiology in 2.14%
children. The clinical characteristics of migraine are described.

PMID: 12881624 [PubMed - indexed for MEDLINE]

2529: J Neurol Neurosurg Psychiatry. 2003 Aug;74(8):1128-30.

Genetic loading in familial migraine with aura.

Noble-Topham SE, Cader MZ, Dyment DA, Rice GP, Brown JD, Ebers GC.

Lawson Health Research Institute, London Health Sciences Centre, London, Ontario,
Canada.

Migraine with aura (MA) arises from a combination of genetic and environmental
factors. The sibling risk, age at onset, and aura type were compared in 54 MA
probands categorised by family history of MA. Three family types were ascertained
each having an MA proband and: (1) an MA parent and MA offspring (three
generation; n=15), (2) either an MA parent or an MA offspring (two generation;
n=20), and (3) neither an MA parent nor an MA offspring (one generation; n=19).
The crude recurrence risk to siblings of probands was 2.7-fold higher in three
generation compared with two generation MA families (chi(2)=6.24, p=0.0125) and
4.8-fold higher in three generation compared with one generation MA families
(chi(2)=9.95, p<0.002). The mean age at onset decreased with an increase in
genetic load. The MA probands from three generation families were significantly
younger than probands from the one generation families (F=5.14, p=0.030). MA
probands from three generation families were more likely to report more than one 
type of aura than MA probands from two generation families (chi(2)=4.44,
p=0.035). The significant difference in genetic loading and the earlier age at
onset in the three generation families add further evidence for a genetic basis
for MA and the difference in sibling risks demonstrates that the MA population is
heterogeneous.

PMID: 12876251 [PubMed - indexed for MEDLINE]

2530: J Neurol Sci. 2003 Sep 15;213(1-2):7-10.

Investigation of an LDLR gene polymorphism (19p13.2) in susceptibility to
migraine without aura.

Mochi M, Cevoli S, Cortelli P, Pierangeli G, Scapoli C, Soriani S, Montagna P.

Department of Neurological Sciences, University of Bologna Medical School,
Bologna, Clinica Neurologica, Via U. Foscolo 7, 40123 Bologna, Italy.
genetica@neuro.unibo.it

We performed a genetic association study with the LDL receptor gene (LDLR) on
chromosome 19p13.2 in 360 migraine patients, 220 with migraine without aura (MO) 
and 140 with migraine with aura (MA), and 200 controls, by analysing two
polymorphic markers, a G142A transition in exon 10 and a triallelic (TA)n repeat 
in exon 18. The allelic distribution of the (TA)n polymorphism was significantly 
different between migraine without aura (MO) and both controls and migraine with 
aura (MA). We suggest a possible predisposition to MO in the studied population
through this polymorphism or another polymorphism in linkage disequilibrium with 
(TA)n.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 12873747 [PubMed - indexed for MEDLINE]

2531: Neuroendocrinology. 2003 Jul;78(1):52-60.

Neuroendocrine response to the serotonin agonist M-chlorophenylpiperazine in
women with menstrual status migrainosus.

Nappi RE, Sances G, Brundu B, Ghiotto N, Detaddei S, Biancardi C, Polatti F,
Nappi G.

Department of Obstetric and Gynecology, IRCCS San Matteo, Pavia, Italy.
renappi@tin.it

To assess the neuroendocrine correlates of menstrual status migrainosus (MSM) and
menstrual migraine (MM), we evaluated the prolactin (PRL) and cortisol responses 
to the direct central serotoninergic (5-HT) agonist meta-chlorophenylpiperazine
(m-CPP) administered orally (0.5 mg/kg) during the follicular (FP: +6, +8) and
luteal phases (LP: -4, -6) of the same menstrual cycle. Ten women with MSM
(migraine attacks occurring within 2 days of the onset of menstrual bleeding but 
lasting more than 72 h) and 9 women with MM (migraine occurring within 2 days of 
the onset of menstrual bleeding with a typical duration of attacks) were studied.
Six healthy women served as controls. Blood samples were taken at times -30, 0
and every 30 min over 4 h. Statistical analysis was performed using MANOVA
followed by Duncan's post hoc comparisons. We found that the PRL response to the 
m-CPP test was significantly blunted in MSM compared with MM and controls in both
phases of the menstrual cycle (F = 4.6; p < 0.001). Indeed, the PRL area under
the curve (AUC) after m-CPP was higher in both MM and controls compared with MSM 
(F = 12.7; p < 0.001). The m-CPP-induced cortisol response was absent in MSM
compared with MM and controls in both FP and LP (F = 4.1; p < 0.001). On the
other hand, the pattern of the plasma cortisol response to m-CPP was similar in
MM and controls throughout the menstrual cycle. In addition, the basal plasma
cortisol levels were significantly higher in MSM compared with controls (p <
0.001) and MM (p < 0.001) during FP, but not in LP, and progressively decreased
over time. Thus, no significant effect of the menstrual cycle phase and diagnosis
on the cortisol AUC was found, while a significant diagnosis effect (F = 25.6; p 
< 0.001) on %delta(max) plasma cortisol levels was evident and consistent with
the lack of cortisol response to m-CPP in MSM during the FP and LP compared with 
MM and controls. A derangement in central 5-HT control of pituitary PRL, and even
more so in cortisol release, is present in women with MSM, but not with MM,
regardless of the phase of the menstrual cycle, suggesting the involvement of
some 5-HT(1) and 5-HT(2) receptor subtypes in the occurrence of extremely severe 
migraine attacks triggered by menstruation. Copyright 2003 S. Karger AG, Basel

Publication Types: 
    Clinical Trial
    Research Support, Non-U.S. Gov't

PMID: 12869800 [PubMed - indexed for MEDLINE]

2532: Neurologist. 2003 Jul;9(4):207-13.

Management of menstrual migraine.

Mannix LK.

LKMannixMD@aol.com

BACKGROUND: Migraine is more prevalent in women than men. Hormonal changes can
influence the occurrence of migraine, particularly related to the menstrual
cycle. Menstrual migraine may require both acute and preventive treatment. REVIEW
SUMMARY: Gender differences in migraine may be a result of variations in the
central nervous system of men and women as well as the effects of estrogen.
Migraine attacks occurring in the perimenstrual period respond well to acute
treatment with triptans. Hormonal manipulation may reduce migraine occurrence,
especially when related to hormonal fluctuations in the perimenstrual period.
CONCLUSIONS: Effective migraine management requires an understanding of the
unique epidemiologic and pathophysiological factors affecting women. An
understanding of associated hormonal influences facilitates development of
individualized treatment plans.

Publication Types: 
    Review

PMID: 12864931 [PubMed - indexed for MEDLINE]

2533: Headache. 2003 Jan;43(1):76-8.

Comment in:
    Headache. 2003 Jul-Aug;43(7):821-2; author reply 822-3.

Safety of a patented special butterbur root extract for migraine prevention.

Danesch U, Rittinghausen R.

Weber and Weber, Inning, Germany.

OBJECTIVE: To report on the safety of a patented special butterbur root extract
used for migraine prevention. BACKGROUND: Two placebo-controlled clinical trials 
have been conducted supporting the beneficial use in humans. METHODS: Results
from acute, subchronic and chronic animal toxicity studies as well as from
mutagenicity studies are reported. Safety data gained from clinical trials,
postmarketing surveillance studies and pharmacovigilance are evaluated and
discussed. CONCLUSION: The patented special butterbur root extract is safe for
the treatment in humans.

Publication Types: 
    Clinical Trial
    Controlled Clinical Trial

PMID: 12864764 [PubMed - indexed for MEDLINE]

2534: Headache. 2003 Jan;43(1):72-5.

Prolonged cortical electrical depression and diffuse vasospasm without ischemia
in a case of severe hemiplegic migraine during pregnancy.

Gonzalez-Alegre P, Tippin J.

Department of Neurology, University of Iowa College of Medicine, Iowa City, IA
52242, USA.

The pathophysiology of the neurological deficits in hemiplegic migraine remains
unclear. Both neurogenic and vascular etiologies have been proposed to explain
this phenomenon. We present the case of a patient with hemiplegic migraine in
whom there was no diffusion weighted magnetic resonance imaging evidence of
cerebral ischemia, despite persistent left hemiplegia and diffuse vasospasm on
cerebral angiography, there was no diffusion weighted magnetic resonance imaging 
evidence of cerebral ischemia. In addition, hypoperfusional changes were seen
diffusely, more so on the less symptomatic hemisphere, whereas depression of
cortical electrical activity was seen for several days on the right side. These
findings support the notion that although both neurogenic and vascular changes
occur in hemiplegic migraine, the former seems to be a more likely explanation
for the neurological deficits.

Publication Types: 
    Case Reports

PMID: 12864763 [PubMed - indexed for MEDLINE]

2535: Headache. 2003 Jan;43(1):69-71.

Dysphonia associated with carotidynia and migraine responding to
dihydroergotamine.

White JR, Bell WL.

MINCEP Epilepsy Care, Minneapolis, MN, USA.

Carotidynia is characterized by throbbing pain over the carotid artery and may be
caused by migraine. We report a case of a 54-year-old woman with recurrent
dysphonia associated with carotidynia and other features of atypical migraine
that resolved after treatment with dihydroergotamine. To our knowledge, this is
the first report of dysphonia associated with migraine.

Publication Types: 
    Case Reports

PMID: 12864762 [PubMed - indexed for MEDLINE]

2536: Headache. 2003 Jan;43(1):54-8.

Transcranial Doppler in migraine attacks before and after treatment with oral
zolmitriptan or sumatriptan.

Thomaides T, Karagounakis D, Spantideas A, Katelanis S.

Neurology Department of Konstandopoulion Complex of Agia Olga General Hospital of
Athens, Greece.

BACKGROUND: Intracranial blood flow velocity (BFV) changes in migraine have been 
studied fairly extensively. Although a number of investigations have been
performed in migraineurs with nitroglycerin-induced attacks, there has been no
reported transcranial study involving such attack treated with zolmitriptan or
sumatriptan. METHODS: With ultrasound, we studied the BFV and pulsatility index
(PI) changes in the middle cerebral artery in 45 symptom free, otherwise healthy,
unmedicated patients with migraine without aura, and in 15 age- and sex-matched
controls before nitroglycerin, at the time of maximum head pain induced by
nitroglycerin and every 30 minutes for 2 hours after zolmitriptan (15 subjects)
or sumatriptan (15 subjects) administration. Headache was rated on a 4-point
scale. RESULTS: During headache attacks, BFV decreased significantly (36.7+/-3.3,
38.4+/-3.4, and 37.4+/-4 cm/sec, respectively, in the zolmitriptan, sumatriptan, 
and nontreated migraine groups, but not in the controls who were migraine free (P
<.01). These abnormalities disappeared 1 hour after zolmitriptan or sumatriptan
administration (49.7+/-3.7 and 48.9+/-3.9 cm/sec, respectively). There were no
significant changes in PI. CONCLUSION: Our data indicate that
nitroglycerin-induced headache in individuals with migraine without aura is
associated with BFV changes that are reversed by administration of an oral
triptan.

Publication Types: 
    Comparative Study

PMID: 12864759 [PubMed - indexed for MEDLINE]

2537: Headache. 2003 Jan;43(1):44-8.

Erratum in:
    Headache. 2003 Jul-Aug;43(7):833.

Comment in:
    Headache. 2003 Jul-Aug;43(7):816-8; author reply 818-9.

Coprescription of triptans with potentially interacting medications: a cohort
study involving 240,268 patients.

Tepper S, Allen C, Sanders D, Greene A, Boccuzzi S.

New England Center for Headache, Stamford, CT, USA.

BACKGROUND: Little information exists about the actual prescription of triptans
within large, geographically diverse populations, in terms of demographic
characteristics and co-prescriptions with other medications with potential
interactions. OBJECTIVES: To investigate the demographic characteristics
associated with triptan use, and examine the rate of co-prescription of triptans 
with specified pharmacologic agents with the potential for drug interactions.
METHODS: This study examined the rate of co-prescription of triptans available in
the US up to May 2001 (sumatriptan, naratriptan, rizatriptan, and zolmitriptan)
with specified agents with potential for drug interactions. A cohort of 240,268
patients receiving pharmacy benefits from Merck-Medco (N = 65 + M) was followed
over a one-year period. This analysis included patients who received at least two
triptan prescriptions during the study (6/00-5/01). Ninety-one percent of the
cohort remained on the same triptan during the study period. 'Co-prescription'
was defined as any fill for a medication that was contraindicated or could
potentially adversely interact with a triptan, obtained between and during the
first and last triptan fills throughout the study period. RESULTS: Mean patient
age was 43 (SD +/- 11.6) and 82% were female. Twenty-one percent were
co-prescribed selective serotonin reuptake inhibitors, reflecting the
considerable co-morbidity of migraine and depression. Patients taking triptans
were almost never co-prescribed monoamine oxidase inhibitors (0.02%), and
co-prescription of ergots was also low (1.45%). Less than one percent (0.45%)
received cimetidine while taking zolmitriptan, while 2.7% of patients taking
rizatriptan 10 mg also took propranolol. While agents unavailable in the U.S.
were not evaluated in this cohort, six percent of patients were treated with
potent CYP 3A4 inhibitors, which would not be expected to cause any problems with
the triptans in the survey. However, such agents are specifically contraindicated
for use with one triptan (eletriptan), recently launched in the EU, suggesting
that continued vigilance will be necessary to avoid coprescription of medicines
with the potential for producing adverse side effects. CONCLUSIONS: Triptan use
mirrors migraine demographics. The frequency of co-prescription of triptans with 
SSRIs is about 20%. Continued vigilance will be necessary to avoid
co-prescription of medicines with the potential for producing adverse drug
events.

PMID: 12864757 [PubMed - indexed for MEDLINE]

2538: Headache. 2003 Jan;43(1):36-43.

Migraine medication attributes important for patient compliance: concerns about
side effects may delay treatment.

Gallagher RM, Kunkel R.

University of Medicine and Dentistry of New Jersey-School of Osteopathic
Medicine, Stratford, NJ, USA.

OBJECTIVES: To determine the level of concern among migraineurs about migraine
prescription medication tolerability and adverse effects and the impact of these 
concerns on their self-management of migraine. METHODS: Self-completion
questionnaires were mailed from the National Family Opinion household panel to a 
prequalified sample of 4000 adults (aged 18 years or older) who reported severe
headache and migraine. Those who met the International Headache Society symptom
criteria for migraine and reported use of prescription medication to treat their 
migraines were included in the descriptive analysis. RESULTS: A total of 2444
(61%) sufferers of severe headache/migraine returned a completed survey, and 56% 
of these (n = 1160) met the target criteria for the study. Of those meeting the
criteria, pain relief and speed of onset were important product attributes for
75% to 77% of sufferers, and the absence of adverse effects was important to over
40%. Two-thirds of sufferers specifically had delayed or avoided taking a current
prescription medication because of concerns about adverse effects. These concerns
led to a delay in taking medication in 37% of treated migraine episodes and to
medication avoidance in 44% of untreated attacks during the previous 6 months,
resulting in more intensive and longer duration of pain, the need to rest and
cancel social activities, and suboptimal performance. Almost 8 of 10 (79%)
sufferers showed an interest in trying a novel product with similar efficacy but 
fewer adverse effects than other prescription migraine medications. CONCLUSIONS: 
Adverse effects are an important factor in migraine management, and concern about
adverse effects significantly affected patient compliance.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 12864756 [PubMed - indexed for MEDLINE]

2539: Headache. 2003 Jan;43(1):27-35.

Hormonal factors in migraine: a population-based study of women aged 40 to 74
years.

Mattsson P.

Department of Neuroscience, Neurology, University Hospital, S-751 85 Uppsala,
Sweden.

OBJECTIVE: This study investigated some of the relationships between migraine and
hormonal factors. METHODS: A neurologist clinically assessed 728 women aged 40 to
74 years attending a population-based mammography screening program. Headache
criteria proposed by the International Headache Society were used. Data on
hormonal factors were obtained by interview and questionnaire. RESULTS:
Twenty-one percent of women with migraine without aura and 4% of women with
migraine with aura reported that they experienced >/=75% of their attacks within 
-2 to +3 days of the menstrual cycle. During pregnancy, women experienced less
frequent or less intense attacks of migraine without aura and migraine with aura.
A small but significant proportion (12%, P =.04) of women with migraine without
aura also had premenstrual disorder. Associations between migraine and menarche, 
pregnancy, pregnancy-related complications, and menopausal complaints were
generally weak and insignificant. Migraine with aura was not related to
menopause. A crude odds ratio of 0.47 (95% confidence interval [CI] 0.24-0.86)
indicated a decrease in risk for migraine without aura in postmenopausal women.
However, after adjusting for differences in age and the use of hormonal
replacement therapy, this association was not statistically significant. Time
since menopause was a significant factor for migraine without aura in
postmenopausal women. CONCLUSION: Although many women with migraine reported a
close relationship between their attacks and menses, and relief during pregnancy,
the cross-sectional associations between migraine and menopause and menopausal
complaints were insignificant.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 12864755 [PubMed - indexed for MEDLINE]

2540: Headache. 2003 Jan;43(1):19-26.

Comment in:
    Headache. 2006 Apr;46(4):692-3.

Migraine prevalence and treatment patterns: the global Migraine and Zolmitriptan 
Evaluation survey.

MacGregor EA, Brandes J, Eikermann A.

City of London Migraine Clinic, London, UK.

OBJECTIVE: The objectives of the Migraine And Zolmitriptan Evaluation (MAZE)
survey were to assess the prevalence of migraine in the general population across
5 different countries, to understand migraineurs' experience of migraine and its 
management on a global level, and to assess patient perceptions and preferences
of current and future treatment formulations. METHODS: A two-phase, international
survey was performed in France, Germany, Italy, the UK, and the USA, and involved
a total of 5553 adults. In Phase I, >/=1000 adults from the general population in
each country were interviewed by telephone using a routine consumer survey. The
proportion of subjects meeting International Headache Society (IHS) criteria for 
migraine was assessed using an adapted Kiel headache questionnaire, whereas the
impact of migraine on daily life was assessed using the Migraine Disability
Assessment Scale (MIDAS) questionnaire. In Phase II, >/=100 clinically diagnosed 
migraineurs per country were recruited through their general practitioners and
migraine clinics. Semi-structured interviews based on written questionnaires
assessed the impact of, and attitudes toward, migraine and its treatments.
Respondents also completed the MIDAS questionnaire. Patients also sampled a
demonstrator version of the new orange-flavored orally disintegrating tablet of
zolmitriptan. RESULTS: Phase I: An estimated 5% to 12% of the population in the
different countries were classified as suffering from migraine, with most attacks
categorized as fairly severe to very severe. Between 23% and 42% of migraineurs
reported>24 attacks in the previous 12 months. Approximately one-half of all
migraineurs did not seek medical advice. Of those who did consult a physician,
only 3% to 19% were prescribed triptans. In all countries, the most commonly used
current treatment was simple analgesics (22% to 54%). Phase II: Current migraine 
therapy was consistently effective in only 19% to 31% of patients, and only 21%
to 50% of patients were satisfied with their current treatment. Many sufferers
supplemented their prescription therapy with alternative management strategies,
including herbal and homeopathic remedies, stress management, relaxation therapy,
avoidance of trigger factors, and bed rest. Patients indicated that the most
important attributes of migraine therapies are high efficacy and rapid pain
relief. When asked to identify delivery options that they would like to see more 
of in the future, most patients (73%) specified "a dissolve-in-the-mouth tablet."
Ninety percent of patients who sampled the demonstrator version of the
zolmitriptan orally disintegrating tablet considered it to be "very easy" to use,
and 99% stated it was suitable for use "anytime/anywhere." CONCLUSIONS: In the
general population samples we surveyed, there was a 5% to 12% prevalence of
migraine across 5 different countries. As reported from previous epidemiologic
studies, we found that many migraineurs still do not consult a physician. Despite
high levels of disability, as assessed by MIDAS scores and evidenced by the need 
for bed rest during attacks, many migraineurs continue to treat their headaches
with simple analgesics, which, if ineffective, leads to dissatisfaction with
treatment. Patients desire a medication with high efficacy and a rapid onset of
action, and an orally disintegrating tablet such as that used for the new
zolmitriptan formulation, is a favored formulation and route of administration.

Publication Types: 
    Multicenter Study
    Research Support, Non-U.S. Gov't

PMID: 12864754 [PubMed - indexed for MEDLINE]

2541: Value Health. 2003 Jul-Aug;6(4):438-47.

Comment in:
    Value Health. 2003 Jul-Aug;6(4):436-7.

A cost-effectiveness analysis of eletriptan 40 and 80 mg versus sumatriptan 50
and 100 mg in the acute treatment of migraine.

Wells N, Hettiarachchi J, Drummond M, DPhil M, Carter D, Parpia T, Pang F.

Outcomes Research, Pfizer Global Research and Development, Sandwich, UK.
Nicholas_Wells@sandwich.pfizer.com

OBJECTIVES: This article explores the application of cost-effectiveness analysis 
in a comparison of eletriptan and sumatriptan in the acute treatment of migraine.
METHODS: The study employs data from a randomized, double-blind,
placebo-controlled clinical trial comparison of oral eletriptan (40 and 80 mg)
and oral sumatriptan (50 and 100 mg). Analyses were undertaken using two
composite measures of treatment outcome constructed to reflect the requirements
of patients more comprehensively than the conventional efficacy indicator of
headache response at 2 hours. On the cost side of the equation, reflecting the
health-care system perspective of the analysis, drug costs for initial dosing,
second dosing for nonresponse, and recurrence and rescue medication were taken
into account. RESULTS: The analysis found that eletriptan treatment resulted in
lower costs per successfully treated attack than those of sumatriptan under both 
outcome criteria. CONCLUSION: Further refinement of outcomes measurement in
migraine would be valuable and eletriptan has a potentially important role to
play in the cost-effective management of the disorder.

Publication Types: 
    Clinical Trial
    Clinical Trial, Phase III
    Comparative Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 12859585 [PubMed - indexed for MEDLINE]

2542: CNS Spectr. 2003 Jun;8(6):446-9.

The link between glutamate and migraine.

Ramadan NM.

Department of Neurology, Finch University of Health Sciences/The Chicago Medical 
School, Chicago, Illinois 60064-3095, USA. ramadan@finchcms.edu

Migraine pain-relay centers, including the trigeminal ganglion, trigeminal
nucleus caudalis, and thalamus, contain glutamate-positive neurons, and glutamate
activates the trigeminal nucleus caudalis. Glutamate is implicated in cortical
spreading depression, trigeminovascular activation, and central sensitization.
Glutamate receptor-subtype antagonists are effective in preclinical models of
migraine, and in the clinic. These preclinical and clinical observations argue
for a strong link between migraine and the glutamatergic system, a link that is
important to further characterize in an effort to better understand migraine
mechanisms and deliver effective therapies.

Publication Types: 
    Review

PMID: 12858134 [PubMed - indexed for MEDLINE]

2543: CNS Spectr. 2003 Jun;8(6):433-4, 437-44.

The comorbidity of migraine.

Low NC, Merikangas KR.

Mood and Anxiety Disorders Program of the Intramural Research Program at the
National Institute of Mental Health, National Institutes of Health, Department of
Health and Human Services in Bethesda, Maryland MD 20892-2670, USA.

This review addresses the methodologic issues relevant to the study of
comorbidity and provides a broad overview of the medical and psychiatric
conditions associated with migraine. Since the body of literature examining the
comorbidity of migraine is enormous, the scope of this review will largely focus 
on community and case-control studies. Among the selected comorbid medical
conditions, including disorders of the cardiovascular, respiratory, neurologic,
gastrointestinal and immunologic systems, stroke, asthma, and allergies appear to
be most strongly associated with migraine. Among the psychiatric illnesses, mood 
and anxiety disorders have been shown to be most strongly associated with
migraine in the general population. Further research is indicated and necessary
to elucidate the precise mechanism of migraine comorbidity.

Publication Types: 
    Review

PMID: 12858133 [PubMed - indexed for MEDLINE]

2544: CNS Spectr. 2003 Jun;8(6):428-32.

Topiramate in the preventive treatment of episodic migraine: a combined analysis 
from pilot, double-blind, placebo-controlled trials.

Edwards KR, Potter DL, Wu SC, Kamin M, Hulihan J.

Department of Neurology, Harvard Medical School School and Beth Israel Deaconess 
Medical Center in Boston, Massachusetts, USA. kedwards@vtneuro.com.

The safety and efficacy of medications for preventive treatment of migraine is
the subject of current concern and investigation in health care. Two
single-center, double-blind, placebo-controlled studies were conducted to
evaluate the efficacy and safety of topiramate for migraine prophylaxis. Seventy 
patients with a diagnosis of migraine were randomly assigned to
topiramate-treated and placebo groups. The studies consisted of a 4-week baseline
phase, a 6-8 week titration, and 8-12 weeks of maintenance. Topiramate was
titrated from an initial dose of 25 mg/day to a target dose of 100 mg BID. The
primary efficacy measure, the mean 28-day migraine frequency, was lower in
topiramate-treated patients than in the placebo group (3.2 versus 3.8, P=.001).
Similarly, topiramate treatment resulted in a significantly greater mean
reduction in migraine frequency than did placebo (1.55 versus 0.47, P=.001) and a
significantly higher responder rate (35.3% versus 8.3%, P=.008). Paresthesia was 
the most common side effect reported with topiramate treatment. Other
topiramate-associated adverse events included altered taste, memory impairment,
diarrhea, and appetite suppression/weight loss. The rates of discontinuation were
similar for the topiramate group (n=10) and the placebo group (n=8). These
results suggest that topiramate is effective and well tolerated in the preventive
treatment of migraine headaches.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 12858132 [PubMed - indexed for MEDLINE]

2545: Curr Opin Neurol. 2003 Jun;16(3):341-5.

The evolving management of migraine.

Ashkenazi A, Silberstein SD.

Jefferson Headache Center, Department of Neurology, Thomas Jefferson University
Hospital, Gibbon Building, Suite #8130, 111 South Eleventh Street, Philadelphia, 
PA 19107, USA.

PURPOSE OF REVIEW: To review recent advances in acute and preventive migraine
treatment. RECENT FINDINGS: The number of migraine drugs continues to expand,
allowing for more flexible and tolerable treatment plans. Two new triptans,
frovatriptan and eletriptan, and a nasal formulation of zolmitriptan have been
recently developed. Eletriptan is effective for acute migraine treatment and may 
have some pharmacologic and clinical advantages. Frovatriptan has a longer
half-life and lower headache recurrence rates compared with other triptans. It
may be useful for patients who have prolonged attacks and high headache
recurrence rate. Zolmitriptan nasal spray has a rapid onset of action and high
efficacy. It should be considered when patients have rapid-onset attacks,
especially when associated with severe nausea or vomiting. The butyrophenone
neuroleptic droperidol is very effective in aborting acute migraine attacks.
Central nervous system side effects are common, however, and the ECG should be
monitored. Botulinum toxin type A shows promise as a safe, tolerable and
effective drug for migraine prevention, with the unique advantages of almost no
systemic adverse events and a long interval between treatments. The
anticonvulsant topiramate is effective for migraine prevention. Cognitive side
effects are of less concern with the lower doses needed for migraine. The
angiotensin converting enzyme receptor blocker candesartan appears to be
effective and highly tolerable in the prevention of migraine, but needs to be
further evaluated. SUMMARY: New drugs expand the spectrum of migraine treatment
both for the acute attack and for prevention.

Publication Types: 
    Review

PMID: 12858071 [PubMed - indexed for MEDLINE]

2546: Curr Opin Neurol. 2003 Jun;16(3):327-31.

The electrophysiology of migraine.

Ambrosini A, Schoenen J.

Headache Clinic, INM Neuromed, IRCCS, Pozzilli, Isernia, Italy.

PURPOSE OF REVIEW: The pathophysiology of migraine is far from being understood. 
Electrophysiological methods are useful to investigate peripheral and central
mechanisms underlying this disorder. The purpose of this review is to highlight
the results of electrophysiological studies published during the last year and to
examine their added value to our previous knowledge. RECENT FINDINGS: Studies by 
visual and auditory evoked potentials and event-related responses suggested that 
lack of habituation is the principal interictal abnormality of sensory processing
in migraineurs. Recently confirmed for somatosensory and laser-evoked cortical
potentials and for brainstem responses, it is also responsible for the increased 
intensity dependence of auditory evoked potentials. This abnormality is possibly 
caused by a reduced cortical preactivation level due to hypofunctioning
subcortico-cortical aminergic pathways. Although studies of cortical excitability
by transcranial magnetic stimulation have yielded conflicting results, results
obtained using habituation of pattern-reversal visual evoked potentials to
explore cortical excitability changes induced by repetitive transcranial magnetic
stimulation strongly favour the hypothesis that migraine is characterized by a
decreased level of preactivation excitability. With regard to pain mechanisms in 
migraine, electrophysiological studies of trigeminal pathways using nociceptive
blink and corneal reflexes have confirmed that sensitization of central
trigeminal nociceptors occurs during the attack, and may even persist
interictally. SUMMARY: Scientific publications over the last year confirmed that 
electrophysiological methods are particularly suited to unravelling some of the
pathophysiological mechanisms of migraine. To improve their future contribution, 
they need to be better standardized and to be correlated with behavioural,
metabolic and genetic studies.

Publication Types: 
    Review

PMID: 12858069 [PubMed - indexed for MEDLINE]

2547: J Med Chem. 2003 Jul 17;46(15):3197-200.

(S)-N-[1-(3-morpholin-4-ylphenyl)ethyl]- 3-phenylacrylamide: an orally
bioavailable KCNQ2 opener with significant activity in a cortical spreading
depression model of migraine.

Wu YJ, Boissard CG, Greco C, Gribkoff VK, Harden DG, He H, L'Heureux A, Kang SH, 
Kinney GG, Knox RJ, Natale J, Newton AE, Lehtinen-Oboma S, Sinz MW, Sivarao DV,
Starrett JE Jr, Sun LQ, Tertyshnikova S, Thompson MW, Weaver D, Wong HS, Zhang L,
Dworetzky SI.

Bristol-Myers Squibb Pharmaceutical Research Institute, 5 Research Parkway,
Wallingford, Connecticut 06492, USA. yong-jin.wu@bms.com

(S)-N-[1-(3-Morpholin-4-ylphenyl)ethyl]-3-phenylacrylamide (2) was synthesized as
an orally bioavailable KCNQ2 potassium channel opener. In a rat model of
migraine, 2 demonstrated significant oral activity in reducing the total number
of cortical spreading depressions induced by potassium chloride.

PMID: 12852750 [PubMed - indexed for MEDLINE]

2548: Lancet Neurol. 2002 Sep;1(5):285-93.

The genetics of migraine.

Ducros A, Tournier-Lasserve E, Bousser MG.

Headache Emergency Department, Lariboisière Hospital, Paris, France.
anne.ducros@lrb.ap-hop-paris.fr

The search for genes involved in the pathophysiology of migraine poses major
difficulties. First, there is no objective diagnostic method to assess the status
of the individuals studied. Second, migraine is a polygenic multifactorial
disorder. Familial hemiplegic migraine (FHM) is the only known autosomal dominant
subtype of migraine. In half the families with FHM who have been studied, there
are mutations in the calcium-channel gene CACNA1A, located on chromosome 19. In
other families, a locus has been mapped on chromosome 1. The role of these loci
in typical migraine is still unknown. A susceptibility locus for migraine with
aura has been located on chromosome 19 (but is distinct from CACNA1A) and a
genome-wide linkage analysis has mapped a susceptibility locus on chromosome 4.
Another locus for migraine may be on the X chromosome. Finally, many positive
association studies have been published, but few have been replicated.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 12849426 [PubMed - indexed for MEDLINE]

2549: Lancet Neurol. 2002 Nov;1(7):437-44.

The hypothalamus in episodic brain disorders.

Overeem S, van Vliet JA, Lammers GJ, Zitman FG, Swaab DF, Ferrari MD.

Narcolepsy Research Group, Department of Neurology, Leiden University Medical
Centre, Leiden, The Netherlands.

Episodic brain disorders (EBD) form an intriguing group of neurological diseases 
in which at least some of the symptoms occur in attacks. The hypothalamus
integrates many brain functions, including endocrine and autonomic control, and
governs various body rhythms. It seems a likely site in which the initiation of
attacks of EBD can be modulated. Indeed, the hypothalamus has a crucial role in
EBD such as narcolepsy and cluster headache. The same may be true for migraine
and depression. Here we summarise the evidence supporting an important role for
the hypothalamus in the initiation of disease episodes in various EBD. Study of
the various pathophysiological concepts of EBD within the context of the
hypothalamus may prove a fruitful example of cross-fertilisation between various 
research areas.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 12849366 [PubMed - indexed for MEDLINE]

2550: Neurology. 2003 Jul 8;61(1):60-3.

Facilitation of extracranial vasodilatation to limb pain in migraine sufferers.

Drummond PD, Granston A.

School of Psychology, Murdoch University, Perth, Western Australia.
drummond@central.murdoch.edu.au

BACKGROUND: Dilatation of pain-sensitized scalp vessels can cause pain in
migraine headache, and extracranial vascular hyperreactivity to psychological
stress and head pain could increase susceptibility to attacks. OBJECTIVE: To
determine whether changes in facial blood flow differed between migraine
sufferers and control subjects during painful stimulation of a limb. METHODS: To 
document changes in facial blood flow, pulse amplitude was monitored with
photoelectric pulse transducers from the frontotemporal region of 23 migraine
sufferers and 22 age- and sex-matched control subjects before, during, and after 
immersion of the nondominant hand in ice water at 2 degrees C for 30 seconds. The
hand was immersed three times at 4-minute intervals. RESULTS: Migraine sufferers 
rated the pain of the ice-water immersion to be more intense and unpleasant than 
control subjects, and pain radiated further up the arm. Increases in pulse
amplitude were greater ipsilateral than contralateral to painful stimulation
(25.1 +/- 2.9 vs 13.7 +/- 4.4%; p < 0.01). Pulse amplitude increased over
repeated immersions (p < 0.01) and peaked after the hand was removed from the ice
water (p < 0.001), more so ipsilaterally than contralaterally (p < 0.001). Pulse 
amplitude increased 26.3 +/- 4.3% in migraine sufferers compared with 12.6 +/-
4.4% in control subjects (p < 0.05), and this group difference persisted 8
minutes after the final immersion. CONCLUSION: Limb pain triggers increases in
facial blood flow and might exacerbate the vascular component of headache during 
attacks of migraine.

Publication Types: 
    Clinical Trial
    Controlled Clinical Trial
    Research Support, Non-U.S. Gov't

PMID: 12847157 [PubMed - indexed for MEDLINE]

2551: Clin J Pain. 2003 Jul-Aug;19(4):255-62.

Pathogenesis of the migraine attack.

Spierings EL.

Department of Neurology, Brigham and Women's Hospital, Harvard Medical School,
Boston, Massachusetts, USA.

BACKGROUND: There is clinical experimental evidence that extracranial arterial
vasodilation, extracranial neurogenic inflammation, and decreased inhibition of
central pain transmission are involved in the pathogenesis of the migraine
headache. The migraine aura is likely caused by a neurophysiologic phenomenon
akin to Leão's cortical spreading depression, a wave of short-lasting neuronal
excitation that travels over the cerebral cortex, followed by prolonged
depression of cortical neuronal activity. METHOD: A concept of the pathogenesis
of the migraine attack is presented, in which the relation of the mechanism of
the migraine aura and that of the migraine headache is considered parallel rather
than sequential in nature. CONCLUSIONS: The process driving the pathogenesis of
the migraine attack and susceptible to the migraine trigger factors may be
located in the brain stem.

Publication Types: 
    Review

PMID: 12840620 [PubMed - indexed for MEDLINE]

2552: Pediatrics. 2003 Jul;112(1 Pt 1):e1-5.

Quality of life in childhood migraines: clinical impact and comparison to other
chronic illnesses.

Powers SW, Patton SR, Hommel KA, Hershey AD.

Division of Psychology, Cincinnati Children's Hospital Medical Center,
Cincinnati, Ohio 45229-3039, USA. Scott.Powers@cchmc.org

OBJECTIVE: Despite the high prevalence of headaches in youths, quality of life
(QOL) has not been well examined. We examined QOL in a clinical sample of
children with headaches and compared it with children with other chronic
diseases. METHODS: A survey study was conducted of 572 consecutive patients (mean
age, 11.4 +/- 3.6 years) who presented with headaches to a children's headache
center. Children and parents completed the Pediatric Quality of Life Inventory,
Version 4.0 and a standardized headache assessment. Results were compared with
established norms for healthy and chronically ill children. RESULTS: Most
patients (99%) had a clinical diagnosis of migraine: 85% met the International
Headache Society migraine criteria, and 40% had chronic daily headaches. Total
Pediatric Quality of Life Inventory, Version 4.0 score was lower for the entire
group (73.1 +/- 14.4) compared with healthy norms (83.0 +/- 14.8) and lowest for 
children with chronic daily headaches (70.5 +/- 15.5). The impact on QOL of
children with migraine was similar to that of children with arthritis and cancer.
CONCLUSIONS: QOL of children with headaches is significantly affected by their
health condition. The impact of headaches on QOL is similar to that found for
other chronic illness conditions, with impairments in school and emotional
functioning being the most prominent.

Publication Types: 
    Comparative Study

PMID: 12837897 [PubMed - indexed for MEDLINE]

2553: Expert Opin Pharmacother. 2003 Jul;4(7):1157-63.

A review of the clinical efficacy and tolerability of almotriptan in acute
migraine.

Dodick DW.

Department of Neurology, Mayo Clinic Scottsdale, 13400 East Shea Boulevard,
Scottsdale, AZ 85259, USA. Dodick.David@mayo.edu

Almotriptan is a serotonin (5-hydroxytryptamine, 5HT)(1B/1D)-receptor agonist
approved for the acute treatment of migraine. In 3500 acute migraine patients
enrolled in short-term trials and 1500 patients in long-term open-label trials,
almotriptan 12.5 mg was effective and well-tolerated. Almotriptan maintains a
consistency of response across three attacks and patients continue to respond to 
almotriptan for up to 1 year. Results from two comparative studies and a
meta-analysis of 53 randomised, placebo-controlled studies of oral triptans in > 
24,000 patients, confirm that almotriptan 12.5 mg demonstrates comparable
efficacy with sumatriptan 50 and 100 mg. The incidence of treatment-related
adverse events with almotriptan is comparable to that of placebo and
significantly lower than that with sumatriptan. Drug-drug interaction studies
indicate that almotriptan may be coadministered with other commonly prescribed
drugs without dose modification. Almotriptan can be recommended as first-line
treatment for acute migraine.

Publication Types: 
    Review

PMID: 12831340 [PubMed - indexed for MEDLINE]

2554: J Neural Transm Suppl. 2003;(64):35-63.

Pharmacological approaches to migraine.

Diener HCh.

Department of Neurology, University Essen, Federal Republic of Germany.
h.diener@uni-essen.de

Migraine is a paroxysmal disorder with attacks of headache, nausea, vomiting,
photo- and phonophobia and malaise. This review summarises new treatment options 
both for the therapy of the acute attack as well as for migraine prophylaxis.
Analgesics like aspirin or nonsteroidal antiinflammatory drugs (NSAIDs) are
effective in treating migraine attacks. Few controlled trials were performed for 
the use of ergotamine or dihydroergotamine. These trials indicate inferior
efficacy compared to serotonin (5-HT)1B/D-agonists (further on called
"triptans"). The triptans (almotriptan, eletriptan, frovatriptan, naratriptan,
rizatriptan, sumatriptan and zolmitriptan) are highly effective. They improve
headache as well as nausea, photo- and phonophobia. The different triptans have
minor differences in efficacy, headache recurrence and adverse effects. The
knowledge of their different pharmacological profile allows a more specific
treatment of the individual migraine characteristics. Migraine prophylaxis is
recommended, when more than 3 attacks occur per month, if attacks do not respond 
to acute treatment or if side effects of acute treatment are severe. Substances
with proven efficacy include the beta-blockers metoprolol and propranolol, the
calcium channel blocker flunarizine, several 5-HT antagonists and amitriptyline. 
Recently antiepileptic drugs (valproic acid, gabapentin, topiramate) were
evaluated for the prophylaxis of migraine. The use of botulinum-toxin is under
investigation.

Publication Types: 
    Review

PMID: 12830928 [PubMed - indexed for MEDLINE]

2555: Dermatol Surg. 2003 Jul;29(7):749-54.

Botulinum toxin: application into acupuncture points for migraine.

Tamura BM, Chang B.

Dermatology Department of Complexo Hospitalar Heliópolis, São Paulo, Brazil.
tamurab@uol.com.br

BACKGROUND. : Botulinum toxin has been employed in orthopedics, physiatrics,
gastroenterology, gynecology, neurology, pediatrics, general surgery, plastic
surgery, and several other specialties. We have applied this drug to treat
hyperhidrosis and wrinkles in dermatology; it offers also a secondary benefit:
relief for headaches. OBJECTIVE. : We have performed studies based on acupuncture
principles in order to develop new botulinum toxin application sites for the
treatment of migraine. These additional sites are helpful when patients expect
results for both their illness and their wrinkles; whereas some patients will
show improvement with the classic treatment for wrinkles, additional sites may be
required. METHODS. : Ten patients suffering from migraine, as diagnosed through
the criteria proposed by the Headache Classification Committee of the
International Headache Society, were selected. We used easily recognizable
acupuncture sites for the injection of botulinum toxin. RESULTS. : There was
significant improvement in patients with acupuncture site-guided botulinum toxin 
injection. It showed to be a safe and effective therapy for migraine. CONCLUSION.
: There are alternative sites besides those used for the treatment of expression 
lines, which bring forth an improvement of migraine.

PMID: 12828700 [PubMed - indexed for MEDLINE]

2556: CNS Drugs. 2003;17(9):653-67.

Speed of onset and efficacy of zolmitriptan nasal spray in the acute treatment of
migraine: a randomised, double-blind, placebo-controlled, dose-ranging study
versus zolmitriptan tablet.

Charlesworth BR, Dowson AJ, Purdy A, Becker WJ, Boes-Hansen S, Färkkilä M.

AstraZeneca, Macclesfield, England. bruce.charlesworth@astrazeneca.com

OBJECTIVE: Zolmitriptan oral tablet is highly effective and well tolerated in the
acute treatment of migraine with and without aura in adults. A nasal spray
formulation has now been developed. The objective of this study was to compare
the efficacy and tolerability of fixed doses of zolmitriptan administered via a
nasal spray with placebo and zolmitriptan oral tablet in the acute treatment of
migraine. PATIENTS AND STUDY DESIGN: This was a randomised, double-blind,
double-dummy, placebo-controlled, parallel-group, multicentre, dose-ranging
study. 1547 patients aged 18-65 years with an established diagnosis of migraine
with or without aura (as defined by International Headache Society criteria) who 
had at least a 1-year history of migraine and an age of onset <50 years were
included. Patients were able to distinguish typical migraine from nonmigraine
headaches and had experienced an average of one to six migraine headaches per
month during the 2 months preceding the study. Patients were randomised to
zolmitriptan (Zomig) The use of tradenames is for product identification purposes
only and does not imply endorsement.) nasal spray (5.0, 2.5, 1.0 or 0.5 mg),
zolmitriptan oral tablet (2.5mg) or placebo for the treatment of three moderate
or severe migraine attacks. The primary outcome measure was headache response at 
2 hours following treatment, defined as reduced intensity of migraine pain (using
a scale of none, mild, moderate or severe) from severe or moderate at baseline to
mild or no pain at 2 hours after treatment. Secondary outcome measures included
early headache response at 15, 30 and 45 minutes and headache response at 1 and 4
hours postdose, as well as pain-free rates at 15, 30 and 45 minutes and 1, 2 and 
4 hours postdose. Laboratory assessments, vital signs, 12-lead ECGs and nose and 
throat examinations were performed at screening and follow-up visits. Adverse
events were recorded throughout the study using Coding Symbols for Thesaurus of
Adverse Reaction Terms (COSTART) terminology. RESULTS: Each dose of zolmitriptan 
nasal spray produced a greater 2-hour headache response rate than placebo (70.3%,
58.6%, 54.8% and 41.5% for zolmitriptan nasal spray 5.0, 2.5, 1.0 and 0.5mg,
compared with 30.6% for placebo [all p < 0.001 vs placebo]). The 2-hour headache 
response rate for zolmitriptan nasal spray 5.0mg was significantly higher than
that of the zolmitriptan 2.5mg oral tablet (61.3%; p < 0.05), while comparisons
of nasal spray 0.5, 1.0 and 2.5mg with zolmitriptan 2.5mg oral tablet were not
statistically significant. The nasal spray 5.0 and 2.5mg showed a rapid onset of 
action, with a significant difference in headache response compared with placebo 
from 15 minutes through 4 hours after administration and a significant difference
between the nasal spray 5.0mg and 2.5mg oral tablet from 15 minutes through to 2 
hours (the other nasal spray doses were not statistically significant compared
with 2.5mg oral tablet). Zolmitriptan nasal spray resulted in pain-free rates
that were dose dependent. While all doses from 1.0 mg upwards produced
significant pain-free outcomes from 30 minutes versus placebo, only the 5.0mg
dose produced pain-free rates significantly superior to both placebo and the
2.5mg oral tablet. Zolmitriptan nasal spray was well tolerated, with the most
common adverse events being unusual taste and paresthesia. The majority of
adverse events were of short duration and mild or moderate intensity. Only ten
patients were withdrawn from the trial because of adverse events. Serious adverse
events were reported by nine patients after taking study medication, but none was
considered to be causally related to study medication. Zolmitriptan was not
associated with any clinically significant changes in laboratory test values or
vital signs. CONCLUSION: All doses of zolmitriptan nasal spray produced
significant 2-hour headache response rates compared with placebo. The 5.0 and
2.5mg doses were also significantly more effective than placebo for the majority 
of secondary efficacy measures. Zolmitriptan nasal spray 5.0mg provided a
headache response statistically superior to both placebo and the 2.5mg tablet as 
early as 15 minutes after administration, while demonstrating pain-free outcomes 
significantly superior to placebo and the 2.5mg tablet as early as 30 minutes
after administration. All doses of zolmitriptan nasal spray were well tolerated, 
resulting in an optimal therapeutic index and clinical recommendation for the
5.0mg dose.

Publication Types: 
    Clinical Trial
    Comparative Study
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 12828501 [PubMed - indexed for MEDLINE]

2557: Neurol Sci. 2003 Jun;24(2):85-9.

Migraine, cortical blindness, multiple cerebral infarctions and hypocoagulopathy 
in celiac disease.

Morello F, Ronzani G, Cappellari F.

Territorial Neurology and Neurophysiology Service, USSL No. 5, Via Trento 4,
I-36071 Arzignano (VI), Italy.

We describe the case of a female patient affected by migraine and untreated adult
celiac disease who presented with a state of acute migraine accompanied by
multiple neurological deficits, including transient cortical blindness with
ischemic CT and MRI alterations, and hypocoagulation due to factor VII
deficiency. She was receiving estroprogestin therapy. There was a prompt response
to cortisone therapy followed by a state of complete well-being, which also led
to the disappearance of migraine attacks after five years of dietary treatment
alone.

Publication Types: 
    Case Reports

PMID: 12827546 [PubMed - indexed for MEDLINE]

2558: Neurol Sci. 2003 Jun;24(2):80-1.

Vestibular migraine: objective diagnostic criteria.

Di Duro JO.

Private Practice in Chiropractic, Via Prati 14, I-36100, Vicenza, Italy.

Classification of migraine or vertigo based only on clinical symptoms is rather
difficult, especially in the postacute stage. The use of diagnostic
instrumentation greatly aids clinicians in offereing objective measures of
patient physiology. In migraine and vertigo, the "gold standard" objective
measure has not been fully defined thereby hindering a criteria for vestibular
migraine. This study proposes the use of two seperate modalities; infrared
videonystagraphy for vertigo and electric pain thresholds for migraine to
quantify patient complaints. While these instruments offer to document patient
pathophsyiology, simple clinical procedures are presented to provoke the
dizzyness of vertigo and the allodynia of migraine in patients being evaluted
allowing clinicians larger diagnostic and therapeutic options

Publication Types: 
    Case Reports

PMID: 12827544 [PubMed - indexed for MEDLINE]

2559: Eur J Neurol. 2003 Jul;10(4):421-7.

Comment in:
    Eur J Neurol. 2004 Feb;11(2):141-2; author reply 142.

Increased risk of migraine with typical aura in probands with familial hemiplegic
migraine and their relatives.

Thomsen LL, Olesen J, Russell MB.

Department of Neurology, The Danish Headache Center, Glostrup Hospital,
University of Copenhagen, Denmark. llt@dadlnet.dk

We investigated the occurrence of migraine without aura (MO) and migraine with
typical aura (MA) amongst probands with familial hemiplegic migraine (FHM) and
their first degree relatives in order to evaluate the relations between these
syndromes. A total of 44 FHM probands and 240 first degree relatives were
identified in the Danish population. The pattern of familial aggregation was
assessed by population relative risk (PRR) calculations. Amongst FHM probands the
PRR of MO was 1.5 (95% CI: 0.8-2.2), whereas the PRR of MA was 7.1 (95% CI:
5.0-9.2). Thus, compared with the general population, FHM probands had no
increased risk of MO but a significantly increased risk of MA. A similar pattern 
was seen amongst their first degree relatives, who had no increased risk of MO,
whereas the risk of MA was significantly increased; 7.6 times in FHM-affected
first degree relatives and 2.4-times in non-FHM-affected first degree relatives. 
These results are contrary to a sharing of genetic mechanisms between FHM and MO.
Furthermore, they suggest that the genetic abnormality causing FHM may also cause
attacks with the symptomatology of MA.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 12823495 [PubMed - indexed for MEDLINE]

2560: J Child Neurol. 2003 May;18(5):361-3.

Moyamoya disease presented with migrainelike headache in a 4-year-old girl.

Aydin K, Okuyaz C, Gücüyener K, Serdaroğlu A, Akpek S.

Department of Pediatric Neurology, Selçuk University Faculty of Medicine, Konya, 
Turkey.

A 4-year-old girl was admitted to our department with the complaints of severe
headache, nausea, vomiting, and photophobia. She had a 1-year history of
migrainelike headache that occurred every 1 to 2 months. Her neurologic
examination was normal, but T-weighted axial magnetic resonance imaging (MRI) of 
the brain showed flow void within the basal ganglia owing to parenchymal vascular
collaterals. Magnetic resonance angiography and digital substraction carotid
angiography showed both occlusion of the internal carotid artery in the
supraclinoid portion and extensive parenchymal vascular collaterals. Because
there was no evidence of risk factors for cerebral arterial occlusion and
cerebral infarct or hemorrhage, she was diagnosed as having moyamoya disease. In 
any case of atypical migrainelike headache, a detailed investigation should be
kept in mind to detect an underlying vascular disease such as moyamoya.

Publication Types: 
    Case Reports

PMID: 12822823 [PubMed - indexed for MEDLINE]

2561: Brain. 2003 Sep;126(Pt 9):2009-15. Epub 2003 Jun 23.

Lack of habituation causes high intensity dependence of auditory evoked cortical 
potentials in migraine.

Ambrosini A, Rossi P, De Pasqua V, Pierelli F, Schoenen J.

Headache Clinic, INM Neuromed, Pozzilli, Isernia, Italy.

Migraineurs are characterized interictally by lack of habituation, or even
potentiation, of cortical evoked potentials during repetitive stimulation and by 
a strong intensity dependence of auditory evoked potentials (IDAP). To determine 
whether these two features of sensory processing are interrelated, we have
studied them simultaneously on the same recordings of auditory evoked potentials 
(AEPs). AEPs were obtained at four different stimulation intensities in 14
patients suffering from migraine without aura (MO) and 14 healthy volunteers
(HV). For each intensity, 120 trials were averaged off-line globally and over
four sequential blocks of 30 trials. IDAP was expressed by the amplitude/stimulus
intensity function (ASF slope) for global and block averages. Habituation was
calculated as the percentage amplitude variation between the first and fourth
blocks for each stimulus intensity. The IDAP slope for global averages was higher
in MO (1.05 +/- 0.27 microV/10 dB) than in HV (0.64 +/- 0.45 microV/10 dB) (P =
0.008), but IDAP slopes for block averages were greater in MO only at the fourth 
block (P = 0.048). First block amplitudes tended to be lower in MO, except at 80 
dB. There was a potentiation of AEP amplitudes at every stimulus intensity in MO,
contrasting with habituation in HV. IDAP slopes were negatively correlated with
mean habituation percentages in pooled data from patients and controls (r =
-0.610; P = 0.0006). This study confirms that IDAP is higher in migraineurs than 
in healthy controls. It also shows that the AEP habituation is replaced by
potentiation at all stimulus intensities. The negative correlation found between 
IDAP and habituation suggests that the latter is able to have a strong influence 
on the former and perhaps even lead to it. In migraine, the habituation deficit
amplifies the IDAP and may thus be the causal functional abnormality. We propose 
that it is due to a decreased pre-activation level of sensory cortices, a
hypothesis also supported in this study by the lower amplitude of first AEP
blocks in patients.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 12821515 [PubMed - indexed for MEDLINE]

2562: J Clin Ultrasound. 2003 Jul-Aug;31(6):308-14.

Color Doppler sonography of orbital and vertebral arteries in migraineurs without
aura.

Kara SA, Erdemoğlu AK, Karadeniz MY, Altinok D.

Department of Radiology, University of Kirikkale, School of Medicine, Sağlik
Caddesi, Fabrikalar Mahallesi, 71100 Kirikkale, Turkey.

PURPOSE: The objective of this study was to investigate whether the retrobulbar
hemodynamics in the ophthalmic (OA), posterior ciliary (PCA), central retinal
(CRA), and vertebral (VA) arteries are affected in migraineurs without aura.
METHODS: The eyes of migraineurs without aura and those of healthy control
subjects were evaluated during both headache and headache-free periods.
Retrobulbar and vertebral blood flow velocities in the OA, PCA, CRA, and the
extracranial part of the VA were measured bilaterally using color Doppler
sonography. The peak systolic and end-diastolic flow velocities and the
pulsatility (PI) and resistance (RI) indices were determined for all arteries.
RESULTS: In total, we enrolled 30 migraineurs and 31 healthy control subjects.
Statistically significant differences between headache-free migraineurs and
control subjects were observed in the PI and RI of both right and left PCAs and
in the RI of both right and left CRAs. The PI and RI of the left VA of the
migraineurs were significantly lower during both headache and headache-free
periods than were those of the control subjects. Among the migraineurs, the peak 
systolic and end-diastolic velocities of the left VA were increased during
headache periods relative to those found during the headache-free periods.
CONCLUSIONS: The retrobulbar circulation and flow hemodynamics in the left VA may
be altered in both headache and headache-free periods in migraineurs without
aura. The differences found between migraineurs and control subjects may
implicate autonomic dysfunction in migraineurs. Copyright 2003 Wiley Periodicals,
Inc. J Clin Ultrasound 31:308-314, 2003

PMID: 12811790 [PubMed - indexed for MEDLINE]

2563: Am J Emerg Med. 2003 May;21(3):173-5.

A prospective double-blind study of nasal sumatriptan versus IV ketorolac in
migraine.

Meredith JT, Wait S, Brewer KL.

The Brody School of Medicine at East Carolina University, Department of Emergency
Medicine, Division of Research, Physician's Quadrangle, Building M, Greenville,
NC 27858, USA.

We conducted a study to compare the efficacy in migraine headache of nasal
sumatriptan and intravenous ketorolac. The study was a prospective, double-blind 
study done with a convenience sample of 29 patients presenting to the emergency
department (ED) with acute migraine. Patients received either 20 mg of nasal
sumatriptan or 30 mg of intravenous ketorolac. Patients scored the severity of
their headache on a 100-mm visual analog scale (VAS) of pain prior to medication,
and again 1 hour after medication. Differences between initial and 1-hour scores 
were analyzed. Before treatment, no difference existed between the groups in the 
intensity of headache. One hour after medication, the sumatriptan group had a
decrease in pain score of 22.937 mm and the ketorolac group a decrease of 71.462 
mm on the VAS. The decrease in pain score with ketorolac was significantly
greater than that with sumatriptan (P < 0.001). The study therefore showed that
both sumatriptan and ketorolac effectively reduced the pain associated with acute
migraine headache, but that intravenous ketorolac produced a greater reduction in
pain than did nasal sumatriptan.

Publication Types: 
    Clinical Trial
    Comparative Study
    Randomized Controlled Trial

PMID: 12811706 [PubMed - indexed for MEDLINE]

2564: Neurol Sci. 2003 May;24 Suppl 2:S149-53.

Concepts of migraine headache pathogenesis: insights into mechanisms of
chronicity and new drug targets.

Welch KM.

Department of Neurology, University of the Health Sciences, Chicago Medical
School, Chicago, IL, USA.

The pathophysiology of migraine is incompletely understood. Neurobiological and
gene regulation studies and advanced brain imaging are providing new insights
into migraine pathogenesis. Recent discoveries have shed light on the neuronal
events mediating both the aura and the headache phases of migraine, identifying a
cerebral cortical origin of migraine aura, susceptibility to attacks based on
cortical hyperexcitability, and the trigeminovascular system and its central
projections as the origin of headache. This review focuses on abnormal modulation
of brain nociceptive systems leading to central sensitization that may explain
prolonged headache of the migraine attack and shift of the migraine phenotype
from episodic to chronic headache.

Publication Types: 
    Lectures

PMID: 12811616 [PubMed - indexed for MEDLINE]

2565: Neurol Sci. 2003 May;24 Suppl 2:S146-8.

Pharmacogenomics: state of the research and perspectives in clinical application.

Severino G, Chillotti C, Stochino ME, Del Zompo M.

Headache Center, Section of Clinical Pharmacology, B.B. Brodie Department of
Neurosciences, University of Cagliari, ASL 8, Cagliari, Italy.

The person-to-person variability of drug response is a major problem in clinical 
practice and in drug development. It can lead to therapeutic failure or adverse
drug reactions (ADRs) in individuals or subpopulation of patients. In addition to
the high occurence of ADRs and the associated morbidity and mortality,
substantial costs are incurred. Potential risk factors for drug inefficacy or
toxicity include drug-drug interactions, the patient's age, renal and liver
functions or other disease factors, and lifestyle variables such as smoking and
alcohol consumption. In addition, it has become clear in recent years that
genetic factors may also significantly modify drug responses or increase the risk
for ADRs. Genetic variations in genes (polymorphisms) for drug-metabolizing
enzymes, drug receptors, and drug transporters have been associated with
individual variability in the efficacy and toxicity of drugs. It is now widely
accepted that migraine is a polygenic and multifactorial disorders, thus
considered to be a genetic complex disease. Genetic studies on migraine suggested
a role of CACNA1A and DRD2 genes as susceptibility genes in this disorder.

Publication Types: 
    Review

PMID: 12811615 [PubMed - indexed for MEDLINE]

2566: Neurol Sci. 2003 May;24 Suppl 2:S138-42.

Non-pharmacological approaches to chronic headaches: transcutaneous electrical
nerve stimulation, lasertherapy and acupuncture in transformed migraine
treatment.

Allais G, De Lorenzo C, Quirico PE, Lupi G, Airola G, Mana O, Benedetto C.

Woman's Headache Center, Department of Gynecology and Obstetrics, Via Ventimiglia
3, I-10126 Turin, Italy.

In an open, randomized trial, we evaluated transcutaneous electrical nerve
stimulation (TENS), infrared lasertherapy and acupuncture in the treatment of
transformed migraine, over a 4-month period free of prophylactic drugs. Sixty
women suffering from transformed migraine were assigned, after a one month run-in
period, to three different treatments: TENS (Group T; n=20), infrared
lasertherapy (Group L; n=20) or acupuncture (Group A; n=20). In each group the
patients underwent ten sessions of treatment and monthly control visits. In Group
T patients were treated for two weeks (5 days/week) simultaneously with three
TENS units with different stimulation parameters (I: pulse rate = 80 Hz, pulse
width = 120 micros; II: 120 Hz, 90 micros; III: 4 Hz, 200 micros). In Group L an 
infrared diode laser (27 mW, 904 nm) was applied every other day on tender scalp 
spots. In Group A acupuncture was carried out twice a week in the first two weeks
and weekly in the next 6 weeks. A basic formula (LR3, SP6, LI4, GB20, GV20 and
Ex-HN5) was always employed; additional points were selected according to each
patient's symptomatology. The number of days with headache per month
significantly decreased during treatment in all groups. The response in the
groups differed over time, probably due to the different timing of applications
of the three methods. TENS, lasertherapy and acupuncture proved to be effective
in reducing the frequency of headache attacks. Acupuncture showed the best
effectiveness over time.

Publication Types: 
    Clinical Trial
    Comparative Study
    Randomized Controlled Trial

PMID: 12811613 [PubMed - indexed for MEDLINE]

2567: Neurol Sci. 2003 May;24 Suppl 2:S118-21.

Hemicrania continua: clinical and nosographic update.

Rapoport AM, Bigal ME.

Department of Neurology, Columbia University College of Physicians and Surgeons, 
New York, NY, USA.

Hemicrania continua (HC) is an uncommon primary headache syndrome. The main
features of HC are: (i) strict unilaterality of the pain (moderate, fluctuating, 
relatively long-lasting); and (ii) absolute response to indomethacin. These two
features may reflect the most reliable characteristics of the syndrome. Autonomic
symptoms are not as prominent in HC as they are in cluster headache and chronic
paroxysmal hemicrania, although they may exist. HC will be addressed in the 2003 
revision of the International Headache Society (IHS). In this paper we review the
clinical features, classification and treatment of HC.

Publication Types: 
    Lectures

PMID: 12811608 [PubMed - indexed for MEDLINE]

2568: Neurol Sci. 2003 May;24 Suppl 2:S94-6.

Neurobiology of chronic migraine.

Moschiano F, D'Amico D, Schieroni F, Bussone G.

L. Mandic Hospital, Via L. Mandic 1, Merate (LC), Italy.

Chronic daily headache (CDH) is an important problem for clinicians. It is
frequent in tertiary care structures, although at present there is no clear
consensus about definitions and operational criteria. In fact, CDH is a group of 
headache disorders that includes chronic migraine (CM). CDH usually evolves from 
an episodic headache form, which was migraine in most cases. Several
psychopathological factors (e.g. psychiatric comorbidity, personality traits or
stressful life events) and some somatic disorders (e.g. like arterial
hypertension, allergic condition, sleep disturbances) are frequent in CM
patients. Caffeine consumption, alcohol overuse and medication overuse (abortive 
drugs for migraine) could favour chronicity. The possible role of these factors
remains poorly understood. Prospective studies and research about the
pathophysiology of chronic pain will lead to a better understanding of CM.

Publication Types: 
    Lectures

PMID: 12811602 [PubMed - indexed for MEDLINE]

2569: Neurol Sci. 2003 May;24 Suppl 2:S90-3.

Chronic migraine and chronic tension-type headache: different aspects of the
chronic daily headache spectrum. Clinical and pathogenetic considerations.

Bussone G.

U.O. Cefalee e malattie cerebro-vascolari, Istituto Nazionale Neurologico C.
Besta, Via Celoria 11, I-20133 Milan, Italy.

Clinicians working in the field of headache face great difficulty in managing
patients with daily headache. Many of these patients have a history of episodic
migraine that over several years has transformed into a chronic headache. Others 
have a history of episodic tension-type headache that also has chronicized. Still
others present clinical characteristics that resemble both headache forms. In
this article, we review the clinical and pathophysiological aspects of chronic
daily headache and discuss the problems associated with its diagnosis.

Publication Types: 
    Review

PMID: 12811601 [PubMed - indexed for MEDLINE]

2570: Neurol Sci. 2003 May;24 Suppl 2:S65-7.

Elusive amines and primary headaches: historical background and prospectives.

D'Andrea G, Terrazzino S, Fortin D, Cocco P, Balbi T, Leon A.

Headache and Comorbidity Center, Department of Clinical Pathology, Este and
Monselice Hospital. Via San Fermo 10, I-35042 Este (PD), Italy.

Although the role of trace amines such as tyramine, octopamine and synephrine in 
the pathogenesis of migraine has been debated for decades, this issue remains
still unresolved. In spite of a relevant body of work, the inability to
demonstrate specific receptors for these compounds and the lack of sensitive
non-radioactive methods for the detection of trace amines in biological samples
have limited their investigation in humans. However, the recent identification of
a new, large family of G protein-coupled receptors, some of which bind and are
activated by trace amines, has focused renewed attention on these compounds. This
discovery, together with the possibility of providing novel insights for
evaluation of the pathophysiological role of trace amines in primary headaches,
may offer new opportunities for pharmacological strategies acting on these
receptors. In light of the new scientific background, this review outlines a
historical perspective and summarizes evidence supporting a role of trace amines 
in the pathogenesis of migraine and cluster headache.

Publication Types: 
    Historical Article
    Review

PMID: 12811595 [PubMed - indexed for MEDLINE]

2571: Cephalalgia. 2003 Jul;23(6):463-71.

Eletriptan for the treatment of migraine in patients with previous poor response 
or tolerance to oral sumatriptan.

Färkkilä M, Olesen J, Dahlöf C, Stovner LJ, ter Bruggen JP, Rasmussen S, Muirhead
N, Sikes C.

Helsinki Headache Centre, Helsinki, Finland. markus.farkkila@fimnet.fi

To determine the tolerability and efficacy of eletriptan in patients who had
discontinued oral sumatriptan due to lack of efficacy or intolerable adverse
events (AEs) during previous clinical treatment (not a controlled trial).
Eletriptan is a potent, selective 5-HT1B/1D receptor agonist with beneficial
pharmacokinetic properties compared with sumatriptan. In a double-blind, parallel
group, placebo-controlled multicentre study, patients with and without aura (n = 
446) were randomized to 40 mg eletriptan (E40, n = 188), 80 mg eletriptan (E80, n
= 171) or placebo (n = 87) for treatment of up to three migraine attacks.
Two-hour headache response, based on first-dose, first-attack data, was 59% for
eletriptan 40 mg, 70% for eletriptan 80 mg, and 30% for placebo (P < 0.0001 for
both doses of eletriptan vs. PBO; P < 0.05 for E80 vs. E40). Onset of action was 
rapid, with 1-h headache response rates significantly superior for E40 and E80
vs. placebo (40%, 48%, 15%; P < 0.0005). Both E40 and E80 were significantly
superior to placebo, based on first-dose, first-attack data, for 2-h pain-free
response (35%, 42%, and 7%; P < 0.0001). Both E40 and E80 demonstrated
significant consistency of response, with headache relief rates at 2 h on at
least two of three attacks in 66% and 72% vs. 15% on placebo (P < 0.001). AEs
were mild to moderate in severity and dose related. The most commonly reported
AEs included nausea, vomiting, asthenia, and chest symptoms. E40 and E80 produce 
an effective response in patients who had previously discontinued treatment with 
sumatriptan due to lack of efficacy or side-effects.

Publication Types: 
    Clinical Trial
    Comparative Study
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 12807526 [PubMed - indexed for MEDLINE]

2572: Cephalalgia. 2003 Jul;23(6):451-5.

Stress, anxiety, depression and migraine.

Wacogne C, Lacoste JP, Guillibert E, Hugues FC, Le Jeunne C.

Centre de Prise en Charge des Migraines et Céphalées, Internal Medicine
Department, Hôpital Européen Georges Pompidou, Paris, France.

This study investigated the intensity of stress, anxiety and depression in a
sample of 141 migraineurs compared with a control group of 109 non-migraine
workers matched for age and sex. Stress was measured using the Perceived Stress
Questionnaire, and anxiety and depression using the Hospital Anxiety and
Depression Scale. Results indicated that stress and anxiety were higher in the
migraine group than in the control group and above the clinical level. Depression
scores remained low in both groups, under clinical relevance. Stress is a
primordial factor in the triggering and perpetuation of migraine attacks. The
high score of the items 'morning fatigue', 'intrusive thoughts about work',
'feeling under pressure', 'impatience', and 'irritability' of the stress
questionnaire in the migraineurs is particularly significant in the intensive
stress response. It seems necessary to manage stress to improve the daily life of
migraineurs and to study the link between stress, anxiety and migraine.

Publication Types: 
    Comparative Study

PMID: 12807524 [PubMed - indexed for MEDLINE]

2573: Cephalalgia. 2003 Jul;23(6):441-50.

Migraine headache disability and health-related quality-of-life: a
population-based case-control study from England.

Lipton RB, Liberman JN, Kolodner KB, Bigal ME, Dowson A, Stewart WF.

Department of Neurology, Albert Einstein College of Medicine, Bronx, New York, NY
10461, USA. rlipton@aecom.yu.edu

The aims of this study were: (i) to compare health-related quality of life
(HRQoL) as measured by the Medical Outcomes Study Short Form 36-Item Health
Survey (SF-36) in a population sample of migraine headache sufferers and controls
without migraine; (ii) to assess the relationship of HRQoL and work-related
disability attributed to headache in a population sample. The study was conducted
in two phases. First, a population-based, telephone interview survey of 5769
residents of greater London, England was conducted to identify individuals with
migraine headache (cases) and controls without migraine. In the second stage,
in-person interviews were conducted in a matched sample of 200 migraine cases and
200 controls selected from survey respondents. At the beginning of the in-person 
interview, participants were asked to complete the SF-36. In addition, a
work-related disability score based on the telephone interview was defined as the
number of lost work days or days when usual activity was reduced by 50% or more
over the previous year. The disability score was trichotomized as mild (n = 98), 
moderate (n = 49), and severe disability (n = 49). Compared with controls,
individuals with migraine headache scored significantly lower in eight of the
nine domains of the SF-36 as well as in the overall Physical Component Summary
(PCS) score and Mental Component Summary (MCS) score. Further, among migraine
sufferers, each of the disability groups scored significantly lower in seven of
the nine domains and in the summary scales. Scores showed greater reductions in
HRQoL for the moderate and severe disability groups vs. the mild disability group
in five of nine scales and in the Total Physical Summary score. We conclude that,
in a population-based sample of migraine headache sufferers, individuals with
migraine headache have lower HRQoL scores compared with controls. Moreover, among
individuals with migraine headache, work-related disability is associated with
lower HRQoL scores. Specifically, individuals classified with moderate to severe 
work-related disability had lower HRQoL scores than those classified with low
disability.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 12807523 [PubMed - indexed for MEDLINE]

2574: Cephalalgia. 2003 Jul;23(6):429-40.

The family impact of migraine: population-based studies in the USA and UK.

Lipton RB, Bigal ME, Kolodner K, Stewart WF, Liberman JN, Steiner TJ.

Department of Neurology, Albert Einstein College of Medicine, Bronx, NY 10461,
USA. rlipton@aecom.yu.edu

Despite an extensive body of research on the individual burden of migraine, few
studies have examined its impact on the family. We aimed to assess the impact of 
migraine on family life both from the perspective of those with migraine and from
the perspective of their partners. A validated computer-assisted telephone
interview (CATI) identified 574 people with migraine from a population sample of 
4007 in mainland England, and 568 from 4376 in Philadelphia County, in the USA.
Migraine cases with six or more migraine attacks per year and living as married
with partners were asked, along with their partners, to participate in this
study. In a follow-up interview, questions were asked of the proband (i.e.
subject identified with migraine in the survey) about the impact of migraine.
Similar questions were also asked of the probands' partners regarding the impact 
of the proband's migraine on their participation in social, family and leisure
activities and on family relationships. The samples from the two countries showed
similar characteristics, and were combined. Of 389 people with migraine living
with a household partner, 85% reported substantial reductions in their ability to
do household work and chores, 45% missed family social and leisure activities,
and 32% avoided making plans for fear of cancellation due to headaches. One half 
believed that, because of their migraine, they were more likely to argue with
their partners (50%) and children (52%), while majorities (52-73%) reported other
adverse consequences for their relationships with their partner and children, and
at work. A third (36%) believed they would be better partners but for their
headaches. Participating partners (n = 100) partly confirmed these findings: 29% 
felt that arguments were more common because of headaches and 20-60% reported
other negative effects on relationships at home. Compared with subjects who did
not have migraine regarding their work performance, a statistically significantly
higher proportion of migraine partners were unsatisfied with work demands placed 
on them (P = 0.02), with their level or responsibilities and duties (P = 0.02),
and with their ability to perform (P = 0.001). Results from this study show that 
the impact of migraine extends to household partners and other family members.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 12807522 [PubMed - indexed for MEDLINE]

2575: Arq Neuropsiquiatr. 2003 Jun;61(2A):313-20. Epub 2003 Jun 9.

The triptan formulations: a critical evaluation.

Bigal ME, Bordini CA, Antoniazzi AL, Speciali JG.

Department of Neurology, Albert Einstein College of Medicine, Bronx, NY, USA.
marcelobigal@aecom.yu.edu

The migraine-specific triptans have revolutionized the treatment of migraine and 
are usually the drugs of choice to treat a migraine attack in progress. Different
triptans are available in different strengths and formulations including oral
tablets, orally disintegrating tablets, nasal sprays and subcutaneous injections.
In Europe, sumatriptan is also available as a suppository. Specific differences
among the triptans exist as evidenced by different pharmacological profiles
including T1/2, Tmax, Cmax, AUC, metabolism, drug-drug interaction profiles,
amongst other parameters. How or whether these differences translate to clinical 
efficacy and tolerability differences is not well differentiated. Clinical
distinctions among these agents are subtle and proper choice of triptan requires 
attention to the specific characteristics of each individual patient, knowledge
of patient preference, accurate history of the efficacy of previous acute care
medications as well as individual features of the drug being considered. Delivery
systems may play an important role in the onset of action of triptans. The
selection of an acute antimigraine drug for a patient depends upon the
stratification of the patient's migraine attack by peak intensity, time to peak
intensity, level of associated symptoms such as nausea and vomiting, time to
associated symptoms, comorbid diseases, and concomitant treatments that might
cause drug-drug interactions. The clinician has in his armamentarium an
ever-expanding variety of medications, available in multiple formulations and
dosages, with good safety and tolerability profiles. Continued clinical use will 
yield familiarity with the various triptans, and it should become possible for
the interested physician to match individual patient needs with the specific
characteristics of a triptan to optimize therapeutic benefit.

Publication Types: 
    Review

PMID: 12806521 [PubMed - indexed for MEDLINE]

2576: Brain. 2003 Jul;126(Pt 7):1660-70. Epub 2003 Apr 22.

Different patterns of parasympathetic activation in uni- and bilateral
migraineurs.

Avnon Y, Nitzan M, Sprecher E, Rogowski Z, Yarnitsky D.

Department of Neurology, Rambam Medical Center, Haifa, Israel.

Several lines of evidence support involvement of the parasympathetic system in
migraine: (i) migraine-associated symptoms, such as exaggerated facial flushing, 
lacrimation and rhinorrhea; (ii) increased levels of cranial venous vasoactive
intestinal peptide in migraineurs during attacks; and (iii) reports of migraine
pain alleviation by intranasal instillation of lidocaine, which can block some of
the parasympathetic outflow to the cranium. This study assessed cranial
parasympathetic function in migraineurs in between attacks, assuming that
abnormal function might imply involvement of the parasympathetics in migraine
pathogenesis. We tested 39 female migraineurs outside attacks, of whom 11 had
bilateral pain, 20 unilateral at a specific side and eight alternating unilateral
head pain, and 16 controls. The trigemino-parasympathetic reflex was studied,
using soapy and saline eye drops for stimulation of the afferent limb of the
reflex arch, and cutaneous vascular response at the forehead for the efferent
limb. The latter was recorded by photoplethysmography on both sides of the
forehead. We found no difference in vasodilatation between migraineurs as a group
and controls (83.7 +/- 6.5% and 80.8 +/- 7.6%, respectively, not significant).
However, when analysing data by the site of pain, we found that those with
bilateral pain had the largest vasodilatation response (141.6 +/- 16.2%, P < 0.05
versus controls, analysis of varance, post hoc Tukey-Kramer HSD), while those
with unilateral pain had the least vasodilatation (45.5 +/- 3.3%, P < 0.05). The 
response of patients with alternating pain (97.2 +/- 12.6%) did not differ from
controls. It is concluded that cranial parasympathetic function does differ among
patients with various migraine types at rest. Based on the understanding of
dysfunctional brainstem pain modulation in migraine, we suggest a model of
within-brainstem interaction between the two locus coeruleus nuclei, which are
involved in control of pain and cranial parasympathetic outflow. The model
assumes various levels of inhibitory inter-relationships between these two
nuclei; diminution or absence of the normal reciprocal inhibitory relationships
between them may underlie the augmented cranial parasympathetic response in
bilateral migraineurs, while an excess of reciprocal inhibitory relationship
between them may underlie the diminished cranial parasympathetic response in
unilateral migraineurs. These findings might help in clarifying
inter-relationships between brainstem nuclei in the context of migraine
pathogenesis.

PMID: 12805117 [PubMed - indexed for MEDLINE]

2577: Clin Neurophysiol. 2003 Jun;114(6):955-72.

Evoked potentials and transcranial magnetic stimulation in migraine: published
data and viewpoint on their pathophysiologic significance.

Schoenen J, Ambrosini A, Sándor PS, Maertens de Noordhout A.

University Department of Neurology, CHR Citadelle, Blvd du XIIèmede Ligne,
1-B-4000, Liège, Belgium. jean.schoenen@chrcitadelle.be

Migraine is a disorder in which central nervous sytem dysfunction might play a
pivotal role. Electroneurophysiology seems thus particularly suited to study its 
pathophysiology. We have extensively reviewed evoked potential and transcranial
magnetic stimulation studies performed in migraineurs in order to identify their 
pathophysiologic significance. Publications available to us were completed by a
Medline search. Retrieved and personal data were compared with respect to
methodology and interpreted according to present knowledge on cortical
information processing. Results are in part contradictory which appears to be
method-, patient- and disease- related. Nonetheless, both evoked potential and
transcranial magnetic stimulation studies demonstrate that the cerebral cortex,
and possibly subcortical structures, are dysfunctioning interictally in both
migraine with and without aura. These electrophysiologic abnormalities tend to
normalise just before and during an attack and some of them seem to have a clear 
familial and predisposing character. Besides the studies of magnetophosphenes
which have yielded contrasting results, chiefly because the method is not
sufficiently reliable, most recent electrophysiologic investigations of cortical 
activities in migraine favour deficient habituation and decreased preactivation
cortical excitability as the predominant interictal dysfunctions. We propose that
the former is a consequence of the latter and that it could favour both
interictal cognitive disturbances as well as a cerebral metabolic disequilibrium 
that may play a role in migraine pathogenesis. To summarize, electrophysiologic
studies demonstrate in migraine between attacks a cortical, and possibly
subcortical, dysfunction of which the hallmark is deficient habituation.

Publication Types: 
    Review

PMID: 12804664 [PubMed - indexed for MEDLINE]

2578: J Neurol. 2003 Jun;250(6):725-32.

Short latency trigemino-sternocleidomastoid response in patients with migraine.

Nardone R, Tezzon F.

Dept. of Neurology, F. Tappeiner Hospital, Via Rossini, 5, 39012 Merano, BZ,
Italy. raffaele.nardone@asbmeran-o.it

OBJECTIVE: To investigate the central trigeminal circuits in migraine patients.
MATERIALS AND METHODS: Short latency responses can be recorded in
sternocleidomastoid (SCM) muscles after stimulation of the trigeminal nerve
(trigemino-cervical reflex). This brainstem reflex was investigated in 20 healthy
subjects, in 20 patients suffering from migraine with aura (MWA) and in 20
patients suffering from migraine without aura (MWOA) during and between the
attacks. RESULTS: The trigemino-cervical responses were bilaterally abnormal in
17 patients with MWA and 15 patients with MWOA during the headache attacks, in 11
patients with MWA and in 10 patients with MWOA during the interictal period. In
the patients with normal trigemino-cervical responses during the pain-free phase 
the triptan was significantly more effective at relieving headache. CONCLUSIONS: 
Our findings further support and emphasise the role of the trigeminal system in
the pathogenesis of migraine. The bilateral location of the abnormalities
suggests a centrally located dysfunction. Therefore, the trigemino-cervical
reflex is sensitive in disclosing a disturbed brainstem activity and may be an
index of neuronal activity in the human brainstem; moreover their assessment may 
help as valuable prognostic tool for predicting the efficacy of triptans therapy.

Publication Types: 
    Clinical Trial
    Comparative Study

PMID: 12796836 [PubMed - indexed for MEDLINE]

2579: Biol Cybern. 2003 Jun;88(6):419-24.

Migraine aura dynamics after reverse retinotopic mapping of weak excitation waves
in the primary visual cortex.

Dahlem MA, Müller SC.

Akinematical model for excitable wave propagation is analyzed to describe the
dynamics of a typical neurological symptom of migraine. The kinematical model
equation is solved analytically for a linear dependency between front curvature
and velocity. The resulting wave starts from an initial excitation and moves in
the medium that represents the primary visual cortex. Due to very weak
excitability the wave propagates only across a confined area and eventually
disappears. This cortical excitation pattern is projected onto a visual hemifield
by reverse retinotopic mapping. Weak excitability explains the confined
appearance of aura symptoms in time and sensory space. The affected area in the
visual field matches in growth and form the one reported by migraine sufferers.
The results can be extended from visual to tactile and to other sensory symptoms.
If the spatiotemporal pattern from our model can be matched in future
investigations with those from introspectives, it would allow one to draw
conclusions on topographic mapping of sensory input in human cortex.

Publication Types: 
    Letter
    Research Support, Non-U.S. Gov't

PMID: 12789490 [PubMed - indexed for MEDLINE]

2580: Headache. 2003 Jun;43(6):672-7.

Clinical characteristics of patients with comorbidity of migraine and epilepsy.

Leniger T, von den Driesch S, Isbruch K, Diener HC, Hufnagel A.

Department of Neurology, University of Essen, Hufelandstrasse 55, 45122 Essen,
Germany.

OBJECTIVE: Neuronal hyperexcitability might explain the comorbidity of migraine
and epilepsy. Spreading depression, a postulated pathophysiological mechanism of 
epileptic seizures and migraine with aura, may hypothetically be the link between
the disorders in these comorbid conditions. The aim of the present study was to
determine whether certain clinical characteristics associated with spreading
depression are overrepresented in patients with comorbidity. METHODS: In an
outpatient clinic-based series, clinical characteristics of 61 patients with a
comorbidity of migraine and epilepsy were compared to those of 280 patients with 
epilepsy alone and 248 patients with migraine alone. Patients were interviewed
with a standardized questionnaire. RESULTS: The proportion of females was
significantly higher in patients with comorbidity and patients with migraine as
compared to patients with epilepsy (P <.001). Comparing patients with epilepsy
and comorbidity, the frequency of epilepsy syndromes and seizure types was not
significantly different. Comparing patients with migraine and comorbidity,
migraine with aura was significantly more frequent in patients with comorbidity
(P =.019). Other migraine features such as moderate to severe pain intensity,
worsening of pain on activity, phonophobia, and photophobia were significantly
more frequent in patients with comorbidity as compared to patients with migraine 
(P < or =.001). CONCLUSION: No specific epileptic characteristics could be found 
in patients with comorbidity. Altered cerebral excitability resulting in an
increased occurrence of spreading depression may explain the differences in
migraine attacks in patients with comorbidity as compared to patients with
migraine alone.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 12786928 [PubMed - indexed for MEDLINE]

2581: Headache. 2003 Jun;43(6):664-71.

Visual distortion provoked by a stimulus in migraine associated with
hyperneuronal activity.

Huang J, Cooper TG, Satana B, Kaufman DI, Cao Y.

Department of Radiology, Michigan State University, East Lansing, MI 48824, USA.

BACKGROUND: Migraineurs with visual aura are highly susceptible to illusions and 
visual distortion and are particularly sensitive to a pattern of regularly spaced
parallel lines or stripes. PURPOSE: To determine whether the high degree of
susceptibility to illusions and visual distortion in migraineurs with aura is
associated with hyperneurological activity of the occipital cortex. METHODS: In
order to investigate any relationships among neuronal activity, spatial frequency
of square-wave gratings, and self-described visual distortion, we investigated
the neuronal and psychophysical responses to square-wave gratings in migraineurs 
with visual aura and in nonheadache controls. RESULTS: Square-wave gratings
provoked various types of visual distortion and illusions and induced a
hyperneuronal response in the visual cortex of migraineurs with visual aura, a
response that strongly depended upon the stimulus spatial frequency. CONCLUSION: 
The hyperneuronal activity of the occipital cortex is consistent with general
cortical hyperexcitability in migraine.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 12786927 [PubMed - indexed for MEDLINE]

2582: Headache. 2003 Jun;43(6):651-63.

Erratum in:
    Headache. 2004 Nov-Dec;44(10):1071. Buenevar, Luis [corrected to Buenaver, Luis].

Differences in anger expression between individuals with and without headache
after controlling for depression and anxiety.

Nicholson RA, Gramling SE, Ong JC, Buenaver L.

Department of Community and Family Medicine, St. Louis University School of
Medicine, 1402 S. Grand Boulevard, St. Louis, MO 63104, USA.

OBJECTIVE: To evaluate whether anger and anger expression are different between
persons with and without headache after controlling for depression and anxiety.
BACKGROUND: Persons with headache may experience more problems with anger and its
expression when compared with persons without headache. It is important to
establish whether differences exist for persons with and without headache on
trait anger and anger expression independent of depression and anxiety. To date, 
however, this issue has received little attention in the empirical literature.
The current study measured trait anger, anger-in, hostility, anxiety, and
depression among persons with and without headache, and evaluated whether trait
anger and anger-in differentiated groups independent of depression and anxiety.
METHODS: Participants were 422 adults recruited from a larger study within a
university setting. Of those, 171 suffered from headache (mean age, 21 years; 81%
were female; 69% were white; mean years with pain, 7.53). Another 251 sex-matched
individuals (mean age, 21 years; 81% female; 62% white) met criteria for the
headache-free group. Participants provided information regarding their headache
characteristics and were administered affective trait measures (Trait version of 
the State-Trait Anxiety Inventory, Brief Symptom Inventory-Depression), trait
anger measures (Trait Anger Scale, Cook-Medley Hostility Scale), and a measure of
the extent to which individuals hold their anger in. RESULTS: Multivariate
analysis of variance revealed significant differences between the 2 groups (Wilks
lambda =.86, P <.001, eta2 =.14). Step-down analysis revealed that even after
controlling for all other variables, those in the headache group had higher
levels of anger-in (P <.001, eta2 =.08; mean, 18.98 versus 15.68). Trait anger
and hostility did not differ between groups after controlling for depression and 
anxiety. Logistic regression revealed that anger-in contributed most to
predicting headache status (P <.001; partial r =.23). CONCLUSIONS: The current
findings indicate that persons with headache hold their anger in more than those 
without headache even after controlling for levels of trait anger, depression,
and anxiety. However, after controlling for depression and anxiety, individuals
no longer differed on trait anger. Also, anger-in was the strongest predictor of 
headache. The current findings suggest that holding anger in is more common among
headache sufferers. Given recent findings regarding the negative effect of
holding anger in among persons with pain conditions, this may be an important
factor to evaluate when considering psychological/emotional factors affecting
headache.

Publication Types: 
    Comparative Study

PMID: 12786926 [PubMed - indexed for MEDLINE]

2583: Headache. 2003 Jun;43(6):645-50.

Reduced impact of migraine in everyday life: an observational study in the Dutch 
Society of Headache Patients.

Vos J, Passchier J.

Department of Medical Psychology and Psychotherapy, NIHES, Erasmus MC Rotterdam, 
3000 DR Rotterdam, The Netherlands.

OBJECTIVE: To explore the percentage of patients who report a reduced impact of
migraine on their life, and to which factors this improvement can be attributed. 
METHODS: Four hundred forty-eight members of the Dutch Society of Headache
Patients answered a set of structured questionnaires, including the
Migraine-Specific Quality of Life instrument (MSQOL). RESULTS: Of this group, 70%
reported a reduced impact of migraine. The most frequently reported reason for
this reduction was a change in medication (77%); in particular, change to a
triptan. Other favorable factors included a change in life-style (56%): 42% of
patients reported more relaxed coping with migraine, a reduction of stress in
general (28%) and of stress related to work (24%), and leading a more regular
life-style (21%). In addition, social support was frequently mentioned,
particularly that offered by the Dutch Society of Headache Patients (58%), family
(46%), and their general practitioner (28%). The patients who reported a reduced 
impact of migraine had less migraine attacks and a higher quality of life than
those who did not report such a reduction. CONCLUSION: The results confirm that
factors that are proven effective in clinical trials on migraine also have these 
effects outside a formal experimental environment.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 12786925 [PubMed - indexed for MEDLINE]

2584: Headache. 2003 Jun;43(6):638-44.

Factors associated with burden of primary headache in a specialty clinic.

Cassidy EM, Tomkins E, Hardiman O, O'Keane V.

Migraine/Headache Clinic, Departments of Psychiatry and Neurology, Beaumont
Hospital, Dublin, Ireland.

OBJECTIVE: To examine factors associated with social, occupational, and
psychological burden of common primary headache (migraine and tension-type
headache). BACKGROUND: The personal and social burden of primary headache is
high. Health, occupational, social, and psychological factors contributing to
burden in people with disabling headache have not been fully unravelled. METHODS:
One hundred eighty consecutive patients with either migraine or tension-type
headache attending a specialty headache outpatient clinic for the first time were
evaluated over a 9-month period. Headache subtype was operationally defined
according to International Headache Society criteria. Headache frequency,
duration, and severity were recorded. Occupational and social disability were
quantified using the Migraine Disability Assessment questionnaire. Psychological 
burden was quantified using the 28-item General Health Questionnaire, the Beck
Depression Inventory, and the State-Trait Anxiety Inventory. Premorbid
vulnerability to life stress was quantified using the neuroticism subscale of the
Eysenck Personality Inventory. RESULTS: Patients with frequent (chronic) headache
scored higher on the Migraine Disability Assessment questionnaire and had higher 
Beck Depression Inventory and General Health Questionnaire depression scores than
those with less frequent (episodic) headache. Frequency of headache, but not pain
severity, duration, or diagnosis, predicted both Migraine Disability Assessment
total disability and General Health Questionnaire/Beck Depression Inventory
depression. Neuroticism was predictive of depression but not disability. Patients
with chronic migraine had the highest depression and disability scores.
CONCLUSION: The number of days per month with headache is a key determinant of
headache-related burden in those attending specialty clinics. Frequent (chronic) 
headache is associated with significantly higher psychopathology scores and
general social impairment, but the direction of this relationship is not clear.
Those with migraine and chronicity are the most impaired.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 12786924 [PubMed - indexed for MEDLINE]

2585: Headache. 2003 Jun;43(6):628-35.

Comment in:
    Headache. 2003 Jun;43(6):636-7.

Assessing the severity of migraine: development of the MIGSEV scale.

El Hasnaoui A, Vray M, Richard A, Nachit-Ouinekh F, Boureau F; MIGSEV Group.

Epidemiology Department, GSK Laboratory, 100 Route de Versailles, 78 163
Marly-le-Roi Cedex, France.

OBJECTIVES: To identify items that serve to assess the severity of migraine with 
a high level of clinical and psychometric relevance and to combine these into a
unitary severity scale. BACKGROUND: Severity of migraine is an important
determinant of patient quality of life and of health care resource utilization.
Despite this, no validated method exists for measuring migraine severity.
METHODS: After selection from the medical literature items of potential relevance
to the severity of migraine, consensus meetings led to a choice of items which
subsequently were refined further on the basis of patient interviews. The
psychometric properties of those items then were assessed in a survey involving
287 migraineurs. The methods used to test reliability and validity included
test-retest, calculation of Cronbach alpha coefficient, analysis of factorial
structure using principal components analysis, a comparison of the agreement
between doctors' and patients' assessments, and correlation with a validated
quality-of-life questionnaire. The most pertinent items revealed by the factorial
analysis were combined in a unitary scale. RESULTS: Seven items reflecting
severity were identified by expert consensus. These were intensity of pain,
tolerability, disability in daily activities, presence of nausea or vomiting,
resistance to treatment, duration of attacks, and frequency of attacks. Principal
components analysis identified 3 dimensions accounting for 65% of the overall
variance related to intensity of attacks, resistance to treatment, and frequency 
of attacks. The internal consistency and the reproducibility of the items
appeared quite satisfactory, and variations in these items were correlated with
quality-of-life scores. The 4 items related to intensity of attacks were combined
into a single scale with 3 response modalities. CONCLUSIONS: The 3 dimensions
identified by this investigation appeared medically relevant and to have good
psychometric properties. The items on the intensity dimension can be used to
generate a simple scale for assessing migraine attack severity.

Publication Types: 
    Comparative Study

PMID: 12786922 [PubMed - indexed for MEDLINE]

2586: Headache. 2003 Jun;43(6):601-10.

Comment in:
    Headache. 2004 May;44(5):445-6.

Oral magnesium oxide prophylaxis of frequent migrainous headache in children: a
randomized, double-blind, placebo-controlled trial.

Wang F, Van Den Eeden SK, Ackerson LM, Salk SE, Reince RH, Elin RJ.

Department of Neurology, Kaiser Permanente, Hayward, CA, USA.

OBJECTIVE: To assess whether, in children, oral magnesium oxide reduces
migrainous headache frequency, severity, and associated features compared to
placebo. BACKGROUND: There is no single, safe, widely well-tolerated, and
effective prophylactic treatment for all children and adolescents with frequent
migrainous headache. DESIGN: Randomized, double-blind, placebo-controlled,
parallel-group trial. METHODS: This study was conducted between June 1997 and
January 2000 using 7 selected Northern California Kaiser Permanente sites. We
recruited children of ages 3 to 17 years who reported a 4-week history of at
least weekly, moderate-to-severe headache with a throbbing or pulsatile quality, 
associated anorexia/nausea, vomiting, photophobia, sonophobia, or relief with
sleep, but no fever or evidence of infection. Subjects were randomly assigned to 
receive either magnesium oxide (9 mg/kg per day by mouth divided 3 times a day
with food) (n = 58) or matching placebo (n = 60) for 16 weeks. The number of
headache days (days with at least one headache) during each of eight 2-week
intervals was chosen to be the primary outcome variable. RESULTS: Of those
enrolled, 86 (73%) completed the study (42 received magnesium oxide and 44
placebo); 74 of 192 eligible subjects declined to participate. Baseline
information on demographic factors, health status, and headache history was
similar comparing the 2 groups. By intention-to-treat analysis, we found a
statistically significant decrease over time in headache frequency in the
magnesium oxide group (P =.0037) but not in the placebo group (P =.086), although
the slopes of these 2 lines were not statistically significantly different from
each other (P =.88). The group treated with magnesium oxide had significantly
lower headache severity (P =.0029) relative to the placebo group. CONCLUSIONS:
This study does not unequivocally determine whether oral magnesium oxide is or is
not superior to placebo in preventing frequent migrainous headache in children,
but treatment with the active agent did lead to a significant reduction in
headache days. Larger trials involving this safe, appealing complementary therapy
are needed.

Publication Types: 
    Clinical Trial
    Comparative Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 12786918 [PubMed - indexed for MEDLINE]

2587: Indian J Pediatr. 2003 Mar;70 Suppl 1:S39-44.

Migraine: a common cause of headache.

Sabharwal RK.

Department of Pediatrics, Sir Ganga Ram Hospital, New Delhi-110060, India.
mukpran@yahoo.com

Acute headaches in a child evoke anxiety in parents, of a possible catastrophic
underlying intracranial pathology. Headaches constitute up to 2 to 6% of all
emergency room visit. The prevalence of migraine is increasing. The majority of
children have migraine without aura, and about one fifth have migraine with aura.
Complicated migraine presents with dramatic neurologic signs and remains a
diagnosis of exclusion. Children with migraine require reassurance, modification 
of life style and food habits, combined with judicious use of simple abortive
medications and antiemetics. Prophylaxis in migraine is recommended for frequent 
or severe attacks and in complicated migraine.

Publication Types: 
    Review

PMID: 12785281 [PubMed - indexed for MEDLINE]

2588: Cephalalgia. 2003 Jun;23(5):389-94.

Migrainous cerebral infarction in the Sagrat Cor Hospital of Barcelona stroke
registry.

Arboix A, Massons J, García-Eroles L, Oliveres M, Balcells M, Targa C.

Acute Stroke Unit, Department of Neurology, Hospital del Sagrat Cor, Barcelona,
Spain. aarboixd@meditex.es

Nine of 2000 consecutive stroke patients included in the Sagrat Cor Hospital of
Barcelona Stroke Registry over a 10-year period fulfilled the strictly defined
International Headache Society criteria for migrainous stroke and in whom other
causes of stroke were ruled out. They accounted for 13% of all first-ever
ischaemic stroke of unusual cause. Migrainous stroke was more common in women
(67%) and in patients aged 45 years or younger (78%) compared to the remaining
ischaemic strokes of unusual cause. No patient died during hospital stay and 67% 
were symptom-free at discharge. In the multivariate analysis, nausea or vomiting 
(odds ratio (OR) 8.40, 95% confidence interval (CI) 1.49-47.21) and age (OR 0.95,
95% CI 0.91-0.99) were predictors of migrainous stroke. Migrainous stroke is a
rare entity. Vascular risk factors are uncommon and the prognosis is generally
good. Patients with migrainous stroke present some different clinical features
from other ischaemic strokes of unusual aetiology.

Publication Types: 
    Comparative Study

PMID: 12780770 [PubMed - indexed for MEDLINE]

2589: Cephalalgia. 2003 Jun;23(5):381-8.

Epidemiological and clinical characteristics of migraine and tension type
headache in 1146 females in Kayseri, Turkey.

Köseoglu E, Naçar M, Talaslioglu A, Cetinkaya F.

Headache Centre, Department of Neurology, University of Erciyes, Kayseri, Turkey.
emelk@erciyes.edu.tr

In a female population of Turkey (1146 adult females), some epidemiological and
clinical characteristics of migraine and tension type headache and their subtypes
were investigated. The relation of the headache severity to clinical
characteristics were inquired. Migraine prevalence was found to be statistically 
higher in the 35-44 years age group (P < 0.01) and those who were university
graduates (P < 0.001), married (P < 0.01) and living in urban areas (P < 0.01).
Tension type headache was found to be higher in the 45-64 years age group (P <
0.05). Chronic tension type headache patients were found to be older than
episodic type (P < 0.01) and frequently were in the lowest education level (P <
0.05). Presence of impact on daily activities because of the severity of headache
was found to be related to aggravation by physical activities (P = 0.001) in
tension type headache, with no clinical characteristics in migraine headache and 
on consideration of all headache patients with throbbing nature (P < 0.05),
aggravation on physical activities (P = 0.001), nausea (P < 0.01), vomiting (P < 
0.05) and phonophobia (P < 0.05).

Publication Types: 
    Comparative Study

PMID: 12780769 [PubMed - indexed for MEDLINE]

2590: Cephalalgia. 2003 Jun;23(5):367-75.

Selective decrease in serotonin synthesis rate in rat brainstem raphe nuclei
following chronic administration of low doses of amitriptyline: an effect
compatible with an anti-migraine effect.

Pringsheim T, Diksic M, Dobson C, Nguyen K, Hamel E.

Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill
University, Montréal, Québec, Canada.

The effects of chronic, low-dose amitriptyline on serotonin (5-HT) synthesis rate
were measured in rat brain using autoradiography and the trapping of
alpha-[14C]-methyl-L-tryptophan (alpha-[14C]-MTrp). Rats received amitriptyline
(2 mg/kg per day) or saline via intraperitoneal osmotic minipumps for 21 days.
Amitriptyline had no effect on any physiological parameters measured, or on free 
or total plasma tryptophan levels. However, amitriptyline exerted selective
decreases of 15% and 17% (P < 0.001) in serotonin synthesis rates in the dorsal
and median raphe nuclei, respectively. There was no reduction in any of the
projection areas studied, including the cerebral cortex, hippocampus, thalamus,
hypothalamus or striatum. The data suggest that chronic low doses of
amitriptyline can lead to sustained 5-HT re-uptake inhibition selectively in the 
raphe nuclei, an effect compatible with tonic activation of 5-HT(1A)
autoreceptors and inhibition of 5-HT synthesis. The failure of chronic
amitriptyline treatment to affect 5-HT synthesis rate in the projection areas may
ensure an adequate regulation of pain pathways implicated in migraine headache,
an effect possibly related to amitriptyline anti-migraine efficacy.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 12780767 [PubMed - indexed for MEDLINE]

2591: Cephalalgia. 2003 Jun;23(5):344-7.

Effect of active treatment is lower when using placebo control in clinical trials
on acute therapy of migraine.

Eikermann A, Diener HC.

Klinik and Poliklinik für Neurologie, Universitätsklinikum Essen, Essen, Germany.
astrid.eikermann@uni-essen.de

Methodological aspects of study design affect therapeutic outcome. We tested the 
hypothesis that treatment effect of an active drug in studies on acute therapy of
migraine is lower in placebo-controlled studies than in those not using a
placebo-controlled design. From 522 eligible studies on acute therapy of migraine
cited in Pubmed database which were published between 1964 and 1997 we randomly
selected 100 studies for evaluation. We excluded five studies because they did
not include a quantitative measurement of pain intensity. Of the 95 studies
included in the analysis, 61 used placebo control. Response to active drug was
significantly lower (P < 0.05) in placebo-controlled studies (61% [lower and
upper quartiles 44% and 75%] vs. 71% [56% and 75%]). We did not find any
significant effect of quality of study design on net effect of verum. This
observation should be taken into account for future planning of controlled
clinical studies in acute migraine.

Publication Types: 
    Comparative Study
    Evaluation Studies

PMID: 12780763 [PubMed - indexed for MEDLINE]

2592: Cephalalgia. 2003 Jun;23(5):336-43.

Migraine and tension-type headache in Croatia: a population-based survey of
precipitating factors.

Zivadinov R, Willheim K, Sepic-Grahovac D, Jurjevic A, Bucuk M, Brnabic-Razmilic 
O, Relja G, Zorzon M.

Department of Clinical Medicine and Neurology, University of Trieste, Trieste,
Italy. zivadinov@hotmail.com

The careful monitoring of the trigger factors of headache could be an important
step in treatment, because their avoidance may lessen the frequency and severity 
of attacks. Furthermore, they may provide a clue to the aetiology of headache.
The aim of the present study was to estimate the prevalence of tension-type
headache (TTH) and to establish the frequency of precipitating factors in
subjects with migraine and TTH in the adult population of Bakar, County of the
Coast and Gorski Kotar, Croatia. Another important purpose of the study was to
examine the relationship of the precipitating factors with migraine and TTH, and 
with migraine subtypes: migraine with aura (MA) and migraine without aura (MO).
We performed a population-based survey using a 'face-to-face door-to-door'
interview method. The surveyed population consisted of 5173 residents aged
between 15 and 65 years. The 3794 participants (73.3%) were screened for headache
history according to the International Headache Society (IHS) criteria. Headache 
screen-positive responders, 2475 (65.2%), were interviewed by trained medical
students with a structured detailed interview focused on the precipitating
factors. The following precipitating factors in lifetime migraineurs and
tension-type headachers have been assessed: stress, sleep disturbances, eating
habits, menstrual cycle, oral contraceptives, food items, afferent stimulation,
changes in weather conditions and temperature, frequent travelling and physical
activity. A total of 720 lifetime migraineurs and 1319 tension-type headachers
have been identified. The most common precipitants for both migraine and TTH were
stress and frequent travelling. Stress (odds ratio (OR) 1.4, 95% confidence
interval (CI) 1.17, 1.69) was associated with migraine, whereas physical activity
(OR 0.72, 95% CI 0.59, 0.87) was related to TTH. Considering MA and MO, frequent 
travelling (OR 2.2, 95% CI 1.59, 2.99), food items (OR 2.2, 95% CI 1.35, 3.51)
and changes in weather conditions and temperature (OR 1.75, 95% CI 1.27, 2.41)
exhibited a significant positive association with MA. The present study
demonstrated that precipitant-dependent attacks are frequent among both
migraineurs and tension-type headachers. Lifetime migraineurs experienced
headache attacks preceded by triggering factors more frequently than tension-type
headachers. MA was more frequently associated with precipitating factors than MO.
We suggest that some triggering factors may contribute to the higher occurrence
of precipitant-dependent headache attacks in susceptible individuals.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 12780762 [PubMed - indexed for MEDLINE]

2593: Neurosci Lett. 2003 Jun 12;343(3):155-8.

Absence of linkage between the interleukin-6 gene (-174 G/C) polymorphism and
migraine.

Rainero I, Salani G, Valfrè W, Savi L, Rivoiro C, Ferrero M, Pinessi L, Grimaldi 
LM.

Neurology III--Headache Center, Department of Neuroscience, University of Torino,
Via Cherasco 15-10126, Turin, Italy. irainero@molinette.piemonte.it

To assess the role of interleukin-6 (IL-6) in migraine, we analyzed the -174 G/C 
IL-6 gene polymorphism in 268 patients with migraine and 305 controls. No
significant difference in the distribution of IL-6 genotypes (chi(2)=0.601,
P=0.74) and allelic frequencies (chi(2)=0.024, P=0.876) was found. When patients 
were subdivided into subgroups (migraine with aura, migraine without aura and
mixed headaches), IL-6 alleles were similarly distributed. Comparison of the
clinical features of the disease with the -174 G/C IL-6 genotypes showed no
significant difference. In conclusion, we found no significant association
between the -174 G/C IL-6 polymorphism and the occurrence or the clinical
features of migraine.

PMID: 12770686 [PubMed - indexed for MEDLINE]

2594: Pharmacol Res. 2003 Jul;48(1):1-9.

Emerging problems in the pharmacology of migraine: interactions between triptans 
and drugs for prophylaxis.

Ferrari A, Sternieri E, Ferraris E, Bertolini A.

Department of Internal Medicine, Centre for the Study of Headache, Largo del
Pozzo 71, 41100 Modena, Italy. annaf@unimore.it

Patients suffering from migraine take drugs for many years in order either to
relieve or to prevent recurrent migraine attacks. When two or more drugs are
co-administered, there is always the possibility of drug-drug interaction.
Interactions can be either kinetic or dynamic. The former are the most frequent
ones. Mechanisms of kinetic interaction can be different, but the most common are
represented by the induction or inhibition of enzymes of the cytochromes p450
(CYP) system. This system plays an important role in the disposition of a large
number of drugs, including those used for migraine. This review examines the
interactions between triptans-the most effective drugs for the therapy of
migraine attacks-and drugs for migraine prophylactic treatment.

Publication Types: 
    Review

PMID: 12770508 [PubMed - indexed for MEDLINE]

2595: Ann Emerg Med. 2003 Jun;41(6):847-53.

Intravenous sodium valproate versus prochlorperazine for the emergency department
treatment of acute migraine headaches: a prospective, randomized, double-blind
trial.

Tanen DA, Miller S, French T, Riffenburgh RH.

Department of Emergency Medicine, Naval Medical Center San Diego, San Diego, CA
92134, USA. Datanen@navy.med.mil

STUDY OBJECTIVE: We compare the efficacy of intravenous sodium valproate versus
prochlorperazine for the emergency department treatment of acute migraine
headache. METHODS: We performed a randomized, prospective, double-blind trial
performed at a tertiary care military ED. Forty patients, aged 18 to 65 years,
presenting with typical migraine symptoms were enrolled. Patients were randomized
to receive either 10 mg of prochlorperazine or 500 mg of valproate intravenously 
over 2 minutes. Pain, nausea, and sedation were assessed by using a standard
visual analog scale (VAS). Changes in VAS scores were compared between groups
from baseline to end point by using a rank sum test, over time by using 2-way
repeated-measures analysis of variance, and by requirement for rescue at 60
minutes by using the Fisher exact test. RESULTS: Comparison of the change in
median VAS scores over 60 minutes revealed that sodium valproate was
significantly less effective than prochlorperazine in reducing pain or nausea (P 
<.001). Median improvements in VAS pain scores (binomial confidence intervals)
were as follows: 64.5 mm (48.1 to 75.6 mm) for prochlorperazine versus 9 mm (-3
to 39.6 mm) for sodium valproate. Median improvements in VAS nausea scores were
as follows: 35.5 mm (13.2 to 47.9 mm) for prochlorperazine versus 2 mm (-1.3 to
11 mm) for sodium valproate. There was no significant difference (P =.603)
detected in the median changes in VAS scores for sedation: -4 mm (-29.9 to 8.6
mm) for prochlorperazine versus 0 mm (-6.6 to 6 mm) for sodium valproate.
Comparison of the mean VAS time curves for pain and nausea also demonstrated a
significant difference (both P <.001) but not for sedation (P =.232). In post hoc
analysis, valproate failed to elicit significant improvement in pain or nausea
scores over time, whereas prochlorperazine improved pain by 30 minutes (P <.001) 
and nausea by 15 minutes (P =.002). At the conclusion of the study, 15 (79%) of
19 patients receiving valproate required rescue treatment compared with 5 (25%)
of 20 patients receiving prochlorperazine (P <.001). CONCLUSION: Prochlorperazine
was statistically and clinically superior to sodium valproate for the treatment
of the pain and nausea associated with acute migraine headaches.

Publication Types: 
    Clinical Trial
    Comparative Study
    Randomized Controlled Trial
    Research Support, U.S. Gov't, Non-P.H.S.

PMID: 12764341 [PubMed - indexed for MEDLINE]

2596: J Orofac Pain. 2003 Winter;17(1):74-8.

Chronic paroxysmal hemicrania: a case report and review of the literature.

Sarlani E, Schwartz AH, Greenspan JD, Grace EG.

Department of Oral and Craniofacial Biological Sciences, Brotman Facial Pain
Center, Dental School, University of Maryland, Room # 2-A-15, 666 West Baltimore 
St, Baltimore, MD 21201, USA.

Chronic paroxysmal hemicrania (CPH) is a rare type of headache that is
characterized by daily, multiple, short-lasting attacks of severe pain and
associated autonomic symptoms. The pain is strictly unilateral and presents most 
commonly in the ocular, temporal, maxillary, and frontal areas. The excruciating,
throbbing pain of CPH can be misdiagnosed as pain associated with dental
pathology, especially when located in the maxillary area. Moreover, pain
manifesting in the maxillary and temporal areas can be confused with
temporomandibular disorders. CPH patients occasionally seek treatment in dental
offices or orofacial pain centers. Accordingly, dentists should be familiar with 
CPH in order to avoid unnecessary, irreversible dental treatment. A case is
presented to highlight many of the features of CPH.

Publication Types: 
    Case Reports
    Review

PMID: 12756934 [PubMed - indexed for MEDLINE]

2597: Arch Neurol. 2003 May;60(5):684-8.

Comment in:
    Arch Neurol. 2003 May;60(5):663-4.

Expanding the phenotypic spectrum of the CACNA1A gene T666M mutation: a
description of 5 families with familial hemiplegic migraine.

Kors EE, Haan J, Giffin NJ, Pazdera L, Schnittger C, Lennox GG, Terwindt GM,
Vermeulen FL, Van den Maagdenberg AM, Frants RR, Ferrari MD.

Department of Neurology, Leiden University Medical Centre, Leiden, The
Netherlands.

BACKGROUND: Familial hemiplegic migraine (FHM) is a rare autosomal dominant
subtype of migraine with aura. Missense mutations in the chromosome 19 CACNA1A
calcium channel gene have been found in approximately half of the families. The
T666M mutation, replacing a threonine by a methionine at residue number 666, is
the most frequent mutation, reported in 14 independent FHM families; other
mutations have so far been described in only 1 or 2 families each. The clinical
features of T666M families have been reported, but the course is unknown.
OBJECTIVE: To present a detailed description of the clinical features of new FHM 
families in which we identified the T666M mutation in our CACNA1A screening
program. METHODS: As part of our ongoing genetic screening, mutation analysis of 
the CACNA1A gene was performed by single-strand conformational polymorphism
analysis in 33 probands of families with FHM. RESULTS: We identified the T666M
mutation in 5 unrelated FHM families. In 3 of the families, patients displayed
cerebellar ataxia. In 1 family, some affected members with the mutation had
attacks with confusion but without hemiparesis. In 1 family, patients had
progressive cognitive dysfunction. CONCLUSIONS: The T666M mutation is the most
frequent CACNA1A mutation in FHM; it was found in 5 of 33 FHM families at our
laboratory, and in 19 of 39 families with a known mutation reported in the
literature (including the present study). Screening for the T666M mutation should
therefore be the first step when screening families with FHM. There is a
remarkable clinical heterogeneity among families with the T666M mutation.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 12756131 [PubMed - indexed for MEDLINE]

2598: Headache. 2003 May;43(5):496-8.

Comment in:
    Headache. 2004 Mar;44(3):291-2.

Transformation into daily migraine with aura following transcutaneous atrial
septal defect closure.

Yankovsky AE, Kuritzky A.

Department of Neurology, Rabin Medical Center, Beilinson Campus, Petah Tiqva and 
Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.

A link between migraine with aura and cardiac right-to-left shunting has been
previously reported. Abortion or decreased frequency of migraine with aura
attacks after atrial septal defect closure has been reported in the literature.
We report the first case of transformation of migraine with aura into a daily
pattern after atrial septal defect closure. A 48-year-old male who had been
suffering from rather infrequent attacks of migraine with sensory and visual aura
underwent transcutaneous closure of an atrial septal defect. His migraine attacks
changed into a daily pattern the day following the procedure and remained so for 
6 months. This change in pattern may be related to a changed intra-atrial
pressure after the closure or some other unknown factor.

Publication Types: 
    Case Reports

PMID: 12752756 [PubMed - indexed for MEDLINE]

2599: Headache. 2003 May;43(5):490-5.

Carnitine palmityltransferase II (CPT2) deficiency and migraine headache: two
case reports.

Kabbouche MA, Powers SW, Vockell AL, LeCates SL, Hershey AD.

Divisions of Neurology, Cincinnati (Ohio) Children's Hospital Medical Center,
Cincinnati, OH 45229, USA.

BACKGROUND: Migraine headache is common and has multiple etiologies. A number of 
mitochondrial anomalies have been described for migraine, and mitochondrial
dysfunction has been implicated as one potential pathophysiological mechanism.
Carnitine is used by mitochondria for fatty acid transportation; its deficiency, 
however, has not been implicated in migraine pathophysiology. METHODS AND
RESULTS: Two adolescent girls presented to the Headache Center at Cincinnati
Children's Hospital Medical Center with frequent headaches and were diagnosed
with migraine by the International Headache Society (IHS) criteria. Both girls
had a history of recurrent fatigue, muscle cramps, and multiple side effects from
their prophylactic treatment. Carnitine levels were measured and found to be low.
Carnitine supplementation was initiated. Both patients had a reduction in
headache frequency, as well as an improvement in their associated symptoms and
other complaints. A skin and muscle biopsy obtained from one patient revealed a
partial carnitine palmityltransferase II deficiency in the muscle only.
CONCLUSIONS: Carnitine palmityltransferase II deficiency may represent another
etiology for migraine headache, and may be useful in further defining the
pathophysiology of migraine. When properly recognized, supplementation with
carnitine may improve the outcome of the migraine as well as the
carnitine-associated symptoms.

Publication Types: 
    Case Reports

PMID: 12752755 [PubMed - indexed for MEDLINE]

2600: Headache. 2003 May;43(5):482-9.

Naratriptan in the preventive treatment of refractory chronic migraine: a review 
of 27 cases.

Rapoport AM, Bigal ME, Volcy M, Sheftell FD, Feleppa M, Tepper SJ.

Department of Neurology, Columbia University College of Physicians and Surgeons, 
New York, NY, USA.

OBJECTIVE: To review the efficacy of naratriptan as preventive treatment in 27
patients with chronic migraine refractory to other commonly used preventive
therapies. BACKGROUND: The treatment of chronic migraine often poses a major
challenge to the clinician. Even when given expert care, patients with chronic
migraine may continue to have daily or near-daily headaches. METHODS: Clinical
records and headache calendars were reviewed of 27 patients fulfilling the
following inclusion criteria: (1) aged 18 to 65 years; (2) diagnosis of chronic
migraine (formerly transformed migraine), according to the criteria proposed by
Silberstein et al; (3) previous failure of at least 4 preventive medications
prescribed as part of a management program that included nonpharmacological
measures, preventive medication, acute care medication, and detoxification from
overused medication; and (4) have used daily naratriptan for no less than 2
consecutive months. The dose of naratriptan prescribed was 2.5 mg twice daily. We
considered the following outcomes: (1) frequency of headache, (2) intensity of
pain, (3) number of days per month with severe headache, (4) headache index
(frequency times intensity), and (5) proportion of patients who reverted to an
episodic pattern of pain after 6 months of treatment. RESULTS: There was a
statistically significant reduction in the frequency of headache days 2 months
(15.3 days versus 24.1 days at baseline, P<.001), 6 months (9.1 days, P<.001),
and 1 year (7.3 days, P<.001) after daily treatment with naratriptan was
initiated. There was also a statistically significant reduction in the number of 
days per month of severe pain at 1 month (5.6 days versus 12.5 days at baseline, 
P<.01), 2 months (5.7 days, P<.01), 6 months (2.8 days, P<.01), and 1 year (2.6
days, P<.01). Similarly, there was a statistically significant reduction in the
headache index at 2 months (33 versus 56.4 at baseline, P<.001), 6 months (19.5, 
P<.001), and 1 year (17.2, P<.001). Of the 20 patients who continued to use
naratriptan daily for at least 6 months, 13 (65%) reverted to an episodic pattern
of pain (migraine). At 1 year, 11 (55%) still continued to experience episodic
headache, 1 (5%) relapsed to chronic migraine, and 2 (10%) were lost to
follow-up. No patients had intolerability to naratriptan during the treatment
period, and no one stopped treatment due to adverse events. CONCLUSIONS:
Naratriptan may have a role in the preventive treatment of intractable chronic
migraine. Prospective, controlled studies should be considered.

Publication Types: 
    Comparative Study

PMID: 12752754 [PubMed - indexed for MEDLINE]

2601: Headache. 2003 May;43(5):470-8.

Comment in:
    Headache. 2004 Jan;44(1):106; author reply 106.

Migraine prevalence during menopausal transition.

Wang SJ, Fuh JL, Lu SR, Juang KD, Wang PH.

Neurological Institute, Taipei Veterans General Hospital and National Yang-Ming
University School of Medicine, Taipei, Taiwan.

BACKGROUND: The effect of menopausal transition on the frequency of migraine has 
never been the focus of a community-based study. METHODS: A cross-sectional
community-based survey was undertaken among Chinese women aged 40 to 54 years in 
Kinmen, Taiwan. Neurologists diagnosed migraine based on the 1988 International
Headache Society classification criteria. Menstrual history including a past or
current history of premenstrual syndrome was obtained. Serum levels of estradiol 
and follicle-stimulating hormone were measured. RESULTS: The 1-year prevalence of
migraine was 16.5% in the 1436 participants. Among the women who had not had
hysterectomies and did not report symptoms of premenstrual syndrome, migraine
prevalence did not vary according to menopausal status. In contrast, in women
with self-reported premenstrual syndrome, menopausal status was a factor in
migraine prevalence: the late perimenopausal group had the highest prevalence
(31%) and the spontaneous menopausal group had the lowest (7%). Among all
menopausal groups, women who had had hysterectomies reported the highest migraine
prevalence (27%), with the highest occurring in those with premenstrual syndrome 
(44%). The presence of low estrogen (<50 pg/mL) and high follicle-stimulating
hormone levels (>30 mIU/mL) was associated with lower migraine prevalence, even
in the premenopausal and early perimenopausal women. CONCLUSIONS: Our data
supported the clinical impression that migraine prevalence increases before
menopause and declines after spontaneous menopause. However, in this study, this 
trend occurred only in women with increased vulnerability to hormonal change,
such as those with premenstrual syndrome. The presence of low estrogen and high
follicle-stimulating hormone levels predicted lower migraine prevalence, whereas 
a history of hysterectomy was related to higher prevalence.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 12752752 [PubMed - indexed for MEDLINE]

2602: Headache. 2003 May;43(5):464-9.

Normalization of high interictal cerebrovascular reactivity in migraine without
aura by treatment with flunarizine.

Dora B, Balkan S, Tercan E.

Departments of Neurology, Akdeniz University Medical School, Antalya, Turkey.

BACKGROUND: Modification of migraine-associated cerebrovascular reactivity may
provide insight into the mechanism of action of a given therapeutic intervention.
METHODS: With transcranial Doppler and a breath-holding index, cerebrovascular
reactivity to hypercapnia was evaluated in 20 patients with migraine without aura
interictally and in 11 healthy controls. Patients were started on prophylactic
treatment with flunarizine 10 mg per day, and measurements were repeated at the
end of every month for 3 months. Headache status was evaluated clinically via a
headache index. Headache index; breath-holding index; systolic, diastolic, and
mean blood flow velocities; and pulsatility index measurements were recorded at
every session. RESULTS: The baseline breath-holding index was significantly
higher in the migraine group compared to the control group (P =.002). No
difference in other parameters was found between the groups. The change in the
headache index was significant (P<.001), indicating a beneficial effect from
flunarizine. The breath-holding index improved significantly after treatment
(P<.001), and the baseline difference in the breath-holding index between the
pretreatment migraine group and the control group was no longer evident at 3
months. There was no significant change with treatment in the other transcranial 
Doppler parameters. CONCLUSIONS: Our finding of unchanged blood flow velocities
but normalized cerebrovascular reactivity after treatment suggests that the
mechanism of action of flunarizine in migraine does not involve a vasodilatory
effect on cerebral vessels. It may be instead that flunarizine modifies
cerebrovascular reactivity through its action on centrally located structures
that subserve autonomic vascular control.

PMID: 12752751 [PubMed - indexed for MEDLINE]

2603: Headache. 2003 May;43(5):458-63.

Cerebrovascular reactivity in adolescents with migraine and tension-type headache
during headache-free interval and attack.

Rosengarten B, Sperner J, Görgen-Pauly U, Kaps M.

Department of Neurology, Justus-Liebig University of Giessen, Germany.

BACKGROUND: Migraine is a common cause of headache in adolescents. Assuming that 
the cerebral vasculature is involved in the pathophysiology of migraine, we
compared cerebral vasoreactivity in adolescents both during a migraine attack and
a headache-free interval. METHODS: A functional transcranial Doppler test
utilizing a visual stimulation paradigm was undertaken to measure the evoked flow
velocity in the posterior cerebral artery of adolescents suffering from a
migraine without aura or a tension-type headache. To serve as a control, data
previously obtained from age-matched adolescents with no primary headache
disorder were used. The flow curves were evaluated by determining the maximal
flow velocity increase and by modeling their time course according to a control
system analysis. In that analysis, the main dynamic features of the flow response
were described mathematically in terms of a control system model of low order.
The parameters were time delay, gain, attenuation, rate time, and natural
frequency. RESULTS: The attenuation parameter (P<.005), indicative of an
increased tone of the vessel, and the resting absolute flow velocity (P<.01) both
showed a significant increase during an attack in the adolescents with migraine; 
the gain parameter showed a trend towards similar increase (P =.07). The maximal 
flow velocity did not increase significantly during an attack. CONCLUSIONS: The
control system approach utilized here appears to be more sensitive for detecting 
migraine-associated changes in cerebral vasoreactivity than examination of the
maximal flow velocities alone.

Publication Types: 
    Comparative Study

PMID: 12752750 [PubMed - indexed for MEDLINE]

2604: Headache. 2003 May;43(5):451-7.

Demographic and migraine characteristics of adolescents with migraine: Glaxo
Wellcome clinical trials' database.

Winner P, Rothner AD, Putnam DG, Asgharnejad M.

Premier Research Institute, Palm Beach Headache Center, West Palm Beach, FL
33407, USA.

OBJECTIVE: To describe the demographics and migraine characteristics of patients 
in the Glaxo Wellcome adolescent clinical trials' database. METHODS: Data from 8 
sumatriptan (tablet and nasal spray) and naratriptan (tablet) trials (6 placebo
controlled and 2 open label) were reviewed. Adolescents aged 12 to 17 years who
had participated in migraine clinical trials and used at least 1 dose of study
medication were summarized using descriptive statistics. Patient demographic
(gender, age, race, height, and weight) and migraine (diagnosis, pain location
and intensity, time and day of migraine onset and treatment, and associated
symptoms) characteristics were examined. RESULTS: One thousand nine hundred
thirty-two adolescents with migraine were identified; mean age was 14.1 years
(standard deviation, 1.64; range, 11 to 18) and 54% of patients were female. More
males were represented in the 12- to 14-year-old group (646 [73%] of 885) than in
the 15- to 17-year-old group (234 [26%] of 885). Most patients reported migraine 
without aura (67%, 1121 of 1672), unilateral migraine pain (58%, 458 of 787), and
pulsating pain (74%, 582 of 790). Migraine was aggravated by physical activity in
most of the adolescents (88%, 526 of 598). Most migraine attacks (73%, 1363 of
1858) began between 6 am and 6 pm, and proportionately more attacks occurred
Monday through Wednesday. Pretreatment vomiting was experienced by 5% (97 of
1830) of patients, nausea by 53% (983 of 1849), and photophobia or phonophobia
(or both) by 88% (1628 of 1858) of patients. The incidence of associated symptoms
was directly related to pretreatment headache severity. CONCLUSIONS: In this
large clinical trials' database, adolescents had migraine without aura
characterized by unilateral and pulsating pain and aggravated by activity. The
incidence of associated symptoms was directly related to pretreatment pain
intensity. More migraines occurred Monday through Wednesday during typical school
hours. These data may facilitate clinicians' efforts to tailor migraine therapy
to the needs of this patient population.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 12752749 [PubMed - indexed for MEDLINE]

2605: Headache. 2003 May;43(5):441-50.

Rapid and sensitive paradigm for screening patients with headache in primary care
settings.

Maizels M, Burchette R.

Department of Family Practice, Kaiser Permanente, Woodland Hills, CA 91365, USA.

OBJECTIVE: To determine the sensitivity and specificity of a brief headache
screening paradigm for primary care clinicians. BACKGROUND: Migraine and drug
rebound headache are disabling primary headache disorders. Both are
underdiagnosed and undertreated. A method for rapid screening of migraine, drug
rebound headache, and other daily headache syndromes would be useful. The Brief
Headache Screen uses 3 questions-the frequency of severe (disabling) headache,
other (mild) headache, and use of symptomatic medication-to generate diagnoses.
METHODS: The Brief Headache Screen was evaluated in an emergency department, a
family practice department, and a referral headache clinic. Diagnoses from the
Brief Headache Screen were compared to diagnoses of trained researchers and
headache specialists. RESULTS: Three hundred ninety-nine patients were screened
and interviewed. The criterion of episodic severe (disabling) headache correctly 
identified migraine in 136 (93%) of 146 patients with episodic migraine and 154
(78%) of 197 patients with chronic migraine, with a specificity for any migraine 
(episodic or chronic) of 32 (63%) of 51. The inclusion of episodic or daily
severe headache identified migraine in 100% of patients with chronic migraine.
Only 6 (1.7%) of 343 patients with migraine were not identified by severe
(disabling) headache. The combination of severe and mild headache frequency was
sensitive to daily headache syndromes in 218 (94%) of 232 patients with a
specificity of 87 (54%) of 162. Medication overuse was correctly identified in
146 (86%) of 169 patients with a specificity of 22 (79%) of 28. CONCLUSIONS: The 
frequency of severe (disabling) and mild headaches and use of symptomatic
medications, rapidly and sensitively screens for migraine, daily headache
syndromes, and medication overuse. The use of this paradigm in primary care
settings may improve the recognition of these important headache syndromes.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 12752748 [PubMed - indexed for MEDLINE]

2606: Sao Paulo Med J. 2003 Jan 2;121(1):31-3.

Crying as a precipitating factor for migraine and tension-type headache.

Fragoso YD, Carvalho R, Ferrero F, Lourenço DM, Paulino ER.

Departamento de Neurologia, Universidade Metropolitana de Santos Avenida Epitácio
Pessoa, 555-Apto. 91 Santos/SP, Brasil-CEP 11030-601. yara@bsnet.com.br

CONTEXT: Scarcely reported in the literature, crying seems to be an important
precipitating factor for both migraine and tension-type headache in daily
practice. OBJECTIVE: To evaluate the role of crying as a precipitating factor for
migraine and tension-type headache. TYPE OF STUDY: Prospective evaluation.
PARTICIPANTS: 163 workers or students from the Universidade Metropolitana de
Santos, who presented at least one attack a month, for at least one year, of
either migraine or tension-type headache. PROCEDURES: Interview by means of
questionnaires and personal evaluations. Details of precipitating factors for the
attacks were assessed. RESULTS: From the total group of 163 individuals, 90
(55.2%) considered crying to be a potential factor for triggering headache
attacks. Of this group of 90 persons, 62 presented migraine (6 males, 56 females)
and 28 presented tension-type headache (5 males, 23 females). Only stress,
anxiety and menstrual periods rated higher or equal to crying as triggering
factors for both types of headache. CONCLUSIONS: The physiology of crying is not 
well documented or understood. The act of crying seems to be an important
precipitating factor for primary headaches and it should be studied further. The 
authors welcome comments on the matter and would like to work in collaboration
with other groups interested in this subject.

PMID: 12751342 [PubMed - indexed for MEDLINE]

2607: J Natl Med Assoc. 2003 Apr;95(4):298-306.

Scheuermann's disease as a model displaying the mechanism of venous obstruction
in thoracic outlet syndrome and migraine patients: MRI and MRA.

Collins JD, Saxton EH, Miller TQ, Ahn SS, Gelabert H, Carnes A.

Department of Radiology, University of California at Los Angeles, CA 90095-0001, 
USA..

Kyphosis of the thoracic spine rotates the scapulae anterior laterally, clavicles
and subclavius muscles anteriorly, displaces the manubrium posteriorly, which
increases the slope of the first ribs. This increases tension on the anterior
scalene muscles and the neurovascular bundles which causes brachial plexopathy
(TOS). Scheuermann's disease (spinal osteochondrosis; juvenile kyphoscoliosis) is
a disorder which consists of vertebral wedging endplate irregularity and
narrowing of the intervertebral disk space causing kyphosis of the thoracic spine
and may also involve the lumbar space. It occurs at puberty and involves both
male and females. Abduction external rotation of the upper extremities (arms
overhead) posterior inferiorly rotate the clavicles and the subclavius muscles
which enhances tension on the venous drainage and neurovascular supply that
diminishes venous return. This triggers complaints of thoracic outlet syndrome
(TOS) and migraine headache. Bilateral magnetic resonance imaging (MRI)
demonstrates compressing abnormalities of the brachial plexus. Five patients with
Scheuermann's disease were imaged with the 1.5 Tesla magnet (Signa; General
Electric Medical Systems, Milwaukee, WI) 3-D reconstruction MRI. T1W and T2W
pulse sequences were performed in transverse, the coronal, transverse oblique,
sagittal, and coronal abduction external rotation planes using 4 mm slice
thickness and 512 x 256 matrix size. Water bags were used to enhance the signal
to noise ratio. Magnetic resonance angiography (MRA) 2-D Time Of Flight (TOF) was
obtained to compression for anatomic display evaluate perfusion of the brachial
plexus. MRI and MRA captured sites of brachial plexus. One patient was selected
for this presentation, which demonstrates the compression of the brachial plexus 
and venous obstruction which triggered complaints of thoracic outlet syndrome.

Publication Types: 
    Case Reports

PMID: 12749621 [PubMed - indexed for MEDLINE]

2608: Clin Ther. 2003 Feb;25(2):331-41.

A review of the effects of almotriptan and other triptans on clinical trial
outcomes that are meaningful to patients with migraine.

Mondell BE.

Department of Neurology, The Johns Hopkins University School of Medicine,
Baltimore, Maryland, USA. bmondell@jhmi.edu

BACKGROUND: Traditional end points in clinical trials of migraine therapy, such
as 2-hour pain response, may not fully address the outcomes patients consider
most important: rapid and sustained freedom from pain over 24 hours, and a low,
placebo-like incidence of adverse events. A composite efficacy measure such as
the sustained pain-free rate (no pain by 2 hours after dosing, no recurrence, no 
use of rescue medication from 2 to 24 hours after dosing) may be more
appropriate. OBJECTIVE: Clinically relevant differences between almotriptan and
other triptans were reviewed in the context of the attributes of acute migraine
treatment that patients consider most important. METHODS: This review was based
on published reports of open-label and placebo-controlled clinical trials of
almotriptan, results of a survey concerning the attributes patients consider most
important in a migraine medication, and a published meta-analysis of 53
placebo-controlled clinical trials of triptans involving >24,000 patients.
RESULTS: Almotriptan was effective and well tolerated in the placebo-controlled
clinical trials; results of the 6- and 12-month open-label studies supported its 
good tolerability profile. A respective 87% and 86% of respondents to the patient
survey indicated that they considered complete freedom from pain and no
recurrence among the most important attributes of migraine treatment, both of
which are included in the sustained pain-free rate. In the meta-analysis,
almotriptan had a favorable efficacy and tolerability profile compared with other
triptans, particularly with respect to sustained pain-free rate, which was
significantly higher with almotriptan 12.5 mg compared with sumatriptan 100 mg
(25.9% vs 20.0%, respectively; P < 0.05). In addition, the placebo-subtracted
rate of adverse events was significantly lower with almotriptan compared with
sumatriptan (1.8% vs 4.4%, respectively; P < 0.05). Results of a head-to-head
placebo-controlled trial of almotriptan 12.5 mg and sumatriptan 100 mg supported 
the balance of efficacy and tolerability observed for almotriptan in the
meta-analysis. CONCLUSIONS: Data from clinical trials suggest that almotriptan is
effective and well tolerated in the treatment of acute migraine pain. Based on a 
sustained pain-free rate that is among the highest and an adverse-event rate that
is among the lowest for the triptans, almotriptan represents a therapeutic option
for the initial treatment of acute migraine with or without aura.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't
    Review

PMID: 12749502 [PubMed - indexed for MEDLINE]

2609: Clin Cornerstone. 2001;4(3):53-64.

Comparative aspects of triptans in treating migraine.

Adelman JU, Lewit EJ.

Department of Neurology, University of North Carolina, Chapel Hill, North
Carolina, USA. jadelman@triad.rr.com

Triptans, beginning with sumatriptan, have revolutionized the treatment of
migraine. New triptans in several formulations will soon become available in the 
United States. Although the similarities of these 5-hydroxytryptamine (5-HT)
1B/1D receptor agonists outweigh their differences, important differences in
pharmacokinetics and clinical responses do exist. Subcutaneous sumatriptan has
the most rapid onset of action and greatest efficacy but the most adverse
effects. Intranasal sumatriptan also has rapid onset of action, but at 2 hours
its efficacy is comparable to that of oral zolmitriptan. Of the oral triptans,
rizatriptan seems to have the greatest early efficacy. Both rizatriptan and
zolmitriptan are now available as rapidly dissolving wafers. Almotriptan, the
newest of the triptans, has a response rate similar to that of oral sumatriptan
and may produce fewer adverse effects. Naratriptan and frovatriptan, with their
slow onset, high tolerability, and long half-lives, may have a role in aborting
prolonged migraine attacks and in headache prevention. Eletriptan at higher doses
(80 mg) has a response rate approaching that of rizatriptan but may be limited by
potential side effects. The many triptans available offer the opportunity to
individualize migraine treatment, depending on the patient's attack
characteristics, tolerance, and preferences.

Publication Types: 
    Comparative Study
    Review

PMID: 12739316 [PubMed - indexed for MEDLINE]

2610: Clin Cornerstone. 2001;4(3):36-52.

Acute and prophylactic management of migraine.

Dodick DW.

Mayo Clinic Scottsdale Headache Program, Department of Neurology, Mayo Clinic,
Scottsdale, Arizona, USA.

Although considerable advances have been made in the understanding and treatment 
of migraine, uncertainty about the management of this disorder remains. Once a
diagnosis is established, an effective treatment plan should be developed that
includes education for the patient about migraine and reassurance that the
headaches are not caused by structural pathology, stress, or psychopathology.
Rapidly effective acute treatment, nonpharmacologic treatment such as behavioral 
and lifestyle changes, preventive measures, and patient follow-up are other
essential elements of migraine management.

Publication Types: 
    Review

PMID: 12739315 [PubMed - indexed for MEDLINE]

2611: Clin Cornerstone. 2001;4(3):26-35.

Pitfalls in migraine diagnosis and management.

Smith TR.

Ryan Headache Center, Mercy Health Research, St. Louis, Missouri, USA.

The decade of the 90s brought about a revolution in our understanding of migraine
and in medications to treat this disorder. Indeed, our understanding of the
pathophysiology of migraine and the pharmacology involved in its treatment has
exploded. Nonetheless, there are still many pitfalls that may occur in the
clinical assessment and management of migraine that may prevent the patient from 
receiving the full benefits of the advances of the past 10 years. This article
explores the reasons for the unsuccessful diagnosis and treatment of migraine and
presents suggestions for improving its management.

Publication Types: 
    Review

PMID: 12739314 [PubMed - indexed for MEDLINE]

2612: Clin Cornerstone. 2001;4(3):18-25.

Clinical manifestations of migraine.

Kunkel RS.

Headache Center, Department of Neurology, Cleveland Clinic Foundation, Cleveland,
Ohio, USA.

Migraine is a disorder with many clinical manifestations that vary from person to
person and often from headache to headache in the same person. Several body organ
systems are involved in a migraine attack. It is a condition that is
underdiagnosed by physicians and misidentified by persons suffering with
headaches. Many individuals with migraine self-diagnose as having sinus headaches
or tension headaches. This article discusses the many symptoms of migraine and
will help the busy practitioner to better recognize and diagnose this common
disorder.

Publication Types: 
    Review

PMID: 12739313 [PubMed - indexed for MEDLINE]

2613: Clin Cornerstone. 2001;4(3):1-17.

Pathophysiology, epidemiology, and impact of migraine.

Mathew NT.

Houston Headache Clinic Houston, Texas, USA.

Despite a decade of progress, migraine headache remains prevalent, disabling,
underdiagnosed, and undertreated in the United States. Migraine affects
approximately 12% of the population, and the economic burden in terms of annual
cost of labor lost to migraine disability is between $5.6 and $17.2 billion. The 
threshold for migraine may be genetically determined, although recent genetic and
neurophysiologic studies point to migraine as possibly a channelopathy. Cerebral 
cortical and brain stem changes occur in migraine. Head pain and associated
symptoms of migraine can be explained by activation of the trigeminal vascular
system. Evidence has also been accumulated that suggests the release of nitric
oxide is an important trigger mechanism. Introduction of the triptans has
dramatically advanced acute migraine pharmacotherapy, and preventive therapy has 
greatly improved; however, public health initiatives may be needed to further
advance diagnosis and treatment of this common and disabling disorder.

Publication Types: 
    Review

PMID: 12739312 [PubMed - indexed for MEDLINE]

2614: Clin Neurophysiol. 2003 May;114(5):889-93.

Decreased habituation of the R2 component of the blink reflex in migraine
patients.

De Marinis M, Pujia A, Natale L, D'arcangelo E, Accornero N.

Department of Neurological Sciences, La Sapienza University, Viale dell'
Università 30, 00185 Rome, Italy. milena.demarinis@uniroma1.it

OBJECTIVE: Activation of the trigemino-vascular system as well as of brainstem
trigeminal nuclei are thought to play an important role in migraine. The aim of
this study was to investigate the habituation phenomenon of the blink reflex in
30 headache-free migraine patients and 30 control subjects. METHODS: An
electromyographic device with a specific habituation test program was used to
elicit and record blink reflex responses on both the right and left sides, and to
randomly repeat the stimulations at different time intervals in order to induce
habituation. RESULTS: Whereas the R1 and R2 latencies, amplitudes and areas in
the basal assessment were similar in patients and control subjects, the blink
reflex habituation responses were markedly reduced in migraine patients who had a
migraine attack within 72 h after testing (group A). In these patients, the
differences between the R2 areas, obtained when stimuli were delivered at
subsequent time intervals ranging between 10-5, 5-4, 4-3 and 3-2 s, were
statistically different (P<0.001) from those of the patients who had a migraine
attack after a longer time interval (group B) and control subjects. CONCLUSIONS: 
Our data suggest that the brainstem pathways involved in the blink reflex may be 
activated in the premonitory phase of migraine attacks, probably through
mechanisms that involve dopaminergic function.

Publication Types: 
    Comparative Study

PMID: 12738435 [PubMed - indexed for MEDLINE]

2615: Doc Ophthalmol. 2003 May;106(3):265-70.

Effects of betaxolol and flunarizine on visual fields and intraocular pressure in
patients with migraine.

Yarangümeli A, Comoglu S, Köz OG, Elhan AH, Kural G.

Ankara Numune Training and Research Hospital, 1st Eye Clinic, Ankara, Turkey.
alperyx@yahoo.com

Fifty-one patients with migraine were divided into four groups to investigate the
effects of topical betaxolol and systemic calcium channel blocker flunarizine on 
visual fields (VF) and intraocular pressure (IOP). The first group (Group 0) was 
followed with no medications, topical betaxolol (bid) was precribed to the second
group (Group B), oral flunarizine (10 mg daily) was prescribed to the third group
(Group F), and the last group (Group BF) was assigned for combined betaxolol and 
flunarizine treatment. After a mean follow-up time of 4.2 +/- 1.2 months (3-6
months), IOP measurements and VF tests were repeated. Group B and Group BF were
found to be statistically different from the other groups in terms of IOP
reduction and VF improvement according to mean deviation and corrected pattern
standard deviation indices in the second examinations. On the other hand, Group F
and Group BF differed from the other two groups considering the improvement in
migrainous complaints. VF findings which are probably influenced by perfusion
problems due to vasospastic mechanisms in migraineurs, improved following topical
betaxolol treatment. However, systemic use of flunarizine--a calcium channel
blocker--did not seem to be effective on visual fields although it had beneficial
effects on migraine.

Publication Types: 
    Comparative Study

PMID: 12737504 [PubMed - indexed for MEDLINE]

2616: Eur Neurol. 2003;49(4):218-22.

Glutathione S-transferase polymorphisms: susceptibility to migraine without aura.

Kusumi M, Ishizaki K, Kowa H, Adachi Y, Takeshima T, Sakai F, Nakashima K.

Department of Neurology, Institute of Neurological Sciences, Faculty of Medicine,
Tottori University, Yonago, Japan. mkusumi@grape.med.tottori-u.ac.jp

Migraine is considered to be a polygenic multifactorial disease with various
environmental and genetic etiologies. We investigated glutathione S-transferase
(GST) P1 Ile(105)Val, T1 and M1 polymorphisms in 174 Japanese headache sufferers 
and 372 Japanese controls. The headache group consisted of 38 cases of migraine
with aura, 95 migraine without aura (MWOA) and 41 tension-type headache
sufferers. The M1 homozygous deletion genotype was significantly higher in MWOA
(64%) compared with controls (46%; p < 0.01; odds ratio = 2.18, 95% confidence
interval: 1.32-3.61, adjusted for age and gender). In a comparison of the current
smokers, the M1 null frequencies in MWOA were further increased. GSTM1 may be one
of the genetic risk factors for MWOA in the Japanese population. Copyright 2003
S. Karger AG, Basel

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 12736537 [PubMed - indexed for MEDLINE]

2617: Curr Pain Headache Rep. 2003 Jun;7(3):229-34.

Is there a role for botulinum toxin in the treatment of migraine?

Evers S.

Department of Neurology, University of Münster, Albert-Schweitzer-Str. 33, 48129 
Münster, Germany. everss@uni-muenster.de

In this review, the studies and case reports that are available from reference
systems and published congress contributions on the treatment of migraine with
botulinum toxin are evaluated. The studies and reports were analyzed with respect
to the study design, the efficacy parameters, and the significance of results.
One double-blind, placebo-controlled, randomized study with negative (for a 75 U 
dose of botulinum toxin) and positive (for a 25 U dose of botulinum toxin)
evidence of efficacy, one that was a partly positive controlled study (pain
intensity, but not attack-frequency improved), and four positive open studies
were available. For the acute treatment of migraine with botulinum toxin, only
positive case reports were published. As a result of this analysis, there is no
sufficient scientific evidence for a treatment recommendation of migraine with
botulinum toxin. Further studies are needed for a definite evaluation of
subgroups with probable benefit from such a treatment and for the comparison of
botulinum toxin with other migraine prophylactic drugs.

Publication Types: 
    Review

PMID: 12720604 [PubMed - indexed for MEDLINE]

2618: Curr Pain Headache Rep. 2003 Jun;7(3):224-8.

Pseudomigraine with lymphocytic pleocytosis.

Pascual J, Valle N.

Service of Neurology, University Hospital Marqués de Valdecilla (UC), 39008
Santander, Spain. juliopascual@telefonica.net

Pseudomigraine with temporary neurologic symptoms and lymphocytic pleocytosis is 
a self-limited syndrome of unknown origin characterized by headache accompanied
by transient neurologic symptoms and cerebrospinal fluid lymphocytosis. Patients 
with this condition are between 15 and 40 years of age. The syndrome is more
frequent in men. The clinical picture encompasses one to 12 episodes of changing 
variable neurologic deficits accompanied by moderate to severe headache and
occasional fever. These headaches are described as predominantly throbbing and
bilateral with a variable duration (mean, 19 hours). The average duration of the 
transient neurologic deficit is 5 hours. Sensory (78% episodes), aphasic (66%),
and motor (56%) disturbances are the most common. Migraine-like visual symptoms
are relatively rare (18% episodes). Patients are asymptomatic between episodes
and after the symptomatic period (duration > 3 months). Lymphocytic pleocytosis
(10 to 760 cells mm(3)) and increased cerebrospinal fluid protein are found with 
negative bacteriologic, viral, fungal, and immunologic studies. Brain computed
tomography and magnetic resonance imaging are normal, but an electroencephalogram
frequently shows focal slowing over the symptomatic brain area. Single photon
emission computed tomography reveals transient focal areas of decreased uptake
consistent with the clinical symptoms. It is possible that pseudomigraine with
temporary neurologic symptoms and lymphocytic pleocytosis could result from an
activation of the immune system secondary to a recent viral infection, which
would produce antibodies against neuronal or vascular antigens. This autoimmune
attack may induce an aseptic leptomeningeal vasculitis, accounting for the
headache and the transient symptoms likely through a spreading depression-like
mechanism.

Publication Types: 
    Review

PMID: 12720603 [PubMed - indexed for MEDLINE]

2619: Curr Pain Headache Rep. 2003 Jun;7(3):212-7.

Migraine genetics.

Kors E, Haan J, Ferrari M.

Department of Neurology, K5Q, Leiden University Medical Centre, PO Box 9600, 2300
RC Leiden, The Netherlands.

The genetics of migraine is a fascinating and moving research area. Familial
hemiplegic migraine, a rare subtype of migraine with a Mendelian pattern of
inheritance, is caused by mutations in the chromosome 19 CACNA1A gene in
approximately 75% of the families. The finding of mutations in an ionchannel
subunit defines migraine as a channelopathy (eg, epilepsy). The genetics of the
more frequent variants, migraine with and without aura, is more complex. Several 
loci have been studied in families and case-control studies, but need to be
confirmed.

Publication Types: 
    Case Reports
    Review

PMID: 12720601 [PubMed - indexed for MEDLINE]

2620: Cephalalgia. 2003 May;23(4):302-8.

Menstrual migraine in a representative Dutch population sample: prevalence,
disability and treatment.

Couturier EG, Bomhof MA, Neven AK, van Duijn NP.

Department of Neurology, Medical Centre Boerhaave, Amsterdam, The Netherlands.
emilecouturier@cs.com

We assessed the prevalence of menstrual migraine and its restrictions on daily
activities in a representative Dutch population sample of 1181 Dutch women, aged 
13-55 years. Further, we evaluated the potential role of oral contraceptives, and
how menstrual migraine is treated. More than half suffered from menstrual
complaints, a substantial proportion reported headache or migraine as a frequent 
problem. Use of oral contraceptives seemed to reduce the occurrence of menstrual 
complaints, but not the occurrence of headache and migraine. In our study, the
prevalence of menstrual migraine (3%) is lower than in the literature, most
probably because we did not use a selected group of patients but a
population-based sample of ordinary women. It was confirmed that attacks of
menstrual migraine are more severe, of longer duration, and more resistant to
treatment than migraine attacks at other times of the month.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 12716349 [PubMed - indexed for MEDLINE]

2621: Cephalalgia. 2003 May;23(4):293-301.

Migraine prophylactic medication usage patterns in The Netherlands.

Rahimtoola H, Buurma H, Tijssen CC, Leufkens HG, Egberts AC.

Department of Pharmacoepidemiology and Pharmacotherapy, Utrecht Institute for
Pharmaceutical Sciences, Utrecht, The Netherlands. h.rahimtoola@pharm.uu.nl

This study aims to investigate usage patterns of specific migraine prophylactic
medications in ergotamine and triptan patients commencing this treatment for the 
first time during 1 January 1992 until 31 December 1998. Usage patterns of
specific migraine prophylactic drugs were evaluated for each patient by accessing
data from a large prescription database and were characterized as continued,
switch or stop use during the patient observation period. Several patient and
medication-related factors were explored in order to identify a possible
relationship with the specific usage pattern defined. Approximately 75% of the
study population (n = 729) had terminated (stop or switch) prophylactic treatment
after 1 year. Age < 40 years (relative risk (RR) 1.9; 95% confidence interval
(CI) 1.2-3.2) and the concomitant use of non-steroidal anti-inflammatory drugs
(RR 3.2; 95% CI 1.2-5.5) or specific abortive migraine drugs resulted in a faster
onset of treatment modification (switch). Overall, migraine prophylactic
treatment is used for a relatively short period, probably attributable to the
common limitations associated with migraine prophylaxis, such as poor compliance 
and/or limited therapeutic efficacy. Patterns of use can be influenced by a
variety of factors, including age, type of prescriber and certain co-medication. 
Patient interview studies are required to clarify these issues further.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 12716348 [PubMed - indexed for MEDLINE]

2622: Cephalalgia. 2003 May;23(4):280-6.

One-year prevalence of migraine in Austria: a nation-wide survey.

Lampl C, Buzath A, Baumhackl U, Klingler D.

Department of Neurology and Psychiatry, Pain and Headache Centre at the General
Hospital, Linz, Austria. christian.lampl@akh.linz.at

This study presents the first nation-wide survey of migraine in Austria. A sample
of 997 Austrian > or = 15 years old were interviewed personally (face-to-face) in
a random sample in the whole country. Diagnosis of migraine was based on the
International Headache Society (IHS) classification. Of the Austrian adult
population 10.2% were identified to suffer from IHS migraine, 5.6% from migraine 
without aura, 2.3% from migraine with aura and 2.3% from borderline migraine.
Another 8.5% have possible migraine. Other primary headaches were reported in
30.7%. Sex, age, working status and region were found to be the main demographic 
influencing factors. Further influences were stress, spinal column problems or
weather changes. The most used acute medications were over-the-counter drugs,
doctor attendance rate was very low. Working people with migraine dropped out of 
work 14 days per year, which adds up to 6.8 million working days per year. This
remains a substantial economic factor. The findings indicate that migraine
sufferers in Austria need to be more informed about their illness and what to do 
against it, especially encouraging doctor visits.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 12716346 [PubMed - indexed for MEDLINE]

2623: Cephalalgia. 2003 May;23(4):271-5.

Co-morbidity of migraine and major depression in the Turkish population.

Kececi H, Dener S, Analan E.

Department of Neurology, Abant Izzet Baysal University School of Medicine, Duzce,
Turkey. hulusikececi@ibuduzce-tip.edu.tr

The aim of the present study was to estimate the co-morbidity of migraine and
major depression in the Turkish population. The households were selected randomly
from all district areas. The study included 947 subjects aged > or = 18 years.
The diagnosis of migraine was made according to the criteria of the International
Headache Society. The diagnosis of major depression was made according to the
Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) criteria. Migraine
was identified in 163 subjects. Major depression was identified in 155 subjects, 
and in 53 subjects with migraine. The lifetime prevalence of major depression was
approximately three times higher in persons with migraine in this Turkish
population.

Publication Types: 
    Comparative Study

PMID: 12716344 [PubMed - indexed for MEDLINE]

2624: Cephalalgia. 2003 May;23(4):264-70.

Comment in:
    Cephalalgia. 2004 Apr;24(4):316-7; author reply 318-9.    Cephalalgia. 2004 Apr;24(4):317-8; author reply 318-9.

Excitability of visual V1-V2 and motor cortices to single transcranial magnetic
stimuli in migraine: a reappraisal using a figure-of-eight coil.

Bohotin V, Fumal A, Vandenheede M, Bohotin C, Schoenen J.

Department of Neurology, University of Liege, Liège, Belgium.

We used transcranial magnetic stimulation (TMS) with a figure-of-eight coil to
excite motor and visual V1-V2 cortices in patients suffering from migraine
without (MO) (n = 24) or with aura (MA) (n = 13) and in healthy volunteers (HV)
(n = 33). Patients who had a migraine attack within 3 days before or after the
recordings were excluded. All females were recorded at mid-cycle. Single TMS
pulses over the occipital cortex elicited phosphenes in 64% of HV, 63% of MO and 
69% of MA patients. Compared with HV, the phosphene threshold was significantly
increased in MO (P = 0.001) and in MA (P = 0.007), but there was no difference
between the two groups of migraineurs. The motor threshold tended to be higher in
both migraine groups than in HV, but the differences were not significant. In
conclusion, this study shows that two-thirds (64.86%) of patients affected by
either migraine type present an increased phosphene threshold in the interictal
period, which suggests that their visual cortex is hypoexcitable.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 12716343 [PubMed - indexed for MEDLINE]

2625: Cephalalgia. 2003 May;23(4):258-63.

The threshold for phosphenes is lower in migraine.

Aurora SK, Welch KM, Al-Sayed F.

Headache Research Center, Henry Ford Health Sciences Center, Detroit, MI, USA.
sheena.aurora@swedish.org

We have reported a preliminary study confirming hyperexicitability of occipital
cortex in migraine with aura (MwA) using transcranial magnetic stimulation (TMS).
We have now completed a blinded study to investigate the occipital cortex in MwA 
and without aura (MwoA) compared with normal controls (NC) using TMS. TMS was
performed using the Caldwell MES-10 stimulator. A circular coil 9.5 cm diameter
was applied to the occipital scalp (7 cm above the inion). Stimulator intensity
was increased in 10% increments until subjects reported visual phenomena or 100% 
intensity was reached. Stimulation intensity was then fine tuned to determine the
threshold at which phosphenes were seen. Fisher's exact t-test and logrank test
were used for statistical comparisons. Ten subjects with MwA and MwoA were
compared to 10 NC. The difference in the proportion of subjects with phosphene
generation was statistically significant (MwA 100%, MwoA 60% and NC 30%) [P =
0.003]. The difference in threshold levels for phosphenes was also significant
for MwA 42.8%, and controls 57.3% [P = 0.0001]. There is a difference in
threshold for excitability of occipital cortex in MwA and MwoA compared to NC.
This is a direct neurophysiological correlate for clinical observations, which
have inferred hyperexicitability of the occipital cortex in migraineurs.

Publication Types: 
    Comparative Study

PMID: 12716342 [PubMed - indexed for MEDLINE]

2626: Cephalalgia. 2003 May;23(4):245-57.

Possible role of alpha-adrenoceptor subtypes in acute migraine therapy.

Willems EW, Valdivia LF, Villalón CM, Saxena PR.

Department of Pharmacology, Cardiovascular Research Institute COEUR, Erasmus MC, 
University Medical Centre Rotterdam EMCR, Rotterdam, The Netherlands.

Even though the underlying mechanisms for the pathophysiology of migraine attacks
are not completely understood, little doubt exists that the headache phase is
explained by dilatation of cranial, extracerebral blood vessels. In this context,
experimental models predictive for anti-migraine activity have shown that both
triptans and ergot alkaloids, which abort migraine headache, produce
vasoconstriction within the carotid circulation of different species. In contrast
to the well-established role of serotonin (5-hydroxytryptamine; 5-HT) 5-HT1B
receptors in the common carotid vascular bed, the role of alpha-adrenoceptors and
their subtypes has been examined only relatively recently. Using experimental
animal models and alpha1- and alpha2-adrenoceptor agonists (phenylephrine and
BHT933, respectively) and antagonists (prazosin and rauwolscine, respectively),
it was shown that activation of either receptor produces a cranioselective
vasoconstriction. Subsequently, investigations employing relatively selective
antagonists at alpha1- (alpha1A, alpha1B, alpha1D) and alpha2- (alpha2A, alpha2B,
alpha2C) adrenoceptor subtypes revealed that specific receptors mediate the
carotid haemodynamic responses in these animals. From these observations,
together with the potential limited role of alpha1B- and alpha2C-adrenoceptors in
the regulation of systemic haemodynamic responses, it is suggested that selective
agonists at these receptors may provide a promising novel avenue for the
development of acute anti-migraine drugs.

Publication Types: 
    Review

PMID: 12716341 [PubMed - indexed for MEDLINE]

2627: Arq Neuropsiquiatr. 2003 Mar;61(1):43-7. Epub 2003 Apr 16.

Overuse of symptomatic medications among chronic (transformed) migraine patients:
profile of drug consumption.

Krymchantowski AV.

Centro de Avalia o e Tratamento da Dor de Cabe a do Rio de Janeiro, Departamento 
de Neurologia, Universidade Federal Fluminense, Rio de Janeiro, RJ, Brazil.
abouchkrym@globo.com

Chronic daily headache and chronic (transformed) migraine (TM) patients represent
more than one third of the subjects seen in specialized headache centers. Most of
these patients may overuse symptomatic medications (SM) taken on a daily basis to
relieve headache and associated symptoms. The conversion to the daily or
near-daily pattern of headache presentation is thought to be related to the
medication overuse. The aim of this study was to evaluate the profile of SM
consumption among transformed migraine patients attending a tertiary center. One 
hundred thirty three consecutive patients (22 men and 111 women, ages 17 to 80)
with TM and overuse of SM according to the proposed criteria of Silberstein et al
(1994, 1996) were prospectively studied. None of the patients were under
treatment for other conditions. Among them, 73 (54.9%) were using one category of
SM, while 55 (41.3%) and 5 (3.8%) patients were taking simultaneously two and
three categories of SM respectively. The categories of overused symptomatic
medications varied from simple analgesics to narcotics, triptans and combinations
of ergot derivatives and caffeine and of analgesics and caffeine. The average
intake per patient per day was of 3 to 4 tablets and mostly of the patients
overused simple analgesics (isolated or in combination with other substances)
(75.2%), caffeine containing drugs (71.4%), drugs containing ergotamine
derivatives (26.1%), triptans (alone or combined) (15.5%), drugs with narcotics
or ansiolitics (13%) and anti-inflammatory drugs (3.7%). The mechanisms by which 
the overuse of symptomatic medications may play a role in this transformation are
uncertain but despite of the necessity of controlled trials to demonstrate the
real role of such compounds in the development of transformed migraine, this
study emphasizes the necessity for more rigorous prescribing guidelines for
patients with frequent headaches.

PMID: 12715017 [PubMed - indexed for MEDLINE]

2628: Neurology. 2003 Apr 22;60(8):1308-12.

Comorbidity of migraine and depression: investigating potential etiology and
prognosis.

Breslau N, Lipton RB, Stewart WF, Schultz LR, Welch KM.

Department of Psychiatry, Henry Ford Health System, Detroit, MI 48202-3450, USA. 
nbresla1@hfhs.org

BACKGROUND: An association between migraine and major depression has been
observed in clinical and community samples. The factors that contribute to this
association and their implications remain unclear. OBJECTIVE: To determine the
factors contributing to the association of migraine and major depression.
METHODS: A cohort study of persons aged 25 to 55 years with migraine (n = 496) or
with other headaches of comparable severity (n = 151) and control subjects with
no history of severe headaches (n = 539) randomly selected from the general
community were interviewed first in 1997 and then reinterviewed in 1999. RESULTS:
Major depression at baseline predicted the first-onset migraine during the 2-year
follow-up period (odds ratio [OR] = 3.4; 95% CI = 1.4, 8.7) but not other severe 
headaches (OR = 0.6; 95% CI = 0.1, 4.6). Migraine at baseline predicted the
first-onset major depression during follow-up (OR = 5.8; 95% CI = 2.7, 12.3); the
prospective association from severe headaches to major depression was not
significant (OR = 2.7; 95% CI = 0.9, 8.1). Comorbid major depression did not
influence the frequency of migraine attacks, their persistence, or the
progression of migraine-related disability over time. CONCLUSIONS: Major
depression increased the risk for migraine, and migraine increased the risk for
major depression. This bidirectional association, with each disorder increasing
the risk for first onset of the other, was not observed in relation to other
severe headaches. With respect to other severe headaches, there was no increased 
risk associated with pre-existing major depression, although the possibility of
an influence in the reverse direction (i.e., from severe headaches to depression)
cannot be securely ruled out.

Publication Types: 
    Comparative Study
    Research Support, U.S. Gov't, P.H.S.

PMID: 12707434 [PubMed - indexed for MEDLINE]

2629: Arch Neurol. 2003 Apr;60(4):610-4.

Phenotypes of spinocerebellar ataxia type 6 and familial hemiplegic migraine
caused by a unique CACNA1A missense mutation in patients from a large family.

Alonso I, Barros J, Tuna A, Coelho J, Sequeiros J, Silveira I, Coutinho P.

UnIGENe, IBMC, and Laboratório de Genética Médica, ICABS, Universidade do Porto, 
Portugal.

BACKGROUND: Different mutations in the alpha 1A-subunit of the brain P/Q-type
calcium channel gene (CACNA1A) are responsible for familial hemiplegic migraine
(FHM), episodic ataxia type 2, and spinocerebellar ataxia type 6 (SCA6). Missense
and splice site mutations have been found in FHM and episodic ataxia type 2,
respectively, whereas a CAG repeat in the CACNA1A gene was found expanded in
patients with SCA6. OBJECTIVE: To identify the disease causing mutation in a
large family of patients with phenotypes of hemiplegic migraine with or without
cerebellar signs or permanent cerebellar ataxia without migraine inherited in a
dominant manner. PATIENTS AND METHODS: We examined 15 patients from a large
family identified through a systematic survey of hereditary ataxias being
conducted in Portugal. Linkage analysis was performed with CACNA1A gene markers, 
and mutation analysis was performed by single strand conformational polymorphism 
analysis and sequencing. RESULTS: Genetic linkage analysis with CACNA1A
intragenic markers showed positive LOD scores. The maximal LOD score was obtained
with the polymorphic CAG repeat (Zmax = 4.47, theta = 0). By single-strand
conformational polymorphism analysis, a shift in exon 13 of the CACNA1A gene was 
detected in all patients. A G-to-A substitution was then identified, resulting in
an arginine-to-glutamine change at codon 583 of this calcium channel alpha
1A-subunit. CONCLUSIONS: The disease-causing mutation in this family was
identified, showing that a unique mutation in the CACNA1A gene causes several
phenotypes, including those of SCA6 and FHM, thus suggesting that SCA6 and FHM
are not only allelic diseases but are the same disorder with a large phenotypic
variability.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 12707077 [PubMed - indexed for MEDLINE]

2630: Clin Chem Lab Med. 2003 Mar;41(3):272-5.

Absence of known familial hemiplegic migraine (FHM) mutations in the CACNA1A gene
in patients with common migraine: implications for genetic testing.

Wieser T, Mueller C, Evers S, Zierz S, Deufel T.

Klinik und Poliklinik fur Neurologie, Martin-Luther-Universität Halle-Wittenberg,
Halle/Saale, Germany. thomas.wieser@medizin.uni-halle.de

Mutations in the gene CACNA1A have been known to cause familial hemiplegic
migraine (FHM); it has been suggested, based on indirect genetic studies, that
this gene may also be involved in common forms of migraine. To obtain data from
direct gene analysis to test this hypothesis, we investigated 143 patients with
common migraine, irrespective of their family history, for the presence of
mutations known to result in the FHM phenotype; the mutations V714A, R192Q,
R583Q, T666M, V1457L, and 11811L were absent in our patient sample. Furthermore, 
exons 4, 16, 17, and 36 were completely screened by single-strand conformation
polymorphism (SSCP), and no other, hitherto unknown, mutations were detected.
Bearing in mind that, in particular, the T666M mutation contributes to a large
proportion of FHM linked to chromosome 19, we conclude that common migraine is
distinct from FHM in its molecular basis and, therefore, most likely also in its 
pathophysiology. The possibility, however, of the existence of allelic disorders,
with mutations located in other regions of the CACNA1A gene, cannot be ruled out.
Molecular testing, therefore, is at present not a feasible option for the
diagnosis and classification of migraine.

PMID: 12705332 [PubMed - indexed for MEDLINE]

2631: Compr Ther. 2003 Spring;29(1):35-42.

The clinical spectrum of migraine.

Rapoport AM, Bigal ME.

Columbia University College of Physicians & Surgeons, New York, NY, USA.

The wide clinical spectrum of migraine frequently challenges the physician's
diagnostic acumen. A structured approach to the patient and a better
comprehension of this variability of presentation, should translate into better
quality of care for migraineurs.

Publication Types: 
    Review

PMID: 12701341 [PubMed - indexed for MEDLINE]

2632: J Neurol Neurosurg Psychiatry. 2003 May;74(5):680-2.

New onset migraine with a brain stem cavernous angioma.

Afridi S, Goadsby PJ.

Headache Group, Institute of Neurology and the National Hospital for Neurology
and Neurosurgery, Queen Square, London WC1, UK.

A case of new onset migraine is described following a pontine bleed from a
cavernous angioma.

Publication Types: 
    Case Reports
    Research Support, Non-U.S. Gov't

PMID: 12700321 [PubMed - indexed for MEDLINE]

2633: Med Hypotheses. 2003 Jun;60(6):852-5.

Neurological theory of hypertension.

Eggers AE.

Department of Neurology, SUNY-Downstate Medical Center, Brooklyn, New York, USA. 
aggersa@aol.com

Review of the older literature on the relationship between migraine and
hypertension, written in the era before either condition could be treated,
discloses a high rate of co-morbidity. A neurological theory of essential
hypertension is proposed in which the two diseases are brought together into one 
entity. It is hypothesized that abnormally functioning serotonergic pacemaker
cells in the dorsal raphe nucleus, as part of a chronic stress response,
inappropriately activate and inhibit parts of the central and autonomic nervous
systems, so as to cause the two conditions. This theory builds on a previously
published neural theory of migraine.

PMID: 12699712 [PubMed - indexed for MEDLINE]

2634: Cephalalgia. 2003;23 Suppl 1:13-31.

Electrophysiological studies in migraine: a comprehensive review of their
interest and limitations.

Ambrosini A, de Noordhout AM, Sándor PS, Schoenen J.

Headache Clinic, INM Neuromed, IRCCS, Pozzilli (Isernia),Italy.

Electrophysiological methods may help to unravel some of the pathophysiological
mechanisms of migraine. Lack of habituation is the principal and most
reproducible interictal abnormality in sensory processing in migraineurs. It is
found in evoked potential (EP) studies for every stimulation modality including
nociceptive stimuli, and it is likely to be responsible for the increased
intensity dependence of EP. We have hypothesized that deficient EP habituation in
migraine could be due to a reduced preactivation level of sensory cortices
because of hypofunctioning subcortico-cortical aminergic pathways. This is not in
keeping with simple hyperexcitability of the cortex, which has been suggested by 
some, but not all, studies of transcranial magnetic stimulation (TMS). A recent
study of the effects of repetitive TMS on visual EP strongly supports the
hypothesis that migraine is characterized by interictal cortical
hypoexcitability. With regard to pain mechanisms in migraine,
electrophysiological studies of trigeminal pathways using nociceptive blink and
corneal reflexes have confirmed that sensitization of central trigeminal
nociceptors occurs during migraine attacks.

Publication Types: 
    Review

PMID: 12699456 [PubMed - indexed for MEDLINE]

2635: Cephalalgia. 2003;23 Suppl 1:5-11.

Erratum in:
    Cephalalgia. 2003 Jul;23(6):483.

Electroencephalography in migraine: a review with focus on quantitative
electroencephalography and the migraine vs. epilepsy relationship.

Sand T.

Department of Clinical Neuroscience, Norwegian University of Science and
Technology, Clinical Neurophysiology Laboratory, Trondheim, Norway.
trond.sand@medisin.ntnu.no

EEG-studies in migraine in the last decade has contributed modestly to the
understanding of headache pathogenesis. Headache patient groups seem to have
increased EEG responses to photic stimulation, but a useful biological marker for
migraine in single patients has not been found. In future EEG and QEEG studies we
recommend to use follow-up designs and record several EEGs across the migraine
cycle. It is also important to use a blinded study design in order to avoid
selection bias. A clinical EEG should be performed in patients with acute
headache attacks when either epilepsy, basilar migraine, migraine with prolonged 
aura or alternating hemiplegia is suspected. Unequivocal epileptiform
abnormalities usually suggest a diagnosis of epilepsy. In children with occipital
spike-wave activity the probable diagnosis is childhood epilepsy with occipital
paroxysms (CEOP). The final diagnosis of either an epilepsy syndrome or migraine 
must be mainly based on a clinical judgement [corrected].

Publication Types: 
    Review

PMID: 12699455 [PubMed - indexed for MEDLINE]

2636: Cephalalgia. 2003;23 Suppl 1:1-4.

Erratum in:
    Cephalalgia. 2003 Jul;23(6):483.

Peripheral and central activation of trigeminal pain pathways in migraine: data
from experimental animal models.

Buzzi MG, Tassorelli C, Nappi G.

IRCCS Neuromed, Pozzilli, Italy.

Animal models for migraine have provided substantial advances on the mechanisms
and mediators underlying migraine attacks. The neurogenic inflammation model has 
helped understanding the perivascular mechanisms underlying the pathophysiology
of migraine attacks, the receptors involved and the effect of specific
antimigraine drugs. The model based on probing the neuronal effects of
nitroglycerin--an organic nitrate known to induce spontaneous-like migraine
attacks in predisposed subjects--in the rat has provided interesting insights
into the neuroanatomic circuits and neuropharmacological mechanisms involved in
the initiation and repetition of migraine attacks [corrected].

Publication Types: 
    Review

PMID: 12699454 [PubMed - indexed for MEDLINE]

2637: CNS Drugs. 2003;17(6):431-47.

The triptan formulations : how to match patients and products.

Rapoport AM, Tepper SJ, Bigal ME, Sheftell FD.

Department of Neurology, College of Physicians and Surgeons, Columbia University,
New York, New York, USA. alanrapoport@nech.net

The 5-HT(1B/1D) receptor agonists (the 'triptans') are migraine-specific agents
that have revolutionised the treatment of migraine. They are usually the drugs of
choice to treat a migraine attack in progress. Different triptans are available
in various strengths and formulations, including oral tablets, orally
disintegrating tablets, nasal sprays and subcutaneous injections. In Europe,
sumatriptan is also available as a suppository. Specific differences among the
triptans exist, as evidenced by different pharmacological profiles including
half-life, time to peak plasma concentrations, peak plasma concentrations, area
under the concentration-time curve, metabolism and drug-drug interaction
profiles. How or whether these differences translate to clinical efficacy and
tolerability advantages for one agent over another is not well differentiated.
However, delivery systems may play an important role in onset of action. Given
that the clinical distinctions among these agents are subtle, identification of
the most appropriate triptan for an individual patient requires consideration of 
the specific characteristics of the patient and knowledge of patient preference, 
an accurate history of the efficacy of previous acute-care medications and
individual features of the drug being considered. The selection of an acute
antimigraine drug also depends upon the stratification of the patient's migraine 
attack by peak intensity, time to peak intensity, level of associated symptoms
such as nausea and vomiting, time to associated symptoms, comorbid diseases and
concomitant treatments that might cause drug-drug interactions. Individual
patient response to the triptans seems to be idiosyncratic and possibly
genetically determined. Therefore, a set of specific questions can be used to
determine whether a currently used triptan is optimally effective, whether the
dose needs to be increased or whether another triptan should be tried. The
clinician has in his/her armamentarium an ever-expanding variety of triptans,
available in multiple formulations and dosages, which have good safety and
tolerability profiles. Continued clinical use will yield familiarity with the
various triptans, and it should become possible for the interested physician to
match individual patient needs with the specific characteristics of a triptan to 
optimise therapeutic benefit. Use of the methods outlined in this review in
choosing a triptan for an individual patient is probably more likely to lead to
migraine relief than making an educated guess as to which triptan is most
appropriate.

Publication Types: 
    Review

PMID: 12697002 [PubMed - indexed for MEDLINE]

2638: CNS Drugs. 2003;17(6):373-81.

Preventative treatment for migraine and tension-type headaches : do drugs having 
effects on muscle spasm and tone have a role?

Freitag FG.

Department of Family Medicine, Finch University of Health Sciences/Chicago
Medical School, North Chicago, Illinois 60614, USA. dhcdoc@aol.com

Baclofen, tizanidine and botulinum toxin A, agents used to treat disorders of
muscle tone, have been studied as potential preventative treatments for migraine,
tension-type headache and other related disorders.The most extensive work has
been completed with botulinum toxin A. However, there is still a paucity of well 
controlled, clinical trials with this agent, and overall there have been
conflicting and oftentimes equivocal results: studies of its use in migraine
headache have suggested efficacy, whereas those of tension-type headache have not
shown significant evidence of efficacy. There were few significant adverse events
associated with the use of botulinum toxin A in these trials. The mechanism by
which botulinum toxin A may work to prevent headache is not clear. Although
changes in muscle tone may play a role in the effect of the drug, central
mechanisms such as effects on neuropeptides involved in the pathogenesis of
migraine may also be relevant. Further clinical trial work is in progress to help
determine optimal administration schedules and choice of injection locations with
botulinum toxin A for specific headache disorders.There has been limited study of
the use of baclofen, an agent that acts centrally via GABA(A) receptors, in
migraine and cluster headache, with only two open trials conducted to date. Both 
of these studies support the use of baclofen in the preventive treatment of
headache.Tizanidine, which may have both a peripheral and a central mechanism in 
the locus ceruleus in migraine headache, has been studied in several clinical
trials. Although the primary mechanism of action of this agent is, like
clonidine, as an alpha-adrenoceptor agonist, it has little antihypertensive
effect. Open trials of tizanidine have shown it to be useful in chronic headache.
One well controlled trial, conducted as a follow-up to an open-label trial in the
preventive treatment of chronic daily headache, reported tizanidine as having a
statistically significant benefit over placebo. Also of interest is its use in
conjunction with a long-acting NSAID to aid in the treatment of rebound headache 
accompanying the discontinuation of overused acute migraine therapies.In
conclusion, though limited, the studies suggest the efficacy of botulinum toxin
A, baclofen and tizanidine in primary headache disorders.

Publication Types: 
    Review

PMID: 12696998 [PubMed - indexed for MEDLINE]

2639: Radiol Technol. 2003 Mar-Apr;74(4):281-314; quiz 316-20, 350.

Diagnosis and treatment of migraines.

Church EJ, Odle TG.

This article offers an overview of migraines, including their causes, symptoms,
differential diagnosis and treatment. After completing it readers will:
Understand the different classifications of headaches and their attributes. Know 
how headaches differ in children and adults. Describe causes, triggers and
precipitating factors for migraines. Summarize the economic impact of migraines
and how migraine headaches affect patients' lives. Describe the role medical
imaging plays in diagnosing and researching migraines. Understand how migraines
are treated and managed. Discuss the future of migraine diagnosis and treatment.

Publication Types: 
    Review

PMID: 12690805 [PubMed - indexed for MEDLINE]

2640: Pharmacotherapy. 2003 Apr;23(4):494-505.

Over-the-counter drugs for acute migraine attacks: literature review and
recommendations.

Wenzel RG, Sarvis CA, Krause ML.

Diamond Headache Clinic Inpatient Unit, St. Joseph Hospital, Resurrection Health 
Care, 2900 North Lake Shore Drive, Chicago, IL 60657, USA. rwenz@hotmail.com

Migraines affect 28 million people in the United States, and most of these
individuals experience attack-related morbidity. Six of every 10 patients with
migraine treat their headache exclusively with over-the-counter (OTC) products.
Overreliance on OTC agents contributes to preventable morbidity and drug-induced 
headaches. To evaluate the role of OTC drugs in the management of migraine
headaches, we performed a qualitative systematic literature search by using
MEDLINE (January 1966-April 2002), analyzed the references of articles returned
by the MEDLINE search, and reviewed other pertinent literature. In the studied
populations, acetaminophen, aspirin, ibuprofen, and an
aspirin-acetaminophen-caffeine combination product were shown to be more
effective than placebo at reducing moderate or severe migraine pain to mild or no
pain by 2 hours after administration. However, published trials of OTC agents
have systematically excluded patients enduring morbidity with 50% or more of
attacks and/or vomiting with 20% or more of attacks. Patients who experience
disability during the predominance of their attacks are poor candidates for
OTC-exclusive therapy and should seek a physician's help for migraine-specific
prescription drugs. For those with migraine who encounter disability with less
than 50% of attacks and/or vomiting with less than 20% of attacks, sole treatment
with OTC products is a feasible option. Patients who fail to obtain acceptable
relief after an adequate trial of OTC agents also should be referred to a
physician. Pharmacists are well positioned to assess whether patients could
benefit from OTC agents or should seek a physician's assistance.

Publication Types: 
    Guideline
    Practice Guideline
    Review

PMID: 12680479 [PubMed - indexed for MEDLINE]

2641: Funct Neurol. 2002 Oct-Dec;17(4):193-7.

A comparison of familial and sporadic migraine in a headache clinic population.

Rainero I, Valfrè W, Gentile S, Lo Giudice R, Ferrero M, Savi L, Pinessi L.

Neurology III, Headache Center, Department of Neuroscience, University of Turin, 
Italy. irainero@molinette.piemonte.it

We compared the clinical, psychological and pharmacological characteristics of
patients with familial migraine and patients with sporadic migraine. Five hundred
and thirty consecutive new patients attending our Headache Center over a two-year
period were involved in the study. The patients were divided into two groups: A. 
Familial migraine (famM)--at least one first-degree relative affected; B.
Sporadic migraine (spoM)--no first-degree relative affected. Four hundred and
twenty-four patients (80%) fulfilled the criteria for famM and 106 (20%) for
spoM. The patients with famM showed a significantly (p<0.01) earlier age at onset
of the disease. No significant difference in all the remaining features examined 
was found. Our data suggest that famM and spoM represent a single disease entity.

Publication Types: 
    Clinical Trial
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 12675262 [PubMed - indexed for MEDLINE]

2642: Neuro Oncol. 2003 Apr;5(2):121-7.

Reversible, strokelike migraine attacks in patients with previous radiation
therapy.

Bartleson JD, Krecke KN, O'Neill BP, Brown PD.

Departments of Neurology, Mayo Clinic, Rochester, MN 55905, USA.
bartleson.john@mayo.edu

We report 2 adults with a past history of radiation therapy to the head for
malignancy (one with primary B-cell lymphoma confined to the skull and the other 
with multiple hemangioendotheliomas) who developed episodes consistent with
migraine with and without aura. In addition to more typical migraine attacks and 
beginning many years after their radiation therapy, both patients have
experienced infrequent, stereotyped, prolonged, reversible neurologic deficits
associated with headache, occasional seizures, and striking, transient, cortical 
gadolinium enhancement of the posterior cerebral gyri on MRI. Interictal MRI
brain scans show stable abnormalities consistent with the patients' previous
radiation therapy. The neurologic deficits often progressed over a few days,
sometimes lasted weeks, and completely resolved. Electroencephalograms did not
show epileptiform activity. Thorough investigation showed no residual or
recurrent tumor and no recognized cause for the patients' attacks. We postulate a
causal relationship between the patients' remote radiation therapy and their
prolonged, strokelike migraine attacks. Radiation-induced vascular changes could 
provoke the episodes, with or without an underlying migraine diathesis.
Recognition of this syndrome can help avoid invasive testing.

Publication Types: 
    Case Reports

PMID: 12672284 [PubMed - indexed for MEDLINE]

2643: Pediatrics. 2003 Apr;111(4 Pt 1):e376-81.

Comparative study of anxiety, depression, somatization, functional disability,
and illness attribution in adolescents with chronic fatigue or migraine.

Smith MS, Martin-Herz SP, Womack WM, Marsigan JL.

Children's Hospital & Regional Medical Center, Department of Pediatrics,
University of Washington, Seattle 98105, USA. mark.smith@seattlechildrens.org

OBJECTIVE: To compare adolescents with migraine, unexplained profound chronic
fatigue of >6 months duration, and normal school controls on measures of anxiety,
depression, somatization, functional disability, and illness attribution.
METHODS: Adolescents referred to Children's Hospital and Regional Medical Center 
for behavioral treatment of migraine (n = 179) or evaluation of chronic fatigue
(n = 97) were compared with a group of healthy controls of similar age and sex
from a middle school (n = 32). Subjects completed the Spielberger State-Trait
Anxiety Inventory-Trait Form, the Children's Depression Inventory, the Childhood 
Somatization Inventory, and estimated the number of school days missed in the
past 6 months because of illness. Migraine and fatigued subjects completed an
illness attribution questionnaire. RESULTS: Subjects in the 3 groups were 56% to 
70% female and ranged from 11 years old to 18 years old with a mean age of 14.0
+/- 2.0. Forty-six of the 97 chronically fatigued adolescents met 1994 Centers
for Disease Control and Prevention (CDC) criteria for chronic fatigue syndrome
(CDC-CFS), while 51 had idiopathic chronic fatigue syndrome (I-CFS) that did not 
meet full CDC criteria. Adolescents with migraine had significantly higher
anxiety scores than those with I-CFS or controls and higher somatization scores
than controls. Adolescents with CDC-CFS had significantly higher anxiety scores
than those with I-CFS or controls, and higher depression and somatization scores 
than all other groups. There were significant differences between all groups for 
school days missed with CDC-CFS more than I-CFS more than migraine more than
controls. Parents of adolescents with unexplained I-CFS had significantly lower
attribution scores relating illness to possible psychological or stress factors
than parents of adolescents with CDC-CFS or migraine. CONCLUSIONS: Adolescents
referred to an academic center for evaluation of unexplained chronic fatigue had 
greater rates of school absenteeism than adolescents with migraine or healthy
controls. Those meeting CDC-CFS criteria had higher anxiety scores than controls 
and higher depression and somatization scores than migraineurs or controls.
Parents of adolescents with I-CFS were less likely to endorse psychological
factors as possibly contributing to their symptoms than parents of adolescents
with CDC-CFS or migraine.

Publication Types: 
    Comparative Study

PMID: 12671155 [PubMed - indexed for MEDLINE]

2644: Pain. 2003 Apr;102(3):235-41.

Somatostatin infusion withdrawal: a study of patients with migraine, cluster
headache and healthy volunteers.

Levy MJ, Matharu MS, Bhola R, Lightman S, Goadsby PJ.

Headache Group, Institute of Neurology, Queen Square, London WC1N 3BG, UK.

Migraine and cluster headache are the most common disabling primary headache
syndromes and are typically episodic. A reliable method of triggering such
headache attacks facilitates the study and treatment of these disorders. There is
sufficient clinical and laboratory evidence to suggest that somatostatin
withdrawal may be a useful way of triggering headache. We studied 15 subjects,
eight migraineurs, four cluster headache sufferers and three healthy controls.
Each subject had a standard somatostatin infusion, 250 microg/h for 3.5h.
Subjects were followed for 24h post-infusion. Growth hormone was suppressed in
each subject demonstrating a biologically active infusion of somatostatin. None
of the non-headache sufferers had pain. Seven of eight migraine sufferers had no 
immediate headache and no delayed headache. One migraineur experienced short
lasting headache with no migrainous features. Three of four patients with cluster
headache had no significant pain with the infusion, while one had pain after 1h. 
The results suggest that somatostatin infusion is not a reliable way to produce
headache in experimental settings in either migraine or cluster headache. The
data do not exclude a role for somatostatinergic mechanisms in primary headache.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 12670664 [PubMed - indexed for MEDLINE]

2645: Neuroradiology. 2003 May;45(5):300-3. Epub 2003 Mar 27.

Serial MRI in a case of familial hemiplegic migraine.

Butteriss DJ, Ramesh V, Birchall D.

Department of Neuroradiology, Regional Neurosciences Centre Newcastle General
Hospital, Westgate Road, Newcastle upon Tyne, NE4 6BE, UK.

We report MRI findings in a patient with familial hemiplegic migraine (FHM) with 
repeated episodes of hemiparesis. FHM is caused by a penetrant autosomal dominant
genetic mutation; several mutations have been genotyped, involving
brain-expressed ion channels. We found cerebral oedema, dilatation of
intracerebral vessels and decreased water diffusion contralateral to the
hemiparesis, not respecting vascular territories, with subsequent complete
resolution of both clinical and imaging abnormalities. These results are thought 
to be consistent with an underlying primary neuronal pathology with secondary
vascular effects, as opposed to the traditional, primarily vascular, model of
migraine aetiology.

Publication Types: 
    Case Reports

PMID: 12669159 [PubMed - indexed for MEDLINE]

2646: Neurosci Lett. 2003 Apr 10;340(2):135-8.

The influence of semantic priming on event-related potentials to painful
laser-heat stimuli in migraine patients.

Weiss T, Miltner WH, Dillmann J.

Friedrich Schiller University, Institute of Psychology, Department of Biological 
and Clinical Psychology, Am Steiger 3, Haus 1, D-07743 Jena, Germany.
weiss@biopsy.uni-jena.de

We investigated the effects of different semantic primes on the processing of
painful stimuli in migraine patients. For prime stimuli, descriptors of three
categories were used: somatosensory pain-related, affective pain-related, and
neutral adjectives. While migraine patients (n = 17) processed these primes, a
painful laser-heat stimulus was applied to the dorsum of the left hand.
Laser-evoked potentials (LEPs) were recorded and pain intensity ratings were
obtained after each single laser stimulus. Pain thresholds were significantly
lower in patients than in control subjects. LEP amplitudes were also
significantly smaller in patients than in controls, but this effect could be
explained by differences in applied stimulus intensity. Within the group of
migraine patients, LEP amplitudes at 300 ms post laser stimulus and N2-P2
peak-to-peak amplitudes were significantly enlarged when applied while subjects
processed pain-related as compared to non-pain-related primes, i.e. patients
showed a pattern of priming effect similar to that of the control group.
Additionally, patients recognised more affective words than control subjects, and
affective pain-related primes tended to enhance the P2 amplitude of LEP more than
somatosensory pain-related primes. It is suggested that pain-related semantic
primes might pre-activate neural networks subserving pain memory and pain
processing. Copyright 2003 Elsevier Science Ireland Ltd.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 12668255 [PubMed - indexed for MEDLINE]

2647: Expert Opin Pharmacother. 2003 Apr;4(4):433-43.

New developments in migraine prophylaxis.

Bigal ME, Krymchantowski AV, Rapoport AM.

Department of Neurology, Albert Einstein College of Medicine, New York, USA.
mbigal@aecom.yu.edu

Migraine is a common neurological disorder that afflicts > or = 12% of the adult 
US population. Severe, frequent and disabling attacks require effective
prophylaxis. Traditional preventive drugs such as beta-blockers, antidepressants 
and calcium antagonists, despite their documented efficacy, fail to offer relief 
for a significant proportion of migraine sufferers. Multiple threads of research 
over the last 15 years have led to the concept that migraine is generated from a 
hyperexcitable brain. This opens new perspectives in terms of preventive options,
especially regarding the anticonvulsants agents. Additionally, different groups
of substances, some of which nominated as non-orthodox agents, have been recently
subjected to clinical trials and found to be effective. The aim of this review is
to present and discuss the new options for migraine prevention.

Publication Types: 
    Review

PMID: 12667107 [PubMed - indexed for MEDLINE]

2648: Clin Auton Res. 2003 Feb;13(1):16-21.

Dysfunction of the pupillary light reflex following migraine headache.

Mylius V, Braune HJ, Schepelmann K.

Medizinisches Zentrum für Nervenheilkunde, Neurologische Klinik mit Poliklinik,
Rudolf-Bultmann-Str 8, 35039 Marburg, Germany.

Using pupillometry and sympathetic skin responses we compared the changes in
local and systemic autonomic function within one week of a migraine attack. We
investigated whether the measurement of the pupillary light reflex provides
further information on the pathophysiology of migraine.Forty-two migraine
patients and forty-two healthy age-matched controls were included. The parameters
that were measured were the amplitude of the pupillary light reflex, the pupil
size at the beginning of the measurement, the latency, the velocity of
constriction and the velocity at the end of the dilatation.The average pupil size
was 6.43 mm in the migraine group and 6.7 mm in the control group (p < 0.01).
Reduced velocity of constriction and smaller amplitude of constriction in
migraine patients within two days of an attack were signs of a parasympathetic
dysfunction (p < 0.05). The sympathetic skin response did not differ
significantly between migraine sufferers and controls.These findings indicate
that both parasympathetic and sympathetic nerves supplying the eye are involved
in migraine headache presumably due to effects on the pericarotid sympathetic
fibers and involvement of trigeminal-parasympathetic reflexes.

Publication Types: 
    Clinical Trial

PMID: 12664243 [PubMed - indexed for MEDLINE]

2649: Cephalalgia. 2003 Apr;23(3):197-205.

Course of migraine during pregnancy and postpartum: a prospective study.

Sances G, Granella F, Nappi RE, Fignon A, Ghiotto N, Polatti F, Nappi G.

Headache Centre, IRCCS C. Mondino Foundation, Institute of Neurology, Pavia,
Italy. grazia.sances@mondino.it

The aim of this study was to investigate prospectively the course of migraine
during pregnancy and postpartum. Of all the pregnant women consecutively
attending an obstetrics and gynaecology department for a routine first-trimester 
antenatal check-up, 49 migraine sufferers--two were affected by migraine with
aura (MA) and 47 by migraine without aura (MO)--who had experienced at least one 
attack during the 3 months preceding pregnancy were identified, enrolled in the
study and given a headache diary. Subsequent examinations were performed at the
end of the second and third trimesters and 1 month after delivery. Migraine was
seen to improve in 46.8% of the 47 MO sufferers during the first trimester, in
83.0% during the second and in 87.2% during the third, while complete remission
was attained by 10.6%, 53.2%, and 78.7% of the women, respectively. Migraine
recurred during the first week after childbirth in 34.0% of the women and during 
the first month in 55.3%. Certain risk factors for lack of improvement of
migraine during pregnancy were identified: the presence of menstrually related
migraine before pregnancy was associated with a lack of headache improvement in
the first and third trimesters, while second-trimester hyperemesis, and a
pathological pregnancy course were associated with a lack of headache improvement
in the second trimester. Breast feeding seemed to protect from migraine
recurrence during postpartum.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 12662187 [PubMed - indexed for MEDLINE]

2650: Cephalalgia. 2003 Apr;23(3):186-92.

Personality traits, depression and migraine in women: a longitudinal study.

Mongini F, Keller R, Deregibus A, Raviola F, Mongini T, Sancarlo M.

Department of Clinical Pathophysiology, Headache and Facial Pain Unit, University
of Turin, Turin, Italy. franco.mongini@unito.it

Our purpose was to examine the association between personality traits, depression
and migraine in the long term. In 56 women with migraine a psychological
assessment was carried out to assess the presence of major depression, and the
Minnesota Multiphasic Personality Inventory (MMPI) and the State and Trait
Anxiety Inventory (STAI) were administered at baseline (T0) and after 6-7 years
(T2). Frequency, severity and duration of migraine were recorded at T0, after
treatment (T1) and at T2, and their relation to the prevalence of depression and 
to the MMPI and STAI data was examined (ANOVA, Student's t-test, chi2 analysis,
and multiple regression analysis). Pain parameters improved in all patients in
T0-T1, but at T2 were higher in patients with depression at T0. The patients
whose migraine improved at T2 had, at T0 and T2, significantly lower MMPI and
STAI scores. Multiple regression analysis showed a correlation of the MMPI
depression score and STAI 1,2 scores at T0 with headache frequency at T2. We
conclude that the co-occurrence of migraine, personality changes and depression
in women does not appear to influence the results of treatment at short-term, but
it seems to be influential on headache history in the long term.

PMID: 12662185 [PubMed - indexed for MEDLINE]

2651: Cephalalgia. 2003 Apr;23(3):183-5.

RPR100893, a substance-P antagonist, is not effective in the treatment of
migraine attacks.

Diener HC; RPR100893 Study Group.

Department of Neurology, University of Essen, Essen, Germany.
h.diener@uni-essen.de

A global, double-blind, randomized, placebo-controlled, dose-finding,
parallel-group trial was conducted to compare three oral doses of RPR100893 (1,
5, 20 mg), a substance-P antagonist, and placebo in 139 patients with migraine
attacks with moderate or severe headache intensity. Headache intensity and
improvement of headache after 2 h were not different in the four treatment
groups. Therefore, it is concluded that this oral substance-P antagonist in the
doses used here is not effective.

Publication Types: 
    Clinical Trial
    Comparative Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 12662184 [PubMed - indexed for MEDLINE]

2652: Pediatr Neurol. 2003 Jan;28(1):9-15.

The diet factor in pediatric and adolescent migraine.

Millichap JG, Yee MM.

Division of Neurology, Children's Memorial Hospital, Chicago, Illinois 60614,
USA.

Diet can play an important role in the precipitation of headaches in children and
adolescents with migraine. The diet factor in pediatric migraine is frequently
neglected in favor of preventive drug therapy. The list of foods, beverages, and 
additives that trigger migraine includes cheese, chocolate, citrus fruits, hot
dogs, monosodium glutamate, aspartame, fatty foods, ice cream, caffeine
withdrawal, and alcoholic drinks, especially red wine and beer. Underage drinking
is a significant potential cause of recurrent headache in today's adolescent
patients. Tyramine, phenylethylamine, histamine, nitrites, and sulfites are
involved in the mechanism of food intolerance headache. Immunoglobulin E-mediated
food allergy is an infrequent cause. Dietary triggers affect phases of the
migraine process by influencing release of serotonin and norepinephrine, causing 
vasoconstriction or vasodilatation, or by direct stimulation of trigeminal
ganglia, brainstem, and cortical neuronal pathways. Treatment begins with a
headache and diet diary and the selective avoidance of foods presumed to trigger 
attacks. A universal migraine diet with simultaneous elimination of all potential
food triggers is generally not advised in practice. A well-balanced diet is
encouraged, with avoidance of fasting or skipped meals. Long-term prophylactic
drug therapy is appropriate only after exclusion of headache-precipitating
trigger factors, including dietary factors.

Publication Types: 
    Review

PMID: 12657413 [PubMed - indexed for MEDLINE]

2653: Headache. 2003 Apr;43(4):404-6.

Chiari-associated exertional, cough, and sneeze headache responsive to medical
therapy.

Buzzi MG, Formisano R, Colonnese C, Pierelli F.

IRCCS Santa Lucia Foundation, Via Ardeatina 306, Pozzilli (IS), 00179 Rome,
Italy.

Benign exertional headache is coded as a separate entity within the International
Headache Society's classification system, but the pathophysiological mechanisms
underlying this clinical headache subtype are unknown and possibly are similar to
those generating migraine. Coexistence of migraine and benign exertional headache
in the same patient is not unusual, and antimigraine pharmacologic treatments are
often effective in both headache types. Regardless, optimal management mandates
that the clinician exclude any intracranial or systemic disease that could mimic 
"primary" exertional headache. The same holds for primary headaches induced by
coughing or sneezing; congenital malformations or neoplasms, particularly within 
the posterior fossa, are not rare in these patients. The neurologic examination
may not be sufficiently sensitive to detect the offending lesion. We describe a
patient with migraine without aura and exertional secondary headache due to
Chiari malformation type I whose headaches responded to treatment with
propranolol and indomethacin.

Publication Types: 
    Case Reports

PMID: 12656713 [PubMed - indexed for MEDLINE]

2654: Headache. 2003 Apr;43(4):400-3.

Sumatriptan in migraine with unilateral cranial autonomic symptoms: an open
study.

Barbanti P, Fabbrini G, Vanacore N, Pesare M, Buzzi MG.

Department of Neurosciences, University La Sapienza, Viale dell'Università 30,
00185 Rome, Italy.

OBJECTIVE: To investigate the response to sumatriptan in migraineurs with
unilateral cranial autonomic symptoms such as lacrimation, eye redness, eyelid
edema, nasal congestion, and rhinorrhea. BACKGROUND: Given the potential
large-scale recruitment of peripheral neurovascular 5-HT1B/1D receptors
consequent to the activation of the trigeminal autonomic reflex in such patients,
the presence of unilateral cranial autonomic symptoms may predict a positive
response to sumatriptan. METHODS: Seventy-two consecutive migraineurs with
unilateral cranial autonomic symptoms were given sumatriptan 50-mg tablets to
treat 1 migraine attack and were asked to record their clinical response to the
drug at different time points. End points were pain-relief and pain-free response
at 1 and 2 hours. RESULTS: Pain relief was reported by 47 patients (65.3%) at 1
hour and by 59 (81.9%) at 2 hours. Pain-free response was reported by 22 patients
(30.6%) at 1 hour and by 44 (61.1%) at 2 hours. Responsiveness to sumatriptan did
not correlate with the type or number of unilateral cranial autonomic symptoms,
demographic characteristics, prophylactic treatments, use of contraceptives, or
concomitant tension-type headache. CONCLUSIONS: Migraineurs with unilateral
cranial autonomic symptoms seem to respond to sumatriptan better than other
migraineurs. The presence of unilateral cranial autonomic symptoms may predict a 
positive response to the triptans.

Publication Types: 
    Clinical Trial

PMID: 12656712 [PubMed - indexed for MEDLINE]

2655: Headache. 2003 Apr;43(4):389-94.

Nalpha-methylhistamine safety and efficacy in migraine prophylaxis: phase I and
phase II studies.

Millán-Guerrero RO, Pineda-Lucatero AG, Hernández-Benjamín T, Tene CE, Pacheco
MF.

Department of Neurology, Unidad de Investigación Médica en Epidemiología Clínica,
Hospital General de Zona UMF No 1 IMSS, Mexico.

OBJECTIVE: To study the therapeutic potential of the subcutaneous administration 
of Nalpha-methylhistamine in migraine prophylaxis. BACKGROUND: The histamine
catabolite, Nalpha-methylhistamine, possesses a selective affinity for H3
receptors. We consequently considered it viable to conduct a clinical
pharmacological study to evaluate the safety and efficacy of this histaminergic
H3 agonist in migraine prophylactic treatment, which specifically may inhibit the
neurogenic edema response involved in migraine pathophysiology. METHODS: Phase
I.-In a clinical trial of 30 healthy volunteers, the effects of the subcutaneous 
administration of Nalpha-methylhistamine and placebo were studied to assess
undesirable symptomatic effects. Phase II.-In a clinical open study, we evaluated
the efficacy of Nalpha-methylhistamine in reducing headache intensity, frequency,
and duration; and in decreasing analgesic intake in 18 patients with migraine.
RESULTS: Phase I.-None of the variables studied showed significant differences
(P>.05), and no secondary effects were observed at doses below 10 ng. Phase
II.-Nalpha-methylhistamine, at doses of 1 to 3 ng, significantly reduced
(P<.0001) the frequency, intensity, and duration of migraine attacks, as well as 
the need for rescue analgesics. However, at doses greater than 3 ng, patients
experienced intense headache. CONCLUSIONS: The present study provides evidence of
the safety and efficacy of Nalpha-methylhistamine applied subcutaneously at doses
of 1 to 3 ng twice a week.

Publication Types: 
    Clinical Trial
    Clinical Trial, Phase I
    Clinical Trial, Phase II
    Comparative Study

PMID: 12656710 [PubMed - indexed for MEDLINE]

2656: Headache. 2003 Apr;43(4):376-88.

Comment in:
    Headache. 2003 Nov-Dec;43(10):1119-21; author reply 1121.

Migraine headache recurrence: relationship to clinical, pharmacological, and
pharmacokinetic properties of triptans.

Géraud G, Keywood C, Senard JM.

Service de Neurologie, CHU Rangueil, 1 Avenue Jean Poulhès, 31054 Toulouse,
France.

BACKGROUND AND OBJECTIVES: Triptan use is associated with headache recurrence,
and this has been cited as an important reason for patient dissatisfaction with
the treatment. The mechanism by which recurrence occurs is not clear, and the
incidence of recurrence varies with the triptan used. In order to explore the
pharmacological and physiological interaction of triptans and migraine headache
recurrence further, some specific clinical, pharmacological, and pharmacokinetic 
factors that might influence migraine recurrence were evaluated in a review of
the major efficacy data for the drugs in the triptan class. These factors were
5-HT1B and 5-HT1D receptor activities, the pharmacokinetic elimination half-life 
of each triptan, and the clinical efficacy of each compound, determined by the
proportion of patients with headache relief and the therapeutic gain over
placebo. METHODS: Clinical data were derived from 31 triptan, placebo-controlled,
major efficacy studies used in a previous meta-analysis. The mean recurrence
rate, mean headache response, and therapeutic gain were calculated using the
results from the individual clinical studies. Mean headache response and
therapeutic gain were calculated at the time point used to define recurrence in
each study. Data for binding affinity and potency were taken from a
direct-comparison in vitro pharmacology study, and the elimination half-life
quoted in the data sheet for each triptan was used. Rank correlation with
recurrence rate was performed for each of the test parameters. RESULTS: Mean
headache recurrence rates ranged from 17% for frovatriptan 2.5 mg to 40% for
rizatriptan. Elimination half-life and recurrence were inversely correlated (r = 
-1.0, P =.0016). There was also a significant inverse correlation between 5-HT1B 
receptor potency and recurrence (r = -0.68, P =.034), but 5-HT1D receptor potency
was not correlated with recurrence (r = -0.20, P =.54). In addition, the binding 
affinities for the 5-HT1B and 5-HT1D receptors were not correlated to headache
recurrence. Importantly, it also was demonstrated that initial clinical efficacy 
was not correlated to headache recurrence. The correlation coefficient for
headache response was 0.18 (P =.53) and for therapeutic gain, -0.11 (P =.71).
CONCLUSION: The incidence of migraine headache recurrence varies between drugs in
the triptan class. Migraine recurrence does not appear to be related to initial
clinical efficacy, but is influenced by the pharmacological and pharmacokinetic
properties of the individual triptans. The triptans with longer half-lives and
greater 5-HT1B receptor potency had the lowest rates of headache recurrence.

Publication Types: 
    Comparative Study
    Review

PMID: 12656709 [PubMed - indexed for MEDLINE]

2657: Headache. 2003 Apr;43(4):369-75.

Peripheral neurostimulation for the treatment of chronic, disabling transformed
migraine.

Popeney CA, Aló KM.

Fort Bend Neurology, Suite 110, 2225 Williams Trace Boulevard, Sugarland, TX
77478, USA.

BACKGROUND: Up to 5% of the general population suffers from transformed migraine.
This study analyzes clinical responses of transformed migraine to cervical
peripheral nerve stimulation. METHODS: Headache frequency, severity, and
disability (Migraine Disability Assessment [MIDAS] scores) were independently
measured in an uncontrolled consecutive case series of 25 patients with
transformed migraine implanted with C1 through C3 peripheral nerve stimulation.
All patients met International Headache Society (IHS) criteria for episodic
migraine, as well as suggested criteria for transformed migraine, and had been
refractory to conventional treatment for at least 6 months. Responses to C1
through C3 peripheral nerve stimulation were recorded. RESULTS: Prior to
stimulation, all patients experienced severe disability (grade IV on the MIDAS)
with 75.56 headache days (average severity, 9.32; average MIDAS score, 121) over 
a 3-month period. Following stimulation, 15 patients reported little or no
disability (grade I), 1 reported mild disability (grade II), 4 reported moderate 
disability (grade III), and 5 continued with severe disability (grade IV), with
37.45 headache days (average severity, 5.72; average MIDAS score, 15). The
average improvement in the MIDAS score was 88.7%, with all patients reporting
their headaches well controlled after stimulation. CONCLUSIONS: These results
raise the possibility that C1 through C3 peripheral nerve stimulation can help
improve transformed migraine symptoms and disability. A controlled study is
required to confirm these results.

PMID: 12656708 [PubMed - indexed for MEDLINE]

2658: Headache. 2003 Apr;43(4):362-8.

Migraine headaches and sleep disturbances in children.

Miller VA, Palermo TM, Powers SW, Scher MS, Hershey AD.

Case Western Reserve University, Cleveland, Ohio, USA.

OBJECTIVE: The aim of the present study was to investigate the prevalence of
sleep disturbances in children with migraine headaches and to describe individual
differences in sleep behaviors based on headache features (eg, frequency,
duration, intensity). BACKGROUND: A relationship between migraine headaches and
sleep disturbances has been suggested in both children and adults, but there is a
lack of research examining the relationship between specific headache features
and the range of sleep behaviors in children. METHODS: One hundred eighteen
children, aged 2 to 12 years (mean, 9.1; standard deviation, 2.3) were evaluated 
for headaches at two pediatric neurology departments. Parents completed the
Children's Sleep Habits Questionnaire and a standardized questionnaire regarding 
headache characteristics. RESULTS: Parents reported a high rate of sleep
disturbances in children, including sleeping too little (42%), bruxism (29%),
child co-sleeping with parents (25%), and snoring (23%). Children with migraine
headaches experienced more sleep disturbances compared to published healthy
control norms. After controlling for child demographics, we found that the
frequency and duration of migraine headaches predicted specific sleep
disturbances, including sleep anxiety, parasomnias, and bedtime resistance.
CONCLUSIONS: Children with migraine headaches have a high prevalence of sleep
disturbances. The direction of the relationship between headaches and sleep is
unknown. Regardless, interventions targeting sleep habits may improve headache
symptoms, and effective treatment of headaches in children may positively impact 
sleep.

Publication Types: 
    Research Support, U.S. Gov't, P.H.S.

PMID: 12656707 [PubMed - indexed for MEDLINE]

2659: Headache. 2003 Apr;43(4):343-52.

Reliability and validity of the Japanese Migraine Disability Assessment (MIDAS)
Questionnaire.

Iigaya M, Sakai F, Kolodner KB, Lipton RB, Stewart WF.

Department of Neurology, Kitasato University, Kitasato 1-15-1, Sagamihara-shi,
Kanagawa, Japan.

OBJECTIVE: This study was designed to assess the test-retest reliability,
internal consistency, and validity of a Japanese translation of the Migraine
Disability Assessment (MIDAS) Questionnaire in a sample of Japanese patients with
headache. BACKGROUND: Previous studies have demonstrated that the
English-language version of the MIDAS Questionnaire is a reliable and valid
instrument for the assessment of migraine-related disability. Any translations of
the MIDAS Questionnaire must also be assessed for reliability and validity.
METHODS: Study participants were recruited from the patient population attending 
either the Neurology Department of Kitasato University or an affiliated clinic.
Participants were eligible for study entry if they had 6 or more primary
headaches per year. For reliability testing, participants completed the MIDAS
Questionnaire on 2 occasions, exactly 2 weeks apart. To assess validity, patients
were also invited to participate in a 90-day daily diary study. Composite
measures from the 90-day diaries were compared to equivalent MIDAS measures (ie, 
5 questions on headache-related disability and 1 question each on average pain
intensity and headache frequency in the last 3 months) and to the total MIDAS
score obtained from a third MIDAS Questionnaire completed at the end of this
90-day period. RESULTS: One hundred one patients between the ages of 21 and 77
years were recruited (81 women and 20 men). Ninety-nine patients (80 women and 19
men) participated in the diary study. At baseline, 46.5% of patients were MIDAS
grade I or II (minimal, mild, or infrequent disability), 22.2% were MIDAS grade
III (moderate disability), and 31.3% were MIDAS grade IV (severe disability).
Test-retest Spearman correlations for the 5 disability questions and the
questions on average pain intensity and headache frequency ranged from 0.59 to
0.80 (P<.0001). The test-retest Spearman correlation coefficient for the total
MIDAS score was 0.83 (P<.0001). The degree to which individual MIDAS questions
correlated with the diary-based measures ranged from 0.36 to 0.88. The
correlation between the total MIDAS score and the equivalent diary-based measure 
was 0.66. In general, the mean and median values for the MIDAS items and total
MIDAS score were similar to the means and medians for the diary-based measures.
However, the mean MIDAS scores for the number of days on which headache was
experienced and the number of missed workdays were significantly different
compared to the diary-based estimates for these items (P<.05). In addition, the
mean MIDAS score for the number of days of missed housework was significantly
higher than the corresponding diary-based estimate (P<.01). CONCLUSIONS: The
results from this study show that the Japanese translation of the MIDAS
Questionnaire is comparable with the English-language version in terms of
reliability and validity.

PMID: 12656705 [PubMed - indexed for MEDLINE]

2660: Headache. 2003 Apr;43(4):336-42.

Assessment of migraine disability using the migraine disability assessment
(MIDAS) questionnaire: a comparison of chronic migraine with episodic migraine.

Bigal ME, Rapoport AM, Lipton RB, Tepper SJ, Sheftell FD.

Department of Neurology, Albert Einstein College of Medicine, Office 334-A,
Rousso Building, 1165 Morris Park Avenue, Bronx, NY 10461, USA.

BACKGROUND: Chronic migraine is the most common type of chronic daily headache
seen in headache tertiary care centers. Most patients with chronic migraine
report their ability to function and feeling of well-being as severely impaired. 
OBJECTIVE: To measure the headache-related disability of patients with chronic
migraine using the Migraine Disability Assessment (MIDAS) Questionnaire,
comparing it with that obtained in a control group of patients with episodic
migraine. METHODS: The clinical records of 703 patients with chronic daily
headache treated in a headache specialty clinic were reviewed to identify 182
with chronic migraine who were evaluated using the MIDAS at their initial visit. 
Our control group consisted of 86 patients with episodic migraine. RESULTS: Of
the 182 patients with chronic migraine, 127 (69.8%) were overusing acute-care
medication. Patients were predominantly women (72.5%), with a mean age of 38.3
years. The group with episodic migraine consisted of 59 women (68.6%), with a
mean age of 36.1 years. No statistically significant demographic differences were
observed between the two groups. The group with chronic migraine had more total
headache days over 3 months (66.7 versus 15.5, P<.001), missed more days of work 
or school (5.3 versus 2.3, P =.0007), had more reduced effectiveness days at work
or school (11.9 versus 4.6, P =.0001), missed more days of housework (16.5 versus
3.3, P<.0001), and missed more days of family, social, or leisure activities (7.0
versus 5.5, P =.03). The group with chronic migraine was more likely to be in
MIDAS grade IV (64.3% versus 43.2%, P =.001), reflecting the great likelihood of 
severe disability in this group. The average total MIDAS score was 34.9 in the
group with chronic migraine versus 19.3 in the group with episodic migraine
(P<.001). CONCLUSION: In subspecialty centers, patients with chronic migraine
demonstrate remarkable impairment of their daily activities and are severely
burdened by their headache syndrome, reflected by their high MIDAS scores. The
chronicity and pervasiveness of migraine thus is associated with increased
functional impairment as well as increase in headache frequency.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 12656704 [PubMed - indexed for MEDLINE]

2661: Headache. 2003 Apr;43(4):330-5.

Health care utilization in patients with migraine: demographics and patterns of
care in the ambulatory setting.

Gibbs TS, Fleischer AB Jr, Feldman SR, Sam MC, O'Donovan CA.

Department of Dermatology, Wake Forest University School of Medicine,
Winston-Salem, NC 27157, USA.

BACKGROUND: Migraine affects people of all races and both sexes. Migraineurs
suffer both financial losses and impaired quality of life. Recent progress in the
treatment of migraine has not been made readily available to all who suffer the
condition. OBJECTIVE: To assess outpatient health care delivery patterns for
migraine sufferers in the United States. METHODS: National Ambulatory Medical
Care Survey data from 1990 to 1998 was used to assess the demographics of
patients seen with a diagnosis of migraine, the types of physicians they saw, and
the medications used to treat migraine. RESULTS: Women accounted for 79% of
visits for migraines and whites for 91% of the visits. There was a dramatic
increase in the number of migraine visits during the study period, from 9.4
visits per 1000 people in 1990 to 18 visits per 1000 in 1998. Primary care
physicians saw the majority of patients (72.2%). Butalbital/aspirin/caffeine was 
the drug most commonly prescribed for migraine treatment, followed by
acetaminophen/dichloralphenazone/isometheptene mucate, propranolol, and
sumatriptan. CONCLUSION: Perhaps in part due to newer treatment options, the
number of visits for the treatment of migraine doubled over the study interval.
Even so, most patients with migraine continue to be treated with older and
presumably less effective medications.

PMID: 12656703 [PubMed - indexed for MEDLINE]

2662: Headache. 2003 Apr;43(4):322-9.

A structural representation of migraine diagnostic criteria: the experts' view.

Nash JG, Nash JM.

Department of Psychology, Stonehill College, Easton, MA 02357, USA.

OBJECTIVE: To generate an empirically derived structural representation of
migraine diagnostic criteria in a group of international headache experts using
the Pathfinder network scaling algorithm in order to evaluate the validity of the
migraine criteria used in the International Headache Society (IHS) classification
system. BACKGROUND: Because it is a disease entity that lacks objective defining 
markers, developing valid diagnostic criteria for migraine is a challenge. The
IHS committee relied on expert consensus to develop their classification system
in 1988. Expert consensus also was used to evaluate the validity of the IHS
classification system, but further studies employing alternative methods still
are needed. METHODS: Headache experts representing the Executive Committee of the
IHS and the Board of Directors of the American Headache Society analyzed 14
criteria (7 IHS and 7 non-IHS) considered relevant in diagnosing migraine. Their 
ratings were submitted to the Pathfinder algorithm to generate a network
structure reflecting the experts' conceptualization of migraine diagnostic
criteria. RESULTS: The expert network had 3 groupings: headache characteristics
(eg, phonophobia, unilateral pain, throbbing pain), biological contributing
factors (eg, family history, hormonal relationship, relief with sleep), and
triggering factors (eg, worse with stress, food triggers). The IHS criteria were 
clustered together in the center portion of the network. A t test showed that
each IHS criterion was closer conceptually to other IHS criteria than to non-IHS 
criteria. Graph theory indices revealed that the most central criteria were
unilateral pain, moderate/severe intensity, and nausea/vomiting. CONCLUSION: The 
structural representation of migraine diagnostic criteria from these
international headache experts is consistent with the migraine diagnostic
criteria set forth in the IHS classification system and thus provides further
support for the validity of migraine criteria in the IHS system.

PMID: 12656702 [PubMed - indexed for MEDLINE]

2663: Headache. 2003 Apr;43(4):309-21.

Medical oophorectomy with and without estrogen add-back therapy in the prevention
of migraine headache.

Martin V, Wernke S, Mandell K, Zoma W, Bean J, Pinney S, Liu J, Ramadan N, Rebar 
R.

Department of Internal Medicine, University of Cincinnati College of Medicine,
231 Albert Sabin Way, ML 6003, Cincinnati, OH 45267-4217, USA.

OBJECTIVES: To determine the preventive benefit of "medical oophorectomy" and
transdermal estradiol in women with migraine. BACKGROUND: Epidemiological studies
have demonstrated that declines in serum estrogen levels occurring during normal 
menstrual cycles can trigger headache in women with migraine. Prior to this
study, no randomized controlled trials have evaluated whether minimizing these
hormonal changes pharmacologically can prevent headache. METHODS: Twenty-one
women with regular menstrual cycles and a diagnosis of migraine headache were
enrolled. After a 2.5-month placebo run-in phase, all patients received a
subcutaneous goserelin implant (a gonadotropin-releasing hormone agonist) to
induce a medical oophorectomy. One month later, while continuing goserelin,
participants were randomized to receive a transdermal patch containing 100 microg
of estradiol-17beta (gonadotropin-releasing hormone agonist/estradiol group, n = 
9) or a placebo patch (gonadotropin-releasing hormone agonist/placebo group, n = 
12) during a 2-month treatment phase. The primary outcome measure was the
headache index, which was defined as the mean of pain severity ratings (0 to 10
scale) recorded three times per day by daily diary. Secondary outcome measures
included headache disability, headache severity, headache frequency, and the
percentage of headaches with a pain severity rating of 7 or greater. RESULTS: The
headache index was significantly lower during the treatment period in the
gonadotropin-releasing hormone agonist/estradiol group than in the
gonadotropin-releasing hormone agonist/placebo group (P =.025). Similar
improvements were observed in the gonadotropin-releasing hormone
agonist/estradiol group for all secondary outcome measures with the exception of 
headache frequency, which was unchanged between the groups. Within the
gonadotropin-releasing hormone agonist/estradiol group, there was a 33.7%
reduction (95% confidence interval, -64.4 to -3.0) in the headache index during
the treatment phase when compared with the placebo run-in phase; no difference
was seen between those phases within the gonadotropin-releasing hormone
agonist/placebo group. CONCLUSIONS: Minimization of hormonal fluctuations with
gonadotropin-releasing hormone agonist therapy alone is inadequate to prevent
headache in women who are premenopausal with migraine. The addition of
transdermal estradiol to existing gonadotropin-releasing hormone agonist therapy 
provides a modest preventive benefit.

Publication Types: 
    Clinical Trial
    Comparative Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 12656701 [PubMed - indexed for MEDLINE]

2664: Neurology. 2003 Mar 25;60(6):935-40.

Premonitory symptoms in migraine: an electronic diary study.

Giffin NJ, Ruggiero L, Lipton RB, Silberstein SD, Tvedskov JF, Olesen J, Altman
J, Goadsby PJ, Macrae A.

Institute of Neurology, Queen Square, London, UK.

BACKGROUND: Migraine is frequently associated with nonheadache symptoms before,
during, and after the headache. Premonitory symptoms occurring before the attack 
have not been rigorously studied. Should these symptoms accurately predict
headache, there are considerable implications for the pathophysiology and
management of migraine. METHODS: Electronic diaries were used in a 3-month
multicenter study to record nonheadache symptoms before, during, and after
migraine. The authors recruited subjects who reported nonheadache symptoms in at 
least two of three attacks that they believed predicted headache. Symptoms were
entered in the diaries by patient initiation and through prompted entries at
random times daily. Entries could not be altered retrospectively. Data recorded
included nonheadache symptoms occurring during all three phases of the migraine, 
prediction of the attack from premonitory symptoms, general state of health, and 
action taken to prevent the headache. RESULTS: One hundred twenty patients were
recruited: 97 provided usable data. Patients correctly predicted migraine
headaches from 72% of diary entries with premonitory symptoms. A range of
cognitive and physical symptoms was reported at a similar rate through all three 
phases of the migraine. The most common premonitory symptoms were feeling tired
and weary (72% of attacks with warning features), having difficulty concentrating
(51%), and a stiff neck (50%). Subjects who functioned poorly in the premonitory 
phase were the most likely to correctly predict headache. CONCLUSIONS: Using an
electronic diary system, the authors show that migraineurs who report premonitory
symptoms can accurately predict the full-blown headache.

Publication Types: 
    Multicenter Study
    Research Support, Non-U.S. Gov't

PMID: 12654956 [PubMed - indexed for MEDLINE]

2665: Brain Res Mol Brain Res. 2003 Mar 17;111(1-2):84-90.

Association of the C677T and A1298C polymorphisms in the 5,10
methylenetetrahydrofolate reductase gene in patients with migraine risk.

Kara I, Sazci A, Ergul E, Kaya G, Kilic G.

Department of Neurological Sciences, Institute for Medical Research, Istanbul
University, 34280 Istanbul, Turkey.

Although controversial, diminished activity of 5,10 methylenetetrahydrofolate
reductase (MTHFR), a regulatory enzyme of homocysteine metabolism, may predispose
to migraine in Turkish people. In a case-control study, we determined the
prevalence of two common MTHFR polymorphisms,C677T and A1298C, in 102 migraine
patients (23 migraine with aura, 70 migraine without aura and nine with
tension-type headache) and compared it to that of 136 healthy controls. The
frequencies of the T allele of MTHFR677 and the C allele of MTHFR1298 were
significantly higher in the total migraine population (33.82%, 33.82%) than in
controls (25.38% and 24.26%), respectively.The genotypes T677T and C1298C were
the only genotypes significantly associated with migraine (OR=5.702; 95%
CI=1.184-27.457; P=0.015) and (OR=8.933; 95% CI=1.953-40.869; P=0.001),
respectively). Individuals with migraine with aura with C1298C and C677C/C1298C
genotypes were even more profoundly associated with migraine risk than others
(OR=14.105; 95% CI=2.417-82.320; P=0.0001) and (OR=10.050; 95% CI=1.580-63.907;
P=0.003), respectively. However individuals with migraine without aura with T677T
and C1298C genotypes showed the same susceptibility (OR=7.444; 95%
CI=1.503-36.863); P=0.005). Patients with C1298C and C677C/C1298C genotypes may
also predispose to tension-type headache (OR=8.375; 95% CI=0.685-102.458);
P=0.049).

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 12654508 [PubMed - indexed for MEDLINE]

2666: Am J Gastroenterol. 2003 Mar;98(3):625-9.

Erratum in:
    Am J Gastroenterol. 2003 Jul;98(7):1674.

Association between migraine and Celiac disease: results from a preliminary
case-control and therapeutic study.

Gabrielli M, Cremonini F, Fiore G, Addolorato G, Padalino C, Candelli M, De Leo
ME, Santarelli L, Giacovazzo M, Gasbarrini A, Pola P, Gasbarrini A.

Department of Internal Medicine, Catholic University of the Sacred Heart, Gemelli
Hospital, Rome, Italy.

OBJECTIVES: Subclinical celiac disease (CD) has been associated with various
neurological disorders, the most common being neuropathy and cerebellar ataxia.
The aims of the present study were to assess the following: 1) the prevalence of 
CD in patients affected by migraine; 2) whether there are regional cerebral blood
flow abnormalities in migraine patients with CD compared to migraine patients
without CD; and 3) the effects of a gluten free diet in migraine patients with
CD. METHODS: A total of 90 patients affected by idiopathic migraine were
enrolled, and 236 blood donors were used as controls. Serum IgG
antitransglutaminase (TgA) and IgA antiendomysial (EmA) were measured. In
positive cases, diagnosis was confirmed endoscopically. A gluten free diet was
started in the patients diagnosed with CD, who were followed for 6 months. A
single photon emission CT brain study was performed before and after a gluten
free diet. RESULTS: Four of 90 (4.4%; 95% CI = 1.2-11.0) migraine patients were
found to have CD compared with 0.4% (95% CI = 0.01-2.3) blood donor controls (p <
0.05). During the 6 months of gluten free diet, one of the four patients had no
migraine attacks, and the remaining three patients experienced an improvement in 
frequency, duration, and intensity of migraine. Single photon emission CT studies
showed a regional baseline reduction in brain tracer uptake in all four patients.
Such reduction in uptake completely resolved at follow-up. CONCLUSIONS: Our
results suggest that a significant proportion of patients with migraine may have 
CD, and that a gluten free diet may lead to a improvement in the migraine in
these patients.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 12650798 [PubMed - indexed for MEDLINE]

2667: Scand J Immunol. 2003 Mar;57(3):286-90.

A correlation between migraine, histamine and immunoglobulin e.

Gazerani P, Pourpak Z, Ahmadiani A, Hemmati A, Kazemnejad A.

Neuroscience Research Center, Shaheed Beheshti University of Medical Sciences,
Tehran, Iran.

Although migraine affects about 15% of population and many studies have been
performed to find the mechanism and a successful management, the physiopathology 
of migraine is still largely unknown. The possibility of an immunoglobulin E
(IgE)-mediated allergic mechanism and the role of histamine remain controversial.
The aim of the present study was to evaluate serum total IgE and histamine levels
in migraine patients and the influence of allergy on them. Seventy patients
(18-58 years) with migraine without aura were divided into two groups according
to their history of allergy (60% with and 40% without allergy). Serum samples
were collected during fasting without allowing any premedication during the two
periods of attack and remission. There was a control group containing 45 healthy 
volunteers. Serum total IgE and histamine levels were measured by enzyme-linked
immunosorbent assay and fluorimetric methods, respectively. Mean and standard
errors of serum histamine (ng/ml) and total IgE (IU/ml) levels were found in the 
control group to be 48.16 +/- 2.70 and 38.31 +/- 3.20, in the migraine with
allergy group 159.11 +/- 4.60 and 303.30 +/- 42.50 and in the migraine without
allergy group 105.01 +/- 8.50 and 79.07 +/- 2.70, respectively. Total IgE levels 
in migraine with allergy group were found to be significantly (P < 0.0001) above 
that in the control and another group, suggesting an influence of an IgE-mediated
mechanism on migraine. Although the plasma histamine levels, which were
significantly elevated (P < 0.0001) in patients with migraine, both during
headache and symptom-free periods, when compared with the control group, indicate
that there is an increased susceptibility to histamine in allergic conditions,
this molecule has also an unrelated role in migraine. The relationship between
allergy and migraine can be based, in part, on an IgE-mediated mechanism, and
histamine release plays an important role. Thus, the avoidance of allergic
conditions in migraine patients may be a simple, helpful way for prophylaxis or
their treatment.

PMID: 12641658 [PubMed - indexed for MEDLINE]

2668: J Neurol Neurosurg Psychiatry. 2003 Apr;74(4):501-3.

A diffusion tensor magnetic resonance imaging study of brain tissue from patients
with migraine.

Rocca MA, Colombo B, Inglese M, Codella M, Comi G, Filippi M.

Neuroimaging Research Unit, Department of Neuroscience, Scientific Institute
Ospedale San Raffaele, University of Milan, Via Olgettina 60, 20132 Milan, Italy.

OBJECTIVE: To measure in vivo, using diffusion tensor magnetic resonance imaging 
(DT-MRI) the extent of pathological damage of normal appearing brain tissue
(NABT) from patients with migraine. METHODS: Dual echo and DT-MRI scans of the
brain were acquired from 34 patients with migraine and 17 sex and age matched
healthy volunteers. Mean diffusivity (MD) and fractional anisotropy (FA)
histograms of the NABT were obtained from all subjects and the histograms' peak
heights and average NABT MD and FA measured. When present, average MD and FA
values of T2 visible lesions were also measured. RESULTS: In comparison with
healthy volunteers, patients with migraine had lower MD histogram peak height
(p=0.02) of the NABT. No differences were found in FA histogram derived metrics
between migraine patients and healthy subjects. No difference was found for any
MD and FA histogram derived metrics between migraine patients with and without
brain MRI lesions, and between patients with and without aura. CONCLUSIONS: This 
study shows that, although brain damage may extend beyond T2 weighted
abnormalities in patients with migraine, the severity of these "occult" changes
is mild compared with that found in other diseases associated with white matter
abnormality.

PMID: 12640073 [PubMed - indexed for MEDLINE]

2669: Clin Ther. 2003 Jan;25(1):235-46.

An open-label study to assess changes in efficacy and satisfaction with migraine 
care when patients have access to multiple sumatriptan succinate formulations.

Weidmann E, Unger J, Blair S, Friesen C, Hart C, Cady R.

South Austin Medical Clinic, Austin, Texas, USA.

BACKGROUND: Because a patient's migraines often differ in duration, intensity,
and accompanying symptoms, as well as the conditions and circumstances at the
time of the headache, the mode for treatment also may change. OBJECTIVE: The goal
of this study was to determine whether migraine management is improved by
providing 3 formulations of sumatriptan succinate to patients, together with
education to assist them in selecting the most appropriate formulation for
specific attacks. METHODS: This was an open-label study conducted in 3 family
practice settings. Patients were recruited who had at least a 1-year history of
migraine meeting International Headache Society criteria and experienced 2 to 6
attacks per month within the previous 3 months. Patients received instructions on
oral, intranasal, and subcutaneous (SC) sumatriptan and were provided with all 3 
formulations to treat 6 headaches. Migraine features, formulation used, reason
for selecting specific formulation, migraine symptom relief, and use of follow-up
doses were recorded in diaries. At follow-up, patients completed a questionnaire 
assessing satisfaction with access to multiple formulations. RESULTS: Of the 33
enrolled patients (26 women, 7 men; mean age, 38.5 years [range, 23-54 years]),
25 (75.8%) completed all visits. Of 149 headaches treated, 39 (26.2%) were mild
at onset, 70 (47.0%) were moderate, and 40 (26.8%) were severe. Eighty (53.7%)
headaches were treated with tablets, 35 (23.5%) with nasal spray, and 34 (22.8%) 
with SC injection. Primary reasons for selecting specific formulations included
"fewer side effects" for tablets, "convenience" for nasal spray, and "quick onset
of action" for SC injection. Twenty-one (84.0%) patients reported being either
very satisfied or satisfied with their ability to manage their headaches.
Physicians reported that 18 of 24 (75.0%) patients had an improved attitude
toward managing their headaches. All formulations were well tolerated. Eight
(32.0%) patients reported adverse events, the 2 most common being chest pressure 
and fatigue. CONCLUSION: The patients in this study reported greater satisfaction
with migraine management when given access to multiple sumatriptan formulations
and education regarding their appropriate use.

Publication Types: 
    Clinical Trial
    Comparative Study
    Multicenter Study
    Research Support, Non-U.S. Gov't

PMID: 12637123 [PubMed - indexed for MEDLINE]

2670: Spat Vis. 2002;16(1):33-43.

Increased visual after-effects in migraine following pattern adaptation extend to
simultaneous tilt illusion.

Shepherd AJ, Palmer JE, Davis G.

School of Psychology, Birkbeck College, University of London, Malet Street,
London WC1E 7HX, UK. a.shepherd@psychology.bbk.ac.uk

Much previous research into visual processing in migraine supports a model of
abnormal cortical processing, in between the headache attacks, that is
characterised by hyperexcitability, heightened responsiveness, a lack of
habituation and/or a lack of intra-cortical inhibition. Shepherd (2001) reported 
two adaptation studies that challenged this view, one using the tilt
after-effect, the second using the motion after-effect. Models of cortical
function in migraine based on hyperexcitability and a lack of inhibition lead to 
specific predictions in an adaptation study: there should have been smaller
after-effects in people with migraine than in people without. Both experiments,
however, revealed larger after-effects in the migraine group than in the control 
group. Here, these results are extended to the simultaneous tilt illusion and an 
identical pattern of results was obtained: there were consistently larger effects
in the migraine group than in the control group. The results from the three
experiments are not consistent with a lack of inhibition in migraine. The results
are discussed in terms of alternative models of cortical function, including a
lack of excitation and reduced central energy reserves.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 12636223 [PubMed - indexed for MEDLINE]

2671: East Afr Med J. 2002 Oct;79(10):519-23.

Headache associated disability in medical students at the Kenyatta National
Hospital, Nairobi.

Amayo EO, Jowi JO, Njeru EK.

Department of Medicine, College of Health Sciences, University of Nairobi, P.O.
Box 19676, Nairobi, Kenya.

OBJECTIVE: To study headache associated disability in a group of medical students
at the Kenyatta National Hospital. STUDY DESIGN: Cross sectional survey. RESULTS:
Between October 1994 and January 1995 we conducted a survey on headache
characteristics on medical students at both the Kenya Medical Training Centre and
the Medical School of the University of Nairobi. Six hundred and twenty-five
(87%) of the 711 students surveyed admitted having had at least one episode of
headache in the last six months. Using the International headache society (IHS)
case criteria 314 students (50%) had tension type headache, 240 (38%) migraine
headache and 71(12%) unclassified headache. Eighty-six percent of the students
with headache had their working ability disturbed to various degrees. Eighty-five
percent of the students reported that their social activities were interfered
with by headache. Migraine headaches had the greatest impact on both the working 
and social activities at a p-value of 0.0005 and 0.0004 respectively. One hundred
and forty-one students (23.6%) had missed at least one day of work or school in
the last one-year as a direct result of the headache. There was an association
between headache severity with working ability and social effect. There was no
association between the days students missed work or classes with the severity of
the headache. No gender difference was found in the headache associated
disability. CONCLUSION: Headache is a prevalent condition with disability both in
working and social activities.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 12635756 [PubMed - indexed for MEDLINE]

2672: Neurol Sci. 2003 Feb;23(6):301-5.

A genetic association study of migraine with dopamine receptor 4, dopamine
transporter and dopamine-beta-hydroxylase genes.

Mochi M, Cevoli S, Cortelli P, Pierangeli G, Soriani S, Scapoli C, Montagna P.

Department of Neurological Sciences, University of Bologna, Via Ugo Foscolo 7,
I-40123 Bologna, Italy.

We assessed the role of some dopamine metabolism genes in the genetic
susceptibility to migraine. We performed an association study using three
functional polymorphisms: a 48-base-pair (bp) tandem repeat in the D4 dopamine
receptor gene ( DRD4), a 40-bp tandem repeat in the dopamine transporter gene (
DAT) and a dinucleotide repeat in the dopamine beta-hydroxylase ( DBH) gene.
Allelic and genotypic frequencies for each polymorphism were assayed in two
migraine populations (93 individuals with migraine with aura (MA) and 101 with
migraine without aura (MO)) and were compared with those in a control group (117 
individuals). No significant differences were found between control and migraine 
groups for DAT and DBH polymorphisms. Instead, the distribution of alleles for
the DRD4 gene in the MO group was significantly different from those in both MA
and control groups, with the shortest and longest alleles being less frequent in 
MO. Our data indicate that MO, but not MA, shows significant genetic association 
with DRD4.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 12624717 [PubMed - indexed for MEDLINE]

2673: Neurol Sci. 2003 Feb;23(6):271-8.

Treatment of migraine with aura: comments and perspectives.

D'Andrea G, Bonavita V, Rigamonti A, Bussone G.

Centre for Headache and Comorbidities, Este Hospital, Monselice (PD), Italy.

Migraine with aura (MwA) is a primary headache that affects about 30% of migraine
sufferers. The main questions for the physician caring for the patient who has
MwA are: when to use preventive medications, what medications to use in acute and
preventive treatment, and whether the aura should be treated. The aim of this
paper is to review the various therapeutic options for MwA proposed in the
current literature and to evaluate their efficacy.

Publication Types: 
    Review

PMID: 12624713 [PubMed - indexed for MEDLINE]

2674: Stroke. 2003 Mar;34(3):665-70. Epub 2003 Feb 13.

Evidence for cortical functional changes in patients with migraine and white
matter abnormalities on conventional and diffusion tensor magnetic resonance
imaging.

Rocca MA, Colombo B, Pagani E, Falini A, Codella M, Scotti G, Comi G, Filippi M.

Neuroimaging Research Unit, Department of Neuroscience, Scientific Institute and 
University Ospedale San Raffaele, Via Olgettina, 60, 20132 Milan, Italy.

BACKGROUND: In this study, we used functional MRI (fMRI) to investigate the
pattern of cortical activations after a simple motor task in patients with
migraine and white matter (WM) abnormalities on conventional MRI scans of the
brain. We also investigated whether the extent of brain activations was
correlated with WM structural pathology measured using diffusion tensor (DT) MRI.
METHODS: From 15 right-handed patients with migraine and 15 sex- and age-matched,
right-handed healthy volunteers, we obtained the following: (1) fMRI (repetitive 
flexion-extension of the last 4 fingers of the right hand), (2) dual-echo turbo
spin echo scans, and (3) pulsed-gradient spin-echo echo-planar sequence to
calculate DT-MRI maps. fMRI analysis was performed using SPM99 and cluster
detection. We measured the volume, the average mean diffusivity (), and the
average fractional anisotropy of all lesions seen on the dual-echo scans.
histograms of the normal-appearing WM were also produced. RESULTS: Compared with 
healthy volunteers, migraine patients had a larger relative activation of the
contralateral primary sensorimotor cortex (P=0.01) and a rostral displacement of 
the supplementary motor area (P=0.03). The shapes of the curves reflecting the
time course for fMRI signal intensity changes were similar between migraine
patients and controls for all of the cortical areas we studied. Compared with
healthy subjects, migraine patients had significantly lower histogram peak height
of the normal-appearing WM histogram (P=0.02), which was found to be correlated
with the extent of displacement of the supplementary motor area (r=-0.80,
P<0.001). CONCLUSIONS: This study suggests that functional cortical changes occur
in patients with migraine and brain MRI abnormalities and that they might be
secondary to the extent of subcortical structural damage.

Publication Types: 
    Clinical Trial
    Controlled Clinical Trial

PMID: 12624289 [PubMed - indexed for MEDLINE]

2675: Rev Hosp Clin Fac Med Sao Paulo. 2002 Nov-Dec;57(6):293-8. Epub 2003 Feb
17.

Comment in:
    Rev Hosp Clin Fac Med Sao Paulo. 2002 Nov-Dec;57(6):249-50.

New migraine preventive options: an update with pathophysiological
considerations.

Bigal ME, Rapoport AM, Sheftell FD, Tepper SJ.

New England Center for Headache, Stamfor, CT, USA.

BACKGROUND: The pharmacological treatment of migraine may be acute or preventive.
Frequent, severe and long-lasting migraine attacks require prophylaxis. Multiple 
threads of research over the last 15 years have led to the concept that migraine 
is generated from a hyperexcitable brain. A variety of causes for
hyperexcitability of the brain in migraine have been suggested. These causes
include low cerebral magnesium levels, mitochondrial abnormalities, dysfunctions 
related to increased nitric oxide or the existence of a P/Q type calcium
channelopathy. The better knowledge about migraine pathophisiology led us to
discuss new treatment options. OBJECTIVES: The aim of the present study is to
present an evidence-based review of some new drugs or some agents that even
though available for a long time, are not frequently used. METHODS/RESULTS: We
present a review of anticonvulsants with various mechanisms of action such as
lamotrigine, gabapentin, topiramate, tiagabine, levetiracetam and zonisamide. We 
also review natural products, like riboflavin and magnesium, botulinum toxin A, a
specific CGRP antagonist and the anti-asthma medication montelukast, with
pathophysiological discussion. CONCLUSIONS: We aimed to present an update of
newer or less frequently used preventive migraine therapies, drugs that might
reduce the burden and the costs of a disease that should be considered as a
public health problem all around the world.

Publication Types: 
    Review

PMID: 12612763 [PubMed - indexed for MEDLINE]

2676: Headache. 2003 Mar;43(3):258-65.

Migraine disability assessment (MIDAS) score: relation to headache frequency,
pain intensity, and headache symptoms.

Stewart WF, Lipton RB, Kolodner K.

Johns Hopkins School of Public Health, Baltimore, MD 21205, USA.

OBJECTIVE: To determine the extent to which variation in the Migraine Disability 
Assessment (MIDAS) score is associated with headache frequency, pain intensity,
headache symptoms, gender, and employment status. BACKGROUND: The MIDAS
questionnaire is a 7-item questionnaire (with 5 scored items) designed to measure
headache-related disability, to improve physician-patient communication, and to
identify patients with high treatment needs. METHODS: Data from 3
population-based studies (total sample, n = 397) conducted in the United States
and the United Kingdom were used to evaluate the relationship between headache
features (attack frequency, pain intensity, pain quality, and associated
symptoms) and MIDAS score. Data on headache features were collected by telephone 
using a standardized interview. The MIDAS questionnaire was completed shortly
after the telephone interview. General linear models were used to determine the
extent to which population variation in the MIDAS score was explained by headache
features. RESULTS: Using linear regression, variables for all headache features
(ie, headache frequency, pain intensity, pain quality, and associated symptoms)
and demographic characteristics explained only 22% of the variation in MIDAS
scores. Almost all (19.9%) the explained variance was accounted for by average
pain intensity (12.0%), number of headache days (6.1%), and exacerbation of pain 
with movement (1.8%). When pain intensity and headache frequency were included in
the model, no statistically significant differences in MIDAS scores were observed
by gender or employment status. Although explaining only 2.1% of the variance,
age was significantly associated with MIDAS scores, with those under 25 years
demonstrating higher MIDAS scores than other age groups. No other variables (ie, 
frequency of occurrence of associated symptoms and other measures of quality of
pain) were associated with MIDAS scores. CONCLUSIONS: Challenges to the utility
of the MIDAS as a measure include whether headache-related disability is largely 
a function of other routine headache features and whether MIDAS is inherently
biased based on work status and gender. While the MIDAS score was associated with
headache frequency and average pain score, these two headache features explain
only a modest proportion of the variation in MIDAS scores. Additionally, gender
and work status were not related to MIDAS scores. These findings suggest that the
MIDAS score captures information about disability that is not inherent to other
headache features and is independent of gender and work status.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 12603645 [PubMed - indexed for MEDLINE]

2677: Headache. 2003 Mar;43(3):251-7.

Effect of autogenic training on drug consumption in patients with primary
headache: an 8-month follow-up study.

Zsombok T, Juhasz G, Budavari A, Vitrai J, Bagdy G.

Laboratory of Neurochemistry and Experimental Medicine, and the Department of
Vascular Neurology, Semmelweis University National Institute of Psychiatry and
Neurology, Budapest, Hungary.

OBJECTIVE: To examine the effects of Schultz-type autogenic training on
headache-related drug consumption and headache frequency in patients with
migraine, tension-type, or mixed (migraine plus tension-type) headache over an
8-month period. BACKGROUND: Behavioral treatments often are used alone or
adjunctively for different types of headache. There are, however, only a few
studies that have compared the efficacy and durability of the same treatment in
different types of primary headache, and the effects of treatment on
headache-related drug consumption rarely have been assessed even in these
studies. METHODS: Twenty-five women with primary headache (11 with mixed
headache, 8 with migraine, and 6 with tension-type headache) were evaluated via
an open-label, self-controlled, 8-month, follow-up study design. After an initial
4 months of observation, patients began learning Schultz-type autogenic training 
as modified for patients with headache. They practiced autogenic training on a
regular basis for 4 months. Based on data from headache diaries and daily
medication records, headache frequencies and the amounts of analgesics,
"migraine-specific" drugs (ergots and triptans), and anxiolytics taken by the
patients were compared in the three subgroups over the 8-month period.
Results.-From the first month of implementation of autogenic training, headache
frequencies were significantly reduced in patients with tension-type and mixed
headache. Significant reduction in frequency was achieved in patients with
migraine only from the third month of autogenic training. Decreases in headache
frequencies were accompanied by decreases in consumption of migraine drugs and
analgesics resulting in significant correlations among these parameters.
Reduction in consumption of anxiolytic drugs was more rapid and robust in
patients with tension-type headache compared to patients with migraine, and this 
outcome failed to show any correlation with change in headache frequency.
CONCLUSION: Schultz-type autogenic training is an effective therapeutic approach 
that may lead to a reduction in both headache frequency and the use of headache
medication.

Publication Types: 
    Clinical Trial
    Comparative Study
    Controlled Clinical Trial
    Research Support, Non-U.S. Gov't

PMID: 12603644 [PubMed - indexed for MEDLINE]

2678: Headache. 2003 Mar;43(3):245-50.

Biofeedback-assisted relaxation in migraine headache: relationship to cerebral
blood flow velocity in the middle cerebral artery.

Vasudeva S, Claggett AL, Tietjen GE, McGrady AV.

Departments of Psychiatry, Medical College of Ohio, Toledo, Spain.

OBJECTIVE: To determine if migraineurs with aura respond differently to
biofeedback/relaxation than those without aura and, if so, whether the
variability in outcome can be explained by blood flow velocity. Background.-The
relationship between cerebral blood flow velocity and treatment response to
biofeedback/relaxation in migraine with and without aura is uncertain. METHOD:
Twenty migraineurs underwent 12 sessions of biofeedback/relaxation therapy, while
20 controls simply were told to relax on their own. Cerebral blood flow velocity 
was measured bilaterally in the middle cerebral artery with transcranial Doppler.
RESULTS: The biofeedback group showed significant (P <.05) reductions in pain,
depression, and anxiety compared to the control group. Patients with and without 
aura did equally well. There were significant (P <.05) left to right blood flow
velocity differences only in the migraine with aura group. Maximum blood flow
velocities were significantly higher (P <.05) in the migraine with aura group
than in the cohort without aura. There was an inverse correlation between
indicators of anxiety and blood flow velocity, perhaps related to
hyperventilation-induced constriction in the small vessels distal to the middle
cerebral artery. CONCLUSION: The positive treatment response to
biofeedback/relaxation in migraine headache is not related to presence of aura,
nor to changes in blood flow velocity, but may be associated with reduction in
anxiety and depression.

Publication Types: 
    Comparative Study

PMID: 12603643 [PubMed - indexed for MEDLINE]

2679: Headache. 2003 Mar;43(3):235-44.

Erratum in:
    Headache. 2003 Jul-Aug;43(7):833`.

Shared rearing environment in migraine: results from twins reared apart and twins
reared together.

Svensson DA, Larsson B, Waldenlind E, Pedersen NL.

Division of Neurology, Neurotec Department, Karolinska Institutet, Stockholm,
Sweden.

BACKGROUND: Studies of twins who are separated from each other early in life and 
are reared in different environments offer the opportunity to resolve variation
in liability to disease. OBJECTIVE: To evaluate the importance of genetic and
environmental influences in migraine; in particular, addressing the role of the
shared rearing environment. METHODS: A population-based cohort of twins,
including a subsample of 314 pairs reared apart and 364 matched control pairs
reared together, was drawn from the Swedish Twin Registry. Data on lifetime
migraine was collected via self-administered questionnaires mailed to twins aged 
42 to 81 years. Quantitative genetic models and regression models were used to
analyze sources of twin similarity. RESULTS: We found nonsignificant shared
rearing environmental influences on migraine for men (17%) and no rearing effects
at all for women. The heritability of migraine was estimated at 38% (95%
confidence interval, 0 to 73) for men and 48% (95% confidence interval, 27 to 65)
for women. Among monozygotic twins reared apart, those separated at 3 years of
age or earlier were more similar for lifetime migraine than those separated
later, and this was especially true for women. CONCLUSION: In agreement with
previous twin data, family resistance in migraine is mainly due to genetic
factors, whereas environmental influences make family members different, not
similar.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.
    Twin Study

PMID: 12603642 [PubMed - indexed for MEDLINE]

2680: Headache. 2003 Mar;43(3):231-4.

Familial occurrence of migraine with aura in a population-based study.

Cologno D, De Pascale A, Manzoni GC.

Headache Centre, Institute of Neurology, University of Parma, Italy.

OBJECTIVE: To better define a possible genetic basis for migraine with aura
(MWA). METHODS: We investigated the familial occurrence of migraine with aura in 
a sample of (MWA) subjects recruited from an epidemiologic study of migraine with
aura involving the general population. The sample with migraine with aura (n =
26) was selected out of a total of 1392 subjects (842 women and 550 men)
representative of the general population aged 18 to 65 years in the southern
Italian town of San Severo. A family history of migraine with aura was determined
via direct interviews with all living first-degree relatives of the 26 subjects
who could be reached by investigators, 119 people: 71 women and 48 men. The
diagnosis of migraine with aura was made according to the 1988 International
Headache Society (IHS) criteria. RESULTS: Of the 26 subjects with migraine with
aura, 7 (6 women and 1 man) had a positive family history, with a total of 7
first-degree relatives affected by the disease (1 mother, 2 fathers, 1 brother, 1
sister, and 2 children). Based on the lifetime prevalence rate of migraine with
aura (1.6%) in the San Severo general population, the relative risk of migraine
with aura in the first-degree relatives of the subjects was 3.68 (4.16 for women 
and 2.77 for men). CONCLUSION: Our subjects' relative risk rate for familial
occurrence of migraine with aura was similar to that reported by one
investigator, but markedly lower than that reported by another group.

PMID: 12603641 [PubMed - indexed for MEDLINE]

2681: Headache. 2003 Mar;43(3):223-30.

Real-world experiences in migraine therapy with rizatriptan.

Jamieson D, Cutrer FM, Goldstein J, Dayno J, Hu XH; USMAP Investigators.

University of Pennsylvania, Philadelphia 19486, USA.

OBJECTIVE: To evaluate the effectiveness of rizatriptan for acute migraine
treatment and patient satisfaction with the drug in usual clinical practice
settings. BACKGROUND: Although rizatriptan has been shown to effectively relieve 
migraine symptoms in clinical trials, we wished to assess its utility in typical 
patient care settings. Design.-Multicenter, open-label design involving the
patients of practicing clinicians. METHODS: Adult migraineurs treated two
migraine attacks with either rizatriptan 10-mg standard tablets or rizatriptan
10-mg orally disintegrating tablets in a crossover manner. Participants had not
taken rizatriptan previously and chose which formulation to take first. Patients 
reported their treatment experiences via an interactive voice response system
approximately 24 hours after treatment. Prior migraine treatment experiences were
reported by patients on a baseline questionnaire completed at participating
clinics. We used conditional logistic regression analysis adjusted for treatment 
sequences to test the statistical significance of comparisons with results
recorded on the baseline questionnaire. RESULTS: Of the 5388 patients enrolled,
3953 (73%) completed at least one follow-up and 3183 (59%) completed two
follow-up reports. Patients reported the following outcomes for attacks treated
with the rizatriptan tablet and orally disintegrating tablet formulations,
respectively, compared with their prior responses to oral usual care medications 
(P <.05 in all comparisons with baseline data): onset of pain relief within 30
minutes postdose: 18% and 23% versus 16%; no or mild headache 2 hours postdose:
66% and 67% versus 37%; largely symptom-free within 2 hours postdose: 52% and 54%
versus 35%; return to usual activities within 2 hours postdose: 50% and 51%
versus 31%; and very or somewhat satisfied with treatment: 72% and 74% versus
53%. CONCLUSIONS: In this "real-world" setting involving a patient population
selected by clinicians, rizatriptan appeared to offer better treatment outcomes
than those from prior treatments with other oral migraine medications.

Publication Types: 
    Clinical Trial
    Controlled Clinical Trial
    Multicenter Study
    Research Support, Non-U.S. Gov't

PMID: 12603640 [PubMed - indexed for MEDLINE]

2682: Headache. 2003 Mar;43(3):214-22.

Comment in:
    Headache. 2003 Sep;43(8):921; author reply 924-8.    Headache. 2003 Sep;43(8):922; author reply 924-8.    Headache. 2003 Sep;43(8):923-4; author reply 924-8.

Comparative efficacy of eletriptan 40 mg versus sumatriptan 100 mg.

Mathew NT, Schoenen J, Winner P, Muirhead N, Sikes CR.

Houston (Tex) Headache Clinic, TX 77004, USA.

OBJECTIVE: To confirm the efficacy advantage of eletriptan 40 mg over sumatriptan
100 mg. Background.-Eletriptan 80 mg has demonstrated significantly greater
efficacy when compared to both sumatriptan 50 mg and 100 mg in two studies.
Eletriptan 40 mg demonstrated significantly greater efficacy than sumatriptan 100
mg in one previous trial. METHODS: Two thousand one hundred thirteen patients
with a diagnosis of migraine according to International Headache Society criteria
were randomized using a double-blind, double-dummy, parallel-group design, and
treated for a single migraine attack with either eletriptan 40 mg, sumatriptan
100 mg, or placebo. The primary endpoint was 2-hour headache response. Secondary 
endpoints included headache response rates at 1 hour, pain-free rates, absence of
associated symptoms, functional response at 1 and 2 hours, and sustained headache
response. RESULTS: Headache response rates at 2 hours postdose were significantly
higher for eletriptan 40 mg (67%) than for sumatriptan 100 mg (59%; P <.001) and 
placebo (26%; P <.0001). Eletriptan 40 mg consistently showed significant (P
<.01) efficacy over sumatriptan 100 mg across secondary clinical outcomes,
including 1-hour headache response; 2-hour pain-free response; absence of nausea,
photophobia, and phonophobia; functional improvement; use of rescue medication;
treatment acceptability; and sustained headache response (P <.05). Overall,
treatment-related adverse events were low, nausea being the only adverse event
with an incidence of 2% or higher (4.9% with eletriptan, 4.2% sumatriptan, 2.8%
placebo). CONCLUSION: This trial confirmed that eletriptan 40 mg offers superior 
efficacy in treating migraine pain and associated symptoms and in restoring
patient functioning when compared with sumatriptan 100 mg.

Publication Types: 
    Clinical Trial
    Comparative Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 12603639 [PubMed - indexed for MEDLINE]

2683: Headache. 2003 Mar;43(3):202-13.

Efficacy, safety, and tolerability of oral eletriptan for treatment of acute
migraine: a multicenter, double-blind, placebo-controlled study conducted in the 
United States.

Sheftell F, Ryan R, Pitman V; Eletriptan Steering Committee.

The New England Center for Headache, Stamford, Conn 06902, USA.

OBJECTIVE: To investigate the efficacy, consistency, safety, and tolerability of 
oral eletriptan in the acute treatment of three migraine attacks. BACKGROUND:
Eletriptan is a selective 5-HT1B/1D agonist member of a class of agents known to 
be effective in the acute treatment of migraine. METHODS: Thirteen hundred
thirty-four patients were randomized to 20 mg, 40 mg, or 80 mg of eletriptan, or 
placebo and could treat up to three attacks. The primary efficacy endpoint was
2-hour headache response for the first attack. Secondary endpoints included
associated symptom relief, and pain-free, sustained pain-free, and consistency of
response. RESULTS: Eletriptan 20 mg, 40 mg, and 80 mg achieved significantly (P
<.0001) better headache response rates than placebo at 2 hours (47%, 62%, and
59%, respectively, versus 22%) and 4 hours (64%, 76%, and 79%, respectively,
versus 25%). Headache response was observed to be rapid, showing improvement at
0.5 hour and 1 hour. Two-hour pain-free response rates for eletriptan 20 mg, 40
mg, and 80 mg were 14%, 27%, and 27%, respectively, compared with 4% for placebo.
Sustained pain-free response rates were significantly (P <.001) better for
eletriptan 20 mg (10%), 40 mg (20%), and 80 mg (18%) compared with placebo (3%). 
Eletriptan had a higher consistency of intrapatient response than placebo in two 
of three (68% to 82%) and three of three attacks (32% to 60%) versus 16% and 8%, 
respectively. All eletriptan doses yielded significant functional improvement at 
2 hours. Adverse events were generally mild or moderate and transient, with
eletriptan 20 mg having an adverse event profile comparable to placebo.
CONCLUSIONS: Eletriptan is efficacious, displaying high consistency of response
over multiple attacks, and is well tolerated for the acute treatment of migraine.

Publication Types: 
    Clinical Trial
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 12603638 [PubMed - indexed for MEDLINE]

2684: Headache. 2003 Mar;43(3):191-201.

The impact of an over-the-counter migraine medication program on quality of life.

Burk CT, Gilderman A, Salas J, Berenbeim D, Nichol MB.

Department Pharmaceutical Economics and Policy, School of Pharmacy, University of
Southern California, CA 92651, USA.

OBJECTIVE: This study was conducted to assess the health-related quality of life 
of patients treated with samples of an over-the-counter migraine medication.
BACKGROUND: Population-based epidemiologic studies have reported that over 90% of
an estimated 28 million migraine sufferers in the United States use both
prescription and nonprescription medications for their migraine headaches, with
60% taking over-the-counter medications exclusively. Despite the widespread use
of nonprescription drugs, no published literature to date has assessed
migraineurs' health-related quality of life associated with use of
over-the-counter headache medication. METHODS: This prospective and observational
study evaluated the impact on health-related quality of life of patients from a
managed care organization who were diagnosed with migraine and prescribed
migraine medications. Patients were enrolled from four different medical groups
and were requested to complete health-related quality-of-life questionnaires 2
and 4 months after they were provided with educational materials on migraine and 
samples of an over-the-counter migraine medication containing a combination of
acetaminophen, aspirin, and caffeine. RESULTS: A total of 99 patients who chose
an over-the-counter medication as their initial treatment for acute migraine
occurring over the ensuing 4 months completed a baseline Short-Form 36, a
validated and reliable general health status questionnaire. They then were
retested at months 2 and 4. Results demonstrated significant improvements at
months 2 and months 4 in one to four of the health-related quality-of-life
dimensions measured relative to scores recorded before the patients were given
access to the over-the-counter medication (P <.05). In addition, patients who
initially took an over-the-counter medication to treat their migraine headaches
reported increased frequency of relief. CONCLUSION: In the 4 months following
availability of an over-the-counter migraine medication and educational migraine 
materials, health-related quality of life and frequency of relief improved for
the managed care migraine sufferers who participated in this study.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 12603637 [PubMed - indexed for MEDLINE]

2685: Headache. 2003 Mar;43(3):171-8.

Comment in:
    Headache. 2003 Nov-Dec;43(10):1116-8; author reply 1118.

Migraine preventive medication reduces resource utilization.

Silberstein SD, Winner PK, Chmiel JJ.

Department of Neurology, Jefferson Headache Center, Thomas Jefferson College of
Medicine, Philadelphia, Pa 19107, USA.

OBJECTIVE: To determine if long-term resource utilization is reduced by adding a 
preventive medication to a migraine management regimen that already includes
acute medication. BACKGROUND: In 2000, new evidence-based guidelines for the
treatment of migraine were released by the US Headache Consortium and the
American Academy of Neurology. Although these guidelines emphasize the role of
preventive medication in achieving significant clinical improvement, little yet
is known concerning the impact of such management on medical and pharmaceutical
resources. Methods.-Resource utilization information in a large claims database
was analyzed retrospectively. RESULTS: Adding a preventive medication to migraine
management reduced the use of other migraine medications, as well as visits to
physician offices and emergency departments. In addition, both acute and
preventive medications were associated with lower utilization of computed
tomography and magnetic resonance imaging scans. CONCLUSION: Migraine preventive 
drug therapy is effective in reducing resource consumption when added to therapy 
consisting only of an acute medication.

Publication Types: 
    Comparative Study
    Research Support, U.S. Gov't, P.H.S.

PMID: 12603635 [PubMed - indexed for MEDLINE]

2686: Cephalalgia. 2003 Mar;23(2):138-45.

The sensitivity and specificity of the case definition criteria in diagnosis of
headache: a school-based epidemiological study of 5562 children in Mersin.

Ozge A, Bŭgdayci R, Saşmaz T, Kaleăgasi H, Kurt O, Karakelle A, Tezcan H, Siva A.

Department of Neurology, Mersin University School of Medicine, Mersin-Istanbul,
Turkey. aozge@mersin.edu.tr

The objectives of the present study were to estimate the prevalence of recurrent 
headaches in schoolchildren (ranging from 2nd to 5th degrees) in Mersin city of
Turkey and to determine the sensitivity, specificity, positive predictive value
and positive likelihood ratio of the diagnostic headache characteristics in
children with migraine and Tension Type Headache (TTH) using neurologist's
diagnosis as the gold standard. The stratified sample of study was composed of
5562 children. The prevalence of recurrent headache was 49.2% (2739 of 5562) and 
the prevalence of current headache was 31.3% (859 of 2739). TTH was more common
than migraine (24.7% vs. 10.4%). The most sensitive headache characteristic for
migraine was 'severity of pain' and the most sensitive definitive symptom is
'duration of headache' in children with TTH. IHS-based symptom definition
criteria are highly beneficial in diagnosis of childhood headache, if used
together with detailed clinical assessment.

Publication Types: 
    Comparative Study
    Validation Studies

PMID: 12603371 [PubMed - indexed for MEDLINE]

2687: Cephalalgia. 2003 Mar;23(2):96-104.

Cranial and peripheral interictal vascular changes in migraine patients.

de Hoon JN, Willigers JM, Troost J, Struijker-Boudier HA, van Bortel LM.

Centre for Clinical Pharmacology, University Hospital Gasthuisberg (K.U. Leuven),
Belgium. jan.dehoon@uz.kuleuven.ac.be

As migraine is associated with an increased risk for ischaemic stroke and
peripheral vasospastic disorders, it was hypothesized that interictal vascular
changes may be present in migraine patients. Using ultrasound and applanation
tonometry, the cardiovascular properties of migraine patients were compared with 
those of matched control subjects. Vascular parameters of the carotid arteries,
cardiac output and systemic vascular resistance did not differ between both
groups. Right temporal artery diameter was larger in migraine patients (mean
difference 101 micro m; 95% confidence interval (CI) 9/194 micro m; P = 0.033).
At the brachial artery, migraine patients displayed a smaller distension
(difference -24 micro m; 95% CI -45/-4 micro m; P = 0.021) and a decreased
compliance (difference -0.025 mm2/kPa; 95% CI -0.047/-0.003 mm2/kPa; P = 0.024). 
Thus, migraine patients display an increased peripheral arterial stiffness. The
presence of these interictal vascular changes suggests that migraine might be
part of a more generalized vascular disorder.

Publication Types: 
    Clinical Trial
    Controlled Clinical Trial

PMID: 12603365 [PubMed - indexed for MEDLINE]

2688: Cephalalgia. 2003 Mar;23(2):79-89.

Symptoms of depression and anxiety, and screening for mental disorders in
migrainous patients.

Kowacs F, Socal MP, Ziomkowski SC, Borges-Neto VF, Toniolo DP, Francesconi CR,
Chaves ML.

Serviço de Neurologia e Pós-Graduação em Medicina, Clínica Médica, Hospital de
Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul School of
Medicine, Brazil. fkowacs@yahoo.com

The purpose of this clinic-based study was the assessment of symptoms of
depression, anxiety, and non-specific psychiatric disorders amongst patients with
migraine, compared with healthy subjects and with individuals with a
non-neurological chronic disease. A cross-sectional study was carried out in
which 178 individuals (migraine 51; psoriasis 35; healthy 92) were submitted to
three scales: MADRS (depression), STAI-T (anxiety) and SRQ (screening for mental 
disorders). The subjects with migraine and psoriasis were from the Out-patient
Clinics of Headache and of Dermatology, and the healthy volunteers were persons
who were accompanying out-patients in the same hospital. Scores were analysed by 
manova and by association analysis and logistic regression. Scores of all
instruments were higher in the migrainous group, but the univariate analysis of
association (using cut-offs) showed significance only for suspicion of mental
disorders (SRQ). By logistic regression, variables with strongest association to 
migraine were gender, education, and SRQ in decreasing order.

Publication Types: 
    Clinical Trial
    Controlled Clinical Trial

PMID: 12603363 [PubMed - indexed for MEDLINE]

2689: Cephalalgia. 2003 Mar;23(2):75-8.

Comment in:
    Cephalalgia. 2003 Mar;23(2):73-4.

Acetazolamide acts on neuromuscular transmission abnormalities found in some
migraineurs.

Ambrosini A, Pierelli F, Schoenen J.

Headache Clinic, INM Neuromed, IRCCS, Pozzilli, Isernia, Italy.

Mild subclinical impairment of neuromuscular transmission can be detected with
single-fibre electromyography (SFEMG) in subgroups of patients suffering from
migraine and could be due to dysfunctioning Ca2+-channels on motor axons
controlling stimulation-induced acetylcholine release. Acetazolamide, which is
thought to ameliorate ion channel function, was shown effective in familial
hemiplegic migraine and episodic ataxia type 2, both of which are associated with
mutations of the neuronal Ca2+-channel gene CACNA1A, as well as in aura status.
We treated therefore in an open pilot study five non-hemiplegic migraineurs
showing mild SFEMG abnormalities with acetazolamide for several weeks. This was
followed by a normalization of SFEMG recordings in all patients and by clinical
improvement in four. These results support the assumption that the subclinical
impairment of neuromuscular transmission found in certain migraineurs might be
due to dysfunctioning Ca2+-channels.

Publication Types: 
    Case Reports
    Research Support, Non-U.S. Gov't

PMID: 12603362 [PubMed - indexed for MEDLINE]

2690: Ann Neurol. 2003 Mar;53(3):376-81.

Familial hemiplegic migraine type 2 is linked to 0.9Mb region on chromosome 1q23.

Marconi R, De Fusco M, Aridon P, Plewnia K, Rossi M, Carapelli S, Ballabio A,
Morgante L, Musolino R, Epifanio A, Micieli G, De Michele G, Casari G.

Department of Neurology, Misericordia Hospital, Grosseto, Italy.

Familial hemiplegic migraine (FHM) is a rare autosomal dominant disorder
characterized by episodes of transient hemiparesis followed by headache. Two
chromosomal loci are associated to FHM: FHM1 on chromosome 19 and FHM2 on
chromosome 1q21-23. Mutations of the alpha-1A subunit of the voltage gated
calcium channel (CACNA1A) are responsible for FHM1. FHM2 critical region spans 28
cM, hence hampering the identification of the responsible gene. Here, we report
the FHM2 locus refining by linkage analysis on two large Italian families
affected by pure FHM. The new critical region covers a small area of 0.9Mb in
1q23 and renders feasible a positional candidate approach. By mutation analysis, 
we excluded the calsequestrin and two potassium channel genes mapping within the 
narrowed FHM2 locus.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 12601705 [PubMed - indexed for MEDLINE]

2691: Neurology. 2003 Feb 25;60(4):717-9.

Migraine-like disorder segregating with mtDNA 14484 Leber hereditary optic
neuropathy mutation.

Cupini LM, Massa R, Floris R, Manenti G, Martini B, Tessa A, Nappi G, Bernardi G,
Santorelli FM.

Clinica Neurologica, Ospedale S. Eugenio, Università di Roma Tor Vergata, Rome,
Italy. lecupini@tin.it

The authors report neurologic features in a large family harboring the
mitochondrial DNA (mtDNA) mutation T14484C associated with Leber hereditary optic
neuropathy (LHON). In the maternal line the mtDNA mutation was associated with
optic neuropathy or migraine with aura or without aura and transient
neurologic/visual disturbances. The segregation of familiar cases of migraine and
LHON mutation broadens the clinical phenotype associated with a primary LHON
mutation.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 12601121 [PubMed - indexed for MEDLINE]

2692: Neurology. 2003 Feb 25;60(4):595-601.

Comment in:
    Neurology. 2003 Feb 25;60(4):536-7.

Evidence for a separate type of migraine with aura: sporadic hemiplegic migraine.

Thomsen LL, Ostergaard E, Olesen J, Russell MB.

Danish Headache Center, Department of Neurology, Glostrup Hospital, University of
Copenhagen, Denmark. LLT@dadlnet.dk

OBJECTIVE: To compare clinical characteristics of patients with sporadic
hemiplegic migraine (SHM) with those of patients with migraine with typical aura 
(MA) and patients with familial hemiplegic migraine (FHM). METHODS: The authors
used a computer search of Denmark's National Patient Register to screen the
population for patients with migraine with aura with motor weakness, and also
examined case records from headache clinics and private practicing neurologists
and placed advertisements. The authors screened patients and their relatives with
a semi-structured validated telephone interview. All recruited patients were then
interviewed by a physician and given a neurologic examination. RESULTS: A total
of 105 patients with SHM were identified. Seventy-two percent had four typical
aura symptoms: visual, sensory, aphasic, and motor. All had at least two symptoms
present during SHM attacks. A gradual progression and sequential appearance of
aura symptoms was typical; compared with MA, the duration of each aura symptom
was usually prolonged and bilateral motor symptoms were more frequent. Of the
patients with SHM, 72% fulfilled the criteria for basilar migraine during SHM
attacks. The aura was usually followed by headache, as is common in FHM but not
MA. CONCLUSIONS: Patients with sporadic hemiplegic migraine had clinical symptoms
identical to familial hemiplegic migraine and significantly different from
migraine with typical aura. Sporadic hemiplegic migraine is a separate entity,
and should be classified with familial hemiplegic migraine.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 12601098 [PubMed - indexed for MEDLINE]

2693: J Neural Transm Suppl. 2002;(63):111-27.

The genetics of migraine: implication for treatment approaches.

Ferrari MD, Haan J.

Department of Neurolgy, Leiden University Medical Center, Leiden, The
Netherlands. M.D.Ferrari@lumc.nl

Migraine is a paroxysmal neurological disorder affecting up to 12% of males and
24% of females in the general population, demonstrated to have a strong, but
complex, genetic component. Genetic investigation of migraine bears great promise
in providing new targets for drug development and optimization of individual
specific therapy. Better, preferably prophylactic, treatment of migraine patients
is desired because the presently used drugs are not effective in all patients,
allow recurrence of the headache in a high percentage of patients and sometimes
have severe adverse side effects. With the recent identification of the
brain-specific P/Q-type calcium channel gene CACNA1A in the pathogenesis of
migraine, the first step has been taken to identify primary biochemical pathways 
leading to migraine. Here, we summarize the current knowledge about the genetics 
of migraine and focus on the implication for treatment approaches.

Publication Types: 
    Review

PMID: 12597612 [PubMed - indexed for MEDLINE]

2694: Acta Biomed. 2002;73(3-4):47-51.

Valproic acid in migraine prophylaxis of young patients. Three new reports.

Fusco C, Pisani F, Capone C, Faienza C.

Department of Pediatrics, Service of Child Neurology and Psychiatry, University
of Parma, Italy.

Several clinical studies report the efficacy of valproic acid in migraine
prophylaxis of adult patients and its well tolerability. In childhood and
adolescent patients its use is usually restricted to epilepsy and very few cases 
have been reported in literature on the use of valproic acid for "juvenile
migraine". We describe three pediatric patients fulfilling the International
Headache Society (IHS) criteria for migraine with and without aura treated with
low dose of sodium valproate (10 mg/Kg/die) for six months. They had previously
undergone other migraine preventive treatment unsuccessfully. We obtained a good 
response in all cases: in only one subject, prophylactic treatment was stopped
because of weight gain, as adverse effect. In conclusion, in accord with other
authors, we suggest that valproic acid may be helpful in the prophylaxis migraine
in pediatric age.

Publication Types: 
    Case Reports

PMID: 12596387 [PubMed - indexed for MEDLINE]

2695: World J Biol Psychiatry. 2001 Jul;2(3):149-55.

Clinical characteristics of patients with major affective disorders and comorbid 
migraine.

Fasmer OB, Oedegaard KJ.

Department of Psychiatry, University of Bergen, Haukeland Hospital, 5021 Bergen, 
Norway. ole.fasmer@psyk.uib.no

The present study was undertaken to examine the clinical characteristics of
patients with major affective disorders and comorbid migraine. Patients (n = 102)
with an index episode of either major depression or mania were interviewed with a
semi-structured interview based partly on DSM-IV criteria and partly on Akiskal's
criteria for affective temperaments. Compared to the patients without migraine (n
= 49), the patients with comorbid migraine (n = 53) had a higher frequency of
bipolar II disorder (43% vs. 10%), a lower frequency of bipolar I disorder (11%
vs. 33%), an approximately equal frequency of unipolar depressive disorder (45%
vs. 57%) and a higher frequency of affective temperaments (45% vs. 22%). The
migraine patients also had a greater number of anxiety disorders (3.0 vs. 1.9)
and a higher frequency of panic disorder and agoraphobia. Gender distribution,
age, age at onset of first affective episode, number of previous episodes and
symptoms during depressive episodes were similar in both groups. Based on these
findings it is suggested that the presence of migraine may be used to delineate a
distinct subgroup of the major affective disorders.

PMID: 12587198 [PubMed - indexed for MEDLINE]

2696: J Child Neurol. 2002 Nov;17(11):857-8.

Migraine-type headaches in children receiving chemotherapy and ondansetron.

Khan RB.

Division of Neurology, St. Jude Children's Research Hospital, Memphis, Tennessee 
38105, USA. raja.khan@stjude.org

Six children developed severe daily migraine-type headaches during cancer
treatment. In addition to chemotherapy drugs, all received daily doses of
ondansetron, a 5-hydroxytryptamine type 3 receptor antagonist.
5-Hydroxytryptamine is considered to play a central role in migraine
pathogenesis, and ondansetron may have caused headaches by producing
5-hydroxytryptamine dysfunction in the brain. All six children had either a
personal or a family history of migraine, and this may be a risk factor for
developing ondansetron-associated migraine-type headaches. Ondansetron-induced
headaches respond to withholding the drug and to standard antimigraine
medications, but further study of a larger group of patients is required to
confirm this impression.

Publication Types: 
    Case Reports

PMID: 12585731 [PubMed - indexed for MEDLINE]

2697: Pain. 2003 Feb;101(3):283-90.

Differing central amine receptor sensitivity in different migraine subtypes? A
neuroendocrine study using buspirone.

Cassidy EM, Tomkins E, Sharifi N, Dinan T, Hardiman O, O'Keane V.

Migraine/Headache Clinic, Department of Neurology, Royal College of Surgeons in
Ireland, Beaumont hospital, Dublin 9, Ireland. eucass@hotmail.com

Despite the importance of the 5HT1A receptor in regulating central serotonergic
tone, there is a dearth of research examining its role in migraine. In this
study, we examined the hypothesis that there would be altered neuroendocrine
responses to a 5HT1A agonist challenge in different migraine subtypes. Prolactin 
(PRL) responses to the 5HT1A receptor agonist drug buspirone were compared in 30 
female subjects with migraine (ten migraine with aura, MA; ten migraine without
aura, MO and ten chronic/transformed migraine, CM), and ten healthy controls
matched for age, gender and menstrual status. None of the subjects were taking
psychotropic medication or migraine prophylactic treatment and those with formal 
psychiatric disorder were excluded. Endocrine responses were determined by
measuring differences between baseline PRL and maximum increases post-buspirone
(deltaPRL). There was no difference in baseline PRL between groups. MA subjects
did not differ in their PRL responses to buspirone compared to healthy controls. 
The MO group had a four-fold increase in mean deltaPRL responses compared to
healthy controls. Mean deltaPRL was also increased in the CM group compared to
controls, but the difference was less exaggerated. This study indicates that
there is supersensitive central amine receptor function in MO and CM, but not in 
MA. These findings support the hypothesis that central 5HT function differs among
the migraine subtypes. The results also suggest that migrainous 'transformation' 
may be associated with adaptive changes in central 5HT receptor sensitivity. The 
relative contribution of 'state' and 'trait' receptor function to these findings 
as well as the possible role of dopamine receptors is discussed.

Publication Types: 
    Clinical Trial
    Comparative Study
    Controlled Clinical Trial
    Research Support, Non-U.S. Gov't

PMID: 12583871 [PubMed - indexed for MEDLINE]

2698: Curr Neurol Neurosci Rep. 2003 Mar;3(2):104-8.

Epidemiology of migraine and other types of headache in Asia.

Wang SJ.

Neurological Institute, Taipei Veterans General Hospital, 112, Taipei, Taiwan.
sjwang@vghtpe.gov.tw

Earlier studies have raised the issue that Asians have a much lower migraine
prevalence than Westerners. This article reviews the recent epidemiologic studies
of headache in Asia using International Headache Society (IHS) classification
criteria. Except for the Korean study and the first Hong Kong study (1992 to
1993), the prevalence of migraine has been quite consistent, ranging from 8.4% to
12.7%. The sex-specific migraine prevalence was 11.3% to 14.4% in women and 3.6% 
to 6.7% in men. The prevalence of IHS tension-type headache has also been similar
among these studies (15.6% to 25.7%). The consistency of the prevalence of
migraine and tension-type headache among these Asian countries is interesting in 
a region where the cultural background and development are so diverse. These IHS 
migraine surveys show that migraine is a significant disease in Asia and that its
prevalence rate is close to but in the low range of the those reported in Western
countries. Two surveys of chronic daily headache conducted in Taiwan, one in the 
general population and the other in the elderly population, have also revealed
prevalence rates (3.2% to 3.9%) similar to those of Western countries (3.0% to
4.7%). The geographic or ethnic diversity of migraine or other types of headache 
could be downplayed if a similar epidemiologic methodology and an identical case 
definition were used in the surveys among different regions of the world.

Publication Types: 
    Review

PMID: 12583837 [PubMed - indexed for MEDLINE]

2699: Drugs Today (Barc). 2002 Sep;38(9):615-29.

Frovatriptan: a selective type 1B/1D serotonin receptor agonist for the treatment
of migraine headache.

Cole P, Rabasseda X.

Medical Information Department, Prous Science, Barcelona, Spain.

Frovatriptan belongs to an innovative family of compounds aimed at breaking
through the long-standing barrier of migraine headache understanding and
treatment. While a typology of headaches has been recognized for some time, and a
number of therapies have been introduced for reduction of headache pain and
duration, the causes of migraine remain a subject of debate. Those prone to
attacks continue to endure them and suffer the related symptoms such as nausea
and disorientation. Frovatriptan, like all the triptans, acts by inducing
vasoconstriction of the meningeal arteries. It has been shown in pharmacological 
tests to act selectively as a potent agonist of serotonin 5-HT1B/1D receptors.
Frovatriptan has been well tolerated in humans and efficacious in reducing
headache pain and duration in clinical trials, which have also indicated that
dose adjustments for age or gender are not necessary for the drug. Patients have 
found the use of frovatriptan acceptable over the long-term, and overall a
low-incidence of adverse effects has been reported. Though not a prophylactic,
frovatriptan has demonstrated the potential to significantly improve the
therapeutic approaches to the treatment of migraine. Copyright 2002 Prous Science

Publication Types: 
    Review

PMID: 12582449 [PubMed - indexed for MEDLINE]

2700: Acta Neurol Scand. 2003 Feb;107(2):158-60.

Antimigraine drug consumption in Spain (1990-2000).

García-del-Pozo J, Carvajal A, Grajal C, Vera E, del Pino A.

Instituto de Farmacoepidemiología, Universidad de Valladolid, Spain.

OBJECTIVES: New marketed antimigraine drugs (triptans) are promising in the
management of migraine pain. The impact of these new drugs on the overall
consumption of the antimigraine drugs merits an analysis. MATERIAL AND METHODS:
The package units of antimigraine drugs, sold and reimbursed by the Spanish
National Health System, are used for estimations. Data are presented as defined
daily doses per 10,000 inhabitants/day. RESULTS: During the 1990-2000 period,
antimigraine drug utilization as a whole decreased by more than 25%; triptan use 
increased while ergot alkaloids' declined. CONCLUSIONS: The pattern of
antimigraine drug utilization in Spain has changed noticeably in accordance with 
recent recommendations.

PMID: 12580869 [PubMed - indexed for MEDLINE]

2701: Neurology. 2003 Feb 11;60(3):441-8.

Patterns of health care utilization for migraine in England and in the United
States.

Lipton RB, Scher AI, Steiner TJ, Bigal ME, Kolodner K, Liberman JN, Stewart WF.

Department of Neurology, Albert Einstein College of Medicine, Bronx, NY 10461,
USA. Rlipton@aecom.yu.edu

OBJECTIVE: To assess patterns of medical consultation, diagnosis, and medication 
use in representative samples of adults with migraine in England and the United
States. METHODS: Validated computer-assisted telephone interviews were conducted 
in the United Kingdom (n = 4,007) and the United States (n = 4,376). Individuals 
who reported six or more headaches per year meeting the criteria for migraine
were interviewed. RESULTS: Patients with migraine in the United Kingdom were more
likely to have consulted a doctor for headache at least once in their lifetime
(86% vs 69%, p < 0.0001), but also were more likely to have lapsed from medical
care (37% vs 21%, p < 0.001). In the United States, patients with migraine who
had consulted made more office visits for headache and were more likely to see a 
specialist. In the United States, but not in the United Kingdom, women with
migraine were more likely than men to consult doctors for headache. Patients with
migraine in the United Kingdom were more likely to receive a medical diagnosis of
migraine (UK 67%, US 56%; p < 0.05). Patterns of medication use were similar in
both countries, with most people treating with over-the-counter (OTC)
medications. Substantial disability occurred in a high proportion of those who
never consulted (UK 60%, US 68%), never received a correct medical diagnosis (UK 
64%, US 77%), and treated only with OTC medication (UK 72%, US 70%). CONCLUSION: 
Medically unrecognized migraine remains an important health problem both in the
United States and the United Kingdom. Furthermore, there may be barriers to
consultation for men in the United States that do not operate in the United
Kingdom.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 12578925 [PubMed - indexed for MEDLINE]

2702: Neurol India. 2002 Dec;50(4):522-3.

A case of hemeplegic migraine with leptomeningeal angiomatosis.

Girija AS, Somanath V.

Department of Neurology, Medical College, Kozhikode, Kerala, India.

A 43 year old man with thirty years history of recurrent hemiplegic migraine,
consistently occurring on one side (left sided paresthesia and weakness of less
than forty five minutes followed by right sided headache) and lately increasing
to once in three days was investigated. CT head and carotid angiogram showed
gyral calcification with prominent medullary and subependymal veins confirming
the diagnosis of leptomeningeal angiomatosis. Management and followup is
discussed.

Publication Types: 
    Case Reports

PMID: 12577115 [PubMed - indexed for MEDLINE]

2703: J Neurol. 2003 Feb;250(2):201-6.

Glaucomatous visual field defects in patients with migraine.

Comoğlu S, Yarangümeli A, Köz OG, Elhan AH, Kural G.

Ankara Numune Training and Research Hospital, Neurology Clinic, Ankara, Turkey.

PURPOSE: To investigate the visual fields in patients with migraine in terms of
glaucomatous visual field defects. METHOD: Patients who attended our Neurology
outpatient clinic complaining of headache and were diagnosed as migraine were
enrolled in the study. Each patient was questioned for the frequency, side,
localisation and severeness of the pain as well as the onset and the duration of 
the symptoms, the existence of aura, the description of the aura - if present -, 
additional systemic problems, and family history of migraine and glaucoma.
Detailed ophthalmological examinations and computerised visual field (VF)
analysis were then performed on each patient in our Ophthalmology Clinic. The
findings of 77 patients (61 female, 16 male) were evaluated and statistical
comparisons were carried out between the group of patients with glaucomatous-like
VF defects and the group without significant defects. RESULTS: VF tests revealed 
glaucomatous-like defects in 48 (62.3 %) patients. Intraocular pressure (IOP)
levels were within normal limits in all cases. There were no statistically
significant differences between the groups with and without VF defects in terms
of sex, the localisation and severeness of pain, the existence and the
description of aura, and family history of glaucoma, as well as the duration of
migraine, IOP and cup/disc ratio. The glaucomatous group was significantly older,
with a significantly higher age of onset for migraine. Risk of having
glaucomatous-like defects was higher in patients who had migraine attacks once a 
month or less frequently. A tendency of pain and VF defects to develop
ipsilaterally was noticed. DISCUSSION: A possible relationship between the
pathophysiology of migraine, visual field defects and glaucomatous optic
neuropathy is emphasized and VF screening for normal tension glaucoma is
recommended in patients with migraine.

Publication Types: 
    Clinical Trial

PMID: 12574951 [PubMed - indexed for MEDLINE]

2704: Curr Med Res Opin. 2002;18(8):471-8.

Management by nurses of primary headache: a pilot study.

Main A, Abu-Saad H, Salt R, Vlachonikolis I, Dowson A.

European Institute of Health and Medical Sciences, Surrey University, Guildford, 
UK. a.main@surrey.ac.uk

Primary headache is a very common condition and one that nurses encounter in many
different care settings. Yet there is a lack of evidence as to whether advice
given to sufferers is effective and what improvements may be expected in the
condition. The aim of this study was to evaluate the advice given by a nurse to
primary headache sufferers. The design was quasi-experimental. An experimental
group (n = 19) and a control group (n = 25) of primary headache sufferers had
their headache parameters of frequency, severity duration and disability
(Migraine Disability Assessment) over the previous six months assessed. The
experimental group then received advice in the form of health education from a
nurse. Both groups kept a headache diary for six months. After six months both
groups had their headache parameters assessed again. Compared to the control
group, there was a significant reduction in the severity of headaches experienced
by the experimental group (p = 0.006). Although there were reductions in
frequency and duration of headaches experienced by the experimental group
compared to the control group, these were not significant (p = 0.664 and p =
0.235, respectively). The Migraine Disability Assessment showed a trend towards
reduced scores in the experimental group compared to controls which were not
significant (p = 0.535). This pilot study suggests that health education can be
effective in reducing the severity of headaches. However, a larger study over a
longer period is needed to evaluate improvements in headache parameters.

Publication Types: 
    Comparative Study

PMID: 12564658 [PubMed - indexed for MEDLINE]

2705: Arq Neuropsiquiatr. 2002 Dec;60(4):912-6. Epub 2003 Jan 15.

Clinical features of episodic migraine and transformed migraine: a comparative
study.

Galego JC, Cipullo JP, Cordeiro JA, Tognola WA.

Departamento de Ciências Neurológicas, Faculdade de Medicina de São José do Rio
Preto, São José do Rio Preto, SP, Brasil. jcgalego@uol.com.br

Transformed migraine (TM) is one of the most frequent types of chronic daily
headache. Eighty patients: 40 with episodic migraine (EM) and 40 with TM with
ages ranging from 18 to 60 years old were studied. Females were the majority. At 
first examination, the mean age was similar in both groups. The initial age of
migraine attacks was significantly smaller in the TM group. Time history of
episodic attacks was similar in both groups. In the EM group, the headache was
predominantly located on only one side of the head; whereas in the TM group, on
more than one side. There was variation in the character of pain and intensity in
the TM group. Nocturnal awakening with headache, aura and family history did not 
show significant association with EM or TM. The TM was distinguished from the EM 
in relation to the frequency, location and pain intensity of the headache.
Patients with early migraine headache onset may exhibit a further risk of
developing TM.

Publication Types: 
    Comparative Study

PMID: 12563379 [PubMed - indexed for MEDLINE]

2706: Headache. 2003 Feb;43(2):144-66.

Ergotamine and dihydroergotamine: history, pharmacology, and efficacy.

Silberstein SD, McCrory DC.

Department of Neurology, Thomas Jefferson University Hospital, Philadelphia, Pa. 
19107, USA.

Ergotamine and dihydroergotamine share structural similarities with the
adrenergic, dopaminergic, and serotonergic neurotransmitters. As a result, they
have wide-ranging effects on the physiologic processes that they mediate.
Ergotamine and dihydroergotamine are highly potent at the 5-HT1B and 5-HT1D
antimigraine receptors and, as a consequence, the plasma concentrations that are 
necessary to produce the appropriate therapeutic and physiologic effects are very
low. The broad spectrum of activity at other monoamine receptors is responsible
for their side effect profile (dysphoria, nausea, emesis, unnecessary vascular
effects). Both ergotamine and dihydroergotamine have sustained vasoconstrictor
actions. In acute migraine treatment, their mechanisms of action involve
constricting the pain-producing intracranial extracerebral blood vessels at the
5-HT1B receptors and inhibiting the trigeminal neurotransmission at the
peripheral and central 5-HT1D receptors. The scientific evidence for efficacy is 
stronger for dihydroergotamine than for ergotamine. Their wide use is based on
long-term experience.

Publication Types: 
    Historical Article
    Review

PMID: 12558771 [PubMed - indexed for MEDLINE]

2707: Headache. 2003 Feb;43(2):109-16.

Single use of sumatriptan: a patient interview study.

Rahimtoola H, Buurma H, Tijssen CC, Leufkens HG, Egberts AC.

Department of Pharmacoepidemiology and Pharmacotherapy, Utrecht Institute for
Pharmaceutical Sciences, The Netherlands.

OBJECTIVE: To investigate the possible reasons associated with the use of a
single prescription of sumatriptan. BACKGROUND: A few population-based studies
concerning the usage patterns of sumatriptan have revealed a relatively high
incidence (approximately 40%) of sumatriptan users who utilize only a single
prescription of the drug. DESIGN AND METHODS: Using automated prescription data
from 11 community pharmacies, we identified single and multiple sumatriptan
prescription recipients. The data were collected from May 1, 1998, to April 30,
2000. Several patient- and medication-related variables possibly associated with 
single recipiency of sumatriptan were analyzed. In addition, single recipients of
sumatriptan were invited for an interview and asked a number of questions related
to their clinical status and their experience with the medication. RESULTS: Four 
hundred ninety-five, first-time users of sumatriptan were identified during the
patient selection period, of whom 38% were single recipients of sumatriptan. Of
the latter, 102 patients were considered eligible for interview. Reasons for
terminating treatment after only 1 prescription included: inefficacy and/or
occurrence of side effects, 78% (n=79); uncertain diagnosis of migraine, 39.2%
(n=40); and reduction in headache frequency, 33.3% (n=34). Almost half of the
population had terminated treatment without having consulted their physician.
More than half relied upon the use of over-the-counter (OTC) analgesics after
having tried sumatriptan. Compared to multiple users of sumatriptan, single
recipients were far less likely to have used another form of migraine treatment
prior to (odds ratio, 0.35; [95% confidence interval, 019 to 0.67]) and after
(odds ratio, 0.34 [95% confidence interval, 0.19 to 0.63]) initiating
sumatriptan. Furthermore, single recipients had demonstrated an increased
tendency towards benzodiazepine use prior to receiving sumatriptan (odds ratio,
1.80 [95% confidence interval, 1.00 to 3.28]). CONCLUSIONS: Single use of a
sumatriptan prescription reveals some issues that may impact negatively the
provision of effective migraine management. These include: rapidly developing
dissatisfaction with the treatment provided and a lower tendency to seek out
medical care. Our results also suggest that the drug may be used
(inappropriately) as a diagnostic tool.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 12558764 [PubMed - indexed for MEDLINE]

2708: Headache. 2003 Feb;43(2):96-8.

Comment in:
    Headache. 2003 Oct;43(9):1013; author reply 1013-4.

Migraine aggravation caused by cephalic venous congestion.

Doepp F, Schreiber SJ, Dreier JP, Einhäupl KM, Valdueza JM.

Department of Neurology, University Hospital Charité, Humboldt University,
Berlin, Germany.

BACKGROUND: Cerebral venous distension is thought by some to serve as a source of
migraine pain. Previous investigators have tried to modify pain intensity by
induction of additional venous congestion via compression of both internal
jugular veins (Queckenstedt's maneuver). The magnitude of blood flow within the
internal jugular veins depends markedly on body position, and inconsistencies in 
positioning may have influenced their results. OBJECTIVE: To investigate the
effect of Queckenstedt's maneuver, performed both in the upright and in the
supine body position, in migraineurs during an acute attack. METHODS: Twenty-five
patients (18 women, 7 men; mean age +/- SD, 35.4 +/- 13.3 years) with
International Headache Society-defined migraine without aura were evaluated.
Queckenstedt's maneuver was performed in both body positions during an acute
migraine attack, involving constant application of manual pressure to both
internal jugular veins for 30 seconds. Headache intensity was rated before,
during, and after Queckenstedt's maneuver on a scale extending from 1 (mild) to
10 (intolerable). RESULTS: Seventeen patients (68%) reported an increase of
headache intensity in the supine position during Queckenstedt's maneuver. In the 
sitting position, pain increase was observed only in 6 patients (24%). The
magnitude of pain increase was significantly greater in the supine position
compared to the upright position (P=.02). CONCLUSIONS: Our results support a role
for cerebral venous congestion in the generation of migraine pain and suggest
body position may influence the clinical expression of that process.

Publication Types: 
    Clinical Trial
    Comparative Study
    Controlled Clinical Trial

PMID: 12558761 [PubMed - indexed for MEDLINE]

2709: Headache. 2003 Feb;43(2):90-5.

The association between migraine and juvenile stroke: a case-control study.

Schwaag S, Nabavi DG, Frese A, Husstedt IW, Evers S.

Department of Neurology, University of Münster, Germany.

BACKGROUND: Several studies suggest an association between migraine and juvenile 
stroke. Because of some shortcomings, we designed another case-control study of a
homogenous group of patients with juvenile cerebral ischemia. This study is part 
of a larger German epidemiological research project on the association of
migraine with cerebrovascular disease. METHODS: We enrolled 160 consecutive
patients under the age of 46 years with first-ever ischemic stroke or transient
ischemic attack and 160 strictly sex- and age-matched controls. Patients
suffering from arterial dissection, brain hemorrhage, cranial sinus thrombosis,
lacunar stroke, or from migrainous infarction were excluded. Migraine was
diagnosed according to the criteria of the International Headache Society by the 
same 2 independent interviewers. For analyzing the data, nonparametric
statistical methods including odds ratio and 95% confidence interval were used.
RESULTS: Migraine was a significant risk factor for juvenile stroke for the total
sample with an odds ratio of 2.11 (confidence interval, 1.16 to 3.82). The odds
ratio was even higher in the subgroup under the age of 35 (3.26) and in the
female subgroup (2.68). We found migraine to be independent from other vascular
risk factors, from etiology, and from the territory of stroke. CONCLUSION: We can
confirm the findings of previous studies showing a significant association
between migraine and juvenile stroke in women. Furthermore, our data suggest
migraine to be an even more significant risk factor for patients under the age of
35 and to be independent from other vascular risk factors.

PMID: 12558760 [PubMed - indexed for MEDLINE]

2710: Am J Med Genet B Neuropsychiatr Genet. 2003 Feb;117B(1):86-9.

An investigation of the 5-HT2C receptor gene as a migraine candidate gene.

Johnson MP, Lea RA, Curtain RP, MacMillan JC, Griffiths LR.

Genomics Research Centre, School of Health Science, Griffith University, Gold
Coast, Australia.

Migraine is a common complex disorder, currently classified into two main
subtypes, migraine with aura (MA) and migraine without aura (MO). The strong
preponderance of females to males suggests an X-linked genetic component. Recent 
studies have identified an X chromosomal susceptibility region (Xq24-q28) in two 
typical migraine pedigrees. This region harbours a potential candidate gene for
the disorder, the serotonin receptor 2C (5-HT(2C)) gene. This study involved a
linkage and association approach to investigate two single nucleotide variants in
the 5-HT(2C) gene. In addition, exonic coding regions of the 5-HT(2C) gene were
also sequenced for mutations in X-linked migraine pedigrees. Results of this
study did not detect any linkage or association, and no disease causing mutations
were identified. Hence, results for this study do not support a significant role 
of the 5-HT(2C) gene in migraine predisposition. Copyright 2003 Wiley-Liss, Inc.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 12555241 [PubMed - indexed for MEDLINE]

2711: Med Care. 2003 Feb;41(2):299-308.

Use of willingness to pay to study values for pharmacotherapies for migraine
headache.

Lenert LA.

Section on Health Services Research, VA San Diego Healthcare System, California, 
USA. llenert@ucsd.edu

BACKGROUND: There is a wide range of therapeutic options for migraine headaches, 
yet little is known about how patients value different treatment alternatives nor
how to tailor treatments to patients' preferences. OBJECTIVE: Assess patients'
preferences for outcomes of treatment of migraine headache based on their
marginal willingness to pay (WTP) for treatment attributes. MATERIALS AND
METHODS: In an Internet-based study, we used computer software to measure
participants' WTP for a hypothetical ideal drug (one that was 100% effective,
worked quickly, and had no adverse effects) and for other hypothetical drugs,
each with one "less than ideal" attribute of performance. SUBJECTS: Two hundred
fifty-seven self-identified migraineurs recruited via an Internet Web site.
RESULTS: A high proportion of participants in the study had symptoms consistent
with migraine etiology of headache (99%). Median "out-of-pocket" monthly WTP cost
for an ideal migraine therapy was 130 dollars. WTP was associated with
participants' own migraine experience: severity of pain, frequency of headaches, 
and the types of medications used in the past. WTP was reduced when
pharmaceuticals offered less benefit, ranging from a mean of 74% of ideal for
treatments that failed to relieve nausea, to 43% of ideal in treatments
associated with a 50% chance of a rebound headache. CONCLUSIONS: There is wide
variability in patients' strength of preference for different attributes of
migraine therapy. Choice of therapy for migraine headache should be
individualized based on patients' preferences. WTP measures appear to be a valid 
and feasible metric for quantifying treatment preferences for migraine therapies.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 12555057 [PubMed - indexed for MEDLINE]

2712: Neurology. 2003 Jan 28;60(2):315-21.

Comment in:
    Neurology. 2003 Dec 23;61(12):1826; author reply 1826.

Acute migraine treatment with droperidol: A randomized, double-blind,
placebo-controlled trial.

Silberstein SD, Young WB, Mendizabal JE, Rothrock JF, Alam AS.

Thomas Jefferson University Hospital, Philadelphia, PA, USA.

BACKGROUND: The treatment of a migraine attack can be difficult when first-line
medication is unsuccessful and options for parenteral "rescue" therapy are
limited. METHODS: A randomized, double-blind, placebo-controlled, dose-ranging,
multicenter study was conducted to assess the efficacy and tolerability of
droperidol 0.1 mg, 2.75 mg, 5.5 mg, and 8.25 mg for the acute treatment of
moderate to severe migraine headache in adults. RESULTS: A total of 331 patients 
were enrolled; 305 were treated. Headache response at 2 hours was better (p <
0.002) in the treatment groups receiving droperidol IM at doses of 2.75 mg (87%),
5.5 mg (81%), and 8.25 mg (85%) compared with placebo (57%). The percent of
patients achieving a pain-free response at 2 hours after treatment was
significantly greater than placebo for the droperidol 2.75-mg, 5.5-mg, and
8.25-mg dose groups. The frequency of headache recurrence (within 24 hours) for
patients initially responding by 2 hours was lower in patients treated with
droperidol than placebo, but differences failed to reach significance. A
significantly greater percentage of patients receiving droperidol 2.75 mg
reported the elimination of migraine-associated symptoms (nausea, vomiting,
photophobia, and phonophobia) than those who received placebo. Although most
adverse events were of mild or moderate intensity, anxiety, akathisia, and
somnolence were rated as severe in 30% of patients who experienced those
symptoms. Hypotension was uncommon. No patient had QT prolongation.

Publication Types: 
    Clinical Trial
    Multicenter Study
    Randomized Controlled Trial
    Research Support, U.S. Gov't, P.H.S.

PMID: 12552051 [PubMed - indexed for MEDLINE]

2713: Curr Opin Pharmacol. 2003 Feb;3(1):73-7.

The neuronal versus vascular hypothesis of migraine and cortical spreading
depression.

Parsons AA, Strijbos PJ.

Neurology Centre of Excellence for Drug Discovery, GlaxoSmithKline
Pharmaceuticals, Third Avenue, Harlow CM19 5AD, UK. Andrew_A_Parsons@GSK.com

Our understanding of the pathophysiological mechanisms of migraine remains poor
despite the availability of clinically effective drugs and many years of
research. Historically, two independent theories regarding the aetiology of
headache were suggested: vascular and neuronal. However, recent data demonstrate 
that neuronal excitation modulates both the pial and meningeal circulation
through a critical interaction with the trigeminal nerve, supporting the concept 
that the integration of neuronal and vascular information in the
trigeminovascular network represents a key event in the aetiology of migraine.

Publication Types: 
    Comparative Study
    Review

PMID: 12550745 [PubMed - indexed for MEDLINE]

2714: Cleve Clin J Med. 2003 Jan;70(1):8-9, 13-4, 16 passim.

Relieving migraine pain: sorting through the options.

Mannix LK.

LKMannixMD@aol.com

Although triptans are a major advance in the treatment of migraine, the optimal
approach for acute treatment involves a combination of lifestyle modifications,
nonpharmacologic symptom relief, and drug therapy.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 12549721 [PubMed - indexed for MEDLINE]

2715: Curr Opin Neurol. 2003 Feb;16(1):5-13.

Migrainous vertigo: development of a pathogenetic model and structured diagnostic
interview.

Furman JM, Marcus DA, Balaban CD.

Department of Otolaryngology, University of Pittsburgh School of Medicine,
Pittsburgh, Pennsylvania 15213, USA. furman@pitt.edu

PURPOSE OF REVIEW: Vestibular symptoms occur frequently in patients with
migraine. This review refines recently proposed diagnostic criteria for
migraine-related vestibular symptoms, and develops a pathophysiological model for
the interface between migraine and the vestibular system. RECENT FINDINGS: The
epidemiological link between migraine and vestibular symptoms and signs suggests 
shared pathogenetic mechanisms. Links between the vestibular nuclei, the
trigeminal system, and thalamocortical processing centers provide the basis for
the development of a pathophysiological model of migraine-related vertigo. During
the last year, several studies have increased understanding of the relationship
between migraine and vestibular symptoms. A study of motion sickness and
allodynia in migraine patients supports the importance of central mechanisms of
sensitization for migraine-related vestibular symptoms. A study has demonstrated 
effective treatment of vertigo with migraine therapy. The identification of
migrainous vertigo, however, is hampered by a lack of standardized assessment
criteria for both clinical and research practices. The application of published
criteria for the diagnosis of migrainous vertigo allows the development of a
standardized, structured assessment interview. SUMMARY: An understanding of the
relationship between migraine and the vestibular system increases knowledge of
the pathogenesis of both migraine and vertigo. In addition, studies have
identified successful treatment, with standard migraine therapies, of vestibular 
symptoms in patients with both migraine and vertigo. The use of a standardized
assessment tool to identify this unique population of patients will help future
studies to test both the pathological model and effective treatment options.

Publication Types: 
    Review

PMID: 12544852 [PubMed - indexed for MEDLINE]

2716: J Intern Med. 2003 Feb;253(2):181-8.

Acupuncture versus placebo versus sumatriptan for early treatment of migraine
attacks: a randomized controlled trial.

Melchart D, Thormaehlen J, Hager S, Liao J, Linde K, Weidenhammer W.

Department of Internal Medicine II, Center for Complementary Medicine Research,
Technical University, Kaiserstrasse 9, 80801 Munich, Germany.
dieter.melchart@lrz.tu-muenchen.de

OBJECTIVES: To investigate whether acupuncture is superior to placebo and
equivalent to sumatriptan for the early treatment of an acute migraine attack.
DESIGN: Randomized, partly double-blind (sumatriptan versus placebo) trial.
SETTING: Two hospitals in Germany (one specialized in traditional Chinese
medicine and one in the treatment of headache). SUBJECTS: A total of 179
migraineurs experiencing the first symptoms of a developing migraine attack.
INTERVENTIONS: Traditional Chinese acupuncture, sumatriptan (6 mg subcutaneously)
or placebo injection. MAIN OUTCOME MEASURE: Number of patients in whom a full
migraine attack (defined as severe migraine headache) within 48 h was prevented. 
In patients who developed a migraine attack in spite of early treatment,
acupuncture and sumatriptan were applied a second time, whilst patients initially
randomized to placebo received sumatriptan. RESULTS: A full migraine attack was
prevented in 21 of 60 (35%) patients receiving acupuncture, 21 of 58 (36%)
patients receiving sumatriptan and 11 of 61 (18%) patients receiving placebo
(relative risk of having a full attack 0.79 (95% CI, 0.64-0.99) for acupuncture
versus placebo, and 0.78 (95% CI, 0.62-0.98) for sumatriptan versus placebo).
Response to the second intervention in patients who developed a full attack was
better with sumatriptan (17/31 patients who received sumatriptan twice and 37/46 
patients who had had placebo first) than with acupuncture (4/31). The number of
patients reporting side-effects was 14 in the acupuncture group, 23 in the
sumatriptan group and 10 in the placebo group. CONCLUSIONS: In this trial
acupuncture and sumatriptan were more effective than a placebo injection in the
early treatment of an acute migraine attack. When an attack could not be
prevented, sumatriptan was more effective than acupuncture at relieving headache.

Publication Types: 
    Clinical Trial
    Comparative Study
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 12542558 [PubMed - indexed for MEDLINE]

2717: Nat Genet. 2003 Feb;33(2):192-6. Epub 2003 Jan 21.

Haploinsufficiency of ATP1A2 encoding the Na+/K+ pump alpha2 subunit associated
with familial hemiplegic migraine type 2.

De Fusco M, Marconi R, Silvestri L, Atorino L, Rampoldi L, Morgante L, Ballabio
A, Aridon P, Casari G.

Human Molecular Genetics Unit, Dibit-San Raffaele Scientific Institute, Via
Olgettina 58, 20132 Milan, Italy.

Headache attacks and autonomic dysfunctions characterize migraine, a very common,
disabling disorder with a prevalence of 12% in the general population of Western 
countries. About 20% of individuals affected with migraine experience aura, a
visual or sensory-motor neurological dysfunction that usually precedes or
accompanies the headache. Although the mode of transmission is controversial,
population-based and twin studies have implicated genetic factors, especially in 
migraine with aura. Familial hemiplegic migraine is a hereditary form of migraine
characterized by aura and some hemiparesis. Here we show that mutations in the
gene ATP1A2 that encodes the alpha2 subunit of the Na+/K+ pump are associated
with familial hemiplegic migraine type 2 (FHM2) linked to chromosome 1q23 (OMIM
602481). Functional data indicate that the putative pathogenetic mechanism is
triggered by a loss of function of a single allele of ATP1A2. This is the first
report associating mutations of Na+K+ pump subunits to genetic diseases.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 12539047 [PubMed - indexed for MEDLINE]

2718: Eur J Neurol. 2003 Jan;10(1):53-7.

No change in the structure of the brain in migraine: a voxel-based morphometric
study.

Matharu MS, Good CD, May A, Bahra A, Goadsby PJ.

Department of Imaging Neuroscience, Institute of Neurology, Queen Square, London,
UK.

Migraine is a common, disabling form of primary neurovascular headache. For most 
of the twentieth century it was regarded as a vascular headache whose primary
pathophysiology lay in the cranial vasculature. Functional brain imaging using
positron emission tomography has demonstrated activation of the rostral brain
stem in acute migraine. Voxel-based morphometry is a new fully automated whole
brain technique that is sensitive to subtle macroscopic and mesoscopic structural
differences between groups of subjects. In this study 11 patients suffering from 
migraine with aura (10 females, one male: 23-52 years, mean 31); 11 controls (10 
females, one male: 23-52, mean 31); 17 patients with migraine without aura (16
females, one male: 24-57, mean 34); 17 controls (16 females, one male: 24-57,
mean 34) were imaged with high resolution volumetric magnetic resonance imaging. 
There was no significant difference in global grey or white matter volumes
between either patients with migraine and controls, or patients with aura and
without aura. This study did not show any global or regional macroscopic
structural difference between patients with migraine and controls, with migraine 
sufferers taken as homogenous groups. If structural changes are to be found,
other methods of phenotyping migraine, such as by genotype or perhaps treatment
response, may be required to resolve completely whether there is some subtle
structural change in the brain of patients with migraine.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 12534993 [PubMed - indexed for MEDLINE]

2719: Cephalalgia. 2003 Feb;23(1):55-8.

Decreased sTNF-RI in migraine patients?

Empl M, Sostak P, Riedel M, Schwarz M, Müller N, Förderreuther S, Straube A.

Department of Neurology, University of Munich, Germany. mempl@ion.ucl.ac.uk

Tumour necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) have recently
been found to have a pain-mediating function in addition to their immunological, 
proinflammatory function. According to the hypothesis of neurovascular
inflammation in migraine, these two cytokines could contribute to migraine pain
generation. We analysed IL-6 and its soluble receptors sIL-6R and sgp130 as well 
as TNF-alpha and its soluble receptor sTNF-RI in 27 migraine patients and eight
headache-free controls. Migraine patients tended to have less sTNF-RI (794 +/-
158 pg/ml) than controls (945 +/- 137 pg/ml). No differences in cytokine
concentrations were observed. If TNF-alpha plays a role in migraine
physiopathology, migraine patients may lack sufficient antagonistic sTNF-RI to
neutralize hyperalgesic TNF-alpha during a migraine attack.

PMID: 12534582 [PubMed - indexed for MEDLINE]

2720: Cephalalgia. 2003 Feb;23(1):43-9.

'Side locked' migraine and trigeminal autonomic cephalgias: evidence for clinical
overlap.

Kaup AO, Mathew NT, Levyman C, Kailasam J, Meadors LA, Villarreal SS.

Clinica de Cefaléias da Unidade Avançada Einstein Alphaville, Hospital Israelita 
Albert Einstein, São Paulo, Brazil. kaup_alex@yahoo.com

This paper will discuss evidence which supports a link between 'side locked'
migraine (SLM) and the trigeminal autonomic cephalgias (TACs). Recent papers
brought strictly unilateral primary headaches into focus, proposing new
classification and discussing pathophysiological mechanisms. We reviewed those
proposals and present evidence that SLM falls in between the well-defined TACs
and side shifting migraine (SSM). It is difficult to differentiate SLM from the
recently proposed headache subtype called hemicrania generis incerti (i.e.
hemicrania continua unresponsive to indomethacin). We also present cases that may
exemplify the considerations made in the paper.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 12534580 [PubMed - indexed for MEDLINE]

2721: Cephalalgia. 2003 Feb;23(1):39-42.

Urinary nitric oxide metabolites and lipid peroxidation by-products in migraine.

Ciancarelli I, Tozzi-Ciancarelli MG, Di Massimo C, Marini C, Carolei A.

Department of Neurology and Laboratory of Applied Physiology, University of
L'Aquila, Italy.

Enhanced endothelium nitric oxide (NO) and superoxide anion release may cause
migraine through related cerebral blood flow changes. Thirty subjects suffering
from migraine with and without aura and 20 healthy controls were investigated.
Urine samples collected for 24 h during and after the migraine attack, and during
the headache-free period, were assayed for urinary NO stable metabolites (NOx)
and thiobarbituric acid reactive substances (TBARS). During the headache-free
period urinary NOx and TBARS levels were higher in migraine sufferers than in
controls (NOx 0.77 +/- 0.14 vs. 0.28 +/- 0.15 mmol/mmol creatinine, P < 0.05;
TBARS 0.40 +/- 0.19 vs. 0.26 +/- 0.13 micro mol/mol creatinine, P < 0.05). Also, 
NOx excretion was higher during the headache-free period than during or after the
migraine attack (P < 0.05). Urinary TBARS were increased during the attack with
respect to the headache-free period (P < 0.05). No differences were observed in
the same parameters between sufferers of migraine with and without aura. Urinary 
NOx and TBARS might be promising as markers of their systemic levels to evaluate 
the increased vulnerability to oxidative stress in migraine sufferers.

PMID: 12534579 [PubMed - indexed for MEDLINE]

2722: Cephalalgia. 2003 Feb;23(1):35-8.

Trigemino-cervical reflex in patients with headache.

Milanov I, Bogdanova D.

Department of Clinical Neurophysiology, University Hospital of Neurology and
Psychiatry 'St Naum', Sofia, Bulgaria. milanovivan@hotmail.com

Neurophysiological studies have shown abnormal activity of some brainstem nuclei 
in headache patients. The trigemino-cervical reflex is an anti-nociceptive reflex
that gives an opportunity for evaluation of the brainstem interneurone activity. 
It has not been previously examined in headache patients. We studied 15 patients 
with predominantly unilateral chronic tension-type headache, 15 patients with
migraine without aura and 32 healthy subjects. The trigemino-cervical reflex was 
recorded bilaterally from the resting sternocleidomastoid muscle using surface
electromyographic recordings. In all headache patients the trigemino-cervical
reflex on the painful side was with shortened latency compared with the
non-painful side and with healthy persons. The results suggest decreased activity
of the brainstem inhibitory interneurones. We suggest that although the
pathophysiological mechanisms of tension-type headache and migraine are
different, they share common mechanisms of abnormal pain control.

PMID: 12534578 [PubMed - indexed for MEDLINE]

2723: Cephalalgia. 2003 Feb;23(1):29-34.

Comment in:
    Cephalalgia. 2004 Jun;24(6):510; author reply 511-2.

Central 5-HT receptor hypersensitivity in migraine without aura.

Cassidy EM, Tomkins E, Dinan T, Hardiman O, O'Keane V.

Migraine/Headache Clinic, Department of Neurology, Royal College of Surgeons in
Ireland, Beaumont Hospital, Dublin, Ireland. eucass@hotmail.com

Serotonin has long been implicated as a key neurotransmitter in migraine. There
is a dearth of research specifically examining 5-HT1A receptor sensitivity in
migraine despite the importance of this receptor in regulating central
serotonergic tone. In this study we examined the hypothesis that migraine without
aura is associated with hypersensitivity of central 5-HT1A receptors, using a
5-HT1A neuroendocrine challenge drug and comparing serum prolactin responses
between a test group with migraine and a matched group of healthy controls.
Twelve female subjects fulfilling International Headache Society (IHS) criteria
for migraine without aura were evaluated. Following an overnight fast, subjects
presented for testing at 9am. An intravenous canula was inserted and serum
prolactin was assessed at baseline and every 30 min for 3 h following a single
dose of 30 mg oral buspirone, a 5-HT1A-receptor agonist. Subjects were assessed
during the first 5 days of the menstrual cycle. No subjects were taking
psychotropic medication or migraine prophylactic treatment. Patients with current
or previous psychiatric disorder, daily headache or analgesic overuse were
excluded. 16 healthy female volunteers matched for age and menstrual status were 
also evaluated and served as controls. There was no difference in baseline
prolactin between groups. There was a significant rise in prolactin following
buspirone in both groups. Subjects with migraine had a significantly increased
prolactin response to buspirone (delta max) compared to controls (P < 0.001).
This study supports the hypothesis that migraine without aura is associated with 
a relative hypersensitivity of central 5-HT1A receptors. This is of relevance
given the role of the 5-HT1A receptor in controlling raphe 5-HT tone and in the
possible association between migraine and anxiety and depression.

Publication Types: 
    Clinical Trial
    Research Support, Non-U.S. Gov't

PMID: 12534577 [PubMed - indexed for MEDLINE]

2724: Cephalalgia. 2003 Feb;23(1):14-9.

Comment in:
    Cephalalgia. 2003 Oct;23(8):775.

Increased frequency of migraine in narcoleptic patients: a confirmatory study.

Dahmen N, Kasten M, Wieczorek S, Gencik M, Epplen JT, Ullrich B.

Department of Psychiatry, University of Mainz, Germany.
mdahmen@mail.psychiatrie.klinik.uni-mainz.de

Previously we have reported an increased prevalence of migraine in narcoleptic
patients. Because of the theoretical and clinical implications of this finding we
recruited an independent new study sample of 100 patients with proven narcolepsy 
and conducted a structured 26-item interview based on the international
diagnostic criteria for headache disorders, the Kiel Headache Questionnaire.
Narcolepsy symptoms were measured by means of the Stanford Centre for Narcolepsy 
Sleep Inventory. Migraine prevalence was twofold to fourfold increased in the
narcoleptic patients and amounted to 44.4% in women and 28.3% in men. The onset
of narcolepsy symptoms was 12.3 +/- 11.4 years before the onset of migraine
symptoms. The results might be regarded as indicative of a common
pathophysiological pathway relevant to both of the two disorders.

PMID: 12534574 [PubMed - indexed for MEDLINE]

2725: Drug Saf. 2003;26(2):93-107.

Tolerability of the triptans: clinical implications.

Nappi G, Sandrini G, Sances G.

University Centre for Adaptive Disorders and Headache, IRCCS C. Mondino
Foundation, University of Pavia, Italy. giuseppe.nappi@mondino.it

The triptans represent a relatively new class of compounds effective in the
treatment of migraine. The safety and tolerability of these drugs have been
extensively investigated since the first triptan (sumatriptan) became
commercially available. A report on a very large population of patients tested
during clinical trials and in postmarketing studies, confirms that these drugs
are safe and well tolerated when correctly used. Adverse events are frequently
reported, but are usually mild and only a few patients discontinue therapy
because of them. These adverse events include, in particular, the so-called
'triptan symptoms' (tingling, sensation of warmth, etc.). The exact mechanism of 
chest symptoms reported by 20% of patients with migraine treated with triptans
remains unclear, but are exceptionally related to a cardiac mechanism. CNS
adverse events (i.e. somnolence) are also reported, but it is a matter of debate 
whether they are related to the pharmacological properties (i.e. lipophilicity)
of the drug or are symptoms of the disease itself. The potential risk for drug
overuse must be taken into account when the triptans are given to patients with a
high frequency of migraine attacks. Clinical interaction of triptans with other
drugs metabolised in the liver may theoretically influence the incidence of
adverse events, but there is little evidence to support this assumption. There is
no evidence of a teratogenic risk of triptans in pregnant women taking these
drugs.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 12534326 [PubMed - indexed for MEDLINE]

2726: Arch Neurol. 2003 Jan;60(1):113-6.

Hearing symptoms in migrainous infarction.

Lee H, Whitman GT, Lim JG, Yi SD, Cho YW, Ying S, Baloh RW.

Department of Neurology, Keimyung University, School of Medicine, Daegu, Korea.

BACKGROUND: In case reports, migraine headaches have been associated with
fluctuating low-frequency hearing loss and sudden, unilateral hearing loss.
Auditory symptoms associated with migrainous infarction have not previously been 
emphasized. OBJECTIVE: To describe migrainous infarction presenting with acute
auditory symptoms. DESIGN: Case reports. SETTING: Tertiary care hospitals.
PATIENTS: A 40-year-old man with a history of migraine suddenly developed
bilateral hearing loss associated with severe, throbbing, occipital headache,
tinnitus, vertigo, speech disturbance, and right hemiparesis. An early audiogram 
showed profound, down-sloping, sensorineural-type hearing loss bilaterally.
Sixteen days later, a follow-up pure tone audiogram documented marked improvement
in both sides to a pure tone average of 30 dB. Right hemiparesis and dysarthria
also improved steadily for 2 months. A 25-year-old woman with a history of
migraine with aura suddenly developed hyperacusis, unilateral hearing loss, and
migraine headache early in migrainous infarction. Magnetic resonance imaging
documented infarcts in the pons and cerebellum. CONCLUSIONS: In these patients,
acute auditory symptoms are a part of the prodrome of migrainous infarction. We
speculate that these symptoms may have resulted from migraine-associated
vasospasm. Migrainous infarction should be considered in the differential
diagnosis of acute auditory symptoms, including sudden, bilateral hearing loss.

Publication Types: 
    Case Reports

PMID: 12533097 [PubMed - indexed for MEDLINE]

2727: Arch Neurol. 2003 Jan;60(1):71-5.

Drop attacks and vertigo secondary to a non-meniere otologic cause.

Ishiyama G, Ishiyama A, Baloh RW.

Department of Neurology, University of California, Los Angeles, UCLA School of
Medicine, Los Angeles, CA 90095, USA.

BACKGROUND: Tumarkin falls are sudden drop-attack falls that occur in a subset of
patients with Meniere syndrome (endolymphatic hydrops), an inner ear disorder
characterized by vertigo spells and hearing loss. OBJECTIVE: To describe the
clinical features and quantitative audiovestibular testing results in a case
series of patients with Tumarkin falls, episodic vertigo, and normal hearing.
SETTING: University referral center for disorders of balance and hearing.
METHODS: Case series (unselected) of all patients with Tumarkin falls and a
normal audiogram at least 1 year after onset of vestibular symptoms (n = 6) from 
a retrospective analysis of the records of all patients with Tumarkin falls
presenting to Neurotology Clinic at UCLA Medical Center, Los Angeles, Calif, from
October 1, 1975, to February 1, 2001 (N = 55). Quantitative audiologic and
vestibular function testing, neurologic history, and examination were performed. 
RESULTS: Five of 6 patients had unilateral caloric paresis, and 1 had bilateral
vestibulopathy. Five of 6 had a personal and/or family history of migraine
headaches meeting International Headache Society criteria. All patients had a
subjective sensation of feeling pushed by an external force, and half of the
patients had a subjective tilt of the environment concurrent with the fall.
CONCLUSIONS: The incidence of migraine is high in this subgroup of patients with 
Tumarkin falls and normal hearing. The clinical description of the falls is
similar to those associated with Meniere syndrome. Further studies are needed to 
understand the etiology of Tumarkin falls in these patients with normal hearing.

Publication Types: 
    Case Reports

PMID: 12533091 [PubMed - indexed for MEDLINE]

2728: J Neurol Neurosurg Psychiatry. 2003 Feb;74(2):238-41.

Lay versus expert interviewers for the diagnosis of migraine in a large sample of
elderly people.

Tzourio C, Gagnière B, El Amrani M, Bousser MG, Alpérovitch A.

INSERM U 360, Hôpital Salpêtrière, 75651 Paris cedex 13, France.
tzourio@chups.jussieu.fr

OBJECTIVE: To determine the agreement between lay interviewers and experts in the
diagnosis of migraine by questionnaire. SUBJECTS: A population based sample of
1188 individuals aged 64 to 73 years. METHODS: Participants who declared that
they had recurrent headaches (n = 238) answered a structured questionnaire by lay
interviewers with special training in migraine. A migraine expert subsequently
interviewed all the headache sufferers using the same questionnaire. Migraine was
defined according to the International Headache Society criteria. RESULTS: In
comparison with the expert, the diagnosis derived by the lay interviewers had
high values for specificity (97%) and positive predictive value (86%), and a low 
sensitivity (50%) and negative predictive value (57%). Agreement between the
expert and the lay interviewers was low, with a kappa value of 0.36 (95%
confidence interval 0.26 to 0.47). The most serious discrepancies concerned the
duration of attacks, the worsening of headaches by physical activity, the
presence of nausea or vomiting, and the unilaterality of headaches. As a result, 
the lifetime prevalence of migraine headaches was greatly underestimated by lay
interviewers (6.5%) in comparison with the expert (11.1%). CONCLUSIONS: A low
level of agreement between lay interviewers and a headache expert in the
diagnosis of migraine headaches by structured questionnaire may result in a
substantial underestimation of migraine prevalence.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 12531958 [PubMed - indexed for MEDLINE]

2729: J Physiol. 2003 Jan 15;546(Pt 2):337-47.

The familial hemiplegic migraine mutation R192Q reduces G-protein-mediated
inhibition of P/Q-type (Ca(V)2.1) calcium channels expressed in human embryonic
kidney cells.

Melliti K, Grabner M, Seabrook GR.

Merck Sharp and Dohme Research Laboratories, The Neuroscience Research Centre,
Terlings Park, Eastwick Road, Harlow, Essex CM20 2QR, UK. karim_melliti@merck.com

Familial hemiplegic migraine is associated with at least 13 different missense
mutations in the alpha1A Ca(2+) channel subunit. Some of these mutations have
been shown to affect the biophysical properties of alpha1A currents. To date, no 
study has examined the influence of such mutations on the G-protein regulation of
channel function. Because G-proteins inhibit movement of the voltage sensor, we
examined the effects of the R192Q mutation, which neutralizes a positive charge
in the first S4 segment. Human wild-type (WT) or R192Q mutant channels were
expressed in human embryonic kidney tsA-201 cells along with dopamine D2
receptors. Application of quinpirole induced fast (approximately 1 s), pertussis 
toxin-sensitive inhibition of alpha1A(WT) and alpha1A(R192Q) Ca(2+) currents,
consistent with the activation of a membrane-delimited pathway. alpha1A(WT)
Ca(2+) currents were inhibited by 62.9 +/- 0.9 % (n = 27), whereas alpha1A(R192Q)
Ca(2+) currents were inhibited by only 47.9 +/- 1.8 % (n = 35; P < 0.001).
Concentration-response analysis showed that only the extent of inhibition was
affected, with no change in agonist potency (EC(50) = 1 nM). Prepulse
facilitation, which is a characteristic of voltage-dependent inhibition, was also
reduced by the R192Q mutation. However, the kinetics of facilitation and slow
activation were not affected, suggesting that G-protein-Ca(2+) channel affinity
was unchanged. These results show that the R192Q mutation reduces the G-protein
inhibition of P/Q-type Ca(2+) channels, probably by altering mechanisms by which 
Gbetagamma subunit binding induces a change in channel gating. Altered G-protein 
modulation and the consequent reduced presynaptic inhibition may contribute to
migraine attacks by favouring a persistent state of hyperexcitability.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 12527722 [PubMed - indexed for MEDLINE]

2730: Neurology. 2003 Jan 14;60(1):120-1.

Comment in:
    Neurology. 2003 Sep 9;61(5):721-2; author reply 722.

Treatment of sporadic hemiplegic migraine with calcium-channel blocker verapamil.

Yu W, Horowitz SH.

Division of Neurology, University of Missouri-Columbia, USA. wyu_1998@yahoo.com

Gene mutations within the P/Q type neuronal calcium channel in familial
hemiplegic migraine (FHM) suggest a therapeutic role for calcium-channel
blockade. The authors have previously reported abortive therapy of FHM with IV
verapamil. Here the authors describe four cases of sporadic hemiplegic migraine
(SHM) responsive to verapamil, administered either orally or IV. The findings
indicate that verapamil is effective therapy for both SHM and FHM.

Publication Types: 
    Case Reports

PMID: 12525732 [PubMed - indexed for MEDLINE]

2731: Curr Pain Headache Rep. 2003 Feb;7(1):63-6.

The role of anticonvulsants in preventive migraine therapy.

Corbo J.

Department of Emergency Medicine, Jacobi Medical Center, 1400 Pelham Parkway
South, Bronx, NY 10462, USA. jillcorbo@aol.com

The mainstay of migraine treatment is pharmacotherapy. There have been numerous
medications used to prevent migraine headaches, including b-blockers,
calcium-channel blockers, anticonvulsants, and nonsteroidal anti-inflammatory
drugs. Sodium valproate is the only antiepileptic drug approved by the Food and
Drug Administration for migraine prevention. Newer antiepileptics, including
gabapentin and topiramate, are being evaluated for their role in preventive
therapy. The mechanism of action of antiepileptics is not fully understood, but
they all share a common role in enhancing gamma-aminobutyric acid-mediated
inhibition. This article reviews the role of anticonvulsants in preventive
migraine therapy.

Publication Types: 
    Comparative Study
    Review

PMID: 12525273 [PubMed - indexed for MEDLINE]

2732: Curr Pain Headache Rep. 2003 Feb;7(1):55-62.

Ergotamine and dihydroergotamine: a review.

Bigal ME, Tepper SJ.

The New England Center for Headache, 778 Long Ridge Road, Stamford, CT 06902,
USA. mbigal@aecom.yu.edu

The ergot alkaloids were the first specific antimigraine therapy available.
However, with the advent of the triptans, their use in the treatment of migraine 
has declined and their role has become less clear. This review discusses the
pharmacology, efficacy, and safety of the ergots. In randomized clinical trials, 
oral ergotamine was found to be superior to placebo, but inferior to 100 mg of
oral sumatriptan. In contrast, rectal ergotamine was found to have higher
efficacy (73% headache relief) than rectal sumatriptan (63% headache relief).
Intranasal dihydroergotamine was found to be superior to placebo, but less
effective than subcutaneous and intranasal sumatriptan. Ergotamine is still
widely used in some countries for the treatment of severe migraine attacks. It is
generally regarded as a safe and useful drug if prescribed for infrequent use, in
the correct dose, and in the absence of contraindications; however, safer and
more effective options do exist in the triptans. In patients with status
migrainous and patients with frequent headache recurrence, ergotamine is still
probably useful.

Publication Types: 
    Comparative Study
    Review

PMID: 12525272 [PubMed - indexed for MEDLINE]

2733: Curr Pain Headache Rep. 2003 Feb;7(1):51-4.

Antidepressants in the treatment of migraine headache.

Punay NC, Couch JR.

The University of Oklahoma Health Sciences Center, Department of Neurology, 711
S.L. Young Boulevard, Oklahoma City, OK 73104, USA. james-couch@ouhsc.edu

Antidepressants, particularly tricyclic antidepressants, have been a mainstay in 
the prophylactic therapy of migraine. The tricyclic antidepressants
amitriptyline, nortriptyline, and doxepin have been the major agents for
prophylactic treatment of migraine. These cause significant side effects in some 
patients. The high-affinity selective serotonin reuptake inhibitors and other
newer antidepressants have been disappointing and much less effective in the
treatment of migraine. In patients who are depressed with severe migraine, a
tricyclic antidepressant may treat both conditions; however, the addition of a
newer atypical antidepressant may be needed.

Publication Types: 
    Review

PMID: 12525271 [PubMed - indexed for MEDLINE]

2734: Pain. 2003 Jan;101(1-2):25-32.

Abnormal brain processing of cutaneous pain in patients with chronic migraine.

de Tommaso M, Valeriani M, Guido M, Libro G, Specchio LM, Tonali P, Puca F.

Department of Psychiatric and Neurological Sciences, University of Bari, Bari,
Italy. m.detommaso@neurol.uniba.it

Syndromes with chronic daily headache include chronic migraine (CM). The reason
for the transformation of migraine into chronic daily headache is still unknown. 
In this study, we aimed to evaluate heat pain thresholds and event-related
potentials following CO(2)-laser thermal stimulation (LEPS) in hand and facial
regions in patients with CM, to show changes in nociceptive brain responses
related to dysfunction of pain elaboration at the cortical level. The results
were compared with findings from normal control subjects and from subjects who
suffer from migraine without aura. The effects of stimulus intensity, subjective 
pain perception and attention were monitored and compared with features of the
LEPS. Twenty-five CM patients, 15 subjects suffering from migraine without aura
and 15 normal control subjects were enrolled in the study. LEPS amplitude
variation was reduced in CM patients with respect to the perceived stimulus
intensity, in comparison with migraine without aura patients and control
subjects. In both headache groups, the distraction from the painful laser
stimulus induced by an arithmetic task failed to suppress the LEPS amplitude, in 
comparison with control subjects. These results suggest an abnormal cortical
processing of nociceptive input in CM patients, which could lead to the chronic
state of pain. In both headache groups, an inability to reduce pain elaboration
during an alternative cognitive task emerged as an abnormal behaviour probably
predisposing to migraine.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 12507697 [PubMed - indexed for MEDLINE]

2735: Invest Ophthalmol Vis Sci. 2003 Jan;44(1):442-8.

Contrast-processing dysfunction in both magnocellular and parvocellular pathways 
in migraineurs with or without aura.

McKendrick AM, Badcock DR.

School of Psychology, University of Western Australia, 35 Stirling Highway,
Crawley 6009, WA, Australia. allisonm@psy.uwa.edu.au

PURPOSE: To assess contrast-discrimination thresholds in patients with migraine
who have manifest visual field loss. This study was undertaken to determine
whether contrast processing abnormalities in migraineurs are more readily
identified by using stimuli that elicit a response from the subject that depends,
at least in part, on adaptation mechanisms, and if so, whether deficits appear
more pronounced in magnocellular (M) or parvocellular (P) visual pathways.
METHODS: Ten patients with migraine who had abnormal visual fields measured with 
flicker perimetry but had normal standard automated perimetry (SAP) thresholds
participated, along with 15 age-matched control subjects. Contrast-discrimination
performance was assessed with the steady-pedestal (magnocellular) and
pulsed-pedestal (parvocellular) stimuli of Pokorny and Smith for seven pedestal
luminances between 15 and 60 cd/m(2) on a background of 30 cd/m(2). Subjects were
tested foveally and midperipherally at 12.5 degrees. Migraineurs were tested in
the quadrant of worst visual field performance. Control subjects were assessed in
locations matched to those of the migraine group. RESULTS: Foveal performance was
not significantly different between the migraine and control groups for either
task. At 12.5 degrees the migraine group had significantly raised thresholds for 
both conditions. Effect size statistics revealed similar deficit magnitudes for
each test (steady pedestal, -1.06; pulsed pedestal, -1.04). CONCLUSIONS:
Dysfunction in both the M and P pathways was identified in the midperipheral
visual field of the migraine group. The P pathway dysfunction was not identified 
by SAP. These findings support the possibility of nonselective neural adaptation 
abnormalities in some subjects with migraine.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 12506107 [PubMed - indexed for MEDLINE]

2736: JAMA. 2003 Jan 1;289(1):65-9.

Prophylactic treatment of migraine with an angiotensin II receptor blocker: a
randomized controlled trial.

Tronvik E, Stovner LJ, Helde G, Sand T, Bovim G.

Department of Neurology and Clinical Neurophysiology, Norwegian University of
Science and Technology, Trondheim, Norway. Erling.Tronvik@medisin.ntnu.no

CONTEXT: There is a paucity of effective, well-tolerated drugs available for
migraine prophylaxis. OBJECTIVE: To determine whether treatment with the
angiotensin II receptor blocker candesartan is effective as a
migraine-prophylactic drug. DESIGN AND SETTING: Randomized, double-blind,
placebo-controlled crossover study performed in a Norwegian neurological
outpatient clinic from January 2001 to February 2002. PATIENTS: Sixty patients
aged 18 to 65 years with 2 to 6 migraine attacks per month were recruited mainly 
from newspaper advertisements. INTERVENTIONS: A placebo run-in period of 4 weeks 
was followed by two 12-week treatment periods separated by 4 weeks of placebo
washout. Thirty patients were randomly assigned to receive one 16-mg candesartan 
cilexetil tablet daily in the first treatment period followed by 1 placebo tablet
daily in the second period. The remaining 30 received placebo followed by
candesartan. MAIN OUTCOME MEASURES: The primary end point was number of days with
headache; secondary end points included hours with headache, days with migraine, 
hours with migraine, headache severity index, level of disability, doses of
triptans, doses of analgesics, acceptability of treatment, days of sick leave,
and quality-of-life variables on the Short Form 36 questionnaire. RESULTS: In a
period of 12 weeks, the mean number of days with headache was 18.5 with placebo
vs 13.6 with candesartan (P =.001) in the intention-to-treat analysis (n = 57).
Some secondary end points also favored candesartan, including hours with headache
(139 vs 95; P<.001), days with migraine (12.6 vs 9.0; P<.001), hours with
migraine (92.2 vs 59.4; P<.001), headache severity index (293 vs 191; P<.001),
level of disability (20.6 vs 14.1; P<.001) and days of sick leave (3.9 vs 1.4; P 
=.01), although there were no significant differences in health-related quality
of life. The number of candesartan responders (reduction of > or =50% compared
with placebo) was 18 (31.6%) of 57 for days with headache and 23 (40.4%) of 57
for days with migraine. Adverse events were similar in the 2 periods. CONCLUSION:
In this study, the angiotensin II receptor blocker candesartan provided effective
migraine prophylaxis, with a tolerability profile comparable with that of
placebo.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 12503978 [PubMed - indexed for MEDLINE]

2737: Curr Med Res Opin. 2002;18(7):414-39.

New guidelines for the management of migraine in primary care.

Dowson AJ, Lipscombe S, Sender J, Rees T, Watson D; MIPCA Migraine Guidelines
Development Group. Migraine In Primary Care Advisors.

King's Headache Service, King's College Hospital, London, UK.

Despite repeated initiatives over the past decade, migraine remains
under-recognised, under-diagnosed and under-treated in everyday clinical
practice. The Migraine in Primary Care Advisors (MIPCA) group has produced new
guidelines for migraine management to attempt to rectify this situation. MIPCA is
a group of physicians, nurses, pharmacists and other healthcare professionals
dedicated to the improvement of headache management in primary care, who have
also worked closely with the Migraine Action Association (the UK patients' group)
in the development of these guidelines. The principles of the new MIPCA
guidelines are: To arrange specific consultations for headache. To institute a
system of detailed history taking, patient education and buy-in at the outset of 
the consultation. To utilise a new screening algorithm for the differential
diagnosis of headache, which can be confirmed by further questioning, if
necessary. To institute a process of management that is individualised for each
patient, using a new algorithm. Assessing the impact on the patient's daily life 
is a key aspect of diagnosis and management. To prescribe only treatments that
have objective evidence of favourable efficacy and tolerability. To utilise
prospective follow-up procedures to monitor the success of treatment. To organise
a team approach to headache management in primary care.

Publication Types: 
    Guideline
    Practice Guideline
    Research Support, Non-U.S. Gov't

PMID: 12487508 [PubMed - indexed for MEDLINE]

2738: Cephalalgia. 2002 Dec;22(10):799-806.

Preclinical studies characterizing the anti-migraine and cardiovascular effects
of the selective 5-HT1D receptor agonist PNU-142633.

McCall RB, Huff R, Chio CL, TenBrink R, Bergh CL, Ennis MD, Ghazal NB, Hoffman
RL, Meisheri K, Higdon NR, Hall E.

Department of Neurobiology and Structural, Analytical and Medicinal Chemistry,
Pharmacia Corporation, Kalamazoo, MI 49001, USA. robert.b.mcall@pharmacia.com

The present study describes the preclinical pharmacology of a highly selective
5-HT1D receptor agonist PNU-142633. PNU-142633 binds with a Ki of 6 nm at the
human 5-HT1D receptor and a Ki of> 18 000 nm at the human 5-HT1B receptor. The
intrinsic activity of PNU-142633 at the human 5-HT1D receptor was determined to
be 70% that of 5-HT in a cytosensor cell-based assay compared with 84% for that
of sumatriptan. PNU-142633 was equally effective as sumatriptan and a half-log
more potent than sumatriptan in preventing plasma protein extravasation induced
by electrical stimulation of the trigeminal ganglion. Like sumatriptan,
PNU-142633 reduced the increase in cat nucleus trigeminal caudalis blood flow
elicited by electrical stimulation of the trigeminal ganglion compared with the
vehicle control. The direct vasoconstrictor potential of PNU-142633 was evaluated
in vascular beds. Sumatriptan increased vascular resistance in carotid, meningeal
and coronary arteries while PNU-142633 failed to alter resistance in these
vascular beds. These data are discussed in relation to the clinical findings of
PNU-142633 in a phase II acute migraine study.

Publication Types: 
    Comparative Study

PMID: 12485205 [PubMed - indexed for MEDLINE]

2739: Am Fam Physician. 2002 Dec 1;66(11):2123-30.

Comment in:
    Am Fam Physician. 2002 Dec 1;66(11):2050.    Am Fam Physician. 2002 Dec 1;66(11):2140-1.

Management of the acute migraine headache.

Aukerman G, Knutson D, Miser WF; Department of Family Medicine, Ohio State
University College of Medicine and Public Health, Columbus, Ohio.

Department of Family Medicine, Ohio State University College of Medicine and
Public Health, Columbus, Ohio 43201, USA. aukerman-1@medctr.osu.edu

As many as 30 million Americans have migraine headaches. The impact on patients
and their families can be tremendous, and treatment of migraines can present
diagnostic and therapeutic challenges for family physicians. Abortive treatment
options include nonspecific and migraine-specific therapy. Nonspecific therapies 
include analgesics (aspirin, nonsteroidal anti-inflammatory drugs, and opiates), 
adjunctive therapies (antiemetics and sedatives), and other nonspecific
medications (intranasal lidocaine or steroids). Migraine-specific abortive
therapies include ergotamine and its derivatives, and triptans. Complementary and
alternative therapies can also be used to abort the headache or enhance the
efficacy of another therapeutic modality. Treatment choices for acute migraine
should be based on headache severity, migraine frequency, associated symptoms,
and comorbidities.

Publication Types: 
    Guideline
    Practice Guideline
    Review

PMID: 12484694 [PubMed - indexed for MEDLINE]

2740: Headache. 2002 Jul-Aug;42(7):680-8.

Comment in:
    Headache. 2003 Jul-Aug;43(7):814-5; author reply 815-6.

Comparison of therapeutic gain with therapeutic ratio for the assessment of
selective 5HT(1B/1D) agonist efficacy in migraine.

Fox AW, Keywood C, Sheftell FD, Spierings EL, Winner P.

EBD Group, Carlsbad, CA 92009, USA.

OBJECTIVE: Comparison of use of therapeutic gain (TG) and therapeutic ratio (TR) 
for relative assessments of selective 5HT(1B/1D) agonist efficacy in the acute
treatment of migraine. BACKGROUND: Comparison of selective 5HT(1B/1D) agonist
efficacy in the acute treatment of migraine is complicated by the impracticality 
of conducting high-quality head-to-head active comparator trials for all
permutations of drug, dose, and route of administration; the clinical trials that
are available are usually noncontemporaneous, and have fluctuating active and
placebo response rates (ARR and PRR, respectively) for the necessarily subjective
endpoints. The standard primary endpoint is conversion of headache score 2
(moderate pain) or score 3 (severe pain) into score 0 (no pain) or score 1 (mild 
pain) at a single timepoint (usually 2 or 4 hours postdose). Two principal
methods have been used for comparison of ARR between studies: TG = ARR - PRR and 
TR = ARR/PRR. Secondary endpoints can be treated in the same way, although the
24-hour remedication rate is the only secondary endpoint that is subject to
regulatory authority standardization. Does either TG or TR have an advantage over
the other? METHODS: Efficacy data were collected from published sources and
included pain score conversion at 2- and 4-hour, as well as 24-hour remedication 
rates. TG and TR were calculated for each endpoint, as shown above. The ranges of
these variables were found from all observed measures. Correlations between TG
and TR were found using least squares methods. The 95% confidence intervals (CI) 
for TG and TR were then found for all clinical trials, and for the whole range of
observed PRR. RESULTS: Values for TR and TG generally were well correlated for
pain score conversion at 2 hours postdose (n = 51 clinical trials). Deviations
from this correlation were greatest for drugs that were evidently very
efficacious. When standardized for the observed ranges of PRR and ARR, the 95% CI
for TR were narrower than for TG. A subset of these studies also reported 4-hour 
data (n = 23 clinical trials), but the correlation between TR and TG was again
good, with narrower 95% CI for TR than TG. For the 24-hour remedication data (n =
18 trials), PRR was less variable; TR and TG again correlated well, but there was
little difference in their relative 95% CI. CONCLUSIONS: For comparison of drugs 
in noncontemporaneous studies, when PRR fluctuates, relative ranges for TR are
narrower than for TG. For assessing single clinical trial results (ie, point
estimates of efficacy) TR will generally be relatively nearer to its mean than
TG. For both these reasons, TR is a more robust statistic than TG.

Publication Types: 
    Comparative Study

PMID: 12482223 [PubMed - indexed for MEDLINE]

2741: Headache. 2002 Jul-Aug;42(7):675-9.

Triptans for migraine management in adolescents.

Winner P.

Premier Research Institute, Palm Beach Headache Center, West Palm Beach, Florida 
33407, USA.

OBJECTIVE: To review triptan efficacy and tolerability data for adolescent
migraine sufferers to assist clinicians in selecting triptans for this age group.
BACKGROUND: Migraine is a common cause of headache among adolescents. To date, no
medications, including those with proven headache relief in adults, have been
approved for treatment of migraine in adolescents. METHODS: Recent triptan
clinical trials conducted in adolescent migraine sufferers 12 to 17 years of age 
were reviewed and results were summarized. RESULTS: The success of individual
triptan clinical trials conducted in adolescent appears related to time to
treatment (1.9 to 6 hours), placebo response (25% to 57%), and day of the week
(weekday versus weekend). Overall, triptan tolerability in adolescents is similar
to that reported in adults. CONCLUSION: Study results suggest that the triptan
class of antimigraine drugs may effectively alleviate migraine in adolescents.
Future research should address placebo response and earlier treatment paradigms.

PMID: 12482222 [PubMed - indexed for MEDLINE]

2742: Headache. 2002 Jul-Aug;42(7):646-8.

Auditory hallucinations associated with migraine.

Rubin D, McAbee GN, Feldman-Winter LB.

Division of Child Neurology, Children's Regional Hospital/UMDNJ-Robert Wood
Johnson School of Medicine, Camden, New Jersey 08013, USA.

OBJECTIVE: Two children experienced auditory hallucinations during migraine (one 
with migraine without aura and one with migraine with aura). These hallucinations
only occurred during headache. BACKGROUND: Auditory hallucinations are rarely
reported in patients with migraine. These patients often have other psychiatric
or neurologic disorders such as affective disorder or epilepsy. METHODS: Case
report and a review of the literature. RESULTS: No other neuropsychiatric
disorder was identified in either patient at presentation or upon follow-up.
CONCLUSIONS: Auditory hallucinations can rarely occur in patients with migraine. 
Further study of this association might provide insight to any relationship
between migraine, auditory hallucinations, and the temporal lobe.

Publication Types: 
    Case Reports

PMID: 12482218 [PubMed - indexed for MEDLINE]

2743: Headache. 2002 Jul-Aug;42(7):642-5.

Labetalol for prophylactic treatment of intractable migraine during pregnancy.

Dey R, Khan S, Akhouri V, Wootton J, Bajwa ZH.

Arnold Pain Center, Department of Anesthesia and Critical Care, Beth Israel
Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02115,
USA.

Headaches tend to improve in the majority of migraineurs during pregnancy, but
some patients report a worsening of migraine and present a management challenge
because of the restrictions of pharmacotherapy during pregnancy. Treatment
options become even more limited for pregnant migraineurs who develop
preeclampsia. Labetalol was tried successfully in reducing the frequency,
duration, and intensity of migraine attacks in a pregnant woman with
preeclampsia. There were no significant side effects and the patient delivered a 
healthy baby without complications.

PMID: 12482217 [PubMed - indexed for MEDLINE]

2744: Headache. 2002 Jul-Aug;42(7):620-9.

Prevalence of migraines in NCAA division I male and female basketball players.
National Collegiate Athletic Association.

Kinart CM, Cuppett MM, Berg K.

School of Health, Physical Education, and Recreation, University of Nebraska,
Omaha, Nebraska, USA.

OBJECTIVE: The purpose of this study was to describe the overall prevalence of
migraines within National Collegiate Athletic Association Division I men's and
women's basketball players. In addition, the prevalence of migraines was
determined across gender and ethnic groups for the same sample. BACKGROUND:
Although numerous studies have assessed the prevalence of migraines within the
general population, college students, professional groups, industrial/work place 
settings, and overseas populations, little has been done with athletes. To the
best of our knowledge, no study of the incidence of migraines in athletes has
been previously conducted. It has also been reported that migraines cause
depression, insomnia, fatigue, anorexia, nausea, and vomiting, all of which might
hinder athletic performance. Sports medicine clinicians and researchers also
agree that migraines in athletes are probably underreported and often
misdiagnosed. METHODS: Seven hundred ninety-one Division I men and women
basketball players representing 51 colleges and universities were mailed a
previously validated survey asking questions about headaches. All surveys were
analyzed with a validated diagnostic algorithm consistent with the International 
Headaches Society's (IHS) criteria for headache diagnosis. Descriptive statistics
were used to report the prevalence rate for gender and ethnic groups, as well as 
the entire sample. Chi-square tests were performed (P = 0.05) to determine if
there were any differences in the prevalence of migraines among gender and ethnic
groups. RESULTS: Results showed that 2.9% (n = 23 of 791) of the total sample was
classified as having migraines meeting IHS guidelines. In addition, 0.9% (n = 3
of 332) of men and 4.4% (n = 20 of 459) of women were classified as having
migraines meeting IHS guidelines. Additionally, results showed that women
reported migraines (chi2 = 8.140, P = 0.004) more often than men. When comparing 
the prevalence rates of migraines between ethnic groups, results showed that
Caucasians had a rate of 3.3% (n = 14 of 429), whereas African Americans had a
rate of 3.1% (n = 9 of 287). There was no significant difference found between
ethnic groups in migraine prevalence (chi2 = 2.491, P = 0.2888). CONCLUSIONS: In 
conclusion, it was found that the prevalence of migraines in National Collegiate 
Athletic Association Division I men's and women's basketball players was
generally less than in the general population, that women showed an increased
prevalence of migraines when compared with men, and that Caucasians and African
Americans did not differ in prevalence of migraines.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 12482214 [PubMed - indexed for MEDLINE]

2745: Headache. 2002 Jul-Aug;42(7):596-602.

Central cholinergic challenging of migraine by testing second-generation
anticholinesterase drugs.

Nicolodi M, Galeotti N, Ghelardini C, Bartolini A, Sicuteri F.

Interuniversity Center, Neurochemistry and Clinical Pharmacology of Idiopathic
Headache, Viale G. Pieraccini 18, 1-50139, Florence, Italy.

The antinociceptive activity of donepezil, a novel cholinesterase inhibitor, was 
investigated in the mouse hot plate test. Donepezil (5 to 10 mg kg(-1) i.p.)
induced a dose-dependent antinociception that reached its maximum effect 15
minutes after injection. Donepezil antinociception was prevented by the
antimuscarinic drug scopolamine. At analgesic doses, donepezil did not alter
gross animal behavior. These results indicate that donepezil is endowed by
muscarinic antinociceptive properties, suggesting this compound as a potential
therapeutic approach for the treatment of painful pathologies. Therefore, we
investigated donepezil's effect in migraine. Donepezil (5 mg per os, evening
assumption) was effective as a prophylatic agent in patients suffering from
migraine with or without aura by reducing the number of hours with pain, the
number of attacks, and the severity of the pain attack. The efficacy of donepezil
was compared with that of the beta-blocker propranolol (40 mg bid per os),
showing higher activity. Response rates of a large-sized open study devoid of
entry criteria regarding migraine subtypes suggest the drug as an excellent
prophylactic compound for migraine in general practice. Clinical results also
indicate that the activation of the cholinergic system can represent a novel
prophylactic approach to migraine.

Publication Types: 
    Clinical Trial
    Comparative Study
    Randomized Controlled Trial

PMID: 12482211 [PubMed - indexed for MEDLINE]

2746: Headache. 2002 Jul-Aug;42(7):588-95.

Platelet serotonin measures in migraine.

Jernej B, Vladić A, Cicin-Sain L, Hranilović D, Banović M, Balija M, Bilić E,
Sucić Z, Vukadin S, Grgicević D.

Laboratory of Neurochemistry and Molecular Neurobiology, Rudjer Boskovic
Institute, Bijenicka 54, Zagreb, Croatia.

OBJECTIVE AND BACKGROUND: Serotonergic mechanisms play an important role in the
pathogenesis of headache. To search for potential indicators of altered serotonin
homeostasis in migraine, we have investigated three parameters of the platelet
serotonin (5HT) system, platelet serotonin level (PSL), platelet serotonin uptake
(PSU), and monoamine oxidase (MAO-B) activity, in a group of 55 patients with
migraine and in 81 healthy controls. METHODS: After platelet separation, PSL was 
determined fluorimetrically; PSU was measured by incubating aliquots of
platelet-rich plasma with six concentrations of 14C-5-HT for 60 seconds at 37
degrees C, followed by vacuum filtration; platelet MAO-B activity (toward
kynuramine as a substrate) was determined fluorimetrically. RESULTS: Values of
the investigated measures, in patients versus controls, amounted to (mean +/- SD)
608 +/- 166 vs. 591 +/- 184 ng/10(9) platelets for PSL, 139 +/- 25 vs. 142 +/- 25
pmol 5HT/10(8) platelets/minute for Vmax of PSU, 376 +/- 62 vs. 404 +/- 72 nM for
Km of PSU, and 15.8 +/- 5.1 vs. 14.3 +/- 5.7 nmol product/10(8) platelets/60
minutes for velocity of MAO-B. Mentioned parameters did not show statistical
differences between patients and controls, with exception of a small difference
in Km of PSU, reaching significance (P<0.01). After subgrouping of patients
according to diagnosis (migraine with aura, migraine without aura, and migraine
attack) and gender, no differences retained significance. CONCLUSIONS: Our
results indicate the absence of a measurable disturbance in 5HT homeostasis in
migraine, as shown by platelet 5HT parameters, and they question the suitability 
of the use of mentioned blood elements in this regard.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 12482210 [PubMed - indexed for MEDLINE]

2747: Headache. 2002 Jul-Aug;42(7):582-7.

Effects of fluoxetine on habituation of pattern reversal visually evoked
potentials in migraine prophylaxis.

Ozkul Y, Bozlar S.

University of Harran, Faculty of Medicine, Department of Neurology, Sanliurfa,
Turkey.

OBJECTIVE: To investigate the effects of fluoxetine in migraine prophylaxis on
habituation of visually evoked potentials. BACKGROUND: Habituation of pattern
reversal visually evoked potentials was found to be abnormal in migraine between 
attack, and this abnormality was most likely due to serotonergic pathway
dysfunction in the brain stem. METHODS: One hundred nineteen subjects were
included in the study: 40 healthy volunteers and 79 migraineurs not taking any
prophylactic migraine medication (44 without aura and 35 with aura). Visually
evoked potentials in migraineurs were recorded in the headache-free interval.
Amplitude change of the visually evoked potentials (N1-P1) was measured between
the first and fifth block of 50 sequential averagings during continuous
stimulation at 3.1 Hz. All migraineurs were placed on fluoxetine 20 mg/day for
prophylaxis of migraine. One month later, visually evoked potentials were
recorded again. RESULTS: Mean amplitude changes in the fifth block expressed as
percentages of the first block were -13.4% +/- 19.2% in healthy volunteers, 9.8% 
+/- 23.3% in migraine without aura, and 4.4% +/- 8.7% in migraine with aura
during the baseline period. The difference was significant between migraineurs
and healthy volunteers (both P= 0.0001), but not between migraineur groups. After
treatment, amplitude changes were -9.3% +/- 14.5% in migraine without aura and
-10.1% +/- 11.5% in migraine with aura. Habituation pattern tended to normalize
with prophylactic treatment, and mean amplitude changes were not significant
between migraineurs and healthy volunteers (both P = 0.4). CONCLUSIONS: We
concluded that the fluoxetine prophylaxis corrects the interictal deficit of
habituation in migraineurs.

Publication Types: 
    Clinical Trial
    Comparative Study
    Controlled Clinical Trial

PMID: 12482209 [PubMed - indexed for MEDLINE]

2748: Headache. 2002 Jul-Aug;42(7):575-81.

Chronic daily headache: identification of factors associated with induction and
transformation.

Bigal ME, Sheftell FD, Rapoport AM, Tepper SJ, Lipton RB.

Department of Neurology and Epidemiology, Albert Einstein College of Medicine,
Bronx, New York, USA.

BACKGROUND: Chronic daily headache (CDH) is one of the more frequently
encountered headache syndromes at major tertiary care centers. The analysis of
factors related to the transformation from episodic to chronic migraine (CM) and 
to the de novo development of new daily persistent headache (NDPH) remain poorly 
understood. OBJECTIVES: To identify somatic factors and lifestyle factors
associated with the development of CM and NDPH. METHODS: We used a randomized
case-control design to study the following groups: 1) CM with analgesic overuse
(ARH), n = 399; 2) CM without analgesic overuse, n = 158; and 3) NDPH, n = 69.
These groups were compared with two control groups: 1) episodic migraine, n =
100; and 2) chronic posttraumatic headache (CPTH); n = 65. Associated medical
conditions were assessed. We investigated the case groups for any association
with somatic or behavioral factors. Data were analyzed by the two-sided Fischer's
exact test, with the odds ratio being calculated considering a 95% confidence
interval using the approximation of Woolf. RESULTS: When the active groups were
compared with the episodic migraine group, the following associations were found:
1) ARH: hypertension and daily consumption of caffeine; 2) CM: allergies, asthma,
hypothyroidism, hypertension, and daily consumption of caffeine; and 3) NDPH:
allergies, asthma, hypothyroidism, and consumption of alcohol more than three
times per week. The following associations were found when comparing the active
groups with CPTH: 1) ARH: asthma and hypertension; 2) CM: allergies, asthma,
hypothyroidism, hypertension, and daily consumption of caffeine; and 3) NDPH:
allergies, asthma, hypothyroidism, and consumption of alcohol more than three
times per week. CONCLUSIONS: Several strong correlations were obtained between
patients with specific types of CDH and certain somatic conditions or behaviors; 
some have not been previously described. Transformation of previously episodic
headache or development of a NDPH thus may be related to certain medical
conditions and behaviors beyond the frequently incriminated precipitant analgesic
overuse. As similar results were obtained when CPTH was used as a control, the
correlation is more complex than simple comorbidity.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 12482208 [PubMed - indexed for MEDLINE]

2749: Headache. 2002 Jul-Aug;42(7):566-74.

2002 Wolff Award. 5 -HT2A receptor activation and nitric oxide synthesis: a
possible mechanism determining migraine attacks.

Srikiatkhachorn A, Suwattanasophon C, Ruangpattanatawee U, Phansuwan-Pujito P.

Department of Physiology, King Chulalongkorn Memorial Hospital and Faculty of
Medicine, Chulalongkorn University, Bangkok 10330, Thailand.

OBJECTIVE: To determine the effect of the 5-HT2A receptor in control of spinal
nociception, cerebral circulation, and nitric oxide synthase (nNOS) expression in
trigeminovascular neurons. BACKGROUND: The plasticity of the 5-HT2A receptor is a
possible factor determining the course of migraine. Up-regulation of this
receptor has been demonstrated to correlate with the increasing frequency of
migraine attacks and may underlie the development of chronic daily headache.
METHODS: Adult male Wistar rats were divided into groups receiving the 5-HT2A
agonist, 1,2,5-dimethoxy-4-iodophenyl-2-aminopropane (DOI), nitroglycerin, or
normal saline. The tail flick test and chemical nociception-evoked Fos-expression
in dorsal horn neurons were used as indicators of nociception. Regional cerebral 
blood flow was monitored using laser Doppler flowmetry. Expression of Fos and
nNOS was studied using immunohistochemical method. RESULTS: Administration of DOI
led to the shortening of tail flick latency (1.3 +/- 0.2 and 7.2 +/- 0.6 seconds 
for DOI-treated and control groups, respectively). The number of
Fos-immunoreactive neurons was also greater in the DOI-treated group compared
with the control group. DOI also produced long-lasting cerebral hyperemia (123%
of baseline value) associated with the enlargement of perivascular
nNOS-immunoreactive nerve fibers and increased nNOS-immunoreactive neurons in
trigeminal ganglia and trigeminal nucleus caudalis. These findings resembled
those observed in the rats exposed to nitroglycerin. CONCLUSION: Our results
suggest that activation of the 5-HT2A receptor leads to an enhancement of NO
production in trigeminovascular pathway. NO may trigger migraine attacks by
inducing cerebral vasodilation and sensitizing the perivascular nociceptors and
central nociceptive neurons in trigeminovascular system. Up-regulation of this
pronociceptive receptor can increase headache attacks and contributes to the
development of chronic daily headache.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 12482207 [PubMed - indexed for MEDLINE]

2750: Complement Ther Med. 2002 Jun;10(2):63-8.

Comment in:
    Complement Ther Med. 2002 Jun;10(2):59-60.

Accruing large numbers of patients in primary care trials by retrospective
recruitment methods.

McCarney R, Fisher P, van Haselen R.

Academic Unit, Royal London Homeopathic Hospital, London, UK.
rob.mccarney@parkside.nhs.uk

There is a need for large scale, pragmatic trials of complementary and
alternative medicine in a primary care setting to answer questions about the
'real world' effectiveness of such methods. Randomisation and treatment in such
trials should be prospective, but retrospective recruitment is possible,
especially in chronic conditions. This involves contacting patients who have
previously consulted their GP (identified through GP database searches) rather
than encouraging GPs to refer patients as they present. We describe a prospective
randomised trial of acupuncture for chronic headache, currently underway, as an
example of retrospective recruitment. A pilot study of recruitment and
recruitment modelling was undertaken. The target sample size was 300, 26% (n =
36) of general practices approached took part in the study, 32 completed the
required database search. Practices used diagnostic term searches, prescription
searches, or a combination of both. On average 1.7% of the total practice
populations were identified as headache consulters, letters were sent to 4128
patients. 12% of identified patients were randomised (n = 401). Retrospective
recruitment methods are feasible for CAM trials in chronic, stable conditions
modelling can provide accurate data for planning such studies. Retrospective
recruitment can be more efficient than prospective, further research is required 
on the generalisibility of results from populations recruited in this way.

Publication Types: 
    Clinical Trial
    Comparative Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 12481953 [PubMed - indexed for MEDLINE]

2751: Neurology. 2002 Dec 10;59(11):1677-81.

Prophylaxis of menstrual migraine with triptans: problems and possibilities.

Loder E.

Harvard Medical School and Pain and Headache Management Programs, Spaulding
Rehabilitation Hospital, Boston, MA, USA. eloder@partners.org

Menstruation is a prominent, predictable attack trigger for many women with
migraine. If abortive therapy of menstrual attacks is ineffective, prophylactic
therapy is used to prevent attacks or render them shorter and less resistant to
acute therapy. Interest is increasing in the use of triptan medications for the
prophylaxis of menstrual migraine, and clinical trials to evaluate this approach 
are underway. Potential problems with triptan prophylaxis of menstrual migraine
that deserve attention include the lack of consensus on the definition of
menstrual migraine and the difficulty in making a reliable diagnosis of the
disorder. Unconvincing demonstrations of efficacy and unresolved cost and safety 
concerns should temper enthusiasm for their use in this manner. Further studies, 
using a consistent definition of menstrual association and employing diary
validation of the diagnosis, are needed to determine the efficacy of the triptans
in women who consistently experience migraine attacks associated with
menstruation. Triptans would have to show compelling advantages over other
therapy to be a plausible prophylactic treatment for menstrual migraine.

Publication Types: 
    Review

PMID: 12481795 [PubMed - indexed for MEDLINE]

2752: Bipolar Disord. 2002 Oct;4(5):290-5.

Laterality of pain in migraine with comorbid unipolar depressive and bipolar II
disorders.

Fasmer OB, Oedegaard KJ.

Department of Psychiatry, University of Bergen, Haukeland Hospital, Bergen,
Norway. ole.fasmer@psyk.uib.no

OBJECTIVES: The purpose of the present study has been to examine differences in
the laterality of pain in patients with migraine and comorbid unipolar depressive
(UP) and bipolar II (BP II) disorders. METHODS: Semi-structured interviews of 102
patients with major affective disorders were conducted, using DSM-IV criteria for
affective disorders combined with Akiskal's criteria for affective temperaments
and International Headache Society criteria for migraine. The group of patients
reported on in the present study encompass 47 subjects with UP (n = 24) or BP 11 
(n = 23) disorders. Fifteen of the bipolar II patients fulfilled DSM-IV criteria 
while eight were diagnosed according to the broader criteria of Akiskal. RESULTS:
Sixteen of the 38 patients with migraine headaches had bilateral pain or pain
equally often on the left or right side while 22 had pain predominantly located
on one side. Among the UP patients the pain was most often on the right side
(8/10) while among the BP II patients the pain was most often on the left (9/12, 
p = 0.01). Apart from the presence of hypomanic symptoms in the BP II group there
were no clinical or demographic characteristics that distinguished these two
sub-groups of affective disorders. CONCLUSIONS: These results indicate that there
may be a differential affection of the cerebral hemispheres in patients with
migraine and comorbid unipolar depressive disorder versus patients with migraine 
and comorbid bipolar II disorder.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 12479660 [PubMed - indexed for MEDLINE]

2753: Brain. 2003 Jan;126(Pt 1):241-7.

Migraine can be induced by sildenafil without changes in middle cerebral artery
diameter.

Kruuse C, Thomsen LL, Birk S, Olesen J.

Department of Neurology, Glostrup Hospital, University of Copenhagen, Glostrup,
Copenhagen, Denmark. ckruuse@dadlnet.dk

Migraine is considered a neurovascular disease involving dilatation of cerebral
arteries. Nitric oxide (NO) donors induce dilatation of cerebral and extracranial
arteries and migraine, but NO has several mechanisms of action in addition to its
cyclic guanosine monophosphate (cGMP)-mediated vasodilatation. We examined
whether sildenafil (Viagra), a selective inhibitor of cGMP-hydrolysing
phosphodiesterase 5 (PDE5), which acts exclusively by increasing cGMP, can induce
migraine and dilatation of cerebral arteries. We included 12 patients with
migraine without aura in this double-blind, placebo-controlled crossover study,
in which placebo or sildenafil 100 mg was administered orally on two separate
days. Blood flow velocity in the middle cerebral artery (V(mca)) was recorded by 
transcranial Doppler ultrasonography and regional cerebral blood flow in the
territory of the middle cerebral artery (rCBF(mca)) was measured using SPECT
(single photon emission computed tomography) and xenon 133 inhalation. Radial and
temporal artery diameters were studied using high-frequency ultrasonography.
Headache response, tenderness of pericranial muscles, blood pressure and heart
rate were measured repeatedly. We found that migraine attack was induced by
sildenafil in 10 of 12 migraine patients and by placebo in two of 12 patients (P 
= 0.01). V(mca) (P = 0.1) and rCBF(mca) (P = 0.93) remained unchanged after
sildenafil. Temporal (P = 0.47) and radial (P = 0.87) artery diameter and
pericranial tenderness (P = 0.16) were unaffected by sildenafil. Systolic and
diastolic blood pressures were unchanged but heart rate increased from a mean of 
62 +/- 2 to 74 +/- 3 beats/min (P = 0.01) after sildenafil. Our results
demonstrate that migraine may be induced via a cGMP-dependent mechanism, and we
show for the first time that this occurs without initial dilatation of the middle
cerebral artery. We propose that triggering mechanisms may reside within the
perivascular sensory nerve terminals or the brainstem. However, other sites of
action may also be possible and future studies are needed to elucidate this. In
the clinical use of sildenafil, patients who have migraine should be informed
about the risk of migraine attacks.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 12477710 [PubMed - indexed for MEDLINE]

2754: Am J Hum Genet. 2003 Jan;72(1):161-7. Epub 2002 Dec 9.

A locus for migraine without aura maps on chromosome 14q21.2-q22.3.

Soragna D, Vettori A, Carraro G, Marchioni E, Vazza G, Bellini S, Tupler R,
Savoldi F, Mostacciuolo ML.

Neurological Institute C. Mondino I.R.C.C.S., Department of Neurological
Sciences, University of Pavia, Pavia, Italy. debora.soragna@unipv.it

Migraine is a common and disabling neurological disease of unknown origin
characterized by a remarkable clinical variability. It shows strong familial
aggregation, suggesting that genetic factors are involved in its pathogenesis.
Different approaches have been used to elucidate this hereditary component, but a
unique transmission model and causative gene(s) have not yet been identified. We 
report clinical and molecular data from a large Italian pedigree in which
migraine without aura (MO) segregates as an autosomal dominant trait. After
exclusion of any association between MO and the known familial hemiplegic
migraine and migraine with aura loci, we performed a genomewide linkage analysis 
using 482 polymorphic microsatellite markers. We obtained significant evidence of
linkage between the MO phenotype and the marker D14S978 on 14q22.1 (maximum
two-point LOD score of 3.70, at a recombination fraction of 0.01). Multipoint
parametric analysis (maximum LOD score of 5.25 between markers D14S976 and
D14S978) and haplotype construction showed strong evidence of linkage in a region
of 10 cM flanked by markers D14S1027 and D14S980 on chromosome 14q21.2-q22.3.
These results indicate the first evidence of a genetic locus associated with MO
on chromosome 14.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 12474141 [PubMed - indexed for MEDLINE]

2755: Neurology. 2002 Dec 10;59(11):1804-7.

Identification of a susceptibility locus for migraine with and without aura on
6p12.2-p21.1.

Carlsson A, Forsgren L, Nylander PO, Hellman U, Forsman-Semb K, Holmgren G,
Holmberg D, Holmberg M.

Umeå Centre for Molecular Medicine, University of Umeå, Sweden.

Migraine is the most common type of chronic episodic headache. To find novel
susceptibility genes for familial migraine with and without aura, a genomewide
screen was performed in a large family from northern Sweden. Evidence of linkage 
was obtained on chromosome 6p12.2-p21.1, with a maximum two-point lod score of
5.41 for marker D6S452. The patients with migraine shared a common haplotype of
10 Mb between markers D6S1650 and D6S1960.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 12473779 [PubMed - indexed for MEDLINE]

2756: Neurology. 2002 Dec 10;59(11):1700-4.

Migraine and Ménière's disease: is there a link?

Radtke A, Lempert T, Gresty MA, Brookes GB, Bronstein AM, Neuhauser H.

Neurologische Klinik, Charité, Humboldt-Universität, Berlin, Germany.
andrea.radtke@charite.de

BACKGROUND: A possible link between Ménière's disease (MD) and migraine was
originally suggested by Prosper Ménière. Subsequent studies of the prevalence of 
migraine in MD produced conflicting results. OBJECTIVE: To determine the lifetime
prevalence of migraine in patients with MD compared to sex- and age-matched
controls. METHODS: The authors studied 78 patients (40 women, 38 men; age range
29 to 81 years) with idiopathic unilateral or bilateral MD according to the
criteria of the American Academy of Otolaryngology. Diagnosis of migraine with
and without aura was made via telephone interviews according to the criteria of
the International Headache Society. Additional information was obtained
concerning the concurrence of vertigo and migrainous symptoms during Ménière
attacks. The authors interviewed sex- and age-matched orthopedic patients (n =
78) as controls. RESULTS: The lifetime prevalence of migraine with and without
aura was higher in the MD group (56%) compared to controls (25%; p < 0.001).
Forty-five percent of the patients with MD always experienced at least one
migrainous symptom (migrainous headache, photophobia, aura symptoms) with Ménière
attacks. CONCLUSIONS: The lifetime prevalence of migraine is increased in
patients with MD when strict diagnostic criteria for both conditions are applied.
The frequent occurrence of migrainous symptoms during Ménière attacks suggests a 
pathophysiologic link between the two diseases. Alternatively, because migraine
itself is a frequent cause of audio-vestibular symptoms, current diagnostic
criteria may not differentiate between MD and migrainous vertigo.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 12473755 [PubMed - indexed for MEDLINE]

2757: Clin Otolaryngol Allied Sci. 2002 Dec;27(6):521-5.

Facial migraine in a rhinological setting.

Daudia AT, Jones NS.

Department of Otorhinolaryngology, Head and Neck Surgery, University of
Nottingham, Nottingham, UK.

This study aims to investigate the incidence of migraine involving the face in a 
rhinology clinic and to describe its characteristics. It is a study of a cohort
of 973 patients consecutively presenting to the outpatient clinic with symptoms
of facial pain and/or rhinosinusitis. The study subgroup consisted of patients
with facial pain and migraine excluding cluster headache and paroxysmal
hemicrania. We studied the features of 51 patients who had facial pain with
migraine. The diagnosis was based on the criteria used by the International
Headache Society and was also supported by the outcome and response to treatment 
after a mean of 2 years and 2 months. Of the 973 consecutive patients, 409 (42%) 
had symptoms of facial pain and/or head pain or pressure. Fifty-one (12%) had
migraine. Of these, 39 (76%) had unilateral pain and, in 12 (24%), it was
bilateral. The distribution affected the forehead and/or eye or cheek in 32 (63%)
patients. Twenty-four (47%) had migraine isolated to the second division of the
trigeminal nerve. Twelve per cent of patients attending a rhinology clinic with
facial pain had migraine. Of particular interest were the 6% of patients with
facial pain who had migraine confined to the second division of the trigeminal
nerve. This entity is not widely recognized and has rarely been described in the 
literature.

PMID: 12472524 [PubMed - indexed for MEDLINE]

2758: Clin Otolaryngol Allied Sci. 2002 Dec;27(6):472-9.

Paroxysmal hemicrania and cluster headache: two discrete entities or is there an 
overlap?

Fuad F, Jones NS.

Department of Otorhinolaryngology, Head and Neck Surgery, University of
Nottingham, Nottingham, UK.

Paroxysmal hemicrania has been described as an excruciating unilateral pain,
which is usually ocular and frontotemporal with short-lasting (2-45 min),
frequent attacks (usually more than five per day); with marked autonomic features
(rhinorrhoea, nasal congestion, conjunctival injection, lacrimation) and
unilateral to the pain. A response to indomethacin is essential using the current
criteria for the diagnosis. It is a rare condition but when it occurs it is
misdiagnosed as being due to sinusitis. A retrospective analysis of 11 patients
seen in the period 1995-2001 suggests that there is an overlap between paroxysmal
hemicrania and cluster headache. Four patients had all the characteristics of
paroxysmal hemicrania and responded to indomethacin. Four other patients
fulfilled the criteria except for the frequency and length of the attacks. They
only had one attack per day and these lasted more than 2 h. Another patient had
all the symptoms of paroxysmal hemicrania and did not respond to indomethacin,
but responded to triptans and pizotifen. Patients with cluster headache typically
respond to these. Two patients were unable to continue taking indomethacin owing 
to severe gastrointestinal upset. In the same period, we also had 30 patients
with cluster headaches. There is increasing evidence that paroxysmal hemicrania
and cluster headache share a similar pathogenesis and that they may not always be
so discrete in either their response to indomethacin or their periodicity.

PMID: 12472514 [PubMed - indexed for MEDLINE]

2759: Int J Clin Pract. 2002 Nov;56(9):704-9.

Sumatriptan nasal spray for migraine: a review of studies in patients aged 17
years and younger.

Hämäläinen M, Jones M, Loftus J, Saiers J.

Helsinki University Central Hospital for Children and Adolescents, Helsinki,
Finland.

This review considers the epidemiology, clinical manifestations and functional
consequences of migraine in children and adolescents and surveys the studies
establishing the efficacy and tolerability of sumatriptan nasal spray in this
patient population. Although therapeutic advances in paediatric and adolescent
migraine have lagged behind those in adult migraine, the first systematic studies
of migraine medications in young patients have brought about progress in the past
five years. These studies show that therapeutic approaches suitable for adult
patients are not always applicable to paediatric and adolescent patients. Because
of the unique characteristics of paediatric and adolescent migraine, it has been 
difficult to demonstrate in young patients the efficacy of oral sumatriptan and
other triptan tablets, which are the medications of choice for adult migraine.
With sumatriptan, this finding has proven to be a consequence of the form in
which the drug was administered rather than the inherent properties of the drug. 
The availability of sumatriptan nasal spray allows the benefits of
migraine-specific therapy to be extended to children and adolescents. In both
well-controlled, single-episode studies and long-term, multiple-episode studies, 
sumatriptan nasal spray has been effective and well tolerated for the acute
treatment of migraine in children and adolescents. Except for unpleasant taste,
which is not significantly distressing to patients, sumatriptan nasal spray has a
tolerability profile similar to thatof placebo in young patients.

Publication Types: 
    Review

PMID: 12469987 [PubMed - indexed for MEDLINE]

2760: Br J Pharmacol. 2002 Dec;137(8):1287-97.

The antimigraine 5-HT 1B/1D receptor agonists, sumatriptan, zolmitriptan and
dihydroergotamine, attenuate pain-related behaviour in a rat model of trigeminal 
neuropathic pain.

Kayser V, Aubel B, Hamon M, Bourgoin S.

NeuroPsychoPharmacologie Moléculaire, Cellulaire et Fonctionnelle, INSERM U288,
Faculté de Médecine Pitié-Salpêtrière, 91 Boulevard de l'Hôpital, 75634 Paris
Cedex 13, France. kayser@ext.jussieu.fr

1. Peripheral lesion to the trigeminal nerve may induce severe pain states.
Several lines of evidence have suggested that the antimigraine effect of the
triptans with 5-HT(1B/1D) receptor agonist properties may result from inhibition 
of nociceptive transmission in the spinal nucleus of the trigeminal nerve by
these drugs. On this basis, we have assessed the potential antinociceptive
effects of sumatriptan and zolmitriptan, compared to dihydroergotamine (DHE), in 
a rat model of trigeminal neuropathic pain. 2. Chronic constriction injury was
produced by two loose ligatures of the infraorbital nerve on the right side.
Responsiveness to von Frey filament stimulation of the vibrissal pad was used to 
evaluate allodynia. 3. Two weeks after ligatures, rats with a chronic
constriction of the right infraorbital nerve displayed bilateral mechanical
hyper-responsiveness to von Frey filament stimulation of the vibrissal pad with a
mean threshold of 0.38+/-0.04 g on the injured side and of 0.43+/-0.04 g on the
contralateral (left) side (versus > or =12.5 g on both sides in the same rats
prior to nerve constriction injury). 4. Sumatriptan at a clinically relevant dose
(100 microg kg(-1), s.c.) led to a significant reduction of the mechanical
allodynia-like behaviour on both the injured and the contralateral sides
(peak-effects 6.3+/-1.1 g and 4.4+/-0.7 g, respectively). A more pronounced
effect was obtained with zolmitriptan (100 microg kg(-1), s.c.) (peak-effects:
7.4+/-0.9 g and 3.2+/-1.3 g) whereas DHE (50-100 microg kg(-1), i.v.) was less
active (peak-effect approximately 1.5 g). 5. Subcutaneous pretreatment with the
5-HT(1B/1D) receptor antagonist, GR 127935 (3 mg kg(-1)), prevented the
anti-allodynia-like effects of triptans and DHE. Pretreatment with the 5-HT(1A)
receptor antagonist, WAY 100635 (2 mg kg(-1), s.c.), did not alter the effect of 
triptans but significantly enhanced that of DHE (peak effect 4.3+/-0.5 g). 6. In 
a rat model of peripheral neuropathic pain, which consisted of a unilateral loose
constriction of the sciatic nerve, neither sumatriptan (50-300 microg kg(-1)) nor
zolmitriptan (50-300 microg kg(-1)) modified the thresholds for paw withdrawal
and vocalization in response to noxious mechanical stimulation. 7. These results 
support the rationale for exploring the clinical efficacy of brain penetrant
5-HT(1B/1D) receptor agonists as analgesics to reduce certain types of trigeminal
neuropathic pain in humans.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 12466238 [PubMed - indexed for MEDLINE]

2761: Eur Neurol. 2003;49(1):20-9.

Crossover comparison of efficacy and preference for rizatriptan 10 mg versus
ergotamine/caffeine in migraine.

Christie S, Göbel H, Mateos V, Allen C, Vrijens F, Shivaprakash M;
Rizatriptan-Ergotamine/Caffeine Preference Study Group.

Ottawa Headache Centre, Ottawa, Canada.

Rizatriptan is a selective 5-HT(1B/1D) receptor agonist with rapid oral
absorption and early onset of action in the acute treatment of migraine. This
randomized double- blind crossover outpatient study assessed the preference for 1
rizatriptan 10 mg tablet to 2 ergotamine 1 mg/caffeine 100 mg tablets in 439
patients treating a single migraine attack with each therapy. Of patients
expressing a preference (89.1%), more than twice as many preferred rizatriptan to
ergotamine/caffeine (69.9 vs. 30.1%, p < or = 0.001). Faster relief of headache
was the most important reason for preference, cited by 67.3% of patients
preferring rizatriptan and 54.2% of patients who preferred ergotamine/caffeine.
The co-primary endpoint of being pain free at 2 h was also in favor of
rizatriptan. Forty-nine percent of patients were pain free 2 h after rizatriptan,
compared with 24.3% treated with ergotamine/caffeine (p < or = 0.001),
rizatriptan being superior within 1 h of treatment. Headache relief at 2 h was
75.9% for rizatriptan and 47.3% for ergotamine/caffeine (p < or = 0.001), with
rizatriptan being superior to ergotamine/caffeine within 30 min of dosing. Almost
36% of patients taking rizatriptan were pain free at 2 h and had no recurrence or
need for additional medication within 24 h, compared to 20% of patients on
ergotamine/caffeine (p < or = 0.001). Rizatriptan was also superior to
ergotamine/caffeine in the proportions of patients with no nausea, vomiting,
phonophobia or photophobia and for patients with normal function 2 h after drug
intake (p < or = 0.001). More patients were (completely, very or somewhat)
satisfied 2 h after treatment with rizatriptan (69.8%) than at 2 h after
treatment with ergotamine/caffeine (38.6%, p < or = 0.001). Recurrence rates were
31.4% with rizatriptan and 15.3% with ergotamine/caffeine. Both active treatments
were well tolerated. The most common adverse events (incidence > or = 5% in one
group) after rizatriptan and ergotamine/caffeine, respectively, were dizziness
(6.7 and 5.3%), nausea (4.2 and 8.5%) and somnolence (5.5 and 2.3%). Copyright
2003 S. Karger AG, Basel

Publication Types: 
    Clinical Trial
    Comparative Study
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 12464714 [PubMed - indexed for MEDLINE]

2762: Curr Med Res Opin. 2001;17 Suppl 1:s87-93.

Comment in:
    Curr Med Res Opin. 2001;17 Suppl 1:s1-3.

Migraine: preventive treatment.

Silberstein SD.

Jefferson Headache Center, Thomas Jefferson University Hospital, Philadelphia,
PA, USA. stephen.silberstein@mail.tju.edu

Preventive treatment is designed to decrease headache frequency. It should be
used if headaches are too frequent, disabling, or associated with worrisome
neurological features or if acute treatment is overused or ineffective. The
chosen drug should be given an adequate trial in the absence of interfering
medications. Choose a drug based on its efficacy, adverse event profile, and the 
presence of coexistent conditions.

Publication Types: 
    Review

PMID: 12463285 [PubMed - indexed for MEDLINE]

2763: Curr Med Res Opin. 2001;17 Suppl 1:s81-6.

Acute treatments: future developments.

Ramadan NM.

Lilly Research Laboratories, Eli Lilly & Co. and Indiana University School of
Medicine, Indianapolis, Indiana 46285, USA. ramadan@lilly.com

In Chapter 14, blind alleys in acute anti-migraine drug development were
discussed. In this chapter, future therapies are covered. There is growing
interest and support for the use of CGRP antagonists, nitric oxide synthase
inhibitors, and ionotropic glutamate receptor antagonists. The hope is to strike 
the balance of high efficacy with minimal to no safety concern and good
tolerability. Some of the targets discussed in this chapter have been in early
efficacy trials and others are in first human dose stages. Large-scale efficacy
and safety trials are eagerly awaited.

Publication Types: 
    Review

PMID: 12463284 [PubMed - indexed for MEDLINE]

2764: Curr Med Res Opin. 2001;17 Suppl 1:s71-80.

Comment in:
    Curr Med Res Opin. 2001;17 Suppl 1:s1-3.

Acute treatments: some blind alleys.

Ramadan NM.

Lilly Research Laboratories, Eli Lilly & Co. and Indiana University School of
Medicine, Indianapolis, Indiana 46285, USA. ramadan@lilly.com

The introduction of sumatriptan, a selective 5-HT(1B/1D) agonist, for the
treatment of migraine sparked a new era of drug research in this field. Many
novel targets have since been developed, and tested in the clinic. The promise of
these approaches is to deliver an anti-migraine compound with the optimal
efficacy and safety profile. In this chapter, blind alleys in anti-migraine
development are discussed. The failing soldiers have included the NK-1
antagonists, some second-generation 5-HT(1B/1D) agonists, CP-122,288, 4991W93,
the neurosteroid ganaxolone, selective 5-HT(1F) (LY334370) and 5-HT(1D) agonists 
(PNU-142,633), and the endothelin-1 antagonist bosentan. Some of these promising 
targets failed to demonstrate clinical efficacy, while others were stopped for
preclinical toxicity.

Publication Types: 
    Review

PMID: 12463283 [PubMed - indexed for MEDLINE]

2765: Curr Med Res Opin. 2001;17 Suppl 1:s68-70.

Frovatriptan: pharmacological differences and clinical results.

Rapoport AM.

The New England Center for Headache, P.C., Stamford, CT 06902-1251,.
nervel@webquill.com

Frovatriptan is a 5-HT(1B/1D) agonist demonstrating consistently effective
headache relief at a low dose of 2.5 mg. A striking pharmacokinetic
characteristic is its long half-life of 25 h. This is balanced by an average Tmax
of 2-3 h, a low degree of lipophilicity and a low oral bioavailability of 24-30%.
Fifty per cent of the drug is renally excreted and the rest is partially
metabolized by P450 CYP 1A2. In three short-term multicentre, double-blind,
placebo-controlled phase III trials, the 2 h headache response for 2.5 mg
frovatriptan varied from 36 to 46% (placebo 21-27%). The 4 h headache responses
were considerably higher--up to 65%. Thirty-five per cent of patients were
consistent rapid responders. The recurrence rate was 10-25%. In addition to
effective and prolonged relief of head pain, frovatriptan reduced associated
migraine symptoms such as nausea, photophobia and phonophobia. There was an
excellent tolerability profile with the incidence of adverse events for
frovatriptan only slightly higher than placebo. The most commonly reported
adverse events for both frovatriptan and placebo were dizziness, nausea, headache
and fatigue.

Publication Types: 
    Review

PMID: 12463282 [PubMed - indexed for MEDLINE]

2766: Curr Med Res Opin. 2001;17 Suppl 1:s63-7.

Almotriptan: pharmacological differences and clinical results.

Pascual J.

Service of Neurology, University Hospital Marqués de Valdecilla, Santander,
Spain. pascualj@unican.es

In this manuscript we review the key basic and clinical data of almotriptan, the 
new selective 5-HT(1B/D) agonist developed for the symptomatc treatment of
migraine. Among triptans, almotriptan has the highest oral bioavailability, with 
more than two-thirds of the administered dose absorbed within the first hourboth 
inside and outside a migraine attack. Gender or the presence of food in the
stomach do not influence this pharmacokinetic profile, and its clean metabolism
results in no relevant interactions with other medications. The dose exhibiting
the best efficacy/ tolerability ratio is 12.5 mg. Efficacy parameters with this
dose are very comparable to those of sumatriptan 100 mg, with a recurrence rate
in the lower range. The tolerability of almotriptan is similar to that for
placebo. The incidence of chest symptoms is very low (<1%), even though this drug
remains contraindicated in patients with ischaemic cardiomyopathy. In summary,
almotriptan's promising basic profile together with its excellent
tolerability/safety profile and good efficacy confirm this new 5-HT(1B/D) agonist
as a drug of choice for the symptomatic treatment of migraine attacks.

Publication Types: 
    Review

PMID: 12463281 [PubMed - indexed for MEDLINE]

2767: Curr Med Res Opin. 2001;17 Suppl 1:s59-62.

Eletriptan: pharmacological differences and clinical results.

Giffin N.

National Hospital, Queen Square, London, UK. n.giffin@ion.ucl.ac.uk

The potential advantages of eletriptan lie firstly in its lipophilicity reflected
as an increased rate of absorption and Tmax compared to sumatriptan. This is
manifested in a modest advantage over sumatriptan in terms of speed of onset, 2 h
headache response and 2 h pain free. However, eletriptan has not yet been shown
to have an advantage over the other triptans for lack of head-to head
comparisons. It does not appear to have an advantage over sumatriptan for
headache recurrence. The second advantage is the partial agonist activity at the 
5-HT(1B) receptor, reducing the potential for cardiovascular side-effects
compared to the other triptans. Although no serious cardiovascular events have
yet been recognized, eletriptan should still be used with extreme caution for
patients with cardiovascular risk factors.

Publication Types: 
    Review

PMID: 12463280 [PubMed - indexed for MEDLINE]

2768: Curr Med Res Opin. 2001;17 Suppl 1:s54-8.

Rizatriptan: pharmacological differences from sumatriptan and clinical results.

Lines CR, McCarroll KA, Visser WH.

Merck Research Laboratories, West Point, PA, USA. chris_lines@merck.com

Rizatriptan and sumatriptan are selective 5-HT(1B/1D) receptor agonists for
theacute treatment of migraine. For oral formulations, the time to maximum plasma
concentration is reached earlier with rizatriptan than with sumatriptan (1 h
versus 2-2.5 h) and rizatriptan has greater bioavailability than sumatriptan (45%
versus 15%). These pharmacological advantages appear to translate into a faster
onset of action and a better overall response for oral rizatriptan versus oral
sumatriptan. The two drugs have been directly compared in randomized,
double-blind, placebo-controlled clinical trials of patients with moderate or
severe migraine attacks. Rizatriptan 10 mg was generally superior to sumatriptan 
on a measure of time-to-pain-relief within 2 h, where pain relief was defined as 
a reduction of pain to mild or none (odds ratio for rizatriptan versus
sumatriptan 100 mg = 1.21; odds ratios for rizatriptan 10 mg versus sumatriptan
50 mg = 1.14 and 1.10 in two studies). Rizatriptan 10 mg was also superior to
sumatriptan on the International Headache Society recommended endpoint of the
percentage of patients pain free at 2 h (40% for rizatriptan 10 mg, 33% for
sumatriptan 100 mg, and 35% for sumatriptan 50 mg). Further advantages for
rizatriptan were seen on stringent outcome measures of the percentage of patients
who were completely free of all symptoms at 2 h, patient satisfaction with
medication at 2 h, and 24-h sustained pain-free response. 5-HT(1B/1D) receptor
agonists are contraindicated in patients with coronary artery disease because of 
their potential to cause vasoconstriction. In clinical trials which excluded such
patients, rizatriptan and sumatriptan were both well-tolerated. The most common
side-effects on both drugs occurred in <10% of patients and consisted of
dizziness, drowsiness, and asthenia/fatigue. The adverse events were usually mild
or moderate in severity and short-lasting.

Publication Types: 
    Review

PMID: 12463279 [PubMed - indexed for MEDLINE]

2769: Curr Med Res Opin. 2001;17 Suppl 1:s51-3.

Naratriptan.

Massiou H.

Hĵpital Lariboisière, Paris, France. hmassiou@club-internet.fr

Naratriptan is a selective 5-HT(1B/1D) receptor agonist, with a high affinity at 
the 5-HT(1B), 5-HT(1D) and 5-HT(1F) receptor subtypes. Naratriptan contracts a
number of large isolated cerebral arteries from several species, and has little
contractile effect on peripheral blood vessels. It has an inhibitory effect on
the cranial neurogenic inflammation model. The clinically recommended dose is 2.5
mg. It was found significantly superior to placebo on headache relief and pain
free at 2 and 4 hours, and in relieving nausea, photophobia and phonophobia. It
also has a good within-patient consistency, and a low recurrence rate. The
side-effect profile is that of the triptan class, wih an incidence no different
from placebo at the 25 mg dose. The contraindications are similar to any triptan,
including coronary disease. Naratriptan is unlikely to affect metabolism of other
drugs. In comparison sumatriptan 100 mg, naratriptan 2.5 mg has a slower onset of
action and a lower response rate at 4 h, but it has a lower recurrence rate, and 
is better tolerated.

Publication Types: 
    Review

PMID: 12463278 [PubMed - indexed for MEDLINE]

2770: Curr Med Res Opin. 2001;17 Suppl 1:s46-50.

Zolmitriptan: differences from sumatriptan.

Goadsby PJ, Boes CJ.

Institute of Neurology, The National Hospital for Neurology and Neurosurgery,
Queen Square, London, UK. peterg@ion.ucl.ac.uk

Zolmitriptan is a potent 5-HT(1B/1D) agonist whose targets include the peripheral
and central components of the trigeminovascular system. It is generally
well-tolerated and has dose-dependent efficacy in the treatment of migraine. The 
2.5 mg dose is felt to provide the best balance between efficacy and adverse
events. In a direct comparative study, the 2 h headache response rate for
zolmitriptan 2.5 mg was statistically superior to sumatriptan 25 and 50 mg,
although at 3.3% not clinically significant. Two comparative studies have found
no difference in adverse event frequency between zolmitriptan and sumatriptan.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 12463277 [PubMed - indexed for MEDLINE]

2771: Curr Med Res Opin. 2001;17 Suppl 1:s35-45.

Sumatriptan: pharmacological basis and clinical results.

Dahlöf CG.

Gothenburg Migraine Clinic, Gothenburg, Sweden. carl.dahlof@migraineclinic.se

Sumatriiptan was the first selective serotonin (5-HT)1B/1D agonist for the acute 
treatment of migraine attacks. Apart from the subcutaneous and oral formulation, 
it is also available as nasal spray and suppository. In placebo-controlled
clinical trials, sumatriptan, administered subcutaneously, orally, intranasally
or rectally was significantly more effective than placebo in relieving migraine
headache and in producing relief or resolution of other symptoms associated with 
migraine, including nausea, photophobia and phonophobia. For patients who desire 
particularly rapid relief that cannot be provided by a tablet form, sumatriptan
injection with a 10-minute onset of action may be an appropriate choice. Patients
with very severe attacks and those with vomiting may also benefit from the
injection. For patients with nausea who do not wish to take tablets or who fear
injections, a sumatriptan nasal spray or a suppository may be appropriate
options. New triptans, zolmitriptan, rizatriptan, and naratriptan began entering 
the market in 1997 but in clinical practice, in particular after dose adjustments
have been made, all triptans appear to be very similar with respect to efficacy
and tolerability as well as safety.

Publication Types: 
    Review

PMID: 12463276 [PubMed - indexed for MEDLINE]

2772: Curr Med Res Opin. 2001;17 Suppl 1:s30-4.

Ergotamine, dihydroergotamine: current uses and problems.

Tfelt-Hansen P.

Department of Neurology, Glostrup Hospital, Glostrup, Denmark. tfelt@inet.uni2.dk

In randomized clinical trials oral ergotamine was found superior to placebo but
inferior to oral sumatriptan 100mg. In contrast rectal ergotamine was found to
have higher efficacy (73% headache relief) than rectal sumatriptan (63% headache 
relief). Intranasal dihydroergotamine (DHE) was found superior to placebo but
less effective than subcutaneous and intranasal sumatriptan. In general, the use 
of the more specific drugs, the triptans, causing less adverse events and being
more effective, is preferable to the use of the ergotamine in the acute treatment
of migraine. If ergotamine is to be used the rectal route is preferable. The
rectal dose of ergotamine should be tailored to the individual patient. The
intranasal dose of DHE , between 1 and 2 mg, should also be tailored to the
individual patient. In order to avoid drug-induced headache ergotamine and DHE
should not be used daily.

Publication Types: 
    Review

PMID: 12463275 [PubMed - indexed for MEDLINE]

2773: Curr Med Res Opin. 2001;17 Suppl 1:s26-9.

Non-steroidal anti-inflammatory drugs in the treatment of migraine.

Rasmussen MK, Binzer M.

MJR@RibeAmt.dk

NSAIDs can be used in both the acute and prophylactic treatment of migraine with 
and without aura. It is a safe therapeutic alternative fore young healthy
patients, but should be used with caution in the elderly. NSAIDs do not influence
blood pressure and can be used in combination with most other migraine agents.
The selective COX-2 inhibitors are an interesting therapeutic possbility for the 
future.

Publication Types: 
    Review

PMID: 12463274 [PubMed - indexed for MEDLINE]

2774: Curr Med Res Opin. 2001;17 Suppl 1:s22-5.

Anti-emetics.

MacGregor EA.

The City of London Migraine Clinic, London, UK. migraine@colmc.org.uk

Nausea and vomiting are common symptoms of migraine, which can be controlled with
a variety of anti-emetics including phenothiazines and antihistamines.
Metoclopramide and domperidone have an additional prokinetic effect which may be 
important in migraine to overcome gastric stasis and enhance absorption of oral
medication.

Publication Types: 
    Review

PMID: 12463273 [PubMed - indexed for MEDLINE]

2775: Curr Med Res Opin. 2001;17 Suppl 1:s17-21.

Medication overuse headache.

Diener HC, Katsarava Z.

Department of Neurology, University of Essen, Germany. h.diener@uni-essen.de

The frequent use (>15 times/month) of medication for the treatment of acute
migraine attacks may cause medication overuse headache. This kind of headache can
be caused by the intake of a combination of analgesics, opioids, ergot alkaloids 
and triptans. The delay between first intake and these attacks is shortest for
triptans (1-2 years), longer for ergots (3-5 years) and longest for analgesics
(5-10 years). Treatment includes drug withdrawal followed by structured acute
therapy and initiation of migraine prophylactic treatment.

Publication Types: 
    Meta-Analysis
    Review

PMID: 12463272 [PubMed - indexed for MEDLINE]

2776: Curr Med Res Opin. 2001;17 Suppl 1:s13-6.

Analgesics.

Diener HC, Limmroth V.

Department of Neurology, University of Essen, Germany. h.diener@uni-essen.de

Analgesics such as acetaminophen (paracetamol), acetylsalicyclic acid and
non-steroidal anti-inflammatory drugs are effective in the treatment of migraine 
attacks. Comparative studies indicate that their efficacy is similar or slightly 
inferior to sumattriptan, a specific antimigraine drug. Few data on the efficacy 
of opioid drugs in the treatment of migraine are available. They seem to be
effective but carry the risk of dependency and may cause drug-induced headache.

Publication Types: 
    Review

PMID: 12463271 [PubMed - indexed for MEDLINE]

2777: Curr Med Res Opin. 2001;17 Suppl 1:s4-12.

Epidemiology and economic impact of migraine.

Lipton RB, Stewart WF, Scher AI.

Department of Neurology, Albert Einstein College of Medicine and Headache Unit,
Montefiore Medical Center, Bronx, NY 10461, USA. rlipton@imrinc.com

Migraine is a very common disorder, affecting about 11% of adult populations in
Western countries. Prevalence is highest during the peak productive
years--between the ages of 25 and 55. The prevalence is higher in females than
males at all post-pubertal ages, but the sex ratio varies with age. In the United
States, migraine prevalence is higher in those with low income or education,
perhaps because migraine interferes with work and school. Most migraineurs mane
their headaches without conventional medical advice and generally treat their
attacks with over-the-counter medication. The indirect costs of migraine greatly 
outweigh the cost of treatment, creating opportunities for cost-effective
intervention. The public health burden of migraine is substantial due to its high
prevalence and prominent temporary disability. The widespread disability produced
by migraine is an important target for treatment.

Publication Types: 
    Review

PMID: 12463270 [PubMed - indexed for MEDLINE]

2778: Expert Opin Investig Drugs. 2002 Dec;11(12):1813-20.

Therapies in development for the treatment of migraine.

Mucke H.

HM Pharma Consultancy, Enenkelstrasse 28/32, A-1160 Vienna, Austria.
h.mucke@hmpharmacon.com

While oral formulations of agonists at the serotonin (5-HT) receptor subdivisions
5-HT(1B/1D)--the "triptan" class of drugs--dominate the market for migraine
therapy and while still more triptans are under development, recent research
efforts have also explored other pharmacological avenues, which are mostly based 
on our extended insights into the neuropathology and genetics of migraine.
Genetic research, in particular, continues to reveal new potential drug targets, 
indicating that the migraine treatment options that may become available by 2010 
might be substantially different from today's scenery. Meanwhile, pharmaceutical 
companies make increasing use of drug delivery and formulation technologies to
improve the action profile and convenience of use for current triptans and this
has even led to a partial revival of "old" migraine drugs, such as ergot
alkaloids. The broadest potential, however, lies in a better understanding of the
molecular pharmacology of migraine.

Publication Types: 
    Review

PMID: 12457440 [PubMed - indexed for MEDLINE]

2779: J Orofac Pain. 2002 Fall;16(4):317-25.

Hemicrania continua.

Benoliel R, Robinson S, Eliav E, Sharav Y.

Orofacial Pain Clinic, Department of Oral Diagnosis, Oral Medicine and Oral
Radiology, Hebrew University, P. O. Box 12272, Hadassah Faculty of Dental
Medicine, Jerusalem, 91120 Israel. benoliel@cc.huji.ac.il

Unilateral throbbing headaches may present similar signs and symptoms as dental
pathology and are a diagnostic challenge for dental practitioners. Cases may be
seen with a primary complaint of unilateral pain or referred by medical
colleagues for exclusion of dental causes. In the present article the authors add
a new case of hemicrania continua (HC), which is one such unilateral headache,
and review the previously published cases. HC is relatively easy to treat since
it responds completely to treatment with indomethacin. However, as is presented
in this case, HC may masquerade as dental pain. Cases secondary to trauma,
systemic disease, and nervous system pathology have been described in the
literature, and the clinician must exclude these possible causes. A thorough
knowledge of this entity is therefore essential.

Publication Types: 
    Case Reports
    Review

PMID: 12455433 [PubMed - indexed for MEDLINE]

2780: Am J Health Syst Pharm. 2002 Nov 15;59(22):2184-93.

Efficacy and safety of almotriptan malate for migraine.

Balbisi EA.

College of Pharmacy and Allied Health Professions, St. John's University, Queens 
Hospital Center, Jamaica, NY, USA. balbisie@stjohns.edu

The pharmacology, pharmacokinetics, clinical efficacy, adverse effects, and
dosage and administration of almotriptan are reviewed. Migraine is a common
disorder with a serious impact on quality of life. Newer serotonin-receptor
agonists have been developed with the aim of improving pharmacokinetic
characteristics. Almotriptan, a selective agonist of serotonin receptors 1B and
1D, carries FDA-approved labeling for use in the management of migraine with or
without aura in adults. The efficacy and receptor affinity resemble those of
sumatriptan, but almotriptan has a more favorable pharmacokinetic profile. It has
a rapid onset of action, an oral bioavailability of 70-80%, and a longer
half-life than sumatriptan. In clinical trials, almotriptan has been
significantly more effective than placebo and as effective as sumatriptan.
However, it has been associated with better tolerability and greater patient
satisfaction. In clinical trials, the most commonly reported adverse effects were
nausea, dry mouth, dizziness, somnolence, fatigue, vomiting, and paresthesia.
Almotriptan is contraindicated in patients with known ischemic heart disease,
coronary vasospasm, and other significant cardiovascular disorders. Almotriptan
has a lower acquisition cost than other triptans and possibly lower overall
health care costs because of a lower frequency of cardiovascular adverse effects.
The recommended dose of almotriptan is one 6.25- or 12.5-mg tablet given at the
onset of symptoms. Almotriptan is effective for the management of migraine and
offers the potential for fewer adverse effects than other agents in its class.

Publication Types: 
    Review

PMID: 12455302 [PubMed - indexed for MEDLINE]

2781: Headache. 2002 Nov-Dec;42(10):1006-15.

Reliability and validity of the migraine therapy assessment questionnaire.

Chatterton ML, Lofland JH, Shechter A, Curtice WS, Hu XH, Lenow J, Smullens SN,
Nash DB, Silberstein SD.

MLG Consulting Services, Inc, Chadds Ford, PA, USA.

OBJECTIVE: To determine the reliability and validity of the Migraine Therapy
Assessment Questionnaire (MTAQ). DESIGN/METHODS: Eligible patients between ages
18 and 65 with at least one migraine per month, a physician visit in the
preceding 6 months, and a migraine diagnosis were recruited from physician
offices in the Philadelphia area. Participants completed the MTAQ, Short Form-36 
(SF-36), the Migraine Disability Assessment Score (MIDAS), the Beck Depression
Inventory, a demographic questionnaire, and a medication use survey. The first
100 participants completed a second MTAQ approximately 2 weeks later. The
test-retest reliability, construct, and predictive validity of the MTAQ were
assessed. RESULTS: Two hundred fifty-one patients were recruited; 243 patients
were assessable. All MTAQ questions had a kappa statistic of.5 or higher and an
agreement of at least 76%. There was a significant level of agreement (.71) for
the MTAQ summary score. MTAQ items regarding control, frequency, work loss,
resource use, and satisfaction were associated with significant differences in
SF-36 scores. MTAQ items related to work loss, emergency department use, headache
frequency, and control were associated with days missed from work and degree of
disability as measured by MIDAS. Suboptimal migraine management was significantly
associated with MTAQ items indicating three or more headaches per month, missing 
time from work or school, taking daily medication for headaches, and having an
emergency department visit in the last 6 months. CONCLUSION: MTAQ is a reliable
and valid questionnaire to identify migraineurs whose migraine management may be 
suboptimal in a primary care setting.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 12453032 [PubMed - indexed for MEDLINE]

2782: Headache. 2002 Nov-Dec;42(10):1000-5.

Migraine headaches in adolescents: a five-year follow-up study.

Camarda R, Monastero R, Santangelo G, Raimondo D, Puma D, Pipia C, Camarda LK,
Camarda C, Raieli V.

Department of Neurology and Rehabilitation, Institute of Neuropsychiatry,
University of Palermo, Italy. rcamarda@neuro.unipa.it

BACKGROUND AND OBJECTIVES: Longitudinal studies of juvenile migraine are very
few. We investigated the prevalence and evolution over 5 years of migraine
without aura (MWOA) and migraineous disorder (MD) in an adolescent population.
METHODS: Sixty-four subjects (34 girls and 30 boys, mean age 17.3+/-1.1 years)
out of 80 selected in our 1989 epidemiological survey were included in the study.
The diagnostic criteria of the International Headache Society were used in both
studies. RESULTS: Thirty-two of 64 subjects (50%) had MWAO, 18 (28.1%) had MD,
and 14 (21.9%) had headache not classifiable (HnC). Our results show that MWOA
persisted in 56.2%, converted to MD or HnC in 9.4% and 3.1% of cases,
respectively, changed to episodic tension-type headache (ETTH) in 12.5%, and
remitted in 18.8%. MD persisted in 11.1%, converted to MWOA or HnC in 27.8% and
5.5% of cases, respectively, changed to ETTH in 11.1%, and remitted in 44.5%. HnC
persisted in 14.3%, converted to MD or MWOA in 21.4% and 14.3% of cases,
respectively, changed to ETTH in 14.3%, and remitted in 35.7%. CONCLUSIONS: Our
data indicate that juvenile-onset MWOA and MD may change in character over time, 
generally with a favorable prognosis.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 12453031 [PubMed - indexed for MEDLINE]

2783: Headache. 2002 Nov-Dec;42(10):984-99.

Costs and outcomes of early versus delayed migraine treatment with sumatriptan.

Halpern MT, Lipton RB, Cady RK, Kwong WJ, Marlo KO, Batenhorst AS.

Exponent Inc, Alexandria, VA 22314, USA. mhalpern@exponent.com

OBJECTIVE: To evaluate the impact on costs and outcomes of early migraine
treatment with sumatriptan while pain is mild versus sumatriptan treatment of
moderate to severe pain. BACKGROUND: Migraines result in substantial pain,
impairment, and costs. Recent clinical studies have shown that early treatment
with sumatriptan when migraine pain is mild is more effective than sumatriptan
treatment when pain is moderate to severe. DESIGN/METHODS: We developed a
decision analytical model to assess the costs and outcomes per treated migraine
attack, comparing early treatment while pain is mild versus delayed treatment
when pain may become moderate/severe using 50 and 100 mg of sumatriptan.
Parameters for the model were derived from published literature and analysis of
migraine patient diary data. For each patient group the model determined the
duration of mild and moderate/severe migraine pain, the proportion of patients
pain free at 4 hours after initial therapy with no recurrence, medical care
costs, and work loss costs (from migraine-related absenteeism and decreased
productivity) during a 24-hour period. Total costs were calculated as the sum of 
medical care costs plus work loss costs. RESULTS: Early treatment with
sumatriptan when migraine pain is mild resulted in substantially decreased total 
costs per treated attack as compared with treatment when pain is moderate/severe.
Early treatment also resulted in decreased time with headache pain, an increased 
proportion of patients pain free at 4 hours without recurrence, and decreased
physician and emergency department visits. Treatment with 100 mg sumatriptan
resulted in better outcomes than did treatment with 50 mg sumatriptan, but
outcomes with either dose for early treatment of mild pain were superior to those
for either dose in delayed treatment when pain may be moderate/severe.
CONCLUSIONS: Model-based results indicate that on a treated attack basis, early
treatment of migraine with sumatriptan while pain is mild leads to decreased
costs and improved outcomes compared to delayed sumatriptan treatment.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 12453030 [PubMed - indexed for MEDLINE]

2784: Headache. 2002 Nov-Dec;42(10):978-83.

Cost-effectiveness of antiepileptic drugs in migraine prophylaxis.

Adelman JU, Adelman LC, Von Seggern R.

Headache Wellness Center, Greensboro, North Carolina, 27401, USA.
jadelman@triad.rr.com

OBJECTIVE: To analyze the cost-effectiveness of antiepileptics in migraine
prophylaxis. METHODS: A cost-effectiveness analysis was performed using efficacy 
data from three recent, double-blind, placebo-controlled, clinical trials of
antiepileptic drugs studied for migraine prevention and cost data. Two measures
of cost-effectiveness were used: cost per headache prevented and the
cost-equivalent number. RESULTS: In the double-blind, placebo-controlled,
clinical trials evaluated, three antiepileptic drugs were shown to be effective
in migraine prevention. All three antiepileptic drugs had high costs per migraine
reduced. Gabapentin was the most costly at dollars 138.00 per migraine prevented,
whereas the cost per migraine prevented with topiramate was US dollars 114.80 and
with divalproex sodium was US dollars 48.00. For migraine prevention divalproex
sodium became cost-effective with 10 migraines per month, whereas gabapentin and 
topiramate required considerably more migraines per month to be cost-effective.
CONCLUSIONS: Antiepileptic drugs have proven effectiveness in migraine
prophylaxis. However, in patients responsive to their acute care medications, the
antiepileptic drugs are only cost-effective for those patients with a high
frequency of migraines and those with comorbid diseases. Future studies should be
done with antiepileptic drugs in patients exhibiting a migraine frequency of 10
or more headaches per month.

Publication Types: 
    Comparative Study

PMID: 12453029 [PubMed - indexed for MEDLINE]

2785: Headache. 2002 Nov-Dec;42(10):963-73.

Prevalence and clinical characteristics of headache in a rural community in Oman.

Deleu D, Khan MA, Al Shehab TA.

Department of Clinical Pharmacology & Therapeutics, Muscat-123, Sultanate of
Oman. dtodeleu@squ.edu.om

OBJECTIVES: To perform a prospective epidemiological study of headache in a rural
community in Oman, assessing prevalence, symptom profile, and health care
utilization pattern. METHODS: Using a door-to-door survey prevalence estimates
were based on a detailed structured headache assessment questionnaire performed
in 1158 subjects. Migraine and tension-type headache were diagnosed according to 
the International Headache Society criteria. RESULTS: The crude lifetime and
last-year prevalence of headache were 83.6% and 78.8%, respectively, with a
female preponderance. The last-year prevalence of migraine and tension headache
was 10.1% and 11.2%, respectively. There was no significant gender difference in 
migraine prevalence (4.5% in male and 5.6% in female), but tension-type headache 
was 2.6 times more common in females (3.1% in male and 8.1% in female). Last-year
prevalence of frequent headaches was 5.4%. Forty eight percent of respondents
sought medical assistance for their headaches and 79% were using medication, 40% 
of them used self-medication. CONCLUSIONS: This prospective study shows that
headache is also highly prevalent in this community. Migraine and tension-type
headache have the same prevalence, but the sex distribution for migraine is
different from that observed in the Western world. Tension-type headache
prevalence was substantially lower than that observed in other parts of the
world. Frequent headaches were as common as in other population-based studies
worldwide. Analgesic use/overuse probably also coexisted with headache, because
self-medication was quite common.

PMID: 12453027 [PubMed - indexed for MEDLINE]

2786: Headache. 2002 Nov-Dec;42(10):953-62.

Quality of life, coping strategies, and family routines in children with
headache.

Frare M, Axia G, Battistella PA.

Department of Developmental and Social Psychology, University of Padova, Italy.

OBJECTIVE: To identify the relationship between headache severity, child coping, 
and quality of life (QoL) in the context of everyday family life. BACKGROUND: In 
the pediatric headache research only 3 studies have examined children's coping
strategies and only 4 studies considered QoL. METHODS: A sample of 48 Italian
families with children seeking treatment for primary headaches was interviewed
using an adaptation of the Ecocultural Family Interview (EFI). The EFI is a
parent interview that explores the daily routines of family life in which the
child and parent participate and the main concerns regarding how that routine is 
organized. RESULTS: As expected the Lisrel analyses consistently showed that QoL 
is affected by a child's coping abilities in a causal direction. Headache
frequency and duration have a significant impact on a child's QoL. The family
daily routine influences significantly both the child's coping ability and QoL.
Surprisingly enough, children's coping strategies are not related to headache
severity. CONCLUSIONS: More research is needed on the causal factors influencing 
child's ability to cope with pain, and in particular more attention should be
devoted to the contextual and family factors related to pediatric headache.

PMID: 12453026 [PubMed - indexed for MEDLINE]

2787: Qual Health Res. 2002 Nov;12(9):1220-34.

The art of watching out: vigilance in women who have migraine headaches.

Meyer GA.

Saint Louis University School of Nursing, MO 63104, USA.

The author used grounded theory methodology to explore the process of vigilance
in women who had migraine headaches. Twenty-two women were interviewed. The basic
social problem identified for women with migraines was the need to maintain
function when faced with unpredictable bouts of pain and associated distress. One
way women maximized their function was through the exercise of vigilance.
Vigilance in these women can be conceptualized as the art of watching out.
Watching out, the core category, had four subprocesses: assigning meaning to what
is, calculating the risk, staying ready, and monitoring the results. Conditions
for watching out were owning the label and making the connections. Deciding what 
to do and acting to maximize function were consequences of vigilance.

PMID: 12448668 [PubMed - indexed for MEDLINE]

2788: Psychosomatics. 2002 Nov-Dec;43(6):502-4.

Triptans.

Armstrong SC, Cozza KL.

Center for Geriatric Psychiatry, Tuality Forest Grove Hospital, Forest Grove, OR 
97116. scott.armstrong@tuality.org

Triptans are potent serotonin (5-HT) 1B/1D receptor agonists used to abort and
treat migraine headaches. Although the triptans share pharmacodynamic
characteristics at 5-HT(1B/1D) receptors, they differ pharmacokinetically. This
column reviews how the triptans are metabolized. Generally, the triptans are
metabolized by phase I monoamine oxidases (MAOs) and by various cytochrome p450
enzymes. However, each triptan has a unique metabolic profile, leading to
significant differences in each triptan's potential for drug-drug interactions.
These differences are detailed in this review.

Publication Types: 
    Review

PMID: 12444236 [PubMed - indexed for MEDLINE]

2789: Am J Emerg Med. 2002 Nov;20(7):618-23.

Do ED patients with migraine headaches meet internationally accepted criteria?

Fiesseler FW, Kec R, Mandell M, Eskin B, Anannab M, Riggs RL, Richman PB.

Department of Emergency Medicine, Morristown Memorial Hospital, Morristown, NJ
07962, USA.

A recent editorial criticized emergency medicine researchers who study the
treatment of acute migraine for failing to standardize patients according to
definitions provided by the International Headache Society (IHS). In fact, most
emergency medicine-based studies of migraine therapies have not used IHS Criteria
(IHSC) for patient inclusion and are not uniform in the definition of acute
migraine. The purpose of this study was to determine the percentage of patients
with complaint of headache who present to the emergency department with a prior
diagnosis of migraine and/or emergency department discharge diagnosis of acute
migraine that meet IHSC. The study was a prospective observational study
performed in a community-based and consisted of consecutive patients with a chief
complaint of headache who presented to any 1 of 6 study investigators. Patients
recorded historical data on a standard form; Clinical data were recorded by the
investigators. Ninety-five percent confidence intervals and the Fisher exact test
were calculated as appropriate. One hundred eighty-five patients were enrolled
(study group): 70% were women, 43% had prior imaging studies to diagnose the
etiology of the headache, and 26% had a diagnostic workup during the current
emergency department visit; the probable headache etiology was found in 12 of
these cases. Only 3 patients that had an ED workup that fit IHSC. Forty-nine
percent of all patients had a prior diagnosis of migraines; 41 of these patients 
(45%) met IHSC. Forty-two percent of all patients had an emergency discharge
diagnosis of acute migraine; of these, 43 (56%) met IHSC. Forty-four out of 96
(46%; 95% confidence interval = 35%-57%) patients with a prior diagnosis of
migraine and/or discharge diagnosis of acute migraine met IHSC. Modification of
the IHSC, by removing restrictions for headache duration and number of prior
episodes, would have markedly increased the percentage of patients with a
previous migraine and/or emergency discharge diagnosis of acute migraine that met
other qualitative IHSC (94%). Of the patients with prior migraine diagnosis
and/or emergency department diagnosis of acute migraine, men and women were
equally as likely to meet IHSC (41% v 48%, P = 0.79). Less than half of patients 
with a prior diagnosis and/or final emergency discharge diagnosis of acute
migraine met IHSC. Our findings raise concerns about the external validity of
prior emergency department-based research of acute migraine therapy and the
utility of the IHSC for future research. Modification of the IHSC for emergency
medicine research should be considered. Copyright 2002, Elsevier Science (USA).
All rights reserved.)

PMID: 12442241 [PubMed - indexed for MEDLINE]

2790: J Neurol Neurosurg Psychiatry. 2002 Dec;73(6):747-50.

Duration, frequency, recency, and type of migraine and the risk of ischaemic
stroke in women of childbearing age.

Donaghy M, Chang CL, Poulter N; European Collaborators of The World Health
Organisation Collaborative Study of Cardiovascular Disease and Steroid Hormone
Contraception.

Department of Clinical Neurology, Radcliffe Infirmary, Oxford, UK.

BACKGROUND: Migraine is recognised increasingly as a risk factor for ischaemic
stroke in women of childbearing age. Migraine with aura poses a higher risk than 
migraine without aura. OBJECTIVE: To investigate further the effect of duration, 
frequency, recency, and type of migraine on the risk of ischaemic stroke.
METHODS: Additional analyses of a previously reported multicentre case-control
study of the relation between stroke and migraine in women aged 20-44 years.
RESULTS: Among 86 cases of ischaemic stroke and 214 controls, the adjusted risk
of ischaemic stroke was significantly associated with: (1) migraine of more than 
12 years duration, odds ratio (OR) 4.61 (1.27-16.8); (2) initial migraine with
aura, OR 8.37 (2.33-30.1); (3) particularly if attacks were more frequent than 12
times per year, OR 10.4 (2.18-49.4). In no case did correction for oral
contraception usage significantly alter these odds ratios. Increasing risk of
ischaemic stroke was related to a change to increased frequency of headaches
(trend p <or= 0.03). CONCLUSIONS: These data support earlier reports of a
relation between ischaemic stroke and migraine with aura. The risk seems
particularly high in those whose initial migraine type involved aura occurring
more than 12 times per year.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 12438482 [PubMed - indexed for MEDLINE]

2791: Sao Paulo Med J. 2002 Jul 4;120(4):118-21.

MIDAS (Migraine Disability Assessment): a valuable tool for work-site
identification of migraine in workers in Brazil.

Fragoso YD.

Universidade Metropolitana de Santos, Brazil.

CONTEXT: MIDAS was developed as a fast and efficient method for identification of
migraine in need of medical evaluation and treatment. It was necessary to
translate MIDAS, originally written in English, so as to apply it in Brazil and
make it usable by individuals from a variety of social-economic-cultural
backgrounds. OBJECTIVE: To translate and to apply MIDAS in Brazil. SETTING:
Assessment of a sample of workers regularly employed by an oil refinery. SETTING:
Refinaria Presidente Bernardes, Cubatão, São Paulo, Brazil. PARTICIPANTS: 404
workers of the company who correctly answered a questionnaire for the
identification and evaluation of headache. When the individual considered it to
be pertinent to his own needs, there was the option to answer MIDAS as well.
METHODS: MIDAS, originally written in English, was translated into Brazilian
Portuguese by a neurologist and by a translator specializing in medical texts.
The final version of the translation was obtained when, for ten patients to whom 
it was applied, the text seemed clear and the results were consistent over three 
sessions. MAIN MEASUREMENTS: Prevalence and types of primary headaches,
evaluation of MIDAS as a tool for identification of more severe cases. RESULTS:
From the total of 419 questionnaires given to the employees, 404 were returned
correctly completed. From these, 160 persons were identified as presenting
headaches, 44 of whom considered it worthwhile answering MIDAS. Nine of these
individuals who answered MIDAS were identified as severe cases of migraine due to
disability caused by the condition. An interview on a later date confirmed these 
results. Three were cases of chronic daily headache (transformed migraine) and
six were cases of migraine. CONCLUSIONS: MIDAS translated to Brazilian Portuguese
was a useful tool for identifying severe cases of migraine and of transformed
migraine in a working environment. The workers did not consider MIDAS to be
difficult to answer. Their high level of voluntary participation demonstrates
that this medical condition was of real interest among the workers, whether they 
were sufferers or not.

PMID: 12436159 [PubMed - indexed for MEDLINE]

2792: Proc West Pharmacol Soc. 2002;45:199-210.

An introduction to migraine: from ancient treatment to functional pharmacology
and antimigraine therapy.

Villalón CM, Centurión D, Valdivia LF, De Vries P, Saxena PR.

Depto de Farmacobiología, CINVESTAV-IPN, Czda. de los Tenorios 235, Col. Granjas 
Coapa, Deleg. Tlalpan, C.P. 14330, México D.F., México.
carlos_villalon@infosel.net.mx

Migraine treatment has evolved from the realms of the supernatural into the
scientific arena, but it seems still controversial whether migraine is primarily 
a vascular or a neurological dysfunction. Irrespective of this controversy, the
levels of serotonin (5-hydroxytryptamine; 5-HT), a vasoconstrictor and a central 
neurotransmitter, seem to decrease during migraine (with associated carotid
vasodilatation) whereas an i.v. infusion of 5-HT can abort migraine. In fact,
5-HT as well as ergotamine, dihydroergotamine and other antimigraine agents
invariably produce vasoconstriction in the external carotid circulation. The last
decade has witnessed the advent of sumatriptan and second generation triptans
(e.g. zolmitriptan, rizatriptan, naratriptan), which belong to a new class of
drugs, now known as 5-HT1B/1D/1F receptor agonists. Compared to sumatriptan, the 
second-generation triptans have a higher oral bioavailability and longer plasma
half-life. In line with the vascular and neurogenic theories of migraine, all
triptans produce selective carotid vasoconstriction (via 5-HT1B receptors) and
presynaptic inhibition of the trigeminovascular inflammatory responses implicated
in migraine (via 5-HT1D/5-ht1F receptors). Moreover, selective agonists at 5-HT1D
(PNU-142633) and 5-ht1F (LY344864) receptors inhibit the trigeminovascular system
without producing vasoconstriction. Nevertheless, PNU-142633 proved to be
ineffective in the acute treatment of migraine, whilst LY344864 did show some
efficacy when used in doses which interact with 5-HT1B receptors. Finally,
although the triptans are effective antimigraine agents producing selective
cranial vasoconstriction, efforts are being made to develop other effective
antimigraine alternatives acting via the direct blockade of vasodilator
mechanisms (e.g. antagonists at CGRP receptors, antagonists at 5-HT7 receptors,
inhibitors of nitric oxide biosynthesis, etc). These alternatives will hopefully 
lead to fewer side-effects.

Publication Types: 
    Historical Article
    Review

PMID: 12434581 [PubMed - indexed for MEDLINE]

2793: Pharmacotherapy. 2002 Nov;22(11):1442-57.

Hormonal interventions for menstrual migraines.

Chavanu KJ, O'Donnell DC.

Department of Pharmacy Practice, Chicago College of Pharmacy, Midwestern
University, Downers Grove, Illinois 60515, USA.

Menstrual migraines are a treatment challenge for both the migraineur and the
health care professional. Although some women with menstrual migraines may
respond to acute and preventive therapies for nonmenstrual migraines, others
continue to suffer from refractory menstrual migraines. These women may respond
to hormonal interventions, which may reduce the frequency of menstrual migraines,
thereby lessening the need for abortive migraine therapies, decreasing
migraine-related disability, and improving quality of life. Menstrual migraines
have a distinct pathophysiology that differs from menstrual-related migraines.
Published studies have shed light on the effectiveness of a variety of hormonal
interventions, including oral contraceptives, which may be administered with an
extended-dosing strategy; estrogen replacement therapy; selective estrogen
receptor modifiers; danazol; and leuprolide.

Publication Types: 
    Review

PMID: 12432971 [PubMed - indexed for MEDLINE]

2794: Neurology. 2002 Nov 12;59(9):1450-3.

Sensitization of trigeminal nociception specific for migraine but not pain of
sinusitis.

Katsarava Z, Lehnerdt G, Duda B, Ellrich J, Diener HC, Kaube H.

Department of Neurology, University of Essen, Germany.
zaza.katsarava@uni-essen.de

Trigeminal pain processing was studied in 14 patients with unilateral migraine
attacks and 14 age- and sex-matched patients with comparable unilateral headache 
from frontal sinusitis. Using a nociception-specific blink reflex method (nBR), a
facilitation of nBR responses predominantly on the headache side was observed in 
migraine, but not in sinusitis. The facilitation of trigeminal nociception may be
specific for migraine rather than a consequence of peripheral pain such as
frontal sinusitis.

Publication Types: 
    Comparative Study

PMID: 12427905 [PubMed - indexed for MEDLINE]

2795: J Pers Assess. 2002 Oct;79(2):235-42.

Differences on the projective hand test among chronic pain patients reporting
three different pain experiences.

Panek PE, Skowronski JJ, Wagner EE.

Department of Psychology, The Ohio State University-Newark 43055, USA.
panek.1@osu.edu

This study examined personality differences among individuals experiencing 3
different types of pain. The projective Hand Test was administered to 90
individuals who were seeking treatment at a pain clinic in an urban area of the
southeast United States. These people were seeking treatment for either arthritis
(n = 31), fibromyalgia (n = 29), or migraine headaches (n = 30). A 2 (gender) x 3
(pain group) x Age Group multivariate analysis of variance was conducted using
the quantitative Hand Test scoring variables as dependent measures. Results
indicated that individuals who were seeking treatment for migraine headaches had 
a higher production rate of responses involving exhibitionistic displays (EXH)
than individuals in the other 2 groups. Individuals who were seeking treatment
for fibromyalgia had a higher production rate of responses indicating fear and
phobic concerns (FEAR) than individuals in the other 2 groups. Individuals who
were seeking treatment for arthritis had a higher production rate of Active (ACT)
responses than individuals in the other 2 groups. Possible causes and
consequences of these effects are discussed.

PMID: 12425388 [PubMed - indexed for MEDLINE]

2796: Can J Clin Pharmacol. 2002 Fall;9(3):158-64.

Impact of migraine symptoms on health care use and work loss in Canada in
patients randomly assigned in a phase III clinical trial.

Lambert J, Carides GW, Meloche JP, Gerth WC, Marentette MA.

Department of Social and Preventive Medicine, University of Montreal, Quebec.
yugboisv@videotron.ca

BACKGROUND: Migraine is prevalent and associated with substantial direct and
indirect costs that may vary across geographic and national boundaries. The
effects of migraine, self-reported by Canadians, on health care resource use as
well as paid and unpaid work loss were examined. PATIENTS AND METHODS: The
Migraine Background Questionnaire (MBQ) was self-administered during the
screening visit of a phase III clinical trial of rizatriptan (a potent, selective
5-hydroxytryptamine(1B/1D)-receptor agonist or 'triptan'). Patients suffering
from moderate to severe migraine in the previous six months were offered the
opportunity to participate. Migraine frequency was determined and costs were
estimated and assigned based on known direct costs of health care resource
utilization, and indirect costs of paid and unpaid work and productivity loss.
RESULTS: One hundred thirty-four patients completed the MBQ. In the previous
year, 89% of those patients reported visiting a clinic, 23% reported visiting an 
emergency room and 5% reported being hospitalized for migraine. Patients reported
an average of 6.5 days absent from work, 44 days working with migraine headache
and 10.4 reduced workday equivalents due to ineffectiveness at work with
migraine. Based on data obtained from the Ontario, the average overall annual
cost due to migraine was estimated to be 3,025 dollars/patient; most of this
(87%) due to indirect costs. CONCLUSION: In Canada, patients with moderate to
severe migraine, as identified in a phase III clinical trial, reported lost work 
days and reduced effectiveness while at work, as well as increased health care
resource utilization due to migraine. The associated cost was estimated to be
substantial.

PMID: 12422253 [PubMed - indexed for MEDLINE]

2797: Cephalalgia. 2002 Nov;22(9):749-57.

Brain blood flow in the nitroglycerin (GTN) model of migraine: measurement using 
positron emission tomography and transcranial Doppler.

Bednarczyk EM, Wack DS, Kassab MY, Burch K, Trinidad K, Haka M, Gona J.

Departments of Nuclear Medicine and Neurology, University at Buffalo School of
Medicine, VAWNYHS, Buffalo, NY 14214, USA. eb@acsu.buffalo.edu

Nitroglycerin has been widely used as a model of experimental migraine. Studies
combining measurement of flow velocity using transcranial Doppler (TCD)
concurrently with measures of cerebral blood flow (CBF) are uncommon. We report
the results of a study combining TCD and positron emission tomography (PET).
Healthy volunteers with no personal or family history of migraine underwent
measurement of CBF using H215O PET, and velocity using TCD. Measurements were
done at baseline, and following i.v. nitroglycerin at 0.125, 0.25 and 0.5 micro
g/kg per min. Subcutaneous sumatriptan (6 mg) was injected, with CBF and velocity
measured 15, 30, and 60 min later. Nitroglycerin was terminated and measurements 
obtained 30 min later. Six male and six female subjects were studied.
Nitroglycerin increased global CBF while flow velocities decreased. Sumatriptan
did not have a significant effect on these values. Regions of increased flow
included the anterior cingulate, while regions of decreased flow included the
occipital cortex. Our data suggest that nitroglycerin induces regional changes in
CBF that are similar to changes reported in spontaneous migraine, but produces
distinctly different effects on global CBF and velocity.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 12421161 [PubMed - indexed for MEDLINE]

2798: Cephalalgia. 2002 Nov;22(9):720-4.

Fatigue in chronic migraine patients.

Peres MF, Zukerman E, Young WB, Silberstein SD.

São Paulo Headache Centre and Albert Einstein Hospital São Paulo, Brazil.
marioperes@yahoo.com

Fatigue is a common symptom frequently reported in many disorders including
headaches, but little is known about its nature. The objective was to determine
the prevalence of fatigue in chronic migraine (CM) patients, to define its
subtypes and its relationship with other conditions comorbid with CM. Sixty-three
CM patients were analysed. The Fatigue Severity Scale (FSS), the Chalder fatigue 
scale and the CDC diagnostic criteria for chronic fatigue syndrome (CFS) were
used. Fifty-three (84.1%) patients had FSS scores greater than 27. Forty-two
(66.7%) patients met the CDC criteria for CFS. Thirty-two patients (50.8%) met
the modified CDC criteria (without headache). Beck depression scores correlated
with FSS, mental and physical fatigue scores. Trait anxiety scores also
correlated with fatigue scales. Women had higher FSS scores than men, P < 0.05.
Physical fatigue was associated with fibromyalgia, P < 0.05. Fatigue as a symptom
and CFS as a disorder are both common in CM patients. Therapeutic interventions
include a graded aerobic exercise program, cognitive behavioural therapy and
antidepressants. Identification of fatigue and its subtypes in headache disorders
and recognition of headaches in CFS patients has implications for the
pathophysiology, diagnosis and treatment of these disorders.

PMID: 12421157 [PubMed - indexed for MEDLINE]

2799: Cephalalgia. 2002 Nov;22(9):711-9.

Comment in:
    Cephalalgia. 2002 Nov;22(9):697-8.

Tinted spectacles and visually sensitive migraine.

Wilkins AJ, Patel R, Adjamian P, Evans BJ.

Visual Perception Unit, University of Essex, Colchester, and Institute of
Optometry, London, UK.

A double-masked randomized controlled study with cross-over design compared the
effectiveness of precision ophthalmic tints in the prevention of headache in
migraine sufferers. Seventeen patients chose the colour of light that optimally
reduced perceptual distortion of text and maximized clarity and comfort. They
were later given glasses with spectral filters providing optimal colour under
conventional white lighting ('optimal' tint) or glasses that provided a slightly 
different colour ('control' tint). The tints were supplied in random order, each 
for 6 weeks, separated by an interval of at least 2 weeks with no tints. Headache
diaries showed that the frequency of headaches was marginally lower when the
'optimal' tint was worn, compared with the 'control'. The trial extends to adults
with migraine, the results of a previous double-masked study demonstrating, in
children with reading difficulty, beneficial effects of precision tints in
reducing symptom frequency. In the present study, however, the effects are
suggestive rather than conclusive.

Publication Types: 
    Clinical Trial
    Comparative Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 12421156 [PubMed - indexed for MEDLINE]

2800: Curr Pain Headache Rep. 2002 Dec;6(6):480-5.

Prophylaxis for chronic daily headache and chronic migraine with neuronal
stabilizing agents.

Krusz JC.

Anodyne Pain Care, 5446 Glen Lakes Drive, Dallas, TX 75231, USA.
nodynia@swbell.net

Approaches to acute and prophylactic migraine and headache treatment are evolving
as our understanding of some of the underlying pathophysiology improves. This
article focuses on the emerging use of medications originally introduced for the 
treatment of seizures (anticonvulsants) as primary therapy for eradicating or
reducing migraine and chronic daily headaches. A more accurate term for their
pharmacologic mechanisms, if they are used to treat headaches and pain disorders,
is neuromodulating or neuronal stabilizing agents. This term refers to their many
cellular actions to reduce pain transmission supraspinally, in the spinal cord,
and in the brainstem.

Publication Types: 
    Review

PMID: 12413407 [PubMed - indexed for MEDLINE]

2801: J Natl Med Assoc. 2002 Oct;94(10):901-7.

Hemicrania continua in African Americans.

Wheeler SD.

Ryan Wheeler Headache Treatment Center, Miami, Florida 33189, USA.
DrHeadache@aol.com

OBJECTIVE: The first six cases of hemicrania continua and episodica in African
Americans are reported, differences from previous accounts noted, and important
diagnostic features described. BACKGROUND: Hemicrania continua is an indomethacin
responsive chronic daily headache. Mild to moderate daily headache is strictly
unilateral, constant but fluctuating. Superimposed severe headache attacks occur,
last seconds to days, and are associated with ipsilateral orbital-nasal autonomic
dysfunction. RESULTS: Severe headache attacks are usually pulsatile, occur one to
four times daily, and last 40 minutes to three days. Daily unilateral background 
headache was typically of a pressure, sharp, dull or pulling quality. Ipsilateral
orbital-nasal autonomic symptoms were noted in all. Serious concomitant medical
illnesses, e.g. coronary artery disease, diabetes, and hypertension, were
frequent in this population. CONCLUSIONS: This is the first report of hemicrania 
continua and episodica in African Americans and the second in persons of African 
descent in the world's literature. Late age of onset, frequent serious medical
illnesses, and family history of migraine differentiate this series from previous
reports. The lack of reports in African Americans most likely reflects
misdiagnosis rather than true prevalence. Thus, whenever any patient presents
with chronic daily unilateral headache, ipsilateral autonomic symptoms should be 
assessed during severe headache attacks, and an indomethacin trial considered.

Publication Types: 
    Case Reports

PMID: 12408695 [PubMed - indexed for MEDLINE]

2802: Neurosci Lett. 2002 Nov 15;333(1):29-32.

Abnormal brain processing of cutaneous pain in migraine patients during the
attack.

de Tommaso M, Guido M, Libro G, Losito L, Sciruicchio V, Monetti C, Puca F.

First Neurologic Clinic, University of Bari, Policlinico, Piazza G Cesare 11,
70124 Bari, Italy. m.detommaso@neurol.uniba.it

We examined cutaneous pain thresholds using CO(2) laser stimuli during migraine
attacks, and defined the evoked cortical potential characteristics. Ten patients 
without aura were studied during attacks and for at least 72 h subsequently. Pain
stimuli were generated on the dorsum of both hands and the right and left
supraorbital zones, using pulses from a CO(2) laser. Absolute latencies of scalp 
potentials were measured at the highest peak of each response component, and the 
peak-to-peak amplitudes of N2a-P2 components were recorded. Cutaneous pain
thresholds were significantly reduced on both the symptomatic and non-symptomatic
sides during the attack, in comparison with the headache-free phase. The N2a-P2
complexes also increased in amplitude during attacks in comparison with the
pain-free side. Thus, cutaneous hyperalgesia occurs during migraine attack, and
is subtended by central sensitization phenomena, probably involving the cortex.
Copyright 2002 Elsevier Science Ireland Ltd.

Publication Types: 
    Comparative Study

PMID: 12401553 [PubMed - indexed for MEDLINE]

2803: Clin Sci (Lond). 2002 Nov;103(5):487-91.

Serum levels of androgens and migraine in postmenopausal women.

Mattsson P.

Department of Neuroscience, Neurology, University Hospital, SE-751 85 Uppsala,
Sweden. Peter.Mattsson@neurologi.uu.se

Female hormones are thought to be of importance in the aetiology of migraine,
which is more common in women than in men. Little attention has been paid to
androgens. This study investigates the associations between migraine and serum
levels of androgens in postmenopausal women not taking oestrogens. A case-control
study was carried out among women participating in a mammography screening
program. A neurologist clinically assessed the participants. Headache criteria
proposed by the International Headache Society were used. Each of the 15 women
with migraine was matched to three controls by time since menopause and by body
mass index. Serum levels of androstenedione and total testosterone were measured 
by radioimmunoassays. Free testosterone was calculated from total testosterone,
immunoassayed sex hormone-binding globulin and albumin. The mean+/-S.D. serum
level of androstenedione was 2.7+/-1.1 nmol/l and 3.4+/-1.9 nmol/l in cases and
controls respectively. The mean serum level of testosterone was 0.8+/-0.4 nmol/l 
and 1.0+/-0.5 nmol/l in cases and controls respectively. The mean serum level of 
free testosterone was 12.5+/-8.5 pmol/l and 14.0+/-7.9 pmol/l in cases and
controls respectively. Conditional logistic regression analysis was used to test 
for differences in serum levels of androstenedione, total testosterone and free
testosterone between cases and controls. No statistically significant differences
were found. To conclude, there was no evidence in this study that differences
within normal levels of androgens play an important role in the aetiology of
migraine in postmenopausal women not taking oestrogens.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 12401121 [PubMed - indexed for MEDLINE]

2804: Neurol Res. 2002 Oct;24(7):663-5.

Migraine and isolated recurrent vertigo of unknown cause.

Lee H, Sohn SI, Jung DK, Cho YW, Lim JG, Yi SD, Yi HA.

Department of Neurology, School of Medicine, Keimyung University, Daegu, South
Korea. hlee@dsmc.or.kr

Chronic recurrent attacks of vertigo, not associated with any auditory or
neurological symptoms, are a common reason for referral to our neurotology
clinic. Even after an extensive neurotological evaluation, some cases remain
undiagnosed. We prospectively evaluated 72 consecutive patients who presented to 
the clinic with isolated recurrent vertigo of unknown cause. All patients
underwent diagnostic evaluation to exclude identifiable causes of isolated
recurrent vertigo. We compared the prevalence of migraine, according to the
International Headache Society (IHS) criteria, in the isolated recurrent vertigo 
group, with a sex- and age-matched control group of orthopedic patients. The
prevalence of migraine according to IHS criteria was higher in the isolated
recurrent vertigo group (61.1%) than in the control group (10%; p < 0.01). Only
16.7% of patients had an abnormal vestibular function test. The most common
abnormal finding was a unilateral vestibular weakness to caloric stimulation. Our
results suggest that migraine should be considered in the differential diagnosis 
of isolated recurrent vertigo of unknown cause.

Publication Types: 
    Comparative Study

PMID: 12392202 [PubMed - indexed for MEDLINE]

2805: Neurology. 2002 Oct 22;59(8):1210-7.

Comment in:
    Neurology. 2003 Apr 8;60(7):1221-2; author reply 1221-2.

Eletriptan vs sumatriptan: a double-blind, placebo-controlled, multiple migraine 
attack study.

Sandrini G, Färkkilä M, Burgess G, Forster E, Haughie S; Eletriptan Steering
Committee.

University Centre for Adaptive Disorders and Headache, IRCCSC. Mondino
Foundation, Pavia, Italy. gsandrini@unipv.it

OBJECTIVE: To compare the efficacy of oral eletriptan, 40 mg and 80 mg, and oral 
sumatriptan, 50 mg and 100 mg, in the acute treatment of migraine. METHODS:
Patients with a history of migraine (n = 1,008) were randomly assigned to receive
placebo, 40 mg of eletriptan, 80 mg of eletriptan, 50 mg of sumatriptan, or 100
mg of sumatriptan to treat up to three attacks. Early headache response (at 1
hour) was the primary endpoint, in addition to the standard endpoint, 2-hour
headache response. RESULTS: Headache response rates were 12% at 1 hour and 31% at
2 hours for placebo; 24% at 1 hour and 50% at 2 hours for sumatriptan 50 mg; 27% 
at 1 hour and 53% at 2 hours for sumatriptan 100 mg; 30% at 1 hour and 64% at 2
hours for eletriptan 40 mg; and 37% at 1 hour and 67% at 2 hours for eletriptan
80 mg. More patients receiving eletriptan 80 mg achieved a 1-hour headache
response than did patients receiving sumatriptan 50 mg (p < 0.05). All doses of
eletriptan were superior to sumatriptan at 2 hours for headache response and
complete pain relief (p < 0.05). Significantly more patients on eletriptan 80 mg 
achieved headache response in all attacks than did patients receiving either
sumatriptan dose. Eletriptan 40 mg was superior to both sumatriptan doses in
functional improvement (p < 0.005). The superior efficacy of both eletriptan
doses was associated with higher rates of patient acceptability than sumatriptan 
50 mg (p < 0.05). Eletriptan and sumatriptan were well tolerated. CONCLUSION:
Oral eletriptan (40 mg and 80 mg) is effective, safe, and tolerable in the acute 
treatment of migraine and yields a consistent response.

Publication Types: 
    Clinical Trial
    Comparative Study
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 12391349 [PubMed - indexed for MEDLINE]

2806: Headache. 2002 Sep;42(8):831-3; discussion 832-3.

Intractable cluster headaches in a migraineur.

Rothrock JF, Mathew NT, Kaup AO, Evans RW.

Some migraineurs have the additional misfortune of suffering from cluster
headaches; this situation can be challenging.

Publication Types: 
    Case Reports

PMID: 12390651 [PubMed - indexed for MEDLINE]

2807: Headache. 2002 Sep;42(8):819-22.

Sodium valproate prophylaxis in childhood migraine.

Serdaroglu G, Erhan E, Tekgul H, Oksel F, Erermis S, Uyar M, Tutuncuoglu S.

Department of Pediatrics, Division of Pediatric Neurology, Ege University Faculty
of Medicine, Izmir, Turkey.

Migraine is a cause of recurrent headache in childhood. The efficacy of sodium
valproate is well known in the prophylactic treatment of adult migraine, but
there are few studies involving the drug's effect in pediatric migraine.
OBJECTIVE: To determine the efficacy of sodium valproate in the prophylactic
treatment of childhood migraine. METHODS: Fifteen children with migraine
according to International Headache Society criteria were included in the study. 
Headache severity was measured and assessed by Algology unit by a using visual
analog scale and a numerical rating scale. All of the subjects were asked to keep
a headache diary for 8 weeks. Three subjects who had no headache attacks during
the baseline period and two cases who were lost to follow up were excluded. Thus,
sodium valproate was initiated in 10 subjects (six boys, four girls), 500
mg/night, and the daily dose was increased up to 1000 mg according to blood
levels. Their ages ranged from 9 to 17 (mean age 13.6 +/- 3.2 years). Therapy
continued for at least 12 weeks. RESULTS: Headache severity as measured via the
mean visual analog score was 6.8 +/- 1.8 at baseline and was 0.7 +/- 1.2 at the
end of the treatment period (P = 0.000). Mean headache attacks per month were 6
+/- 4.2 at baseline and were 0.8 +/- 1.9 at the end of the treatment period (P = 
0.002). The duration of headache was significantly decreased from a mean of 5.5
+/- 3.9 hours to 1.1 +/- 2.5 hours with treatment (P = 0.001). The observed side 
effects were dizziness, drowsiness, and increase in appetite; none required drug 
withdrawal. In two cases, headache attacks recurred after the cessation of
valproate, and therapy was restarted. Headache control lasted for six months
following cessation of the drug in the remainder of the subjects. CONCLUSION:
Sodium valproate appears to be effective and safe in selected patients with
childhood migraine.

Publication Types: 
    Clinical Trial

PMID: 12390647 [PubMed - indexed for MEDLINE]

2808: Headache. 2002 Sep;42(8):810-8.

Effectiveness of topiramate in the prevention of childhood headaches.

Hershey AD, Powers SW, Vockell AL, LeCates S, Kabbouche M.

Division of Neurology, University of Cincinnati, College of Medicine, Cincinnati,
Ohio, 45229-3039, USA.

BACKGROUND: Migraine is a significant problem for many children. Topiramate has
been suggested to be effective for the prophylaxis of migraine in adults, but has
not yet been examined in children. The drug has been demonstrated to be safe and 
effective for childhood seizure disorders. The objective of this study was to
demonstrate the safety and efficacy of topiramate for the prevention of pediatric
migraine. METHODS: Children with frequent migraine were prescribed topiramate for
headache prevention. Dosages, serum levels, and Serum Glutamic Oxalacetic
Transaminase (SGOT) levels were monitored. Changes in frequency, severity, and
duration of headaches were recorded and changes in headache-related disability
using PedMIDAS also were measured. RESULTS: Ninety-seven children were treated
with topiramate, and 75 were reevaluated 88.7 +/- 35.7 days later, 41 were seen
at a second follow-up, and 17 were seen at a third follow-up evaluation. The
daily dose reached at second evaluation was 84.0 +/- 38.6 mg/day or 1.42 +/- 0.74
mg/kg/day. This corresponded to a mean serum level of 2.8 +/- 1.6 micro g/mL. The
mean headache frequency was reduced from 16.5 +/- 10.0 to 11.6 +/- 10.2 days per 
month (P<0.001) with a further reduction to 9.4 +/- 8.4 days by the second
follow-up (P<0.001). Severity and duration of headache also were reduced.
Headache disability improved, with a reduction of Pediatric Migraine Disability
Assessment score from 36.0 +/- 42.3 to 20.8 +/- 34.0 at the first follow-up
(P<0.05), 19.1 +/- 22.0 at the second follow-up (P<0.005), and 10.9 +/- 16.9 at
the third follow-up (P<0.001). Most patients tolerated topiramate well. The most 
common side effects reported were cognitive (12.5%), weight loss (5.6%), and
sensory (2.8%). CONCLUSIONS: Topiramate is potentially an effective prophylactic 
medication for children with frequent migraine.

Publication Types: 
    Clinical Trial

PMID: 12390646 [PubMed - indexed for MEDLINE]

2809: Headache. 2002 Sep;42(8):804-9.

Efficacy of topiramate in migraine prophylaxis: a retrospective chart analysis.

Von Seggern RL, Mannix LK, Adelman JU.

Headache Wellness Center, Greensboro, North Carolina 27401, USA.

OBJECTIVE: Topiramate, a broad-spectrum anticonvulsant with multiple mechanisms
of action, may be effective in preventing migraine headaches. We report the
results of a retrospective chart review of patients treated with topiramate for
prophylaxis of migraine. METHODS: Patients with a diagnosis of migraine who had
at least one follow-up visit after > or =4 weeks on topiramate were eligible; 69 
patients (56 women and 13 men) aged 18 to 68 years met these criteria. Charts
were reviewed for frequency of mild or moderate/severe headaches at the start of 
topiramate (baseline) and at all subsequent visits up to 24 weeks. RESULTS: The
28-day frequency of moderate/severe migraines declined significantly from
baseline to end of treatment (10.6 +/- 8.4 to 7.4 +/- 7.7, respectively; P =
0.0004), whereas that of mild headaches did not demonstrate a significant change 
(from 11.8 +/- 8.9 to 11.0 +/- 10.0). Among the 38 patients who had not responded
previously to >or =9 preventive medications, the monthly frequency of
moderate/severe (but not mild) headaches decreased significantly from baseline to
end of treatment. Patients who previously had not responded to <9 prior
medications experienced significant declines in both mild and moderate/severe
headaches. The most common adverse events were paresthesias, drowsiness,
diarrhea, decreased appetite, and weight loss. Twenty-seven patients discontinued
topiramate therapy, 20 as a result of adverse events and 7 due to lack of
response. CONCLUSION: Topiramate may be effective in reducing the frequency of
both mild and moderate/severe migraine headaches. In particular, topiramate may
offer relief to patients with moderate/severe migraines who do not respond to
other treatments.

PMID: 12390645 [PubMed - indexed for MEDLINE]

2810: Headache. 2002 Sep;42(8):796-803.

Prophylaxis of migraine, transformed migraine, and cluster headache with
topiramate.

Mathew NT, Kailasam J, Meadors L.

Houston Headache Clinic, Houston, Texas 77004, USA.

OBJECTIVE: To assess the efficacy and tolerability of topiramate for prophylaxis 
of migraine and cluster headache via a retrospective chart analysis. BACKGROUND: 
Topiramate has multiple mechanisms of action that could potentially contribute to
migraine prophylaxis. We conducted a retrospective chart review to assess the
efficacy of topiramate as add-on therapy in patients with transformed migraine or
cluster headache, and as first-line therapy in patients with episodic migraine.
METHODS: Patients diagnosed with transformed migraine, episodic migraine, or
cluster headache, who received topiramate either as add-on therapy or monotherapy
were selected via retrospective chart review. Patients had begun topiramate
therapy at 25 mg/day for the first week and increased their dosage by 25 mg/week 
to a maximum of 200 mg/day. Topiramate was used as add-on therapy for patients
with transformed migraine and cluster headache, and as a first-line monotherapy
in patients with episodic migraine who had no previous prophylactic therapy. The 
outcome parameters examined included a mean 28-day migraine frequency, migraine
severity, number of headache days/month, number of abortive medication
tablets/month, patient global evaluation, and the MIDAS scale. RESULTS: One
hundred seventy-eight patients (transformed migraine: n = 96; episodic migraine: 
n = 70; and cluster headache: n = 12) were included in the retrospective
analysis. The mean dose of topiramate for all patients was 87.5 mg/day. For
patients with transformed migraine, mean migraine frequency decreased from 6.3/28
days to 3.7 (P = 0.005). Mean severity decreased from 7.1 to 3.8 on a 10-point
scale, with 10 representing the most severe pain (P = 0.003). The mean number of 
headache days/month decreased from 22.1 to 9.6 (P = 0.001), and the mean number
of abortive medication tablets decreased from 28.7/month to 10.6 (P = 0.001).
Patient global evaluation indicated substantial or moderate improvement in 53% of
patients with transformed migraine who used topiramate as add-on therapy. Mean
MIDAS scale values decreased from 90.2 to 24.9 (P< 0.0001). The 70 episodic
migraine patients who were administered topiramate as first-line therapy
exhibited a decrease in mean migraine frequency (5.8/28 days to 1.9, P = 0.001), 
while mean migraine severity decreased from 8.1 to 2.0 (P = 0.003). Sixty-one
percent of patients reported marked improvement. Nine of the 12 cluster headache 
patients exhibited substantial or moderate improvement in symptoms, whereas three
had no improvement. The most common adverse effects were paresthesias (12%),
cognitive effects (11%), and dizziness (6%). Eight patients discontinued
topiramate due to adverse effects; cognitive effects were the most common reason.
No patient discontinued topiramate treatment due to lack of efficacy. Twelve
percent of patients lost more than 5 lbs during treatment (a range of 5-120 lbs).
CONCLUSION: For both patients with transformed migraine (add-on therapy) and
patients with episodic migraine (first-line monotherapy), topiramate yielded
significant reductions in migraine frequency, migraine severity, number of
headache days/month, and use of abortive medications. Topiramate also appears to 
be well tolerated and useful in the adjunctive treatment of cluster headache.
Prospective double-blind, placebo-controlled trials will be required to confirm
our results.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 12390644 [PubMed - indexed for MEDLINE]

2811: Headache. 2002 Sep;42(8):780-6.

Children's ibuprofen suspension for the acute treatment of pediatric migraine.

Lewis DW, Kellstein D, Dahl G, Burke B, Frank LM, Toor S, Northam RS, White LW,
Lawson L.

Division of Pediatric Neurology, Norfolk, Va 23510, USA.

OBJECTIVE: To compare the efficacy of a single over-the-counter dose (7.5 mg/kg, 
p.o.) of children's ibuprofen suspension vs. placebo for the acute treatment of
pediatric migraine. BACKGROUND: Migraine occurs in 4% of young children. There is
a paucity of controlled clinical research in the treatment of childhood migraine 
and there are currently no approved drugs in the USA for treatment of migraine in
children < or = 12 years of age. The purpose of this study is to assess the
efficacy and tolerability of a single OTC dose of ibuprofen suspension for the
acute treatment of childhood migraine. METHODS: Prospective, double-blind,
placebo-controlled, parallel group, randomized study of children 6-12 yrs with
migraine (I.H.S.-R 1997) treating 1 attack with a 7.5 mg/kg liq. ibuprofen vs
matching placebo. Efficacy measures: (1). Headache severity based upon a 4 pt
scale (severe, mod., mild, no headache) at 30, 60, 90, 120, 180 and 240 minutes
post dose, and (2). nausea, vomiting, and photo/phonophobia at 120 min. The 1
degrees endpoint was cumulative % of responders (severe or mod. headache reduced 
to mild or none) by 120 minutes. Secondary endpoints were headache recurrence
within 4-24 hours and need for rescue medicines within 4 hours. RESULTS: 138
enrolled; 84 treated/completed diary. 45 active agent, 39 placebo. The 2 groups
were comparable (active: placebo) - Ages: 9: 9.1, gender boy/girl - 1.25: 1.6,
and diagnosis: migraine w/o aura - 86%: 79%. Concomitant use of prophylactic Rx: 
24%: 10% (Table 3). Nausea was eliminated in 60% of the ibuprofen treated
patients and 39% of the placebo group (p<0.001). Vomiting, photophobia and
phonophobia had marginal, but not statistically significant, decreases at 2
hours. A striking gender difference was noted (Table 4): No AE's were reported.
CONCLUSION: Children's ibuprofen suspension at an OTC dose of 7.5 mg/kg is an
effective and well-tolerated agent for pain relief in the acute treatment of
childhood migraine, particularly in boys. There is a striking difference in
gender response rates and placebo responder rates between girls and boys. The
boys responded at a statistically significant rate, and girls failed to do so
because of a very high placebo responder rate. Multi-center trials are
recommended.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial

PMID: 12390641 [PubMed - indexed for MEDLINE]

2812: Headache. 2002 Sep;42(8):776-9.

Cognitive development in children with migraine and their healthy unaffected
siblings.

Haverkamp F, Hönscheid A, Müller-Sinik K.

Department of Pediatrics, Children's Hospital, University of Bonn, Bonn, Germany.

The discussion about neuropsychological sequalae from migraine occurring in
adults is controversial. The purpose of our study was to examine whether children
with migraine may be at risk for impaired intellectual development compared with 
their siblings free of migraine.

Publication Types: 
    Comparative Study

PMID: 12390640 [PubMed - indexed for MEDLINE]

2813: Headache. 2002 Sep;42(8):754-65.

Lifetime prevalence and characteristics of recurrent primary headaches in a
population-based sample of Swedish twins.

Svensson DA, Ekbom K, Larsson B, Waldenlind E.

Division of Neurology, Neurotec, Karolinska Institutet, Huddinge University
Hospital, Stockholm, Sweden.

OBJECTIVE: To examine the lifetime prevalence and other characteristics of
recurrent primary headaches in twins. BACKGROUND: The twin model may provide
insights into the role of genetic and environmental influences in headache
disorders. However, assumptions as to whether twins are representative of the
general population, and whether monozygotic and dizygotic twins are similar have 
rarely been addressed. METHODS: The study population consisted of a random sample
of 17- to 82-year-old twins from the Swedish Twin Registry (n = 1329). Structured
interviews on the telephone by lay personnel and the International Headache
Society criteria were used for assessment and diagnosis of recurrent primary
headaches. Prevalence data of the general population for migraine and
tension-type headache was obtained from various published reports. RESULTS: A
total of 372 subjects (29%) had ever had recurrent headaches. In total, 241
recurrent headache sufferers fulfilled the criteria for migraine or tension-type 
headache, and the lifetime prevalence was 7.1% for migraine without aura, 1.4%
for migraine always with aura, 1.9% for migraine occasionally with aura, 9.4% for
episodic tension-type headache, and 1.3% for chronic tension-type headache. The
lifetime prevalence of all migraine and all tension-type headache, including
another 84 subjects fulfilling all but one of the criteria for migraine or
tension-type headache, was 13.8% and 13.5%, respectively. The corresponding
prevalence risk for women was 2.4 (95% confidence interval [CI] 1.7, 3.4) and 1.5
(95% CI 1.1, 2.1), respectively. Zygosity was not a significant predictor for
migraine. In tension-type headache, the prevalence risk for dizygotic twins and
unlike-sexed twins as compared with monozygotic twins was 1.9 (95% CI: 1.2, 3.1) 
and 1.8 (95% CI: 1.1, 2.9), respectively. CONCLUSION: There is no twin-singleton 
or monozygotic-dizygotic difference for the risk of migraine. In tension-type
headache, twins seem to have a lower risk than singletons, and this is especially
true for monozygotic twins.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.
    Twin Study

PMID: 12390638 [PubMed - indexed for MEDLINE]

2814: Headache. 2002 Sep;42(8):747-53.

Health resource utilization of the emergency department headache "repeater".

Maizels M.

Department of Family Practice, Kaiser Permanente, Woodland Hills, Calif 91367,
USA.

OBJECTIVE: To document the health resource utilization of patients who repeatedly
use emergency department services for headache care. BACKGROUND: Patients with
headache who frequently use emergency department services may differ from
patients with more typical, episodic migraine. Previous studies of health
resource utilization have often failed to distinguish the high utilizer as a
specific subset of the migraine population. DESIGN: Retrospective review of
urgent care/emergency department charts, clinic charts, and pharmacy rosters.
PATIENTS AND METHODS: Patients who made three or more visits for headache to an
urgent care/emergency department (UC/ED) facility for headache over a 6-month
study period were identified and designated as "repeaters" for this study.
Pharmacy profiles and appointment histories of 52 of the 54 repeaters whose
records were available were reviewed for the 12 months prior to the study period.
RESULTS: Over the 6-month study period, 518 patients visited the UC/ED 1004 times
for primary headache complaints. Fifty-four (10%) repeaters made 502 visits (50% 
of total visits; mean 9.3, range 3-50). In the 12 months prior to the study
period, 52 of these repeaters made 1832 visits to the UC/ED or clinic (mean 35.2,
range 0-178): 1458 (79.6%) were headache related, and 1271 (69.4%) of all visits 
were to the UC/ED. An estimated 12-month cost for all visits was $183,760.
Pharmacy rosters showed use of narcotics in 41 of the 52 patients (annual mean
+/- SD, 613 +/- 670 tablets), benzodiazepines in 30 patients (500 +/- 486
tablets), and butalbital products in 27 patients (395 +/- 590 tablets). Mean
daily use of all symptomatic medications combined was 3.9 +/- 3.2 doses/day.
CONCLUSION: Health resource utilization of emergency department headache
repeaters is predominantly headache-related acute care. Associated medication
overuse is frequently present. Efforts to improve care for patients with headache
will benefit from distinguishing the high utilizer as a subset of the migraine
population.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 12390637 [PubMed - indexed for MEDLINE]

2815: Headache. 2002 Sep;42(8):715-27.

Comment in:
    Arch Intern Med. 2007 Nov 12;167(20):2263-4.    Headache. 2003 Jun;43(6):697; author reply 696-7.

Migraine and coronary heart disease in women and men.

Cook NR, Benseñor IM, Lotufo PA, Lee IM, Skerrett PJ, Chown MJ, Ajani UA, Manson 
JE, Buring JE.

Department of Medicine, Brigham and Women's Hospital, Harvard Medical School,
Boston, MA 02215, USA.

OBJECTIVE: We evaluated migraine as an independent risk factor for subsequent
coronary heart disease (CHD) events among women in the Women's Health Study (WHS)
and men in the Physicians' Health Study (PHS). BACKGROUND: Although several
studies have suggested that migraine is associated with increased risk of stroke,
there are few and conflicting data on whether migraine predicts risk of future
CHD events. METHODS: The WHS is an ongoing randomized, double-blind,
placebo-controlled trial of low-dose aspirin and vitamin E in the primary
prevention of cardiovascular disease and cancer in 39876 women health
professionals aged > or =45 years in 1993, and the PHS is a completed randomized,
double-blind, placebo-controlled trial of aspirin and beta-carotene in the
primary prevention of cardiovascular disease and cancer in 22071 men physicians
aged 40 to 84 years in 1982. Primary endpoints were defined as major CHD
(nonfatal myocardial infarction [MI] or fatal CHD) and total CHD (major CHD plus 
angina and coronary revascularization). RESULTS: After adjusting for other CHD
risk factors, female health professionals and male physicians reporting migraine 
were not at increased risk for subsequent major CHD (women: relative risk [RR],
0.83; 95% confidence interval [CI], 0.53 to 1.29; men: RR, 1.02; 95% Cl, 0.79 to 
1.31) or total CHD (women: RR, 1.01; 95% Cl, 0.76 to 1.34; men: RR, 0.98; 95% Cl,
0.82 to 1.18). When considered separately, there was also no increase in risk of 
MI or angina. CONCLUSION: These prospective data suggest that migraine is not
associated with increased risk of subsequent CHD events in women or men.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 12390634 [PubMed - indexed for MEDLINE]

2816: Headache. 2002 Oct;42(9):934-44.

Comment in:
    Headache. 2002 Oct;42(9):843-4.

Migraine and psychiatric comorbidity: from theory and hypotheses to clinical
application.

Sheftell FD, Atlas SJ.

New England Center for Headache, Stamford, Connecticut, and Atlas Biomedical
Communications, Columbia, Maryland, USA.

OBJECTIVE: To review psychiatric issues that accompany migraine and means of
addressing these issues. BACKGROUND: Psychiatric factors and migraine may
interact in three general ways, etiologically, psychophysiologically or
biobehaviorally, and comorbidly (the two disorders coexist), which is the present
focus. There are several possible mechanisms of comorbidity. The relation between
two disorders may be a result of chance. One disorder can cause another disorder:
Diabetes can cause diabetic neuropathy. There might be shared environmental
risks: Head trauma can cause both posttraumatic epilepsy and posttraumatic
headache. And there may be environmental or genetic risk factors that produce a
brain state giving rise to both conditions, that is, there may be some common
biology underlying both conditions. This last mechanism seems to be the most
likely one underlying comorbidity of migraine and psychiatric disorders. We
introduce a possible role for classical paradigms of learned helplessness in
regard to psychiatric comorbid depressive and anxiety disorders and migraine.
RESULTS: There appears to be an association between migraine and affective
disorders, particularly depression and anxiety. There are a number of formal
tools for recognizing depression, but clinical evaluation should not be
overlooked. Once diagnosed, depression and anxiety should be treated, both to
improve the success of migraine treatment and to improve the patient's quality of
life. Patients with recurring headaches are much more likely to overuse and
misuse, rather than abuse, pain medications. It is important to be alert for
signs that the patient may be misusing medication. Behavioral approaches can
surround and support pharmacological therapy. CONCLUSIONS: Migraine is often
comorbid with psychiatric disorders, particularly depression and anxiety. The
relationship is likely based on shared mechanisms and successful treatment is
possible.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 12390624 [PubMed - indexed for MEDLINE]

2817: Headache. 2002 Oct;42(9):930-3.

Transient visual disturbances during migraine without aura attacks.

Cologno D, Torelli P, Manzoni GC.

Headache Centre, Institute of Neurology, University of Parma, Parma, Italy.

OBJECTIVE: To evaluate the prevalence and clinical features of transient visual
disturbances (TVDs) during migraine without aura (MO) attacks and to point out
any similarities with the disturbances listed among the diagnostic criteria of
the International Headache Society (IHS) classification for migraine with aura
(MA). METHODS: We studied a sample of 191 patients (145 women and 46 men) with MO
and no other associated forms of primary headache who had been referred to the
University of Parma Headache Centre between December 1, 1999 and December 1,
2000. RESULTS: A total of 165 patients reported that they had never experienced
TVDs during their MO attacks. In the remaining 26 patients (19 women and 7 men), 
MO attacks were at times accompanied by TVDs, which were present in over 30% of
MO attacks in 65.4% of patients. In about 60% of cases, TVDs lasted less than
half a minute. TVDs consisted of phosphenes in most patients, general blurring of
vision in about one-fourth, and scintillating scotomas in 15%. In 73% of cases,
TVDs occurred during the headache phase, whereas in the remainder they preceded
it. Strict application of the IHS diagnostic criteria would have led to a
diagnosis of MA in 12 cases, corresponding to 46% of our MO patients with TVDs
and to 6.3% of all patients with an established clinical diagnosis of MO.
CONCLUSION: The results of our study suggest that current IHS diagnostic criteria
for MA may lead to an overestimation of MA cases.

Publication Types: 
    Comparative Study

PMID: 12390623 [PubMed - indexed for MEDLINE]

2818: Headache. 2002 Oct;42(9):924-9.

Erratum in:
    Headache. 2003 Feb;43(2):172.    Headache. 2003 Mar;43(3):310.

Hormone supplementation differently affects migraine in postmenopausal women.

Facchinetti F, Nappi RE, Tirelli A, Polatti F, Nappi G, Sances G.

University Centre for Adaptive Disorders and Headache, Pava, Italy.

OBJECTIVE: To evaluate the effects of three schemes of oral hormone replacement
therapy (HRT) on migraine course in postmenopausal women. METHODS: Thirty-eight
patients presenting for clinical evaluation of menopausal status and suffering
from migraine were enrolled. The observational period lasted 7 months, during
which women filled in a daily diary with the clinical features of headache
attacks and analgesic use. We evaluated climacteric symptoms, anxiety and
depression. After a 1-month run-in period, women were assigned to one of three
regimens of HRT: estradiol hemihydrate 1 mg/day plus norethisterone 0.5 mg/day
for 28 days, in a continuous combined scheme; oral conjugated estrogens 0.625
mg/day for 28 days plus medroxyprogesterone acetate 10 mg/day in the last 14
days, in a sequential continuous scheme; and estradiol valerate 2 mg/day for 21
days plus cyproterone acetate 1 mg/day from day 12 to 21 in a sequential cyclical
scheme. Follow-up evaluations were performed at 3 and 6 months. RESULTS: During
the run-in period, the three subgroups of patients were similar as far as the
features of migraine are concerned. Overall, a progressive increase in attack
frequency (from 2.2 +/- 1.0 to 3.8 +/- 1.3, P<.001), days with headache (from 3.4
+/- 1.3 to 4.9 +/- 1.9, P<.001), and analgesic consumption (from 3.4 +/- 1.3 to
5.6 +/- 2.2, P<.001) was observed after 6 months. Duration of attacks decreased
(from 18.1 +/- 7.4 to 13.6 +/- 4.2 hours, P =.005), whereas severity worsened
(from 1.9 +/- 0.2 to 2.1 +/- 0.2, P<.001). The increase in number of days with
headache and number of analgesics used was smaller in the group receiving the
continuous combined regimen than in the other two groups. CONCLUSION: Although
HRT typically will lead to some worsening of headache syndrome, estradiol
hemihydrate plus norethisterone given in a combined continuous scheme was the
regimen best tolerated by our patients.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 12390622 [PubMed - indexed for MEDLINE]

2819: Headache. 2002 Oct;42(9):917-23.

Further evaluation of rizatriptan in menstrual migraine: retrospective analysis
of long-term data.

Silberstein SD, Massiou H, McCarroll KA, Lines CR.

Jefferson Headache Center, Thomas Jefferson University Hospital, Philadelphia,
Pennsylvania, USA.

OBJECTIVE: To determine the long-term efficacy of oral rizatriptan 10-mg wafers
in the treatment of menstrual migraine attacks. METHODS: Data from an extension
study where patients with migraine used rizatriptan 10 mg to treat moderate or
severe migraine attacks occurring over periods of up to 6 months were included in
a retrospective analysis. Patients used a diary card to record details of each
migraine attack and onset of menstruation. Attacks in women were classified as
menstrual or nonmenstrual according to 3 time windows relative to onset of
menstruation (day 0): -3 to +3 days (7-day window), -2 to + 2 days (5-day
window), and 0 to +1 days (2-day window). The analysis looked at the efficacy of 
rizatriptan 10 mg by menstrual category of attack for each definition on three
measures: pain relief at 2 hours (reduction of pain to mild or none), pain free
at 2 hours, 24-hours sustained pain free (pain free at 2 hours with no headache
recurrence and no use of additional medications from 2 to 24 hours). RESULTS:
Ninety-five women used rizatriptan 10 mg to treat a total of 1,839 attacks. The
percentage of menstrual attacks was 30% for the -3 to +3 days definition, 23% for
the -2 to +2 days definition, and 11% for the 0 to +1 days definition.
Rizatriptan 10 mg was equally effective in menstrual and nonmenstrual migraine
attacks regardless of the definition used. For example, using the -3 to +3 days
definition, 78% of menstrual migraine attacks were relieved at 2 hours after
dosing compared with 78% of nonmenstrual attacks. Pain relief rates for the other
definitions were as follows: -2 to +2 days, menstrual = 78%, nonmenstrual = 78%; 
0 to +1 days, menstrual = 79%, and nonmenstrual = 78%. No differences between
menstrual and nonmenstrual attacks were found for the 2-hour pain free and
24-hour sustained pain free measures for any of the three definitions.
CONCLUSIONS: Rizatriptan 10-mg wafers were equally effective in the treatment of 
menstrual and nonmenstrual migraine attacks occurring over 6 months, regardless
of the precise definition of menstrual association used and even when the outcome
criteria were very stringent. These data provide further evidence that triptans
are effective treatments for menstrual migraine.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 12390621 [PubMed - indexed for MEDLINE]

2820: Headache. 2002 Oct;42(9):903-7.

Triptans versus analgesics.

Robbins L.

Department of Neurology, Rush Medical College, Chicago, IL 60062, USA.

OBJECTIVES: To retrospectively assess patient preferences between triptans and
analgesics in treating migraine headache. METHODS: The study assessed patient
preferences for triptans versus commonly used migraine analgesic preparations.
Over a 3-month period, 663 patients with migraine between the ages of 17 and 62
years completed an office-based survey. RESULTS: Most patients preferred a
treatment regimen that included either a triptan alone (52%) or a triptan with an
analgesic medication within 1 hour (18%). Overall, 70% of patients who had been
given triptans in the past chose to continue to use them, either alone or with an
analgesic. Patients who preferred analgesics alone comprised 21% of the total.
Nine percent preferred not to take either triptans or analgesic medications.
Among the patients who preferred triptans, 62% stated that increased efficacy was
the primary reason for their preference. Thirty percent cited both efficacy and
decreased adverse events. The remaining 8% believed that decreased adverse events
was the basis for their preference. CONCLUSIONS: Despite cost and other
limitations of triptans, most patients prefer them over nontriptan medications.
Enhanced efficacy was the main reason for choosing triptans over analgesics.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 12390618 [PubMed - indexed for MEDLINE]

2821: Headache. 2002 Oct;42(9):896-902.

Efficacy and tolerability of prochlorperazine buccal tablets in treatment of
acute migraine.

Sharma S, Prasad A, Nehru R, Anand KS, Rishi RK, Chaturvedi S, Bapna JS, Sharma
DR.

Departments of Neuropsychopharmacology, Institute of Human Behaviour & Allied
Sciences, Delhi, India.

OBJECTIVES: To study the efficacy and tolerability of prochlorperazine (PCZ)
management of acute migraine. DESIGN AND METHODS: A double blind comparative
study was conducted to assess the efficacy of buccal PCZ 3 mg compared with oral 
ergotamine tartarate 1 mg plus caffeine 100 mg (ERG) or placebo (buccal or oral) 
for treatment of acute migraine. In all, 114 episodes of acute migraine were
evaluated. Patients graded symptoms on a four-point scale before and up to 4
hours after treatment. The primary efficacy parameters included headache
resolution within 2 hours (grade 3 or 2 to grade 0) and alleviation of other
accompanying symptoms of migraine. The supplementary endpoints included
improvement in quality of life (QOL). RESULTS: The percentage of patients
reporting resolution of headache (to grade 0) was 51.4% for buccal PCZ and 21.7% 
for buccal placebo, 23.1% for oral ERG and 28.6% for oral placebo, headache
tended to recur in both the placebo and ERG groups after initial improvement.
Buccal PCZ was well tolerated; no signs of local irritation were evident, and
patients found the formulation easy to use. Mild but transient sedation and
drowsiness were observed in 41%. CONCLUSIONS: In the present study, PCZ 3 mg via 
the buccal route produced faster improvement and greater efficacy than placebo
(oral as well as buccal) or oral ERG. The global QOL score 2 hours after
treatment scores was higher in the PCZ group. Buccal PCZ may represent a
particularly effective alternative for acute migraine treatment.

Publication Types: 
    Clinical Trial
    Comparative Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 12390617 [PubMed - indexed for MEDLINE]

2822: Headache. 2002 Oct;42(9):893-5.

A polymorphism in the serotonin transporter gene regulatory region and frequency 
of migraine attacks.

Kotani K, Shimomura T, Shimomura F, Ikawa S, Nanba E.

Department of Clinical Laboratory Medicine, Faculty of Medicine, Tottori
University, Yonago 683-8503, Japan.

BACKGROUND: The serotonergic system has been thought to play an important part in
the pathophysiology of migraine. OBJECTIVE: To study an association between the
polymorphism of serotonin (5-hydroxytryptamine [5-HT]) transporter gene-linked
polymorphic region (5-HTTLPR) and migraine. Method.-We compared 151 patients with
migraine with 190 healthy unrelated control subjects. The 5-HTTLPR polymorphism
was detected using polymerase chain reaction. Migraine patients were interviewed 
regarding attack frequency in the last 6 months. RESULTS: We denoted the products
of the 484-base pair (bp) fragments as the short (s) and those of 528 bp as the
long (l) allele according to the previously reported manner. Migraine patients
with s/s genotype were compared with those with l/s and l/l genotype. We did not 
find significant differences in the genotype and allele frequencies of 5-HTTLPR
between patients with migraine and control subjects. Among patients with
migraine, those with s/s type had significantly more frequent attacks than those 
with the l/s or l/l type. CONCLUSIONS: This polymorphism does not appear to be
involved in a genetic predisposition to the disease but may affect the frequency 
of attacks in patients with migraine. These findings may contribute to our
understanding of factors that influence the clinical severity of migraine.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 12390616 [PubMed - indexed for MEDLINE]

2823: Headache. 2002 Oct;42(9):878-82.

Prevalence of migraine among Mexican Americans in San Diego, California: survey
1.

Molgaard CA, Rothrock J, Stang PE, Golbeck AL.

Department of Preventive Medicine and Public Health, University of Kansas School 
of Medicine-Wichita, KS 67214-3199, USA.

OBJECTIVE: To determine the population-based prevalence of migraine in a
cross-sectional random sample of Mexican Americans aged at least 45 years in San 
Diego County, California. BACKGROUND: The prevalence of migraine has been
assessed in various populations in the United States and Mexico, but no study of 
migraine prevalence in Mexican Americans has been reported in the literature to
date. DESIGN/METHODS: Using an epidemiological cross-sectional research design,
the population-based prevalence and associated descriptive epidemiology of
self-reported migraine was estimated in Mexican Americans aged at least 45 years 
in San Diego County, California from a random sample of size 657. RESULTS: The
lifetime migraine prevalence was 9.2% (95% confidence interval, 6.8 to 11.6) and 
current prevalence was 7.4% (95% confidence interval, 5.3 to 9.5). The prevalence
of migraine was higher in women than in men, higher in low income groups than in 
high income groups, and decreased with increasing age. Prevalence among Mexican
Americans born in Mexico was twice that of American-born Mexican Americans.
CONCLUSIONS: These population-based data on migraine prevalence in Mexican
Americans aged 45 and over contribute substantially to the understanding of this 
disease. A second study addressing migraine prevalence in Mexican Americans
younger than 45 years in San Diego County will be reported.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 12390613 [PubMed - indexed for MEDLINE]

2824: Headache. 2002 Oct;42(9):872-7.

Migraine with aura versus migraine without aura: pain intensity and associated
symptom intensities after placebo.

Bigal ME, Bordini CA, Sheftell FD, Speciali JG, Bigal JO.

Department of Neurology, Albert Einstein College of Medicine, Bronx, New York,
USA.

OBJECTIVE: To compare the intensity of pain and associated symptoms after placebo
administration in patients with migraine with aura and migraine without aura.
BACKGROUND: Studies that evaluate drugs used in the acute treatment of migraine
ideally should include a placebo arm. The International Headache Society also
recommends stratification according to age and sex but not by the presence versus
absence of aura. METHODS: The study was conducted as part of a placebo controlled
randomized survey comparing four active drugs against placebo in the acute
treatment of migraine. Patients were blinded as to treatment received. Placebo
consisted of 10 mL of normal saline (0.9%) intravenously. Pain intensity was
evaluated by a 10-point analogical-verbal scale. Nausea, photophobia, and
phonophobia were evaluated by a four-point analogical-verbal scale. For
statistical analysis, unpaired t-test with Welch correction was used. RESULTS:
After placebo administration, reduction of symptom intensity (pain, nausea,
photophobia, and phonophobia) in patients with migraine without aura was
significantly greater than that observed in patients with migraine with aura.
CONCLUSIONS: Our findings suggest that studies comparing placebo against an
active drug should use stratification according to the presence versus absence of
aura.

Publication Types: 
    Clinical Trial
    Comparative Study
    Randomized Controlled Trial

PMID: 12390612 [PubMed - indexed for MEDLINE]

2825: Headache. 2002 Oct;42(9):862-71.

Intravenous dipyrone in the acute treatment of migraine without aura and migraine
with aura: a randomized, double blind, placebo controlled study.

Bigal ME, Bordini CA, Tepper SJ, Speciali JG.

Department of Neurology, Albert Einstein College of Medicine, Bronx, New York,
USA.

BACKGROUND: Dipyrone (Metamizol) has been used in the acute treatment of
migraines in Brazil. Some investigators have found it to be a highly effective
medication for migraine pain and associated symptoms. OBJECTIVE: To conduct a
randomized, placebo controlled, double blind study to assess the effect of
dipyrone on the pain and symptoms associated with migraine without aura or with
aura and the adverse effect profile of this medication. METHODS: For the migraine
without aura group, 44 patients were assigned at random to receive 1 g
intravenous dipyrone, and 30 patients received 10 mL 0.9% physiological saline.
For the migraine with aura group, 30 patients received both dipyrone or placebo. 
We used seven parameters of analgesic evaluation and an analog scale to assess
nausea, photophobia, and phonophobia. RESULTS: Patients receiving dipyrone
demonstrated a statistically superior improvement (P<.05 and P<.01) in pain and
all associated symptoms compared with control subjects. CONCLUSIONS: Dipyrone is 
an effective drug for the relief of acute migraine pain and associated symptoms.

Publication Types: 
    Clinical Trial
    Comparative Study
    Randomized Controlled Trial

PMID: 12390611 [PubMed - indexed for MEDLINE]

2826: Headache. 2002 Oct;42(9):855-61.

Acupuncture in the prophylactic treatment of migraine without aura: a comparison 
with flunarizine.

Allais G, De Lorenzo C, Quirico PE, Airola G, Tolardo G, Mana O, Benedetto C.

Woman's Headache Center, Department of Gynecology and Obstetrics, University of
Turin, Turin, Italy.

OBJECTIVES: In a randomized controlled trial extending over 6 months, we
evaluated the effectiveness of acupuncture versus flunarizine in the prophylactic
treatment of migraine without aura. METHODS: One hundred sixty women with
migraines were randomly assigned to acupuncture treatment (group A, n = 80) or to
an oral therapy with flunarizine (group F, n = 80). In group A, acupuncture was
carried out in weekly sessions for the first 2 months and then once a month for
the next 4 months. The same acupoints were used at each treatment: LR3 Taichong, 
SP6 Sanyinjiao, ST36 Zusanli, CV12 Zhongwan, LI4 Hegu, PC6 Neiguan, GB20 Fengchi,
GB14 Yangbai, EX-HN5 Taiyang, GV20 Baihui. In group F, 10 mg flunarizine were
given daily for the first 2 months and then for 20 days per month for the next 4 
months. RESULTS: The frequency of attacks and use of symptomatic drugs
significantly decreased during treatment in both groups. The number of attacks
after 2 and 4 months of therapy was significantly lower in group A than in group 
F, and analgesic consumption was significantly lower in group A at 2 months of
treatment. At 6 months no such differences existed between the two treatment
groups. Pain intensity was significantly reduced only by acupuncture treatment.
Side effects were significantly less frequent in group A. CONCLUSIONS:
Acupuncture proved to be adequate for migraine prophylaxis. Relative to
flunarizine, acupuncture treatment exhibited greater effectiveness in the first
months of therapy and superior tolerability.

Publication Types: 
    Clinical Trial
    Comparative Study
    Randomized Controlled Trial

PMID: 12390610 [PubMed - indexed for MEDLINE]

2827: Headache. 2002 Oct;42(9):845-54.

Effectiveness of multidisciplinary intervention in the treatment of migraine: a
randomized clinical trial.

Lemstra M, Stewart B, Olszynski WP.

Department of Medicine, University of Alberta, Edmonton, Alberta.

OBJECTIVE: To test the effectiveness of a multidisciplinary management program
for migraine treatment in a group, low cost, nonclinical setting. DESIGN: A
prospective, randomized, clinical trial. BACKGROUND: Although numerous studies
document the efficacy of pharmacological migraine management, it is unclear
whether an effective long-term management approach exists. METHODS: Eighty men
and women were randomly assigned to 1 of 2 groups. The intervention group
consisted of a neurologist and physical therapist intake and discharge, 18
group-supervised exercise therapy sessions, 2 group stress management and
relaxation therapy lectures, 1 group dietary lecture, and 2 massage therapy
sessions. The control group consisted of standard care with the patient's family 
physician. Outcome measures included self-perceived pain intensity, frequency,
and duration; functional status; quality of life; health status; depression;
prescription and nonprescription medication use; and work status. Outcomes were
measured at the end of the 6-week intervention and at a 3-month follow-up.
Results.-Forty-one of 44 patients from the intervention group and all 36 patients
from the control group completed the study. There were no statistically
significant differences between the 2 groups before intervention. Intention to
treat analysis revealed that the intervention group experienced statistically
significant changes in self-perceived pain frequency (P =.000), pain intensity (P
=.001), pain duration (P =.000), functional status (P =.000), quality of life (P 
=.000), health status (P =.000), pain related disability (P =.000), and
depression (P =.000); these differences retained their significance at the
3-month follow-up. There were no statistically significant changes in medication 
use or work status. CONCLUSIONS: Positive health related outcomes in migraine can
be obtained with a low cost, group, multidisciplinary intervention in a community
based nonclinical setting.

Publication Types: 
    Clinical Trial
    Comparative Study
    Randomized Controlled Trial

PMID: 12390609 [PubMed - indexed for MEDLINE]

2828: Scand J Prim Health Care. 2002 Sep;20(3):157-60.

Patient satisfaction with a neurological specialist consultation for headache.

Bekkelund SI, Salvesen R.

Department of Neurology, Tromsø University Hospital, Norway. nevrsib@rito.no

OBJECTIVE: To evaluate patient satisfaction with a specialist consultation for
headache and thus identify subgroups of headache patients more satisfied than
others. DESIGN: A survey of consecutive patients referred to a neurologist for
headache. SETTING: Neurological outpatient clinics in North Norway. PATIENTS: We 
included 889 consecutive patients referred to a specialist centre for headache
during a period of 2 years. Using a questionnaire, we recorded patients'
satisfaction with the potential treatment initiated by the specialist. RESULTS:
Sixty-three percent of migraine patients (95% CI, 0.58 to 0.68) were satisfied
with the consultation, compared to 44% of patients with non-migrainous headache
(95% CI, 0.40 to 0.70), (p = 0.01). Altogether 481 patients had some kind of
measure recommended by the neurologist, and 317 of these (66%) were satisfied
(95% CI, 0.62 to 0.70). Patients with tension-type headache and those who were
not prescribed specific treatment modalities were less satisfied. CONCLUSION: The
study confirms that patients with headache are satisfied with a neurological
specialist consideration, especially in the case of migraine.

Publication Types: 
    Comparative Study

PMID: 12389752 [PubMed - indexed for MEDLINE]

2829: Neurosci Lett. 2002 Oct 31;332(2):115-8.

Multimodal functional imaging of prolonged neurological deficits in a patient
suffering from familial hemiplegic migraine.

Gutschalk A, Kollmar R, Mohr A, Henze M, Ille N, Schwaninger M, Hartmann M,
Hähnel S, Haberkorn U, Rupp A, Meyding-Lamade U.

Department of Neurology, University of Heidelberg, 69120 Heidelberg, Germany.
alexander_gutschalk@med.uni-heidelberg.de

The case of a patient with familial hemiplegic migraine (FHM) suffering from
prolonged right sided hemiparesis and aphasia that persisted for more than 10
days is reported. The symptoms were accompanied by slowing of the
magnetoencephalogram over the left hemisphere, which normalized parallel to the
clinical improvement. Positron emission tomography obtained on the 6th day
revealed glucose-hypometabolism (hemispheric difference > or =10%) in left
hemisphere's fronto-basal cortex, caudate nucleus, and thalamus. In contrast,
magnetic resonance imaging including perfusion and diffusion weighted imaging was
normal and did not show significant alterations of cortical perfusion or water
mobility during the episode. We hypothesize that this finding provides evidence
for a primary neuronal dysfunction causing the prolonged neurological deficits in
FHM. Copyright 2002 Elsevier Science Ireland Ltd.

Publication Types: 
    Case Reports

PMID: 12384224 [PubMed - indexed for MEDLINE]

2830: Cephalalgia. 2002 Oct;22(8):686-91.

The early use of ergotamine in migraine. Edward Woakes' report of 1868, its
theoretical and practical background and its international reception.

Koehler PJ, Isler H.

Departments of Neurology, Atrium Medical Centre, Heerlen, The Netherlands.
pkoehler@knmg.nl

Although ergot had been used in obstetrics for several centuries, it was proposed
for the treatment of migraine only in the 19th century. The British ENT-surgeon
Edward Woakes (1837-1912) recommended ergot as a vasoconstricting agent for
migraine and other neurogenic conditions associated with vasodilatation in 1868. 
He subscribed to the theory of vasodilatation by sympathetic deficit, presented
in the early 1850s by Brown-Séquard and Claude Bernard. Du Bois-Reymond proposed 
vasoconstriction by sympathetic overactivity as the cause of migraine in 1860;
Brown-Séquard opposed this in favour of vasodilatation. Vasodilatation due to
sympathetic deficit in migraine was again supported by Möllendorf, with clinical 
evidence, in 1867. Woakes' paper of 1868 introduced ergot as a vasoconstrictor
for the same condition. Reception abroad was prompt. A German version appeared in
1869, and Eulenburg cited Woakes in his textbook of 1871. Eulenburg presented the
use of ergot for migraine as a routine measure in the second edition of his
textbook in 1878, and in a paper published in 1883. The method was
internationally accepted, but it became really popular only after the isolation
of pure ergotamine in 1918, resulting in the first reliable compounds with stable
properties and predictable effects. Contrary to Woakes' theory, in the early 20th
century ergot was used for migraine because of its well-documented adrenolytic
properties, as migraine was by then again believed to be a sympathotonic and
vasospastic condition.

Publication Types: 
    Biography
    Historical Article

Personal Name as Subject: 
    Woakes E

PMID: 12383066 [PubMed - indexed for MEDLINE]

2831: Cephalalgia. 2002 Oct;22(8):680-5.

Determinants of migraine-specific quality of life.

Santanello NC, Davies G, Allen C, Kramer M, Lipton R.

Merck Research Laboratories, West Point, PA 19486, USA.
nancy_santanello@merck.com

This paper reports an analysis of two randomized controlled trials of
rizatriptan, in which the 24-h Migraine Quality of Life QuestionnaireCopyright
was used to assess migraine-specific quality of life in patients receiving acute 
treatment. The objective of the analysis was to determine which clinical effects 
of a migraine medication, as measured by traditional clinical trial endpoints,
contribute to a better short-term health-related quality of life. The results
demonstrate that patients who experience complete pain relief and are able to
function at their normal ability within 2 h and experience no headache recurrence
have the highest migraine-specific quality of life scores. Patients who were
satisfied with medication at 2 h had higher migraine-specific quality of life
scores than those who were not satisfied. In conclusion, migraine therapy that
provides rapid, complete, and sustained pain relief, with restoration of
functional ability, has the most beneficial impact on short-term health-related
quality of life for migraineurs.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial

PMID: 12383065 [PubMed - indexed for MEDLINE]

2832: Cephalalgia. 2002 Oct;22(8):664-6.

Sum of Pain Intensity Differences (SPID) in migraine trials. A comment based on
four rizatriptan trials.

Tfelt-Hansen P, McCarroll K, Lines C.

Department of Neurology, Glostrup Hospital, University of Copenhagen, Glostrup,
Denmark. tfelt@inet.uni2.dk

Sum of Pain Intensity Difference (SPID) is an outcome measure that summarizes
treatment response over a clinically relevant period. SPID is widely reported in 
clinical trials of analgesics but has been little used in migraine trials. We
compared SPID over 2 h with the standard migraine outcome measures of pain-free
at 2 h and headache relief at 2 h using data from four published clinical trials 
of rizatriptan in migraine patients. In assessing treatment response (rizatriptan
and sumatriptan versus placebo, rizatriptan versus sumatriptan, within-treatment 
dose effects), SPID usually yielded similar results to the more easily understood
pain-free measure.

Publication Types: 
    Comparative Study

PMID: 12383062 [PubMed - indexed for MEDLINE]

2833: Cephalalgia. 2002 Oct;22(8):659-63.

Topiramate: a case series study in migraine prophylaxis.

Young WB, Hopkins MM, Shechter AL, Silberstein SD.

Department of Neurology and Jefferson Headache Center, Thomas Jefferson
University, Philadelphia, PA 19107, USA. William. B. Young@mail.tju.edu

We reviewed the electronic records of 74 migraine patients treated with
topiramate for more than 6 weeks. Twenty-four patients had episodic migraine and 
50 had chronic (transformed) migraine. Most (81%) started treatment at 25 mg per 
day and reached a dose of 100 mg twice a day (mean dose on the last follow-up
visit was 208 mg). The mean headache frequency decreased from 20.6 days to 13.6
days per month (P<0.0001) for all headaches (9.9-5.1 (P<0.0001) and 25.7-17.7
(P<0.001) for episodic migraine and chronic migraine, respectively). The
percentage of patients whose headache frequency was reduced by > or =50% was
44.6% for all patients; 58.3 for episodic migraine and 38.0 for chronic migraine.
For all patients mean headache severity (10-point scale) was reduced from 6.2 to 
4.8 (P<0.0001). Patients on monotherapy (20%) and polytherapy (80%) had similar
reductions in headache frequency. Adverse events were usually mild to moderate
and were seen in 58.1% (paresthesias in 25%, cognitive difficulties 14.9%). Mean 
weight loss was 3.1 +/- 4 kg (3.8% of total body weight).

PMID: 12383061 [PubMed - indexed for MEDLINE]

2834: Cephalalgia. 2002 Oct;22(8):633-58.

Erratum in:
    Cephalalgia. 2003 Feb;23(1):71..

Comment in:
    Cephalalgia. 2004 Aug;24(8):688.

Triptans (serotonin, 5-HT1B/1D agonists) in migraine: detailed results and
methods of a meta-analysis of 53 trials.

Ferrari MD, Goadsby PJ, Roon KI, Lipton RB.

Department of Neurology, Leiden University Medical Centre, Leiden, The
Netherlands. M.D.Ferrari@LUMC.NL

The triptans, selective serotonin 5-HT1B/1D agonists, are very effective acute
migraine drugs. Soon, seven different triptans will be clinically available at 13
different oral doses, making evidence-based selection guidelines necessary.
Triptan trials have similar designs, facilitating meta-analysis. We wished to
provide an evidence-based foundation for using triptans in clinical practice, and
to review the methodological issues surrounding triptan trials. We asked
pharmaceutical companies and the principal investigators of company-independent
trials for the 'raw patient data' of all double-blind, randomized, controlled,
clinical trials with oral triptans in migraine. All data were cross-checked with 
published or presented data. We calculated summary estimates across studies for
important efficacy and tolerability parameters, and compared these with those
from direct, head-to-head, comparator trials. Out of 76 eligible clinical trials,
53 (12 not yet published) involving 24089 patients met the criteria for
inclusion. Mean results (and 95% confidence intervals) for sumatriptan 100 mg,
the first available and most widely prescribed oral triptan, are 59% (57-60) for 
2 h headache response (improvement from moderate or severe to mild or no pain);
29% (27-30) for 2 h pain free (improvement to no pain); 20% (18-21) for sustained
pain free (pain free by 2 h and no headache recurrence or use of rescue
medication 2-24 h post-dose), and 67% (63-70) for consistency (response in at
least two out of three treated attacks); placebo-subtracted proportions for
patients with at least one adverse event (AE) are 13% (8-18), for at least one
central nervous system AE 6% (3-9), and for at least one chest AE 1.9% (1.0-2.7).
Compared with these data: rizatriptan 10 mg shows better efficacy and
consistency, and similar tolerability; eletriptan 80 mg shows better efficacy,
similar consistency, but lower tolerability; almotriptan 12.5 mg shows similar
efficacy at 2 h but better sustained pain-free response, consistency, and
tolerability; sumatriptan 25 mg, naratriptan 2.5 mg and eletriptan 20 mg show
lower efficacy and better tolerability; zolmitriptan 2.5 mg and 5 mg, eletriptan 
40 mg, and rizatriptan 5 mg show very similar results. The results of the 22
trials that directly compared triptans show the same overall pattern. We received
no data on frovatriptan, but publicly available data suggest substantially lower 
efficacy. The major methodological issues involve the choice of the primary
endpoint, consistency over multiple attacks, how to evaluate headache recurrence,
use of placebo-subtracted proportions to control for across-study differences,
and the difference between tolerability and safety. In addition, there are a
number of methodological issues specific for direct comparator trials, including 
encapsulation and patient selection. At marketed doses, all oral triptans are
effective and well tolerated. Differences among them are in general relatively
small, but clinically relevant for individual patients. Rizatriptan 10 mg,
eletriptan 80 mg and almotriptan 12.5 mg provide the highest likelihood of
consistent success. Sumatriptan features the longest clinical experience and the 
widest range of formulations. All triptans are contra-indicated in the presence
of cardiovascular disease.

Publication Types: 
    Meta-Analysis
    Research Support, Non-U.S. Gov't

PMID: 12383060 [PubMed - indexed for MEDLINE]

2835: Cephalalgia. 2002 Oct;22(8):624-32.

Comment in:
    Cephalalgia. 2003 Nov;23(9):931; author reply 931.

What is the evolutionary advantage of migraine?

Loder E.

Headache and Pain Management Programs, Spaulding Rehabilitation Hospital, and
Harvard Medical School, Boston, MA 02114, USA. eloder@partners.org

Susceptibility to migraine is determined by genetic factors and is therefore
subject to the forces of natural selection. Migraine is a common and ancient
disorder whose prevalence may be increasing, suggesting that a migraine-prone
nervous system may be associated with reproductive or survival advantages. Five
evolutionary explanations are reviewed that might account for the persistence of 
migraine: (i). migraine as a defence mechanism; (ii). migraine as a result of
conflict with other organisms; (iii). migraine as result of novel environmental
factors; (iv). migraine as a trade-off between genetic harms and benefits; and
(v). migraine as a design constraint. An evolutionary perspective on migraine
allows the generation of important hypotheses about the disorder and suggests
rewarding possibilities for further research.

Publication Types: 
    Review

PMID: 12383059 [PubMed - indexed for MEDLINE]

2836: Eur Neurol. 2002;48(3):172-7.

Restoring migraine sufferers' ability to function normally: a comparison of
rizatriptan and other triptans in randomized trials.

Bussone G, D'Amico D, McCarroll KA, Gerth W, Lines CR.

National Neurological Institute C. Besta, Milan, Italy.

BACKGROUND: Many migraine patients are unable to function normally during a
migraine attack. Assessments of treatment efficacy have tended to focus on
migraine symptoms, rather than looking at functional impact. This study compared 
the efficacy of different oral triptans for restoring normal function in migraine
sufferers. METHODS: Retrospective subgroup analysis of data from five randomized,
placebo-controlled, double-blind clinical trials in which oral rizatriptan was
directly compared with oral sumatriptan 100 mg (772 attacks), 50 mg (2,227
attacks), and 25 mg (1,182 attacks), naratriptan 2.5 mg (413 attacks), and
zolmitriptan 2.5 mg (578 attacks) for the acute treatment of a moderate or severe
migraine attack. Functional disability was evaluated by patients on a 4-grade
scale ('normal', 'mild impairment', 'severe impairment', 'requires bedrest') at
baseline and at 0.5, 1, 1.5, 2, 3 and 4 h after dosing. This analysis looked at
the percentage of patients who had normal functional ability at 2 h, the last
time point before escape medications were allowed, in the subgroup of patients
who had some level of disability at baseline. RESULTS: Most patients in each
trial and treatment group had some level of disability at baseline (range =
94-100%). At 2 h, more patients on rizatriptan 10 mg were able to function
normally compared with sumatriptan 100 mg (39 vs. 32%, odds ratio = 1.4, p =
0.021), sumatriptan 50 mg (47 vs. 42%, odds ratio = 1.2, p = 0.033), sumatriptan 
25 mg (48 vs. 36%, odds ratio = 1.7, p < 0.001), naratriptan 2.5 mg (39 vs. 22%, 
odds ratio = 2.5, p < 0.001), and zolmitriptan 2.5 mg (45 vs. 36%, odds ratio =
1.6, p = 0.008). CONCLUSION: In direct head-to-head comparative clinical trials, 
oral rizatriptan 10 mg enabled more migraine sufferers to function normally at 2 
h after dosing than oral sumatriptan, naratriptan, and zolmitriptan. Copyright
2002 S. Karger AG, Basel

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 12373035 [PubMed - indexed for MEDLINE]

2837: Neurology. 2002 Oct 8;59(7):1099-101.

Migraine with aura is not linked to the FHM gene CACNA1A or the chromosomal
region, 19p13.

Noble-Topham SE, Dyment DA, Cader MZ, Ganapathy R, Brown JD, Rice GP, Ebers GC.

Lawson Health Research Institute, London Health Sciences Centre, University of
Western Ontario, London, Canada.

Two microsatellite markers, tightly linked to CACNA1A, were genotyped in migraine
with aura (MA) families to determine if this gene, which underlies the 19p13
linked forms of familial hemiplegic migraine, is also linked to MA. Two-point
parametric lod and nonparametric linkage scores did not support linkage.
Transmission disequilibrium testing provided no evidence for linkage of MA to
CACNA1A. In a large dataset of 64 Canadian MA families, the authors did not find 
evidence to support an MA susceptibility gene in the region of 19p13.

PMID: 12370474 [PubMed - indexed for MEDLINE]

2838: Arq Neuropsiquiatr. 2002 Sep;60(3-B):695-8.

Hemicrania continua: a report of ten new cases.

Bigal ME, Tepper SJ, Sheftell FD, Rapoport AM.

International Headache Society Fellow, The New England Center for Headache, New
York, NY, USA. marcelobigal@hotmail.com

Hemicrania continua (HC) is an uncommon primary headache first described as a
syndrome in 1984. Being quite unusual, its clinical characterization still
demands better description. The aim of this study is to present the main clinical
characteristics of 10 patients with the diagnosis of HC seen in a tertiary
center, critically discussing their main features. All subjects had strictly
unilateral headache without side shift and absolute response to indomethacin.
Seven patients (70%) presented autonomic features during pain exacerbations. Four
(40%) had migrainous symptoms during the exacerbations and one presented partial 
relief with dihydroergotamine. One patient had pain excruciatingly severe during 
the exacerbations. Although the cardinal features of HC - continuous, unilateral,
indomethacin responsive, remain strongly reliable, a refinement on the clinical
characterization is needful and desired.

Publication Types: 
    Case Reports

PMID: 12364931 [PubMed - indexed for MEDLINE]

2839: Compr Ther. 2002 Fall;28(3):241-54.

Erratum in:
    Compr Ther. 2002 Winter;28(4):180.

Mechanism and management of migraine.

Spierings EL.

Department of Neurology, Brigham and Women's Hospital, Harvard Medical School,
Boston, Mass., USA.

Migraine is a condition that affects 10%-15% of the population. Abortive
treatment is always indicated because the intense headaches interfere with normal
functioning. Preventive treatment is indicated when the headaches exceed 3-4 per 
month.

Publication Types: 
    Review

PMID: 12360637 [PubMed - indexed for MEDLINE]

2840: J Emerg Med. 2002 Aug;23(2):141-8.

Comment in:
    J Emerg Med. 2003 Oct;25(3):322-3.

Intravenous chlorpromazine in the emergency department treatment of migraines: a 
randomized controlled trial.

Bigal ME, Bordini CA, Speciali JG.

Department of Neurology, School of Medicine at Ribeirão Preto, São Paulo
University, Ribeirão Preto, SP, Brazil.

The aim of this study is to assess, in a double blind randomized clinical trial, 
the effect of chlorpromazine (CPZ) on the pain and associated symptoms in
patients with migraine. Sixty patients with migraine with aura and 68 patients
with migraine without aura were assigned at random to receive IV 0.1 mg/Kg CPZ or
placebo. We assessed pain intensity, nausea, photophobia, and phonophobia at
baseline, 30 min, and 60 min post-IV administration. End-point efficacy at 60 min
was used to calculate the number needed to treat (NNT). We also recorded adverse 
effects, need for rescue medication at 24 h, and recurrence of headache at 24 h. 
We found clinically and statistically significant (p < 0.01) improvement
associated with CPZ in pain scores, nausea, photophobia, phonophobia, and need
for rescue medication, all at 60 min, and in rate of recurrence at 24 h, both in 
patients with and without aura. NNT = 2. Those allocated to CPZ had less nausea
and dyspepsia, but more drowsiness and postural hypotension than those receiving 
placebo. CPZ is an excellent option for the treatment of migraines, with and
without aura, in the Emergency Department.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial

PMID: 12359281 [PubMed - indexed for MEDLINE]

2841: Eur J Pharmacol. 2002 Oct 4;452(2):223-8.

The effect of anti-migraine compounds on nitric oxide-induced dilation of dural
meningeal vessels.

Akerman S, Williamson DJ, Kaube H, Goadsby PJ.

Headache Group, Institute of Neurology and Neurosurgery, The National Hospital
for Neurology, Queen Square, WC1N 3BG, London, UK.

Migraine is characteristically accompanied by a throbbing quality of head pain
thought to involve trigeminovascular afferents. Administration of nitric oxide
(NO) donors provides the most reliable model of migraine induction in humans. The
present studies used intravital microscopy to monitor the effect of local
meningeal nerve stimulation and NO on dural blood vessels and any modulation of
that effect by anti-migraine compounds. NO caused an immediate and reproducible
dilation of meningeal blood vessels that was partially blocked by sumatriptan and
indomethacin, while flunarizine and histamine H(1) and H(2) receptor antagonists 
were unable to block the dilation. Indomethacin also inhibited the neurogenic
dilation while flunarizine did not. The present studies demonstrate that NO is
unlikely to interact with histamine to produce its dilatory response. Sumatriptan
and indomethacin inhibit the NO response by inhibiting trigeminal activation and 
calcitonin gene-related peptide (CGRP) release. Flunarizine does not modify
either the neurogenic vasodilator response or the NO meningeal dilator response
at least acutely.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 12354573 [PubMed - indexed for MEDLINE]

2842: CNS Drug Rev. 2002 Fall;8(3):217-34.

Almotriptan, a new anti-migraine agent: a review.

Gras J, Llenas J, Jansat JM, Jáuregui J, Cabarrocas X, Palacios JM.

Pharmacological Development Department, Almirall Prodesfarma, Research Center,
Barcelona, Spain. jgras@almirallprodesfarma.com.

Almotriptan is a new anti-migraine agent with nanomolar affinity for human
5-HT(1B), 5-HT(1D), and 5-HT(1F) receptors, weak affinity for 5-HT(1A) and
5-HT(7) receptors and no significant affinity for more than 20 other
pharmacological receptors. Almotriptan was effective in animal models predictive 
of anti-migraine activity in humans and had a good safety profile in animal
studies. From the toxicological point of view, almotriptan has a profile similar 
to that of other marketed triptans. In animal studies, at levels substantially
higher than required for therapeutic activity in humans, almotriptan was devoid
of any oncogenic, genotoxic or teratogenic effects. Almotriptan is well absorbed 
orally; its absolute bioavailability in humans is 70%. Its peak plasma levels are
reached at 1 to 3 h after its administration; its elimination half-life is 3 to 4
h. Almotriptan is metabolized by monoamine oxidase-mediated oxidative deamination
and cytochrome P450-mediated oxidation as the major metabolic route and by flavin
monooxygenase as the minor route. No dose adjustment is required for gender or
age, and only in the case of severe renal impairment the dose should not exceed
12.5 mg over a 24-h period. There was no significant interaction between a single
dose of almotriptan and propranolol, fluoxetine or verapamil, at multiple doses. 
The efficacy of almotriptan in the treatment of acute migraine was demonstrated
in clinical trials on more than 3000 patients with migraine. At two h after oral 
administration of almotriptan, 12.5 mg, the percentages of patients showing pain 
relief and a pain-free score were 64 and 36%, respectively. The effects of
almotriptan were significantly better than those of placebo. When almotriptan was
administered in the early phase of migraine, the percentage of pain-free patients
at 2 h rose to 84%. In a phase III, double-blind and placebo-controlled study,
the incidence of adverse events with almotriptan was not statistically different 
from that of placebo. Based on the available data, it appears that almotriptan is
the triptan of choice when good efficacy and high tolerability are desired.

Publication Types: 
    Review

PMID: 12353056 [PubMed - indexed for MEDLINE]

2843: J Neuroophthalmol. 2002 Sep;22(3):215-21.

Comment in:
    J Neuroophthalmol. 2003 Sep;23(3):240; author reply 240-1.

Oculomotor ophthalmoplegic migraine: is it really migraine?

Carlow TJ.

School of Medicine, University of New Mexico, 302 Juniper Hill Road, Albuquerque,
NM 87122, USA. tjcarlow@swcp.com

Oculomotor ophthalmoplegic migraine is a rare episodic childhood condition in
which a unilateral oculomotor palsy is preceded by headache. I describe six new
cases that had magnetic resonance imaging signal abnormalities during the acute
phase, consisting of a thickened and enhancing ipsilateral oculomotor nerve at
its exit from the midbrain. During the quiescent phase, when the headache had
resolved, the signal abnormalities were still present but less dramatic.
Seventeen similar cases have been previously reported. The pathophysiology may be
a trigeminovascular migraine epiphenomenon that is dependent on the unique
oculomotor nerve anatomy and porous blood-nerve barrier at the emergence of the
oculomotor nerve from the brainstem and the sequelae of demyelination. Early
high-dose corticosteroid treatment is recommended to rapidly resolve an acute
episode and to potentially prevent permanent abnormal oculomotor nerve signs.

Publication Types: 
    Case Reports
    Lectures

PMID: 12352586 [PubMed - indexed for MEDLINE]

2844: Neurology. 2002 Sep 24;59(6):904-8.

Migraine and cognitive function: a life-course study.

Waldie KE, Hausmann M, Milne BJ, Poulton R.

Department of Psychology, University of Auckland, New Zealand.
k.waldie@auckland.ac.nz

OBJECTIVE: To investigate the association between migraine and cognitive ability 
among members of a longitudinal birth cohort study. METHODS: Headache status was 
determined at age 26 (migraine, tension-type headache [TTH], headache-free
control subjects) according to International Headache Society criteria, and data 
relating to cognitive and academic performance from ages 3 to 26 years were
analyzed. RESULTS: Study members diagnosed with migraine were subtly but
significantly impaired, compared with those with TTH and headache-free control
subjects, on tests of verbal ability (especially language reception) from ages 3 
to 13, independent of headache history. Performance on other tasks, including
reading, arithmetic, motor, and spatial ability, was normal. The association
between migraine and verbal functioning also appeared to impact on later academic
success. CONCLUSION: Findings suggest that the poorer verbal performance was
unlikely to have resulted from cumulative attacks and may be due to developmental
factors beginning in utero.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 12297575 [PubMed - indexed for MEDLINE]

2845: Adolesc Med. 2002 Oct;13(3):413-32.

Migraine headaches in the adolescent.

Lewis DW.

Departments of Pediatrics and Neurology, Eastern Virginia Medical School,
Norfolk, Virginia 23510, USA.

Migraine headaches are common in adolescents. Characterized by recurring attacks 
of intense, pounding, and nauseating frontal or temporal head pain, migraine
headaches are a significant contributor to school absences and lost productivity 
during the adolescent years and beyond. A systematic management program can be
instituted to minimize these deleterious effects. The first step is to establish 
the diagnosis and reassure the patient that there is no serious underlying cause 
such as a brain tumor. The next step involves identification of lifestyle
contributors followed by appropriate modification of sleep, activity, stress,
diet, and other provocative influences, often with behavioral therapies. There is
a vast, new pharmacologic armamentarium for the acute and preventative management
of migraine. The choices depend on the headache burden: the individual patient's 
pattern, frequency, intensity, disability, and pain tolerance. This chapter
reviews the phenomena of adolescent migraine with emphasis on office management.

Publication Types: 
    Review

PMID: 12270792 [PubMed - indexed for MEDLINE]

2846: CNS Drugs. 2002;16(10):715-20.

Spotlight on rizatriptan in migraine.

Wellington K, Jarvis B.

Adis International Limited, Mairangi Bay, Auckland, New Zealand.
demail@adis.co.nz

Rizatriptan is an orally active serotonin 5-HT(1) receptor agonist that potently 
and selectively binds to 5-HT(1B/1D) subtypes. Earlier clinical trials
demonstrated that rizatriptan 5 or 10mg is more effective than placebo at
providing pain relief and a pain-free state, relieving associated symptoms of
migraine, normalising functional ability and improving patient quality of life,
and showed that rizatriptan provides faster freedom from pain and reduces nausea 
to a greater extent than oral sumatriptan. More recently, rizatriptan 10mg was
shown to be more effective than zolmitriptan 2.5mg or naratriptan 2.5mg at
producing a pain-free state 2 hours postdose. Furthermore, compared with
naratriptan, significantly more patients who received rizatriptan were pain free 
or had pain relief from 1 hour onwards. The number of patients with normal
functional ability at 2 hours was significantly higher after rizatriptan than
after naratriptan or zolmitriptan. Rizatriptan was also generally more effective 
than zolmitriptan or naratriptan at relieving migraine-associated symptoms.
Rizatriptan is generally well tolerated, and adverse events are usually mild and 
transient. The most common adverse events associated with rizatriptan in recent
randomised trials were asthenia/fatigue, dizziness, somnolence and nausea. There 
was a trend towards a lower incidence of adverse events with rizatriptan compared
with zolmitriptan (31.2 vs 38.8%). However, rizatriptan was associated with a
significantly higher incidence of adverse events than naratriptan (39 vs 29%).
The incidence of chest pain was similar after the administration of rizatriptan, 
zolmitriptan or naratriptan (2-4%). In conclusion, rizatriptan is an effective
drug for the acute treatment of moderate or severe migraine. Oral rizatriptan 5
and 10mg have shown greater efficacy than placebo in providing pain relief, an
absence of pain, relief from associated symptoms, normal functional ability and
an improvement in patient quality of life. Earlier results showed that
rizatriptan provides faster freedom from pain and reduces nausea to a greater
extent than oral sumatriptan. More recent studies have shown that rizatriptan
10mg provides faster pain relief and a higher percentage of patients with an
absence of pain and normal functional ability at 2 hours than naratriptan 2.5mg
or zolmitriptan 2.5mg. The efficacy of rizatriptan is retained when used in the
long term, and the drug is generally well tolerated. Although well designed
studies comparing rizatriptan with almotriptan, eletriptan and frovatriptan would
further define the position of rizatriptan, current data suggest that rizatriptan
should be considered as a first-line treatment option in the management of
migraine.

Publication Types: 
    Review

PMID: 12269863 [PubMed - indexed for MEDLINE]

2847: Nurs Times. 2002 Sep 3-9;98(36):22-4.

Migraine: management aetiology and diagnosis.

Fontebasso M.

Headache Clinic, York District Hospital, York.

Migraine is an episodic condition that significantly affects the quality of life 
of those who experience it. The headache may manifest with or without sensory or 
visual aura. This article explains what migraine is, why it differs from other
headaches and what drug therapies are available to treat it. It also includes
health promotion advice on the best ways to prevent attacks. The author stresses 
that the impact of migraine on quality of life should not be underestimated. It
is vital to give control back to sufferers rather than let migraine control them.

PMID: 12244664 [PubMed - indexed for MEDLINE]

2848: Manag Care Interface. 2002 Sep;15(9):40-3, 49.

A comparison of office-based physician visits for irritable bowel syndrome and
for migraine and asthma.

Kozma CM, Barghout V, Slaton T, Frech F, Reeder CE.

Strategic Outcomes Services of CareScience, Inc., Research Triangle Park, North
Carolina, USA. ckozma@carescience.com

Three years of data from the National Ambulatory Medical Care Survey were
analyzed to assess resource utilization for patients with irritable bowel
syndrome (IBS), asthma, and migraine. Adjusted for prevalence, IBS-related
physician visits occurred at approximately the same rate as those for asthma and 
2.6 times the rate of visits for migraine. Specialist consultations for IBS were 
of similar frequency to those for migraine and more frequent than those for
asthma. Diagnostic and screening tests were ordered more often during IBS-related
visits than during migraine- or asthma-related visits. Prescription rates were
similar for all three conditions. In terms of resource consumption, this chronic 
disorder places a burden on patients that is comparable with that of such costly 
conditions as asthma and migraine.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 12244649 [PubMed - indexed for MEDLINE]

2849: Arq Neuropsiquiatr. 2002 Sep;60(3-A):628-30.

Recurrent abdominal pain: when should an epileptic seizure be suspected?

Franzon RC, Lopes CF, Schmutzler KM, Morais MI, Guerreiro MM.

Departamento de Neurologia, Faculdade de Ciências Medicas, Universidade Estadual 
de Campinas, Campinas, SP, Brasil.

Recurrent episodes of abdominal pain are common in childhood. Among the
diagnostic possibilities are migraine and abdominal epilepsy (AE). AE is an
infrequent syndrome with paroxystic episodes of abdominal pain, awareness
disturbance, EEG abnormalities and positive results with the introduction of
antiepileptic drugs. We present one 6 year-old girl who had short episodes of
abdominal pain since the age of 4. The pain was followed by cry, fear and
occasionally secondary generalization. MRI showed tumor in the left temporal
region. As a differential diagnosis, we report a 10 year-old boy who had long
episodes of abdominal pain accompanied by blurring of vision, vertigo, gait
ataxia, dysarthria, acroparesthesias and vomiting. He received the diagnosis of
basilar migraine. In our opinion, AE is part of a large group (partial
epilepsies) and does not require a special classification. Pediatric neurologists
must be aware of these two entities that may cause abdominal pain.

Publication Types: 
    Case Reports

PMID: 12244404 [PubMed - indexed for MEDLINE]

2850: Arq Neuropsiquiatr. 2002 Sep;60(3-A):542-7.

Computed tomography scan of the head in patients with migraine or tension-type
headache.

Valenca MM, Valenca LP, Menezes TL.

Disciplina de Neurologia e Neurocirurgia, Departamento de Neuropsiquiatria,
Centro de Ciências da Saúde, Universidade Federal de Pernambuco, Recife, PE,
Brasil.

A retrospective study was performed in order to evaluate the frequency of
abnormalities found by computed tomography (CT) scan of the head in 78 patients
with migraine or tension-type headache. In the present study CT scan was normal
in 61.5% of the patients with migraine or tension-type headache. A number of
abnormalities were encountered in more than one third of the patients studied,
including inflammatory sinus disease (19.2%), cysticercosis (3.9%), unruptured
cerebral aneurysm (2.6%), basilar impression (2.6%), intracranial lipoma (2.6%), 
arachnoid cyst (2.6%), empty sella (2.6%), intracranial neoplasm (2.6%), and
others (2.6%). None of these lesions were symptomatic or responsible by the
headache picture, therefore, considered incidental findings. In conclusion, the
fortuitous encounter of some abnormalities on CT scan of the head is often higher
than what we could predict in patients suffering migraine or tension-type
headache. We briefly discuss clinical, epidemiologic, and practical management of
some of the abnormalities detected by CT scan as well as the indication to
request a neuroimaging investigation.

PMID: 12244387 [PubMed - indexed for MEDLINE]

2851: J Am Acad Nurse Pract. 2002 Aug;14(8):354-9; quiz 360-2.

Migraine and its treatment with 5-HT1B/1D agonists (triptans).

Moriarty-Sheehan M.

Headache Clinic, Department of Neurology, Georgetown University Hospital, USA.
MAM49@gunet.georgetown.edu

PURPOSE: To review the epidemiology and clinical features of migraine and to
discuss the use of the 5-HT1B/1D agonists (triptans) in the treatment of moderate
to severe migraine. DATA SOURCES: A Medline search was conducted for relevant
recent articles on migraine and the efficacy and safety of the triptans.
CONCLUSIONS: With the advent of a standardized classification system for headache
to simplify migraine diagnosis, new approaches to treatment, and effective new
therapies, such as the triptans, many patients have obtained significant relief
from the pain and disability associated with migraine. IMPLICATIONS FOR PRACTICE:
The key to successful migraine management is to provide the most effective
treatment at the earliest possible time. Under the step-care approach to migraine
management, the mildest and most conservative treatment was recommended as a
first step, without regard for the degree of the patient's pain or disability.
This approach has been replaced by stratified care, in which migraine management 
is based on the severity of the patient's pain and disability. Under the
stratified approach, patients with moderate or severe migraine would be
prescribed effective migraine-specific drugs, such as the triptans, as first-line
therapy.

Publication Types: 
    Review

PMID: 12242852 [PubMed - indexed for MEDLINE]

2852: J Neurol. 2002 Sep;249(9):1268-71.

Comparison of cortical excitability in chronic migraine (transformed migraine)
and migraine without aura. A transcranial magnetic stimulation study.

Ozturk V, Cakmur R, Donmez B, Yener GG, Kursad F, Idiman F.

Dokuz Eylül University, Medical School, Department of Neurology, 35340, Izmir,
Turkey. vesile.ozturk@deu.edu.tr

We studied the excitability of the motor cortex in patients with migraine without
aura (MWOA) (n = 20) and with chronic migraine (CM) (n = 20) using transcranial
magnetic stimulation (TMS). By using a 90-mm circular coil placed over the vertex
and recording of the first dorsal interosseous muscle, we measured thresholds,
latencies and amplitudes of motor evoked potentials and duration of cortical
silent periods in patient groups and in controls (n = 20). No differences were
found between groups for threshold, latency and amplitude values. However, the
duration of the cortical silent period was longer in CM patients, being
significantly different from both controls and MWOA. We suggest that either this 
difference in cortical excitability may develop during transformation from MWOA
to CM or different pathophysiological mechanisms may play a role in these two
headache syndromes.

Publication Types: 
    Comparative Study

PMID: 12242552 [PubMed - indexed for MEDLINE]

2853: Psychopathology. 2002 Jul-Aug;35(4):254-8.

Personality traits in migraine and tension-type headaches: a five-factor model
study.

Cao M, Zhang S, Wang K, Wang Y, Wang W.

Center for Psychological Counseling, Capital Normal University, Beijing, China.

Although abnormal personality traits have been frequently reported in patients
with primary headaches, the overlaps between these domains need a clear standard 
definition, for example, by a five-factor personality model. Moreover,
personality abnormalities in patients with episodic tension-type headache (ETH)
and migraine with aura (MA) are less well studied. Therefore, we administered
Zuckerman-Kuhlman's Personality Questionnaire to 72 patients suffering from
chronic tension-type headaches (CTH), 33 with ETH, 15 with MA and 57 with
migraine without aura (MO), as well as 58 healthy subjects. Depressive trends
were measured with Plutchik-van Praag's Depression Inventory. Compared to healthy
controls, the CTH, ETH and MO groups showed significantly greater
neuroticism-anxiety and depression. In addition, the MO group scored
significantly higher on aggression-hostility than healthy controls. No abnormal
personality traits were found in patients with MA. This study, from the
perspective of a five-factor model, confirms most previous reports about
personality in patients with primary headaches and establishes elevated
aggression-hostility only in MO sufferers. Copyright 2002 S. Karger AG, Basel

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 12239443 [PubMed - indexed for MEDLINE]

2854: J Med Chem. 2002 Sep 26;45(20):4383-6.

Ethyl (3S,4aR,6S,8aR)-6-(4-ethoxycar-
bonylimidazol-1-ylmethyl)decahydroiso-quinoline-3-carboxylic ester: a prodrug of 
a GluR5 kainate receptor antagonist active in two animal models of acute
migraine.

Filla SA, Winter MA, Johnson KW, Bleakman D, Bell MG, Bleisch TJ, Castaño AM,
Clemens-Smith A, del Prado M, Dieckman DK, Dominguez E, Escribano A, Ho KH,
Hudziak KJ, Katofiasc MA, Martinez-Perez JA, Mateo A, Mathes BM, Mattiuz EL,
Ogden AM, Phebus LA, Stack DR, Stratford RE, Ornstein PL.

Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana, 46285,
USA. filla_sandra_a@lilly.com

Amino diacid 3, a highly selective competitive GluR5 kainate receptor antagonist,
exhibited high GluR5 receptor affinity and selectivity over other glutamate
receptors. Its diethyl ester prodrug 4 was orally active in two models of
migraine: the neurogenic dural plasma protein extravasation model and the nucleus
caudalis c-fos expression model. These data suggest that a GluR5 kainate receptor
antagonist might be an efficacious antimigraine therapy with a novel mechanism of
action.

PMID: 12238915 [PubMed - indexed for MEDLINE]

2855: Br J Gen Pract. 2002 Sep;52(482):723-7.

Comment in:
    Br J Gen Pract. 2003 Feb;53(487):151.

Association between migraine and asthma: matched case-control study.

Davey G, Sedgwick P, Maier W, Visick G, Strachan DP, Anderson HR.

Department of Public Health Sciences, St George's Hospital Medical School,
London.

BACKGROUND: Earlier studies have suggested a link between asthma and severe
headache, and also between migraine and wheezing illness. Recent analysis have
also shown an increase of asthma among cases with a prior history of migraine but
without a history of hay fever, allergic rhinitis or eczema. AIM: To examine
whether there is an association between migraine and asthma in the United
Kingdom. DESIGN OF STUDY: Matched case-control study using the General Practice
Research Database (GPRD). SETTING: Practices in the United Kingdom providing data
on 5,110,619 patients to the GPRD. METHOD: The subjects were the patients with
one or more diagnoses of migraine plus treatment for migraine. Each case was
matched by general practice, sex, and age, with one control who had never been
given a diagnosis of migraine. Case and control groups were compared for
prevalence of asthma, chronic obstructive pulmonary disease, respiratory symptoms
treated with inhalers or hay fever. Investigations were carried out to determine 
whether the association between migraine and asthma was stronger among patients
with hayfever or those without hayfever, and whether patients with migraine had
an increased prescription of other (non-migraine and non-asthma) medications.
RESULTS: Among 64 678 case-control pairs, the relative risk of asthma in patients
with migraine was 1.59 (95% CI = 1.54 to 1.65) among definite cases, and 0.75
(95% CI = 0.67 to 0.83) among those whose selection as case included beta-blocker
prophylaxis. Among definite migraine cases, relative risks of chronic obstructive
pulmonary disease, respiratory symptoms, eczema, and hay fever (pollinosis), were
all raised (at 1.22, 1.85, 1.55, and 1.67, respectively). The association between
migraine and asthma was stronger in patients without a diagnosis of hay fever,
than in those with hayfever (relative risk = 1.32 and 1.19, respectively). The
relative risk of prescription for a range of non-migraine, non-asthma medications
was raised, the exception being anti-diabetic medication. CONCLUSION: This large 
case-control study provides evidence for an association between migraine and
asthma. Frequent attendance at a general practice surgery may confound this
association. However, if the association is real, its elucidation may help the
understanding of disease mechanisms shared by migraine and asthma.

PMID: 12236275 [PubMed - indexed for MEDLINE]

2856: Proc Natl Acad Sci U S A. 2002 Oct 1;99(20):13284-9. Epub 2002 Sep 16.

Familial hemiplegic migraine mutations increase Ca(2+) influx through single
human CaV2.1 channels and decrease maximal CaV2.1 current density in neurons.

Tottene A, Fellin T, Pagnutti S, Luvisetto S, Striessnig J, Fletcher C, Pietrobon
D.

Department of Biomedical Sciences, University of Padova, 35121 Padova, Italy.

Insights into the pathogenesis of migraine with aura may be gained from a study
of human Ca(V)2.1 channels containing mutations linked to familial hemiplegic
migraine (FHM). Here, we extend the previous single-channel analysis to human
Ca(V)2.1 channels containing mutation V1457L. This mutation increased the channel
open probability by shifting its activation to more negative voltages and reduced
both the unitary conductance and the density of functional channels in the
membrane. To investigate the possibility of changes in Ca(V)2.1 function common
to all FHM mutations, we calculated the product of single-channel current and
open probability as a measure of Ca(2+) influx through single Ca(V)2.1 channels. 
All five FHM mutants analyzed showed a single-channel Ca(2+) influx larger than
wild type in a broad voltage range around the threshold of activation. We also
expressed the FHM mutants in cerebellar granule cells from Ca(V)2.1alpha(1)-/-
mice rather than HEK293 cells. The FHM mutations invariably led to a decrease of 
the maximal Ca(V)2.1 current density in neurons. Current densities were similar
to wild type at lower voltages because of the negatively shifted activation of
FHM mutants. Our data show that mutational changes of functional channel
densities can be different in different cell types, and they uncover two
functional effects common to all FHM mutations analyzed: increase of
single-channel Ca(2+) influx and decrease of maximal Ca(V)2.1 current density in 
neurons. We discuss the relevance of these findings for the pathogenesis of
migraine with aura.

PMID: 12235360 [PubMed - indexed for MEDLINE]

2857: Cephalalgia. 2002 Sep;22(7):555-6.

Reflux-triggered migraine headache originating from the upper gum/teeth.

Spierings EL.

Department of Neurology, Brigham and Women's Hospital, Harvard Medical School,
Boston, Massachusetts, USA. ESpierings@Partners.org

Two patients with migraine are described who also suffered from gastric reflux.
The reflux triggered headaches that originated from the upper gum/teeth and
responded to specific reflux treatment.

Publication Types: 
    Case Reports

PMID: 12230598 [PubMed - indexed for MEDLINE]

2858: Cephalalgia. 2002 Sep;22(7):543-51.

Migraine, major depression, panic disorder, and personality traits in women aged 
40-74 years: a population-based study.

Mattsson P, Ekselius L.

Department of Neuroscience, Neurology, University Hospital, Uppsala, Sweden.
Peter.Mattsson@neurologi.uu.se

This study investigates the associations between migraine on the one hand and
lifetime major depression, lifetime panic disorder, and neuroticism evaluated
using the Swedish universities Scales of Personality on the other. A neurologist 
clinically assessed 728 women aged 40-74 years attending a population-based
mammography screening programme. The associations between lifetime migraine and
personality traits and psychiatric disorders were insignificant in multivariable 
analysis. However, in old women (60-74 years) the risk for active migraine was
strongly associated with a history of major depression and high levels of stress 
susceptibility and somatic trait anxiety. Furthermore, in old women, high levels 
of stress susceptibility and somatic trait anxiety were associated with low
ratings of migraine pain intensity and lower levels of these traits with high
ratings after controlling for disability during migraines, whereas there were
only small differences in middle-aged women. The results suggest that certain
aspects of neuroticism are important mental correlates of the ability of old
women to endure migraine pain.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 12230596 [PubMed - indexed for MEDLINE]

2859: Cephalalgia. 2002 Sep;22(7):523-32.

The efficacy and safety of Tanacetum parthenium (feverfew) in migraine
prophylaxis--a double-blind, multicentre, randomized placebo-controlled
dose-response study.

Pfaffenrath V, Diener HC, Fischer M, Friede M, Henneicke-von Zepelin HH;
Investigators.

Munich, Department of Neurology, University of Essen, Essen. Germany.
Vpfa@aol.com

Tanacetum parthenium (feverfew), is a well-known herb for the prophylactic
treatment of migraine. The primary objective was to show a dose-response of a new
stable extract (MIG-99) reproducibly manufactured with supercritical CO2 from
feverfew (T. parthenium). Furthermore, the study should provide data on the
safety and tolerability of MIG-99. In a randomized, double-blind, multicentre,
controlled trial with an adaptive design, the clinical efficacy and safety of
three dosages of MIG-99 (2.08 mg; 6.25 mg; 18.75 mg t.i.d.) were compared with
placebo. The patients (n = 147) suffered from migraine with and without aura
according to International Headache Society (IHS) criteria and were treated with 
one of the study medications for 12 weeks after a 4-week baseline period. The
primary efficacy parameter was the number of migraine attacks during the last 28 
days of the treatment period compared with baseline. Secondary endpoints were
total and average duration and intensity of migraine attacks, mean duration of
the single attack, number of days with accompanying migraine symptoms, number of 
days with inability to work due to migraine as well as type and amount of
additionally taken medications for the treatment of migraine attacks. The design 
of the study included a pre-planned adaptive interim analysis for patients with
at least four migraine attacks within the baseline period. With respect to the
primary and secondary efficacy parameter, a statistically significant difference 
was not found between the overall and the confirmatory intention-to-treat (ITT)
sample in the exploratorily analysed four treatment groups. The frequency of
migraine attacks for the predefined confirmatory subgroup of patients (n = 49)
with at least four migraine attacks during the baseline period decreased in a
dose-dependent manner (P = 0.001). The highest absolute change of migraine
attacks was observed under treatment with 6.25 mg t.i.d. (mean +/- SD = -1.8 +/- 
1.5 per 28 days) compared with placebo (-0.3 +/- 1.9; P = 0.02). Overall, 52 of
147 (35%) patients reported at least one adverse event (AE). The incidence of AEs
in the active treatment groups was similar to that in the placebo group, and no
dose-related effect was observed in any safety parameter. MIG-99 failed to show a
significant migraine prophylactic effect in general. Accordingly, in the ITT
analysis a dose-response relationship could not be observed. MIG-99 was shown to 
be effective only in a small predefined subgroup of patients with at least four
attacks during the 28-day baseline period where the most favourable benefit-risk 
ratio was observed with a dosage of three capsules of 6.25 mg MIG-99 extract per 
day. Because of the low number of patients, these findings need to be verified in
a larger sample. The incidence of AEs was similar for all treatment groups.

Publication Types: 
    Clinical Trial
    Comparative Study
    Multicenter Study
    Randomized Controlled Trial

PMID: 12230594 [PubMed - indexed for MEDLINE]

2860: Cephalalgia. 2002 Sep;22(7):513-9.

Comment in:
    Cephalalgia. 2002 Sep;22(7):489-90.

Hydroxocobalamin, a nitric oxide scavenger, in the prophylaxis of migraine: an
open, pilot study.

van der Kuy PH, Merkus FW, Lohman JJ, ter Berg JW, Hooymans PM.

Department of Clinical Pharmacy and Toxicology, Academic Hospital Maastricht,
Maastricht, The Netherlands. hkuy@kfls.azm.nl

Drugs which directly counteract nitric oxide (NO), such as endothelial receptor
blockers, NO-synthase inhibitors, and NO-scavengers, may be effective in the
acute treatment of migraine, but are also likely to be effective in migraine
prophylaxis. In the underlying pilot study the prophylactic effect of the NO
scavenger hydroxocobalamin after intranasal administration in migraine was
evaluated. Twenty patients, with a history of migraine of > 1 year and with two
to eight migraine attacks per month, were included in an open trial. A baseline
period was followed by an active treatment period of 3 months with 1 mg
intranasal hydroxocobalamin daily. Patients were instructed to complete a diary
in which details of each attack were described. A reduction in migraine attack
frequency of >/ or = 50% was seen in 10 of 19 patients, which corresponds to 53% 
of the patients (responders). A reduction of > or = 30% was noted in 63% of the
patients. The mean attack frequency in the total study population showed a
reduction from 4.7 +/- 1.7 attacks per month to 2.7 +/- 1.6 (P < 0.001). For the 
responders the migraine attack frequency was reduced from 5.2 +/- 1.9 (baseline) 
to 1.9 +/- 1.3 attacks per month (P < 0.005), while for those who did not respond
a non-significant reduction was found: 4.1 +/- 1.4 to 3.7 +/- 1.5 (P > 0.1). A
reduction was also observed for the total duration of the migraine attacks per
month, the total number of migraine days per month and the number of medication
doses for acute treatment used per month. This is the first prospective, open
study indicating that intranasal hydroxocobalamin may have a prophylactic effect 
in migraine. As a percentage of responders in prophylactic trials of > 35-40% is 
unlikely to be a placebo effect, a double-blind study is warranted.

Publication Types: 
    Comparative Study

PMID: 12230592 [PubMed - indexed for MEDLINE]

2861: Cephalalgia. 2002 Sep;22(7):491-512.

Comment in:
    Cephalalgia. 2004 Oct;24(10):908; author reply 908-9.

Migraine: preventive treatment.

Silberstein SD, Goadsby PJ.

Jefferson Headache Center, and Thomas Jefferson University Hospital,
Philadelphia, PA 19107, USA. Stephen.Silberstein@mail.tju.ed

Migraine is a common episodic headache disorder. A comprehensive headache
treatment plan includes acute attack treatment to relieve pain and impairment and
long-term preventive therapy to reduce attack frequency, severity, and duration. 
Circumstances that might warrant preventive treatment include: (i) migraine that 
significantly interferes with the patient's daily routine despite acute
treatment; (ii) failure, contraindication to, or troublesome side-effects from
acute medications; (iii) overuse of acute medications; (iv) special
circumstances, such as hemiplegic migraine; (v) very frequent headaches (more
than two a week); or (vi) patient preference. Start the drug at a low dose. Give 
each treatment an adequate trial. Avoid interfering, overused, and
contraindicated drugs. Re-evaluate therapy. Be sure that a woman of childbearing 
potential is aware of any potential risks. Involve patients in their care to
maximize compliance. Consider co-morbidity. Choose a drug based on its proven
efficacy, the patient's preferences and headache profile, the drug's
side-effects, and the presence or absence of coexisting or co-morbid disease.
Drugs that have documented high efficacy and mild to moderate adverse events
(AEs) include beta-blockers, amitriptyline, and divalproex. Drugs that have lower
documented efficacy and mild to moderate AEs include selective serotonin reuptake
inhibitors (SSRIs), calcium channel antagonists, gabapentin, topiramate,
riboflavin, and non-steroidal anti-inflammatory drugs.

Publication Types: 
    Review

PMID: 12230591 [PubMed - indexed for MEDLINE]

2862: Biomed Pharmacother. 2002 Aug;56(6):283-8.

Randomized, controlled trial of phytoestrogen in the prophylactic treatment of
menstrual migraine.

Burke BE, Olson RD, Cusack BJ.

Research Service, Department of Veterans Affairs Medical Center, Boise, ID 83702,
USA. drq10@iglide.net

Approximately 30% of women afflicted with migraine have menstrually associated
attacks. These migraines are often refractory to treatment. Evidence suggests
estrogen and progestin fluctuations may influence menstrual migraine.
Phytoestrogens have demonstrated estrogenic effects in some tissues, but are
without stimulation of the endometrium, suggesting decreased risk with long-term 
use. This study was undertaken to assess the efficacy of a phytoestrogen
combination in the prophylactic treatment of menstrual migraine. Forty-nine
patients were randomized to receive either placebo, or a daily combination of 60 
mg soy isoflavones, 100 mg dong quai, and 50 mg black cohosh, with each component
standardized to its primary alkaloid. Patients received study medication for 24
weeks. Average frequency of menstrually associated migraine attacks during weeks 
9-24 was reduced from 10.3 +/- 2.4 (mean +/- s.e.m.) in placebo treated patients 
to 4.7 +/- 1.8 (P < 0.01) in patients treated with the phytoestrogen preparation.

Publication Types: 
    Clinical Trial
    Comparative Study
    Multicenter Study
    Randomized Controlled Trial

PMID: 12224599 [PubMed - indexed for MEDLINE]

2863: Acta Paediatr. 2002;91(8):980-2.

Idiopathic intracranial hypertension presenting as hemiplegic migraine.

Stanley TV.

Department of Paediatrics, Wellington School of Medicine and Health Sciences,
University of Otago, New Zealand.

A 14-y-old girl presented with a 2 h history of left hemiplegia preceded by mild 
left-sided sensory disturbance. She had experienced migraines for several years
and there was a strong family history of migraine, including hemiplegic migraine 
in one of her sisters. Her hemiplegia and headache responded to sumatriptan but
her headache and vomiting subsequently returned. She was found to have
intracranial hypertension and developed papilloedema and paracentral scotomas.
Further history revealed she had been taking minocycline for acne. Conclusion: An
association between hemiplegic migraine and pseudotumour cerebri has not
previously been reported. There may be a case for examining patients with
pseudotumour cerebri for the calcium channel mutation (CACNA1A).

Publication Types: 
    Case Reports

PMID: 12222727 [PubMed - indexed for MEDLINE]

2864: Pharmacol Res. 2002 Sep;46(3):245-50.

Indomethacin, caffeine and prochlorperazine alone and combined revert
hyperalgesia in in vivo models of migraine.

Galeotti N, Ghelardini C, Grazioli I, Uslenghi C.

Department of Preclinical and Clinical Pharmacology, University of Florence,
Florence, Italy.

The combination of indomethacin, caffeine, and prochlorperazine (hereinafter
IndoProCaf) represents an effective antimigraine drug available on the Italian
market. The aim of this study was to test the efficacy of the three active
principles alone and in combination in reverting hyperalgesia. Hyperalgesia was
induced by morphine withdrawal in mice treated with morphine for 15 days and then
made hyperalgic by morphine substitution with water. This study showed that
indomethacin 0.3 mg kg(-1), i.p.; caffeine 0.1 and 0.3 mg kg(-1), i.p.; and
prochlorperazine 0.1 mg kg(-1), i.p.; as well as the combination of the three
active principles, were able to revert morphine withdrawal induced hyperalgesia, 
causing a statistically significant increase of pain threshold in hyperalgic
mice. In a second model, hyperalgesia was induced by the i.p. injection of a 0.3%
solution of acetic acid in mice and was evaluated counting the number of
abdominal constrictions. Indomethacin (0.1 mg kg(-1), i.p.), caffeine (0.3 mg
kg(-1), i.p.), and prochlorperazine (0.1 mg kg(-1), i.p.) reduced the number of
abdominal constrictions, while the combination of the three active principles was
able to abolish almost completely the abdominal constrictions, with a
significantly higher efficacy compared to the single active principles. In both
models, indomethacin, caffeine, and prochlorperazine reverted hyperalgesia at
dosages 10 times lower than the corresponding analgesic ones. These data provide 
the pharmacologic evidence of the efficacy of IndoProCaf in reverting
hyperalgesia, a condition of reduction of pain threshold similar to that
occurring in migraine. Copyright 2002 Elsevier Science Ltd.

PMID: 12220967 [PubMed - indexed for MEDLINE]

2865: Appl Psychophysiol Biofeedback. 2002 Sep;27(3):203-13.

On the pathophysiology of migraine--links for "empirically based treatment" with 
neurofeedback.

Kropp P, Siniatchkin M, Gerber WD.

Institute of Medical Psychology, University of Kiel, Niemannsweg 147, D-24105
Kiel, Germany. kropp@med-psych.uni-kiel.de

Psychophysiological data support the concept that migraine is the result of
cortical hypersensitivity, hyperactivity, and a lack of habituation. There is
evidence that this is a brain-stem related information processing dysfunction.
This cortical activity reflects a periodicity between 2 migraine attacks and it
may be due to endogenous or exogenous factors. In the few days preceding the next
attack slow cortical potentials are highest and habituation delay experimentally 
recorded during contingent negative variation is at a maximum. These striking
features of slow cortical potentials are predictors of the next attack. The
pronounced negativity can be fed back to the patient. The data support the
hypothesis that a change in amplitudes of slow cortical potentials is caused by
altered habituation during the recording session. This kind of neurofeedback can 
be characterized as "empirically based" because it improves habituation and it
proves to be clinically efficient.

Publication Types: 
    Review

PMID: 12206051 [PubMed - indexed for MEDLINE]

2866: Appl Psychophysiol Biofeedback. 2002 Jun;27(2):163-81.

Behavioral management of recurrent headache: three decades of experience and
empiricism.

Penzien DB, Rains JC, Andrasik F.

UMC Head Pain Center-Psychiatry, University of Mississippi Medical Center, 2500
North State Street, Jackson, Mississippi 39216-4505, USA.
dpenzien@psychiatry.umsmed.edu

In the past three decades, behavioral interventions (chiefly relaxation,
biofeedback, and stress-management) have become standard components of the
armamentarium for management of migraine and tension-type headaches.
Meta-analytic literature reviews of these behavioral interventions have
consistently identified clinically significant reductions in recurrent headache. 
Across studies, behavioral interventions have yielded approximately 35-50%
reduction in migraine and tension-type headache activity. Although we have only
recently begun to directly compare standard drug and nondrug treatments for
headache, the available evidence suggests that the level of headache improvement 
with behavioral interventions may rival those obtained with widely used
pharmacologic therapies in representative patient samples. In recent years, some 
attempts have been made to increase the availability and cost effectiveness of
behavioral interventions through alternative delivery formats and mass
communications. Recent developments within diagnosis and classification are
summarized, pointing out implications for behavioral researchers. Select future
directions are discussed, which include impact of the triptans, cost and cost
effectiveness, and integration of behavioral treatments into primary care
settings, the place where the great majority of headache sufferers receive
treatment.

Publication Types: 
    Review

PMID: 12206049 [PubMed - indexed for MEDLINE]

2867: Psychophysiology. 2002 Mar;39(2):166-74.

Reduced sensory anticipation in migraine.

Mulder EJ, Linssen WH, de Geus EI.

Department of Biological Psychology, Vrije Universiteit, Amsterdam, The
Netherlands. EJCM.Mulder@psy.vu.nl

We examined differences between migraine patients and matched healthy controls in
anticipatory processes preceding a warning stimulus and preceding a response
stimulus during a forewarned choice reaction time task. We manipulated stimulus
preceding negativity (SPN) by inserting full response information either at the
instant of the warning stimulus (cue) or at the instant of the response stimulus.
In contrast to control subjects, migraineurs with aura show low anticipation
towards an informative cue and high anticipation towards a noninformative cue.
Migraineurs without aura showed a cortical hypoactivation during motor
preparation prior to the response stimulus. We propose a functional deficiency
within frontal structures or the anterior cingulate cortex in migraine. This
might explain the reduced anticipation, as well as the slow responses during
selective attention that we previously reported in these patients.

Publication Types: 
    Clinical Trial
    Research Support, Non-U.S. Gov't

PMID: 12212665 [PubMed - indexed for MEDLINE]

2868: Med Hypotheses. 2002 Sep;59(3):316-20.

What is the genetic factor in migraine?

Eidelman D.

daveid@netvision.net.il

Migraine is frequently assumed to have an hereditary origin, but what this
hereditary factor is, no one really knows. Researchers are currently trying to
find defects in genes which could either cause, or tend towards, the development 
of migraine. This approach is deemed mistaken for two reasons: firstly, pain,
being only a signal of an essential monitoring system, cannot be an inheritable
factor on its own without the accompanying physiological or pathological
processes which give rise to it; and secondly, physicians, almost universally,
fail to examine a large part of the head, viz., the mandible and maxillae and
their appendages, before making their diagnoses or providing treatment, thereby
contravening the fundamental principle of properly examining patients. It is
hereby suggested, and evidence is offered showing that impacted teeth could be
the long sought-after 'hereditary' factor causing migraine.

PMID: 12208160 [PubMed - indexed for MEDLINE]

2869: Value Health. 2002 Sep-Oct;5(5):422-30.

Validation of the Patient Perception of Migraine Questionnaire.

Davis KH, Black L, Sleath B.

Global Health Outcomes, GlaxoSmithKline, PO Box 13398, Research Triangle Park, NC
27709-3398, USA. khd64468@gsk.com

OBJECTIVE: The purpose of this study was to assess the psychometric properties of
the Patient Perception of Migraine Questionnaire (PPMQ), which measures patient
satisfaction with migraine therapy. METHODS AND DATA: The PPMQ was administered
to 940 patients as part of a 3-month, multinational, open-label, clinical trial
comparing the effects of oral naratriptan 2.5 mg with the patient's customary
therapy for the treatment of migraine. Psychometric properties of the PPMQ were
evaluated in terms of its latent factor structure, validity, reliability,
sensitivity, and development of a scoring method. Classical Test theory and Item 
Response theory (IRT) modeling were both used to measure reliability. RESULTS:
The PPMQ was able to detect treatment differences (P >.001), and all items
significantly correlated with diary ratings of headache pain (r =.18-.51, p
>.0001) and the Medical Outcomes Short Form-36 pain scale (r =.27, p >.0001). A
principal components factor analysis revealed that the items on the PPMQ were
psychometrically distinct and unidimensional (loadings, 0.74-0.91), with the
exclusion of two items. The reliability (i.e., internal item consistency) of the 
PPMQ post-trial was high in both treatment groups (Cronbach's alpha = 0.96). An
IRT analysis also ensured the formation of homogenous items, which were stable on
repeat administration. Items did not require weighting and can be simply summed
to yield a total score. CONCLUSION: Based on the data from this one clinical
trial, the 15-item PPMQ was shown to be a valid and reliable instrument that
seems to efficiently and comprehensively measure patient perception of drug
attributes in relation to the treatment of symptoms associated with migraine
headaches.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Validation Studies

PMID: 12201859 [PubMed - indexed for MEDLINE]

2870: Pharmacoeconomics. 2002;20(11):715-25.

Prospective study designs in outcomes research: the case of migraine.

Rothermich EA, Brod MI, Schonfeld WH, Rowland CR, Gomez-Mancilla B.

Quintiles Late Phase, San Francisco, California 94107, USA.
betsy.rothermich@quintiles.com

Patient-reported outcomes (PROs), including resource utilisation, productivity
and quality of life, are important outcomes in the field of migraine. Clinical
trials have begun to incorporate PROs; however, not all research questions can be
answered fully within the framework of a clinical trial design. Other prospective
designs, including effectiveness trials, observational studies, and study hybrids
may be used to answer many of the different research questions related to PROs.
This paper reviews prospective study designs, their strengths and weaknesses, and
examples of their application in migraine health-outcomes research. Guidance is
provided for researchers in the selection of prospective research designs and the
incorporation of PROs-research objectives.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 12201791 [PubMed - indexed for MEDLINE]

2871: Neurology. 2002 Aug 27;59(4):606-8; discussion 481.

Parry-Romberg syndrome with migraine and intracranial aneurysm.

Pichiecchio A, Uggetti C, Grazia Egitto M, Zappoli F.

Neuroradiology Department, Istituto Neurologico IRCCS Fondazione C. Mondino via
Palestro, Pavia, Italy. anna.pichiecchio@mondino.it

Parry-Romberg syndrome or progressive facial hemiatrophy (PFH) is a rare disease 
of unknown etiology characterized by atrophy of the skin and subcutaneous tissue 
on one side of the face. The authors present the case of a 32-year-old woman with
PFH who had migraine and an intracranial aneurysm. The findings support the
hypothesis that the disease could be related to a neural crest migration
disorder, from which both fronto-nasal mass and cranial vessels take origin.

Publication Types: 
    Case Reports

PMID: 12196658 [PubMed - indexed for MEDLINE]

2872: CNS Drugs. 2002;16 Suppl 1:19-24.

Patient perceptions and treatment preferences in migraine management.

Dodick D.

Mayo Clinic Graduate School of Medicine, Scottsdale, Arizona, USA.

As the characteristics of migraine vary among patients and between attacks,
multiple factors must be considered clinically to ensure that patients receive
the most effective treatment strategy. Critical information required from the
patient is general medical history, migraine-specific history, and the impact of 
migraine. Once the strategy of care and the optimal therapeutic plan are decided,
the choice of therapeutic delivery must take into account patient preferences,
compliance and clinical need. During the symposium, a case review and interview
with a patient were conducted to illustrate the complex nature of integrating the
assessment of signs, symptoms, disability, comorbidities and patient preferences.
At the woman's first clinic visit, her Migraine Disability Assessment Scale
(MIDAS) score was 70. Previous acute therapies had been only marginally
effective, while previous prophylactic therapies had been discontinued because of
adverse events or had also proved to be ineffective. The patient's current acute 
therapy was zolmitriptan 5mg, which she responds to well. Seven months after her 
first clinic visit, the patient's MIDAS score had decreased to 25. When asked
about the relevance and utility of the MIDAS questionnaire, the patient felt that
it asked about things that are important, helped her to understand the impact of 
migraine on her life, and accurately reflected her improvement. The patient also 
expressed an interest in trying more rapidly acting formulations of
migraine-specific therapies in the future, such as a nasal spray formulation of
zolmitriptan. The MIDAS questionnaire facilitates communication between
physicians and patients to enable greater understanding of the impact of
migraine. MIDAS grades can also be used in the stratification of treatment and
for monitoring the course of illness and treatment outcomes. By increasing
available treatment options, patient needs and preferences can be matched with
specific features of migraine therapies. Taking patient preferences into account 
is likely to increase patient satisfaction and compliance, hopefully decreasing
the degree of undertreatment of migraine that has been reported globally.

Publication Types: 
    Case Reports
    Research Support, Non-U.S. Gov't
    Review

PMID: 12196036 [PubMed - indexed for MEDLINE]

2873: CNS Drugs. 2002;16 Suppl 1:13-8.

Global trends in migraine care: results from the MAZE survey.

Brandes JL.

Vanderbilt University School of Medicine, Nashville, Tennessee, USA.

INTRODUCTION: Many patients with migraine do not consult a physician, or do not
achieve adequate relief after consulting a physician because of undertreatment.
The objective of the Migraine and Zomig Evaluation study was to provide insights 
into the management of migraine in the general population. METHODS: In phase I,
5553 members of the general public in the UK, France, Germany, Italy, and the US 
were interviewed by telephone and classified according to International Headache 
Society criteria. The Migraine Disability Assessment Scale (MIDAS) questionnaire 
was used to assess the impact of migraine on work, home and social lives. In
phase II, 516 patients with clinically diagnosed migraine were interviewed to
assess the impact of migraine on daily life, attitudes towards migraine,
perceptions of current treatments and aspirations for future treatments. RESULTS:
In phase I, the average prevalence of migraine over the five countries was 9%.
Migraine posed a significant burden in terms of the impact on patients' daily
lives, and attack severity and frequency. However, medical consultation rates
were low; reasons for this included patients not recognising that they had
migraine or having low expectations about treatment benefits. On average, only
10% of patients who had consulted a physician had been prescribed a triptan. Only
22% of participants in phase II thought that migraine did not markedly affect
their lives. In each of the five countries, > or = 50% of patients required bed
rest to manage migraine attacks, demonstrating the impact of migraine-related
disability on patients' lives. Assessment of MIDAS scores confirmed the
debilitating effect of migraine; > 50% of respondents had a MIDAS grade of III or
IV, indicating moderate or severe disability. Less than one-third of patients
reported that their current medication was consistently effective and only 36%
were 'very satisfied' with their current therapy. High efficacy and rapid pain
relief were rated as the most important attributes of migraine medications. When 
asked which formulation they would like to see more of, most patients chose a
tablet that dissolves in the mouth without the need to take liquids. CONCLUSIONS:
These results show that migraine patients worldwide are still not receiving
adequate treatment and there remains a significant unmet need in migraine care.
The challenge for the future is to diagnose migraine early and offer patients
effective migraine-specific therapies. Physicians particularly need to reach
patients who do not realise they have migraine and those who have lapsed from
care.

Publication Types: 
    Multicenter Study
    Research Support, Non-U.S. Gov't

PMID: 12196035 [PubMed - indexed for MEDLINE]

2874: CNS Drugs. 2002;16 Suppl 1:5-11.

Need for care and perceptions of MIDAS among headache sufferers study.

Stewart W, Lipton R.

Johns Hopkins School of Public Health, Baltimore, Maryland, USA.

INTRODUCTION: Patients with migraine have varying medical care needs. To
effectively stratify patients to appropriate care, physicians should consider the
frequency and intensity of attacks, and their overall impact on ability to
function. The Migraine Disability Assessment Scale (MIDAS) measures
headache-related disability. The MIDAS Perceptions Study investigated whether
MIDAS scores reflect headache severity and the need for medical care, and
assessed whether the MIDAS questionnaire is meaningful and relevant to patients, 
and easy to use. DESIGN: The Perceptions Study was conducted as a follow-up to a 
baseline telephone interview. Upon completion of the baseline survey, 471
individuals were invited to participate in the Perceptions Study and 420
participated: 168 patients with migraine headaches and 253 with non-migraine
headaches. Patients with migraine or non-migraine headaches completed the MIDAS
questionnaire and the Center of Epidemiologic Studies of Depression (CES-D)
questionnaire, and were then interviewed by telephone within 48 hours of
receiving the questionnaires. RESULTS: Headache frequency and pain intensity
increased significantly with increasing MIDAS grade (p < 0.0001). A pattern of
decreasing quality-of-life scores on the physical and mental subscales of the
Short Form-12 was also seen with increasing MIDAS grade. Scores on the CES-D
scale increased significantly with increasing MIDAS grade (p < 0.0001),
indicating a greater likelihood of depression and more severe depression with
higher grades. There were significant associations between increasing MIDAS grade
and an increasing proportion of individuals who had consulted a doctor within the
past year, lower use of over-the-counter medication, and greater use of
prescription medications (p < 0.0001 for all three variables). Satisfaction with 
current therapy decreased significantly with increasing MIDAS grade, mirroring
the frequency with which individuals achieved complete relief from headache. The 
MIDAS questionnaire was rated as easy to use by the vast majority of respondents,
and ratings of its perceived value increased significantly as MIDAS grade
increased. CONCLUSIONS: A low MIDAS score generally seems to indicate a low need 
for care, while individuals in MIDAS grades III and IV appear to have significant
unmet medical care needs. The MIDAS questionnaire had increasingly perceived
relevance as MIDAS grade increased, helped the majority of those in MIDAS grades 
III and IV to understand the impact of their headaches, and encouraged those with
the greatest disability to seek medical care. The MIDAS questionnaire may
facilitate communication between doctors and patients, and help physicians to
identify those receiving inadequate medical care.

Publication Types: 
    Comparative Study

PMID: 12196034 [PubMed - indexed for MEDLINE]

2875: Dis Mon. 2002 May;48(5):323-35.

Botulinum toxin type A (BOTOX) for treatment of migraine.

Binder WJ, Brin MF, Blitzer A, Pogoda JM.

An open-label study and 2 double-blind, placebo-controlled studies have provided 
supporting evidence of botulinum toxin type A (BTX-A) as an effective,
well-tolerated treatment for migraine. Observed durations of benefit were
consistent with known properties of BTX-A. Findings suggest that response may
vary by features of preinjection headaches, such as migraine frequency. The
precise mechanism by which BTX-A provides pain relief is hypothesized to be
related not only to acetylcholine inhibition but also to a blocking action on the
parasympathetic nervous system. Additional studies that control factors likely to
be related to response may lead to better understanding of the BTX-A effect on
migraine and an optimal treatment protocol.

Publication Types: 
    Review

PMID: 12195263 [PubMed - indexed for MEDLINE]

2876: Pharmacol Ther. 2002 Apr-May;94(1-2):77-92.

New insights into the molecular actions of serotonergic antimigraine drugs.

Durham P, Russo A.

Department of Biology, 225 Temple Hall, Southwest Missouri State University,
Springfield, MO 65804, USA. pauldurham@smsu.edu

Migraine is a painful and debilitating neurological disorder that affects
approximately 10% of the adult population in Western countries. Sensitization and
activation of the trigeminal ganglia nerves that innervate the meningeal blood
vessels is believed to play an important role in the initiation and maintenance
of migraine pain. In this capacity, release of the neuropeptide calcitonin
gene-related peptide (CGRP) and the resultant neurogenic inflammation is thought 
to underlie the pathophysiology of migraine. Largely due to the success of the
serotonin Type 1 migraine drugs such as sumatriptan, migraine pathology and
therapy has become a focus of intensive clinical and physiological research
during the past decade. The effectiveness of these drugs is thought to be due to 
their ability to block the stimulated secretion of neuropeptides from trigeminal 
nerves to break the vicious nociceptive cycle of migraine. A component of this
nociceptive cycle involves activation of mitogen-activated protein kinase
signaling pathways. Indeed, activation of mitogen-activated protein kinase
pathways can increase CGRP neuropeptide synthesis and secretion. Recently, the
serotonin Type 1 agonists have been shown to cause a prolonged increase in
intracellular Ca(2+) in trigeminal ganglia neurons and an increased phosphatase
activity that can repress stimulated CGRP secretion and transcription.
Identification of molecular signaling events in migraine pathology and therapy
has provided new insight into the pharmacology and signaling mechanisms of
sumatriptan and related drugs, and may provide the foundation for development of 
novel treatments for migraine.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.
    Review

PMID: 12191595 [PubMed - indexed for MEDLINE]

2877: Clin Pharmacokinet. 2002;41(11):801-11.

Clinical pharmacokinetics of intranasal sumatriptan.

Fuseau E, Petricoul O, Moore KH, Barrow A, Ibbotson T.

EMF Consulting France, Aix en Provence, France.

A substantial proportion of migraine patients have gastric stasis and suffer
severe nausea and/or vomiting during their migraine attack. This may lead to
erratic absorption from the gastrointestinal tract and make oral treatment
unsatisfactory. For such patients, an intranasal formulation may be advantageous.
Sumatriptan is a potent serotonin 5HT(1B/1D) agonist widely used in the treatment
of migraine; the effectiveness of the intranasal formulation (20mg) has been well
established in several clinical studies. This article reviews the
pharmacokinetics of intranasal sumatriptan and includes comparisons with oral and
subcutaneous administration. After intranasal administration, sumatriptan is
directly and rapidly absorbed, with 60% of the maximum plasma concentration
(C(max)) occurring at 30 minutes after administration of a single 20mg dose.
Following intranasal administration, approximately 10% more sumatriptan is
absorbed probably via the nasal mucosa when compared with oral administration.
Mean C(max) after a 20mg intranasal dose is approximately 13.1 to 14.4 ng/mL,
with median time to C(max) approximately 1 to 1.75 hours. When given as a single 
dose, intranasal sumatriptan displays dose proportionality in its extent of
absorption and C(max) over the dose range 5 to 10mg, but not between 5 and 20mg
for C(max). The elimination phase half-life is approximately 2 hours, consistent 
with administration by other routes. Sumatriptan is metabolised by monoamine
oxidase (MAO; predominantly the A isozyme, MAO-A) to an inactive metabolite.
Coadministration with a MAO-A inhibitor, moclobemide, leads to a significant
increase in sumatriptan plasma concentrations and is contraindicated. Single-dose
pharmacokinetics in paediatric and adolescent patients following intranasal
sumatriptan were studied to determine the effect of changes in nasal morphology
during growth, and of body size, on pharmacokinetic parameters. The
pharmacokinetic profile observed in adults was maintained in the adolescent
population; generally, factors such as age, bodyweight or height did not
significantly affect the pharmacokinetics. In children below 12 years, C(max) is 
comparable to that seen in adolescents and adults, but total exposure (area under
the concentration-time curve from zero to infinity) was lower in children
compared with older patients, especially in younger children treated with 5mg.
Clinical experience suggests that intranasal sumatriptan has some advantages over
the tablet (more rapid onset of effect and use in patients with gastrointestinal 
complaints) or subcutaneous (noninvasive and fewer adverse events) formulations.

Publication Types: 
    Review

PMID: 12190330 [PubMed - indexed for MEDLINE]

2878: Neurology. 2002 Aug 13;59(3):435-7.

Migraine and the risk of cervical artery dissection: a case-control study.

Tzourio C, Benslamia L, Guillon B, Aïdi S, Bertrand M, Berthet K, Bousser MG.

INSERM U360, Service de Neurologie, Hôpital de la Salpêtrière, 75651 Paris cedex 
13, France. tzourio@chups.jussieu.fr

The association between migraine and cervical artery dissection (CAD) was
explored in a hospital-based case-control study. Migraine was present in 49.1%
(23/47) of patients with CAD and in 21% (11/52) of patients hospitalized for a
cerebral ischemic event not related to a CAD (adjusted odds ratio = 3.6; 1.5 to
8.6, p = 0.005). This result supports the hypothesis that an underlying arterial 
wall disease could be a predisposing condition for migraine.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 12177380 [PubMed - indexed for MEDLINE]

2879: Paediatr Drugs. 2002;4(9):555-61.

Behavioral treatment of migraine in children and adolescents.

Baumann RJ.

Department of Neurology, College of Medicine, University of Kentucky, Lexington, 
Kentucky 40536-0284, USA. Baumann@UKY.EDU

Behavioral interventions, particularly biofeedback and relaxation therapy, have
demonstrated their effectiveness in the treatment of both adults and older
children with migraine in controlled trials. The physiological basis for their
effectiveness is unclear, but data from one trial suggest that levels of plasma
beta-endorphin can be altered by relaxation and biofeedback therapies. The data
supporting the effectiveness of behavioral therapies are less clear-cut in
children than in adults, but that is also true for the data supporting medical
treatment. This is due in part to methodological issues, especially the lack of a
specific test for migraine, which has hampered research and helped lead to an
inappropriate de-emphasis on care for childhood headache. In addition, migraine
headaches in children are often briefer and have a higher rate of spontaneous
remission than those experienced by adults, making it difficult to separate
effective from ineffective treatments. While it is widely believed that stress is
a major factor in childhood migraine, well-designed studies have had difficulty
developing data to support this viewpoint. Many clinicians utilize 'confident
reassurance', reassuring the family that the child is not seriously ill, in the
belief that having migraine headaches can be stressful. They also modify
behaviors that are believed to trigger migraine headaches, such as poor sleep
habits or irregular meal times. Relaxation therapies use techniques such as
progressive relaxation, self-hypnosis, and guided imagery. Several studies have
found relaxation therapies to be as effective, or more effective, in reducing the
frequency of migraine headaches than modest doses of a beta-blockade medication, 
although one study found relaxation therapy to be no more effective than a
control program. Several studies have demonstrated that these therapies can be
taught to children in a low cost but effective manner. Biofeedback therapies
commonly use an apparatus to demonstrate a physiological effect. Most commonly in
pediatrics, children are taught to raise the temperature of one of their fingers.
This can be done with or without a thermometer. Several groups have shown that
these techniques can be taught to children and that their use is associated with 
fewer and briefer migraine headaches. People who experience migraines can also
experience episodic headaches throughout life. An important consideration is
preparing children to deal with future headaches, allowing them to feel in
control of their health. Behavioral therapies have the potential to do this,
giving the child access to a technique that can be easily resumed without a
medical visit or prescription.

Publication Types: 
    Review

PMID: 12175270 [PubMed - indexed for MEDLINE]

2880: J Child Neurol. 2002 Jun;17(6):470-2.

Magnetic resonance angiogram evidence of vasospasm in familial hemiplegic
migraine.

Prodan CI, Holland NR, Lenaerts ME, Parke JT.

Department of Neurology University of Oklahoma, Oklahoma City, USA.

We report a case of familial hemiplegic migraine in an 11-year-old girl who
presented with coma and left hemiparesis. Magnetic resonance imaging showed
reversible vasospasm and evidence of oligemia, bringing new information regarding
neurovascular changes in familial hemiplegic migraine.

Publication Types: 
    Case Reports

PMID: 12174974 [PubMed - indexed for MEDLINE]

2881: Pharmacotherapy. 2002 Aug;22(8):1029-35.

Do butalbital-containing products have a role in the management of migraine?

Wenzel RG, Sarvis CA.

Diamond Headache Clinic Inpatient Unit, St. Joseph Hospital, Resurrection Health 
Care, Chicago, IL 60657, USA. rwenz@hotmail.com

STUDY OBJECTIVE: To evaluate the role of butalbital-containing products in the
management of migraine. METHODS: Qualitative systematic search using MEDLINE
(January 1966-November 2001), review of the United States Headache Consortium's
evidence-based guidelines for migraine treatment, and review of other pertinent
literature. RESULTS: Over 28 million people suffer with migraine, yet this
illness is less than optimally diagnosed and managed. Between 14% and 36% of
diagnosed migraineurs are prescribed butalbital-containing products, often as
initial therapy. However, the only identified controlled trial of these drugs for
migraine treatment showed that butalbital-containing products were inferior to
butorphanol. The consortium's guidelines specifically discourage administration
of butalbital-containing products for migraine. In addition, other published
literature highlights the frequent adverse consequences of butalbital-containing 
products for migraineurs, such as poor migraine control, disability, drug-induced
headaches, and withdrawal symptoms. CONCLUSION: Although butalbital-containing
products commonly are prescribed for migraine, no evidence in the literature
demonstrates their benefit over other agents or placebo. Drugs with proven
migraine efficacy, as listed in the consortium's evidence-based guidelines,
should be prescribed instead.

Publication Types: 
    Review

PMID: 12173787 [PubMed - indexed for MEDLINE]

2882: Otol Neurotol. 2002 Jul;23(4):483-7.

Vestibular rehabilitation outcomes in patients with a history of migraine.

Wrisley DM, Whitney SL, Furman JM.

Department of Otolaryngology, School of Medicine, University of Pittsburgh, 6035 
Forbes Tower, Pittsburgh, PA 15260, U.S.A.

OBJECTIVES: The purpose of this study was to assess the efficacy of physical
therapy for patients with vestibular disorders with and without a history of
migraine headaches. STUDY DESIGN: Retrospective case series. SETTING: Outpatient 
physical therapy clinic. PATIENTS: Thirty patients with both a history of
migraine and a diagnosis of vestibular/balance disorder considered unrelated to
migraine were identified by retrospective chart review. Thirty patients without a
history of migraine, matched retrospectively by diagnosis, vestibular function,
and age (+/-5 years), were used as a comparison group. INTERVENTIONS: Both groups
were treated with a custom-designed physical therapy program for a mean of 4.1
visits over a mean of 3.3 months. MAIN OUTCOME MEASURES: Patients completed the
Dizziness Handicap Inventory, the Activities-Specific Balance Confidence Scale,
the Dynamic Gait Index, and the Timed Up & Go Test and rated the severity of
their dizziness on an analog scale of 0 to 100. RESULTS: Significant differences 
were demonstrated within both groups between initial evaluation and discharge in 
each of the assessment measures used. Patients with a history of migraine
demonstrated worse scores on all outcome measures than did the patients without a
history of migraine. There were no statistically significant differences between 
the two groups' scores before and after therapy except for the total Dizziness
Handicap Inventory score at discharge (p < 0.05). CONCLUSIONS: Patients with
vestibular disorders with or without a history of migraine demonstrated
improvements in both subjective and objective measures of balance after physical 
therapy. Patients with a history of migraine perceived a greater handicap from
dizziness than did patients without a history of migraine that was greater than
the difference in physical function performance measures between groups.

Publication Types: 
    Research Support, U.S. Gov't, P.H.S.

PMID: 12170150 [PubMed - indexed for MEDLINE]

2883: Curr Neurol Neurosci Rep. 2002 Sep;2(5):432-5.

Ophthalmologic migraine.

Saul RF.

Department of Neurology, Virginia Commonwealth University, PO Box 980599,
Richmond, VA 23298-0599, USA. rfsaul@vcu.edu

A fair portion of the diagnostic practice of the neurologist and ophthalmologist 
involves the deciphering of visual symptoms in patients known to have migraine,
and many who at the time of their initial presentation do not. The most common
visual disorder in this category, migraine with aura, has been studied
extensively, but no conclusive evidence has been proven linking the visual aura, 
believed to result from a spreading depression, to the subsequent development of 
the cephalgia. Vasospasm remains controversial in the pathophysiology of
migraine, but may play a role in patients who suffer more permanent or
complicated neurovisual dysfunction. This paper reviews some of the current
thoughts on the subject, and hopefully will stimulate the reader to explore the
complex issue of this common malady.

Publication Types: 
    Review

PMID: 12169224 [PubMed - indexed for MEDLINE]

2884: Headache. 2002 Jun;42(6):530-1.

Hemicrania continua responds to cyclooxygenase-2 inhibitors.

Peres MF, Silberstein SD.

Jefferson Headache Center, Department of Neurology, Thomas Jefferson University
Hospital, Philadelphia, Pa., USA.

BACKGROUND: Hemicrania continua is a primary headache disorder defined by its
absolute responsiveness to indomethacin. We report the treatment response to two 
cyclooxygenase-2 inhibitors, celecoxib and rofecoxib, in a series of patients
with hemicrania continua. METHODS: Fourteen patients were treated, 9 with
rofecoxib and 5 with celecoxib. RESULTS: Three patients in each group had a
complete response to treatment. CONCLUSION: The cyclooxygenase-2 inhibitors may
represent an alternative to indomethacin in the treatment of hemicrania continua.
Their mechanism of action for this potential indication is unknown.

PMID: 12167145 [PubMed - indexed for MEDLINE]

2885: Headache. 2002 Jun;42(6):519-22.

Intravenous valproate sodium in the treatment of daily headache.

Schwartz TH, Karpitskiy VV, Sohn RS.

Department of Neurology, Washington University, St. Louis, MO 63110, USA.

BACKGROUND: Treatment of chronic daily headache/transformed migraine is
challenging, especially when it is complicated by overuse of analgesics,
triptans, or both. One common approach involves the use of repetitive intravenous
dihydroergotamine. We investigated the use of intravenous valproate sodium in the
treatment of chronic daily headache/transformed migraine in patients who had
contraindications to the use of or had failed treatment with dihydroergotamine.
METHODS: We administered intravenous valproate sodium (Depacon) to patients with 
chronic daily headache/transformed migraine (loading dose 15 mg/kg, followed by 5
mg/kg every 8 hours). All analgesics and triptans were discontinued prior to
treatment with divalproex sodium, and preventative medications for migraine were 
begun or continued. All patients received instruction in behavioral modification 
and the proper use of analgesics and triptans. RESULTS: Improvement in headache
was reported by 80% of the patients treated, and valproate sodium was tolerated
well by most. CONCLUSION: Intravenous valproate sodium may be of assistance in
the initial management of patients with chronic daily headache/transformed
migraine and analgesic/triptan overuse, especially when dihydroergotamine is
ineffective or contraindicated.

Publication Types: 
    Clinical Trial

PMID: 12167141 [PubMed - indexed for MEDLINE]

2886: Headache. 2002 Jun;42(6):515-8.

Olanzapine in the treatment of refractory migraine and chronic daily headache.

Silberstein SD, Peres MF, Hopkins MM, Shechter AL, Young WB, Rozen TD.

Jefferson Headache Center, Department of Neurology, Thomas Jefferson University
Hospital, Philadelphia, PA 19107, USA.

BACKGROUND: Olanzapine, a thienobenzodiazepine, is a new "atypical" antipsychotic
drug. Olanzapine's pharmacologic properties suggest it would be effective for
headaches, and its propensity for inducing acute extrapyramidal reactions or
tardive dyskinesia is relatively low. We thus decided to assess the value of
olanzapine in the treatment of chronic refractory headache. METHODS: We reviewed 
the records of 50 patients with refractory headache who were treated with
olanzapine for at least 3 months. All previously had failed treatment with at
least four preventative medications. The daily dose of olanzapine varied from 2.5
to 35 mg; most patients (n = 19) received 5 mg or 10 mg (n = 17) a day. RESULTS: 
Treatment resulted in a statistically significant decrease in headache days
relative to baseline, from 27.5 +/- 4.9 before treatment to 21.1+/-10.7 after
treatment (P <.001, Student t test). The difference in headache severity (0 to 10
scale) before treatment (8.7+/-1.6) and after treatment (2.2 +/- 2.1) was also
statistically significant (P <.001). CONCLUSION: Olanzapine may be effective for 
patients with refractory headache, including those who have failed a number of
other prophylactic agents. Olanzapine should receive particular consideration for
patients with refractory headache who have mania, bipolar disorder, or psychotic 
depression or whose headaches previously responded to other neuroleptic
medications.

PMID: 12167140 [PubMed - indexed for MEDLINE]

2887: Headache. 2002 Jun;42(6):510-4.

Amitriptyline versus amitriptyline combined with fluoxetine in the preventative
treatment of transformed migraine: a double-blind study.

Krymchantowski AV, Silva MT, Barbosa JS, Alves LA.

Headache Center of Rio and Instituto de Neurologia Deolindo Couto/UFRJ, Rio de
Janeiro, Brazil.

BACKGROUND AND OBJECTIVES: Antidepressants are often used to treat chronic daily 
headache disorders such as transformed migraine, in part because of the high
prevalence of associated mood disorder. We conducted this study to evaluate the
efficacy and tolerability of combined treatment with amitriptyline and fluoxetine
compared with amitriptyline alone for chronic daily headache due to transformed
migraine. PATIENTS AND METHODS: Thirty-nine patients, 26 women and 13 men, aged
20 to 69 years (mean, 36.4; SD, 2.5) who fulfilled criteria for transformed
migraine proposed by Silberstein et al were studied prospectively. Amitriptyline 
was dosed as follows: 8 mg/day for 6 days, 8 mg twice a day for 6 days, 20 mg/day
for 6 days, and 20 mg twice a day for 45 days. In the group receiving combination
therapy, fluoxetine was dosed and administered identically. The initial and end
of the study (9 weeks) headache indices (frequency x intensity) were compared
between groups. RESULTS: Twenty-seven patients completed the study, 13 in the
amitriptyline-alone group (group 1) and 14 in the combination-therapy group
(group 2). The most frequent adverse event in both groups was dry mouth, and
there was no significant difference in the occurrence of this or other adverse
events between the two groups. Initial headache indices were similar for groups 1
and 2. The mean difference between the initial and final headache index for group
1 was 513.5 (P<.0005) and 893 (P<.0017) for group 2. The difference between the
final headache index for the two groups was not significant (P>.207).
CONCLUSIONS: We were unable to demonstrate any significant benefit from
amitriptyline plus fluoxetine over amitriptyline alone in the treatment of
chronic daily headache/transformed migraine. Because of the small number of
subjects involved and the short duration of our study, a type II error cannot be 
excluded.

Publication Types: 
    Clinical Trial
    Comparative Study
    Randomized Controlled Trial

PMID: 12167139 [PubMed - indexed for MEDLINE]

2888: Headache. 2002 Jun;42(6):501-9.

The economic impact of migraine: an analysis of direct and indirect costs.

Edmeads J, Mackell JA.

Sunnybrook and Women's Health Science Centre, The University of Toronto, Toronto,
Ontario, Canada.

OBJECTIVE: This study examined whether individuals with migraine incurred greater
direct and indirect costs than a matched group free of migraines. METHODS: Using 
population-based survey data, we matched individuals with migraine (n = 1087) and
a migraine-free control group one-to-one for age, sex, employment status, and
number of comorbidities. We assessed the prior six months' direct medical care in
terms of self-reported hospital days and emergency department and physician
visits. Costs were computed by multiplying utilization by unit costs and summing 
across categories. Indirect costs were calculated based on the number of days
missed from employment or household activities. RESULTS: The sample was 80%
female and had an average of 39 years and 0.4 comorbid conditions. Two-thirds
were employed. Migraineurs had higher direct medical costs over the prior six
months (522 dollars versus 415 dollars, P =.039), primarily due to a greater
frequency of physician and emergency department visits. The cost of lost
productivity for the migraine group was also higher, by more than 200 dollars (P 
=.014). The combined total for direct and indirect costs was 1,242 dollars for
migraineurs and 929 dollars for the comparison group (P =.006). Additional
analyses comparing those with moderate versus severe migraine demonstrated that
more severe migraineurs had higher costs for lost productivity (1,021 dollars
versus 251 dollars, P<.001) and higher costs when direct and indirect costs were 
combined (1,656 dollars versus 685 dollars, P<.001). CONCLUSION: Migraine is an
expensive illness and two-thirds of the financial burden is linked to indirect
costs. Consequently, individuals with migraine, employers, and insurance
companies all have an economic stake in reducing the migraine burden.

Publication Types: 
    Comparative Study

PMID: 12167138 [PubMed - indexed for MEDLINE]

2889: Headache. 2002 Jun;42(6):483-90.

Behavioral and pharmacologic treatment of transformed migraine with analgesic
overuse: outcome at 3 years.

Grazzi L, Andrasik F, D'Amico D, Leone M, Usai S, Kass SJ, Bussone G.

Headache Center, National Neurological Institute C. Besta, Milan, Italy.

OBJECTIVE: To determine whether combined treatment using medication and
biofeedback would be more effective than drug treatment alone for treating
transformed migraine complicated by analgesic overuse. BACKGROUND: Headaches that
are chronic, daily, and aggravated by medication overuse are particularly
difficult to treat. METHODS: Sixty-one consecutive patients with transformed
migraine and analgesic overuse were treated with inpatient pharmacologic therapy 
alone or with inpatient pharmacologic therapy combined with biofeedback-assisted 
relaxation. All patients then were followed prospectively for 3 years. RESULTS:
Both treatment groups exhibited similar levels of improvement immediately
following treatment and for 1 year thereafter. At year 3, participants receiving 
combined treatment showed greater sustained improvement on two of three outcome
measures assessed (ie, fewer days of headache and reduced consumption of
analgesic medication). In addition, a greater number of patients assigned to
pharmacologic treatment alone relapsed (ie, resumed overuse of analgesics)
compared to patients receiving combined treatment. CONCLUSIONS: These results
suggest that a combination of pharmacologic and behavioral treatment is more
effective than drug therapy alone in the long-term management of transformed
migraine with analgesic overuse. Confirmation of these findings, as well as
extension to other forms of behavioral and cognitive-behavioral treatment, is
required.

Publication Types: 
    Clinical Trial

PMID: 12167136 [PubMed - indexed for MEDLINE]

2890: Dev Med Child Neurol. 2002 Jul;44(7):490-3.

Benign paroxysmal torticollis of infancy: four new cases and linkage to CACNA1A
mutation.

Giffin NJ, Benton S, Goadsby PJ.

Headache Group, Institute of Neurology, London, UK. n.griffin@ion.ucl.ac.uk

Benign paroxysmal torticollis of infancy (BPTI) is a disorder characterized by
recurrent episodes of head tilt secondary to cervical dystonia. Attacks are often
accompanied by vomiting, pallor, and ataxia, settling spontaneously within hours 
or days. Episodes begin within the first 12 months of life and resolve by 5
years. We report four patients with BPTI. Symptoms started from 3 months of age, 
with head tilting lasting between 10 minutes and 2 months; the shorter episodes
were followed by vomiting, apathy, and unsteadiness. Head tilt became less
prominent after infancy, replaced by vertigo and eventually by migraine
headaches. Two patients came from a kindred with familial hemiplegic migraine
linked to CACNA1A mutation. BPTI may be regarded as a migraine aura equivalent.
The syndrome poses interesting questions regarding varying phenotypic expression 
of calcium channelopathies at different stages of development.

Publication Types: 
    Case Reports

PMID: 12162387 [PubMed - indexed for MEDLINE]

2891: CNS Drugs. 2002;16(9):611-34.

New and emerging prophylactic agents for migraine.

Krymchantowski AV, Bigal ME, Moreira PF.

Department of Neurology, Universidade Federal Fluminense and Institute of
Neurology Deolindo Couto, Rio de Janeiro, Brazil. abouchkrym@globo.com

Frequent, severe and long-lasting migraine attacks require prophylaxis.
Established drugs used for the prevention of migraine such as beta-adrenoceptor
antagonists (beta-blockers), calcium channel antagonists, antidepressants and
others have an unknown mode of action in migraine. Their prophylactic effect in
migraine was discovered by chance in clinical practice when these drugs were used
for other purposes. Recently, research into the mechanisms of migraine and the
progressive recognition that cortical hyperexcitability and an imbalance between 
neuronal inhibition [mediated by gamma-aminobutyric acid (GABA)] and excitation
(mediated by excitatory amino acids) may play an important role in migraine
pathophysiology have lead to the identification of potential new agents for the
prevention of migraine attacks. This paper reviews the recent literature on these
new agents. A search was conducted using MEDLINE from 1998 to November 2001 with 
the following search terms: migraine, preventive, prophylactic and treatment.
Headache textbooks edited in 2000 and 2001 were also used. After analysing the
available controlled and uncontrolled clinical studies as well as abstracts,
divalproex sodium (valproate semisodium) can be recommended for the prevention of
migraine. Lamotrigine may be useful for preventing aura associated with migraine,
and topiramate seems a promising option pending trials with more patients, which 
are currently underway. Riboflavin (which is possibly involved in improving
neuronal energy production) appears to be a promising agent, although comparisons
with established prophylactic medications are needed. Gabapentin, magnesium,
lisinopril and botulinum toxin A have recently been suggested to be effective;
however, at present, there are insufficient rigorous and reliable controlled data
on these drugs for them to be indicated for such use. Emerging options such as
tiagabine, levetiracetam, zonisamide and petasites may all be useful, but
controlled data are required to confirm their efficacy. The anti-asthma
medication montelukast was found to be effective in an open trial, but
ineffective in a recently completed controlled trial. There is an expectation
that modern neuroscience will soon provide more efficacious and better tolerated 
prophylactic medications for migraine.

Publication Types: 
    Review

PMID: 12153333 [PubMed - indexed for MEDLINE]

2892: N Y State Dent J. 2002 Jun-Jul;68(6):24-6.

Migraine, tension-type headache and facial pain. A common intraoral etiology and 
treatment.

Friedman MH.

A maxillary alveolar mucosal inflammation, demonstrated by local tenderness and
increased temperature, is present in migraine, tension-type headache and facial
pain patients even when the patient is asymptomatic. Research is presented
showing effective treatment of these conditions with fewer side effects than with
standard medication by local anti-inflammatory methods. These alternative methods
include: chilling, application of anti-inflammatory gel and low-level
(non-cutting) laser. Local treatment also mediates cervical muscle spasm, adding 
to its overall effectiveness.

PMID: 12149787 [PubMed - indexed for MEDLINE]

2893: Can J Neurol Sci. 2002 Jun;29 Suppl 2:S8-10.

Communication issues in migraine diagnosis.

Edmeads J.

University of Toronto and Sunnybrook and Women's College Health Sciences Centre, 
ON, Canada.

OBJECTIVES: To examine the importance of good communication when informing the
patient of the diagnosis of migraine; to review the essentials of successful
communication between physician and patient on the aspect of diagnosis; to survey
learning resources for physicians on communicating information to patients.
METHODS: This paper is based on observations made by the author of the successful
interactions of numerous international "headache experts" with their patients, on
a review of the medical education literature pertaining to the teaching of
communication skills, and on 30 years of not always successful communication with
patients. RESULTS: Communicating the diagnosis of migraine is an opportunity to
educate and reassure the patient, to lay the foundation for rational treatment
and to help establish the successful doctor-patient relationship which is
essential for effective management. No matter how accurate the diagnosis, failure
to communicate it effectively to the patient (and often to significant others)
may impair interactions with the patient and compromise therapy. Effective
communication of a diagnosis requires clarity, relevance to the patient, a
positive attitude, and reinforcement through repetition, questioning and
dialogue. In terms of using the diagnosis to lay a foundation for therapy, it is 
useful to explain the symptoms as transient physical dysfunction of normal
tissues, to indicate that there are multiple mechanisms underlying the
dysfunction of which only some may presently be susceptible to treatment and to
stress the relevance of emotions as factors which may powerfully affect, for
better or worse, the underlying disturbed physiology of migraine. Into this model
can be "plugged" all the relevant therapies for migraine. This is the ideal, but 
every day experience in the headache consultant's office suggest that in both
primary care and specialist practice, it is infrequently attained. There are
scant resources other than example for physicians to learn communication of
headache diagnosis specifically but there are numerous print and web resources
available to physicians wh wish to learn and/or teach the generic principles of
effective communication, and these principles require little or no modification
to be applied to the headache patient and the headache doctor.

Publication Types: 
    Review

PMID: 12139087 [PubMed - indexed for MEDLINE]

2894: Can J Neurol Sci. 2002 Jun;29 Suppl 2:S40-3.

Improving patient compliance to prophylactic migraine therapy.

Aubé M.

Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill
University, Québec, Canada.

As in many other chronic conditions, adherence to prophylactic treatment in
migraine is probably poor. In chronic diseases, compliance at one year does not
exceed 50%. That could explain the low therapeutic gain seen with migraine
preventive medications. It also renders difficult the evaluation of clinical
trials on migraine prophylaxis since in most of these trials compliance is not
properly assessed. From the patients' perspective, there are several factors that
could explain poor adherence to recommended treatments. Essentially, these
factors are the expression of the patients' subjective perception of their
disease and potential remedies in a context of a positive patient-physician
relationship. When migraine prophylactic treatment is considered, patients should
be informed of the natural history of their disease and a diagnosis of an
accelerated form of migraine should be confirmed. Prophylactic treatment at best 
would reduce by 50% the frequency of migraine attacks. In most studies, however, 
the therapeutic gain is in the order of 30-40%. Treatment should be instituted
for a minimum time of two to three months and if effective maintained for 6-12
months. The outcome of prophylaxis can rarely be determined in a prospective way.
The choice of prophylactic regimens remains empirical, often based on the
physician's experience and perception of the mechanism of migraine. A better
adherence to prophylactic treatment of migraine could possibly improve outcomes
but current methods of improving adherence for chronic health problems are mostly
complex and not very effective.

Publication Types: 
    Review

PMID: 12139086 [PubMed - indexed for MEDLINE]

2895: Can J Neurol Sci. 2002 Jun;29 Suppl 2:S3-7.

Migraine: the doctor-patient link. results of a needs assessment.

Purdy RA.

Division of Neurology, Dalhousie University and Queen Elizabeth II Health
Sciences Centre, Halifax, Nova Scotia, Canada.

OBJECTIVES: To do a needs assessment directed to neurologists attending a
workshop on communication skills emphasizing relationships between physician and 
patient, assessment of disability and quality of life of migraine patients, and
communication of therapies for migraine. METHODS: A structured questionnaire was 
sent to all participants related to the issues indicated in the objective. This
was prepared by the faculty and the results were collated by the author and
presented at the beginning of the workshop. This paper overviews the use and
results of a needs assessment to highlight learning needs of the participants and
to focus the issues, interest and interactions of neurologists in a workshop. The
workshop focused primarily on communication skills and on the understanding of
disability and quality of life issues in migraine patients. RESULTS: In general
the responses revealed that the attendees were neurologists in practice for more 
than 15 years, that over 50% had prior knowledge of communication skills and used
them in various ways, and 74% were involved in teaching family physicians. Some
knew and used disability and quality of life tools but up to one third of
participants did not assess disability in their patients. Most wanted to learn
more about communication skills and other objectives noted and 19% of respondents
wanted to learn more about prophylactic antimigraine treatments and how to
differentiate/contrast the triptans. CONCLUSION: Using a needs assessment tool
allowed organizers of an educational workshop to determine the current knowledge 
and perceived and unperceived needs of the participants with respect to
communication skills, assessing disability and quality of life issues, and
communication of treatments to migraine patients.

PMID: 12139083 [PubMed - indexed for MEDLINE]

2896: Can J Neurol Sci. 2002 Jun;29 Suppl 2:S16-22.

Assessing health-related quality of life in patients with migraine.

Becker WJ.

BACKGROUND: The place of health-related quality of life (HRQoL) instruments in
clinical research trials and clinical practice as compared to more traditional
clinical outcome measures such as headache intensity and frequency is unclear.
OBJECTIVES: To review the current status of HRQoL measurement in migraine.
METHODS: A literature search was done for HRQoL and migraine. Selected articles
dealing with migraine and commonly used HRQoL instruments and HRQoL measures used
in recent clinical trials were reviewed. RESULTS: Several general and migraine
specific HRQoL instruments can detect changes over time in response to at least
major changes in migraine therapy. Both also show a correlation with clinical
headache features. However, their sensitivity to detect clinically significant
changes over time is not clear. CONCLUSION: The SF-36, a general HRQoL measure
and several migraine-specific HRQoL instruments are useful endpoints for migraine
clinical trials. Their role in clinical practice is yet to be established.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 12139081 [PubMed - indexed for MEDLINE]

2897: Can J Neurol Sci. 2002 Jun;29 Suppl 2:S11-5.

Evaluating migraine disability: the headache impact test instrument in context.

Pryse-Phillips W.

Department of Medicine, Memorial University of Newfoundland, St John's NF,
Canada.

Migraine impairs physical, social and emotional functioning but the diagnosis is 
not always made despite the availability of helpful tools. Poor patient-physician
communication is one reason cited for this. It is arguable that if the impact
that headaches are having on a person's life can be communicated adequately to
the physician, the likelihood of appropriate management will increase. The tools 
currently employed for assessing headache impact are reviewed briefly and the
Headache Impact Test (HIT) and HIT-6 described as validated and reliable measures
of the effect that headaches are having on patients. The availability of the
standard test on the internet, with feedback provided, indicates that this is a
potentially useful tool enabling headache sufferers to realize the extent of the 
burden of migraine and empowering them to seek appropriate management strategies.

Publication Types: 
    Evaluation Studies
    Review

PMID: 12139080 [PubMed - indexed for MEDLINE]

2898: Can J Neurol Sci. 2002 Jun;29 Suppl 2:S1-2.

Communication with the migraine patient.

Becker WJ.

University of Calgary and Calgary Regional Health Authority, Alberta, Canada.

Much has been added to our knowledge of effective physician-patient communication
by the research of the past two decades. Good communication skills are especially
important for the clinician dealing with a migraine patient, as neither
laboratory tests nor diagnostic physical findings are available to assist the
physician in diagnosis and treatment. It is important for clinicians to
understand that effective communication skills can be taught and learned and
that, once mastered, they have the potential to improve patient outcomes.

PMID: 12139079 [PubMed - indexed for MEDLINE]

2899: Middle East J Anesthesiol. 2002 Jun;16(5):499-504.

Blockade of branches of the ophthalmic nerve in the management of acute attack of
migraine.

Dimitriou V, Iatrou C, Malefaki A, Pratsas C, Simopoulos C, Voyagis GS.

Department of Anaesthesia, Pain Clinic, Democritus University of Thrace,
University Hospital, 19 Dimitras Str, 68100 Alexandroupolis, Greece.
vdimitri@med.duth.gr

The aim of this study was the evaluation of the blockade of branches of
ophthalmic nerve in the management of the acute attack of migraine headache
localized to the ocular region. The study included 70 female patients 23-60 years
old who presented to the pain clinic at our hospital with an acute attack of
migraine headache localized to the ocular and retro-ocular region. A targeted
history and a neurologic examination were performed in all patients to confirm
the diagnosis and at the same time to rule out life-threatening neurological
dysfunction. The method applied was the blockade of the supraorbital and
supratrochlear nerves which are branches of the ophthalmic nerve. By the use of a
fine short needle 27G the nerves were sought for until paraesthesia is obtained
and then 1 ml of lignocaine 2% with adrenaline 1:200,000 was injected in every
one of the three sites of the nerves. The migraine acute attack was relieved in
58/70 patients (82%), while in 12/70 patients (18%) the results were poor. The
pain relief started 3-4 min after the injection and was completed in 10-15 min.
Our results support that the blockade of the branches of the ophthalmic nerve
seems to be a safe and effective technique in the management of the acute attack 
of migraine localized to the ocular and retro-ocular region.

Publication Types: 
    Clinical Trial

PMID: 12138513 [PubMed - indexed for MEDLINE]

2900: Curr Opin Investig Drugs. 2002 Jun;3(6):921-3.

DP-VPA D-Pharm.

Labiner DM.

labinerd@u.arizona.edu

Shire is developing DP-VPA, a prodrug of valproic acid (VPA) licensed from
D-Pharm, for the potential treatment of severe forms of epilepsy, including
status epilepticus, acute repetitive seizures in children and possibly manic
depression and migraine [242649], [385958]; the drug is also being developed for 
bipolar disorder and migraine prophylaxis [385862]. By March 2000, phase I trials
had been completed [359581], [373232] and in October 2000, the compound entered
phase II trials for the treatment of epilepsy, bipolar disorder and migraine
[385862]; these trials were ongoing in November 2001 [429470]. In October 2001,
Shire initiated multicenter, multinational phase II trials of SPD-421 as add-on
therapy in the treatment of complex partial seizures [425660]. In February 2002, 
Shire reported that it planned to make a decision regarding the future of the
compound by the second half of 2002 [441819]. DP-VPA is based on D-Pharm's
regulation activation of prodrugs (RAP) technology, which designs drugs to be
internalized within cells and to be activated only when the tissue becomes
diseased. In the case of DP-VPA, the pathological epilepsy process activates it
on demand [342433]. RAP-prodrugs are composed of the active drug moiety attached 
via a chemical linkage to a hydrophobic molecule which allows the agent to
penetrate into the cell [182806]. In October 2000, D-Pharrm received patent
US-06077837 from the USPTO covering novel 'Prodrugs with enhanced penetration
into cells'. This patent claims prodrugs, comprising a pharmacologically active
compound covalently linked to an intracellular transporter by a bond which is
preferentially cleaved by disease-associated supranormal enzyme activity
[385507]. In April 2000, Lehman Brothers predicted the launch of DP-VPA during
2003 [365103]. In December 2001, Lehman Brothers suggested that the product would
be approved in 2004. The analysts estimated a 25% probability of the drug
reaching the market, and envisaged peak sales of $200 million [434768]. Analysts 
at Schroder Salomon Smith Barney predicted in March 2002, that sales for Shire of
DP-VPA would reach US $9.5 million in 2005, rising to US $31 million in 2006
[449087].

Publication Types: 
    Review

PMID: 12137414 [PubMed - indexed for MEDLINE]

2901: Neurology. 2002 Jul 23;59(2):232-7.

Prevalence and clinical characteristics of migraine in France.

Henry P, Auray JP, Gaudin AF, Dartigues JF, Duru G, Lantéri-Minet M, Lucas C,
Pradalier A, Chazot G, El Hasnaoui A.

Service de Neurologie, Hôpital Pellegrin-Tripode, Bordeaux, France.
patrick.henry@chu-bordeaux.fr

OBJECTIVE: To determine the prevalence and clinical features of migraine and
related headache types in France. METHODS: The authors recruited a population of 
subjects with headache representative of the national population using a
stratified sampling method. They screened 10,585 subjects aged 15 and older who
were representative of the general population. They identified 1,486 of these as 
having headaches, and these subjects were subsequently interviewed for
information on clinical features, natural history, and functional impact of
headache. The authors categorized subjects based on the International Headache
Society (IHS) classification and assessed disability using the MIDAS
questionnaire. RESULTS: The authors found a standardized prevalence for migraine 
(IHS categories 1.1 and 1.2) of 7.9% (11.2% for women and 4.0% for men) and 9.1% 
for migrainous disorder (IHS category 1.7). Migraine attacks were associated with
a considerable degree of handicap in activities of daily living, with a MIDAS
grade distribution of 74.7% (grade 1), 13.3% (grade 2), 7.7% (grade 3), and 4.3% 
(grade 4). The prevalence of migraine with MIDAS grade 3 or 4 was 1.6%.
CONCLUSIONS: The prevalence of migraine (IHS categories 1.1 and 1.2) in France is
7.9%, and that of total migraine is 17.0%; this does not seem to have evolved
over the past 10 years.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 12136063 [PubMed - indexed for MEDLINE]

2902: Cephalalgia. 2002 Jul;22(6):453-61.

Almotriptan is an effective and well-tolerated treatment for migraine pain:
results of a randomized, double-blind, placebo-controlled clinical trial.

Dowson AJ, Massiou H, Laínez JM, Cabarrocas X.

Kings Headache Service, Kings College Hospital, Denmark Hill, London SE5 9RS, UK.
drandydowson@dowsona.fsnet.co.uk

Almotriptan is a novel and specific serotonin 5-HT1B/1D agonist for the acute
treatment of migraine. This randomized, single-dose, double-blind, multicentre,
study assessed the efficacy and safety of oral almotriptan (12.5 mg and 25 mg) in
patients with migraine, and compared it with the standard treatment (sumatriptan 
100 mg) and placebo. A total of 668 patients treated one migraine attack of
moderate or severe intensity with study medication. The primary efficacy
assessment was migraine pain relief, improvement from severe or moderate pain to 
mild or no pain, at 2 h after treatment. Response rates, stratified for variation
in baseline pain levels, for both almotriptan doses were equivalent to
sumatriptan and significantly better than placebo. Other efficacy assessments
confirmed the equivalence of the almotriptan groups with the sumatriptan group.
Almotriptan 12.5 mg was as well tolerated as placebo (P=0.493) and significantly 
better tolerated than sumatriptan (P<0.001), in terms of the overall incidence of
adverse events. There was no statistically significant difference in the
incidence of adverse events between almotriptan 25 mg and sumatriptan 100 mg
(P=0.376). The results from this large clinical study indicate that the new,
specific 5-HT1B/1D agonist, almotriptan, is an effective and well-tolerated
treatment for migraine pain.

Publication Types: 
    Clinical Trial
    Comparative Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 12133045 [PubMed - indexed for MEDLINE]

2903: Cephalalgia. 2002 Jul;22(6):444-52.

Exteroceptive suppression patterns of masseter and temporalis muscles in central 
and peripheral headache disorders.

Tataroglu C, Kanik A, Sahin G, Ozge A, Yalçinkaya D, Idiman F.

Faculty of Medicine, Mersin University, Mersin, and Faculty of Medicine, Dokuz
Eylul University, Izmir, Turkey. cengizta@hotmail.com

The objective of this study was to compare the exteroceptive suppression patterns
of masseter and temporalis muscles in patients with primary and secondary
headache disorders originating from peripheral joint dysfunction. We accomplished
the temporalis and masseter exteroceptive suppression in 28 patients with
migraine, 25 patients with chronic tension-type headache (CTH), 22 patients with 
temporomandibular joint (TMJ) dysfunction and 18 healthy controls. The onset
latencies and duration of the first suppression period (S1) was not significantly
different between the patients and controls. The duration of the second
suppression period (S2) was shorter in patients with CTH, migraine (analysed
during attack) and TMJ dysfunction than those obtained from controls. A
distinctive finding was significantly prolonged onset latency in patients with
TMJ over those obtained from patients with CTH and migraine. We concluded that
the onset latency of the S2 period is a useful parameter in the differential
diagnosis of primary and peripheral headache disorders.

Publication Types: 
    Comparative Study

PMID: 12133044 [PubMed - indexed for MEDLINE]

2904: Cephalalgia. 2002 Jul;22(6):416-23.

Efficacy and safety of eletriptan 20 mg, 40 mg and 80 mg in Japanese migraineurs.

Eletriptan Steering Committee in Japan.

This prospective multicentre, double-blind, randomized, parallel-group,
placebo-controlled trial evaluated the efficacy and safety of a single dose of
eletriptan 20 mg, 40 mg and 80 mg in Japanese migraineurs. A total of 402 adult
Japanese migraineurs were diagnosed using International Headache Society (IHS)
criteria. At 2 h after a single dose, the headache response rates of eletriptan
20 mg, 40 mg, 80 mg and placebo were 64%, 67%, 76% and 51%, respectively, with
all doses significantly superior to placebo (P<0.05). Eletriptan had a
statistically significant dose response for headache relief and pain-free
response at 2 h post-dose (P=0.0011 and P=0.0291, respectively). Most
all-causality adverse events were mild and there were no deaths or
discontinuations. Saliva samples were used to assess serum eletriptan levels 2 h 
post-dose. Pharmacokinetic evaluations showed no clinically significant
differences between Japanese and Western subjects. Eletriptan was shown to be
efficacious, safe, and well tolerated in Japanese migraineurs.

Publication Types: 
    Clinical Trial
    Clinical Trial, Phase II
    Comparative Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 12133040 [PubMed - indexed for MEDLINE]

2905: Cephalalgia. 2002 Jul;22(6):411-5.

A prospective study of the headache phase in 32 migraine with aura patients.

Cologno D, Torelli P, Manzoni GC.

Headache Centre, Institute of Neurology, University of Parma, Parma, Italy.
dcologn@tin.it

For an accurate description of the clinical features of the headache phase in
migraine with aura (MA) attacks, we thought it useful to conduct a prospective
study of consecutively referred MA patients seeking treatment at the Headache
Centre of the University of Parma Institute of Neurology. The case series
included 32 patients (22 women and 10 men). At the time of the first visit, each 
patient was given a questionnaire to be filled in at the next MA attack. Six
patients (four women and two men) had attacks of migraine aura without headache. 
Among the remaining 26 patients (18 women and eight men), the duration of the
headache phase was <24 h in 23 (88.5%); pain location was bilateral in 14 (53.8%)
and unilateral in 12, but occurring on the opposite side to aura only in one
patient; pain intensity was mild or moderate in 13 (50.0%). The headache phase of
MA appeared to have clinical features that differed widely from patient to
patient and was consistent with the International Headache Society diagnostic
criteria for migraine without aura in 26.9% of patients and for tension-type
headache (TTH) in 23.1%.

PMID: 12133039 [PubMed - indexed for MEDLINE]

2906: J Hypertens. 2002 Jul;20(7):1303-6.

Migraine is more frequent in individuals with optimal and normal blood pressure: 
a population-based study.

Wiehe M, Fuchs SC, Moreira LB, Moraes RS, Fuchs FD.

Division of Cardiology, Hospital de Clínicas de Porto Alegre, RS, Brazil.

BACKGROUND : The notion that hypertension causes headache is widely accepted
despite the absence of confirmation by well-designed studies. OBJECTIVE : To
investigate the association between headache, characterized as tension type and
migraine like, with blood pressure and hypertension. METHODS : In a
cross-sectional study we evaluate this association in a sample of 1174
individuals older than 17 years, representative of inhabitants of Porto Alegre,
RS, Brazil. Headache and its subtypes were defined according to International
Headache Society criteria. Hypertension was defined as the mean of two blood
pressure readings >or=140/90 mmHg or use of antihypertensive drugs. RESULTS :
Headache in lifetime, in the last year, and defined as episodic and chronic
tension-type headache was not associated with hypertension. Individuals with
optimal or normal blood pressure (Sixth Joint National Committee criteria)
complained of migraine more frequently than the participants with high-normal
blood pressure or hypertension. This association persisted after adjustment for
several potential confounding factors (risk ratio, 0.56; confidence interval,
0.41-0.77). CONCLUSION : Our findings confirm that high blood pressure is not
associated with the complaint of headache in the population. Individuals with
migraine-like episodes of headache may have lower blood pressure than individuals
without headache.

Publication Types: 
    Comparative Study
    Evaluation Studies
    Research Support, Non-U.S. Gov't

PMID: 12131526 [PubMed - indexed for MEDLINE]

2907: J Neuroophthalmol. 2002 Jun;22(2):82-7.

Comment in:
    J Neuroophthalmol. 2003 Jun;23(2):182-3.

Migraine-like visual hallucinations in occipital lesions of cysticercosis.

Sharma K, Wahi J, Phadke RV, Varma A, Jain VK.

Department of Neurosurgery (Neuro-Ophthalmology), Sanjay Gandhi Post Graduate
Institute of Medical Sciences, Lucknow, India.

Four Indian patients with occipital lesions of cysticercosis presented with
visual hallucinations. Neuro-ophthalmic and systemic examinations were normal in 
all cases except for one patient who had a partial homonymous hemianopia.
Electroencephalography was normal in all cases. Neuroimaging revealed
ring-enhancing lesions in the occipital lobe typical of neurocysticercosis. In
endemic regions like India, neurocysticercosis should be suspected in patients
presenting with visual hallucinations, even when there are no other clinical
findings.

Publication Types: 
    Case Reports

PMID: 12131464 [PubMed - indexed for MEDLINE]

2908: J Adolesc Health. 2002 Aug;31(2):154-61.

Supplementation with omega-3 polyunsaturated fatty acids in the management of
recurrent migraines in adolescents.

Harel Z, Gascon G, Riggs S, Vaz R, Brown W, Exil G.

Divisions of Adolescent Medicine, Providence, Rhode Island 02903, USA.
zharel@lifespam.org

PURPOSE: To examine whether dietary supplementation with fish oil rich in very
long-chain n-3 polyunsaturated fatty acids might reduce frequency and severity of
migraines in adolescents. METHODS: Twenty-seven adolescents suffering from
frequent migraines for at least 1 year (mean 4 +/- 1 years since migraine onset) 
participated in a randomized, double-blind, cross-over study consisting of 2
months of fish oil, 1-month washout period, and 2 months of placebo (olive oil). 
Participants self-assessed severity and duration of headache episodes (7-point
faces and 10-point visual analog pain scales, 5-point frequency and severity
rating scale) throughout the study. At the end of every 2-month treatment period,
participants rated the effectiveness of treatment on a 7-point Likert scale
(1,"not effective, not worthwhile"; 4,"moderately effective, moderately
worthwhile"; 7, "totally effective, totally worthwhile"). A score of > or = 4 on 
the Likert scale was considered as improvement. RESULTS: Twenty-three adolescents
(16 girls, 7 boys, 18 Whites, 3 Hispanics, 1 African-American, 1 Cape Verdean,
mean age 15 +/- 1 years) completed the study. Compared with frequency of
headaches before the study (31 +/- 4 episodes/2 months), there was a significant 
(p <.0001) reduction in headache frequency during fish oil treatment (4 +/- 1
episodes/2 months) and during placebo (olive oil) treatment (4 +/- 1 episodes/2
months) but no significant (NS) difference between treatments. Likewise,
self-assessment on a 7-point faces pain scale revealed a significant reduction in
headache severity during fish oil treatment (2.9 +/- 0.5, p =.01) and during
placebo (olive oil) treatment (3.5 +/- 0.4, <p =.03), compared with headache
severity before study (5.0 +/- 0.3) and no significant difference between
treatments. Patients' ratings of treatments revealed that 87% experienced
reduction in headache frequency, 74% experienced reduction in headache duration, 
and 83% experienced reduction in headache severity during treatment with fish
oil, compared with 78% who experienced reduction in headache frequency, 70% who
experienced reduction in headache duration, and 65% who experienced reduction in 
headache severity during treatment with placebo (olive oil, NS). About 91% stated
that they would recommend fish oil to friends or relatives with headaches vs. 91%
who would recommend placebo (olive oil, NS). CONCLUSIONS: Patients experienced a 
similar reduction in frequency, duration, and severity of headaches during
treatment with fish oil and during treatment with olive oil. Although there was
no significant difference between treatments, the marked improvement from
baseline experienced by the patients suggests that the effect should not be
dismissed as simply a placebo effect. In fact, results of this preliminary study 
suggest that both fish oil and olive oil may be beneficial in the treatment of
recurrent migraines in adolescents. Further studies are warranted to compare each
of these treatments with other interventions.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 12127385 [PubMed - indexed for MEDLINE]

2909: Arch Neurol. 2002 Jul;59(7):1084-8.

Mechanisms of action of the 5-HT1B/1D receptor agonists.

Tepper SJ, Rapoport AM, Sheftell FD.

New England Center for Headache, 778 Long Ridge Rd, Stamford, CT 06902-1251, USA.
SJTepper@aol.com

Recent studies of the pathophysiology of migraine provide evidence that the
headache phase is associated with multiple physiologic actions. These actions
include the release of vasoactive neuropeptides by the trigeminovascular system, 
vasodilation of intracranial extracerebral vessels, and increased nociceptive
neurotransmission within the central trigeminocervical complex. The 5-HT(1B/1D)
receptor agonists, collectively known as triptans, are a major advance in the
treatment of migraine. The beneficial effects of the triptans in patients with
migraine are related to their multiple mechanisms of action at sites implicated
in the pathophysiology of migraine. These mechanisms are mediated by 5-HT(1B/1D) 
receptors and include vasoconstriction of painfully dilated cerebral blood
vessels, inhibition of the release of vasoactive neuropeptides by trigeminal
nerves, and inhibition of nociceptive neurotransmission. The high affinity of the
triptans for 5-HT(1B/1D) receptors and their favorable pharmacologic properties
contribute to the beneficial effects of these drugs, including rapid onset of
action, effective relief of headache and associated symptoms, and low incidence
of adverse effects.

Publication Types: 
    Review

PMID: 12117355 [PubMed - indexed for MEDLINE]

2910: Am J Med Genet. 2002 Jun 1;110(1):62-4.

Anticipation in migraine with affective psychosis.

Kaiser F.

Kneesworth House, Psychiatric Hospital, Herts, United Kingdom, UK.
slees@piclibrary.freeserve.co.uk

Anticipation is the term given to the apparent occurrence of an inherited
disorder at a progressively earlier age of onset in successive generations. A
family of a mother and two children, a 17-year-old girl and a 13-year-old boy,
all experienced migraine with affective psychosis. There is a strong genetic
predisposition to the psychiatric disorder of affective psychosis along with a
dominant pattern of migraine in the family, which suggests a genetic connection
between migraine and affective psychosis. Copyright 2002 Wiley-Liss, Inc.

Publication Types: 
    Case Reports

PMID: 12116273 [PubMed - indexed for MEDLINE]

2911: Neurol Sci. 2002 Apr;23(1):7-10.

Familial hemiplegic migraine: clinical features and probable linkage to
chromosome 1 in an Italian family.

Cevoli S, Pierangeli G, Monari L, Valentino ML, Bernardoni P, Mochi M, Cortelli
P, Montagna P.

Institute of Clinical Neurology, University of Bologna Medical School, Via Ugo
Foscolo 7, I-40123 Bologna, Italy.

We describe an Italian family with familial hemiplegic migraine (FHM), subtle
cerebellar signs and probable linkage to chromosome 1. FHM is genetically
heterogeneous; in about 50% of families it is caused by mutations within the
CACNA1A gene on chromosome 19. Linkage to 1q31 and 1g21-23 has also been
established. Other families do not link either to chromosome 19 or 1. Chromosome 
19-linked FHM may display nystagmus and cerebellar ataxia. Affected family
members were neurologically examined; linkage analysis was performed with markers
for chromosomes 19p13, 1q21-23, and 1q32. Five family members had hemiplegic
migraine, and 3 displayed additional cerebellar signs (scanning speech and
nystagmus). In 1 patient, episodes of hemiplegic migraine triggered by mild head 
trauma. Epilepsy and mental retardation were also found in 1 affected relative
each. Lod scores for linkage to 19p13 were negative, while the maximum two-point 
lod score was 1.81 to 1q21-23. This family with FHM and associated subtle
cerebellar signs, epilepsy and mental retardation showed probable linkage to
1q21-23.

Publication Types: 
    Case Reports
    Research Support, Non-U.S. Gov't

PMID: 12111614 [PubMed - indexed for MEDLINE]

2912: Neurol Sci. 2002 Apr;23(1):1-5.

Is the CACNA1A gene involved in familial migraine with aura?

Brugnoni R, Leone M, Rigamonti A, Moranduzzo E, Cornelio F, Mantegazza R, Bussone
G.

Department of Neuromuscular Diseases, C. Besta National Neurological Institute,
Milan, Italy.

The discovery of mutations in the neural calcium channel (CACNA1A) gene in
familial hemiplegic migraine (FHM), variant of migraine with aura, led to the
suggestion that this gene might be involved in familial migraine with aura (FMA).
We investigated whether the mutations in FHM are present in FMA patients,
analyzing genomic DNA by PCR, single stranded conformation polymorphism,
sequencing and restriction enzyme. No mutations were found. A known polymorphism 
(5682-14C>T) was found in exon 36. These findings suggest that the mutations
found in FHM and the other known mutations of the CACNA1A gene are not the
genetic basis of FMA. Genetic alterations in FMA patients may be localized on
chromosome 19 but not in the CACNA1A exons we investigated.

PMID: 12111613 [PubMed - indexed for MEDLINE]

2913: Exp Brain Res. 2002 Jul;145(2):177-81. Epub 2002 May 9.

Modulation of visual cortical excitability in migraine with aura: effects of 1 Hz
repetitive transcranial magnetic stimulation.

Brighina F, Piazza A, Daniele O, Fierro B.

Istituto di Neuropsichiatria, Università di Palermo, via G. La Loggia 1, 90129
Palermo, Italy.

Recent studies showed hyperexcitability of the occipital cortex in subjects
affected by migraine with aura. It has been shown that 1 Hz repetitive
transcranial magnetic stimulation (rTMS) reduces excitability of visual cortex in
normal subjects. The aim of the study was to investigate the effects of low
frequency (1 Hz) rTMS on visual cortical excitability by measuring changes in
phosphene threshold (PT) in subjects with migraine with aura. Thirteen patients
with migraine with aura and 15 healthy controls were examined. Using a
standardized transcranial magnetic stimulation protocol of the occipital cortex, 
we assessed the PT (the lowest magnetic stimulation intensity at which subjects
just perceived phosphenes) before and after a 1-Hz rTMS train delivered at PT
intensity for 15 min. The difference in the proportion of subjects reporting
phosphenes in migrainer and control groups was significant (migrainers: 100% vs
controls 47%; P<0.05), and 1 Hz rTMS over the occipital cortex led to a
significantly increased visual cortex excitability expressed as a decrease in PT 
in subjects affected by migraine with aura. Conversely, after a 1-Hz TMS train
normal subjects showed increased PT values, which suggests a decreased visual
cortex excitability. Our findings confirm that the visual cortex is
hyperexcitable in migrainers and suggest a failure of inhibitory circuits, which 
are unable to be upregulated by low frequency rTMS.

Publication Types: 
    Comparative Study

PMID: 12110957 [PubMed - indexed for MEDLINE]

2914: Cephalalgia. 2002 Jun;22(5):376-83.

Zolmitriptan is effective and well tolerated in Japanese patients with migraine: 
a dose-response study.

Sakai F, Iwata M, Tashiro K, Itoyama Y, Tsuji S, Fukuuchi Y, Sobue G, Nakashima
K, Morimatsu M.

Department of Neurology, Kitasato University, Kitasato 1-15-1, Sagamihara-Shi,
Kanagawa, Japan. fskai@kitasato-u.ac.jp

This phase II study investigated the efficacy, tolerability and dose-response
relationship of oral zolmitriptan in the treatment of a single migraine attack in
Japanese patients. A bridging analysis then assessed the validity of
extrapolating western clinical data to these Japanese patients. In this
multicentre, randomized, double-blind, placebo-controlled study, patients
received a single dose of placebo or zolmitriptan 1, 2.5 or 5 mg. The primary
endpoints were 2-h headache response and the tolerability of zolmitriptan. A
statistically significant dose-response relationship was observed for the 2-h
headache response (P=0.003). The 2.5 mg group had significantly greater 2-h
headache response than the placebo group (P=0.032). The adverse event profile was
similar to that reported in western patients, and no adverse events unique to the
Japanese population were observed. The bridging analysis report confirmed similar
efficacy and tolerability of zolmitriptan in Japanese and western populations. In
the Japanese patients, the estimated response rates were 34.3%, 45.2%, 57.7% and 
66.2% for placebo, and zolmitriptan 1, 2.5 and 5 mg, respectively, while in the
western population the corresponding rates were 39.9%, 49.6%, 61.2% and 71.7%.
Zolmitriptan is effective and well tolerated in the acute treatment of migraine
in Japanese patients. The optimal dose was 2.5 mg, although the 5 mg dose may
provide further benefit for some patients. The bridging analysis supports
extrapolation of data from western to Japanese patients.

Publication Types: 
    Clinical Trial
    Clinical Trial, Phase II
    Multicenter Study
    Randomized Controlled Trial

PMID: 12110113 [PubMed - indexed for MEDLINE]

2915: Cephalalgia. 2002 Jun;22(5):361-75.

An epidemiological survey of hemiplegic migraine.

Lykke Thomsen L, Kirchmann Eriksen M, Faerch Romer S, Andersen I, Ostergaard E,
Keiding N, Olesen J, Russell MB.

The Danish Headache Center, University of Copenhagen, Department of Neurology,
Glostrup Hospital, Ndr. Ringvej Ringvej 57, DK-2600 Glostrup, Denmark.
LLT@dadlnet.dk

The objective of the present study was to use systematic nation-wide case-finding
methods to establish the prevalence and sex ratio of hemiplegic migraine (HM) in 
the entire Danish population of 5.2 million inhabitants. Affected patients were
identified from three different recruitment sources: the National Patient
Register, case records from private practising neurologists and advertisements.
Based on the observed number of affected patients from each case-finding method, 
it was attempted to estimate the total number of affected patients by means of
the statistical method known as capture-recapture. Two hundred and ninety-one
affected patients were identified; 147 were familial HM from 44 different
families, 105 were sporadic HM and 39 were unclassifiable HM. The HM sex ratio
(M:F) was 1:3. Based on the identified number of affected patients the prevalence
of HM at the end of 1999 was estimated to be 0.01% in Denmark, where the familial
and sporadic form were equally frequent.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 12110112 [PubMed - indexed for MEDLINE]

2916: Cephalalgia. 2002 Jun;22(5):345-53.

Intravenous magnesium sulphate in the acute treatment of migraine without aura
and migraine with aura. A randomized, double-blind, placebo-controlled study.

Bigal ME, Bordini CA, Tepper SJ, Speciali JG.

Department of Neurology, São Paulo University, School of Medicine at Ribeirão
Preto, 3900, 14049-900 Ribeirão Preto, SP, Brazil. marcelobigal@hotmail.com

Magnesium sulphate has been used in the acute treatment of migraines; some
studies found it to be a highly effective medication in the acute control of
migraine pain and associated symptoms. This randomized, double-blind,
placebo-controlled study assesses the effect of magnesium sulphate on the pain
and associated symptoms in patients with migraine without aura and migraine with 
aura. Sixty patients in each group were assigned at random to receive magnesium
sulphate, 1000 mg intravenously, or 0.9% physiological saline, 10 ml. We used
seven parameters of analgesic evaluation and an analogue scale to assess nausea, 
photophobia and phonophobia. In the migraine without aura group there was no
statistically significant difference in the patients who received magnesium
sulphate vs. placebo in pain relief. The analgesic therapeutic gain was 17% and
number needed to treat was 5.98 at 1 h. There was also no statistical difference 
in relief of nausea. We did observe a significant lower intensity of photophobia 
and phonophobia in patients who received magnesium sulphate. In the migraine with
aura group patients receiving magnesium sulphate presented a statistically
significant improvement of pain and of all associated symptoms compared with
controls. The analgesic therapeutic gain was 36.7% at 1 h. A smaller number of
patients continued to have aura in the magnesium sulphate group compared with
placebo 1 h after the administration of medication. Our data support the idea
that magnesium sulphate can be used for the treatment of all symptoms in migraine
with aura, or as an adjuvant therapy for associated symptoms in patients with
migraine without aura.

Publication Types: 
    Clinical Trial
    Comparative Study
    Multicenter Study
    Randomized Controlled Trial

PMID: 12110110 [PubMed - indexed for MEDLINE]

2917: Cephalalgia. 2002 Jun;22(5):340-4.

Muscle tenderness in pericranial and neck-shoulder region in children with
headache. A controlled study.

Anttila P, Metsähonkala L, Mikkelsson M, Aromaa M, Kautiainen H, Salminen J,
Viander S, Jäppilä E, Sillanpää M.

Child and Adolescent Health Care, City of Turku, Department of Public Health,
University of Turku, Turku, Finland. pirjoa.anttila@pp.fimnet.fi

Increased pericranial muscle tenderness is connected with tension-type headache
in adults. In children, the importance of muscle tenderness in the pericranial or
neck-shoulder region in the pathogenesis of different types of headache is
unknown. The present study evaluated muscle tenderness in the pericranial and
neck-shoulder region in children with migraine, those with tension-type headache 
and those without headache. An unselected population-based questionnaire study
concerning headache was carried out in 1135 Finnish schoolchildren aged 12 years.
Of them, 183 children were randomly selected for a face-to-face interview and a
clinical examination. Muscle tenderness was recorded by manual palpation and
dolorimeter. Children with migraine had increased overall tenderness, recorded by
manual palpation, compared with those without headache. They also self-reported
tenderness in the neck-shoulder region during daily activities more often than
the children of the other groups. Muscle tenderness was not associated with
paediatric tension-type headache. The mean pressure pain thresholds did not
differ among the three groups. However, a negative correlation between the total 
tenderness score and the dolorimeter score was found in each group. In
conclusion, children with migraine had increased muscle tenderness at palpation
of the pericranial and neck-shoulder muscles and they also reported pain symptoms
in the neck-shoulder region most frequently. Instead, increased pericranial and
neck-shoulder muscle tenderness was not associated with tension-type headache in 
children.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 12110109 [PubMed - indexed for MEDLINE]

2918: Neurology. 2002 Jul 9;59(1):72-8.

Functional MRI-BOLD of brainstem structures during visually triggered migraine.

Cao Y, Aurora SK, Nagesh V, Patel SC, Welch KM.

Department of Neurology, Henry Ford Health Systems, Detroit, MI, USA.
yue@radiology.msu.edu

BACKGROUND: Previously, hyperoxia and blood volume increase were reported in the 
red nucleus and substantia nigra during spontaneous migraine with aura.
OBJECTIVE: To further understand the pathophysiologic role of these centers,
activation of brainstem structures was investigated in patients with visually
triggered migraine. METHODS: Twenty-six patients with migraine (23 with aura and 
3 without aura), and 10 normal control subjects were studied with blood oxygen
level-dependent (BOLD) fMRI during repeated checkerboard visual stimulation.
Three axial image sections, which covered the occipital cortex and brainstem,
were acquired 224 times with a temporal resolution of 3.5 seconds. RESULTS:
Repetitive visual stimulation triggered symptoms in 12 patients; four who had
migraine with aura developed both visual symptoms and headaches, and six who had 
migraine with aura and two who had migraine without aura had headaches only. Four
patients who had migraine with aura experienced the onset of their usual aura or 
onset of their typical headache either during the experiment or immediately
after. In the remaining 10 patients with migraine, and all control subjects,
visual stimulation failed to trigger symptoms at any time. In 75% of the patients
who developed symptoms during stimulation, baseline T2*-weighted MR signal
intensities increased in the red nucleus and substantia nigra before occipital
cortex signal elevation or the onset of visually triggered symptoms. CONCLUSION: 
Activation (hyperoxia and blood volume increase) of the red nucleus and
substantia nigra in association with visually triggered symptoms of migraine
suggest that these brainstem structures are a part of a neuronal network
activated during an attack.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 12105310 [PubMed - indexed for MEDLINE]

2919: Cephalalgia. 2002 May;22(4):309-12.

Rizatriptan combined with rofecoxib vs. rizatriptan for the acute treatment of
migraine: an open label pilot study.

Krymchantowski AV, Barbosa JS.

Rio Military Police, Department of Neurology, Universidade Federal Fluminense,
Headache Center of Rio, Rio de Janeiro, Brazil. abouchkrym@globo.com

Rizatriptan is an effective and fast acting drug for the acute treatment of
migraine. As with any other acute treatment for migraine, headache recurrence may
occur in up to one-third of responders. Combination with non-steroidal
anti-inflammatory drugs (NSAIDs) seems to reduce the incidence of headache
recurrence in clinical practice. Rofecoxib is a member of a new class of NSAIDs, 
which selectively inhibits the COX-2 enzyme and therefore is associated with a
lower risk of gastrointestinal side-effects; the drug has a long plasma half-life
(17 h). This open label study compared rizatriptan with rizatriptan plus
rofecoxib in the acute treatment of migraine. Fifty-six triptan naive patients
from a tertiary centre (37 women and 19 men, ages 16-55 years, mean 35 years)
with International Headache Society migraine were randomized into two groups.
They were instructed to treat three consecutive moderate or severe attacks with
either 10 mg rizatriptan (group 1: 18 women and 10 men) or with 10 mg rizatriptan
plus 25 mg rofecoxib (group 2: 19 women and 9 men). The presence of headache and 
nausea at 1, 2 and 4 h, and of side-effects, use of rescue medication and
recurrence were compared. Fifty-four patients completed the study. Group 1
treated 76 attacks and group 2 treated 81 attacks. Absence of headache at 1 h was
seen in 19 attacks (25%) in group 1 and in 34 attacks (42%) in group 2 (P=0.082);
at 2 h absence of headache was seen in 60% of group 1 attacks and in 76% of group
2 attacks (P=0.115). At 4 h, 75% of group 1 attacks and 88% of group 2 attacks
were pain free (P=0.122). With regard to nausea, of those who had nausea at
baseline, 31% and 49% of attacks in groups 1 and 2, respectively, were nausea
free at 1 h (P=0.091), 75% and 79% at 2 h (P=0.736) and 82% and 91% (P=0.479) at 
4 h. Recurrence, based on all attacks of those patients who achieved pain free at
4 h, was observed in 53% of group 1 and 20% of group 2 attacks (P<0.001).
Sustained pain-free rates (for the 4-h time point) were 45.6% of group 1 and
78.9% of group 2 attacks. There were no significant differences with regard to
rescue medication consumption after 4 h and side-effects in both groups. There
was a non-significant trend for the combination group to have a higher response
rate. The group treated with rizatriptan and rofecoxib had a lower recurrence
rate than the group treated with rizatriptan. This study demonstrated that
combining a fast acting triptan such as rizatriptan with rofecoxib reduced
headache recurrence rates, was well tolerated and may be more effective than the 
use of rizatriptan alone. Double-blind, placebo-controlled studies are necessary 
to confirm these observations.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial

PMID: 12100094 [PubMed - indexed for MEDLINE]

2920: Cephalalgia. 2002 May;22(4):291-302.

Cognitive disturbances and regional cerebral blood flow abnormalities in migraine
patients: their relationship with the clinical manifestations of the illness.

Calandre EP, Bembibre J, Arnedo ML, Becerra D.

Institute of Neurosciences, University of Granada, Spain. epita@ugr.es

The purpose of the present study was to evaluate neuropsychological performance
and regional cerebral blood flow in migraine patients, and to investigate whether
possible abnormalities in any of these fields could be related to the chronicity 
of the disease. The sample included 60 patients and 30 healthy control subjects; 
all of them were subjected to a complete neuropsychological assessment, including
emotional variables. In addition an interictal 99Tc-HMPAO SPECT was performed in 
56 patients and 15 controls. Disturbances in memory, attention and visuomotor
speed processing were observed among migraineurs experiencing higher frequency of
attacks and in those with a long history of migraine. Anxiety levels were higher 
in patients than in controls and were positively correlated with attack
frequency, but not with cognitive test scores. Brain perfusion abnormalities,
mostly hypoperfusion areas, were found in the 43% of patients; poorer performance
in two tests, measuring verbal and visual memory, respectively, was found in
these patients.

PMID: 12100092 [PubMed - indexed for MEDLINE]

2921: Cephalalgia. 2002 May;22(4):288-90.

Exaggerated interictal cerebrovascular reactivity but normal blood flow
velocities in migraine without aura.

Dora B, Balkan S.

Department of Neurology, Akdeniz University Medical School, Antalya, Turkey.
bdora@ada.net.tr

Interictal cerebrovascular reactivity and blood flow velocities were tested in 23
patients with migraine without aura and 10 age- and sex-matched healthy controls 
by using the breath holding index (BHI). The mean systolic, diastolic and mean
velocities and pulsatility indices were not different in the controls and
patients. The BHI was found to be significantly greater (P=0011) in the patients 
(1.64 +/- 0.33) compared with the controls (1.26 +/- 0.37), showing an
exaggerated reactivity to hypercapnia in migraineurs. Reactivity to pCO2
theoretically depends on pre-existing arteriolar tone and thereby on baseline
velocity. Our finding of similar blood flow velocities in controls and patients
suggests that the underlying cause for this high reactivity may not be an
increased vasotonus but an increased sensitivity to changes in blood CO2 levels.

Publication Types: 
    Comparative Study

PMID: 12100091 [PubMed - indexed for MEDLINE]

2922: Cephalalgia. 2002 May;22(4):265-70.

A quantification of the placebo response in migraine prophylaxis.

van der Kuy PH, Lohman JJ.

Department of Clinical Pharmacy, Academic Hospital, Maastricht, The Netherlands. 
hkuy@kfls.azm.nl

To quantify the placebo response of prophylactic therapy in migraine, a
meta-analysis of prophylactic, double-blind, placebo controlled migraine studies 
was performed. The total analysis included 22 studies testing 19 different
products, including 2013 patients, of which 828 were treated with placebo. A
reduction in migraine attacks of 50% or more (responders) was seen in 23.5%+/-8.0
(95% C.I. 18.3-28.8%) of the patients in the placebo groups and 45.5%+/-15.5 (95%
C.I. 37.4-53.6%) in the active groups. A reduction in migraine attacks of
16.8%+/-12.7 (95% C.I. 10.9-22.6%) was observed in the placebo groups and
41.8%+/-11.7 (95% C.I. 36.9-46.6%) in the active groups. We propose that if the
percentage of responders in an open-label prophylactic trial in migraine is above
35-40%, or if a reduction in migraine attack frequency is found of 40% or more,
further studies are indicated to determine the prophylactic activity of the drug.
In all studies included in this analysis, no placebo response was seen above
these limits.

Publication Types: 
    Meta-Analysis

PMID: 12100088 [PubMed - indexed for MEDLINE]

2923: Cephalalgia. 2002 May;22(4):256-9.

Unilateral cranial autonomic symptoms in migraine.

Barbanti P, Fabbrini G, Pesare M, Vanacore N, Cerbo R.

Department of Neurological Sciences, University La Sapienza, Rome, Italy.
piero.barbanti@uniroma1.it

Unilateral cranial autonomic symptoms (UAs) such as lacrimation, conjunctival
injection, eyelid oedema and nasal congestion, which are the hallmark of
trigeminal autonomic cephalgias, may also occur in an as yet undetermined
proportion of migraine patients. We studied 177 consecutive migraineurs to assess
the frequency of UAs and the clinical characteristics of such patients. UAs were 
reported by 81 patients (45.8%), ocular symptoms alone or in combination with
nasal symptoms being the most frequent. The headache was more severe (P<0.0002)
and more strictly unilateral (P<0.0004) in patients who reported UAs than in
those without. Thus, the presence of UAs suggests an activation of the
trigeminal-autonomic reflex, probably related to an over-activation of the
trigeminal afferent arm. These findings could have therapeutic implications,
given the potential large-scale recruitment of peripheral neurovascular
5-HT(1B/1D) receptors (the target of acute migraine treatment) in such patients.

PMID: 12100086 [PubMed - indexed for MEDLINE]

2924: Curr Pain Headache Rep. 2002 Aug;6(4):320-3.

The use of botulinum toxin in the treatment of headaches.

Mauskop A.

New York Headache Center, 30 East 76th Street, New York, NY 10021, USA.
NYheadache@aol.com

The use of botulinum toxin for movement disorders and cosmesis led to an
accidental discovery of its beneficial effect on headaches. Extensive anecdotal
evidence and several controlled trials suggest that intermittent and chronic
migraines and chronic tension headaches may respond to this treatment. The effect
of a single treatment, which is simple to administer, can last for 3 months.
Botulinum toxin does not cause systemic or any other serious side effects.
Prophylactic pharmacotherapy of migraine headaches is limited in its efficacy and
has a potential for systemic side effects. This makes botulinum toxin a preferred
treatment for many patients. The large controlled trials that are underway may
lead to a wider acceptance of this treatment by neurologists and pain
specialists.

Publication Types: 
    Review

PMID: 12095468 [PubMed - indexed for MEDLINE]

2925: Drugs. 2002;62(10):1539-74.

Rizatriptan: an update of its use in the management of migraine.

Wellington K, Plosker GL.

Adis International Limited, 41 Centorian Drive, PB 65901, Mairangi Bay, Auckland 
10, New Zealand. demail@adis.co.nz

Rizatriptan is an orally active serotonin 5-HT(1) receptor agonist that potently 
and selectively binds to 5-HT(1B/1D) subtypes. Earlier clinical trials
demonstrated that rizatriptan 5 or 10mg is more effective than placebo at
providing pain relief and a pain-free state, relieving associated symptoms of
migraine, normalising functional ability and improving patient quality of life,
and showed that rizatriptan provides faster freedom from pain and reduces nausea 
to a greater extent than oral sumatriptan. More recently, rizatriptan 10mg was
shown to be more effective than zolmitriptan 2.5mg or naratriptan 2.5mg at
producing a pain-free state 2 hours postdose. Furthermore, compared with
naratriptan, significantly more patients who received rizatriptan were pain free 
or had pain relief from 1 hour onwards. The number of patients with normal
functional ability at 2 hours was significantly higher after rizatriptan than
after naratriptan or zolmitriptan. Rizatriptan was also generally more effective 
than zolmitriptan or naratriptan at relieving migraine-associated symptoms.
Rizatriptan is generally well tolerated and adverse events are usually mild and
transient. The most common adverse events associated with rizatriptan in recent
randomised trials were asthenia/fatigue, dizziness, somnolence and nausea. There 
was a trend towards a lower incidence of adverse events with rizatriptan compared
with zolmitriptan (31.2 vs 38.8%). However, rizatriptan was associated with a
significantly higher incidence of adverse events than naratriptan (39 vs 29%).
The incidence of chest pain was similar after the administration of rizatriptan, 
zolmitriptan or naratriptan (2 to 4%). CONCLUSION: Rizatriptan is an effective
drug for the acute treatment of moderate or severe migraine. Oral rizatriptan 5
and 10mg have shown greater efficacy than placebo in providing pain relief, an
absence of pain, relief from associated symptoms, normal functional ability and
an improvement in patient quality of life. Earlier results showed that
rizatriptan provides faster freedom from pain and reduces nausea to a greater
extent than oral sumatriptan. More recent studies have shown that rizatriptan
10mg provides faster pain relief and a higher percentage of patients with an
absence of pain and normal functional ability at 2 hours than naratriptan 2.5mg
or zolmitriptan 2.5mg. The efficacy of rizatriptan is retained when used in the
long term and the drug is generally well tolerated. Although well designed
studies comparing rizatriptan with almotriptan, eletriptan and frovatriptan would
further define the position of rizatriptan, current data suggest rizatriptan
should be considered as a first-line treatment option in the management of
migraine.

Publication Types: 
    Review

PMID: 12093318 [PubMed - indexed for MEDLINE]

2926: J Occup Environ Med. 2002 Jun;44(6):523-9.

The economic burden of lost productivity due to migraine headache: a specific
worksite analysis.

Burton WN, Conti DJ, Chen CY, Schultz AB, Edington DW.

Bank One, Mail Code IL 1-0006, 1 Bank One Plaza, Chicago, IL 60670-0006, USA.
wayne_n_burtonmd@bankone.com

Large, epidemiologic survey studies have established that migraine headaches
affect approximately 6% of men and 18% of women in the United States and that the
condition peaks during the prime working years (25 to 55 years of age). The
consequent economic burden experienced by employers is substantial. The majority 
of this economic burden is realized by employers in terms of lost productivity, a
combination of costs attributable to absenteeism and to lost productivity while
on the job ("presenteeism"). Although large survey studies have produced
estimates of national prevalence and have suggested substantial national costs,
specific employers are rarely able to apply these projections to their specific
workforce. Using demographic and payroll data available from a large financial
services corporation with over 80,000 employees, this study used established
prevalence data to estimate corporate costs stemming from migraine-related
absenteeism and reduced on-the-job productivity to total at least $21.5 M and
$24.4 M. In addition, a comparison of predicted prevalence and cost impact was
conducted using a simpler and less costly health risk appraisal. This assessment 
proved to be a reliable tool in assessing prevalence of migraineurs in this
corporation's workforce. Its use with a sample of 19,853 employees at this
corporation produced prevalence rates of 7.7% of men and 23.4% of women,
estimates closely comparable to those of national surveys. Suggestions are made
regarding a corporate response to the substantial costs of lost productivity
associated with migraine headache.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 12085478 [PubMed - indexed for MEDLINE]

2927: Expert Opin Pharmacother. 2002 Jul;3(7):993-1005.

Review of zolmitriptan and its clinical applications in migraine.

Dowson AJ, Charlesworth B.

Director, Kings Headache Services, Kings College Hospital, Denmark Hill, London, 
UK. DrAndyDowson@dowsona.fsnet.co.uk

Preclinical studies have shown that zolmitriptan is a selective serotonin
5-HT(1B/1D) receptor agonist (triptan). Randomised, placebo-controlled,
double-blind trials in patients with migraine have shown that zolmitriptan has
good efficacy measured using 2 h response and pain-free rates.
Migraine-associated symptoms, including nausea, photophobia and phonophobia, are 
also improved with zolmitriptan. Oral zolmitriptan (2.5 and 5 mg) has an onset of
action within 45 min and efficacy is sustained in most patients who respond at 2 
h. The orally-disintegrating zolmitriptan tablet has the advantage that it may be
taken immediately, without the need for additional fluids, any time a migraine
headache occurs. Patients may benefit in terms of improved efficacy from the
convenience of the disintegrating tablet, since there is evidence that taking
triptan therapy as early as possible in an attack is advantageous. For similar
reasons, as well as improved efficacy, a nasal spray formulation is in
development. Zolmitriptan is effective in the treatment of migraine associated
with menses and migraine with aura. There is no tachyphylaxis following repeated 
doses for multiple attacks of migraine over a prolonged period of time. Compared 
to placebo, the incidence of persistent migraine headache is reduced by
zolmitriptan and recurrent migraine headache occurs less frequently. Zolmitriptan
has also shown efficacy in the treatment of persistent and/or recurrent migraine 
headache. Comparative clinical studies have shown overall that zolmitriptan has
similar or superior efficacy to sumatriptan in the treatment of migraine.
Specifically, zolmitriptan 2.5 mg was significantly more effective than
sumatriptan 25 or 50 mg according to a number of end points, including headache
response at 2 h. Oral zolmitriptan is also effective in the acute treatment of
cluster headache. Zolmitriptan is generally well tolerated, with most adverse
events being mild-to-moderate, transient and resolving without intervention or
the need for treatment withdrawal. The consistent efficacy in treating all types 
of migraine and the choice of available formulations make zolmitriptan acceptable
to patients and a suitable first-line therapy for the treatment of migraine.

Publication Types: 
    Review

PMID: 12083998 [PubMed - indexed for MEDLINE]

2928: Eur J Neurosci. 2002 Jun;15(11):1803-9.

Effect of systemic nitroglycerin on CGRP and 5-HT afferents to rat caudal spinal 
trigeminal nucleus and its modulation by estrogen.

Pardutz A, Multon S, Malgrange B, Parducz A, Vecsei L, Schoenen J.

Research Center for Cellular & Molecular Neurobiology, Neuroanatomy & Physiology 
Laboratories, University of Liège, 20, rue de Pitteurs, B-4020 Belgium.

Systemic administration of nitroglycerin, a nitric oxide donor, triggers in
migraine patients a delayed attack of unknown mechanism. After puberty migraine
is more prevalent in women. Attacks can be triggered by abrupt falls in plasma
estrogen levels, which accounts in part for sexual dimorphism, but lacks an
established neurobiological explanation. We studied the effect of nitroglycerin
on the innervated area of calcitonin gene-related peptide (CGRP) and
serotonin-immunoreactive afferents to the superficial laminae of the spinal
portion of trigeminal nucleus caudalis, and its modulation by estrogen. In male
rats, nitroglycerin produced after 4 h a significant decrease of the area
innervated by CGRP-immunoreactive afferents and an increase of that covered by
serotonin-immunoreactive fibres. These effects were not observed in the
superficial laminae of thoracic dorsal horns. The effect of nitroglycerin was
similar in ovariectomized females. In estradiol-treated ovariectomized females
the area in the spinal portion of trigeminal nucleus caudalis laminae I-II
covered by CGRP-immunoreactive fibres was lower and that of
serotonin-immunoreactive fibres was higher than in males and for both
transmitters not significantly changed after nitroglycerin. The bouton size of
CGRP profiles was smaller in estradiol-treated ovariectomized females, whereas
after nitroglycerin it decreased significantly but only in males and
ovariectomized females. Nitroglycerin, i.e. nitric oxide, is thus able to
differentially influence afferent fibres in the superficial laminae of rat spinal
trigeminal nucleus caudalis. Estradiol modulates the basal expression of these
transmitters and blocks the nitroglycerin effect. These data may contribute to
understanding the mechanisms by which estrogens influence migraine severity and
the triggering of attacks by nitric oxide.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 12081660 [PubMed - indexed for MEDLINE]

2929: Adv Neurol. 2002;90:25-40.

Migraine and other headache conditions.

Hainline B.

Migraine and other headache conditions are relatively common during pregnancy.
Physicians and other primary health care providers should not assume that because
a patient presents with headache alone, such symptoms can be taken lightly. Most 
patients do not develop new-onset headache during pregnancy, and all patients who
do develop such a condition must be evaluated thoroughly. Similarly, patients who
develop any change in their headache condition must undergo a careful evaluation.
Fig. 3.1 is an algorithm to aid in evaluating pregnant patients with headache.
Postpartum headaches also must be evaluated and treated appropriately. In most
cases of headache during pregnancy and postpartum, the patient is suffering with 
a benign medical condition. Even so, quality of life is an important
consideration in preserving the patient's physical and emotional well-being (102,
103). A stepwise approach to symptomatic treatment should be provided for all
patients. A high index of suspicion for nonbenign causes of headache will assist 
in decreasing morbidity and mortality to the mother and fetus.

Publication Types: 
    Review

PMID: 12068456 [PubMed - indexed for MEDLINE]

2930: Neurology. 2002 Jun 11;58(11):1660-5.

Efficacy of oral ketoprofen in acute migraine: a double-blind randomized clinical
trial.

Dib M, Massiou H, Weber M, Henry P, Garcia-Acosta S, Bousser MG; Bi-Profenid
Migraine Study Group.

Service de Neurologie, Hôpital Lariboisière, 2 rue Ambroise Paré, 75475 Paris
Cedex, France.

BACKGROUND: Certain nonsteroidal anti-inflammatory drugs are effective in the
acute treatment of migraine attacks. The authors report a double-blind,
placebo-controlled, randomized cross-over trial of a dual-release formulation of 
oral ketoprofen in the acute treatment of migraine attacks. METHODS: The authors 
compared the efficacy of two doses of ketoprofen (75 or 150 mg) with that of
placebo (primary analysis) and zolmitriptan 2.5 mg (secondary analysis) on one to
four consecutive attacks in 235 intent-to-treat patients (out of 257 randomized
patients) with migraine with or without aura. The principal efficacy outcome was 
headache relief (reduction in headache severity from severe or moderate to mild
or absent at 2 hours). RESULTS: Results are based on 838 attacks with a severe or
moderate headache that were evaluable at 2 hours. Relief was reported for 62.6%
of headaches treated with ketoprofen 75 mg, 61.6% with ketoprofen 150 mg, and
66.8% with zolmitriptan. The difference between the three active treatments and
placebo (27.8% relief) was highly significant, both tests of ketoprofen vs
placebo being globally controlled at a 5% level for the type I error (primary
analysis). Headaches at 2 hours disappeared more frequently for the active
treatments than for placebo. The authors also demonstrated efficacy on most other
secondary outcomes. The tolerance of ketoprofen was good (similar to that of
placebo). CONCLUSIONS: Oral ketoprofen (75 mg or 150 mg) in a dual-release
formulation is an effective and well-tolerated drug in the acute treatment of
migraine attacks.

Publication Types: 
    Clinical Trial
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 12058095 [PubMed - indexed for MEDLINE]

2931: Neurology. 2002 Jun 11;58(11):1652-9.

A randomized trial of divalproex sodium extended-release tablets in migraine
prophylaxis.

Freitag FG, Collins SD, Carlson HA, Goldstein J, Saper J, Silberstein S, Mathew
N, Winner PK, Deaton R, Sommerville K; Depakote ER Migraine Study Group.

Diamond Headache Clinic, 467 W. Deming Place, Chicago, IL 60614, USA.

OBJECTIVE: To evaluate the efficacy and safety of extended-release divalproex
sodium compared with placebo in prophylactic monotherapy treatment of migraine
headache. METHODS: This was a double-blind, randomized, placebo-controlled,
parallel-group study. Subjects with more than two migraine headache attacks
during a 4-week baseline were randomly assigned in a 1:1 ratio at each center to 
receive either extended-release divalproex sodium or matching placebo once daily 
for 12 weeks. Subjects initiated treatment on 500 mg once daily for 1 week, and
the dose was then increased to 1,000 mg once daily with an option, if intolerance
occurred, to permanently decrease the dose to 500 mg during the second week.
Reduction from baseline in 4-week migraine headache rate was the primary efficacy
variable. Migraine headaches separated by a < 24-hour headache-free interval were
counted as single migraines in calculating migraine headache rates. Tolerance and
safety were also evaluated. RESULTS: The mean reductions in 4-week migraine
headache rate were 1.2 (from a baseline mean of 4.4) in the extended-release
divalproex sodium group and 0.6 (from a baseline mean of 4.2) in the placebo
group (p = 0.006); reductions with extended-release divalproex sodium were
significantly greater than with placebo in all three 4-week segments of the
treatment period. No significant differences were detected between treatment
groups in either the overall incidence or in the incidence of any specific
treatment-emergent adverse event; 8% of subjects treated with extended-release
divalproex sodium and 9% of those treated with placebo discontinued for adverse
events. CONCLUSION: Extended-release divalproex sodium is an efficacious,
well-tolerated, safe, and easy-to-use once-a-day prophylactic antimigraine
medication.

Publication Types: 
    Clinical Trial
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 12058094 [PubMed - indexed for MEDLINE]

2932: Pediatr Neurol. 2002 May;26(5):365-8.

Comment in:
    Pediatr Neurol. 2002 Nov;27(5):410; author reply 410-1.

Pediatric migraine equivalents: occurrence and clinical features in practice.

Al-Twaijri WA, Shevell MI.

Department of Neurology/Neurosurgery, McGill University, Division of Pediatric
Neurology, Montreal Children's Hospital, Quebec, Canada.

Migraine equivalents of infancy, childhood, and adolescence are recognized
periodic, paroxysmal syndromes without associated headache that are thought to be
migrainous in etiology. Five such equivalents are presently recognized. Their
clinical features and relative frequency in ambulatory pediatric neurology
practice have not been well documented. Utilizing a comprehensive, standardized
computer database, the occurrence of these migraine equivalents in a single
pediatric neurology practice together with their observed clinical features were 
documented over an 8-year period. Of a total of 5,848 patients in the database,
of whom 1,106 were migraineurs, 108 patients (1.8% of total, 9.8% of migraineurs)
were identified to have migraine equivalents. The following distribution among
migraine equivalents was observed: benign paroxysmal torticollis 11 (10.2% of
patients with migraine equivalents), benign paroxysmal vertigo 41 (38%),
abdominal migraine/cyclical vomiting 20 (18.5%), acephalgic migraine 31 (28.7%), 
and acute confusional migraine 5 (4.6%). In each type, with the exception of
benign paroxysmal torticollis and acute confusional migraine, females clearly
predominated, and in all types a strong positive family history of migraine was
elicited (68%-100%). There was variation in the age of onset of a particular
equivalent with considerable overlap observed. Coexisting more typical migraines 
were observed in from 10% (benign paroxysmal torticollis) to 70% (abdominal
migraines/cyclical vomiting) of the cases. In conclusion, pediatric migraine
equivalents occur with relative frequency in ambulatory practice, possessing
discrete clinical features that have a clear relationship to more typical
migrainous phenomena.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 12057796 [PubMed - indexed for MEDLINE]

2933: Arch Neurol. 2002 Jun;59(6):1016-8.

Mutation analysis of the CACNA1A calcium channel subunit gene in 27 patients with
sporadic hemiplegic migraine.

Terwindt G, Kors E, Haan J, Vermeulen F, Van den Maagdenberg A, Frants R, Ferrari
M.

Department of Neurology, Leiden University Medical Centre, PO Box 9600, 2300 RC
Leiden, the Netherlands.

BACKGROUND: Familial hemiplegic migraine is a rare autosomal dominant subtype of 
migraine with aura that in half of the families is caused by mutations in the
CACNA1A gene on chromosome 19p13. In sporadic hemiplegic migraine (SHM), that is,
hemiplegic migraine without affected family members, the contribution of the
CACNA1A gene is unknown. OBJECTIVE: To investigate the involvement of the CACNA1A
calcium channel subunit gene in SHM. METHODS: We screened 27 patients with SHM
for mutations in the CACNA1A gene by a combination of single-strand
conformational polymorphism analysis and sequence analysis. RESULTS: One patient 
with SHM also had ataxia, nystagmus, and cerebellar atrophy on computed
tomography and carried a T666M mutation. Another patient with SHM who had no
cerebellar signs carried an R583Q mutation. No mutations or interictal
neurological abnormalities were found in the remaining 25 patients with SHM.
CONCLUSIONS: Most patients with SHM do not have a CACNA1A mutation. The results
of this study, combined with the findings reported in the literature, show that
the presence of cerebellar symptoms in addition to the hemiplegic attacks
increases the chance of finding a CACNA1A mutation. In addition, to our
knowledge, we have found a first patient with SHM without cerebellar signs with a
mutation.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 12056940 [PubMed - indexed for MEDLINE]

2934: CNS Drugs. 2002;16(7):501-7.

Spotlight on almotriptan in migraine.

Keam SJ, Goa KL, Figgitt DP.

Adis International Limited, Mairangi Bay, Auckland, New Zealand.
demail@adis.co.nz

Almotriptan is a selective serotonin 5-HT(1B/1D) receptor agonist ('triptan').
Its efficacy and tolerability have been assessed in a number of randomised,
controlled trials in over 4800 adults with moderate or severe attacks of
migraine. Oral almotriptan has a rapid onset of action (significant headache
relief is observed 0.5 hours after administration of a 12.5mg dose) and efficacy 
is sustained in most patients who respond by 2 hours. The drug is significantly
more effective than placebo as measured by a number of parameters including
2-hour headache response and pain-free response rates. Other symptoms of
migraine, including nausea, photophobia and phonophobia, are also alleviated by
almotriptan. The efficacy of oral almotriptan appears to be maintained over
repeated doses for multiple attacks of migraine treated over a long period (up to
1 year). High headache response rates were reported over all attacks without
tachyphylaxis. For the relief of single attacks of migraine, oral almotriptan
12.5mg had similar efficacy to oral sumatriptan 50mg. Patients given almotriptan 
report less concern with adverse effects than patients given sumatriptan. The
lower incidence of chest pain following treatment with almotriptan than with
sumatriptan may lead to a reduction in direct costs, with fewer patients
requiring management of chest pain. Almotriptan is well tolerated. Most adverse
events were of mild or moderate intensity, transient and generally resolved
without intervention or the need for treatment withdrawal. The most common
adverse events associated with oral almotriptan 12.5mg treatment were dizziness, 
paraesthesia, nausea, fatigue, headache, somnolence, skeletal pain, vomiting and 
chest symptoms. The incidence of adverse events did not differ from placebo and
decreased in the longer term. Almotriptan can be coadministered with drugs that
share a common hepatic metabolic path; in addition, dosage reduction is required 
only in the presence of severe renal or hepatic impairment. CONCLUSIONS:
Almotriptan is an effective drug for the acute treatment of moderate or severe
attacks of migraine in adults. An oral dose of almotriptan 12.5mg has shown
greater efficacy than placebo; current data indicate that efficacy is similar to 
that of oral sumatriptan 50mg, and is maintained in the long term (< or = 1
year). Almotriptan has a good adverse event profile and a generally similar
overall tolerability profile to sumatriptan; of note, almotriptan is associated
with a significantly lower incidence of chest pain than sumatriptan. However,
further clinical experience is required to clearly define the place of
almotriptan among the other currently available triptans. Nevertheless, because
triptans have an important place in various management regimens, and because the 
nature of individual patient response to triptans is idiosyncratic, almotriptan
is likely to become a useful treatment option in the management of adults with
moderate or severe migraine headaches.

Publication Types: 
    Review

PMID: 12056924 [PubMed - indexed for MEDLINE]

2935: Cephalalgia. 2002 Apr;22(3):246-8.

Hemicrania continua with aura.

Peres MF, Siow HC, Rozen TD.

Department of Neurology, Jefferson Headache Center, Thomas Jefferson University
Hospital, Philadelphia, Pennsylvania, USA. marioperes@yahoo.com

Hemicrania continua is a primary headache disorder that is characterized by a
continuous unilateral headache of moderate severity, exacerbations of severe pain
and complete responsiveness to indomethacin. We report four patients with a
unique variant of hemicrania continua: visual auras that precede or accompany the
pain exacerbations.

Publication Types: 
    Case Reports

PMID: 12047466 [PubMed - indexed for MEDLINE]

2936: Cephalalgia. 2002 Apr;22(3):242-5.

Hemicrania continua: comparison between two different classification systems.

Bigal ME, Tepper SJ, Rapoport AM, Sheftell FD.

The New England Center for Headache, Stamford, Connecticut, USA.

Hemicrania continua is an uncommon primary headache disorder. This study of nine 
patients compares two different classification systems, proposed by Pareja et al.
and Goadsby and Lipton. Although it seems logical to position the nosologic
status of hemicrania continua under group 3 of the International Headache Society
Classification, as proposed by Pareja et al., the Goadsby and Lipton
classification is more clinically useful and should be included in future
International Headache Society reclassification.

Publication Types: 
    Comparative Study

PMID: 12047465 [PubMed - indexed for MEDLINE]

2937: Cephalalgia. 2002 Apr;22(3):222-5.

Comment in:
    Cephalalgia. 2003 Apr;23(3):240; author reply 240-1.

Helicobacter pylori infection and migraine.

Ciancarelli I, Di Massimo C, Tozzi-Ciancarelli MG, De Matteis G, Marini C,
Carolei A.

Department of Neurology, University of L'Aquila, 67100 L'Aquila-Coppito, Italy.

The study is aimed to ascertain whether the Helicobacter pylori (Hp) infection is
responsible for the vulnerability to oxidative stress observed in migraineurs. Hp
serological positivity was assessed by ELISA evaluation of specific IgA and IgG
antibodies in 30 subjects (11 males and 19 females) suffering from migraine
without aura during the headache-free period. The Hp infection was detected in
16.7% of migraineurs. Plasma accumulation of peroxidative substances (TBA-RS), an
index of systemic oxidative status, was increased in migraineurs without Hp
infection with respect to controls (P< 0.001), while no significant differences
of TBA-RS were found in migraineurs with or without Hp infection. Unmodified
values of plasma nitrite/nitrate concentrations, expression of systemic nitric
oxide (NO), were obtained in migraineurs in comparison to controls indicating
that Hp infection does not modify the plasma oxidative status and the systemic NO
bioavailability of migraineurs. In conclusion, our results do not support any
specific correlation between Hp infection and migraine.

Publication Types: 
    Comparative Study

PMID: 12047462 [PubMed - indexed for MEDLINE]

2938: Cephalalgia. 2002 Apr;22(3):209-21.

Erratum in:
    Cephalalgia. 2002 Jul;22(6):488.

Efficacy and tolerability in migraine prophylaxis of flunarizine in reduced
doses: a comparison with propranolol 160 mg daily.

Diener HC, Matias-Guiu J, Hartung E, Pfaffenrath V, Ludin HP, Nappi G, De
Beukelaar F.

Department of Neurology, University Essen, Germany. h.diener@uni-essen.de

This was a phase-IV double-blind equivalence trial designed to assess the
efficacy and tolerability of two doses of flunarizine (10 mg o.d.=FLU 10 mg and 5
mg o.d.=FLU 5 mg) in the prophylaxis of migraine, in comparison with slow-release
propranolol (160 mg o.d.). A total of 808 subjects were treated in a treatment
period of 16 weeks. 142 subjects discontinued the trial prematurely, mainly
because of adverse events (n=58). The mean attack frequency in the double-blind
period was 2.0 for the FLU 5 mg group, 1.9 for the FLU 10 mg group, and 1.9 for
the propranolol group. The mean attack frequency in the last 28 days of the
double-blind period was 1.8 for FLU 5 mg, 1.6 for FLU 10 mg, and 1.7 for
propranolol. Both flunarizine groups were at least as effective as propranolol
(P<0.001 in one-sided test). The percentage of responders (defined as subjects
for whom attack frequency decreased by at least 50% compared to run-in) in the
last 28 days of the double-blind period was 46% (118/259) for FLU 5 mg, 53%
(141/264) for FLU 10 mg, and 48% (125/258) for propranolol. Statistical analysis 
showed that FLU 10 mg is at least as effective as propranolol (P<0.001) and
showed a trend for noninferiority of FLU5 and propranolol (P=0.053). No
statistically significant differences between the treatment groups were found for
any of the secondary parameters. Overall, 190 subjects reported one or more
adverse events during the run-in phase: 54 (20.5%) in the FLU 5 mg group, 76
(27.7%) in the FLU 10 mg group and 60 (22.3%) in the propranolol group. The
results of this equivalence trial show that 10 mg flunarizine daily with a
drug-free weekend is at least as effective as 160 mg propranolol in the
prophylaxis of migraine for all evaluated parameters (one-sided equivalence
tests) after 16 weeks of treatment. In addition, 5 mg flunarizine proves to be at
least as effective as 160 mg propranolol when looking at the mean attack
frequency for both the whole double-blind period and the last 28 days of
treatment. However, in the analysis of responders, 160 mg propranolol seems to be
slightly better than 5 mg flunarizine. In addition, no significant differences
between the three treatments were found with regard to safety: all three
treatments were generally well-tolerated and safe.

Publication Types: 
    Clinical Trial
    Clinical Trial, Phase IV
    Comparative Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 12047461 [PubMed - indexed for MEDLINE]

2939: Cephalalgia. 2002 Apr;22(3):172-8.

A comparison of disability and psychological factors in migraine and transformed 
migraine.

Magnusson JE, Becker WJ.

Department of Clinical Neurosciences, University of Calgary and the Calgary
Regional Health Authority, Calgary, Alberta, Canada.
jane.magnusson@calgaryhealthregion.ca

The classification of patients with migraine who develop chronic daily headache
is controversial, with some classifying such patients as 'transformed migraine'. 
We compared patients with intermittent migraine attacks and patients with
transformed migraine in terms of mean headache intensity on days with headache,
depression, pain-related anxiety and headache-related disability. Patients
classified clinically as also having tension-type headache were excluded. Aside
from the number of days with headache per month, patients with intermittent
migraine attacks and patients with transformed migraine were very similar in
terms of all parameters studied. Our results support the concept that these two
headache groups are closely related.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 12047453 [PubMed - indexed for MEDLINE]

2940: Headache. 2002 May;42(5):356-8.

Disappearance of migraine attacks during long-lasting postdural puncture
headache: a case report.

Oomura M, Yamawaki T, Miyashita K, Yamagami H, Naritomi H.

Department of Cerebrovascular Medicine, National Cardiovascular Center, Osaka,
Japan.

We report a patient with a history of frequent migraine attacks who developed
postdural puncture headache that persisted for 3 months. His migraine attacks
ceased during the period of his postdural puncture headache, but resumed 3 days
after disappearance of that headache. This case suggests an interrelationship
between the mechanisms of postdural puncture headache and migraine.

Publication Types: 
    Case Reports

PMID: 12047336 [PubMed - indexed for MEDLINE]

2941: Headache. 2002 May;42(5):352-5.

Livedo reticularis and migraine: a marker for stroke risk?

Tietjen GE, Al-Qasmi MM, Shukairy MS.

Department of Neurology, Medical College of Ohio, Toledo, USA.

BACKGROUND AND PURPOSE: Livedo reticularis is a dermatopathy characterized by an 
irregular, violaceous, netlike pattern which spares the face. Associated with a
variety of conditions, it occurs consequent to pathological or physiological
narrowing of small and medium arteries at the dermis-subcutis border. Sneddon
syndrome refers to the idiopathic coupling of livedo reticularis and stroke in
the absence of traditional vascular risk factors. Over 50% of persons with
Sneddon syndrome describe a history of headache. We undertook this study to
determine the frequency of livedo reticularis in our headache clinic. METHODS: We
performed a retrospective chart review of consecutive patients attending a
headache clinic over a period of 6 months. The patients had all been seen by one 
physician (G.E.T.) who noted the presence or absence of livedo reticularis. The
charts were reviewed for age, sex, and vascular risk factors, including current
use of oral contraceptives, and history of smoking, coronary artery disease,
hypertension, diabetes mellitus, stroke, or arthritis. RESULTS: Charts from 133
patients with headache were reviewed (24 men [18%], 109 women [82%]; mean age, 42
+/- 13 years). Livedo reticularis was observed in 29 patients (22%) and in a
similar proportion in men (25%) and women (21%). When we stratified the migraine 
population by presence or absence of livedo, we found no significant difference
in age (44.5 versus 41.7 years, P =.16). There was a higher frequency of stroke
diagnosis in the cohort with livedo reticularis (28%[8 of 29] versus 7%[7 of
104], P =.005), but we found no significant differences in frequency of
hypertension, oral contraceptive use, diabetes mellitus, coronary artery disease,
arthritis, or cigarette smoking. CONCLUSIONS: In our headache clinic, livedo
reticularis is present in more than one fifth of patients. A history of stroke is
more frequent in this subset of migraineurs, raising the possibility that livedo 
reticularis can be used as a clinical marker to identify those migraineurs with
an increased risk of stroke.

PMID: 12047335 [PubMed - indexed for MEDLINE]

2942: Headache. 2002 May;42(5):346-51.

Dopamine receptor genes and migraine with and without aura: an association study.

Shepherd AG, Lea RA, Hutchins C, Jordan KL, Brimage PJ, Griffiths LR.

Genomics Research Centre, School of Health Science, Griffith University, Gold
Coast, Queensland, Australia.

OBJECTIVE: To investigate the role of the dopamine receptor genes, DRD1, DRD3,
and DRD5 in the pathogenesis of migraine. BACKGROUND: Migraine is a chronic
debilitating disorder affecting approximately 12% of the white population. The
disease shows strong familial aggregation and presumably has a genetic basis, but
at present, the type and number of genes involved is unclear. The study of
candidate genes can prove useful in the identification of genes involved in
complex diseases such as migraine, especially if the contribution of the gene to 
phenotypic expression is minor. Genes coding for proteins involved in dopamine
metabolism have been implicated in a number of neurologic conditions and may play
a contributory role in migraine. Hence, genes that code for enzymes and receptors
modulating dopaminergic activity are good candidates for investigation of the
molecular genetic basis of migraine. METHODS: We tested 275 migraineurs and 275
age- and sex-matched individuals free of migraine. Genotypic results were
determined by restriction endonuclease digestion of polymerase chain reaction
products to detect DRD1 and DRD3 alleles and by Genescan analysis after
polymerase chain reaction using fluorescently labelled oligonucleotide primers
for the DRD5 marker. RESULTS: Results of chi-square statistical analyses
indicated that the allele distribution for migraine cases compared to controls
was not significantly different for any of the three tested gene markers (chi2 = 
0.1, P =.74 for DRD1; chi2 = 1.8, P =.18 for DRD3; and chi2 = 20.3, P =.08 for
DRD5). CONCLUSIONS: These findings offer no evidence for allelic association
between the tested dopamine receptor gene polymorphisms and the more prevalent
forms of migraine and, therefore, do not support a role for these genes in the
pathogenesis of the disorder.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 12047334 [PubMed - indexed for MEDLINE]

2943: Headache. 2002 May;42(5):341-5.

Tumor necrosis factor gene polymorphism in migraine.

Trabace S, Brioli G, Lulli P, Morellini M, Giacovazzo M, Cicciarelli G,
Martelletti P.

Section of Medical Genetics, Department of Experimental Medicine and Pathology,
University La Sapienza, Rome, Italy.

OBJECTIVE: To better define the involvement of human leukocyte antigen region
(HLA) genes in migraine via an association study of the tumor necrosis factor
(TNF) genes, located in the HLA class III region, with migraine with and without 
aura. BACKGROUND: Migraine without aura and migraine with aura are disorders
involving multiple factors-environmental and genetic. In a previous study, we
hypothesized a protective role for the HLA-DR2 antigen, providing additional
basis for the proposed genetic heterogeneity between migraine without aura and
migraine with aura. The cytokines produced by TNF genes are polypeptide effectors
of inflammatory reaction and endothelial function.METHODS: Tumor necrosis factor 
(TNF)-308 (TNF-308A and TNF-308G alleles) and lymphotoxin alpha (TNFB*1 and
TNFB*2 alleles) polymorphisms were analyzed by the NcoI-cleaved polymerase chain 
reaction-amplified fragments in 47 patients with migraine without aura, 32
patients with migraine with aura, and 101 migraine-free controls.RESULTS: The
frequency of TNFB*2 allele was significantly increased in our patients with
migraine without aura as compared with the control group (78.72% versus 61.4%, Pc
=.004), but no significant differences were found between patients with migraine 
with aura and controls. Additionally, there was a significant decrease of TNFB*1 
homozygotes in patients with migraine without aura compared with the control
group (2.13% versus 16.8%, Pc =.0201). Carriage of the TNFB*2 allele confers a
high risk for the development of migraine without aura. No significant
association was found at TNF-308 polymorphism. CONCLUSION: These data support the
hypothesis that lymphotoxin alpha could be a susceptibility gene in migraine
without aura and confirm previous data indicating that migraine with and without 
aura are distinct entities with different genetic backgrounds.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 12047333 [PubMed - indexed for MEDLINE]

2944: Headache. 2002 May;42(5):337-40.

A polymorphism in the interleukin-1alpha gene influences the clinical features of
migraine.

Rainero I, Pinessi L, Salani G, Valfrè W, Rivoiro C, Savi L, Gentile S, Giudice
RL, Grimaldi LM.

Neurology III, Headache Center, Department of Neuroscience, University of Torino,
Italy.

OBJECTIVE: To evaluate whether a particular genotype of the interleukin-1alpha
(IL1A) gene affects the clinical features of migraine.BACKGROUND: Proinflammatory
mediators have been reported to play a role in the pathophysiology of migraine.
Recent studies suggest that polymorphisms in the interleukin-1 genes influence
the age at onset and subsequent course of several chronic inflammatory
diseases.METHODS: In a group of 269 patients with migraine, we tested the
association of the -889 C/T biallelic polymorphism of the IL1A gene with several 
clinical features of the disease. RESULTS:Patients with migraine carrying the T/T
genotype show an age at onset of the disease that is significantly (P <.01) lower
than IL1A C/C or C/T carriers. In addition, the same genotype was significantly
(P <.05) more frequent in patients with migraine with aura than in patients with 
migraine without aura.CONCLUSIONS: The results of our study suggest a role for
the IL1A gene in modifying the clinical features of migraine.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 12047332 [PubMed - indexed for MEDLINE]

2945: Headache. 2002 May;42(5):332-6.

Migraine without aura and migraine with aura are distinct disorders. A
population-based twin survey.

Russell MB, Ulrich V, Gervil M, Olesen J.

Department of Neurology, University of Copenhagen, Gentofte Hospital, Denmark.

OBJECTIVE: To investigate the co-occurrence of migraine without aura (MWOA) and
migraine with aura (MWA) in a population-based twin survey. BACKGROUND: Migraine 
without aura and MWA are multifactorial disorders. If MWOA and MWA share common
genes, co-occurrence should be observed more frequently than expected, ie, the
product of the prevalence in the general population. MATERIAL AND METHODS: The
study population included all living Danish monozygotic (MZ) and same-gender
dizygotic (DZ) twin pairs born between 1953 and 1960: 5360 twins (2026 MZ, 3334
DZ). The sample included 2840 men and 2520 women. All received a posted
questionnaire, and those with possible migraine were interviewed via telephone by
trained physicians (V.U. or M.G.). Twins who did not respond to the questionnaire
and who had a co-twin with possible migraine were contacted by telephone. The
questionnaire response rate was 87% (4660 of 5360), and the telephone interview
was participated in by 90% (2035 of 2272). The physician interviewers were
unaware of questionnaire answers, zygosity, and the clinical diagnosis of the
co-twin. The criteria of the International Headache Society were used to
establish a diagnosis of migraine. RESULTS: Lifetime prevalence in the twin
sample: 7% of men and 19% of women had MWOA, while 7% of men and 8% of women had 
MWA. Lifetime prevalence of MWA in twin pairs with MWOA: MZ men, 2% (1 of 47); MZ
women, 6% (5 of 90); DZ men, 9% (7 of 75); and DZ women, 10% (19 of 182).
Lifetime prevalence of MWOA in twin pairs with MWA: MZ men, 3% (1 of 33); MZ
women, 5% (3 of 58); DZ men, 9% (4 of 44); and DZ women, 13% (10 of 76). The
observed and the expected numbers of twins with co-occurrence of MWOA and MWA
based on the prevalence in the general population were not significantly
different in either men or women (men, P=.1 and women, P=.5). CONCLUSION: The
results strongly suggest that MWOA and MWA are distinct disorders, and
identification of common genes for MWOA and MWA, thus, should not be expected to 
result from future genetic research.

Publication Types: 
    Comparative Study
    Twin Study

PMID: 12047331 [PubMed - indexed for MEDLINE]

2946: Curr Opin Neurol. 2002 Jun;15(3):317-22.

Integrating the triptans into clinical practice.

Dahlöf C.

Institute of Clinical Neuroscience, Gothenburg Migraine Clinic, Sociala Huset,
Uppgang D, S-41117 Gothenburg, Sweden. carl.dahlof@migraineclinic.se

The triptans (selective serotonin agonists) are becoming the first-line
alternatives in the acute pharmacological treatment of migraine, at least for
attacks of moderate-to-severe intensity. Although clinical trials demonstrate
significant differences in efficacy between triptan tablets, they often appear
similar in efficacy when used in clinical practice, particularly after dose
adjustments. Most patients with migraine consider drugs that can be administered 
orally to be the most user-friendly. However, gastrointestinal absorption may be 
impaired during migraine attacks because gastric motility is inhibited, and there
is a risk that nausea during the attack will culminate in vomiting. Furthermore, 
in addition to their antimigraine properties, triptans may prolong the gastric
emptying time. For this reason the absorption of any triptan taken orally during 
the migraine attack will be erratic and treatment effects inconsistent. Despite
these barriers to good efficacy and high reliability, the tablet is the most
commonly used triptan formulation.

Publication Types: 
    Review

PMID: 12045731 [PubMed - indexed for MEDLINE]

2947: Curr Opin Neurol. 2002 Jun;15(3):311-6.

Calcium channel mutations and migraine.

Kors EE, van den Maagdenberg AM, Plomp JJ, Frants RR, Ferrari MD.

Department of Neurology, Leiden University Medical Centre, 2300 RC Leiden, The
Netherlands.

An increasing number of mutations in the CACNA1A gene have been identified, which
are associated with a broad clinical spectrum, including familial hemiplegic
migraine. Transfection studies and mouse model analyses are currently being
undertaken to study the correlation between CACNA1A mutations and disease.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 12045730 [PubMed - indexed for MEDLINE]

2948: Curr Opin Neurol. 2002 Jun;15(3):303-9.

The electrophysiology of migraine.

Giffin NJ, Kaube H.

Headache Group, Institute of Neurology, Queen Square, London WC1N 3BG, UK.

Migraine is currently regarded as a neurovascular disorder of trigeminal sensory 
processing, generated centrally, probably at the level of the brainstem. In the
past, electrophysiological techniques have drawn no definite conclusions on
either interictal or ictal changes in migraineurs compared with controls, largely
because of methodological differences. Recently, two findings have been shown
consistently: an interictal increasing lack of habituation of evoked potentials
with a normalization at the start of the attack and strong intensity dependence
of auditory evoked potentials. These findings substantiate migraine sufferers as 
having an abnormal trait interictally, with the attack characterized by a change 
in the state of central processing. Exploitation of these differences may be a
useful tool to study the mechanism of action of drugs used for the treatment of
migraine.

Publication Types: 
    Review

PMID: 12045729 [PubMed - indexed for MEDLINE]

2949: Plast Reconstr Surg. 2002 Jun;109(7):2183-9.

Comment in:
    Plast Reconstr Surg. 2003 Feb;111(2):967-8; author reply 969.    Plast Reconstr Surg. 2003 May;111(6):2103-4.

Surgical treatment of migraine headaches.

Guyuron B, Tucker T, Davis J.

Department of Plastic Surgery, Case Western Reserve University, Cleveland, OH
44124, USA. bguyuron@aol.com

This prospective study was conducted to investigate the role of removal of
corrugator supercilii muscles, transection of the zygomaticotemporal branch of
the trigeminal nerve, and temple soft-tissue repositioning in the treatment of
migraine headaches. Using the criteria set forth by the International Headache
Society, the research team's neurologist evaluated patients with moderate to
severe migraine headaches, to confirm the diagnosis. Subsequently, the patients
completed a comprehensive migraine headaches questionnaire and the team's plastic
surgeon injected 25 units of botulinum toxin type A (Botox) into each corrugator 
supercilii muscle. The patients were asked to maintain an accurate diary of their
migraine headaches and to complete a monthly questionnaire documenting pertinent 
information related to their headaches. Patients in whom the injection of Botox
resulted in complete elimination of the migraine headaches then underwent
resection of the corrugator supercilii muscles. Those who experienced only
significant improvement underwent transection of the zygomaticotemporal branch of
the trigeminal nerve with repositioning of the temple soft tissues, in addition
to removal of the corrugator supercilii muscles. Once again, patients kept a
detailed postoperative record of their headaches. Of the 29 patients included in 
the study, 24 were women and five were men, with an average age of 44.9 years
(range, 24 to 63 years). Twenty-four of 29 patients (82.8 percent, p < 0.001)
reported a positive response to the injection of Botox, 16 (55.2 percent, p <
0.001) observed complete elimination, eight (27.6 percent, p < 0.04) experienced 
significant improvement (at least 50 percent reduction in intensity or severity),
and five (17.2 percent, not significant) did not notice a change in their
migraine headaches. Twenty-two of the 24 patients who had a favorable response to
the injection of Botox underwent surgery, and 21 (95.5 percent, p < 0.001)
observed a postoperative improvement. Ten patients (45.5 percent, p < 0.01)
reported elimination of migraine headaches and 11 patients (50.0 percent, p <
0.004) noted a considerable improvement. For the entire surgical group, the
average intensity of the migraine headaches reduced from 8.9 to 4.1 on an
analogue scale of 1 to 10, and the frequency of migraine headaches changed from
an average of 5.2 per month to an average of 0.8 per month. For the group who
only experienced an improvement, the intensity fell from 9.0 to 7.5 and the
frequency was reduced from 5.6 to 1.0 per month. Only one patient (4.5 percent,
not significant) did not notice any change. The follow-up ranged from 222 to 494 
days, the average being 347 days. In conclusion, this study confirms the value of
surgical treatment of migraine headaches, inasmuch as 21 of 22 patients benefited
significantly from the surgery. It is also evident that injection of Botox is an 
extremely reliable predictor of surgical outcome.

PMID: 12045534 [PubMed - indexed for MEDLINE]

2950: Pain. 2002 Jun;97(3):259-65.

ATP can enhance the proton-induced CGRP release through P2Y receptors and
secondary PGE(2) release in isolated rat dura mater.

Zimmermann K, Reeh PW, Averbeck B.

Institute of Physiology and Experimental Pathophysiology, University of
Erlangen-Nürnberg, Universitätsstrasse 17, Germany.
zimmermann@physiologie1.uni-erlangen.de

Trigeminal afferent neurons express ionotropic P2X receptors for extracellular
ATP which are known to be sensitive to low interstitial pH. Both conditions - ATP
release and tissue acidosis - may occur in the dura following the ischemia phase 
of migraine attacks. Aim of this study was to investigate whether and how ATP and
protons may cooperate in exciting meningeal afferents. After removal of the
cerebral hemispheres hemisected scull cavities of adult Wistar rats were used as 
organ bath of their own lining, the dura mater. The dura was chemically
stimulated and the amounts of immunoreactive calcitonin gene-related peptide
(iCGRP) and prostaglandin E(2) (PGE(2)) released into incubation fluid were
measured using enzyme immunoassays. Stimulation with ATP (10(-4) and 10(-3)M)
augmented iPGE(2) release dose-dependently whereas iCGRP secretion was minimally 
enhanced only if the dura had previously been depleted of extracellular ATP using
hexokinase. Acid buffer solutions (pH 5.9 and 5.4) resulted in pH-dependent
increase of iCGRP release but reduced iPGE(2) release. Purines (ATP 10(-3)>UTP
10(-4)M>ATP 10(-4)M) and PGE(2) (10(-5)M) were found to facilitate the
proton-induced increase in iCGRP release. The proton-reduction of PGE(2) release 
was overcome by adding ATP (10(-3)M). S(+)-flurbiprofen (10(-6)M) suppressed both
the basal and stimulated iPGE(2) release and prevented the ATP(10(-4)M)-induced
facilitation of the proton response. The facilitating effect of ATP was also
blocked under suramin, a non-selective P2 antagonist, and under reactive blue, an
non-selective P2Y-antagonist, but not under
pyridoxalphosphate-6-azophenyl-2',4'-disulphonic acid, a P2X-antagonist. The
present results provide evidence that ATP has poor, if at all, direct excitatory 
effects on CGRP-containing trigeminal nerve endings in the isolated dura and its 
facilitatory action seems to depend on G-protein coupled P2Y receptors and
secondary PGE(2) release. The UTP effect and the antagonist profile is indicative
for the P2Y(2) receptor subtype.

Publication Types: 
    In Vitro
    Research Support, Non-U.S. Gov't

PMID: 12044622 [PubMed - indexed for MEDLINE]

2951: Pain. 2002 Jun;97(3):247-57.

Comment in:
    ACP J Club. 2002 Nov-Dec;137(3):103.

Pharmacological treatments for acute migraine: quantitative systematic review.

Oldman AD, Smith LA, McQuay HJ, Moore RA.

Pain Research, Nuffield Department of Anaesthetics, Oxford Radcliffe Hospital,
University of Oxford, The Churchill, Headington, UK.

We wanted to compare the analgesic efficacy and adverse effects of
pharmacological treatments for acute migraine through a systematic review of
randomised controlled trials in patients with acute migraine pain of moderate to 
severe intensity. Trials were identified from systematic searching of
bibliographic databases. For eletriptan information from all trials was supplied 
by Pfizer Inc. Outcomes sought were headache relief at 1 and 2h, patients pain
free at 2h and sustained relief over 24h for treatments compared with placebo.
Numbers-needed-to-treat (NNTs) were calculated, together with relative benefit.
Information on adverse effects was also collected. Comparisons of relative
efficacy used the same definition of headache, the same degree of pain at the
start of treatment and the same definitions of outcomes, and always compared with
placebo. Forty-eight publications reporting on 54 trials were included in the
meta-analyses, with 79 placebo comparisons for the primary outcome of headache
relief at 2h. Information on any outcome was available for nine oral medications,
two intranasal medications and subcutaneous sumatriptan in 21,022 patients. For
headache relief at 2h NNTs ranged from 2.0 for subcutaneous sumatriptan 6mg to
5.4 for naratriptan 2.5mg. For patients pain free at 2h NNTs ranged from 2.1 for 
subcutaneous sumatriptan 6mg to 8.6 for aspirin 900mg plus metoclopramide 10mg.
For sustained relief over 24h NNTs ranged from 2.8 for eletriptan 80mg to 8.3 for
rizatriptan 5mg. It was not possible to systematically review adverse effects
data. Most interventions are effective. There is considerable information on
relative efficacy for a number of outcomes.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 12044621 [PubMed - indexed for MEDLINE]

2952: Int J Psychophysiol. 2002 Jun;44(3):239-49.

Modulation of trigeminal reflex excitability in migraine: effects of attention
and habituation on the blink reflex.

de Tommaso M, Murasecco D, Libro G, Guido M, Sciruicchio V, Specchio LM, Gallai
V, Puca F.

Clinical Neurologica I Policlinico, Piazza G. Cesare II, 70124, Bari, Italy.
m.detommaso@neurol.uniba.it

The modulation of trigeminal reflex excitability in migraine patients was
evaluated during the asymptomatic phase by studying the effects of attention,
habituation and preconditioning stimulus on the R2 and R3 components of the blink
reflex (BR). Fifty patients suffering from migraine without aura, 20 affected by 
migraine with aura and 35 sex- and age-matched controls were selected. In
subgroups of migraine with-aura and without-aura patients, and normal controls,
the blink reflex was elicited during different cognitive situations: (a)
spontaneous mental activity; (b) stimulus anticipation; (c) recognition of target
numbers. In the remaining subjects, R2 and R3 habituation was evaluated by
repetitive stimulation at 1, 5, 10, 15, 20, 25 and 30 s intervals. The R2 and R3 
recovery curves were also computed. A reduced R3 threshold with a normal pain
threshold was found in migraine with-aura and without-aura patients; the R3
component was not significantly correlated with the pain thresholds in patients
and controls. The R2 and R3 components were less influenced by the warning of the
stimulus in migraine without-aura and migraine with-aura patients, in comparison 
with the control group. A slight increase of both R2 and R3 recovery after
preconditioning stimulus was also observed in migraine patients, probably caused 
by a phenomenon of trigeminal hyperexcitability persisting after the last attack.
The abnormal BR modulation by alerting expresses in migraine a dysfunction of
adaptation capacity to environmental conditions, probably predisposing to
migraine.

PMID: 12031298 [PubMed - indexed for MEDLINE]

2953: Neurogenetics. 2002 Mar;4(1):17-22.

A typical migraine susceptibility region localizes to chromosome 1q31.

Lea RA, Shepherd AG, Curtain RP, Nyholt DR, Quinlan S, Brimage PJ, Griffiths LR.

Genomics Research Centre, School of Health Sciences, Griffith University,
Southport, Queensland, Australia.

Migraine (with and without aura) is a prevalent neurovascular disease that shows 
strong familial aggregation, although the number of genes involved and the mode
of inheritance is not clear. Some insight into the disease has been gained from
genetic studies into a rare and very severe migraine subtype known as familial
hemiplegic migraine (FHM). In this study, we took a family-based linkage and
association approach to investigate the FHM susceptibility region on chromosome
1q31 for involvement in typical migraine susceptibility in affected Australian
pedigrees. Initial multipoint ALLEGRO analysis provided strong evidence for
linkage of Chrlq31 markers to typical migraine in a large multigenerational
pedigree. The 1-LOD* unit support interval for suggestive linkage spanned
approximately 18 cM with a maximum allele sharing LOD* score of 3.36 obtained for
marker D1S2782 (P=0.00004). Subsequent analysis of an independent sample of 82
affected pedigrees added support to the initial findings with a maximum LOD* of
1.24 (P=0.008). Utilising the independent sample of 82 pedigrees, we also
performed a family-based association test. Results of this analysis indicated
distortion of allele transmission at marker D1S249 [global chi2 (5) of 15.00,
P=0.010] in these pedigrees. These positive linkage and association results will 
need further confirmation by independent researchers. However, overall they
provide good evidence for the existence of a typical migraine locus near these
markers on Chrlq3l, and reinforce the idea that an FHM gene in this genomic
region may also contribute to susceptibility to the more common forms of
migraine.

PMID: 12030327 [PubMed - indexed for MEDLINE]

2954: Headache. 2002 Apr;42 Suppl 2:S93-9.

Comment in:
    Headache. 2007 Jun;47(6):934; discussion 934.

Tolerability and safety of frovatriptan with short- and long-term use for
treatment of migraine and in comparison with sumatriptan.

Géraud G, Spierings EL, Keywood C.

CHU de Rangueil, Service de Neurologie, Toulouse, France.

OBJECTIVE: To evaluate the tolerability and safety of frovatriptan 2.5 mg in
patients with migraine. BACKGROUND: Frovatriptan is a new, selective serotonin
agonist (triptan) developed for the acute treatment of migraine. Dose
range-finding studies identified 2.5 mg as the dose that conferred the optimal
combination of efficacy and tolerability. METHODS: The tolerability and safety of
frovatriptan 2.5 mg were assessed during controlled, acute migraine treatment
studies, including a study that compared frovatriptan 2.5 mg with sumatriptan 100
mg, as well as a 12-month open-label study during which patients could take up to
three doses of frovatriptan 2.5 mg within a 24-hour period. Safety and
tolerability were assessed through the collection of adverse events, monitoring
of heart rate and blood pressure performance of 12-lead electrocardiogram,
hematology screen, and blood chemistry studies. RESULTS: In the short-term
studies, 1554 patients took frovatriptan 2.5 mg and 838 took placebo. In the
12-month study, 496 patients treated 13 878 migraine attacks. Frovatriptan was
well tolerated in the short- and long-term studies with 1% of patients in the
short-term studies and 5% of patients in the long-term study withdrawing due to
lack of tolerability. The incidence of adverse events was higher in the
frovatriptan-treated patients than in the patients who took placebo (47% versus
34%) and the spectrum of adverse events was similar. When compared to sumatriptan
100 mg, significantly fewer patients taking frovatriptan experienced adverse
events (43% versus 36%; P=.03) and the number of adverse events was lower (0.62
versus 0.91), there were also fewer adverse events suggestive of cardiovascular
symptoms in the frovatriptan group. Analysis of the entire clinical database
(n=2392) demonstrated that frovatriptan was well tolerated by the patients
regardless of their age, gender, race, concomitant medication, or the presence of
cardiovascular risk factors. No effects of frovatriptan on heart rate, blood
pressure, 12-lead electrocardiogram, hematology screen, or blood chemistry were
observed. No patient suffered any treatment-related serious adverse event.
CONCLUSIONS: Short- and long-term use of frovatriptan 2.5 mg was well tolerated
by a wide variety of patients. Frovatriptan treatment produced an adverse events 
profile similar to that of placebo, and in a direct comparison study was better
tolerated than sumatriptan 100 mg.

Publication Types: 
    Clinical Trial
    Comparative Study
    Controlled Clinical Trial

PMID: 12028325 [PubMed - indexed for MEDLINE]

2955: Headache. 2002 Apr;42 Suppl 2:S84-92.

Clinical efficacy of frovatriptan: placebo-controlled studies.

Ryan R, Géraud G, Goldstein J, Cady R, Keywood C.

Ryan Headache Center, St. Louis, MO, USA.

OBJECTIVE: To confirm the clinical efficacy of frovatriptan 2.5 mg. BACKGROUND:
Frovatriptan is a new 5-hydroxytryptamine (5-HT)(1B/1D) receptor agonist being
developed for the acute treatment of migraine with or without aura. Results from 
preclinical and clinical pharmacology studies showed frovatriptan to be a potent 
5-HT(1B) receptor agonist with a long terminal elimination half-life (26 hours)
and a broad therapeutic index. DESIGN: Three randomized, placebo-controlled,
double-blind, parallel-group trials, in a total of 2676 patients, were performed 
to confirm the clinical efficacy of frovatriptan 2.5 mg for the acute treatment
of migraine. RESULTS: In all three studies, headache response 2 hours after
frovatriptan dosing was significantly greater than that seen with placebo (P < or
= .001) with approximately a two-fold measure of effect over placebo for headache
response at 2 and 4 hours postdosing. Time to headache response occurred within
1.5 hours in a substantial proportion of patients. The incidence of 24-hour
headache recurrence with frovatriptan was low (10% to 25%). Frovatriptan therapy 
also was associated with a high degree of patient satisfaction. CONCLUSIONS:
Frovatriptan represents a consistently effective acute treatment for migraine and
accompanying symptoms.

Publication Types: 
    Clinical Trial
    Multicenter Study
    Randomized Controlled Trial

PMID: 12028324 [PubMed - indexed for MEDLINE]

2956: Headache. 2002 Apr;42 Suppl 2:S74-83.

Dose range-finding studies with frovatriptan in the acute treatment of migraine.

Rapoport A, Ryan R, Goldstein J, Keywood C.

The New England Center for Headache, Stamford, Conn 06902-1251, USA.

OBJECTIVE: To determine the optimum dose of frovatriptan for the acute treatment 
of migraine. BACKGROUND: Frovatriptan is a new triptan developed for the acute
treatment of migraine. The dose-response characteristics and safety of
frovatriptan have been investigated across a broad range of doses from 0.5 to 40 
mg. DESIGN: Two randomized, placebo-controlled, double-blind, parallel-group
trials, with a total of 1453 patients, were performed to determine the optimal
dose of the 5-HT(B/1D)agonist, frovatriptan, for the acute treatment of migraine.
The dose ranges studied were 2.5 to 40 mg in the high-dose study and 0.5 to 5 mg 
in the low-dose study. RESULTS: At 2 hours postdosing for initial moderate or
severe headache (International Headache Society grades 2 or 3), there was an
approximate two-fold difference in the proportion of patients taking frovatriptan
doses of 2.5 to 40 mg with mild or no headache compared to placebo. Frovatriptan 
doses of 0.5 mg and 1 mg were not more effective than placebo at 2 hours
postdose, and 2.5 mg was identified as the lowest effective dose for the relief
of migraine and accompanying symptoms. Above 2.5 mg, no dose-response
relationship was observed for any efficacy parameters. There was an increase in
the incidence of adverse events from 10 mg and above, but the vast majority were 
rated as mild in severity and did not impact upon tolerability in a significant
manner. CONCLUSIONS: Frovatriptan was well tolerated throughout the dose range of
0.5 to 40 mg. The 2.5-mg dose confers the optimal balance of efficacy and
tolerability for the acute treatment of migraine.

Publication Types: 
    Clinical Trial
    Multicenter Study
    Randomized Controlled Trial

PMID: 12028323 [PubMed - indexed for MEDLINE]

2957: Headache. 2002 Apr;42 Suppl 2:S63-73.

Frovatriptan: a review of drug-drug interactions.

Buchan P, Wade A, Ward C, Oliver SD, Stewart AJ, Freestone S.

Vernalis Ltd, Winnersh,UK.

OBJECTIVE: To investigate the potential for interactions involving drugs likely
to be coadministered with frovatriptan. BACKGROUND: Frovatriptan is a new
5-hydroxytryptamine (5-HT)(1B/1D) agonist. Preclinical data suggest that the
pharmacokinetic and pharmacological profile of frovatriptan may differ from that 
of the currently available triptans. METHODS: The potential for interactions
between frovatriptan and other drugs was investigated using in vitro methods,
studies in healthy volunteers, and retrospective analysis of data from phase I
trials. RESULTS: In vitro, frovatriptan was principally metabolized by cytochrome
P-450 (CYP) 1A2 but was found not to be an inhibitor or inducer of this or other 
CYP isoenzymes. Frovatriptan was only a weak inhibitor of monoamine oxidase at
very high concentrations in vitro and was not a substrate for this enzyme (unlike
some other triptans). Coadministration with moclobemide, at doses known to
inhibit monoamine oxidase-A, did not affect the pharmacokinetics of frovatriptan.
Binding to plasma proteins was low (15%), and binding to erythrocytes was
moderate (60%) and unlikely to be a source of interaction with other drugs. The
pharmacokinetics of frovatriptan were not affected by moderate alcohol intake.
There were slight increases in area under the curve and maximum concentration on 
concomitant administration with the combined oral contraceptives, propranolol,
and fluvoxamine; and slight decreases in these parameters on concomitant
administration with ergotamine and in tobacco smokers; these findings were
considered to have no clinical significance in view of frovatriptan's large
therapeutic index (well tolerated at doses ranging from 2.5 to 40 mg). These
effects can be attributed primarily to modification of CYP1A2 activity but their 
impact is limited, probably due to frovatriptan also undergoing renal clearance
and the likely role of blood cell binding in controlling the amount of unbound
drug available for elimination. CONCLUSIONS: Because it has no inhibitory or
inducing effect on CYP isoenzymes and is only slightly bound to plasma proteins, 
it is unlikely that frovatriptan will alter the pharmacokinetics of concomitantly
administered drugs. Frovatriptan, therefore, appears to have a low risk of
interaction with other drugs, and adjustments of dose are unlikely to be required
when it is coadministered with other agents.

PMID: 12028322 [PubMed - indexed for MEDLINE]

2958: Headache. 2002 Apr;42 Suppl 2:S54-62.

Clinical pharmacokinetics of frovatriptan.

Buchan P, Keywood C, Wade A, Ward C.

Vernalis Ltd, Winnersh, UK.

OBJECTIVE: To review available data on the clinical pharmacokinetics of
frovatriptan. BACKGROUND: Preclinical data suggest that the pharmacokinetic
profile of frovatriptan may differ from that of the currently available triptans.
METHODS: Studies of healthy volunteers, subjects with renal or hepatic
impairment, elderly subjects, and patients with migraine during and between
attacks were reviewed. RESULTS: Oral bioavailability of frovatriptan is 22% to
30%, and although the time to maximum concentration is typically 2 to 3 hours,
approximately 60% to 70% of plasma maximum concentration is achieved within 1
hour of dosing. Frovatriptan distributes into erythrocytes, with binding
reversible and time dependent. The relatively long terminal elimination half-life
(about 26 hours) confers good systemic exposure and may produce a long duration
of therapeutic action, thus reducing migraine recurrence and the need for
redosing. Systemic exposure to frovatriptan generally correlates with dose
between 1 and 100 mg. Blood and plasma frovatriptan concentrations are
consistently higher in females, but there is no need to adjust dose according to 
gender. Pharmacokinetics are essentially unaffected by food and were predictable 
after repeat dosing; steady state is approached in about 4 to 5 days.
Pharmacokinetics were changed only slightly in subjects with renal impairment or 
mild-to-moderate hepatic impairment, elderly individuals, and during migraine
attacks. Frovatriptan is principally metabolized by the CYP1A2 isoenzyme of
cytochrome P-450 and is cleared by the kidney and liver, each having sufficient
capacity to compensate for impairment of the other. CONCLUSIONS: Frovatriptan can
be taken without regard for food intake, and because of the large therapeutic
margin and shallow dose-response curve, there is no need for dosage adjustment in
the elderly, in women taking a combined oral contraceptive, in patients with
mild-to-severe renal impairment, mild-to-moderate hepatic impairment, or
according to gender. The long duration of exposure may reduce the likelihood of
early migraine recurrence.

Publication Types: 
    Clinical Trial
    Comparative Study
    Randomized Controlled Trial

PMID: 12028321 [PubMed - indexed for MEDLINE]

2959: CNS Drugs. 2002;16(6):385-403.

Practical approaches to migraine management.

Diamond S, Wenzel R.

Diamond Inpatient Headache Unit, Diamond Headache Clinic, St. Joseph Hospital,
and Finch University of Health Sciences/The Chicago Medical School, North
Chicago, Chicago, Illinois 60614, USA.

Migraine is a recurrent clinical syndrome characterised by combinations of
neurological, gastrointestinal and autonomic manifestations. The exact
pathophysiological disturbances that occur with migraine have yet to be
elucidated; however, cervico-trigemino-vascular dysfunctions appear to be the
primary cause. Despite advances in the understanding of the pathophysiology of
migraine and new effective treatment options, migraine remains an
under-diagnosed, under-treated and poorly treated health condition. Most patients
will unsuccessfully attempt to treat their headaches with over-the-counter
medications. Few well designed, placebo-controlled studies are available to guide
physicians in medication selection. Recently published evidence-based guidelines 
advocate migraine-specific drugs, such as serotonin 5-HT(1B/1D) agonists (the
'triptans') and dihydroergotamine mesylate, for patients experiencing moderate to
severe migraine attacks. Additional headache attack therapy options include other
ergotamine derivatives, phenothiazines, nonsteroidal anti-inflammatory agents and
opioids. Preventative medication therapy is indicated for patients experiencing
frequent and/or refractory attacks.

Publication Types: 
    Review

PMID: 12027785 [PubMed - indexed for MEDLINE]

2960: Brain. 2002 Jun;125(Pt 6):1379-91.

A population-based study of familial hemiplegic migraine suggests revised
diagnostic criteria.

Thomsen LL, Eriksen MK, Roemer SF, Andersen I, Olesen J, Russell MB.

Copenhagen Headache Center, Department of Neurology, Glostrup Hospital, Denmark.

Familial hemiplegic migraine (FHM) is a rare autosomal dominantly inherited
subtype of migraine with aura. The clinical characteristics of FHM have been
described previously in selected materials or case studies, but population-based 
studies are important in order to analyse the full spectrum of the disorder. The 
aim of the present study was to perform a systematic search for familial cases of
migraine with an aura that included motor weakness in order to generate
non-selected material of as many FHM cases as possible in the Danish population
of 5.2 million inhabitants, and to compare this material with already available
population-based clinical descriptions of migraine with typical aura (MA). Due to
the rarity of FHM, traditional population-based methods were not feasible.
Therefore, the search strategy employed a computer search of the National Patient
Register, screening >27 000 case records from headache clinics and private
neurologists, and advertisements. A total of 147 affected FHM patients from 44
families were identified. FHM patients most often had all four 'typical' aura
symptoms (visual, sensory, aphasic and motor symptoms) and all had at least two
of these aura symptoms during FHM attacks. The motor, sensory and visual aura
symptoms were all similar in type to the motor, sensory and visual aura symptoms 
in MA, but FHM had a statistically significantly longer duration of the visual
and sensory aura symptoms, and these and other aura symptoms often fulfilled the 
criteria of the International Headache Society for prolonged aura. In addition,
69% had basilar migraine (BM) symptoms during FHM attacks. The order of the aura 
symptoms was usually visual, followed by sensory, aphasic, motor and, lastly,
basilar-type migraine symptoms. Headache was present in 99% of FHM patients
during FHM attacks, whereas the aura symptoms more often occurred without
headache in MA. Headache duration was significantly longer in FHM compared with
MA. Based on these data, we suggest more precise diagnostic criteria for FHM and 
a more clear clinical distinction between FHM and BM. Our results have
significant implications for case finding in genetic studies and for clinical
migraine differential diagnosis.

PMID: 12023326 [PubMed - indexed for MEDLINE]

2961: Clin Ther. 2002 Apr;24(4):520-9.

Use of rescue medication in trials of almotriptan versus placebo in the treatment
of acute migraine.

Mathew NT.

Houston Headache Clinic, Texas 77004, USA.

BACKGROUND: Almotriptan malate is a recently marketed triptan for the treatment
of acute migraine. Results from controlled clinical trials demonstrate efficacy
superior to placebo and an adverse event rate comparable to that with placebo.
OBJECTIVE: The goal of this study was to assess the effect of oral almotriptan on
the use of rescue medication in the treatment of acute migraine attacks. METHODS:
Three Phase II and III, placebo-controlled, randomized, double-blind studies of
almotriptan used as the basis for regulatory approval of the drug were included
in the analysis. Two studies (1 single dose, 1 multiple dose) assessed
almotriptan 6.25 mg and 12.5 mg and a third compared almotriptan 12.5 mg and
sumatriptan 100 mg. Primary results from all 3 trials were previously published. 
Rescue medication was permitted if migraine pain had not decreased to mild
severity or to no pain at 2 hours after study medication. The primary end point
of this analysis was use of rescue medication. RESULTS: A total of 1777 patients 
were included in the analysis. Mean patient age ranged from 39.4 to 44.0 years;
approximately 87% were women, and >98% were white. Patients were well matched for
demographic characteristics. Overall, use of rescue medication was significantly 
lower with almotriptan 6.25 mg and 12.5 mg compared with placebo (P < or = 0.05
for each group). No significant difference was noted between the almotriptan
12.5-mg and sumatriptan 100-mg groups. In 2 of the studies, patients with
moderate or severe baseline pain used significantly less rescue medication in the
almotriptan groups compared with placebo. CONCLUSIONS: Oral almotriptan 6.25 mg
or 12.5 mg significantly reduced use of rescue medication compared with placebo
among patients with acute migraine. Use of rescue medication was comparable with 
almotriptan 12.5 mg and sumatriptan 100 mg.

Publication Types: 
    Clinical Trial
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 12017397 [PubMed - indexed for MEDLINE]

2962: Ophthalmic Physiol Opt. 2002 Mar;22(2):130-42.

Optometric function in visually sensitive migraine before and after treatment
with tinted spectacles.

Evans BJ, Patel R, Wilkins AJ.

The Institute of Optometry, London, UK. bruce.evans@virgin.net

Optometrists frequently encounter patients with migraine and patients and
practitioners sometimes suspect that visual stimuli or visual anomalies trigger
headaches. There is a lack of evidence-based research on the issue, however. Some
patients with migraine may be hypersensitive to visual stimuli, and it has been
suggested that individually prescribed coloured filters might be an effective
treatment to reduce symptoms from such stimuli. A recent randomised controlled
trial showed such a treatment to be effective and the present paper reports on
the optometric characteristics of the patients in this study. Twenty-one patients
with neurologically diagnosed migraine were compared with 11 controls. No
significant differences were found between the two groups with respect to
refractive error, ocular pathology, colour vision, contrast sensitivity,
accommodative function, strabismus and hyperphoria. The migraine group tended to 
be a little more exophoric, but by most criteria they were able to compensate for
their exophoria as well as the control group. The migraine group were more prone 
to pattern glare than the controls (p = 0.004). The effects of precision tinted
and control tinted lenses were investigated. The only variable to show a
consistent and marked improvement with tinted lenses was pattern glare. The most 
likely mechanism for the benefit from individually prescribed coloured filters in
migraine is the alleviation of cortical hyperexcitability (Wilkins et al. 1994)
and associated pattern glare.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 12014487 [PubMed - indexed for MEDLINE]

2963: Eur J Clin Pharmacol. 2002 May;58(2):149-55. Epub 2002 Apr 5.

Incidence and determinants of migraine prophylactic medication in the
Netherlands.

Rahimtoola H, Buurma H, Tijssen CC, Leufkens HG, Egberts AC.

SIR Institute for Pharmacy Practice Research, Leiden, The Netherlands.
h.rahimtoola@pharm.uu.nl

OBJECTIVE: To estimate and examine the incidence and determinants of initiation
of migraine-prophylactic therapy as well as the corresponding drug of choice over
a period of 5 years following the use of specific abortive migraine
drugs.METHODS: By accessing data from a large prescription database, an
identification of patients treated with ergotamine or a triptan from 1 January
1994 to 31 December 1998 was made. The cumulative incidence of initiation of
migraine-prophylactic drugs (beta-blockers, serotonin antagonists, specific
calcium antagonists, amitriptyline, clonidine and valproic acid) was estimated in
patients following the use of ergotamine or a triptan. An assessment of the
migraine-prophylactic drug of first choice was also performed. A few baseline
determinants were analysed to highlight a possible association with the
initiation of prophylactic therapy: age, gender, type of abortive migraine drug
use and year of prophylaxis. Additional determinants included the analysis of
drug-utilisation patterns, such as the consumption and switch patterns of
abortive migraine drug use as well as co-medication use prior to prophylaxis. For
this particular analysis a reference group (patients not having commenced
prophylaxis) was selected from the initial study population.RESULTS: After having
satisfied eligibility criteria, a total of 3999 first-time users of ergotamine
and triptans were included of whom 479 (12%) had initiated migraine-prophylactic 
therapy. This corresponded to an incidence density of 6.0 per 100 person-years
and was highest for patients younger than 45 years and for multiple abortive
migraine drug users. The incidence fell considerably from 12.0 person-years in
1994 to 5.1 person-years in 1998. More than half of the patients had been
prescribed a beta-blocker as the migraine-prophylactic drug of first choice by
both general practitioners and neurologists. The use of antidepressants and/or
benzodiazepines and oral contraceptives was significantly higher in patients
starting prophylaxis compared with those who did not. The consumption of abortive
migraine drug use (4.0 defined daily doses per month vs 3.7 defined daily doses
per month), and switch patterns (27.1% vs 30.9%) were similar for patients
starting and not starting prophylaxis.CONCLUSION: The overall incidence of
initiation of migraine-prophylactic therapy following the use of abortive
migraine analgesics was 6.0% per year and fell considerably during 5 years of the
study. Beta-blockers were the migraine-prophylactic drugs of first choice for
general practitioners and neurologists. In our study we could not determine any
factors clearly associated with the initiation of migraine prophylaxis besides
prior use of antidepressants and benzodiazepines. A future assessment of the
usage patterns of migraine-prophylactic drugs may provide detailed information
concerning the effectiveness and tolerability.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 12012149 [PubMed - indexed for MEDLINE]

2964: Am J Obstet Gynecol. 2002 May;186(5 Suppl Understanding):S215-9.

Linking olfaction with nausea and vomiting of pregnancy, recurrent abortion,
hyperemesis gravidarum, and migraine headache.

Heinrichs L.

Department of Gynecology and Obstetrics, Stanford University School of Medicine, 
CA 94305-5466, USA.

OBJECTIVE: The experience of women was sought about nausea and vomiting, its
relation to olfaction, its occurrence among pregnant women with anosmia, and the 
potential association of hyperemesis gravidarum and migraine headache. METHODS:
We performed a community-based study with a physician/patient-directed
questionnaire, and a retrospective analysis of hospital records. RESULTS: Nearly 
all women (n = 163 parous women) experience nausea (98%) and vomiting (97%). The 
highest frequency causes of nausea and vomiting were "food poisoning" (65%),
"flu" (58%), pregnancy (54%), and offensive odors (52%); vomiting occurred as
frequently as nausea for the first 2 causes, and one half as often for the latter
causes. Most women reported that the pain experienced during vomiting exceeded
that of parturition. Among 9 women with hypogonadotropic anosmia with advanced
reproductive technology-induced pregnancies, 2 experienced nausea and vomiting,
one from "food poisoning." Among 37 women with migraine headache, 10 (27%) had
experienced hyperemesis gravidarum, and among 16 who experienced hyperemesis
gravidarum, 5 (37%) had migraine headaches. CONCLUSIONS: The frequency of nausea 
and vomiting, caused most often by nonpregnancy-related triggers, is high among
women. In a small sample of women with congenital anosmia, nausea and vomiting of
pregnancy occurred in only 1 pregnancy, suggesting that olfaction is a highly
selected trigger for nausea and vomiting of pregnancy. The shared nausea and
vomiting experience of hyperemesis gravidarum and migraine headache among women
suggests a common mechanism, possibly based on allelic variations within the DRD2
(dopaminergic receptor) gene. Because olfactory receptors, odor types, and MHC
antigens are closely integrated, and because olfactory stimuli often incite
episodes of pregnancy, nausea, and vomiting, hyperemesis gravidarum, and migraine
headache, these genes and their products invite further scrutiny. The
pregnancy-conserving effect of PNV and the MHC antigen overlap in couples with
recurrent abortion are important clues possibly relating olfaction, MHC antigens,
and reproductive success or failure.

PMID: 12011889 [PubMed - indexed for MEDLINE]

2965: Neurology. 2002 May 14;58(9 Suppl 6):S27-31.

Diagnostic lessons from the spectrum study.

Lipton RB, Cady RK, Stewart WF, Wilks K, Hall C.

IMR, Stamford, Connecticut, USA.

Article abstract Migraine is a heterogeneous condition that causes symptoms that 
vary both among individuals and within individuals from attack to attack. We
examined and reviewed several important lessons on the diagnosis of migraine
learned from the distribution of headache types and patterns of treatment
response in the Spectrum Study, including recruitment and diagnostic issues. The 
accuracy of an initial diagnosis, assigned by a clinician in the context of a
clinical trial, was compared with the results of a final diagnosis, assigned by a
neurologist, reviewing the initial evaluation as well as headache diaries for up 
to 10 attacks. Several lessons can be learned from the Spectrum Study.
Recruitment difficulties teach us that disabling tension-type headache is
difficult to find, suggesting that it is rare. Examination of the final diagnosis
given after diary evaluations suggests that a diagnosis of migraine can usually
be confirmed for patients with disabling headache. After reclassification of the 
final sample of 432 subjects, 24/75 (32%) patients initially clinically
classified as having disabling episodic tension-type headache proved to have
migraine or migrainous headache after a diary review. Among study participants,
90% of subjects with disabling headache (HIMQ score >250) had a migraine-related 
disorder. Treatment response suggests that, in migraineurs, tension-type
headaches may have a pathophysiology similar to that of migraine. The diary data 
show that mild headaches in patients with disabling migraine often evolve into
full-blown migraine. The Spectrum Study supports the view that, for patients with
disabling episodic headache, migraine is often the correct diagnosis. In clinical
practice, the suspicion of migraine should be high for patients experiencing
episodic disabling headache. Assessment of headache-related disability may assist
practitioners in making a diagnosis of migraine.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 12011271 [PubMed - indexed for MEDLINE]

2966: Neurology. 2002 May 14;58(9 Suppl 6):S21-6.

Self-awareness of migraine: interpreting the labels that headache sufferers apply
to their headaches.

Lipton RB, Stewart WF, Liberman JN.

IMR, Stamford, Connecticut and Hunt Valley, Maryland, USA.

Although people with migraine are aware of their headaches they are often not
aware that they have migraine. This can lead to inappropriate or ineffective use 
of treatments, delays in seeking appropriate care, and miscommunication during
clinical encounters. This article assesses self-recognition of migraine and
identifies terms used by migraine sufferers to describe their migraine headaches.
Individuals were selected for telephone interview by random digit dialing in
several large United States cities as a part of a clinical trials recruiting
initiative. Individuals (n = 30,758) aged 18 to 65 years of age were interviewed 
about their headaches using a validated computer-assisted telephone interview.
Among the 23,564 respondents who reported headache, their headaches were
classified as migraine (with or without aura) by the criteria of the
International Headache Society (IHS). The relationships among the terms subjects 
used for their headaches and their IHS diagnosis of migraine were assessed. Of
the 23,564 respondents, 4,967 individuals called their headache migraine and
3,074 individuals reported headache that met the IHS criteria for migraine. The
positive predictive value for self-assessed migraine is 33.1%; the negative
predictive value for a self-assessment other than migraine is 92.3%. Therefore,
individuals who called their headaches migraine were about three times more
likely to meet IHS criteria for migraine. Among the 3,074 individuals meeting IHS
criteria for migraine, only 53.4% recognized their headaches as migraine
(sensitivity 54%; specificity 83.8%). Among migraineurs, stress headaches (n =
345) and sinus headaches (n = 365) were the most common erroneous labels
reported. Age influenced the erroneous terminology. Individuals less than 40
years of age were more likely to misidentify their migraine as stress headaches, 
whereas individuals 40 years of age and older were more likely to misidentify
their migraines as sinus headaches. In a population sample, 54% of individuals
with IHS migraine did not know that their headaches are migraine. Those who
called their headaches migraine were much more likely to have migraine. Migraine 
awareness programs that rely solely on the term "migraine" may miss individuals
who urgently need to be reached. Therefore, public education should target people
with severe or disabling headache and aim to create awareness of the diagnostic
possibilities.

PMID: 12011270 [PubMed - indexed for MEDLINE]

2967: Neurology. 2002 May 14;58(9 Suppl 6):S15-20.

Migraine and tension-type headache: an assessment of challenges in diagnosis.

Kaniecki RG.

University of Pittsburgh Headache Center, Pittsburgh, Pennsylvania 15213, USA.

The difficulty in distinguishing episodic tension-type headache from migraine
headache is widely acknowledged. The misdiagnosis of migraine as tension-type
headache has potentially significant consequences because it may preclude
patients with disabling headaches from receiving appropriate treatment. This
article explores the symptomatologic, epidemiologic, and pathophysiologic
relationships among migraine and tension-type headaches with the aim of
elucidating ways to improve their diagnosis and treatment. Clinical,
epidemiologic, and pharmacologic data converge to suggest that rigid adherence to
the IHS criteria in diagnosing migraine and tension-type headache may result in
misdiagnosis of some headaches. Many migraine attacks are accompanied by tension 
headache-like symptoms, such as neck pain. Conversely, IHS-defined tension-type
headaches are often accompanied by migraine-like symptoms, such as photophobia or
phonophobia and aggravation by activity. The health-care provider caring for
patients with headache should be cognizant of these overlaps and their
implications for the management of patients with headache.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 12011269 [PubMed - indexed for MEDLINE]

2968: Neurology. 2002 May 14;58(9 Suppl 6):S10-4.

Sinus headache or migraine? Considerations in making a differential diagnosis.

Cady RK, Schreiber CP.

Headache Care Center, Springfield, Missouri 65804, USA.

Sinus headache is commonly diagnosed, and patients with headache often cite sinus
pain and pressure as a cause of their headaches. A high frequency of diagnosis of
sinus headache, which specialists consider to be relatively rare, among patients 
meeting International Headache Society (IHS) diagnostic criteria for migraine
raises the possibility that migraine and perhaps other headache types are
sometimes mistaken for sinus headache. This article considers clinical,
epidemiologic, and pathophysiologic relationships between sinus headache and
migraine and discusses the implications for clinical management of headache. Both
historic and new data show that nasal symptoms frequently accompany migraine,
although these symptoms are not part of the IHS diagnostic criteria for migraine.
Parasympathetic activation, as well as the hypothesized mechanism of neurogenic
or immunogenic switching (i.e., crossover interactions of neurogenic and
immunogenic inflammation), may account for both the frequent occurrence of nasal 
symptoms in migraine and the possibility that sinus inflammation can sometimes
act as a migraine trigger. Considered in aggregate, the data show that the
occurrence of nasal symptoms associated with a headache should neither trigger a 
diagnosis of sinus disease nor exclude a diagnosis of migraine. It should, in
fact, prompt diagnostic consideration of both conditions.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 12011268 [PubMed - indexed for MEDLINE]

2969: Neurology. 2002 May 14;58(9 Suppl 6):S3-9.

The role of concomitant headache types and non-headache co-morbidities in the
underdiagnosis of migraine.

Diamond ML.

Diamond Headache Clinic, Chicago, IL 60614, USA.

That migraine is significantly underdiagnosed in the United States and other
countries is well established. New data from a follow-up survey to the American
Migraine Study II reveal that the presence of concomitant headache types and
co-morbid conditions significantly affects the ability to detect and diagnose
migraine. This article describes these data and explores the contribution of
concomitant headache types and co-morbidities to the problem of underdiagnosis of
migraine. Migraine continues to be underdiagnosed because of failure to recognize
it (missed diagnosis) and because of misdiagnosis of migraine as another headache
type. First, a diagnosis of migraine may be missed in the presence of other
headache types that occur proportionally more frequently than migraine and
thereby overshadow migraine. Second, migraine may be misdiagnosed when
health-care providers inappropriately interpret specific symptoms and co-morbid
conditions as indicators of the presence of a non-migraine headache type such as 
sinus or tension. By becoming aware of these diagnostic pitfalls and being more
judicious and deliberate in diagnosing migraine and other headache types,
health-care providers can improve the diagnosis of migraine and help patients to 
receive appropriate therapy.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 12011267 [PubMed - indexed for MEDLINE]

2970: Headache. 2002 Apr;42(4):294-6.

Diffusion-weighted magnetic resonance imaging during the aura of pseudomigraine
with temporary neurologic symptoms and lymphocytic pleocytosis.

Gekeler F, Holtmannspötter M, Straube A, Klopstock T.

Department of Neurology, Klinikum Grosshadern, Ludwig-Maximilians-Universität,
Munich, Germany.

A typical feature of pseudomigraine with temporary neurologic symptoms and
lymphocytic pleocytosis (PMP) is the long duration of aura symptoms. To determine
if these prolonged auras cause early ischemic parenchymal changes, we performed
diffusion-weighted magnetic resonance imaging during the aura of a patient with
PMP and found no reduction of water diffusion.

Publication Types: 
    Case Reports

PMID: 12010388 [PubMed - indexed for MEDLINE]

2971: Headache. 2002 Apr;42(4):287-90.

Prevalences of migraine and tension-type headache in adolescent girls of Shiraz
(southern Iran).

Ayatollahi SM, Moradi F, Ayatollahi SA.

Department of Biostatistics and Epidemiology, School of Public Health, Shiraz
University of Medical Sciences, Islamic Republic of Iran.

OBJECTIVE: To determine the prevalences of migraine and tension-type headache in 
teenaged girls attending schools in Shiraz (southern Iran). BACKGROUND: Studies
of headache prevalence are numerous, and findings have varied according to the
specific population and region involved. No data are available regarding headache
prevalence among Iranian teenagers. METHODS: A random sample of 1868 teenaged
girls (aged 11 to 18 years) was evaluated, and 507 subjects reported headache.
The headache disorders were classified on the basis of a clinical interview,
general physical and neurologic examinations, and the diagnostic criteria of the 
International Headache Society. Logistic regression was used for data analysis.
RESULTS: Overall prevalence rate for migraine was 6.1% (95% CI, 5.0 to 7.2) and
for tension-type headache, 12.1% (95% CI, 10.6 to 13.6). Migraine and
tension-type headache were significantly associated. CONCLUSIONS: It is concluded
that exposition of subjects to sunlight, type of food, and a family history of
headache had most significant effects on occurrence of migraine and tension-type 
headaches.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 12010386 [PubMed - indexed for MEDLINE]

2972: Headache. 2002 Apr;42(4):281-6.

Headache syndromes amongst schoolchildren in Riyadh, Saudi Arabia.

Al Jumah M, Awada A, Al Azzam S.

Section of Neurology, King Fahd National Guard Hospital, Riyadh, Saudi Arabia.

We evaluated 1,400 randomly selected Saudi children in grades 1 through 9 to
determine the prevalence of migraine and tension-type headache. Of the 1400
distributed questionnaires, 1,181 (84.3%) were completed properly and so served
as the basis for analysis. There were 573 boys (48.5%) and 608 girls (51.5%).
Ages ranged from 6 to 18 years. Five hundred eighty-eight children (49.8%; 272
boys and 316 girls) had recurrent headache episodes not related to febrile
illness in the year preceding the survey. Eighty-four children (7.1%; 37 boys and
47 girls) had recurrent episodes of migraine, and 504 (42.7%; 232 boys and 272
girls) had recurrent episodes of nonmigraine headache. For both boys and girls,
the age-specific prevalence rate for nonmigraine headache rose steadily from
around 15% at aged 6 to 7 years to nearly 60% after aged 15. For migraine, there 
was a sharp increase in the prevalence rate (from around 2% to around 9%) at aged
10 to 11, also in both boys and girls. Age-adjusted prevalence for migraine
between aged 6 and 15 was 6.2%. Due to the relatively poor sensitivity of some of
the IHS criteria in children, this figure may underestimate the true magnitude of
migraine in the population studied.

PMID: 12010385 [PubMed - indexed for MEDLINE]

2973: Headache. 2002 Apr;42(4):275-80.

Epidemiological and clinical characteristics of migraine in Sivas, Turkey.

Kececi H, Dener S.

Department of Neurology, AIBU Duzce Medical Faculty, Turkey.

OBJECTIVE: To investigate the epidemiology of migraine in Sivas, Turkey,
including its prevalence, clinical characteristics, and impact according to age, 
sex, and socioeconomic status. METHODS: Thirteen hundred twenty subjects were
personally interviewed by a neurologist. Each household member with headache was 
asked questions regarding their headaches including age at onset, frequency,
duration, character, location, severity, aggravating and ameliorating factors,
and prodromal and associated symptoms. Migraine diagnoses were determined in
accordance with the classification criteria of the International Headache
Society. RESULTS: Migraine was identified in 173 subjects (45 males and 128
females), and lifetime prevalence of migraine was 7.9% (95% CI, 5.66 to 10.1) in 
males and 17.1% (95% CI, 14 to 20) in females. Aura was reported by 1.4% of males
and 3.3% of females. CONCLUSION: Migraine prevalence in Turkey is similar to that
reported in Europe and the United States.

PMID: 12010384 [PubMed - indexed for MEDLINE]

2974: Headache. 2002 Apr;42(4):263-7.

Migraine is associated with livedo reticularis: a prospective study.

Tietjen GE, Gottwald L, Al-Qasmi MM, Gunda P, Khuder SA.

Department of Neurology, Medical College of Ohio, Toledo, USA.

OBJECTIVE: To investigate the relationship of livedo reticularis, an ischemic
dermatopathy, and migraine, an ischemic stroke risk factor. BACKGROUND: Livedo
reticularis refers to the reddish-blue reticular mottling of the skin resulting
from narrowing of small and medium arteries at the dermis-subcutis border. A
subset of patients with livedo reticularis develop stroke in the absence of other
vascular risk factors, which has been termed Sneddon syndrome. We undertook this 
prospective study in a non-neurology clinic to delineate further the relationship
of livedo reticularis and migraine. METHODS: Patients in a general dermatology
clinic were interviewed for vascular risk factors and history of migraine in
accordance with the International Headache Society (IHS) criteria. A
dermatologist, not familiar with the interview, recorded the primary
dermatological diagnosis and the presence or absence of livedo reticularis on
examination. RESULTS: Two hundred eighty-one consecutive patients (184 women and 
97 men; average age, 52 years) were interviewed and examined. Seventy-five (27%) 
had migraine (IHS codes 1.1, 1.2) and an additional 18 (6%) had atypical migraine
(IHS 1.7). Livedo reticularis was noted in 46 patients (16%), with the frequency 
higher in women than men (42 [23%] of 184 versus 4 [4%] of 97; P <.0001). The
frequency of livedo reticularis in patients with migraine was higher than in
those without migraine (24 [26%] of 93 versus 22 [12%] of 188; P =.002), and
higher in female than male migraineurs (23 [32%] of 72 versus 1 [5%] of 21; P
=.012). In logistic regression analysis of the women, migraine was associated
with livedo reticularis (odds ratio [OR], 2.3; confidence interval [CI], 1.08 to 
4.71), as well as with stroke (OR, 4.0; CI, 0.87 to 18.21), coronary artery
disease (OR, 3.5; CI, 1.16 to 10.33), and deep venous thrombosis (OR, 3.2; CI,
0.98 to 10.32). CONCLUSIONS: In women, migraine is associated with stroke,
coronary artery disease, deep venous thrombosis, as well as livedo reticularis, a
dermatopathy which has been pathologically linked to cerebral vasculopathy.
Whether migraineurs with livedo reticularis compose a subset at higher risk of
thrombosis, including stroke, deserves further investigation.

PMID: 12010382 [PubMed - indexed for MEDLINE]

2975: Headache. 2002 Apr;42(4):249-55.

Mouth-dispersible aspirin in the treatment of migraine: a placebo-controlled
study.

MacGregor EA, Dowson A, Davies PT.

City of London Migraine Clinic, UK.

OBJECTIVE: To compare the efficacy of mouth-dispersible aspirin 900 mg and
placebo in the treatment of migraine. BACKGROUND: Aspirin is widely accepted as
an effective therapy for migraine. Previous studies have indicated that gastric
stasis and delayed gastric emptying, which occur during migraine attacks, delay
aspirin absorption. Mouth-dispersible formulations are considered to be more
quickly absorbed than solid formulations and, therefore, may be more effective in
treating migraine. DESIGN: Randomized, double-blind, placebo-controlled,
crossover study in four specialized migraine clinics in the United Kingdom.
METHODS: One hundred one patients diagnosed with migraine (according to the
International Headache Society diagnostic criteria) participated in the study.
Patients received either single doses of mouth-dispersible aspirin (3 x 300 mg)
or placebo for moderate pain in the treatment of two migraine attacks. Rescue
medication could be taken after 2 hours, if required. The primary efficacy
parameter was response to therapy at 2 hours posttreatment. Other efficacy
parameters were response to treatment, pain-free, and pain intensity at all other
time points. Functional disability, nausea, vomiting, photophobia, phonophobia,
symptom relief, patient and investigator global evaluation, use of rescue
medication, headache recurrence, and palatability and convenience were also
recorded. RESULTS: Of 101 patients, 73 took both treatments. At 2 hours, 48% of
patients taking mouth-dispersible aspirin responded, compared to only 19% taking 
placebo (P =.0005). Mouth-dispersible aspirin was significantly better than
placebo for response to treatment (P<.05) and pain intensity difference (P<.01)
at all time points from 30 minutes posttreatment; for pain-free (P<.05) and use
of rescue medication (P<.01) from 3 hours posttreatment; for headache recurrence 
(P<.05); and for patients' and investigators' global evaluations of efficacy (P
=.0001 in both cases). CONCLUSIONS: Mouth-dispersible aspirin 900 mg is effective
compared with placebo for the treatment of moderate migraine head pain, with
relief seen from as early as 30 minutes after taking medication.

Publication Types: 
    Clinical Trial
    Comparative Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 12010380 [PubMed - indexed for MEDLINE]

2976: Headache. 2002 Apr;42(4):242-8.

Serum ionized magnesium levels and serum ionized calcium/ionized magnesium ratios
in women with menstrual migraine.

Mauskop A, Altura BT, Altura BM.

New York Headache Center, SUNY Downstate Medical Center, Brooklyn 11203, USA.

OBJECTIVE: It has been suggested that magnesium deficiency may play an important 
role in menstrual migraine and that the serum ionized calcium (ICa2+)/ionized
magnesium (IMg2+) ratio is important in migraine headache. Studies were designed 
to test these hypotheses. DESIGN: We prospectively evaluated 270 women seen at a 
headache clinic and in 61 women with menstrual migraine measured IMg2+, total
magnesium, and ICa2+ levels so as to calculate the ICa2+/IMg2+ ratio. RESULTS:
The incidences of IMg2+ deficiency were 45% during menstrual attacks, 15% during 
nonmenstrual attacks, 14% during menstruation without a migraine, and 15% between
menstruations and between migraine attacks. The serum ICa2+ levels were within
our reference range, but the ICa2+/IMg2+ ratio was elevated (P<.01) in menstrual 
migraine. CONCLUSIONS: The high incidence of IMg2+ deficiency and the elevated
ICa2+/IMg2+ ratio during menstrual migraine confirm previous suggestions of a
possible role for magnesium deficiency in the development of menstrual migraine.

Publication Types: 
    Comparative Study
    Research Support, U.S. Gov't, P.H.S.

PMID: 12010379 [PubMed - indexed for MEDLINE]

2977: Headache. 2002 Feb;42(2):99-113.

How does almotriptan compare with other triptans? A review of data from
placebo-controlled clinical trials.

Dahlöf CG, Dodick D, Dowson AJ, Pascual J.

Gothenburg Migraine Clinic, Sociala Huset, Sweden.

Almotriptan, the new selective 5-HT1B/1D agonist, has a higher oral
bioavailability than any other triptan, with more than two thirds of the
administered dose absorbed within the first hour both inside and outside of a
migraine attack. Gender or the presence of food in the stomach does not affect
its pharmacokinetic profile, and the compound has no clinically relevant
interactions with other drugs. Among the available triptans, response rates at 2 
hours range from 50% to 80%, with 20% to 50% of patients pain-free. Almotriptan
12.5 mg provides similar efficacy, with significant advantage over placebo at 30 
minutes and a reliable consistency (75% in two of three attacks). Headache
typically recurs in 25% to 45% of patients with most triptans. The recurrence
rate with almotriptan 12.5 mg, 18% to 27%, is among the lowest reported. The
tolerability of almotriptan 12.5 mg is close to that of placebo with a low
incidence of central nervous system side effects and chest symptoms. In
conclusion, almotriptan's consistent pharmacokinetics and good efficacy, in
combination with excellent tolerability, make it an attractive choice in the
acute treatment of migraine attacks.

Publication Types: 
    Comparative Study
    Review

PMID: 12005302 [PubMed - indexed for MEDLINE]

2978: Headache. 2002 Feb;42(2):93-8.

Comparison of triptan tablet consumption per attack: a prospective study of
migraineurs in Spain.

Pascual J, Fité B, López-Gil A.

Servicio de Neurología, Hospital Valdecilla, Santander, Spain.

OBJECTIVES: To compare patient self-reported tablet consumption of rizatriptan 10
mg per attack (24 hours) with that of sumatriptan 50 mg, zolmitriptan 2.5 mg, and
naratriptan 2.5 mg on an unselected, prescription-based, Spanish migraine
population. METHODS: One hundred twenty community pharmacies recruited patients
with migraine, who used their pharmacies, to fill a triptan prescription. In
diaries, patients recorded baseline pain intensity and the number of triptan
tablets and additional medication taken per attack. Patients treated a maximum of
three attacks. Analysis of variance or the Student t test and chi-square or
Fisher exact tests were used for univariate comparisons. Hochberg corrections
were used for multiple-group comparisons. A generalized estimating equation
method was used to correct for within-subject correlation. Adjusted odds ratios
(ORs) and 95% confidence intervals (CIs) were calculated. RESULTS: Two hundred
thirty-one patients (84% women) treated 589 evaluable migraine attacks
(sumatriptan, n = 135; naratriptan, n = 90; zolmitriptan, n = 149; rizatriptan, n
= 149). Triptan tablet consumption per attack (mean +/- SD) for rizatriptan (1.24
+/- 0.56) was significantly lower than that of sumatriptan (1.75 +/- 1.2; P<
.05), zolmitriptan (1.61 +/- 0.86; P < .05), or naratriptan (1.46 +/- 0.62; P=
.05). The average number of triptan tablets taken and additional medication use
increased according to baseline pain severity. More attacks were treated with one
tablet of rizatriptan (81.2%) than with one tablet of sumatriptan (51.9%),
zolmitriptan (55.7%), or naratriptan (60%). The probability of using more than
one triptan tablet per attack (24 hours) was more than three times greater for
sumatriptan (adjusted OR = 3.71; CI, 2.05 to 6.7; P = .001) and zolmitriptan
(adjusted OR = 3.32; CI, 1.82 to 6.17; P = .001), and more than two times greater
for naratriptan (adjusted OR = 2.66; CI, 1.36 to 5.21; P =.004) than for
rizatriptan. CONCLUSIONS: Rizatriptan was associated with significantly lower
triptan tablet use and additional medication use per attack than the other
triptans. Additional randomized studies are needed to confirm the conclusions of 
this study.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 12005301 [PubMed - indexed for MEDLINE]

2979: Headache. 2002 Feb;42(2):152-3.

Migraine prevention and errors in living: Dr. Graham's lessons for patients and
physicians.

Spierings EL.

Department of Neurology, Brigham and Women's Hospital, Harvard Medical School,
Boston, Mass, USA.

John R. Graham, MD (1909-1990), the "father of headache management," left us and 
our patients with migraine with valuable advice ... advice based on extensive
experience in headache management which, at the time of his retirement, spanned
more than half a century.

PMID: 12005293 [PubMed - indexed for MEDLINE]

2980: Headache. 2002 Feb;42(2):147-51.

Red ear syndrome and migraine: report of eight cases.

Raieli V, Monastero R, Santangelo G, Eliseo GL, Eliseo M, Camarda R.

Child Headache Center, Division of Child Neuropsychiatry, GF Ingrassia Hospital, 
Palermo, Italy.

We describe eight idiopathic cases of red ear syndrome in seven children and one 
adult. All were migraineurs with a history of paroxysmally painful and red ear,
unilateral or alternating, in isolation or associated with migraine attacks. The 
reported duration of these episodes varied from 30 minutes to 1 hour. Neurologic 
examination, brain MRI and CT scans, and x-rays of the cervical spine were
normal. The close temporal relationship between the "red ear episodes" and
migraine attacks suggests an association between the two conditions.

Publication Types: 
    Case Reports

PMID: 12005292 [PubMed - indexed for MEDLINE]

2981: Headache. 2002 Feb;42(2):140-1.

Ophthalmoplegic migraine with reversible enhancement of intraparenchymal abducens
nerve on MRI.

Lee TG, Choi WS, Chung KC.

Department of Neurology, Kyung-Hee University Hospital, Seoul, Korea.

We describe a patient with ophthalmoplegic migraine and right abducens nerve
palsy, in whom serial magnetic resonance imaging showed a transient,
gadolinium-enhancing lesion in the right lower pons, during both headache and the
headache-free period. The enhancing linear lesion was felt to represent
intraparenchymal fibers of the affected abducens nerve. The possible
pathophysiology of this unique finding is discussed.

Publication Types: 
    Case Reports

PMID: 12005290 [PubMed - indexed for MEDLINE]

2982: Headache. 2002 Feb;42(2):132-5.

Ophthalmoplegic migraine with reversible thalamic ischemia shown by brain SPECT.

Shin DJ, Kim JH, Kang SS.

Department of Neurology, Gil Medical Center, Gachon Medical College, Inchon,
South Korea.

Two patients who presented with ophthalmoplegic migraine underwent
electroencephalography, brain magnetic resonance imaging, cerebral angiography,
and technetium Tc 99m ethyl cysteinate dimer single photon emission computed
tomography (SPECT) during an attack. Follow-up SPECT was performed after
neurologic symptoms resolved. In both patients, SPECT during an attack of
ophthalmoplegia and headache demonstrated significantly decreased regional
cerebral blood flow (rCBF) in the thalamus on the side of the ophthalmoplegia;
rCBF reverted to normal on a follow-up SPECT during the symptom-free period.
These findings suggest reversible ischemia in the territories of perforating
branches of the posterior cerebral artery may accompany ophthalmoplegic migraine 
and possibly bear some relationship to the clinical features.

Publication Types: 
    Case Reports

PMID: 12005288 [PubMed - indexed for MEDLINE]

2983: Headache. 2002 Feb;42(2):114-9.

Oral magnesium load test in patients with migraine.

Trauninger A, Pfund Z, Koszegi T, Czopf J.

Department of Neurology, Medical Faculty, University of Pécs, Hungary.

OBJECTIVE: To determine whether migraineurs may have a systemic deficiency of
magnesium. BACKGROUND: Magnesium deficiency has been shown to play a potential
role in the pathogenesis of migraine, but there are no data on total body
magnesium status in migraineurs. METHODS: An oral magnesium load test was
performed by giving 3000 mg of magnesium lactate during a 24-hour interictal
period to 20 patients with migraine (15 women and 5 men; mean age, 37.9 years)
and 20 healthy volunteers (16 women and 4 men; mean age, 39.6 years). Baseline
and postload magnesium concentrations were determined from serum and 24-hour
urine specimens. RESULTS: There was no significant difference between the groups 
in the baseline serum and urine magnesium concentrations, although the latter
tended to be lower (P = .064) in the migraine group. The postload magnesium
concentrations were significantly higher within both the migraine (P < .0001 and 
P < .0001) and the control (P = .0009 and P < .0001) groups compared to the
baseline values. After loading, the 24-hour urinary magnesium excretions were
significantly lower (P = .0007) in the patients with migraine than in the
controls, but serum values did not differ. CONCLUSIONS: Magnesium retention
occurs in patients with migraine after oral loading, suggesting a systemic
magnesium deficiency.

PMID: 12005285 [PubMed - indexed for MEDLINE]

2984: Headache. 2002 Jan;42(1):58-69.

New paradigms in the recognition and acute treatment of migraine.

Sheftell FD, Tepper SJ.

New England Center for Headache, Stamford, Conn 06902, USA.

It would be ideal if clinical decisions regarding acute migraine treatment could 
be made on the basis of three parameters: a critical appraisal of available
scientific evidence, clinical experience (including knowledge of the individual
patient and his/her attack characteristics), and, of course, patient preferences.
Patients are likely to prefer agents that offer rapid relief, pain-free status
within 2 hours, no recurrence or need for rescue medication, extended time to
recurrence (if present), consistency of therapeutic effect over multiple attacks,
oral administration. good tolerability, safety, and minimal drug interactions.
Fortunately, a number of specific therapies now are available which place these
objectives within the patient's reach. Ongoing barriers to optimal migraine care 
include underrecognition, underconsultation, undertreatment, restrictions imposed
by insurance companies, and exaggerated concerns regarding the safety of the
triptans. Overcoming these barriers is likely to prove a more important
contribution to patient care than endeavoring to establish the relative merits of
one triptan over another. We have described in detail a number of strategies for 
improving recognition and treatment of migraine. Many headache specialists now
believe that recurrent episodes of disabling headache, with a stable pattern over
years, should be viewed as migraine until proven otherwise. In the end, this may 
represent the most useful paradigm in the primary care setting, where time is of 
the essence. Studies to validate this approach are needed. Acute treatment
intervention that is based on scientific evidence, clinical experience, and
patients' needs and desires will provide better outcomes than those presently
obtained. Preliminary evidence favors early intervention with oral triptans, and 
randomized, prospective, double-blind, placebo-controlled studies, ideally
employing a crossover design, are required to confirm this. The US Consortium's
evidence-based guidelines, the National Headache Foundation's standards of care, 
and the Canadian guidelines have applied the standards of scientific inquiry to
the field of headache management and "translation" of these guidelines into
practical instruments for clinicians through vehicles such as the Primary Care
Network's Patient-Centered Strategies for Effective Management of Migraine should
raise the general standard of care for patients with migraine. Last, but far from
least, initiatives undertaken by the World Health Organization (WHO) will add
credibility to the many layfolk and professionals who have struggled to present
headache as a disabling disorder worthy of scientific investigation and
aggressive medical management. The WHO states: "These common complaints impose a 
significant health burden ... Despite this, both the public and the majority of
healthcare professionals tend to perceive headache as a minor or trivial
complaint. As a result, the physical, emotional, social and economic burdens of
headache are poorly acknowledged in comparison with those of other, less
prevalent, neurologic disorders." Migraine is finally out of the closet.

Publication Types: 
    Review

PMID: 12005277 [PubMed - indexed for MEDLINE]

2985: Headache. 2002 Jan;42(1):49-55.

Rizatriptan 5 mg for the acute treatment of migraine in adolescents: a
randomized, double-blind, placebo-controlled study.

Winner P, Lewis D, Visser WH, Jiang K, Ahrens S, Evans JK; Rizatriptan Adolescent
Study Group.

Palm Beach Headache Center at Premiere Research Institute, West Palm Beach, Fla, 
USA.

OBJECTIVE: To investigate the tolerability and efficacy of rizatriptan 5 mg in
adolescent migraineurs. METHODS: Randomized, double-blind, placebo-controlled
study. Patients aged 12 to 17 years received rizatriptan 5 mg (n = 149) or
placebo (n = 147) for a moderate or severe headache and for up to two
recurrences. Headache severity, presence or absence of associated symptoms, and
functional disability were assessed over a 4-hour postdose period, and any
adverse events were recorded. The primary efficacy measure was pain-free status
at 2 hours postdose. RESULTS: Rizatriptan 5 mg was well tolerated. The most
commonly reported adverse events (all with incidence of 5% or less) among
patients receiving rizatriptan were dry mouth, dizziness, asthenia/fatigue,
nausea, and somnolence. The percentage of patients pain-free at 2 hours was 32%
for rizatriptan 5 mg versus 28% for placebo (P=.474). The percentage of patients 
with pain relief (reduction of predose pain intensity to mild or none) at 2 hours
was 66% for rizatriptan versus 56% for placebo (P=.079). Placebo response rates
were higher than those typically observed in previous studies of rizatriptan in
adults. Compared with placebo, rizatriptan significantly improved functional
disability at 1.5 and 2 hours, and nausea at 1 and 1.5 hours. Post hoc analysis
showed a significant benefit of rizatriptan versus placebo in the percentage of
patients who had pain relief when their migraine attacks were treated on weekends
(65% versus 36%, P=.046) compared with weekdays (66% versus 61%, P=.365), and the
weekend placebo response rate was similar to that seen in adults. CONCLUSIONS:
Rizatriptan 5 mg was well tolerated and effective on some measures when used in
adolescents for the treatment of a migraine attack.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 12005275 [PubMed - indexed for MEDLINE]

2986: Headache. 2002 Jan;42(1):41-8.

Frovatriptan for the acute treatment of migraine: a dose-finding study.

Goldstein J, Keywood C; 251/96/14 Study Group.

San Francisco Clinical Research Center, Calif, USA.

OBJECTIVE: To determine the optimal dose and tolerability of frovatriptan in the 
acute treatment of migraine. BACKGROUND: Frovatriptan has a distinctive
pharmacological and pharmacokinetic profile compared with sumatriptan. A previous
study has shown that frovatriptan doses of 2.5, 5, 10, 20, and 40 mg are equally 
effective in relieving headache with no evidence of a dose-response relationship.
The incidence of adverse events tended to increase with doses of 10 mg and above.
METHODS: This study was a randomized, double-blind, placebo-controlled,
parallel-group multicenter trial. Patients (n=635) took a single oral dose of
placebo or frovatriptan, 0.5, 1, 2.5, or 5 mg, at the onset of a moderate or
severe migraine headache and recorded headache intensity, functional impairment, 
and migraine-associated symptoms over 24 hours. RESULTS: Frovatriptan 2.5 mg
produced clinically and statistically significant headache relief 2 hours
post-dose, whereas the effect of lower doses was not significantly different from
that of placebo at that time point. The 2.5-mg dose also produced significant
symptom relief and improvement in functional impairment. All doses of
frovatriptan were well tolerated, and the majority of adverse events were of mild
or moderate severity. CONCLUSION: It is concluded that the 2.5-mg dose of
frovatriptan offers optimal efficacy and tolerability in the treatment of acute
migraine. Higher doses do not appear to confer greater efficacy and are
associated with an increased incidence of adverse effects.

Publication Types: 
    Clinical Trial
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 12005274 [PubMed - indexed for MEDLINE]

2987: Headache. 2002 Jan;42(1):32-40.

A long-term open-label study of oral almotriptan 12.5 mg for the treatment of
acute migraine.

Mathew NT; Oral Almotriptan Study Group.

Houston (Tex) Headache Clinic, 77004, USA.

OBJECTIVE: Evaluate the long-term tolerability of almotriptan 12.5 mg for the
treatment of acute migraine attacks occurring over a 6-month period. BACKGROUND: 
Almotriptan is a second-generation 5-HT(1B/1D) agonist that exhibits vascular
selectivity for meningeal arteries and has demonstrated efficacy for the
treatment of acute migraine in short-term controlled trials. METHODS: This was a 
6-month open-label study. Adults (18 years of age or older) were required to have
a diagnosis of acute migraine with or without aura (according to the diagnostic
criteria of the International Headache Society), a history of at least 1 year of 
moderate-to-severe migraine pain with at least two and a maximum of six migraines
per month, and at least 24 hours of freedom from head pain between attacks.
Patients were instructed to take a single 12.5-mg dose of almotriptan at the
onset of a migraine attack. If migraine pain did not disappear in 2 hours, escape
medication could be taken; if relapse occurred in less than 24 hours, a second
12.5-mg dose could be taken. Tolerability was assessed from the nature and
incidence of all adverse events, and efficacy was assessed according to the end
point of pain relief 2 hours following almotriptan administration. RESULTS: Of
585 patients treated, 582 were included in the intent-to-treat population. The
most frequent drug-related adverse events were nausea (3.1%) and dizziness
(2.4%). No serious drug-related adverse events were reported, and no deaths
occurred. Adverse events led to discontinuation of treatment in 36 patients
(6.2%). Drug-related chest pain was reported in 9 patients (1.5%). Seventy-six
percent of patients achieved pain relief at 2 hours for all attacks treated, and 
49% were pain-free at 2 hours. After a second dose of almotriptan 12.5 mg, pain
relief was achieved in 87% of attacks, and 59% were pain-free. Pain relief and
pain-free rates were higher among those with moderate baseline pain. CONCLUSIONS:
When taken at attack onset, almotriptan 12.5 mg is well tolerated, safe, and
effective for the long-term treatment of acute migraine.

Publication Types: 
    Clinical Trial
    Multicenter Study
    Research Support, Non-U.S. Gov't

PMID: 12005273 [PubMed - indexed for MEDLINE]

2988: Headache. 2002 Jan;42(1):28-31.

Within-patient early versus delayed treatment of migraine attacks with
almotriptan: the sooner the better.

Pascual J, Cabarrocas X.

Service of Neurology, University Hospital Marqués de Valdecilla, Santander,
Spain.

BACKGROUND: Migraine sufferers typically have been instructed to delay triptan
therapy until headache intensity is at least moderate. Recent data suggest that
earlier use of triptans may be more beneficial. OBJECTIVE: To address the
potential "within-patient" benefit of intervention with almotriptan 12.5 mg for
migraine headache of mild intensity. METHODS: We performed a post hoc analysis of
a subgroup of patients from a large, open-label, long-term clinical trial wherein
762 migraineurs used almotriptan 12.5 mg for headache attacks of any severity.
Specifically, we evaluated the efficacy and safety of treatment in those patients
who had treated at least 3 "mild" attacks and 3 "moderate/severe" attacks,
examining rates of pain-free status, use of rescue medication, early recurrence, 
and adverse events for the first 3 mild and the first 3 moderate/severe attacks
treated. RESULTS: There were 118 migraineurs and 708 attacks available for
analysis. At 1 hour following treatment, pain-free status was achieved in 47% of 
mild attacks versus 14% of moderate/severe attacks (P<.001); incidences at 2
hours were 84% of mild attacks and 53% of moderate/severe attacks (P<.001). The
chance of achieving pain-free status at 1 hour in at least 2 of 3 treated attacks
was 45% for mild attacks and 9% for moderate/severe attacks; at 2 hours the
percentages were 88% for mild attacks and 56% for moderate/severe attacks. Rescue
medication was required in 8% of mild attacks and in 13% of moderate/severe
attacks (P<.01). The incidence of early recurrence was 28% for mild attacks and
33% for moderate/severe attacks (P<.01). There was no difference in the incidence
of adverse events for mild versus moderate/severe attacks (6% versus 7%).
CONCLUSION: These results support early intervention with oral triptan therapy.
When used for mild intensity head pain, almotriptan 12.5 mg produced a
significantly higher incidence of pain-free status at 1 and 2 hours and lower
incidences of early headache recurrence or need for rescue medication.

Publication Types: 
    Clinical Trial
    Multicenter Study

PMID: 12005272 [PubMed - indexed for MEDLINE]

2989: Headache. 2002 Jan;42(1):21-7.

Almotriptan increases sustained pain-free outcomes in acute migraine: results
from three controlled clinical trials.

Dodick DW.

Department of Neurology, Mayo Clinic Scottsdale, Ariz 85259, USA.

OBJECTIVE: Evaluate the effect of almotriptan on sustained pain-free outcome in
patients with acute migraine. METHODS: Three randomized, double-blind,
placebo-controlled trials of almotriptan for the treatment of acute migraine were
examined. Two trials evaluated almotriptan 6.25 mg and 12.5 mg, and the third
evaluated almotriptan 12.5 mg and sumatriptan 100 mg. Patients aged 18 to 65
years were instructed to take 1 dose of study medication at the onset of a
moderate-to-severe migraine headache. A second dose was allowed for relapse.
Sustained pain-free was defined as a decrease in pain severity from moderate or
severe at baseline to no pain at 2 hours postdose and without relapse or the use 
of escape medication between 2 and 24 hours. RESULTS: A total of 1791 adult
migraine sufferers were studied. The proportion of patients achieving a sustained
pain-free state was significantly (P<.05) higher in the almotriptan 6.25-mg
(21.7% to 22.5%) and 12.5-mg (24.6% to 27.6%) groups than in the placebo group
(7.5% to 12.1%). The proportion of patients achieving a sustained pain-free state
was comparable between almotriptan 12.5 mg (24.6%) and sumatriptan 100 mg (28.5%)
and significantly (P<.05) greater than with placebo (12.1%). Among patients with 
severe baseline pain, a sustained pain-free state was achieved in significantly
more patients (P<.05) with almotriptan 12.5 mg (17.3% to 20.9%) than with placebo
(3.1% to 3.2%). Among those with moderate baseline pain, a sustained pain-free
state was achieved in significantly more patients (P<.01) with almotriptan 12.5
mg (31.3% to 32.0%) than with placebo (10.2% to 16.1%). CONCLUSIONS: Almotriptan 
12.5 mg is significantly better than placebo and comparable to sumatriptan 100 mg
for achieving a sustained pain-free state.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial

PMID: 12005271 [PubMed - indexed for MEDLINE]

2990: Headache. 2002 Jan;42(1):16-20.

Treatment of migraine with rizatriptan: when to take the medication.

Hu XH, Raskin NH, Cowan R, Markson LE, Berger ML; United States Migraine Study
Protocol (USMAP) Group.

Outcomes Research & Management, US Human Health, Merck & Co, Inc, West Point, PA,
USA.

OBJECTIVE: To assess, in the setting of routine clinical practice, rizatriptan's 
effectiveness in treating acute migraine at its onset versus in a later phase of 
the attack. BACKGROUND: Although the efficacy and tolerability of rizatriptan
have been well documented in clinical trials, no information is available about
the impact of the timing of medication use on clinical outcome. METHODS:
Migraineurs were enrolled in a prospective study and treated with rizatriptan 10 
mg for two migraine attacks. Patients reported how they used the medication and
treatment outcomes via an interactive voice response system. Outcome variables
assessed included: time to onset of headache relief, headache severity 2 hours
postdose and whether or not patients became largely symptoms-free (including
associated symptoms), and when they were able to resume normal activities.
Episodes in which patients took rizatriptan immediately after experiencing
headache were designated "early use" and those in which patients delayed
treatment until their headaches evolved to become moderate or severe were
designated as "delayed use." Generalized estimating equations were used to assess
the impact of early drug use and to control for age, gender, drug formulation,
use of other migraine prescription medications before taking rizatriptan, attack 
sequence, migraine attack frequency, and recent migraine severity. RESULTS: A
total of 1919 migraineurs with 3450 migraine attack episodes were evaluated, of
which 1369 episodes were early use and 2081 delayed use. Compared to delayed-use 
episodes, episodes wherein patients took rizatriptan early were 1.33 times more
likely to be characterized by onset of headache relief within 30 minutes
posttreatment (95% confidence interval [CI], 1.11 to 1.60), 1.32 times more
likely to result in a largely symptom-free state (95% CI, 1.12 to 1.57), and 1.34
times more likely to be associated with a return to normal activities (95% CI,
1.13 to 1.58) within 1 hour posttreatment. No significant difference between
early-use and delayed-use episodes was observed with respect to the likelihood of
there being no or mild headache 2 hours posttreatment (odds ratio, 1.05; 95% CI, 
0.90 to 1.24). CONCLUSIONS: Whether taken at headache onset or later in the
attack, rizatriptan was equally effective in relieving acute migraine headache by
2 hours postdose. Taking rizatriptan at the onset of headache was associated with
more rapid relief of headache and reversal of functional disability.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 12005270 [PubMed - indexed for MEDLINE]

2991: Curr Pain Headache Rep. 2002 Jun;6(3):233-9.

Complicated migraine and migraine variants.

Rothner AD.

Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, OH 44195-0001, USA.
Rothned@ccf.org

This article reviews the less frequently encountered varieties of migraine. It is
suggested that these disorders be approached by evaluating possible underlying
etiologies before positively diagnosing migraine. This decreases the likelihood
of "missing" structural or metabolic disorders. The classification, diagnostic
evaluation, differential diagnosis, and treatment options of these disorders is
reviewed and a selection of references appended for additional information.

Publication Types: 
    Review

PMID: 12003695 [PubMed - indexed for MEDLINE]

2992: Curr Med Res Opin. 2002;18(1):1-9.

Usage of triptans among migraine patients: an audit in nine GP practices.

Williams D, Cahill T, Dowson A, Fearon H, Lipscombe S, O'Sullivan E, Rees T,
Strang C, Valori A, Watson D.

The Willows Surgery, Barry, South Glamorgan, Wales, UK.

A retrospective audit was carried out to investigate triptan usage over a period 
of one year among 360 adult patients with migraine in nine GP practices in the UK
and the Republic of Ireland. Data from patient records were analysed, in
conjunction with replies to a questionnaire about patients' perceptions of their 
migraine and its treatment. The majority of patients included in the audit were
women (83%), and most patients (81%) were aged between 35 and 64 years. Most
patients in the audit population (60%) were in the lowest band of triptan usage
(1-36 tablets prescribed over 12 months); 7% had moderate usage (37-53 tablets). 
A minority of patients appeared to be taking triptans in higher quantities: about
15% of patients had been prescribed 54-94 triptan tablets over a year, 9% had
received prescriptions for 95-149 tablets and 7% had received prescriptions for
150 or more tablets. These results indicated that some migraine patients were
using triptans at higher than expected rates, and suggested that some patients
might have been using their prescribed triptans inappropriately to treat a
headache that they incorrectly perceived as migraine (e.g. chronic daily
headache). Analyses were carried out to identify predictors of high usage.
Predictors identified included the use of several other (non-triptan) medications
to treat conditions other than migraine, one triptan dose being reported as
sufficient to treat an attack, patient's perception of all headaches as migraine 
and lack of concern about taking too much medication. Patients identified as
using triptans at a higher than expected rate can be called in for review of
migraine diagnosis, identification of possible causes of any increased frequency 
of attacks, and investigation of suspected non-migrainous headaches, such as
chronic daily headache and medication-induced headaches. For GPs, such actions
would help achieve and maintain a high standard of care for their migraine
patients, thus helping to contribute towards meeting the demands of the clinical 
governance agenda. Audit of triptan usage may also offer financial benefits for
the practice, since helping patients to avoid the inappropriate use of triptans
could lead to reductions in the overall costs of triptan prescribing within the
practice. The high usage predictors could be developed into a checklist of
potential indicators for GPs to identify patients who may become high users if
prescribed triptans and who might require closer monitoring. We recommend that
patients identified as having a potential for high usage should be routinely
reviewed, every 3-6 months, to ensure that they are using triptans appropriately 
to treat migraine. Although triptans are generally safe and well tolerated,
unnecessary use of any medication should be avoided.

Publication Types: 
    Multicenter Study
    Research Support, Non-U.S. Gov't

PMID: 11999139 [PubMed - indexed for MEDLINE]

2993: Cephalalgia. 2002 Feb;22(1):62-5.

Splitting of the body image as somesthetic aura symptom in migraine.

Podoll K, Robinson D.

Department of Psychiatry and Psychotherapy, University of Technology Aachen,
Germany.

Splitting of the body image was illustrated as a somesthetic aura symptom in
three of the 562 entries to the national Migraine Art competitions, confirming
previous descriptions of this rare phenomenon in the migraine literature. In this
type of self-experienced paroxysmal body schema disturbance, the own body is
perceived as being split, usually in the mid-line, into two halves that may be
displaced or separated from each other. Splitting of the body image most
frequently applies to the migraine sufferer's head. The said phenomenon, the
pathomechanisms of which are obscure, must not be confused with the visual
illusion of illusory splitting.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 11993615 [PubMed - indexed for MEDLINE]

2994: Cephalalgia. 2002 Feb;22(1):54-61.

CGRP may play a causative role in migraine.

Lassen LH, Haderslev PA, Jacobsen VB, Iversen HK, Sperling B, Olesen J.

Department of Neurology, Glostrup Hospital, University of Copenhagen, Denmark.
l.h.lassen@dadlnet.dk

Calcitonin gene-related peptide (CGRP) has been detected in increased amounts in 
external jugular venous blood during migraine attacks. However, it is unknown
whether this is secondary to migraine or whether CGRP may cause headache. In a
double-blind crossover study, the effect of human alphaCGRP (2 microg/min) or
placebo infused intravenously for 20 min was studied in 12 patients suffering
from migraine without aura. Headache intensity was scored on a scale from 0 to
10. Two patients were excluded due to severe hypotension and one because she had 
an infection. In the first hour median peak headache score was 1.0 in the
halphaCGRP group vs. 0 in the placebo group (P < 0.01). During the following 11 h
all patients experienced headaches after halphaCGRP vs. one patient after placebo
(P = 0.0004). The median maximal headache score was 4 after CGRP and 0 after
placebo (P = 0.006). In three patients after halphaCGRP, but in no patients after
placebo, the delayed headache fulfilled the IHS criteria for migraine without
aura. As intravenous administration of halphaCGRP causes headache and migraine in
migraineurs, our study suggests that the increase in CGRP observed during
spontaneous migraine attacks may play a causative role.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 11993614 [PubMed - indexed for MEDLINE]

2995: Cephalalgia. 2002 Feb;22(1):48-53.

A neural network model of sensitization of evoked cortical responses in migraine.

Thomas E, Sándor PS, Ambrosini A, Schoenen J.

Research Center for Cellular and Molecular Neurobiology, University of Liège,
Belgium. ethomas@ulg.ac.be

Migraine patients show abnormalities of cerebral electrophysiology that manifest 
themselves mainly during the attack interval. Cortical-evoked potentials of
migraineurs fail to habituate to repetitive presentations of visual stimuli, and 
the amplitude of components of their auditory cortical-evoked potentials have a
higher dependence on the stimulus intensities than in healthy subjects. A
computer model of a neural hetwork has been developed that is able to reproduce
both these neurophysiological dysfunctions. It predicts a positive correlation
between the magnitudes of both these dysfunctions. The model also offers an
explanation of why mutations in the same ion channel gene with opposite
consequences on channel function, e.g. P/Q Ca2+ channels in migraine, may lead to
similar electrophysiological abnormalities.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 11993613 [PubMed - indexed for MEDLINE]

2996: Cephalalgia. 2002 Feb;22(1):33-6.

Increased plasma nitrites in migraine and cluster headache patients in interictal
period: basal hyperactivity of L-arginine-NO pathway?

D'Amico D, Ferraris A, Leone M, Catania A, Carlin A, Grazzi L, Bussone G.

Neurological Institute C. Besta, Milan, Italy.

Nitrite concentrations in plasma were investigated in a population of migraine
and cluster headache patients and a group of healthy non-headache controls. A
hundred migraine patients and 69 cluster headache patients in the interictal
period, and 112 controls, were studied. Significantly higher nitrite
concentrations were found in migraine patients, with and without aura, and
cluster headache patients, in remission and cluster phase, than in controls.
These findings suggest that a basal dysfunction in the L-arginine-NO pathway may 
be involved in the peripheral mechanisms predisposing subjects with neurovascular
headaches to individual attacks.

PMID: 11993611 [PubMed - indexed for MEDLINE]

2997: Cephalalgia. 2002 Feb;22(1):23-32.

Efficacy, safety and tolerability of oral eletriptan in the acute treatment of
migraine: results of a phase III, multicentre, placebo-controlled study across
three attacks.

Stark R, Dahlöf C, Haughie S, Hettiarachchi J; Eletriptan Steering Committee.

Alfred Hospital, Prahran, Australia. richard.stark@med.monash.edu.au

The efficacy, safety and tolerability of the 5-HT1B/D receptor agonist eletriptan
(40 mg and 80 mg) in acute treatment of migraine was evaluated in a
multinational, randomized, double-blind, parallel-group, placebo-controlled,
three-attack study treating 1153 patients. In the initial attack, significantly
more eletriptan patients reported headache relief and complete pain relief at 2 h
vs. placebo (40 mg 62% and 32%, 80 mg 65% and 34%, placebo 19% and 3%; P <
0.0001). Headache relief occurred faster after eletriptan, with more patients at 
both doses reporting relief 30 min (P < 0.01) and 1 h (P < 0.0001) after
treatment than after placebo. There was a significantly lower recurrence rate
with eletriptan 80 mg compared with placebo (P < 0.01). Adverse events for all
treatments were generally mild or moderate and self-limiting. Eletriptan 40 mg
and eletriptan 80 mg both appear to be effective and well-tolerated acute
migraine treatments.

Publication Types: 
    Clinical Trial
    Clinical Trial, Phase III
    Comparative Study
    Evaluation Studies
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 11993610 [PubMed - indexed for MEDLINE]

2998: Cephalalgia. 2002 Feb;22(1):2-11.

Migraine and the extrapyramidal system.

Barbanti P, Fabbrini G.

Department of Neurological Sciences, University La Sapienza, Rome, Italy.
piero.barbanti@uniroma1.it

This review explores a large series of observations from clinical and
experimental studies on the interactions between migraine and the extrapyramidal 
system (EPS). A critical appraisal of these data suggests that the EPS is somehow
involved in migraine. However, primary involvement of the EPS in the
pathophysiology of migraine, as hinted at by the apparent concomitance of
migraine, extrapyramidal symptoms and diseases, as well as by the common
involvement of neurotransmitters and pathways, cannot as yet be proven. On the
other hand, the involvement of EPS in migraine may reflect its more general role 
in the processing of nociceptive information and/or may be part of the complex
behavioural adaptive response that characterizes migraine.

Publication Types: 
    Review

PMID: 11993609 [PubMed - indexed for MEDLINE]

2999: J Am Med Womens Assoc. 2002 Spring;57(2):73-8.

Migraine and women's health.

Rains JC, Penzien DB, Martin VT.

Center for Sleep Evaluation, Elliot Hospital, Manchester, New Hampshire, USA.

Migraine is a significant women's health concern. Epidemiological research has
demonstrated that migraine is one of the most common pain conditions and that
women are disproportionately affected. Recent advances in pathophysiology
highlight the hormonal antecedents of these sex differences in migraine and the
potential influence of hormones on migraine pain pathways. Migraine spawns
substantial suffering and disability and gives rise to great economic and
personal burden. Despite the availability of effective pharmacological and
nonpharmacological treatments, only a fraction of migraine sufferers receive
state-of-the-art treatment. Access to effective treatment is limited by economic 
and social barriers to care, including the long-standing social stigma that
trivializes headache. Although doubtless a women's health issue, migraine has
been largely overlooked in the women's health initiatives. This paper argues that
migraine is an important women's health concern and that greater attention to
migraine promises to make a demonstrable improvement in the quality of life of
many women.

Publication Types: 
    Review

PMID: 11991424 [PubMed - indexed for MEDLINE]

3000: Eur J Neurol. 2002 May;9(3):227-32.

Median nerve somatosensory evoked potentials in migraine.

Ozkul Y, Uckardes A.

Department of Neurology, Faculty of Medicine, University of Harran, Sanliurfa,
Turkey. yasarozkul@yahoo.com

In visual evoked potential studies, habituation during stimulus repetition with
the same stimulus at a constant intensity has been found to be abnormal in
migraineurs between attacks. The purpose of this study was to investigate
habituation of somatosensory evoked potentials (SEPs) and the effects of migraine
on them. Eighty-five subjects were included in the study: 30 healthy volunteers
(HVs) and 55 migraineurs [30 with migraine without aura (MO), 25 with migraine
with aura (MA)]. During continuous stimulation at 3 Hz, four blocks of 100
responses were sequentially averaged of Erb's point (N9), cervical (N13), and
cortical (N20) median nerve SEPs. Mean amplitude changes in the second, third and
fourth blocks are expressed as percentages of the first block. There was
habituation to N13 and N20 in the second, third and fourth blocks in HVs. In the 
migraine groups, there was no habituation; on the contrary, potentiation was
found. This potentiation was statistically significant only in the second blocks 
for N13 (MO P=0.007, MA P=0.01 versus HVs). However, in both migraineur groups,
the rate of N20 potentiations was statistically significant versus that in HVs
for all blocks (all P < 0.05). It is concluded that whilst physiological
habituation occurs in HVs for cervical and cortical SEPs, in migraine patients
there is an interictal deficit of habituation of this sensory modality.

PMID: 11985630 [PubMed - indexed for MEDLINE]

3001: J Neurol. 2002 Feb;249(2):206-11.

Efficacy and tolerability of acetazolamide in migraine prophylaxis: a randomised 
placebo-controlled trial.

Vahedi K, Taupin P, Djomby R, El-Amrani M, Lutz G, Filipetti V, Landais P,
Massiou H, Bousser MG; DIAMIG investigators.

Service de Neurologie Hĵpital Lariboisière, Paris, France. vahedi@ccr.jussieu.fr

BACKGROUNDS: Familial hemiplegic migraine and episodic ataxia type 2 (EA2) are
allelic disorders with distinct types of mutations in the CACNA1A gene. EA2
attacks are remarkably sensitive to acetazolamide, a carbonic anhydrase
inhibitor. The effectiveness of acetazolamide in migraine prophylaxis is unknown.
OBJECTIVES: To evaluate the efficacy and the tolerability of acetazolamide in
migraine prophylaxis. METHODS: We compared daily oral 500 mg acetazolamide and
placebo in patients with migraine in a multicentre, double-blind, randomised
trial of 12 weeks duration after a run-in period of 4 weeks without treatment.
Frequency of attacks at the last trial period of 4 weeks was the primary efficacy
criterion. Secondary efficacy criteria were the frequency of attacks per 4 weeks,
the severity and duration of attacks, the number of hours with migraine as well
as the number of responders with more than 50% reduction in attack frequency.
RESULTS: 53 patients had been enrolled when the study was prematurely stopped
because of a high number of withdrawals (34%), primarily linked to acetazolamide 
related side effects. Considering the primary and secondary efficacy criteria,
among the 53 included patients (27 in the placebo group and 26 in the
acetazolamide group), no difference between the 2 study groups could be
demonstrated. The most frequent adverse events related to acetazolamide were
paresthesias and asthenia. CONCLUSIONS: In this trial, migraine sufferers poorly 
tolerated acetazolamide given in an oral dose of 500 mg daily. No obvious
prophylactic beneficial effect of acetazolamide appeared on migraine attacks.

Publication Types: 
    Clinical Trial
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 11985388 [PubMed - indexed for MEDLINE]

3002: Otol Neurotol. 2002 May;23(3):364-71.

Migraine-associated dizziness: patient characteristics and management options.

Reploeg MD, Goebel JA.

Department of Neurology, Washington University School of Medicine, Campus Box
8115, 660 S. Euclid Avenue, St. Louis, MO 63110, U.S.A.
reploegm@medicine.wustl.edu

OBJECTIVE: To determine patient characteristics and effectiveness of therapy for 
migraine-associated dizziness. STUDY DESIGN: Retrospective chart review. SETTING:
Tertiary referral center. PATIENTS: Patients were identified through a code query
of billing records for the diagnosis of migraine-associated vertigo or
disequilibrium, based on the International Headache Society criteria. There were 
81 patients (61 women, 20 men) with an average age of 36.6 years (range, 8-71
yr); all except four patients were evaluated between 1995 and 1999. Follow-up was
obtained from chart review. Mean follow-up time was 54.5 weeks, with a range of 4
to 456 weeks. INTERVENTION: One or more treatment methods, including dietary
manipulation, medication (tricyclic antidepressants, beta-blockers or
calcium-channel blockers), and neurology consultation, were applied sequentially 
as necessary. MAIN OUTCOME MEASURE: Response to therapy was defined as greater
than 75% reduction in symptom recurrence rate. RESULTS: Overall, 72% of patients 
experienced resolution or dramatic reduction of their attacks of vertigo or
disequilibrium. Of the 13 patients treated with the introduction of dietary
manipulation alone, 100% received significant relief. Of the 31 patients treated 
with dietary manipulation and the addition of a medication, 77% of these patients
had significant relief. Of the final group of 37 patients treated with another
medication or a neurology consultation, 57% received substantial relief. Of the
responders, the majority (>95%) experienced an equal reduction in both vertigo or
disequilibrium and headache symptoms. Interestingly, 100% of the patients in the 
migraine without active headache group received substantial relief of their
vertigo or disequilibrium symptoms with migraine therapy. CONCLUSION: We conclude
that there is effective therapy for the common problem of migraine-associated
dizziness.

PMID: 11981397 [PubMed - indexed for MEDLINE]

3003: J Fam Pract. 2002 Feb;51(2):142-7.

Perceptions and needs of patients with migraine: a focus group study.

Cottrell CK, Drew JB, Waller SE, Holroyd KA, Brose JA, O'Donnell FJ.

Headache Treatment & Research Project, esterville, OH, USA.

OBJECTIVE: This study's purpose was to identify the areas that people find most
difficult in living with migraines and, in that regard, what kinds of assistance 
would be most helpful to them and to other people who have migraine headaches.
STUDY DESIGN: Four focus groups, each consisting of 4 to 8 participants, were
held. Discussions, which were recorded and organized according to category and
theme, focused on problems in living with migraines and effective treatment of
migraines. POPULATION: Participants were 24 people who had been experiencing 1 to
2 migraines a month, each lasting 1 to 2 days, for at least 6 months. RESULTS:
Five themes emerged: (1) impact on family, (2) misunderstanding by others, (3)
effect on work, (4) physician care issues, and (5) issues related to medical
insurance and drug companies. A majority of participants identified early
treatment as the most important consideration for new migraine sufferers. Many
participants preferred to have a relationship with their physicians in which they
developed a treatment plan together rather than receiving generic educational
materials. CONCLUSIONS: Results suggest that patients are interested in
understanding their migraines and securing relevant information in addition to
obtaining pain relief. Patients desired collaborative relationships with their
physicians and a team approach to treatment. Suggestions for physicians who treat
patients who have migraines are reviewed.

PMID: 11978212 [PubMed - indexed for MEDLINE]

3004: Electromyogr Clin Neurophysiol. 2002 Apr-May;42(3):175-9.

Visual evoked potential & brainstem auditory evoked potentials in acute attack & 
after the attack of migraine.

Kochar K, Srivastava T, Maurya RK, Jain R, Aggarwal P.

Department of Medicine, S.P. Medical College, Bikaner-334003, Rajasthan, India.

PURPOSE: To study the effect on visual evoked potential (VEP) and brainstem
auditory evoked potential (BAEP) at time of acute attack and after 7 days of the 
attack of migraine. MATERIAL AND METHODS: We studied BAEP and pattern reversal
VEP in 25 patients during acute attack and after 7 days of the attack. The
diagnosis of migraine was established according to criteria given by
international headache society (IHS). Peak and interpeak latencies (IPL's) of
BAEP and P100 latency of VEP were the main criteria to judge abnormalities.
RESULTS: There were prolonged peak and interpeak latencies in BAEP and prolonged 
peak latency (P100) in VEP at the time of acute attack of migraine. The data of
these abnormal recording were highly significant. After 7 days when the attack
was over, we recorded the BAEP and VEP again. The observation obtained at this
time was comparable to normal values. CONCLUSIONS: From the observation of this
study we can safely conclude that in acute attacks of migraine there may be some 
pathological changes in different areas of brain and brainstem, producing changes
in evoked potential which are statistically highly significant. However, these
changes are reversible, as the values of BAEP & VEP on 7th day after the attack
were comparable to those observed in normal healthy control.

PMID: 11977431 [PubMed - indexed for MEDLINE]

3005: Neurol Sci. 2002 Mar;22(6):455-8.

Occurrence of factor V Leiden mutation (Arg506Gln) and anticardiolipin antibodies
in migraine patients.

Intiso D, Crociani P, Fogli D, Grandone E, Cappucci G, Di Rienzo F, Di Viesti P, 
Simone P, Tonali P.

Department of Neurology, IRCCS Casa Sollievo della Sofferenza, Viale dei
Cappuccini 1, I-71013 San Giovanni Rotondo (FG), Italy.

The occurrences of factor V Leiden mutation (Arg506Gln) and antiphospholipid
antibodies (APA) in migraine patients have been reported, but the findings are
controversial. We investigated the presence of factor V Leiden and the serum
level of anticardiolipin antibodies (aCL) in a consecutive series of 70 migraine 
patients (47 women; mean age, 34.1 years). Of these, 40 patients had migraine
with aura. A matched sample of 70 healthy people was considered as the control
group. Heterozygous genotype for factor V Leiden mutation was detected in 4
(5.7%) migraine patients (of which 2 had migraine with aura) and in 2 (2.8%)
subjects of the control group. Although proportionally more migraine patients
harbored the factor V Leiden mutation, this difference was not statistically
significant, perhaps due to the small number of patients involved. We found
normal serum levels of aCL in all migraine patients. Further studies and a
long-term follow-up are warranted to determine the significance of this genetic
abnormality in migraine.

PMID: 11976977 [PubMed - indexed for MEDLINE]

3006: Heart Dis. 2001 Nov-Dec;3(6):357-61.

Intraoral chilling versus oral sumatriptan for acute migraine.

Friedman MH, Peterson SJ, Behar CF, Zaidi Z.

Department of Dentistry, Westchester Medical Center, New York Medical College,
Valhalla, New York, USA.

Migraine pathophysiology is associated with a dural inflammation. Recent evidence
suggests that the primary inflammation occurs in a maxillary nerve segment,
accessible intraorally. Local tenderness, related to symptom laterality, has been
palpated consistently in asymptomatic migraine patients, and significant migraine
relief has been obtained from chilling confined to this area. Thirty-five
symptomatic episodic migraine patients were enrolled in this study, comparing 40 
minutes of bilateral intraoral chilling, 50 mg of oral sumatriptan, and 40
minutes of sham (tongue) chilling. Hollow metal tubes chilled by circulating ice 
water were held in the maxillary molar periapical areas by the patient. Pain and 
nausea were recorded at baseline and 1, 2, 4, and 24 hours after start of
treatment, using a numeric symptom-relief scale. Significant mean headache relief
was obtained by maxillary chilling and sumatriptan at all four time intervals,
with poor relief obtained by placebo. Maxillary chilling was more effective than 
sumatriptan at all four time intervals. Significant nausea relief was obtained by
maxillary chilling and sumatriptan at posttreatment and 2 and 4 hours later. At
24 hours, some headache and nausea recurrence was noted with sumatriptan. The
repeated-measures analysis of variance indicated that both treatments, drug (P = 
0.024) and maxillary chilling (P = 0.001), reduced the headache, as compared with
the control group. Tenderness suggests local inflammation associated with
vasodilatation and edema. Because chilling can resolve local edema, these
findings raise the possibility that an intraoral inflammation may be a factor in 
migraine etiology.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 11975819 [PubMed - indexed for MEDLINE]

3007: Cephalalgia. 2002 Mar;22(2):142-5.

Spatial contrast sensitivity of migraine patients without aura.

Benedek K, Tajti J, Janáky M, Vécsei L, Benedek G.

Department of Neurology, University of Szeged, Hungary.

Visual disturbances are frequent symptoms in migraine. Since there is a
possibility of separate damage in the magno- or parvo-cellular visual pathway in 
migraine patients, we performed a study including the measurement of static and
dynamic spatial contrast sensitivity on 15 patients suffering from migraine
without aura under photopic and scotopic conditions. Fifteen healthy volunteers
without primary headache served as controls. The results revealed a marked
decrease in contrast sensitivity at low spatial frequencies in the migraine
patients. Spatial contrast sensitivity demonstrated some lateralization, as the
sensitivity to low spatial frequencies obtained through separate eyes showed
significantly larger side-differences in migraine patients than in control
subjects. These findings suggest that the mechanisms responsible for vision at
low spatial frequencies are impaired in migraine patients. This might indicate
impaired function of the magnocellular pathways in this condition.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 11972583 [PubMed - indexed for MEDLINE]

3008: Cephalalgia. 2002 Mar;22(2):137-41.

Open label trial of coenzyme Q10 as a migraine preventive.

Rozen TD, Oshinsky ML, Gebeline CA, Bradley KC, Young WB, Shechter AL,
Silberstein SD.

Jefferson Headache Center/Thomas Jefferson University, Philadelphia,
Pennsylvania, USA. RozenT@ccf.org

The objective was to assess the efficacy of coenzyme Q10 as a preventive
treatment for migraine headaches. Thirty-two patients (26 women, 6 men) with a
history of episodic migraine with or without aura were treated with coenzyme Q10 
at a dose of 150 mg per day. Thirty-one of 32 patients completed the study; 61.3%
of patients had a greater than 50% reduction in number of days with migraine
headache. The average number of days with migraine during the baseline period was
7.34 and this decreased to 2.95 after 3 months of therapy, which was a
statistically significant response (P < 0.0001). Mean reduction in migraine
frequency after 1 month of treatment was 13.1% and this increased to 55.3% by the
end of 3 months. Mean migraine attack frequency was 4.85 during the baseline
period and this decreased to 2.81 attacks by the end of the study period, which
was a statistically significant response (P < 0.001). There were no side-effects 
noted with coenzyme Q10. From this open label investigation coenzyme Q10 appears 
to be a good migraine preventive. Placebo-controlled trials are now necessary to 
determine the true efficacy of coenzyme Q10 in migraine prevention.

Publication Types: 
    Clinical Trial
    Research Support, Non-U.S. Gov't

PMID: 11972582 [PubMed - indexed for MEDLINE]

3009: Cephalalgia. 2002 Mar;22(2):132-6.

Lack of age-dependent development of the contingent negative variation (CNV) in
migraine children?

Bender S, Weisbrod M, Just U, Pfüller U, Parzer P, Resch F, Oelkers-Ax R.

Department for Child and Adolescent Psychiatry, University of Heidelberg,
Heidelberg, Germany. Stephan_Bender@med.uni-heidelberg.de

Increased negativity of contingent negative variation (CNV) in adult migraineurs 
is thought to reflect cortical hyperexcitability. CNV amplitude changes with age 
in healthy adults. Recently, evidence emerged that this might not be the case for
migraineurs. Our study investigates age-dependency of CNV during childhood age.
Seventy-six healthy controls and 61 children with migraine without aura (IHS code
1.1) between 6 and 18 years were examined using an acoustic S1-S2-CNV-paradigm
with a 3-s inter-stimulus interval. The amplitude of the late component of CNV,
as well as total CNV at the vertex (Cz according to the international 10-20
system), were significantly higher in migraineurs without aura than in controls. 
Healthy controls showed increasing amplitudes of CNV with age, whereas in
migraine children without aura amplitudes did not change. Thus group differences 
were reduced during adolescence. Increased CNV negativity might reflect a
biological vulnerability to migraine, rather than being a result of
chronification. Migraineurs seem to lack age-dependent development of CNV also
during early age, which supports the hypothesis of migraine as a maturation
disorder.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 11972581 [PubMed - indexed for MEDLINE]

3010: Cephalalgia. 2002 Mar;22(2):125-31.

The movement-related potential in children with migraine and tension-type
headache.

Müller BW, Sartory G, Tackenberg A.

Clinic for Psychiatry and Psychotherapy, University Psychiatry Clinics, Essen,
Germany.

Migraine is characterized by an elevated contingent negative variation (CNV) in
adults and children. In the present study the movement-related potential
preceding self-initiated movements, the Bereitschaftspotential, was investigated 
in 30 children (mean age 12 years) who were suffering from migraine and
tension-type headache and in 16 healthy age-matched controls. Children pressed a 
button 80 times with the right index finger while movement-related potentials
were recorded from frontal and central electrodes. Whereas healthy children
evidenced positive movement-related potentials at left and midline positions,
children with migraine and tension-type headache showed negative movement-related
potentials at midline leads without lateralization. Negativity was even more
pronounced in cases of migraine with than without aura symptoms.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 11972580 [PubMed - indexed for MEDLINE]

3011: Cephalalgia. 2002 Mar;22(2):117-24.

Motion sickness and migraine: optokinetic stimulation increases scalp tenderness,
pain sensitivity in the fingers and photophobia.

Drummond PD.

School of Psychology, Murdoch University, Perth, Western Australia.
drummond@central.murdoch.edu.au

The aim of this study was to determine whether scalp tenderness and photophobia, 
two well-recognized symptoms of migraine, develop during the motion sickness
induced by optokinetic stimulation. To investigate whether motion sickness has a 
general influence on pain perception, pain was also assessed in the fingertips.
After optokinetic stimulation, nausea increased more and headache persisted
longer in 21 migraine sufferers than in 15 non-headache controls. Scalp
tenderness increased during optokinetic stimulation in nauseated subjects, and
pain in the fingertips increased more and photophobia persisted longer in
migraine sufferers than controls. These findings suggest that the disturbance
responsible for nausea also sensitizes trigeminal nociceptive neurones or
releases inhibitory controls on their discharge. A low nausea threshold and a
propensity for sensitization to develop rapidly in nociceptive pathways may
increase susceptibility to migraine.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 11972579 [PubMed - indexed for MEDLINE]

3012: Cephalalgia. 2002 Mar;22(2):107-11.

Neurovascular headache and a midbrain vascular malformation: evidence for a role 
of the brainstem in chronic migraine.

Goadsby PJ.

Headache Group, Institute of Neurology and The National Hospital for Neurology
and Neurosurgery, London, UK. peterg@ion.ucl.ac.uk

Migraine is a common, disabling form of primary headache that has been linked by 
functional imaging studies to activation in the rostral brainstem. In specialty
clinics migraine is most commonly seen in association with frequent less feature 
full headache that has been called transformed migraine or more recently termed
chronic migraine. A patient is described with frequent migraine, 3 days per week,
and less feature full headaches on other days. The patient has a cavernoma in the
midbrain that has bled. She was previously headache free and now has
contralateral daily headache. The patient supports the functional imaging
observations from positron emission tomography (PET) that the rostral brainstem
is pivotal in migraine pathophysiology, particularly the contralateral midbrain
periaqueductal grey matter. Moreover, the patient's lesion provides biologically 
plausible support that a single entity causes her clinical presentation: chronic 
migraine, not two-disorders, migraine and tension-type headache.

Publication Types: 
    Case Reports

PMID: 11972577 [PubMed - indexed for MEDLINE]

3013: Cephalalgia. 2002 Mar;22(2):101-6.

Zolmitriptan orally disintegrating tablet is effective in the acute treatment of 
migraine.

Dowson AJ, MacGregor EA, Purdy RA, Becker WJ, Green J, Levy SL.

The Kings Headache Services, Kings College Hospital, London, UK.
ANDYDOWSON@DOWSONA.fsnet.co.uk

A new formulation of zolmitriptan has been developed that dissolves on the tongue
without the need for additional fluid intake. In this double-blind, parallel
study, 471 patients were randomized to receive the zolmitriptan orally
disintegrating tablet 2.5 mg (n=231) or matching placebo (n=240) to treat a
single moderate or severe migraine. Headache relief following zolmitriptan 2.5 mg
(63%) was significantly greater than with placebo (22%) at 2 h post-dose (primary
endpoint; P < 0.0001). The zolmitriptan orally disintegrating tablet was also
significantly more effective than placebo for 1-, 2- and 4-h pain-free response
(8% vs. 3%, P=0.0207, 27% vs. 7%, P < 0.0001, and 37% vs. 11%, P < 0.0001,
respectively). Of those patients stating a preference, 70% of patients preferred 
the orally disintegrating tablet to a conventional tablet. Zolmitriptan orally
disintegrating tablets are an effective and convenient alternative to a
conventional tablet, allowing migraine attacks to be treated anytime a migraine
strikes, which can facilitate earlier treatment.

Publication Types: 
    Clinical Trial
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 11972576 [PubMed - indexed for MEDLINE]

3014: Neurology. 2002 Apr 23;58(8):1234-8.

Acute migraine headache: possible sensitization of neurons in the spinal
trigeminal nucleus?

Kaube H, Katsarava Z, Przywara S, Drepper J, Ellrich J, Diener HC.

Institute of Neurology, National Hospital for Neurology and Neurosurgery, London,
UK. holgerk@ion.ucl.ac.uk

OBJECTIVE: To investigate trigeminal sensory processing in patients with migraine
using a novel "nociception-specific" blink reflex. METHODS: Seventeen patients
with unilateral migraine headache were studied within 6 hours of onset. Blink
reflexes were elicited with a standard stimulating electrode (standard blink
reflex) and concentric stimulating electrode (nociception-specific blink reflex) 
during the acute migraine attack, after treatment with IV lysine acetylsalicylate
(1,000 mg) or oral zolmitriptan (5 mg) and interictally. RESULTS: After standard 
stimulation, no differences were detected for the R1 and R2 onset latencies and
areas under the curve (AUC) between the different time points and the headache
and nonheadache side. Nociception-specific stimulation revealed a shortening of
R2 onset latencies (44.3 +/- 5.4 ms for headache side vs 48.9 +/- 5.8 ms for
nonheadache side) during the acute migraine attack compared with the
headache-free interval (49.8 +/- 5.3 vs 49.8 +/- 4.5 ms). The AUC of the R2
increased on the headache side by 680% and on the nonheadache side by 230%
compared with the headache-free interval. Drug treatment parallel to pain relief 
increased the onset latencies (zolmitriptan: 48.0 +/- 8.2 ms for headache side vs
52.3 +/- 7.6 ms for nonheadache side; lysine acetylsalicylate: 48.0 +/- 5.0 ms
for headache side vs 51.2 +/- 5.6 ms for nonheadache side) and reduced the AUC of
R2 (zolmitriptan by 45% and lysine acetylsalicylate by 48%). CONCLUSION: The data
suggest temporary sensitization of central trigeminal neurons during acute
migraine attacks.

Publication Types: 
    Clinical Trial

PMID: 11971092 [PubMed - indexed for MEDLINE]

3015: Neurology. 2002 Apr 23;58(8):1227-33.

Contrasts in cortical magnesium, phospholipid and energy metabolism between
migraine syndromes.

Boska MD, Welch KM, Barker PB, Nelson JA, Schultz L.

Department of Neurology, Henry Ford Hospital, Detroit, MI, USA.

BACKGROUND: Previous single voxel (31)P MRS pilot studies of migraine patients
have suggested that disordered energy metabolism or Mg(2+) deficiencies may be
responsible for hyperexcitability of neuronal tissue in migraine patients. These 
studies were extended to include multiple brain regions and larger numbers of
patients by multislice (31)P MR spectroscopic imaging. METHODS: Migraine with
aura (MWA), migraine without aura (MwoA), and hemiplegic migraine patients were
studied between attacks by (31)P MRS imaging using a 3-T scanner. RESULTS:
Results were compared with those in healthy control subjects without headache. In
MwoA, consistent increases in phosphodiester concentration [PDE] were measured in
most brain regions, with a trend toward increase in [Mg(2+)] in posterior brain. 
In MWA, phosphocreatine concentration ([PCr]) was decreased to a minor degree in 
anterior brain regions and a trend toward decreased [Mg(2+)] was observed in
posterior slice 1, but no consistent changes were found in phosphomonoester
concentration [PME], [PDE], inorganic phosphate concentration ([Pi]), or pH. In
hemiplegic migraine patients, [PCr] had a tendency to be lower, and [Mg(2+)] was 
significantly lower than in the posterior brain regions of control subjects.
Trend analysis showed a significant decrease of brain [Mg(2+)] and [PDE] in
posterior brain regions with increasing severity of neurologic symptoms.
CONCLUSIONS: Overall, the results support no substantial or consistent
abnormalities of energy metabolism, but it is hypothesized that disturbances in
magnesium ion homeostasis may contribute to brain cortex hyperexcitability and
the pathogenesis of migraine syndromes associated with neurologic symptoms. In
contrast, migraine patients without a neurologic aura may exhibit compensatory
changes in [Mg(2+)] and membrane phospholipids that counteract cortical
excitability.

Publication Types: 
    Clinical Trial
    Research Support, U.S. Gov't, P.H.S.

PMID: 11971091 [PubMed - indexed for MEDLINE]

3016: Headache. 2002 Jan;42 Suppl 1:38-43.

Impact of chest pain on cost of migraine treatment with almotriptan and
sumatriptan.

Wang JT, Barr CE, Goldfarb SD.

Global Medical Affairs, Pharmacia Corporation, 100 Route 206 North, Peapack, NJ
07110, USA.

Chest-related symptoms occur with all triptans; up to 41% of patients with
migraine who receive sumatriptan experience chest symptoms, and 10% of patients
discontinue treatment. Thus, the cost of chest pain-related care was estimated in
migraineurs receiving almotriptan 12.5 mg versus sumatriptan 50 mg. A
population-based, retrospective cohort study used data to quantify the incidence 
and costs of chest pain-related diagnoses and procedures. An economic model was
constructed to estimate annual cost savings per 1000 patients receiving
almotriptan versus sumatriptan based on the reported rates of chest pain. Annual 
direct medical cost avoided was calculated for a hypothetical health plan
covering 1 million lives. Among a cohort of 1390 patients, the incidence of chest
pain-related diagnoses increased significantly by 43.6% with sumatriptan
(P=.003). Aggregate costs for chest pain-related diagnoses and procedures
increased from $22,713 to $30,234. Payments for inpatient hospital services,
costs for primary care visits, and costs for outpatient hospital visits increased
by over 100%, 53.1%, and 14.4%, respectively. The model predicted $11,215 in
direct medical cost savings annually per 1000 patients treated with almotriptan
versus sumatriptan. Annual direct medical costs avoided totaled $194,358, and
when applied to recent estimates of 86 million lives currently covered by
almotriptan treatment, translates into an annual cost savings of just under $17
million for chest pain and associated care. Thus, using almotriptan in place of
sumatriptan will likely reduce the cost of chest pain-related care.

Publication Types: 
    Comparative Study

PMID: 11966863 [PubMed - indexed for MEDLINE]

3017: Headache. 2002 Jan;42 Suppl 1:32-7.

Almotriptan increases pain-free status in patients with acute migraine treated in
placebo-controlled clinical trials.

Mathew NT.

Houston, Headache Clinic, 1213 Hermann Drive, Houston, TX 77004, USA.

OBJECTIVES: Evaluate the efficacy of a single oral dose of almotriptan in
achieving pain-free status during treatment of acute migraine attacks. METHODS:
This pooled analysis (N=1321) used data from two randomized, placebo-controlled, 
phase III trials (studies A and B) to determine the proportion of patients with
migraine achieving pain-free status 2 hours after a single oral dose of study
medication (almotriptan or placebo). Pain was assessed using a 4-point integer
scale (0=no headache, 3=severe headache), and recorded in a patient
self-assessment booklet. RESULTS: The proportion of patients pain-free at 2 hours
after study medication was significantly greater with almotriptan 6.25 mg (both
studies P<or=.002) and almotriptan 12.5 mg (both studies P<or=.001) than with
placebo. In study A, 11.6% of patients taking almotriptan 12.5 mg versus 2.5% of 
patients receiving placebo were pain-free at 1 hour (P=.016). At 1.5 hours, 26.8%
of patients taking almotriptan 12.5 mg versus 8.8% receiving placebo (P=.001)
were pain-free, and at 2 hours, 38.4% on almotriptan versus 11.3% on placebo were
pain-free (P<.001). In study B, 23.8% of patients taking almotriptan 12.5 mg were
free from pain at 1.5 hours versus 10.2% receiving placebo (P<.001). At 2 hours, 
39.2% taking almotriptan 12.5 mg versus 15.3% receiving placebo were pain-free
(P<.001). Increases in pain-free status with almotriptan generally occurred in a 
dose-dependent manner. CONCLUSION: Compared with placebo, almotriptan 12.5 mg
significantly increases the proportion of patients who are pain-free by as early 
as 1 hour, and consistently by 1.5 hours, after a single dose.

Publication Types: 
    Meta-Analysis

PMID: 11966862 [PubMed - indexed for MEDLINE]

3018: Headache. 2002 Jan;42 Suppl 1:26-31.

Almotriptan reduces the incidence of migraine-associated symptoms: a pooled
analysis.

Cady R.

Primary Care Network, Springfield, MO 65084, USA.

OBJECTIVES: Evaluate the reduction in migraine-associated symptoms after
administration of a single oral dose of almotriptan. METHODS: This pooled
analysis (N=1773) used data from three randomized, placebo-controlled, phase III 
trials (studies A, B, and C) to determine the incidence of migraine-associated
symptoms (defined as nausea, vomiting, photophobia, and phonophobia) 2 hours
after a single oral dose of study medication (almotriptan, sumatriptan, or
placebo). Outcome data was extracted from studies A and B for placebo and the
almotriptan 6.25-mg and 12.5-mg groups, and from study C for placebo, almotriptan
12.5-mg, and sumatriptan 100-mg groups. RESULTS: The incidence of nausea,
photophobia, and phonophobia at 2 hours after dosing with study medication was
significantly reduced (all P <.05) with almotriptan 6.25 mg or 12.5 mg compared
with placebo. The percentage of patients with vomiting was lower with both doses 
of almotriptan in studies A and B compared with placebo, although differences
were significant only for the 6.25-mg dose in study A (P <.001). For study C, the
incidence of nausea, vomiting, photophobia, and phonophobia was similar for
almotriptan and sumatriptan and lower than with placebo at 2 hours after dosing. 
Significant reductions (all P <.05) versus placebo were observed in the incidence
of vomiting and phonophobia with almotriptan 12.5 mg, and photophobia and
phonophobia with sumatriptan 100 mg. CONCLUSION: Almotriptan provides relief from
migraine-associated symptoms of nausea, vomiting, photophobia, and phonophobia,
and thus represents an attractive treatment option for a wide spectrum of
migraine symptomatology.

Publication Types: 
    Meta-Analysis

PMID: 11966861 [PubMed - indexed for MEDLINE]

3019: Headache. 2002 Jan;42 Suppl 1:10-7.

Clinical benefits of early triptan therapy for migraine.

Pascual J.

Department of Neurology, Hospital Universitario Marqués de Valdecilla, Santander,
Spain.

Although triptans have been proven effective for acute treatment of migraine,
reserving them for moderate or severe pain may produce suboptimal pain relief and
higher rates of recurrence. Recent evidence indicates that early intervention at 
the onset of pain improves outcomes. Post hoc analysis of a long-term, open-label
European study of almotriptan 12.5 mg found that the percentage of attacks
rendered pain-free at 2 hours was significantly greater when patients treated
mild pain (84%) than when the intervention occurred during moderate or severe
pain (53%). A similar pattern emerged with respect to the consistency of pain
relief, with a significant advantage for early intervention (88% versus 56%,
respectively). A difference in favor of early intervention was also seen with
respect to recurrence, need for rescue medication, and adverse events. The
recurrence rate was significantly lower in patients treating mild pain (28%) than
in those delaying treatment until the pain became moderate or severe (33%), which
suggests that achieving pain freedom results in less recurrence. These results
were generally replicated in post hoc analysis of a subgroup of patients from a
randomized, placebo-controlled trial (the Spectrum Study) of oral sumatriptan 50 
mg in migraineurs. This analysis demonstrated that with early intervention, pain 
was less likely to intensify, fewer attacks required redosing, more attacks
remained pain-free 24 hours postdose, and normal function returned more quickly. 
In sum, early intervention with triptans can improve outcomes, avoiding much of
the pain and disability associated with treating moderate or severe attacks.

PMID: 11966859 [PubMed - indexed for MEDLINE]

3020: Headache. 2002 Jan;42 Suppl 1:3-9.

What do patients with migraine want from acute migraine treatment?

Lipton RB, Hamelsky SW, Dayno JM.

Department of Neurology, Albert Einstein College of Medicine, Bronx, NY, USA.

Migraine is a common chronic condition with an ever-expanding therapeutic
armamentarium. As therapeutic options multiply, it is increasingly important to
understand patients' attitudes and preferences regarding various treatment
characteristics. Several strategies have evolved to establish treatment
priorities in migraine and rationalize and prioritize end points and outcomes to 
meet the needs of patients. A survey of a population-based sample of migraineurs 
indicated that an overwhelming majority of patients consider complete relief of
head pain, no recurrence, and rapid onset of action as important or very
important attributes of acute migraine therapy. An analysis of the relationship
between clinical end points and satisfaction found that more than 90% of patients
who were pain-free at 2 hours were at least somewhat satisfied with treatment,
but satisfaction was dependent on relatively rapid relief. Using a
"willingness-to-pay" approach, results indicated that while patients will pay
more for migraine treatment that produces rapid, consistent relief without
adverse effects or recurrence, speed of complete relief is the most valued
attribute. By assessing physician preferences and practices, degree of pain
relief and rapid onset were identified as the most important attributes of acute 
therapy. Based on results from preference studies of triptans, 50% of patients
cited more rapid pain relief as the most important determinant of treatment
preference. Based on these various approaches, the consensus view is that both
clinicians and patients desire a broad range of positive migraine treatment
attributes, but rapid onset of complete pain relief is a particularly important
priority.

PMID: 11966858 [PubMed - indexed for MEDLINE]

3021: J Child Neurol. 2002 Feb;17(2):134-8.

Pseudomigraine with prolonged aphasia in a child with cranial irradiation for
medulloblastoma.

Murthy SN, Cohen ME.

Department of Neurology, SUNY/Buffalo, Children's Hospital of Buffalo, New York
14222, USA. mecohen@acsu.buffalo.edu

We report a 12-year-old child with episodes of migraine-like headaches with
visual and motor auras a year after the surgical resection and radiation therapy 
for medulloblastoma The patient presented with an episode of headache, prolonged 
aphasia, right hemiparesis, status epilepticus, and salt wasting. There was no
evidence of a structural lesion. The neurologic deficits resolved over a period
of 6 weeks. Because of the progressive deterioration in neurologic deficits, the 
patient underwent an extensive battery of laboratory tests and multiple
neuroimages, all of which were normal. The unusually prolonged neurologic deficit
in this patient without demonstrable structural lesions and his eventual complete
recovery were most likely caused by ischemia in the left hemisphere secondary to 
vasospasm. This presentation mimics migraine headache. Evidence suggesting that
this represents a long-term complication of treatment of children with central
nervous system neoplasia is presented.

Publication Types: 
    Case Reports

PMID: 11958186 [PubMed - indexed for MEDLINE]

3022: Neuropharmacology. 2002 Mar;42(4):568-76.

Efficacy of the non-peptide CGRP receptor antagonist BIBN4096BS in blocking
CGRP-induced dilations in human and bovine cerebral arteries: potential
implications in acute migraine treatment.

Moreno MJ, Abounader R, Hébert E, Doods H, Hamel E.

Laboratory of Cerebrovascular Research, Montreal Neurological Institute, McGill
University, 3801 University Street, Montréal, QC, Canada H3A 2B4.

Calcitonin gene-related peptide (CGRP) is a potent vasodilator in brain vessels
and it has been implicated in the pathogenesis of migraine headache. Blocking
post-junctional CGRP receptors, mediators of trigeminal-induced vasodilation, has
been suggested as a potential antimigraine strategy. In this study, we tested the
ability of a new non-peptide CGRP receptor antagonist, BIBN4096BS, to inhibit the
CGRP-induced dilation in human and/or bovine brain vessels and compared it to
that of the antagonist alpha-CGRP(8-37). BIBN4096BS and alpha-CGRP(8-37) both
blocked the alpha-CGRP-induced dilation in bovine middle artery segments with
respective potency (pK(B) values) of 6.3 and 7.8. In human pial vessels,
BIBN4096BS was particularly potent. When tested at 10(-14)-10(-9) M
concentrations, it induced a rightward shift in the alpha-CGRP
concentration-response curve and yielded a biphasic Schild plot suggesting
interaction with more than one receptor population, as was also indicated by the 
significant best fit of the alpha-CGRP-induced dilation in human brain vessels
with a two receptor site interaction. Schild plot analysis in the linear portion 
of the BIBN4096BS inhibition curve revealed interaction with one high affinity
site (pA(2) value approximately 14). In bovine vessels, both alpha-CGRP(8-37) and
BIBN4096BS concentration-dependently reversed a pre-established CGRP-induced
dilation ( approximately 59 and 85%, respectively), BIBN4096BS being
approximately tenfold more potent than alpha-CGRP(8-37) (respective pIC(50)
values of 7.5 and 6.75). In human middle cerebral and middle meningeal arteries, 
BIBN4096BS reversed the alpha-CGRP-induced dilation (> or =70%) by interaction
with two different receptor populations: it exhibited a high affinity for one
population (pIC(50) value approximately 13) and a lower affinity for the other
(pIC(50) value approximately 8). The present data demonstrate that BIBN4096BS is 
a very potent antagonist that could, depending on its bioavailability and in vivo
affinity, be of potential benefit in the acute treatment of migraine headache by 
blocking and/or reversing the CGRP-mediated dilation of intracranial vessels
induced by activation of trigeminovascular afferents.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 11955527 [PubMed - indexed for MEDLINE]

3023: J Psychosom Res. 2002 Apr;52(4):215-22.

Slow cortical potentials in migraine families are associated with psychosocial
factors.

Gerber WD, Stephani U, Kirsch E, Kropp P, Siniatchkin M.

Institute of Medical Psychology, University of Kiel, Neimannsweg 147, Germany.
gerber@med-psych.uni-kiel.de

OBJECTIVE: The aim of the study was the determination of the relationships
between neurophysiological and psychosocial factors within the pathogenesis of
migraine. METHODS: The contingent negative variation (CNV), parent-child
interactions and theirs relationship were investigated in 30 families with a
migraine child and 20 healthy families. RESULTS: (1) None of the groups of
children, independent of diagnosis, differed according to amplitude or
habituation of the CNV. (2) Parents from migraine families exerted significantly 
more control over migraine children compared with interactions with healthy
brothers/sisters. (3) The strong relation between CNV habituation/amplitude and
abnormal pattern of parent-child interactions (especially overwhelming dominance 
and control) was found only for young migraineurs. This relation was not seen in 
healthy families or for healthy siblings of migraine children. CONCLUSION: This
study provides significant evidence for a strong influence of family interactions
on the development and maintenance of neurophysiological abnormalities in the
migraineous headache. The role of psychosocial factors in the etiopathogenesis of
migraine has to be investigated in further studies in more detail.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 11943240 [PubMed - indexed for MEDLINE]

3024: Neurology. 2002 Apr 9;58(7):1066-9.

Transcranial magnetic stimulation of visual area V5 in migraine.

Battelli L, Black KR, Wray SH.

Department of Psychology, Harvard University, Cambridge, MA 02138, USA.
Battelli@wjh.harvard.edu

OBJECTIVE: To examine visual cortical excitability in persons with migraine using
transcranial magnetic stimulation (TMS) over an extrastriate area of the brain,
area V5. BACKGROUND: Previous studies found that persons with migraine have a
lower phosphene threshold than healthy control subjects with TMS delivered over
the primary visual cortical area V1. The result suggests that the occipital
cortex in migraineurs between migraine attacks is hyperexcitable. However, it is 
not known whether interictal cortical hyperexcitability is also present in areas 
of the association visual cortex. METHOD: To investigate this, single-pulse TMS
was delivered over visual area V5, the motion cortex, to 16 persons with migraine
and visual aura, nine migraineurs without visual aura, and 16 healthy control
subjects. TMS was delivered at intensities ranging from 30 to 100% of maximum
stimulator output or until the participant reported seeing phosphenes (visual
illusions characterized by flashes of light). Thresholds to phosphenes were
obtained for each participant using a staircase procedure. RESULT: Significantly 
lower phosphene thresholds for TMS delivered over V5 were found in migraineurs as
compared with control subjects. Qualitatively, the migraineurs' experience of
phosphenes were more vivid, florid, and sustained compared with that of control
subjects. CONCLUSION: Results of this study indicate that hyperexcitability of
the visual cortex in migraine goes beyond visual area V1 and demonstrates for the
first time a significant difference in threshold for excitability of visual area 
V5 in persons with migraine.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 11940694 [PubMed - indexed for MEDLINE]

3025: Eur J Pharmacol. 2002 Mar 29;439(1-3):1-11.

Is the 5-HT(7) receptor involved in the pathogenesis and prophylactic treatment
of migraine?

Terrón JA.

Departamento de Farmacología, Centro de Investigación y de Estudios Avanzados del
Instituto Politécnico Nacional, Apdo. Postal 14-740, Zacatenco 07000, México
D.F., Mexico. jterron@mail.cinvestav.mx

The mechanisms underlying the pathogenesis of migraine and their possible
association with serotonin (5-hydroxytryptamine; 5-HT) have not yet been
elucidated. One of the major obstacles in achieving this goal is the lack of
information on the mechanisms by which the monoamine could possibly trigger
and/or modulate the basic pathophysiological features of the condition, that is, 
cranial vasodilatation and neurogenic inflammation. This information should
provide a useful theoretical framework to insight the nature of the postulated
fundamental triggering mechanism in the brain that ultimately results in head
pain. Novel avenues for research and drug development may be envisaged upon the
recent observations showing that 5-HT is actually able to produce vasodilatation 
of intra- and extra-cranial blood vessels through a mechanism pharmacologically
resembling the 5-HT(7) receptor type, and that the messenger RNA (mRNA) encoding 
for this receptor is highly expressed in cranial vessels. Other lines of evidence
have suggested that the 5-HT(7) receptor may play an excitatory role in neuronal 
systems and that it may be involved in hyperalgesic pain and neurogenic
inflammation. On the basis of these observations, it is proposed that the 5-HT(7)
receptor may well represent a link between the abnormal phenomena of 5-HT
processing and neurotransmission that are observed in migraine patients, and the 
vascular and neurogenic alterations that account for migraine headache. This view
is supported by the fact that most of the migraine prophylactic 5-HT receptor
antagonists display relatively high affinity for the 5-HT(7) receptor, which
significantly correlates with their pharmaceutically active oral doses.

Publication Types: 
    Review

PMID: 11937086 [PubMed - indexed for MEDLINE]

3026: Br J Neurosurg. 2002 Feb;16(1):55-8.

Neurosurgical treatment of short-lasting, unilateral, neuralgiform hemicrania
with conjunctival injection and tearing.

Hannerz J, Linderoth B.

Department of Neurology, Karolinska Hospital, Stockholm, Sweden.

Trigeminal neuralgia solely involving the upper trigeminal nerve branch is rare. 
The SUNCT syndrome (short-lasting, unilateral, neuralgiform hemicrania with
conjunctival injection and tearing) in which the periorbital pain lasts for
60-120 s, and is accompanied by conjunctival injection and tearing is even less
common. Unlike trigeminal neuralgia, SUNCT is usually not relieved by medication.
Three patients with SUNCT were treated with retrogasserian glycerol rhizolysis,
two of them twice. All five treatments provided complete pain relief and the
duration of the effects was 2 to more than 4 years. One of these three patients
also had a third treatment with compression of retroganglionic fibres with a
Fogarthy balloon, according to Mullan, of the upper trigeminal nerve with
excellent results.

Publication Types: 
    Case Reports

PMID: 11926467 [PubMed - indexed for MEDLINE]

3027: Curr Med Res Opin. 2001;17(4):298-309.

Assessing the impact of migraine.

Dowson AJ.

King's Headache Service, King's College Hospital, London, UK.

Migraine is a remarkably disabling condition, although unpredictable and
heterogeneous in frequency, duration and severity. It can be difficult to manage 
in primary care, where it is under-recognised, under-diagnosed and under-treated.
Proposals have been made that migraine care could be improved by incorporating
assessments of migraine impact into management strategies. Research has shown
that measuring headache-related disability, together with assessments of pain
intensity, headache frequency, tiredness, mood alterations and cognition can be
used to assess the impact of migraine on sufferers' lives and society. From this 
research, two simple and brief impact tools were developed: the Migraine
Disability Assessment (MIDAS) Questionnaire and the Headache Impact Test (HIT).
Both tools are scientifically valid measures of migraine severity and have the
potential to improve communication between patients and their physicians, assess 
migraine severity and act as outcome measures to monitor treatment efficacy. Each
of these tools offers its own advantages. For example, HIT was designed for
greater accessibility (on the Internet at www.headachetest.com and
www.amlhealthy.com, and as a paper-based form known as HIT-6) and has a wider
coverage of the spectrum of headache than MIDAS. Impact tools are also being
increasingly recommended as part of generalised headache management guidelines to
produce an individualised treatment plan for each patient in concert with other
clinical assessments. It is not possible as yet to recommend unequivocally the
optimal impact tool for use in primary care, but it should be usable by GPs,
pharmacists, nurses and patients, and for research purposes.

Publication Types: 
    Review

PMID: 11922404 [PubMed - indexed for MEDLINE]

3028: Ann Neurol. 2002 Apr;51(4):507-16.

Nuclear factor-kappaB as a molecular target for migraine therapy.

Reuter U, Chiarugi A, Bolay H, Moskowitz MA.

Stroke and Neurovascular Regulation Laboratory, Radiology Department,
Massachusetts General Hospital, Harvard Medical School, Boston, MA 02129, USA.

Nitric oxide (NO) generated from inducible NO synthase (iNOS) participates in
immune and inflammatory responses in many tissues. The NO donor glyceryl
trinitrate (GTN) provokes delayed migraine attacks when infused into migraineurs 
and also causes iNOS expression and delayed inflammation within rodent dura
mater. Sodium nitroprusside, an NO donor as well, also increases iNOS expression.
Because inflammation and iNOS are potential therapeutic targets, we examined
transcriptional regulation of iNOS following GTN infusion and the consequences of
its inhibition within dura mater. We show that intravenous GTN increases NO
production within macrophages. L-N(6)-(1-iminoethyl)lysine, a selective iNOS
inhibitor, attenuates the NO signal, emphasizing the importance of enzymatic
activity to delayed NO production. iNOS expression is preceded by significant
nuclear factor kappa B (NF-kappaB) activity, as reflected by a reduction in the
inhibitory protein-kappa-Balpha (IkappaBalpha) and activation of NF-kappaB after 
GTN infusion. IkappaBalpha degradation, NF-kappaB activation, and iNOS expression
were attenuated by parthenolide (3mg/kg), the active constituent of feverfew, an 
anti-inflammatory drug used for migraine treatment. These findings suggest that
GTN promotes NF-kappaB activity and inflammation with a time course consistent
with migraine attacks in susceptible individuals. We conclude, based on results
with this animal model, that blockade of NF-kappaB activity provides a novel
transcriptional target for the development of anti-migraine drugs.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 11921057 [PubMed - indexed for MEDLINE]

3029: Ann Neurol. 2002 Apr;51(4):499-506.

Cortical spreading depression and gene regulation: relevance to migraine.

Choudhuri R, Cui L, Yong C, Bowyer S, Klein RM, Welch KM, Berman NE.

Department of Anatomy and Cell Biology, University of Kansas Medical Center,
Kansas City, KS 66160, USA.

Cortical spreading depression (CSD) may be the underlying mechanism of migraine
aura. The role of CSD in initiating a migraine headache remains to be determined,
but it might involve specific changes in gene expression in the brain. To examine
these changes, four episodes of CSD at 5-minute intervals were induced in the
mouse brain by application of 300mM KCl, and gene expression was examined 2 hours
later using cDNA array and reverse transcriptase-polymerase chain reaction.
Controls consisted of groups that received anesthesia only, attachment of
recording electrodes only, and application of 0.9% NaCl. Of the over 1,180 genes 
examined in our experiments, those consistently regulated by CSD included
vasoactive peptides; the vasodilator atrial natriuretic peptide was induced by
CSD, while the vasoconstrictor neuropeptide Y was downregulated. Other genes
specifically regulated by CSD were involved in oxidative stress responses (major 
prion protein, glutathione-S-transferase-5, and apolipoprotein E). L-type calcium
channel mRNA was upregulated. In summary, CSD regulates genes that are intrinsic 
to its propagation, that identify accompanying vascular responses as a potential 
source of pain, and that protect against its potential pathological consequences.
We believe these observations have strong relevance to the mechanisms of migraine
and its outcomes.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 11921056 [PubMed - indexed for MEDLINE]

3030: Compend Contin Educ Dent. 2002 Feb;23(2):105-8, 110, 112-3; quiz 114.

Corrected and republished from:
    Compend Contin Educ Dent. 2001 Dec;22(12):1075-80, 1082; quiz 1084.

Nociceptive trigeminal inhibition--tension suppression system: a method of
preventing migraine and tension headaches.

Shankland WE.

TMJ & Facial Pain Center, Columbus, Ohio, USA.

Dentists and physicians see countless patients suffering from various types of
headaches. Various modes of therapy are used in an attempt to treat these
patients. As a result of this study, it appears that a common factor to migraine 
and tension-type headaches may be chronic clenching. If this is the case, then
dentists may be able to treat headache patients more effectively than previously 
suspected through the use of a dental appliance.

Publication Types: 
    Clinical Trial
    Comparative Study
    Corrected and Republished Article
    Randomized Controlled Trial

PMID: 11915652 [PubMed - indexed for MEDLINE]

3031: Neurology. 2002 Mar 26;58(6):885-94.

Migraine in the United States: epidemiology and patterns of health care use.

Lipton RB, Scher AI, Kolodner K, Liberman J, Steiner TJ, Stewart WF.

Department of Neurology, Albert Einstein College of Medicine, and Headache Unit, 
Montefiore Medical College, Bronx, NY, USA. rlipton@imrinc.com

OBJECTIVE: To determine the prevalence and distribution of migraine in the United
States as well as current patterns of health care use. METHODS: A
random-digit-dial, computer-assisted telephone interview (CATI) survey was
conducted in Philadelphia County, PA, in 1998. The CATI identifies individuals
with migraine (categories 1.1 and 1.2) as defined by the diagnostic criteria of
the International Headache Society with high sensitivity (85%) and specificity
(96%). Interviews were completed in 4,376 subjects to identify 568 with migraine.
Those with 6 or more attacks per year (n = 410) were invited to participate in a 
follow-up interview about health care utilization and family impact of migraine; 
246 (60.0%) participated. RESULTS: The 1-year prevalence of migraine was 17.2% in
females and 6.0% in males. Prevalence was highest between the ages of 30 and 49. 
Whereas 48% of migraine sufferers had seen a doctor for headache within the last 
year (current consulters), 31% had never done so in their lifetimes and 21% had
not seen a doctor for headache for at least 1 year (lapsed consulters). Of
current or lapsed consulters, 73% reported a physician-made diagnosis of
migraine; treatments varied. Of all migraine sufferers, 49% were treated with
over-the-counter medications only, 23% with prescription medication only, 23%
with both, and 5% with no medications at all. CONCLUSION: Relative to prior
cross-sectional surveys, epidemiologic profiles for migraine have remained stable
in the United States over the last decade. Self-reported rates of current medical
consultation have more than doubled. Moderate increases were seen in the
percentage of migraine sufferers who use prescription medications and in the
likelihood of receiving a physician diagnosis of migraine.

Publication Types: 
    Clinical Trial
    Comparative Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 11914403 [PubMed - indexed for MEDLINE]

3032: Ann Otol Rhinol Laryngol. 2002 Mar;111(3 Pt 1):229-36.

Occurrence of familial Meniere's syndrome and migraine in Brasília.

Oliveira CA, Ferrari I, Messias CI.

Department of Otolaryngology, Brasília University Medical School and Institute of
Biology, Brazil.

Since 1941, many families with several members affected by Meniere's syndrome
have been described. "Migraine-like" headache was always mentioned. In 1997, we
described a large family with Meniere's syndrome and migraine, both transmitted
in an autosomal dominant mode. Recently, a gene that could be responsible for
Meniere's symptoms has been identified. However, the incidence of familial
Meniere's syndrome is still unknown. A. W. Morrison et al estimated this
incidence as between 2.9% and 12%. During the years 1997 and 1998, we saw 8 new
patients with typical Meniere's syndrome in our outpatient department. They were 
referred to Dr Messias, who did a careful search for other affected family
members. Six of them had relatives with Meniere's syndrome and migraine
transmitted in an autosomal dominant mode. The familial incidence of Meniere's
syndrome and migraine in Brasília seems to be higher than the figures of Morrison
et al for the United Kingdom. The 6 families are described herein.

PMID: 11913683 [PubMed - indexed for MEDLINE]

3033: J Child Neurol. 2002 Jan;17(1):80-1.

Hemiplegic migraine with prolonged symptoms: case report.

Serdaroglu G, Tütüncüoglu S, Calli C, Sarioglu B, Korkmaz H.

Department of Pediatrics, Division of Child Neurology, Ege University Faculty of 
Medicine, Izmir, Turkey. gul.s@turk.net

Hemiplegic migraine is defined by the occurrence of migraine during attacks of
unilateral weakness. Neurologic symptoms last for 15 to 60 minutes in most cases.
Attacks usually start in childhood, adolescence, or early adulthood. Diagnosis
may be delayed if there is no relevant family history. A 16-year-old girl who was
diagnosed with hemiplegic migraine presenting with prolonged left hemiparesis is 
reported. The importance of this case is that the pediatrician will also consider
migraine in the differential diagnosis of a child presenting with hemiparesis
even if there is no previous headache and family history.

Publication Types: 
    Case Reports

PMID: 11913583 [PubMed - indexed for MEDLINE]

3034: Brain. 2002 Apr;125(Pt 4):912-22.

Effects of repetitive transcranial magnetic stimulation on visual evoked
potentials in migraine.

Bohotin V, Fumal A, Vandenheede M, Gérard P, Bohotin C, Maertens de Noordhout A, 
Schoenen J.

Department of Neurology, University of Liège, Liège, Belgium.

Between attacks, migraine patients are characterized by potentiation instead of
habituation of stimulation-evoked cortical responses. It is debated whether this 
is due to increased or decreased cortical excitability. We have studied the
changes in visual cortex excitability by recording pattern-reversal visual evoked
potentials (PR-VEP) after low- and high-frequency repetitive transcranial
magnetic stimulation (rTMS), known respectively for their inhibitory and
excitatory effect on the cortex. In 30 patients (20 migraine without, 10 with
aura) and 24 healthy volunteers, rTMS of the occipital cortex was performed with 
a focal figure-of-eight magnetic coil (Magstim). Nine hundred pulses were
delivered randomly at 1 or 10 Hz in two separate sessions. Stimulus intensity was
set to the phosphene threshold or to 110% of the motor threshold if no phosphenes
were elicited. Before and after rTMS, PR-VEP were averaged sequentially in six
blocks of 100zztieresponses during uninterrupted 3.1 Hz stimulation. In healthy
volunteers, PR-VEP amplitude was significantly decreased in the first block after
1 Hz rTMS and the habituation normally found in successive blocks after sustained
stimulation was significantly attenuated. In migraine patients, 10 Hz rTMS was
followed by a significant increase of first block PR-VEP amplitude and by a
reversal to normal habituation of the potentiation (or dishabituation)
characteristic of the disorder. This effect was similar in both forms of migraine
and lasted for at least 9 min. There were no significant changes of PR-VEP
amplitudes after 1 Hz rTMS in migraineurs and after 10 Hz rTMS in healthy
volunteers, nor after sham stimulation. The recovery of a normal PR-VEP
habituation pattern after high-frequency rTMS is probably due to activation of
the visual cortex and the dishabituation in healthy volunteers to cortical
inhibition. We conclude, therefore, that the deficient interictal PR-VEP
habituation in migraine is due to a reduced, and not to an increased,
pre-activation excitability level of the visual cortex.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 11912123 [PubMed - indexed for MEDLINE]

3035: Headache. 2002 Mar;42(3):227-9.

Migraine and Raynaud phenomenon: possible late complications of Kawasaki disease.

Constantinescu CS.

Division of Clinical Neurology, University Hospital, Queen's Medical Centre,
Nottingham, UK.

Migraine and Raynaud phenomenon often coexist and may reflect similar vascular
reactions. Both have been associated with vascular endothelial cell dysfunction. 
Kawasaki disease is a systemic vasculitis of unknown etiology that affects
children and may lead to the formation of coronary artery aneurysms. Endothelial 
cell dysfunction has been demonstrated late in Kawasaki disease and is not
restricted to coronary vessels. We report the case of a patient who developed
typical migraine with aura and Raynaud phenomenon at the age of 14, 12 years
after onset of Kawasaki disease. His migraine responded well to pizotifen, and
both migraine and Raynaud phenomenon improved after initiation of treatment with 
valproic acid. We postulate that both migraine and Raynaud phenomenon in this
case represent late consequences of Kawasaki disease and result from
extracoronary endothelial dysfunction.

Publication Types: 
    Case Reports

PMID: 11903548 [PubMed - indexed for MEDLINE]

3036: Headache. 2002 Mar;42(3):204-16.

Primary headaches: a convergence hypothesis.

Cady R, Schreiber C, Farmer K, Sheftell F.

Headache Care Center, Springfield, MO 65804, USA.

After reviewing the historic differentiation between migraine and tension-type
headache, the authors note that the similarities between these two types of
primary headaches outweigh the differences, and so hypothesize that these
headaches share a common pathophysiology. The convergence hypothesis for primary 
headaches links the clinical features of an evolving headache to current
pathophysiological models. The authors suggest that successive symptoms
experienced clinically reflect an escalating pathophysiological process,
beginning with the premonitory period and progressing into tension-type headache 
and, if uninterrupted, finally into migraine. The clinical manifestations of
other headache types, such as so-called sinus headache or temporomandibular
headache, may also be explained by this model. A convergence hypothesis for
primary headaches has important implications for earlier recognition, diagnosis, 
and treatment.

Publication Types: 
    Review

PMID: 11903544 [PubMed - indexed for MEDLINE]

3037: Headache. 2002 Mar;42(3):200-3.

Potential validity of conducting research on headache in internet populations.

Lenert LA, Looman T, Agoncillo T, Nguyen M, Sturley A, Jackson CM.

Department of Medicine, University of California, San Diego, CA, USA.

OBJECTIVE: While it is technically feasible to conduct migraine research on the
Internet, can one be sure that the subjects who participate actually have the
disorder? We examined this issue in 109 sequential subjects in an Internet study 
of migraineurs' symptoms. BACKGROUND: The increasing use of the Internet by the
US population provides an opportunity for using this medium in clinical research,
but, to be useful, the results of such research must be valid and generalizable. 
METHODS: Using postings to Internet newsgroups of migraineurs, we recruited
subjects to a migraine research site. We examined reported symptoms by comparing 
them with the International Headache Society's criteria for diagnosis of migraine
and by subjective review by a neurologist. We also attempted to contact the
subject's primary care physicians to confirm their diagnosis. RESULTS: We found
considerable evidence for the validity of the participants' self-reported
diagnoses. Most subjects with professed migraine reported quality of pain (97%)
and associated symptoms (92%) consistent with that diagnosis, and review of their
symptoms and questionnaire responses by the neurologist suggested that almost all
subjects (97%) had migraine. Personal physicians confirmed a diagnosis of
migraine in 90% of consenting subjects (n=49). CONCLUSIONS: The validity of
self-reported diagnosis of migraine does not appear to be an obstacle to
conducting research in subject populations on the Internet.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Validation Studies

PMID: 11903543 [PubMed - indexed for MEDLINE]

3038: Headache. 2002 Mar;42(3):185-93.

Prevalence of menstrually related migraine and nonmigraine primary headache in
female students of Belgrade University.

Dzoljic E, Sipetic S, Vlajinac H, Marinkovic J, Brzakovic B, Pokrajac M, Kostic
V.

Institute of Neurology, School of Medicine, University of Belgrade, Belgrade,
Yugoslavia.

OBJECTIVES: To determine prevalence and characteristics of menstrually related
migraine and nonmigraine headache in female students of Belgrade University.
METHODS: A questionnaire was administered to female students during randomly
selected classes of the Schools of Medicine and Pharmacy. Diagnoses were assigned
according to the criteria of the International Headache Society and MacGregor's
stricter definition of "menstrual" migraine. RESULTS: Of 1943 female students (18
to 28 years old), 1298 (66.8%) had primary headaches. Among 1298 students with
headache, 245 (12.6%) had migraine and 1053 (54.2%) had nonmigraine headache. The
prevalence rates of migraine versus nonmigraine headache in relation to the
menstrual cycle were: premenstrual, 0.9% versus 4.4%; menstrual, 1.5% versus
1.5%; menstrually associated, 6.1% versus 10.1%; menstrually unchanged, 2.7%
versus 19.2%; and menstrually unrelated, 1.4% versus 18.9%. Female students with 
migraine had menstrually related attacks more frequently than students with
nonmigraine headache (67.7% versus 29.5%). This difference was most prominent
among students with menstrual migraine compared with students with menstrual
nonmigraine headache (12.2% versus 2.7%). Exacerbation of migraine during
menstruation was slightly more severe and more complex than exacerbation of
nonmigraine headache. Female students with migraine versus nonmigraine headache
did not differ significantly in age, age at onset of menarche, or age at onset of
headache. Female students with migraine were significantly more likely to report 
a positive family history for migraine and menstrual migraine, severe attacks,
reduced work activity, and aura. CONCLUSION: The results obtained are in accord
with the prevailing opinion that there is a relationship between migraine and
female sex hormones, and suggest that women with nonmigraine headache are also
susceptible to hormonal fluctuations.

PMID: 11903541 [PubMed - indexed for MEDLINE]

3039: Headache. 2002 Mar;42(3):178-84.

Coping style and social support in men and women suffering from cluster headache 
or migraine.

Blomkvist V, Hannerz J, Katz L, Theorell T.

National Institute for Psychosocial Factors and Health, Stockholm, Sweden.

OBJECTIVE: To investigate similarities and differences between patients with
cluster headache and patients with migraine. BACKGROUND: Patients with migraine
and patients with cluster headache are considered, by many clinical neurologists,
to be different psychologically and socially. METHODS: Twenty-five age-matched
pairs of men and 24 age-matched pairs of women with either migraine or episodic
cluster headache (men aged 31 to 62 years; mean, 47 years; women aged 23 to 72
years; mean, 44 years) were compared with regard to coping profiles as reflected 
in two "coping wheels," one for the present situation and one for the future. In 
addition, availability of attachment and social interaction was assessed by means
of the ISSI (Interview Schedule for Social Interaction). RESULTS: Women with
cluster headache anticipated fewer activities for themselves than women with
migraine, and findings were similar in the male pairs. The men with cluster
headache also anticipated significantly fewer activities for themselves in the
present and with others in the present and in the future than the men with
migraine. There was no significant difference as to emotional loading between the
two groups. A tendency to more optimistic anticipation was found in the women
with cluster headache. There were highly significant differences between the two 
groups in the "future" wheel. The group with migraine expected more concrete
activities and more activities with their families in the future, and they also
described their present situation to involve more activities with others.
CONCLUSIONS: Results from the present study differ from those from studies
utilizing more conventional questionnaires. In particular, we found that patients
with cluster headache have fewer close social contacts than patients with
migraine.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 11903540 [PubMed - indexed for MEDLINE]

3040: Headache. 2001 Nov-Dec;41 Suppl 1:S18-24.

Antiepileptic drugs in migraine prevention.

Mathew NT.

University of Texas Medical School and Houston Headache Clinic, Houston, TX
77004, USA.

Migraineurs may continue to experience attacks, despite daily use of one or more 
agents from a wide range of drugs, including beta-blockers, calcium channel
blockers, serotonin antagonists, tricyclic antidepressants, monoamine oxidase
inhibitors, and antiepileptic agents. Divalproex sodium is the only antiepileptic
drug approved for migraine prevention. Gabapentin, topiramate, and other
antiepileptic agents are being evaluated for migraine prevention and treatment.
Prospective, double-blind, placebo-controlled clinical trials of divalproex,
gabapentin, and topiramate for migraine prevention generally were composed of a
prospective baseline period, a dose titration period, and a fixed-dose treatment 
period. The primary efficacy variable was a reduction in the 28-day frequency of 
migraine headache. Patients receiving divalproex for 12 weeks at doses up to 1500
mg/day achieved significant decreases in the migraine frequency (P<.05),
corresponding to reductions of 30% to 40% compared with baseline. Nearly half of 
the divalproex-treated patients had a 50% or more reduction from baseline in
headache frequencies (P< or =.05). Asthenia, vomiting, somnolence, tremor, and
alopecia were common adverse events associated with divalproex. Significant
reductions in migraine frequency were also observed with gabapentin (1800 to 2400
mg/day) when compared with placebo (P<.01), and nearly half of all patients
treated at the highest dose experienced a reduction in headache rate of 50% or
more. Somnolence was the most commonly reported adverse event among the
gabapentin-treated patients. Two single-center, double-blind, placebo-controlled 
clinical trials evaluated topiramate for migraine prevention. A lower 28-day
migraine frequency was seen during 18 weeks of administration at a maximum daily 
dose of 200 mg (P =.09). In a second study, a significantly lower mean 28-day
migraine frequency was observed during 16 weeks of treatment with topiramate (P
=.0015). Mean reduction in migraine frequency was also significantly greater in
topiramate-treated patients (P =.0037). Paresthesias, diarrhea, somnolence, and
altered taste were commonly reported adverse events in the topiramate-treated
patients. Unlike some patients given divalproex or gabapentin, some given
topiramate reported weight loss. Large, double-blind, placebo-controlled trials
may prove the effectiveness of novel antiepileptic drugs in migraine prevention.

Publication Types: 
    Review

PMID: 11903536 [PubMed - indexed for MEDLINE]

3041: Headache. 2001 Nov-Dec;41 Suppl 1:S11-7.

Shared mechanisms and comorbidities in neurologic and psychiatric disorders.

Silberstein SD.

Department of Neurology, Jefferson Medical College and Jefferson Headache Clinic,
Philadelphia, PA 19107, USA.

Migraine may be comorbid with several other neurologic and psychiatric
conditions, including mood disorders (eg, depression, anxiety, panic disorder),
epilepsy, stroke, and essential tremor. Comorbidity presents physicians with
opportunities and challenges for both diagnosis and treatment. All diseases must 
be considered, and therapeutic strategies may need to be modified to avoid
potential drug interactions. Comorbidities also may provide clues to the
pathophysiologies and any shared mechanisms of the two disorders. Longitudinal
studies have demonstrated a bidirectional influence between migraine and major
depression, but not between migraine and other severe headache. Migraine is
strongly and consistently associated with panic disorder. The risk of migraine in
epilepsy is increased particularly in individuals with head trauma, partial
seizures, and a positive family history of migraine. The influence is
bidirectional. There is also growing evidence of an association between migraine 
and stroke, particularly among women of childbearing age and individuals who
experience migraine with aura. Lastly, a bidirectional association between
migraine and essential tremor also exists. These findings suggest that migraine, 
major depression, epilepsy, and essential tremor share one or more common
etiologies. Clinicians should be mindful of them as they design treatment
strategies, and also should consider the use of a single pharmacologic agent that
is effective for all conditions.

Publication Types: 
    Review

PMID: 11903535 [PubMed - indexed for MEDLINE]

3042: Headache. 2001 Nov-Dec;41(10):981-4.

Triptans in the treatment of basilar migraine and migraine with prolonged aura.

Klapper J, Mathew N, Nett R.

Colorado Neurology and Headache Center, Denver, CO 80218, USA.

OBJECTIVE: To report on the use of triptans in migraine with prominent neurologic
symptoms. BACKGROUND: As stated in their package inserts, the triptans are
contraindicated in patients with basilar or familial hemiplegic migraine, and
physicians are reluctant to prescribe these drugs to other patients with
prominent or prolonged aura. METHODS: We evaluated 13 patients with basilar
migraine, familial hemiplegic migraine, or migraine with prominent or prolonged
aura who had received triptans. RESULTS: Excellent; no adverse events.
CONCLUSION: The contraindication of triptans in basilar migraine should be
reconsidered. Similarly, prominent or prolonged aura may not represent a
reasonable contraindication to triptan therapy.

Publication Types: 
    Case Reports

PMID: 11903526 [PubMed - indexed for MEDLINE]

3043: Headache. 2001 Nov-Dec;41(10):976-80.

Comparison of intravenous valproate versus intramuscular dihydroergotamine and
metoclopramide for acute treatment of migraine headache.

Edwards KR, Norton J, Behnke M.

Western New England Pain and Headache Center, Southwestern Vermont Medical
Center, Bennington, VT 05201, USA.

OBJECTIVE: To determine the effectiveness and tolerability of intravenous
valproate for the acute treatment of migraine headache with or without aura
(International Headache Society diagnostic criteria 1.1 and 1.2) compared with
intramuscular metoclopramide 10 mg followed 10 minutes later by intramuscular
dihydroergotamine 1 mg. BACKGROUND: Divalproex sodium is approved for prophylaxis
of migraine headache. We studied the possible effectiveness of intravenous sodium
valproate for the treatment of acute migraine headache. Valproate offers a
treatment option for patients with migraine who recently have used a triptan or
dihydroergotamine, theoretically avoiding the risk of drug interactions or
cardiovascular complications. DESIGN/METHODS: In an open-label randomization,
patients with an established diagnosis of migraine with or without aura were
administered either intravenous valproate or intramuscular dihydroergotamine with
metoclopramide to treat moderate-to-severe migraine headache of 24 to 96 hours'
duration. Forty patients alternately received either 500 mg intravenous valproate
or 10 mg metoclopramide intramuscularly followed by 1 mg dihydro- ergotamine.
Patients rated severity of headache and the presence or absence of nausea,
photophobia, or phonophobia at baseline, and at 1, 2, 4, and 24 hours. RESULTS:
With intravenous valproate, 50% of patients reported headache improvement from
moderate or severe to none or mild at 1 hour following treatment, 60% reported
such improvement at 2 hours, 60% at 4 hours, and 60% at 24 hours. Corresponding
improvement rates for dihydroergotamine were 45% at 1 hour, 50% at 2 hours, 60%
at 4 hours, and 90% at 24 hours. Intravenous valproate and intramuscular
dihydroergotamine provided similar relief from associated migrainous symptoms
(nausea, photophobia, and phonophobia) during the first 4 hours following
treatment. While none of the patients who received intravenous valproate
experienced drug-related side effects during treatment, 15% of patients who took 
dihydroergotamine experienced one or more episodes of nausea and diarrhea during 
the first 4 hours of treatment. CONCLUSIONS: Intravenous valproate is similar in 
effectiveness to dihydroergotamine/metoclopramide as abortive therapy for
prolonged moderate-to-severe acute migraine headache. Although the results were
not statistically significant (P =.3635), intravenous valproate appears to offer 
a safe, effective, and well-tolerated treatment for patients with acute migraine.
Relative to dihydroergotamine/metoclopramide, however, headache relief was not as
likely to be sustained at 24 hours as with intravenous valproate.

Publication Types: 
    Clinical Trial
    Comparative Study
    Randomized Controlled Trial

PMID: 11903525 [PubMed - indexed for MEDLINE]

3044: Headache. 2001 Nov-Dec;41(10):968-75.

Topiramate in migraine prevention: a double-blind, placebo-controlled study.

Storey JR, Calder CS, Hart DE, Potter DL.

Upstate Neurology Consultants, Albany, NY, USA.

OBJECTIVE: To evaluate the efficacy of topiramate in the preventative treatment
of episodic migraine. BACKGROUND: Topiramate is a broad-spectrum antiepileptic
drug effective for treatment of multiple seizure types in adults and children.
Antiepileptic agents have demonstrated efficacy in migraine prevention, and
open-label experience from our clinic has suggested that topiramate might be
effective for this use. We consequently conducted a single-center, double-blind, 
placebo-controlled trial to evaluate the efficacy and safety of topiramate for
the preventative treatment of migraine. METHODS: Forty patients, aged 19 to 62
years (mean, 38.2 years), were randomly assigned in a 1:1 ratio to receive
topiramate (n = 19; all women) or placebo (n = 21; 20 women, 1 man). Following a 
prospective baseline phase of 4 weeks, the study drug dose was titrated weekly in
25-mg increments over 8 weeks to 200 mg per day or to the maximum tolerated dose.
The titration phase was followed by an 8-week maintenance phase. RESULTS: During 
the entire double-blind phase, topiramate-treated patients experienced a
significantly lower 28-day migraine frequency (3.31 +/- 1.7 versus 3.83 +/- 2.1; 
P =.002) compared to placebo, irrespective of use of concomitant migraine
prevention medications. The mean 28-day migraine frequency was reduced by 36% in 
patients receiving topiramate as compared with 14% in patients receiving placebo 
(P =.004). Twenty-six percent of the patients on topiramate and 9.5% of the
patients on placebo achieved a 50% reduction in migraine frequency (P >.05). The 
mean dose of topiramate was 125 mg per day (range, 25 to 200 mg per day).
Topiramate was well tolerated; 2 of 19 topiramate-treated patients discontinued
treatment due to adverse events. Adverse effects that occurred more frequently in
topiramate-treated patients included paresthesia, weight loss, altered taste,
anorexia, and memory impairment. CONCLUSIONS: Preventative therapy with
topiramate significantly reduced migraine frequency. Larger multicenter clinical 
studies may further delineate the role of topiramate in migraine prevention.

Publication Types: 
    Clinical Trial
    Comparative Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 11903524 [PubMed - indexed for MEDLINE]

3045: Cephalalgia. 2001 Nov;21(9):906-10.

Dose, efficacy and tolerability of long-term indomethacin treatment of chronic
paroxysmal hemicrania and hemicrania continua.

Pareja JA, Caminero AB, Franco E, Casado JL, Pascual J, Sánchez del Río M.

Department of Neurology, Fundación Hospital Alcorcón, Juan Carlos I University,
Madrid, Spain. JAPareja@fhalcorcon.es

Indomethacin has consistently been proven to provide complete and sustained
relief of symptoms in hemicrania continua (HC) and chronic paroxysmal hemicrania 
(CPH), but is not devoid of side-effects. The goal of this retrospective study is
to assess the dose and side-effects of prolonged indomethacin treatment of HC and
CPH. Twenty-six patients with either HC or CPH were followed during an average of
3.8 years after onset of treatment with indomethacin. Relief of symptoms occurred
within 3 days of treatment, with 84 +/- 32 mg/day of indomethacin. With time, 42%
of patients experienced a decrease of up to 60% in the dose of indomethacin
required to maintain a pain-free state. Six (23%) patients showed adverse events,
mostly gastrointestinal and relieved with ranitidine. No major side-effects were 
observed. These results indicate that prolonged indomethacin treatment of HC or
CPH has a good safety and tolerability profile with a reduction of up to 60% in
the initial dose.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 11903285 [PubMed - indexed for MEDLINE]

3046: Cephalalgia. 2001 Nov;21(9):900-5.

Prevalence and clinical features of migraine in a population of visually impaired
subjects in Curitiba, Brazil.

Kowacs PA, Piovesan EJ, Lange MC, Werneck LC, Tatsui CE, Ribas LC, Scapucin L,
Marques LE, Moreira AT.

Division of Neurology, Hospital de Clínicas da Universidade Federal do Paraná,
Curitiba, Brazil. cefaleia@hc.ufpr.br

To investigate the relevance of lacking or diminished visual input on the
expression of migraine, we evaluated its prevalence and clinical features in a
population of visually impaired subjects. Between September 1999 and April 2000, 
203 visually impaired subjects with a headache inventory were surveyed. Those
with headache were assessed according to IHS criteria for the presence of
migraine. Migraineurs had their symptoms further detailed through an interview
and a headache diary. Of the 104 subjects reporting headaches during the last 6
months, 29 had migraine (14.2%). The prevalence of migraine was not influenced by
whether the visual impairment was complete or partial. Mean frequency of migraine
attacks was 2.7/month. Most subjects (96%) reported severe and/or moderate
attacks. Nausea, vomiting, aggravation by activity and phonophobia were reported 
by 62%, 37.9%, 86.2% and 96.6% of the subjects, respectively. Visual impairment
does not seem to influence prevalence of migraine or its clinical features.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 11903284 [PubMed - indexed for MEDLINE]

3047: Cephalalgia. 2001 Nov;21(9):894-9.

The prevalence of migraine in patients with bipolar and unipolar affective
disorders.

Fasmer OB.

Department of Psychiatry, University of Bergen, Bergen, Norway.
ole.fasmer@psyk.uib.no

There is a well-known association between migraine and affective disorders, but
the information is sparse concerning the prevalence of migraine in subgroups of
the affective disorders. The present study was undertaken to investigate the
prevalence of migraine in unipolar depressive, bipolar I and bipolar II
disorders. Patients with major affective disorders (n = 62), consecutively
admitted to an open psychiatric ward, were examined with a semi-structured
interview based on DSM-IV diagnostic criteria, combined with separate criteria
for affective temperaments. Diagnosis of unipolar and bipolar I disorders
followed the DSM-IV criteria, while bipolar II disorder encompassed patients with
either discrete hypomanic episodes or a cyclothymic temperament. Migraine was
diagnosed according to IHS-criteria. Symptoms of migraine were found to be common
in these patients, both in those with unipolar depression (46% prevalence of
migraine) and in those with bipolar disorders (44% prevalence). Among the bipolar
patients there was, however, a striking difference between the two diagnostic
subgroups, with a prevalence of 77% in the bipolar II group compared with 14% in 
the bipolar I group (P = 0.001). These results support the contention that
bipolar I and II are biologically separate disorders and point to the possibility
of using the association of bipolar II disorder with migraine to study both the
pathophysiology and the genetics of this affective disorder.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 11903283 [PubMed - indexed for MEDLINE]

3048: Cephalalgia. 2001 Nov;21(9):874-7.

Comment in:
    Cephalalgia. 2001 Nov;21(9):869-72.

Hemicrania continua: diagnostic criteria and nosologic status.

Pareja JA, Vincent M, Antonaci F, Sjaastad O.

Hospital Ruber Internacional, Servicio de Neurología, Madrid, Spain.
jpg03m@nacom.es

Proposals for the diagnostic criteria for hemicrania continua (HC) and also for
the nosological status of HC are set forth. The clinical constellation of
symptoms and signs making up HC consists of: unilaterality without side shift;
absolute indomethacin effect; and long-lasting repetitive attacks of varying
duration, eventually with a chronic pattern, the pain being mild to severe. For
the typical clinical picture of HC, including a positive 'indotest', we propose
the term hemicrania continua vera. More or less analogous, but
'indotest-negative' clinical pictures have provisionally been termed hemicrania
generis incerti (of undetermined nature). At the present level of knowledge, the 
diagnosis of hemicrania generis incerti should be made mostly by exclusion. HC
may possibly best be classified along with chronic paroxysmal hemicrania (CPH) as
this is the only other headache absolutely responsive to indomethacin. The bond
between these two headaches on the one hand and cluster headache on the other
should, at most, be a loose one. Interrelationships of these four classifiable
headaches are briefly discussed.

PMID: 11903280 [PubMed - indexed for MEDLINE]

3049: Curr Neurol Neurosci Rep. 2001 Mar;1(2):125-32.

Acute treatment of migraine and the role of triptans.

Freitag FG.

Diamond Headache Clinic, 467 W. Deming Place, Suite 500, Chicago, IL 60614, USA. 
dhcdoc@aol.com

The use of triptans has improved the ability to treat migraine successfully
compared with older treatments. Speed of relief, consistency of effect, and good 
tolerability have been the hallmarks of these agents. All of the currently
available triptans have comparable efficacy and tolerability. Variables between
the agents may lead to one agent or dose form being preferred over another in
various clinical scenarios. The triptans that are forthcoming may improve on
these options through enhanced efficacy rates, tolerability, and headache
recurrence rates. There exist increasing options for migraine treatment that may 
further improve the clinical effects of the older and newer triptans through
early treatment of migraine at the stages of mild migraine pain, or even during
the prodromal phase of the attack. Additionally, recent work suggests that
mini-prophylaxis of migraine at the menses is a highly successful treatment
option with the triptans. In this age of managed care, providing cost-effective
treatment of headache will take on increasing importance. Techniques such as
stratification of acute treatments may enhance cost-effective care, whereas ready
availability of the triptans may lead to significant improvements in utilization 
of parameters such as office visits, emergency room treatment, and even
hospitalization.

Publication Types: 
    Review

PMID: 11898508 [PubMed - indexed for MEDLINE]

3050: Curr Neurol Neurosci Rep. 2002 Mar;2(2):108-13.

Hemicrania continua: recent treatment strategies and diagnostic evaluation.

Peres MF.

Sao Paulo Headache Center, Rua. Maestro Cardim 887, Sao Paulo, 01323-001, Brazil.
marioperes@yahoo.com

Hemicrania continua (HC) is a primary headache disorder that is characterized by 
a continuous unilateral headache of moderate severity, exacerbations of severe
pain, and complete responsiveness to indomethacin. HC was once thought to be a
rare headache disorder, but now many cases have been reported. It is an
underecognized headache syndrome. HC can be of continuous or remitting form.
Variants such as hemicrania continua with aura have been described, and secondary
cases may occur. Indomethacin is the best treatment, although HC could respond to
other nonsteroidal anti-inflammatory drugs, such as the selective
cyclo-oxygenase-2 inhibitors.

Publication Types: 
    Review

PMID: 11898476 [PubMed - indexed for MEDLINE]

3051: Neurology. 2002 Mar 12;58(5):802-5.

Comment in:
    Neurology. 2003 Aug 12;61(3):425; author reply 425.

Trochleitis and migraine headache.

Yangüela J, Pareja JA, Lopez N, Sánchez Del Río M.

Department of Ophthalmology, Fundación Hospital Alcorcón, Juan Carlos I
University, Madrid, Spain. jyanguela@fhalcorcon.es

Idiopathic trochleitis is a cause of superimposed ocular pain in patients with
migraine. Trochleitis usually presents as an orbital pain without obvious ocular 
signs. Like greater occipital neuralgia, trochleitis may sustain or trigger the
pain of chronic migraine. Diagnosis is confirmed by peritrochlear steroid
injection, which produces a quick relief of periocular symptoms and may improve
headache control.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 11889246 [PubMed - indexed for MEDLINE]

3052: Pharmacoeconomics. 2002;20(2):91-100.

Cost-effectiveness analysis of stratified versus stepped care strategies for
acute treatment of migraine: The Disability in Strategies for Care (DISC) Study.

Sculpher M, Millson D, Meddis D, Poole L.

Centre for Health Economics, University of York, Heslington, York, United
Kingdom.

BACKGROUND: The Disability in Strategies for Care (DISC) study was the first
large randomised controlled trial to compare alternative treatment strategies in 
the acute treatment of migraine. With 835 patients in its intention-to-treat
efficacy analysis, DISC compared a stratified care strategy, where initial
therapy was based on clinical need as determined by the Migraine Disability
Assessment Scale (MIDAS) and two stepped care strategies (across attacks and
within attacks), where first-line therapy with a simple combination analgesic was
escalated, if response had been inadequate, to zolmitriptan, a migraine-specific 
therapy. OBJECTIVE: To report on the cost effectiveness of these three strategies
from a societal perspective. STUDY DESIGN AND METHODS: A cost-effectiveness
analysis was undertaken using data from the DISC study, and including both health
service and productivity costs. Data were collected prospectively on drug usage
(main therapy and rescue medication); resource use associated with adverse events
was estimated by a clinician blinded to treatment strategy. Health service
resource use was costed using UK unit costs (1999 to 2000 values). Data were
collected using diary cards on the amount of time patients lost from work, and on
reduced effectiveness at work, due to a migraine attack. This facilitated an
estimate of the productivity costs associated with the treatment strategies. To
assess cost effectiveness, the differences in costs between the strategies were
related to the two primary outcome measures in the trial: headache response 2
hours after initial therapy and disability-adjusted time during the first 4 hours
after initial therapy. RESULTS: Although the mean health service cost was higher 
in the stratified care group (mean over 6 attacks of pound 28.25 versus pound
11.74 and pound 23.15 in the stepped care across attacks group and within attacks
group, respectively), mean productivity costs over 6 attacks were lower in the
stratified group (pound 112.22 versus pound 144.70 and pound 127.53). The total
mean cost over six attacks was, therefore, lowest in the stratified care group
(pound 138.95 compared with pound 157.19 in the stepped care across attacks group
and pound 148.53 in the stepped care within attacks group), although these
differences did not reach statistical significance. In terms of headache
response, stratified care was statistically significantly more effective than
both forms of stepped care. Using disability-adjusted time, stratified care was
statistically significantly more effective than stepped care across attacks, but 
not against stepped care within attacks. CONCLUSION: Given its lower mean costs
and higher mean effectiveness, a stratified care strategy, which included
zolmitriptan, was the dominant strategy and was unequivocally more cost effective
from a societal perspective than either stepped care strategy. When the
uncertainty around these means was considered, stratified care had the highest
probability of being cost effective.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 11888361 [PubMed - indexed for MEDLINE]

3053: CNS Drugs. 2002;16(3):181-96.

Assessing the efficacy of drugs for the acute treatment of migraine: issues in
clinical trial design.

Ramadan NM.

Eli Lilly & Company, and Indiana University School of Medicine, Indianapolis,
Indiana 46285, USA. ramadan_nabih@lilly.com

Clinical trials of therapies for acute migraine attacks have evolved over the
years from open-label, small observational studies to highly structured
randomised, controlled trials. The International Headache Society Committee on
Clinical Trials in Migraine developed a tool to guide in designing scientifically
sound trials. The proof of effect is best achieved in a clinical trial with:
clearly defined objectives;a well-characterised study population, identified
using well-validated diagnostic tools;proper randomisation and blinding;inclusion
of a placebo arm, with proper balancing of patients receiving placebo and those
receiving active drug;adequate study power; and appropriate statistical methods. 
Both parallel and crossover studies may be suitable in clinical trials of
antimigraine agents, although the latter are a better choice in patient
preference and bioequivalence studies. Although various efficacy measures are
used to assess treatment effect, the 2-hour pain free rate (total resolution of
pain within 2 hours after an initial moderate to severe headache) is preferred
because it is clinically relevant and is relatively 'placebo-insensitive'.
Various migraine surveys have indicated that a rapid onset of therapeutic effect 
is a highly desirable attribute of an antimigraine drug. Therefore, accurate
measurements of treatment effect before 2 hours are becoming increasingly
emphasised. Consistency of effect across multiple attacks adds to the
understanding of the therapeutic efficacy of a test drug. Finally, preference and
satisfaction studies allow us to assess patients' global impression of a
particular treatment, weighing the positive effects on pain and associated
symptoms of migraine against potential adverse effects.

Publication Types: 
    Review

PMID: 11888339 [PubMed - indexed for MEDLINE]

3054: Mayo Clin Proc. 2002 Mar;77(3):255-61.

Comment in:
    Mayo Clin Proc. 2002 Aug;77(8):876; author reply 876-7.

Diagnosis and treatment of migraine.

Cady R, Dodick DW.

Headache Care Center, Primary Care Network, Springfield, MO 65804, USA.
rcady@primarycarenet.org

Despite recent advances in understanding the pathophysiology and treatment of
migraine, considerable uncertainty remains surrounding the diagnosis and
treatment of this disorder. This uncertainty is reflected in studies that show
both underdiagnosis and undertreatment of migraine. While the diagnosis can be
assisted by criteria from the International Headache Society, other approaches
may be useful in clinical practice. Treatment of migraine must be based on an
individualized patient strategy that integrates education, patient participation,
and effective use of pharmacological interventions. Many patients, despite
self-treatment with simple analgesics, continue to suffer considerable disability
associated with their migraines. Triptans, which are more effective at relieving 
migraine symptoms and maintaining patient function than are nonspecific
therapies, are used in only a minority of patients with migraine. Treatment goals
of rapid, complete relief with no recurrence and minimal adverse effects can be
achieved when effective therapy is matched to individual patient goals. For
prophylaxis, anticonvulsant drugs emerging as effective options are being added
to the armamentarium with traditional compounds such as tricyclic antidepressants
and beta-blockers.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 11888029 [PubMed - indexed for MEDLINE]

3055: Compend Contin Educ Dent. 2001 Dec;22(12):1075-80, 1082; quiz 1084.

Corrected and republished in:
    Compend Contin Educ Dent. 2002 Feb;23(2):105-8, 110, 112-3; quiz 114.

Nociceptive trigeminal inhibition--tension suppression system: a method of
preventing migraine and tension headaches.

Shankland WE.

TMJ & Facial Pain Center, Columbus, Ohio, USA.

Dentists and physicians see countless patients suffering from various types of
headaches. Various modes of therapy are used in an attempt to treat these
patients. As a result of this study, it appears that a common factor to migraine 
and tension-type headaches may be chronic clenching. If this is the case, then
dentists may treat headache patients more effectively than previously suspected
through the use of a dental appliance.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial

PMID: 11887670 [PubMed - indexed for MEDLINE]

3056: Panminerva Med. 2002 Mar;44(1):27-31.

Food and headache attacks. A comparison of patients with migraine and
tension-type headache.

Savi L, Rainero I, Valfrè W, Gentile S, Lo Giudice R, Pinessi L.

Neurology III, Headache Center, Department of Neuroscience, University of Turin, 
Turin, Italy. lsavi@molinette.piemonte.it

BACKGROUND: The role of foods as headache precipitants is still matter of debate.
Several studies reported that dietary constituents may precipitate migraine
attacks. Some authors reported that also tension type headache attacks may be
provoked by foods. The purpose of this study was to evaluate the role of foods as
headache triggers in both groups of patients. METHODS: We compared the role of
foods as headache trigger in patients with migraine and tension type headache.
Three hundred and nine patients were involved in the study and divided into six
groups: 1) migraine without aura, 2) migraine with aura, 3) episodic tension type
headache, 4) chronic tension type headache, 5) migraine without aura associated
with episodic tension type headache, 6) migraine without aura associated with
chronic tension type headache. RESULTS: Approximately one third of the patients
reported susceptibility to certain foods. The percentage of food sensitivity was 
not significantly different between patients with migraine or tension type
headache. The foods more commonly reported as headache triggers were alcoholic
drinks, chocolate and cheese. No difference in specific food sensitivity between 
groups was found. The comparison of food-sensitive with food non-sensitive
patients showed no significant difference in the clinical features. CONCLUSIONS: 
Our study suggests that foods may trigger not only migraine but also tension type
headache attacks.

Publication Types: 
    Comparative Study

PMID: 11887088 [PubMed - indexed for MEDLINE]

3057: Acta Neurol Scand. 2002 Mar;105(3):189-95.

Classic risk factors, hypercoagulability and migraine in young women with
cerebral lacunar infarctions.

Salobir B, Sabovic M, Peternel P, Stegnar M, Grad A.

Department of Vascular Diseases, University Clinical Center, Ljubljana, Slovenia.

OBJECTIVE: Lacunar cerebral infarctions (LACI) in young women is a rare condition
which pathogenesis is still not fully recognized. We explored the presence of
classic risk factors, hypercoagulability and migraine in young women with LACI.
METHODS: Charts of 192 consecutive premenopausal women suffering cerebrovascular 
insult [125 (65%) haemorhagic, 58 (30%) ischaemic and 9 (5%) unclassified] during
a period of 5 years were reviewed. Sixteen out of 58 (27%) patients with
ischaemic stroke were identified to have LACI and included in a study. RESULTS:
Ten and seven out of 16 LACI women had at least one classical risk factor
(hypertension, hyperlipidaemia, smoking or oral contraceptives) or migraine,
respectively. LACI patients had slight hypercoagulable state indicated by shorter
thrombin and thromboplastin times, higher fibrinogen and higher t-PA antigen than
47 age matched controls (all P < 0.05). In addition in LACI patients with
migraine the trend toward more pronounced hypercoagulable state in comparison to 
LACI patients without migraine was found. The combination of migraine, at least
one classic risk factor and hypercoagulability was present in 5/16 (31.25%) of
patients. CONCLUSIONS: The combination of slightly to moderately expressed
classic risk factors, hypercoagulability and migraine might be a risk profile for
LACI in young women. Further studies are needed to clarify risk profile, rather
than isolated risk factors, for LACI in a specific group as young women are.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 11886363 [PubMed - indexed for MEDLINE]

3058: J Sch Nurs. 2001 Jun;17(3):120-5.

"Nurse, my head hurts": a review of childhood headaches.

Kolar KR, Fisher W, Gordon V.

Department of Women's and Children's Health, School of Nursing, University of
Mississippi Medical Center, Jackson, MS, USA.

Headache, a frequent occurrence during childhood, can have a number of
etiologies. Most headaches are benign, but all require appropriate assessment.
Common types include sinusitis, migraine, and muscle contraction (tension).
Headache assessment includes both history and physical examination. The headache 
history consists of the history of present illness, past history, family history,
and environmental and social history. Physical examination begins with general
observation and vital sign measurement and proceeds to specific inspection of the
head, neck, and facial structures. The nursing interventions carried out are
dependent on the interpretation of assessment findings. Pharmacologic
interventions, commonly acetaminophen or ibuprofen, may be appropriate if pain
management protocols exist. Nonpharmacologic strategies for headache relief
include reassurance, rest, ingestion of simple and complex carbohydrate foods,
relaxation exercises, or home care. Children with migraine headaches benefit from
specific interventions, and children exhibiting headache warning signs should
have emergency measures instituted.

Publication Types: 
    Comparative Study
    Review

PMID: 11885441 [PubMed - indexed for MEDLINE]

3059: Eur J Neurol. 2002 Mar;9(2):171-4.

Epidemiological aspects of headache in a workplace setting and the impact on the 
economic loss.

Pop PH, Gierveld CM, Karis HA, Tiedink HG.

St Elisabeth Hospital, Merseloseweg 130, 5801 CE Venray, The Netherlands.
PHMPOP@KNMG.NL

The objective of this study was to assess the epidemiological aspects of headache
in a workplace setting and the economical impact. By sending a questionnaire to
1781 employees of a Dutch manufacturing company we tried to assess the prevalence
of headache and headache subtype within this working place. Besides the personal 
view of each responder regarding his/her headache subtype, the International
Headache Society (IHS) criteria were used to classify headaches on the basis of
reported features. Moreover the missing labour days, as a result of headache,
during the previous 4 weeks were measured, as well as the loss of productivity at
the working place during an episode of headache; from this an estimate of the
economic loss could be calculated. The response rate of the questionnaire was
60.8%. The lifetime prevalence of headache amongst the responders was 53.3%. Of
these, 34.5% thought their headache was tension-type headache, 10.6% thought it
was migraine, 5.4% mentioned daily headache, and 18.2% mentioned another type of 
headache. According to the IHS criteria the differentiation was somewhat
different: 26.2% of the headache could be classified as tension-type headache and
15% as migraine. When the costs for lost labour days and loss of productivity as 
a result of all types of headache were accumulated, the economic loss was
estimated at 18.933 US dollars in 4 weeks (for the group of responders). In
conclusion, headache is related to a substantial economic loss; migraine is
probably underestimated in a workplace setting.

PMID: 11882058 [PubMed - indexed for MEDLINE]

3060: J Neurosci. 2002 Mar 1;22(5):RC213.

P/Q-type calcium-channel blockade in the periaqueductal gray facilitates
trigeminal nociception: a functional genetic link for migraine?

Knight YE, Bartsch T, Kaube H, Goadsby PJ.

Headache Group, Institute of Neurology, London, WC1N 3BG, United Kingdom.

The discovery of mis-sense mutations in the alpha1A subunit of the P/Q-type
calcium channel in patients with familial hemiplegic migraine indicates the
potential involvement of dysfunctional ion channels in migraine. The
periaqueductal gray (PAG) region of the brainstem modulates craniovascular
nociception and, through its role in the descending pain modulation system, may
contribute to migraine pathophysiology. In this study we sought to investigate
the possible link between the genetic mutations found in migraineurs and the PAG 
as a modulator of craniovascular nociception. We microinjected the P/Q-type
calcium-channel blocker omega-agatoxin IVA into the rat ventrolateral PAG
(vlPAG). We examined its effect on the nociceptive transmission of second-order
neurons recorded in the trigeminal nucleus caudalis and activated by stimulation 
of the parietal dura mater. After injection of agatoxin into the vlPAG (n = 20)
responses to dural stimulation were facilitated by 143% (p < 0.0001) for
Adelta-fiber activity and 180% for C-fiber activity (p < 0.05). Similarly,
spontaneous background activity increased by 163% (p < 0.0001). These results
demonstrate that P/Q-type calcium channels in the PAG play a role in modulating
trigeminal nociception and suggest a role for dysfunctional P/Q-type calcium
channels in migraine pathophysiology.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 11880534 [PubMed - indexed for MEDLINE]

3061: Pediatrics. 2002 Mar;109(3):460-72.

Comment in:
    ACP J Club. 2002 Nov-Dec;137(3):113.

The usefulness of children's drawings in the diagnosis of headache.

Stafstrom CE, Rostasy K, Minster A.

Departments of Pediatrics and Neurology, Division of Pediatric Neurology,
Floating Hospital for Children, New England Medical Center, Tufts University
School of Medicine, Boston, Massachusetts, USA. stafstrom@neurology.wisc.edu

OBJECTIVE: To determine whether drawings can aid in the differential diagnosis of
headaches in children. METHODS: Before taking any history, 226 children who were 
seen consecutively for the evaluation of headache were asked to draw a picture to
show how their headache felt. The pictures were then scored as migraine or
nonmigraine by pediatric neurologists who were blinded to the clinical history. A
clinical diagnosis of headache type was determined independently by another
pediatric neurologist using the usual history and examination. The diagnoses of
headache type based on the pictures drawn and the clinical findings obtained were
then compared to calculate the sensitivity, specificity, and predictive values of
the drawings for the diagnosis of migraine. RESULTS: Children produced dramatic
and insightful headache drawings. Compared with the clinical diagnosis (gold
standard), headache drawings had a sensitivity of 93.1%, a specificity of 82.7%, 
and a positive predictive value (PPV) of 87.1% for migraine. That is, drawings
that contained an artistic feature consistent with migraine (eg, pounding pain,
nausea/vomiting, desire to lie down, periorbital pain, photophobia, visual
scotoma) predicted the clinical diagnosis of migraine in 87.1% of cases.
Predictive values were also calculated for specific migraine-associated features 
on drawings: artistic depiction of focal neurologic signs, periorbital pain,
recumbency, visual symptoms (photophobia, scotomata), or nausea/vomiting had a
PPV of >90% for migraine; severe or pounding pain had a PPV of >80% for migraine.
Band-like pain was not predictive of migraine (PPV of 11.1%). Features on
drawings such as sadness or crying did not differentiate migraine from
nonmigraine headaches. CONCLUSIONS: Children's headache drawings are a simple,
inexpensive aid in the diagnosis of headache type, with a very high sensitivity, 
specificity, and predictive value for migraine versus nonmigraine headaches. We
encourage the use of drawings in the evaluation of any child with a headache, as 
an adjunct to the clinical history and physical examination.

Publication Types: 
    Evaluation Studies

PMID: 11875142 [PubMed - indexed for MEDLINE]

3062: Curr Pain Headache Rep. 2002 Apr;6(2):162-7.

Do over-the-counter medications for migraine hinder the physician?

Tonore TB, King DS, Noble SL.

University of Mississippi Medical Center, Department of Family Medicine, 2500
North State Street, Jackson, MS 39216, USA. ttonore@familymed.umsmed.edu

The availability of many over-the-counter drugs that were formerly prescription
medications enable patients with migraine to self-medicate easily and delay entry
into the appropriate medical management. The potential for adverse effects, drug 
interactions, and analgesic rebound headaches can often be complications that
hinder treatment. Over-the-counter products force the patient to employ a less
effective step-care approach as opposed to evidence-based guidelines.

PMID: 11872189 [PubMed - indexed for MEDLINE]

3063: Curr Pain Headache Rep. 2002 Apr;6(2):156-61.

Do over-the-counter medications help the physician manage migraine headache?

Freitag FG.

Diamond Headache Clinic, 467 West Deming Place, Chicago, IL 60614-1726, USA.
dhcdoc@aol.com

The use of over-the-counter-medication in migraine treatment is commonplace. They
are often used in addition to physician-prescribed medications and may be used
without the full knowledge of the physician. Although considerable evidence
suggests their efficacy in migraine treatment, they are rarely used to maximal
levels of efficacy and safety. A review of the evidence for these treatments is
important for cost effective, well-tolerated, and specific treatment of migraine 
headache.

Publication Types: 
    Comparative Study
    Review

PMID: 11872188 [PubMed - indexed for MEDLINE]

3064: Cerebrovasc Dis. 2002;13(2):102-6.

Patent foramen ovale, a possible cause of symptomatic migraine: a study of 74
patients with acute ischemic stroke.

Sztajzel R, Genoud D, Roth S, Mermillod B, Le Floch-Rohr J.

Department of Neurology, Neurosonology Unit, Geneva, Switzerland.
Roman.Sztajzel@hcuge.ch

Recent studies reported an increased prevalence of patent foramen ovale (PFO) in 
patients with migraine with aura (MA+). To investigate the possible relationship 
between MA+ and paradoxical embolism, we studied the prevalence of both
conditions. Investigation of PFO was undertaken in 74 consecutive patients
presenting with an acute stroke of undetermined origin. The patients were
questioned about MA+ or migraine without aura (MA-) according to the criteria of 
the International Headache Society. Follow-up was performed to investigate the
evolution of MA+ and MA- according to different treatments of stroke. PFO was
found in 44 of 74 patients, 16 of whom had MA+ (36%), compared to 4 (13%) MA+
patients without PFO (p = 0.03). Of 25 patients in whom the PFO was considered to
play a causal role in the stroke, 13 (52%) had MA+, whereas only 3 (16%) of 19
patients in whom PFO was considered unrelated had MA+ (p = 0.014). Thirty-nine of
the patients with MA+ and MA- were studied over a mean follow-up of 13 months.
Seven of 15 patients with MA+ and PFO, treated either with surgical closure or
anticoagulants, noticed complete disappearance of MA+ attacks. The prevalence of 
MA+ is high among stroke patients with PFO. In patients with a high presumption
of paradoxical embolism, the proportion of MA+ is increased, and this suggests a 
possible role of this association in the occurrence of the cerebrovascular event.
Forty-seven percent of patients with PFO and MA+ reported complete suppression of
their aura attacks after surgical closure or anticoagulant treatment. This
finding suggests that at least in some patients, MA+ attacks may be due to
paradoxical embolism. Copyright 2002 S. Karger AG, Basel

Publication Types: 
    Comparative Study

PMID: 11867883 [PubMed - indexed for MEDLINE]

3065: Expert Opin Pharmacother. 2002 Mar;3(3):237-48.

Pharmacoeconomic evidence and considerations for triptan treatment of migraine.

Caro JJ, Getsios D.

Caro Research Institute, 336 Baker Avenue, Concord, MA, USA.
jcaro@caroresearch.com

The 5-hydroxytriptamine (5-HT)(1B/1D) agonists (i.e., the triptans) are highly
effective in migraine but their high cost relative to other treatments
necessitates careful analysis of their cost-effectiveness. The majority of
pharmacoeconomic evaluations, nearly all of which deal with sumatriptan, indicate
that from the societal perspective triptans are dominant: health outcomes are
improved while the overall cost of migraine is reduced. However, the results are 
more ambiguous from the perspective of the health care payer: reductions in
non-drug medical costs are unlikely to offset fully the high drug cost. Thus far,
few analyses have explicitly included quality of life (QOL) in their analyses and
pharmacoeconomic analyses comparing the different triptans are scant. More
research is required in these areas.

Publication Types: 
    Review

PMID: 11866674 [PubMed - indexed for MEDLINE]

3066: J Am Osteopath Assoc. 2002 Feb;102(2):92-4.

Divalproex sodium in the treatment of migraine and cluster headaches.

Gallagher RM, Mueller LL, Freitag FG.

University Headache Center, Moorestown, NJ 08057-1550, USA.

The discovery of a new class of effective migraine-abortive medications, the
triptans, has sparked a new interest in the study of vascular headache. Over the 
past few years, the Food and Drug Administration (FDA) has approved six new
abortive pharmacologic therapies, with several others in various stages of
clinical trials. Unfortunately, concurrent pharmacologic changes in headache
prophylaxis have not kept pace with their abortive counterparts. However,
divalproex sodium (Depakote), which is approved by the FDA as a migraine
prophylactic agent, is the first in the anticonvulsant class of medication for
migraine headache and has expanded the options in headache treatment. The
objective of this retrospective multicenter study of 284 patients with migraine
or cluster headaches was to examine the clinical efficacy and safety of
divalproex sodium as prophylaxis in monotherapy and in polytherapy. Sixty-one
percent of migraineurs and 73% of cluster patients noted a decrease in pain with 
divalproex sodium and continued that therapy for more than 3 months. Reported
negative side effects included weight gain, nausea, somnolence, tremor, alopecia,
dysequilibrium, and rash. However, only 14% of subjects discontinued therapy due 
to these side effects. Overall, divalproex sodium was found to be an effective
and generally well-tolerated prophylactic treatment option as monotherapy or in
polytherapy for migraine and cluster headache.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 11866398 [PubMed - indexed for MEDLINE]

3067: Am J Manag Care. 2002 Feb;8(3 Suppl):S94-101.

Comment in:
    Am J Manag Care. 2002 Aug;8(8):693-4; author reply 694-5.

Almotriptan versus sumatriptan in migraine treatment: direct medical costs of
managing adverse chest symptoms.

Mannix LK, Adelman JU, Goldfarb SD, Von S, Kozma CM.

Headache Wellness Center, Greensboro, North Carolina, USA.

OBJECTIVE: Triptans, a popular class of drugs for treatment of migraine
headaches, can cause adverse events including chest symptoms. This study
estimated the direct medical costs of managing chest symptoms in patients treated
for acute migraine with almotriptan or sumatriptan using an economic model.
METHODS: The economic model of this study combined data from a randomized
clinical trial that compared almotriptan with sumatriptan and data from a
practice pattern survey of physicians. The pertinent clinical evaluation period
was the time immediately after administration of the first medication dose. The
model was developed from the perspective of a managed care payer. RESULTS: The
average direct medical cost of managing chest symptoms that appeared after the
first dose of an oral triptan was $0.22 for patients treated with almotriptan and
$1.64 for patients treated with sumatriptan, a difference of $1.42 per patient.
CONCLUSION: Relative to sumatriptan, treatment with almotriptan is likely to
reduce patient care costs associated with chest symptom adverse events.

Publication Types: 
    Clinical Trial
    Comparative Study
    Randomized Controlled Trial
    Review

PMID: 11859910 [PubMed - indexed for MEDLINE]

3068: Am J Manag Care. 2002 Feb;8(3 Suppl):S85-93.

Health outcomes evaluations: estimating the impact of almotriptan in managed care
settings.

Mayo KW, Osterhaus JT.

Pharmacia Corporation, Peapack, New Jersey, USA.

OBJECTIVE: Almotriptan, a new treatment for acute migraine attacks, may improve
health outcomes while reducing expenditures on drug costs and the costs
associated with unwanted adverse events. This article describes the clinical,
humanistic, and economic data available for almotriptan and compares these data
with published data for sumatriptan, which is considered the gold standard
comparator for triptans. PATIENTS AND METHODS: Clinical trial data and published 
materials describing the pharmacoeconomics of sumatriptan were reviewed. RESULTS:
Formulary and prescribing decision makers consider clinical, humanistic, and
economic dimensions when evaluating migraine treatments. Within those dimensions,
critical elements to consider include efficacy, tolerability, health-related
quality of life, patient satisfaction, productivity, medication cost, and
healthcare resource use. In direct comparisons, almotriptan has demonstrated
efficacy, short-term health-related quality of life, and productivity results
similar to sumatriptan 50 mg. Almotriptan also has an improved tolerability
profile compared with sumatriptan, including a lower incidence of drug-related
adverse events, a lower incidence of chest pain, and better patient satisfaction 
in terms of adverse events. CONCLUSIONS: Almotriptan and sumatriptan exhibit
comparable efficacy for the treatment of acute migraine. The acquisition cost of 
almotriptan is lower than sumatriptan, and given its excellent tolerability
profile, almotriptan may be preferred by patients for the treatment of migraine
attacks.

Publication Types: 
    Comparative Study
    Review

PMID: 11859909 [PubMed - indexed for MEDLINE]

3069: Am J Manag Care. 2002 Feb;8(3 Suppl):S80-4.

Economic comparison of oral triptans for management of acute migraine:
implications for managed care.

Reeder CE, Steadman S, Goldfarb SD.

College of Pharmacy, University of South Carolina, Columbia, USA.

Sound, informed decision making regarding which drugs to include on a formulary
should be based on the best available evidence of their clinical efficacy and
incidence of adverse events. Comparative drug costs and clinical effectiveness
should also be considered during the formulary development process. Clinical
trials traditionally evaluate efficacy and adverse events independently, whereas 
effectiveness in real-life conditions is defined as some combination of efficacy 
and side effects. When evaluating similar medications, head-to-head efficacy and 
effectiveness studies are preferred. For oral triptans (serotonin 5-HT(1B,1D)
receptor agonists), there are many placebo-controlled trials and several active
trials that compare newer oral triptans with sumatriptan; however, there have
been few comparisons of triptans in head-to-head trials. Meta-analysis is an
appropriate method to evaluate multiple clinical trials critically and combine
the results. A recently published meta-analysis used patient-level data to assess
efficacy and adverse events across multiple triptan clinical trials. In this
analysis, we combined those results with medication costs to assess the overall
value among oral triptans. Using this combined approach, almotriptan was found to
have the greatest economic value. It delivers comparable efficacy, placebo-like
tolerability, and the highest value when compared with other triptans currently
marketed in the United States.

Publication Types: 
    Comparative Study
    Review

PMID: 11859908 [PubMed - indexed for MEDLINE]

3070: Am J Manag Care. 2002 Feb;8(3 Suppl):S74-9.

Almotriptan: a review of pharmacology, clinical efficacy, and tolerability.

Von S.

Clinical Research Headache Wellness Center, Greensboro, North Carolina, USA.

OBJECTIVE: This article summarizes preclinical and clinical data for almotriptan.
METHODS: Almotriptan has been evaluated in more than 3,500 acute migraine
patients in phase 2 and 3 double-blind, randomized trials and in 1,500 patients
in long-term open-label trials. RESULTS: Controlled clinical trials show that
almotriptan 12.5 mg is significantly more effective than placebo. These results
are observed across different endpoints examined, including pain relief at 2
hours, pain-free outcome at 2 hours, recurrence rate, use of escape medication,
and sustained pain-free outcome. The onset of pain relief is observed as early as
30 minutes after administration. Results from a multiple-attack study show that
almotriptan maintains a consistency of response across 3 attacks, and results
from long-term studies confirm that patients continue to respond to almotriptan
for up to 1 year. Results from 2 comparative studies show that almotriptan 12.5
mg has comparable efficacy to sumatriptan 50 or 100 mg, but almotriptan has a
superior tolerability profile. Early use of almotriptan results in a higher
proportion of patients achieving pain relief or complete freedom from pain.
CONCLUSIONS: Because almotriptan has a tolerability profile comparable to that of
placebo, it may be more acceptable for early administration. The incidence of
treatment-related adverse events with almotriptan is comparable to that of
placebo and significantly lower than recorded with sumatriptan. In addition,
almotriptan has a low incidence of chest symptoms, an adverse event associated
with triptan use. Because of its comparable efficacy and superior tolerability
profile, almotriptan offers a potential improvement over existing triptans for
the treatment of acute migraine.

Publication Types: 
    Review

PMID: 11859907 [PubMed - indexed for MEDLINE]

3071: Am J Manag Care. 2002 Feb;8(3 Suppl):S58-73.

Migraine: diagnosis, management, and new treatment options.

Gallagher RM, Cutrer FM.

University of Medicne and Dentistry of New Jersey, School of Medicine, Stratford,
USA.

OBJECTIVE: The safety and tolerability of medications used to treat acute
migraine attacks are summarized, the classification of headaches and the causes
of and diagnostic criteria for migraine are reviewed, and the clinical
tolerability profiles and therapeutic benefits of second-generation triptans are 
presented. BACKGROUND: Migraine is a paroxysmal disorder characterized by attacks
of headache, nausea, vomiting, photophobia, and phonophobia. Drugs used to
prevent migraine and those that effectively treat acute migraine attacks are
readily available. METHODS: Mild or moderate migraines are often treated with
aspirin, acetaminophen, nonsteroidal anti-inflammatory drugs, antiemetic drugs,
or isometheptene. Triptans (5-HT1 receptor agonists) are used to treat moderate
or severe migraine and when nonspecific medications have been ineffective.
Because sumatriptan, the first triptan used, is effective but can induce adverse 
events, second-generation triptans (zolmitriptan, naratriptan, rizatriptan, and
almotriptan) were developed to increase the benefit-to-risk ratio in migraine
management. RESULTS: Important pharmacologic, pharmacokinetic, and clinical
differences exist among those drugs, but the tolerability profile of the newer
triptans is very good, and they provide rapid relief from headache and sustained 
duration of effect. CONCLUSION: Primary care physicians must manage migraine
patients with treatments that demonstrate a balance between efficacy and
tolerability.

Publication Types: 
    Review

PMID: 11859906 [PubMed - indexed for MEDLINE]

3072: Am J Manag Care. 2002 Feb;8(3 Suppl):S102-7.

Comment in:
    Am J Manag Care. 2002 Aug;8(8):693-4; author reply 694-5.

Cost savings in migraine associated with less chest pain on new triptan therapy.

Wang JT, Barr CE, Torigoe Y, Wang E, Rowland CR, Goldfarb SD.

Pharmacia Corporation, Peapack, New Jersey, USA.

OBJECTIVES: This article constructs an economic model to estimate cost of
chest-pain-related care in migraine patients receiving almotriptan 12.5 mg
compared with those receiving sumatriptan 50 mg. STUDY DESIGN: This
population-based, retrospective cohort study used data from the MEDSTAT
Marketscan database (Ann Arbor, Michigan) to quantify incidence and costs of
chest-pain-related diagnoses and procedures. After a 6-month exclusion period,
the study used a pre-post design, with baseline and treatment periods defined,
respectively, as 5 months before and after receiving sumatriptan therapy. An
economic model was constructed to estimate annual cost savings per 1,000 patients
receiving almotriptan instead of sumatriptan as a function of differing rates of 
chest pain. Annual direct medical cost avoided was calculated for a hypothetical 
health plan covering 1 million lives. RESULTS: Among a cohort of 1,390 patients, 
the incidence of chest-pain-related diagnoses increased significantly (43.6%)
with sumatriptan, from 110 during the baseline period to 158 during the treatment
period (P= .003). Aggregate costs for chest-pain-related diagnoses and procedures
increased 33.1%, from $22,713 to $30,234. Payments for inpatient hospital
services rose 10-fold; costs for primary care visits and outpatient hospital
visits rose 53.1% and 14.4%, respectively. Payments for angiography increased
from $0 to $462, and costs for chest radiographs and electrocardiograms increased
58.7% and 31.2%, respectively. Sumatriptan treatment was associated with a 3-fold
increase in payments for services for painful respiration and other chest pain.
The model predicted $11,215 in direct medical cost savings annually per 1000
patients treated with almotriptan instead of sumatriptan. Annual direct medical
costs avoided for the health plan totaled $195,913. CONCLUSION: Using almotriptan
instead of sumatriptan will likely reduce the cost of chest-pain-related care for
patients with migraine headaches.

Publication Types: 
    Comparative Study

PMID: 11859905 [PubMed - indexed for MEDLINE]

3073: Arch Ophthalmol. 2002 Feb;120(2):154-61.

Short-wavelength sensitivity deficits in patients with migraine.

McKendrick AM, Cioffi GA, Johnson CA.

Discoveries in Sight, Devers Eye Institute, Legacy Clinical Research and
Technology Center, 1225 NE Second Ave, PO Box 3950, Portland, OR 97208-3950, USA.

OBJECTIVE: To examine short-wavelength sensitivity in patients with migraine
using short-wavelength automated perimetry (SWAP) and Stiles 2-color increment
threshold procedures. METHODS: Twenty-five subjects with migraine with (n = 11)
and without (n = 14) aura and 20 age-matched headache-free subjects underwent
testing. All subjects underwent standard automated perimetry (SAP) and SWAP
(using a Humphrey field analyzer; 24-2 presentation pattern). In 2 migraine
patients (one with and another without aura), the 2-color increment threshold
procedure was used to determine whether sensitivity losses were specific to
short-wavelength sensitivity pathways or a generalized loss to multiple pathways.
RESULTS: No statistically significant differences between migraine patients and
controls were found for mean deviation (MD) or pattern-standard deviation (PSD)
for SAP. However, for SWAP, MD and PSD were worse for the migraine group (P
=.04). Twelve migraine patients had more than 4 locations with sensitivity worse 
than the 5% probability level (reference value). Increment threshold
determinations in the 2 selected migraine patients indicated a selectively
greater loss for short-wavelength sensitivity mechanisms. CONCLUSIONS:
Approximately 50% of subjects with migraine (with or without aura) demonstrate
SWAP sensitivity losses, at times between migraine events. These findings, in
conjunction with previous results for SAP and flicker perimetry, suggest that
migraine patients should be excluded from normative databases of visual function,
and warrant further investigations of the relationship between migraine and
glaucoma.

Publication Types: 
    Research Support, U.S. Gov't, P.H.S.

PMID: 11831917 [PubMed - indexed for MEDLINE]

3074: Complement Ther Nurs Midwifery. 2000 Aug;6(3):138-42.

Migraine and photic stimulation: report on a survey of migraineurs using
flickering light therapy.

Noton D.

Forest Institute, Petaluma, California 94952, USA.

Users of a commercial light therapy device who were using it to treat migraine
were surveyed prospectively to determine what results they obtained after 30 days
of daily use. Out of a total of 55 migraineurs, 44% reported that the frequency
of their migraine attacks after the treatment was 'Somewhat Less' or 'Much Less' 
(under a conservative interpretation of these categories). Considering only the
28 migraineurs who stated that their migraine attacks were normally preceded by
warning signs, 53% reported that the frequency of their migraine attacks was
'Somewhat Less' or 'Much Less'. In view of the limited efficacy and undesirable
side-effects of the available migraine preventive drugs, photic stimulation
(flickering light therapy) must be considered a possible preventive treatment for
migraine.

Publication Types: 
    Clinical Trial

PMID: 11858471 [PubMed - indexed for MEDLINE]

3075: Clin Excell Nurse Pract. 2000 Jan;4(1):41-9.

Quality of life and locus of control of migraineurs.

Allen LL, Haririfar M, Cohen J, Henderson MJ.

Kaiser Permanente Emergency Department, and Rotacare, San Jose, California, USA. 
dhallen@ix.netcom.com

Advanced practice nurses (APNs) are essential primary healthcare providers
actively engaged in health promotion, illness prevention, and the management of
acute and chronic diseases. The purpose of this study was to measure the quality 
of life and locus of control (LOC) among three different groups of migraineurs. A
retrospective quantitative study was conducted using Ferrans and Powers' (1985)
Quality of Life Index and Martin, Holroyd, and Penzien's (1990) Headache Specific
Locus of Control questionnaire. The analysis of 79 adult migraineurs indicated
that those who received headache education had a higher quality of life and
higher external LOC scores than those without the intervention. This study's
findings reinforce the notion that disease-specific education is an effective
practice intervention. APNs can positively affect the quality of life for
migraineurs by providing an educational intervention as part of high-quality,
accessible, and cost-effective primary care.

Publication Types: 
    Comparative Study

PMID: 11858296 [PubMed - indexed for MEDLINE]

3076: Eur Neurol. 2002;47(2):99-107.

Efficacy, tolerability and safety of oral eletriptan and ergotamine plus caffeine
(Cafergot) in the acute treatment of migraine: a multicentre, randomised,
double-blind, placebo-controlled comparison.

Diener HC, Jansen JP, Reches A, Pascual J, Pitei D, Steiner TJ; Eletriptan and
Cafergot Comparative Study Group.

Department of Neurology, University of Essen, Essen, Germany.
h.diener@uni-essen.de

The 5-HT(1B/1D/1F) agonist eletriptan, at an oral dose of 80 mg, has been shown
to be more efficacious than sumatriptan 100 mg and placebo in the treatment of
migraine attacks with or without aura. Another commonly prescribed oral treatment
for migraine attacks is Cafergot (1 mg ergotamine tartrate with 100 mg caffeine
per tablet). The efficacy, tolerability and safety of 40- and 80-mg doses of
eletriptan and 2 tablets of Cafergot were compared in a double-blind, randomised,
placebo-controlled, parallel-group trial involving 733 migraine patients.
Patients recorded symptoms at baseline (before treatment) and 1, 2, 4 and 24 h
after dosing. Headache intensity was assessed on a 4-point scale (3 = severe
pain, 2 = moderate pain, 1 = mild pain, 0 = no pain). Significantly more
eletriptan-treated patients (80 mg, 68%; 40 mg, 54%) than Cafergot-treated
patients (33%; p < 0.001) reported headache response (improvement from
moderate-to-severe to mild or no pain) at 2 h. Substantially more eletriptan
recipients reported no pain (80 mg, 38%; 40 mg, 28%; Cafergot, 10%; placebo, 5%; 
p < 0.001). Eletriptan headache response rates at 1 h were significantly higher
(80 mg, 39%; 40 mg, 29%; Cafergot, 13%; placebo, 13%; p < 0.002 for each
comparison). Both doses of eletriptan were significantly more effective than
Cafergot in reducing nausea (p < 0.0001), photophobia (80 mg, p < 0.0001; 40 mg, 
p < 0.002), phonophobia (80 mg, p < 0.0001; 40 mg, p < 0.003) and functional
impairment (p < or = 0.001) at 2 h. Adverse events were generally mild or
moderate and transient. This randomised trial shows that oral eletriptan is more 
efficacious in the acute treatment of migraine than oral Cafergot and is well
tolerated. Copyright 2002 S. Karger AG, Basel

Publication Types: 
    Clinical Trial
    Comparative Study
    Multicenter Study
    Randomized Controlled Trial

PMID: 11844898 [PubMed - indexed for MEDLINE]

3077: Eur Neurol. 2002;47(2):88-98.

Zolmitriptan versus a combination of acetylsalicylic acid and metoclopramide in
the acute oral treatment of migraine: a double-blind, randomised, three-attack
study.

Geraud G, Compagnon A, Rossi A; COZAM Study Group.

Service de Neurologie, CHU de Rangueil, Toulouse, France.
geraud.g@chu-toulouse.fr

This multicentre, randomised, double-blind study compared oral zolmitriptan 2.5
mg with a combination of oral acetylsalicylic acid 900 mg and metoclopramide 10
mg as acute anti-migraine therapy for 3 migraine attacks. In total, 666 patients 
took at least one dose of study medication (326 took zolmitriptan and 340 took
acetylsalicylic acid plus metoclopramide). The percentage of patients with a
2-hour headache response after the first dose for all 3 attacks (the primary end 
point) was 33.4% with zolmitriptan and 32.9% with acetylsalicylic acid plus
metoclopramide [odds ratio 1.06, 95% confidence interval (CI) 0.77-1.47; p =
0.7228]. For the majority of secondary end points, the two treatments
demonstrated comparable efficacy. However, post hoc analysis showed that
significantly more patients receiving zolmitriptan were free of pain 2 h after
the first dose in all 3 attacks compared with patients receiving acetylsalicylic 
acid plus metoclopramide (10.7 vs. 5.3%; odds ratio 2.19, 95% CI 1.23-4.03; p =
0.0095). In addition, post hoc analysis showed that the overall 2-hour pain-free 
response rate was consistently higher with zolmitriptan (34.6%) than with
acetylsalicylic acid plus metoclopramide (27.9%) (odds ratio 1.40, 95% CI
1.09-1.78; p = 0.007). Both treatments reduced migraine-associated nausea,
vomiting, phonophobia and photophobia. There were no important inter-group
differences with respect to the onset of meaningful migraine relief, the
frequency of headache recurrence, the usage or efficacy of a second dose of
medication or the use of escape medication. However, at the last attack, the
proportion of patients who expressed overall satisfaction with the treatment was 
significantly higher in the zolmitriptan group, i.e. 83.7%, versus 75.0% with
acetylsalicylic acid plus metoclopramide (p = 0.0346). Both agents were well
tolerated. Adverse events were reported by 40.8% (133/326) of
zolmitriptan-treated patients and 29.1% (99/340) of those treated with
acetylsalicylic acid plus metoclopramide. The incidence of withdrawals due to
adverse events was very low with both zolmitriptan (0.9%) and the combination
regimen (1.5%); the latter percentage included 1 patient who withdrew from the
study due to phlebitis, which was classified as a serious adverse event. This
study showed that zolmitriptan is effective and well tolerated for the acute
treatment of moderate to severe migraine. Zolmitriptan was at least as effective 
as acetylsalicylic acid plus metoclopramide in achieving a 2-hour headache
response, but significantly more effective than the combination therapy for other
end points, including the 2-hour pain-free response. Copyright 2002 S. Karger AG,
Basel

Publication Types: 
    Clinical Trial
    Comparative Study
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 11844897 [PubMed - indexed for MEDLINE]

3078: Cephalalgia. 2001 Dec;21(10):990-2.

Recurrent Lilliputian hallucinations as visual aura symptom in migraine.

Podoll K, Robinson D.

Department of Psychiatry and Psychotherapy, University of Technology Aachen,
Germany.

Since her early 30s a 72-year-old female migraine sufferer has experienced
recurrent episodes of Lilliputian hallucinations occurring at the peak of her
severe migraine attacks and lasting between 2 min and 5 min, suggesting that her 
miniature hallucinations represent a visual migraine aura symptom. The existence 
of Lilliputian hallucinations of a migrainous nature is confirmed by four similar
case reports reviewed from the migraine literature. The occurrence of similar
Lilliputian hallucinations in the syndrome of peduncular hallucinosis, due to
mesencephalic and/or thalamic lesions, supports the notion that the patient's
recurrent Lilliputian hallucinations might have been aura symptoms of basilar
migraine.

Publication Types: 
    Case Reports
    Research Support, Non-U.S. Gov't

PMID: 11843872 [PubMed - indexed for MEDLINE]

3079: Cephalalgia. 2001 Dec;21(10):987-9.

Leukocyte mitochondrial DNA A to G polymorphism at 11084 is not a risk factor for
Japanese migraineurs.

Takeshima T, Fukuhara Y, Adachi Y, Ishizaki K, Kusumi M, Kowa H, Iigaya M, Sakai 
F, Nakashima K.

Division of Neurology, Institute of Neurological Sciences, Tottori University
Faculty of Medicine, Yonago, Japan. ttakeshi@grape.med.tottori-u.ac.jp

Mitochondrial dysfunction has been reported in patients with migraine. We
investigated leukocyte mitochondrial DNA 11084 A to G polymorphism in 166
Japanese migraineurs and 483 Japanese controls. The migraine group consisted of
43 patients suffering from migraine with aura (MWA) and 123 from migraine without
aura (MOA). The frequency of the transition was 7.2% (12/166) in the migraine
group and 7.3% (35/483) in the controls. The frequency of the transition was 4.7%
in MWA and 8.1% in MOA. There was no significant difference among the groups
(chi-square test). The mitochondrial DNA 11084 A to G transition was more common 
in Japanese subjects than reported in Caucasians; however, this polymorphism is
not a genetic risk factor for migraine in Japanese patients.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 11843871 [PubMed - indexed for MEDLINE]

3080: Cephalalgia. 2001 Dec;21(10):947-52.

The Migraine Disability Assessment (MIDAS) questionnaire: translation and
reliability of the Italian version.

D'Amico D, Mosconi P, Genco S, Usai S, Prudenzano AM, Grazzi L, Leone M, Puca FM,
Bussone G.

Neurological Institute Carlo Besta, Milano, Italy.

We have developed and tested an Italian version of the Migraine Disability
Assessment (MIDAS) questionnaire, an established instrument for assessing
headache-related disability. A multistep process was used to translate and adapt 
the questionnaire into Italian, which was then tested on 109 Italian migraine
without aura patients, 86 (78.9%) of whom completed the form a second time 21
days later. Overall MIDAS score had good test-retest reliability (Spearman's
correlation 0.77), closely similar to that found in English-speaking migraineurs,
and individual responses were also satisfactorily reliable. Internal consistency 
was good (Cronbach's alpha 0.7). These findings support the use of the MIDAS
questionnaire as a clinical and research tool with Italian patients.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 11843865 [PubMed - indexed for MEDLINE]

3081: Neurology. 2002 Feb 12;58(3):422-7.

Comment in:
    Neurology. 2003 Aug 12;61(3):424-5.

Migraine and autonomic nervous system function: a population-based, case-control 
study.

Shechter A, Stewart WF, Silberstein SD, Lipton RB.

Department of Epidemiology, the Johns Hopkins School of Hygiene and Public
Health, Baltimore, MD, USA. ashechter@hotmail.com

OBJECTIVE: This study determines if measures of the function of the autonomic
nervous system (ANS) differ in a population study of 80 migraine cases vs 85
controls matched for age, race, and sex. BACKGROUND: The authors sought to
confirm clinic-based studies suggesting that migraine is associated with abnormal
ANS function. METHODS: Resting systolic and diastolic blood pressure, Valsalva
maneuver, heart rate variability (pulse rate [RR] variation) during deep
breathing, and cardiovascular reactivity were measured during headache-free
intervals. Migraineurs were subdivided into those with (n = 28) and without (n = 
52) disabling headaches. RESULTS: Resting diastolic, but not systolic, blood
pressure was elevated in disabled (73.2 mm) compared with nondisabled cases (71.6
mm; p < 0.10) and controls (69.8 mm; p < 0.096). RR variation also was
significantly different among the three groups. Disabled migraine cases (1.19)
had significantly lower RR variation compared with nondisabled migraine cases
(1.26; p < 0.001) and controls (1.26; p < 0.001). The Valsalva ratio and mean
circular resultant were lower in disabled cases compared with other migraine
cases and with controls, but the differences were not statistically significant. 
No differences were found between the three groups when comparing blood pressure 
response to a psychological stressor. CONCLUSIONS: Migraineurs with disabling
attacks may be prone to ANS hypofunction. These findings may suggest that ANS
dysfunction either may be a risk factor for migraine headaches or be a
consequence of frequent disabling attacks. Moreover, ANS dysfunction and migraine
may share a common neural substrate.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 11839842 [PubMed - indexed for MEDLINE]

3082: Am J Hum Genet. 2002 Mar;70(3):652-62. Epub 2002 Feb 8.

A susceptibility locus for migraine with aura, on chromosome 4q24.

Wessman M, Kallela M, Kaunisto MA, Marttila P, Sobel E, Hartiala J, Oswell G,
Leal SM, Papp JC, Hämäläinen E, Broas P, Joslyn G, Hovatta I, Hiekkalinna T,
Kaprio J, Ott J, Cantor RM, Zwart JA, Ilmavirta M, Havanka H, Färkkilä M,
Peltonen L, Palotie A.

Department of Pathology and Laboratory Medicine, University of California, Los
Angeles, Los Angeles 90095-7088, USA.

Migraine is a complex neurovascular disorder with substantial evidence supporting
a genetic contribution. Prior attempts to localize susceptibility loci for common
forms of migraine have not produced conclusive evidence of linkage or
association. To date, no genomewide screen for migraine has been published. We
report results from a genomewide screen of 50 multigenerational, clinically
well-defined Finnish families showing intergenerational transmission of migraine 
with aura (MA). The families were screened using 350 polymorphic microsatellite
markers, with an average intermarker distance of 11 cM. Significant evidence of
linkage was found between the MA phenotype and marker D4S1647 on 4q24. Using
parametric two-point linkage analysis and assuming a dominant mode of
inheritance, we found for this marker a maximum LOD score of 4.20 under locus
homogeneity (P=.000006) or locus heterogeneity (P=.000011). Multipoint parametric
(HLOD = 4.45; P=.0000058) and nonparametric (NPL(all) = 3.43; P=.0007) analyses
support linkage in this region. Statistically significant linkage was not
observed in any other chromosomal region.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 11836652 [PubMed - indexed for MEDLINE]

3083: Am J Med. 2002 Feb 1;112(2):135-40.

The safety of triptans in the treatment of patients with migraine.

Jamieson DG.

Department of Neurology, University of Pennsylvania, Philadelphia, Pennsylvania, 
USA.

The introduction of the triptans (5-hydroxytryptophan [5-HT] (1B/1D) agonists) in
the past decade has brought migraine-specific pain relief to those suffering from
migraine. These drugs activate the serotonin receptors 5-HT(1B) and 5-HT(1D) on
cerebral vessels. Concerns about their safety, particularly in patients with
vascular risk factors, have been raised because triptans also activate the
5-HT(1B) receptors on coronary arteries. Although triptans are contraindicated in
patients with cardiac or cerebrovascular disease, they are safer than many other 
medications used to treat patients with migraine, including the nonspecific
serotonin-agonist ergot preparations.

Publication Types: 
    Review

PMID: 11835952 [PubMed - indexed for MEDLINE]

3084: Brain. 2002 Jan;125(Pt 1):102-12.

Endothelin-1 potently induces Leão's cortical spreading depression in vivo in the
rat: a model for an endothelial trigger of migrainous aura?

Dreier JP, Kleeberg J, Petzold G, Priller J, Windmüller O, Orzechowski HD,
Lindauer U, Heinemann U, Einhäupl KM, Dirnagl U.

Department of Experimental Neurology, Charité, Humboldt-University, Berlin,
Germany. jens.dreier@charite.de

According to the 'neuronal' theory, cortical spreading depression (CSD) is the
pathophysiological correlate of migrainous aura. However, the 'vascular' theory
has implicated altered vascular function in the induction of aura symptoms. The
possibility of a vascular origin of aura symptoms is supported, e.g. by the
clinical observation that cerebral angiography frequently provokes migrainous
aura. This suggests that endothelial irritation may somehow initiate one of the
pathways resulting in migrainous aura. Up to now, an endothelium-derived factor
has never been shown to trigger CSD. Here, for the first time, we demonstrate and
characterize the ability of the vasoconstrictor and astroglial/neuronal modulator
endothelin-1 to trigger Leão's 'spreading depression of activity' in vivo in
rats. At a concentration range between 10 nM and 1 microM, endothelin-1 induced
changes characteristic of CSD with regard to the rate of propagation, steady
(direct current) potential and extracellular K(+)-concentration. A spreading
hyperaemia followed by oligaemia was observed similar to those in K(+)-induced
CSD. Endothelin-1 did not provoke changes characteristic of a terminal
depolarization. The mechanism by which endothelin-1 generated CSD involved the
N-methyl-D-asparate receptor. Cerebral blood flow decreased slightly, but
significantly, before endothelin-1 generated CSD. A vasodilator (NO*-donor)
shifted the threshold for CSD induction to higher concentrations of endothelin-1.
Endothelin-1, in contrast to K(+), did not induce CSD in rat brain slices
suggesting indirectly that endothelin-1 may require intact perfusion to exert its
effects. In conclusion, endothelin-1 was found in the experiment to be the most
potent inducer of CSD currently known. We propose endothelin-1 as a possible
candidate for the yet enigmatic link between endothelial irritation and
migrainous aura.

Publication Types: 
    In Vitro
    Research Support, Non-U.S. Gov't

PMID: 11834596 [PubMed - indexed for MEDLINE]

3085: Acta Odontol Scand. 2001 Dec;59(6):413-7.

Signs and symptoms of temporomandibular disorders in children with different
types of headache.

Liljeström MR, Jämsä A, Le Bell Y, Alanen P, Anttila P, Metsähonkala L, Aromaa M,
Sillanpää N.

Institut of Dentistry and Department of Child Neurology, University of Turku,
Finland. marjo-riitta.liljestrom@utu.fi

Headache is a common symptom among children and teenagers. Both bruxism and
muscle and joint tenderness have been found in children with headache. Children
with migraine headache report more temporomandibular disorder (TMD) symptoms than
do those with tension-type headache. The aim of the present study was to
investigate the association of different types of headache with TMD and sex in
children. Altogether 297 randomly selected schoolchildren aged 13-14 years
participated in a blind study setting. There were no statistically significant
differences between the headache groups with regard to TMD signs, although the
migraine and migraine-type headache groups had the highest percentage of subjects
with more severe TMD signs. Nor were there any statistical differences between
sexes or between the headache groups with regard to subjective symptoms of TMD.
The present results with children differed from earlier results with adults.
First, no association was found between tension headache and TMD, and, second, no
sex difference in TMD children was observed at this age.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 11831493 [PubMed - indexed for MEDLINE]

3086: Expert Opin Pharmacother. 2001 Oct;2(10):1649-54.

Review of botulinum toxin type A and its clinical applications in migraine
headache.

Silberstein SD.

Jefferson Headache Center, Thomas Jefferson University Hospital, Philadelphia,
Pennsylvania 19107, USA. Stephen.Silberstein@mail.tju.edu

Botulinum toxin type A (BTX-A) has been used successfully for many disorders
related to excessive muscle contraction. It works, in part, by causing a
dose-dependent, reversible muscle relaxation. BTX-A has also been used for
migraine prevention. The mechanism by which BTX-A acts in migraine is probably
unrelated to its effect on muscle relaxation. BTX-A may have a distinct
antinociceptive mechanism, either through action on the muscle spindles or
through a direct effect on the central nervous system. Several trials and case
reports have demonstrated the safety and efficacy of BTX-A in migraine headache. 
BTX-A is distinct from other preventive medications. Adverse events (AEs) are
rare and mild. BTX-A is convenient, since the dosing interval may be 3 months or 
longer. However, before BTX-A can be considered a first-line agent for migraine, 
larger studies need to be conducted to determine optimum dosing and
administration sites as well as patient characteristics that are predictive of
response.

Publication Types: 
    Review

PMID: 11825307 [PubMed - indexed for MEDLINE]

3087: Nat Med. 2002 Feb;8(2):136-42.

Comment in:
    Nat Med. 2002 Feb;8(2):110-2.

Intrinsic brain activity triggers trigeminal meningeal afferents in a migraine
model.

Bolay H, Reuter U, Dunn AK, Huang Z, Boas DA, Moskowitz MA.

Stroke and Neurovascular Regulation Laboratory, Department of Radiology,
Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts,
USA.

Although the trigeminal nerve innervates the meninges and participates in the
genesis of migraine headaches, triggering mechanisms remain controversial and
poorly understood. Here we establish a link between migraine aura and headache by
demonstrating that cortical spreading depression, implicated in migraine visual
aura, activates trigeminovascular afferents and evokes a series of cortical
meningeal and brainstem events consistent with the development of headache.
Cortical spreading depression caused long-lasting blood-flow enhancement
selectively within the middle meningeal artery dependent upon trigeminal and
parasympathetic activation, and plasma protein leakage within the dura mater in
part by a neurokinin-1-receptor mechanism. Our findings provide a neural
mechanism by which extracerebral cephalic blood flow couples to brain events;
this mechanism explains vasodilation during headache and links intense
neurometabolic brain activity with the transmission of headache pain by the
trigeminal nerve.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 11821897 [PubMed - indexed for MEDLINE]

3088: J Pediatr Psychol. 2002 Mar;27(2):109-19.

A controlled study of minimal-contact thermal biofeedback treatment in children
with migraine.

Scharff L, Marcus DA, Masek BJ.

Pain Treatment Service, Children's Hospital, Boston, Massachusetts 02115, USA.
lisa.scharff@tch.harvard.edu

OBJECTIVE: To evaluate the effectiveness of handwarming biofeedback (HWB) and
stress management training in comparison to attention (handcooling, HCB) and
wait-list control groups. Thermal biofeedback has been used in many pediatric
migraine treatment studies and has demonstrated a consistent therapeutic effect. 
No published studies to date have compared this treatment modality with credible 
attention control using biofeedback technology. METHODS: Thirty-six children and 
adolescents (mean age: 12.8 years), as well as the mothers and fathers of these
children enrolled in the study, were randomly assigned to the three groups.
Thirty-four children completed treatment. Both treatment groups received four
sessions of biofeedback training and a portable biofeedback device for home
practice. Ratings of treatment credibility showed that the children rated the two
treatments as equally credible. Assessment included anxiety and depression
questionnaires for the children and both of their parents. RESULTS: Children who 
had been assigned to the HWB group were more likely to achieve clinical
improvement in migraine after treatment than the children in the HCB group.
Treatment gains were maintained up to 6 months after treatment. Home practice
data reflected a general increase in temperature in the HWB group and a decrease 
in temperature for the HCB group. CONCLUSIONS: The results of this study confirm 
the findings of earlier pediatric migraine biofeedback treatment studies and also
provide support for the specific effect of treatments including stress management
and HWB. Future studies with larger sample sizes will aid in delineating the
appropriateness of HCB as a control treatment.

Publication Types: 
    Clinical Trial
    Comparative Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 11821495 [PubMed - indexed for MEDLINE]

3089: Paediatr Drugs. 2002;4(1):1-8.

Abdominal migraine: evidence for existence and treatment options.

Russell G, Abu-Arafeh I, Symon DN.

Department of Child Health, University of Aberdeen, Foresterhill, Aberdeen, AB25 
2ZG, Scotland. libra@ifb.co.uk

There is evidence to suggest that, in children, episodic abdominal pain occurring
in the absence of headache may be a migrainous phenomenon. There are four
separate strands of evidence for this: the common co-existence of abdominal pain 
and migraine headaches; the similarity between children with episodic abdominal
pain and children with migraine headaches, with respect to social and demographic
factors, precipitating and relieving factors, and accompanying gastrointestinal, 
neurological and vasomotor features; the effectiveness of nonanalgesic migraine
therapy (such as pizotifen, propanolol, cyproheptadine and the triptans) in
abdominal migraine; and the finding of similar neurophysiological features in
both migraine headache and abdominal migraine. Abdominal migraine is rare, but
not unknown, in adults. Many families are content with a diagnosis and
reassurance that the episodes, though distressing, are not the result of serious 
pathology. Some patients respond to simple dietary and other prophylactic
measures. There is scant evidence on which to base recommendations for the drug
management of abdominal migraine. What little literature exists suggests that the
antimigraine drugs pizotifen, propanolol and cyproheptadine are effective
prophylactics. Nasal sumatriptan (although not licensed for pediatric use) may be
effective in relieving abdominal migraine attacks.

Publication Types: 
    Review

PMID: 11817981 [PubMed - indexed for MEDLINE]

3090: Drugs. 2002;62(2):387-414.

Almotriptan: a review of its use in migraine.

Keam SJ, Goa KL, Figgitt DP.

Adis International Limited, Mairangi Bay, Auckland, New Zealand.
demail@adis.co.nz

Almotriptan is a selective serotonin 5-HT(1B/1D) receptor agonist ('triptan').
Its efficacy and tolerability have been assessed in a number of randomised,
controlled trials in over 4800 adults with moderate or severe attacks of
migraine. Oral almotriptan has a rapid onset of action (significant headache
relief is observed 0.5 hours after administration of a 12.5mg dose) and efficacy 
is sustained in most patients who respond by 2 hours. The drug is significantly
more effective than placebo as measured by a number of parameters including
2-hour headache response and pain-free response rates. Other symptoms of
migraine, including nausea, photophobia and phonophobia, are also alleviated by
almotriptan. The efficacy of oral almotriptan appears to be maintained over
repeated doses for multiple attacks of migraine treated over a long period (up to
1 year). High headache response rates were reported over all attacks without
tachyphylaxis. For the relief of single attacks of migraine, oral almotriptan
12.5mg had similar efficacy to oral sumatriptan 50mg. Patients given almotriptan 
report less concern with adverse effects than patients given sumatriptan. The
lower incidence of chest pain following treatment with almotriptan than with
sumatriptan may lead to a reduction in direct costs, with fewer patients
requiring management of chest pain. Almotriptan is well tolerated. Most adverse
events were of mild or moderate intensity, transient, and generally resolved
without intervention or the need for treatment withdrawal. The most common
adverse events associated with oral almotriptan 12.5mg treatment were dizziness, 
paraesthesia, nausea, fatigue, headache, somnolence, skeletal pain, vomiting and 
chest symptoms. The incidence of adverse events did not differ from placebo and
decreased in the longer term. Almotriptan can be coadministered with drugs that
share a common hepatic metabolic path; in addition, dosage reduction is required 
only in the presence of severe renal or hepatic impairment. CONCLUSIONS:
Almotriptan is an effective drug for the acute treatment of moderate or severe
attacks of migraine in adults. An oral dose of almotriptan 12.5mg has shown
greater efficacy than placebo; current data indicate that efficacy is similar to 
that of oral sumatriptan 50mg, and is maintained in the long term (<or=1 year).
Almotriptan has a good adverse event profile and a generally similar overall
tolerability profile to sumatriptan; of note, almotriptan is associated with a
significantly lower incidence of chest pain than sumatriptan. However, further
clinical experience is required to clearly define the place of almotriptan among 
the other currently available triptans. Nevertheless, because triptans have an
important place in various management regimens, and because the nature of
individual patient response to triptans is idiosyncratic, almotriptan is likely
to become a useful treatment option in the management of adults with moderate or 
severe migraine headaches.

Publication Types: 
    Review

PMID: 11817980 [PubMed - indexed for MEDLINE]

3091: Acta Neurol Belg. 2001 Sep;101(3):166-70.

Neuromuscular transmission in migraine patients with prolonged aura.

Ambrosini A, de Noordhout AM, Schoenen J.

Headache Clinic IRCCS INM Neuromed, Pozzilli, Isernia, Italy.

P/Q Ca2+ channels are genetically abnormal in most cases of familial hemiplegic
migraine (FHM) and may be involved in other types of migraine. They are also
found at the neuromuscular junctions, where they control stimulation-induced
acetylcholine release. Prolonged aura is a very frequent clinical feature in FHM 
patients. The objective of this study was thus to explore neuromuscular
transmission in migraine with typical and prolonged aura patients. We performed
single fiber electromyography (SFEMG) in such patients and compared them to a
group of healthy volunteers. Results were expressed as mean jitter (MCD) and
percentage of single endplate abnormalities. Mean MCD was on average comparable
in controls and migraineurs. By contrast, single endplate abnormalities were only
found in patients (p < 0.01), especially in those with prolonged aura (p <
0.001). These results suggest subtle impairment of neuromuscular transmission in 
a subgroup of migraineurs characterized by prolonged aura, which might be due to 
dysfunctioning P/Q Ca(2+)-channels.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 11817265 [PubMed - indexed for MEDLINE]

3092: Pediatr Neurol. 2002 Jan;26(1):47-50.

Wide clinical variability in a family with a CACNA1A T666m mutation: hemiplegic
migraine, coma, and progressive ataxia.

Wada T, Kobayashi N, Takahashi Y, Aoki T, Watanabe T, Saitoh S.

Department of Pediatrics, Hokkaido University School of Medicine, N-15 W-7,
Kita-ku, Sapporo 060-8638, Japan.

We report a Japanese family carrying a T666M missense mutation of CACNA1A.
Affected members demonstrated a strikingly wide clinical spectrum including
migraine, hemiplegia, coma, and progressive cerebellar ataxia. Despite such
variability of the clinical features, they demonstrated similar magnetic
resonance imaging findings demonstrating cerebellar atrophy predominantly of the 
cerebellar vermis. These magnetic resonance images appeared not to correlate with
clinical severity. Our findings should indicate that a T666M mutation of CACNA1A 
may be associated with more variable clinical features and that paroxysmal
hemiplegic migraine attacks and progressive cerebellar atrophy should have
distinct mechanisms of pathogenesis.

Publication Types: 
    Case Reports

PMID: 11814735 [PubMed - indexed for MEDLINE]

3093: Coll Antropol. 2001 Dec;25(2):695-701.

Population variation in migraine prevalence--the unsolved problem.

Lusić I.

Department of Neurology, University Hospital Split, Croatia.

Migraine is one of the most prevalent types of headache, which imposes a
substantial burden on society as measured by direct and indirect costs. In the
present work we review the obstacles to carrying out migraine epidemiological
studies. Knowledge of the epidemiology of migraine has expanded because of the
recent proliferation of large scale population-based studies using standardized
case definitions. Previous surveys of the prevalence of migraine have given
widely differing results. Even in population-based studies, there have been wide 
variations in estimates of migraine prevalence. The development of International 
Headache Society (IHS) criteria for migraine has facilitated international
comparisons in epidemiologic studies by providing explicit and consistent
diagnostic criteria, Recent studies using IHS diagnostic criteria have given
relatively consistent estimates of migraine prevalence (about 15-18% of women and
6% of men). Studies of racial diversity in the prevalence of migraine and other
headaches are still not conclusive. Further work is needed on epidemiology of
migraine and collaboration between epidemiologists and clinicians seems the most 
likely way to advance understanding in this field.

PMID: 11811301 [PubMed - indexed for MEDLINE]

3094: Am J Med Genet. 2001 Dec 8;105(8):707-12.

Investigation of the CACNA1A gene as a candidate for typical migraine
susceptibility.

Lea RA, Curtain RP, Hutchins C, Brimage PJ, Griffiths LR.

Genomics Research Centre, School of Health Science, Griffith University, Gold
Coast, Queensland, Australia.

Typical migraine is a complex neurological disorder comprised of two main
subtypes: migraine with (MA) and without aura (MO). The disease etiology is still
unclear, but family studies provide strong evidence that defective genes play an 
important role. Familial hemiplegic migraine (FHM) is a very rare and severe
subtype of MA. It has been proposed that FHM and MA may have a similar genetic
etiology. Therefore, genetic studies on FHM provide a useful model for
investigating the more prevalent types of typical migraine. FHM in some families 
has been shown to be caused by mutations in a brain-specific P/Q-type calcium
channel alpha1 subunit gene (CACNA1A) on chromosome 19p13. There has also been a 
report of a CACNA1A mutation being associated with MA in a patient from a family 
with predominant FHM. We have previously demonstrated suggestive linkage of
typical migraine in a large Australian family to the FHM region on chromosome
19p13. These findings suggest that CACNA1A may also be implicated in the etiology
of typical migraine in this pedigree. To investigate this possibility, we
sequenced two patients carrying the critical susceptibility haplotype surrounding
CACNA1A. No disease-causing mutations or polymorphisms were revealed in any of
the 47 exons screened. To determine whether the CACNA1A gene was implicated in
typical migraine susceptibility in the general Caucasian population, we also
analyzed 82 independent pedigrees and a large case control group. We did not
detect any linkage or association in these groups and conclude that if CACNA1A
plays a role in typical migraine, it does not confer a major effect on the
disease. Copyright 2001 Wiley-Liss, Inc.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 11803518 [PubMed - indexed for MEDLINE]

3095: Clin Neuropharmacol. 2001 Nov-Dec;24(6):307-12.

Migraines.

Hui JS.

Department of Neurological Sciences, Rush-Presbyterian-St. Luke's Medical Center,
1725 W. Harrison Street, Chicago, IL 60612, USA.

A 26-year-old woman is evaluated for headaches, which began when she was 14 years
old. She states that she initially sees bright zig-zag bands, which expand in the
shape of a horseshoe in her right visual field. Twenty minutes later, she
develops a throbbing headache over the left frontal area, associated with
photophobia and nausea. The headaches last 1-3 days and they occur once a month. 
There is no medical history, and she takes only multivitamin supplements. Her
sister has been diagnosed with migraines. Her examination is normal, including
equal and reactive pupils, full extraocular movements, and normal strength and
sensation. A magnetic resonance scan of the brain shows no abnormalities.

Publication Types: 
    Case Reports

PMID: 11801805 [PubMed - indexed for MEDLINE]

3096: Int Clin Psychopharmacol. 2002 Jan;17(1):33-6.

Sumatriptan challenge in bipolar patients with and without migraine: a
neuroendocrine study of 5-HT1D receptor function.

Mahmood T, Silverstone T, Connor R, Herbison P.

Psychopharmacology Research Group, Department of Psychological Medicine,
University of Otago, Dunedin, New Zealand. tariq.mahmood@lcmhst-tr.northy.nhs.uk

An association between bipolar disorder and migraine has been lately recognized
and an abnormality of central serotonergic function is suggested as the
underlying neurophysiological disturbance. To examine the role of serotonin in
bipolar disorder and migraine, we used the neuroendocrine challenge paradigm, and
we chose sumatriptan, a 5HT1D agonist, as the pharmacological probe. We studied
nine bipolar patients with migraine, nine bipolar patients without it, seven
migraine patients, and nine matched normal controls. A post-hoc analysis showed
subsensitivity of serotonergic function, reflected in a blunted growth hormone
response to sumatriptan challenge in bipolar patients who also suffered from
migraine.

Publication Types: 
    Clinical Trial
    Research Support, Non-U.S. Gov't

PMID: 11800504 [PubMed - indexed for MEDLINE]

3097: J Child Neurol. 2001 Dec;16(12):882-4.

Sphenoid sinusitis masquerading as migraine headaches in children.

Ng YT, Butler IJ.

Department of Neurology, University of Texas-Houston Medical School, 77030, USA.

The sphenoid sinus is often referred to as the "neglected sinus." Isolated
sphenoid sinusitis is a rare disease with potentially devastating complications. 
It occurs at an incidence of about 2.7% of all sinus infections. Although
headache is the most common presenting symptom, there is no typical headache
pattern. Three cases of children with isolated sphenoid sinusitis presenting with
acute, subacute, and chronic headache symptoms are presented. The sensory
innervation of the sphenoid sinus is derived from the ophthalmic and maxillary
branches of the trigeminal nerve, which may explain the pathophysiology of the
headache, similar to the trigeminovascular pain theory of migraine. There are few
reports on sphenoid sinusitis and headache; however, modern neuroimaging has made
this probably under-recognized disorder easier to diagnose and treat. Although
the diagnosis can be difficult to differentiate from migraine headache, early and
appropriate treatment usually results in an excellent outcome without morbidity.

Publication Types: 
    Case Reports

PMID: 11785500 [PubMed - indexed for MEDLINE]

3098: J Neurol Neurosurg Psychiatry. 2002 Jan;72(1):86-92.

Physical and psychological correlates of primary headache in young adulthood: a
26 year longitudinal study.

Waldie KE, Poulton R.

Department of Psychology, University of Auckland, New Zealand.
k.waldie@auckland.ac.nz

OBJECTIVES: To determine if physical and/or psychological risk factors could
differentiate between subtypes of primary headache (migraine, tension-type
headache (TTH), and coexisting migraine and TTH (combined)) among members of a
longitudinal birth cohort study. METHODS: At age 26, the headache status of
members of the Dunedin Multidisciplinary Health and Development Study (DMHDS) was
determined using International Headache Society criteria. Headache history and
potential physical and psychological correlates of headache were assessed. These 
factors included perinatal problems and injuries sustained to age 26; and
behavioural, personality, and psychiatric disorders assessed between ages 5 to
21. RESULTS: The 1 year prevalences for migraine, TTH, and combined headache at
the age of 26 were 7.2%, 11.1%, and 4.3%, respectively. Migraine was related to
maternal headache, anxiety symptoms in childhood, anxiety disorders during
adolescence and young adulthood, and the stress reactivity personality trait at
the age of 18. TTH was significantly associated with neck or back injury in
childhood (before the age of 13). Combined headache was related to maternal
headache and anxiety disorder at 18 and 21 only among women with a childhood
history of headache. Headache status at the age of 26 was unrelated to a history 
of perinatal complication, neurological disorder, or mild traumatic head injury. 
CONCLUSIONS: Migraine and TTH seem to be distinct disorders with different
developmental characteristics. Combined headache may also have a distinct
aetiology.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 11784831 [PubMed - indexed for MEDLINE]

3099: Eur J Neurol. 2002 Jan;9(1):35-40.

Visual cortex excitability in migraine before and after valproate prophylaxis: a 
pilot study using TMS.

Mulleners WM, Chronicle EP, Vredeveld JW, Koehler PJ.

Department of Neurology, Atrium Medical Center, Heerlen, The Netherlands.
w.mulleners@freeler.nl

We examined the effect of standard migraine prophylaxis with sodium valproate on 
repeated measures of occipital excitability using transcranial magnetic
stimulation (TMS). We predicted that, comparing pre- and post-treatment
assessments, a reduction in clinical migraine parameters would be paralleled by a
decrease in excitability measurements.A total of 31 migraine patients enrolled in
the study, for assessment prior to and 1 month after commencement of sodium
valproate prophylaxis. At each assessment, we used a standardized protocol to
stimulate the occipital cortex with a 90-mm circular (coil A) and 70 mm
figure-of-eight (coil B) coil. We recorded the threshold stimulation intensity at
which subjects just perceived phosphenes. Subjects kept detailed records of
headache parameters 1 month before and also during the study period.Valproate
therapy significantly improved headache indexes, as expected. In MA subjects
assessed with coil B, phosphene thresholds were significantly higher
post-treatment than pre-treatment, but those for MO did not change. Modest
correlations were observed in MA patients between increase in phosphene threshold
and decrease in headache index. Although preliminary, the findings with coil B
lend some support to the notion that effective migraine prophylaxis may be
achieved through lowering cortical excitability by gamma-aminobutyric acid
(GABA)-ergic intervention. Further investigation of the effect of sodium
valproate or other similarly acting substances on cortical excitability in
migraine is warranted.

Publication Types: 
    Clinical Trial
    Research Support, Non-U.S. Gov't

PMID: 11784374 [PubMed - indexed for MEDLINE]

3100: Eur J Neurol. 2001 Nov;8(6):693-9.

Low headache prevalence amongst women with high TSH values.

Hagen K, Bjøro T, Zwart JA, Vatten L, Stovner LJ, Bovim G.

Department of Clinical Neuroscience, Section of Neurology, Norwegian University
of Science and Technology, Trondheim, Norway. knut.hagen@medisin.ntnu.no

The aim of this large cross-sectional population-based study was to examine a
possible positive or negative association between thyroid dysfunction and
headache. Between 1995 and 1997, all 92 566 adults in Nord-Trøndelag County in
Norway were invited to participate in a health survey. A total of 51 383 (56%)
responded to a headache questionnaire, whereof thyroid-stimulating hormone (TSH) 
was measured in 28 058 individuals. These included 15 465 women and 8019 men
above 40 years of age, 1767 randomly selected individuals between 20 and 40 years
of age, and 2807 (97%) with thyroid dysfunction. Associations between thyroid
dysfunction and headache were assessed in multivariate analyses, estimating
prevalence odds ratios (OR) with 95% confidence intervals (CIs). High TSH values 
were associated with low prevalence of headache. This was most evident amongst
women with no history of thyroid dysfunction. Amongst these, headache was less
probable (OR=0.5, 95% CI 0.3-0.7) if TSH > or = 10 mU/l than in women with normal
TSH (0.2-4 mU/l). In all age groups between 40 and 80 years, TSH was lower
amongst headache sufferers, especially migraineurs, than in those without
headache complaints.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 11784355 [PubMed - indexed for MEDLINE]

3101: Am J Emerg Med. 2002 Jan;20(1):39-42.

A randomized clinical trial to assess the efficacy of intramuscular droperidol
for the treatment of acute migraine headache.

Richman PB, Allegra J, Eskin B, Doran J, Reischel U, Kaiafas C, Nashed AH.

Department of Emergency Medicine, Morristown Memorial Hospital, Morristown, NJ,
USA. PRichmanMD@aol.com

In a recent case series, we reported that intramuscular droperidol appeared to be
an effective therapy for the treatment of acute migraine headache. The objective 
of the study was to further assess the efficacy of intramuscular droperidol for
the treatment of acute migraine headache. The study design was a randomized,
clinical trial set in a community-based ED. The population was a convenience
sample of ED patients who met International Headache Society acute migraine
criteria. Exclusions included pregnancy, use of narcotic or phenothiazine
medications within 24 hours. For the protocol, patients were randomized to 1 of 2
treatment groups. Patients and physicians were blinded as to the treatment
provided. Patients recorded their initial pain on a 100mm Visual Analog Scale
(VAS) Patients were randomized to receive either 2.5 mg droperidol
intramuscularly; the other group received 1.5 mg/kg meperidine intramuscularly.
After 30 minutes patients recorded their pain on the VAS and recorded their
preference for the medication on a Likert Scale. Physicians recorded the
incidence of any side effects and the need for rescue medication. Statistical
analysis consisted of categorical variables that were analyzed by chi-square,
continuous interval data by t-tests and ordinal data by Mann-Whitney U test. The 
primary outcome parameters were mean VAS score change and the percentage of
patients who wanted to go home without rescue medication. The study had an 80%
power to detect a 26 mm difference in the mean change in VAS between groups. Of
the 29 patients who were enrolled, 15 received droperidol. Both groups were
similar with respect to age (30.7 +/- 8.9 years droperdol v 32.7 +/- 9.9 years
meperidine; P =.59), female sex (73% v 71%; P =.91), mean headache duration (24.7
+/- 28.3 v 18.3 +/- 25.8 hours; P =.55). The droperidol group had a higher mean
initial VAS score (88 v 76 mm; P =.03). The 2 groups were similar with regard to 
outcome, including: mean change in VAS score (47 v 37 mm; P =.33), average Likert
score (1.1 v 1.9; P =.85), and the percentage of patients who did not want rescue
medication (67% v 57%; P =.61). The incidence of sedation was 6.7 v 14.3%.
Akathisia occurred in 13.3% of pts who received droperidol. We found that
intramuscular droperidol was similar in efficacy to meperidine with a low
incidence of side effects.

Publication Types: 
    Clinical Trial
    Comparative Study
    Randomized Controlled Trial

PMID: 11781912 [PubMed - indexed for MEDLINE]

3102: J Clin Epidemiol. 2002 Jan;55(1):77-85.

Should systematic reviews include non-randomized and uncontrolled studies? The
case of acupuncture for chronic headache.

Linde K, Scholz M, Melchart D, Willich SN.

Institute for Social Medicine & Epidemiology, Charité Hospital,
Humboldt-Universität, 10098, Berlin, Germany. Klaus.Linde@lrz.tu-muenchen.de

We aimed to investigate: (1) whether patient and intervention characteristics,
design-independent quality aspects, and response rates differ between randomized 
and non-randomized trials of acupuncture for chronic headache; (2) whether
non-randomized studies provide useful additional information (regarding long-term
effects, prognostic factors, adverse effects, and generalizability); (3) reasons 
for potential differences in response rates. Studies including at least five
patients and reporting clinical outcome data were identified through searches in 
Medline, Embase, the Cochrane Controlled Trials Register, other databases and
checking of bibliographies. Twenty-four randomized trials and 35 non-randomized
studies (five non-randomized controlled cohort studies, 10 prospective
uncontrolled studies, 10 case series, and 10 cross-sectional surveys) met the
inclusion criteria. Studies were heterogeneous regarding patients, interventions,
outcome measurements and results. On average, randomized trials had smaller
sample sizes, met more quality criteria, and had lower response rates (0.59 [95% 
confidence interval 0.48-0.69] vs. 0.78 [0.72-0.83]). Whether randomized or not, 
studies meeting more quality criteria had lower response rates. Non-randomized
studies did not have significantly longer follow-up periods, three included an
analysis of prognostic variables, only one reported on adverse effects, and the
degree of generalizability was unclear. In the case of acupuncture for chronic
headache, non-randomized studies confirmed the finding of a systematic review of 
randomized trials that the treatment is likely to be effective but provided
little relevant additional information on long-term effects, prognostic factors, 
and adverse effects.

Publication Types: 
    Meta-Analysis
    Research Support, U.S. Gov't, P.H.S.

PMID: 11781125 [PubMed - indexed for MEDLINE]

3103: Int J Clin Pract. 2001 Dec;55(10):684-9.

Migraine: assessment and management.

Dowson AJ.

King's Headache Service, London, UK.

Headaches occur at some time in the vast majority of the population. For most
people headaches are a nuisance but for some they can be disabling. Two per cent 
of the population at any time have chronic daily headache, with or without
analgesic dependence, but most disabling headaches are intermittent and migranous
in nature. Before hoping to make an appropriate intervention, an accurate
diagnosis must be made.The first part of this paper examines the differential
diagnosis and in particular separates benign from sinister, acute from chronic
and tension-type from migranous. The second half focuses on the management of
migraine. An individualised approach is usually the most effective, with the
patient drawing from the broad areas of attention to trigger factors and
lifestyle, finding an acute or rescue medication that consistently returns them
to normal activities within a few hours, and prophylaxis to reduce the rate of
attack by 50% in those with high frequency migraine. The expession of migraine
may well vary during an individual's life and in order to achieve the best
lifelong control, adjustment of the blend of management options may be needed.
The aim of the adviser is to enable patients to feel in control of their migraine
rather than feeling that migraine controls them.

Publication Types: 
    Review

PMID: 11777294 [PubMed - indexed for MEDLINE]

3104: Ear Nose Throat J. 2001 Dec;80(12):881-5.

Spontaneous vertigo and headache: endolymphatic hydrops or migraine?

Boismier TE, Disher MJ.

Balance Care Center, Ear, Nose, and Throat Associates, 10021 Dupont Circle Ct.,
Fort Wayne, IN 46825, USA. Boismier@fwi.com

We undertook a study to assess whether patients who had both spontaneous vertigo 
and headache would respond to treatment for endolymphatic hydrops rather than
treatment for migraine. We also attempted to discover if there were any
individual characteristics that might predict which patients with an equivocal
history and symptoms would be more likely to have either of the two conditions as
opposed to the other. All patients were initially treated for endolymphatic
hydrops with sodium restriction and increased water intake. Response to treatment
was assessed by three tools: the Dizziness Handicap Inventory, a symptom severity
scale, and a disability scale. Patients who did not respond to treatment for
endolymphatic hydrops were switched to treatment for migraine. At the first
follow-up period, 23 patients were available for analysis by telephone survey.
According to data obtained by the three assessment tools, 14 patients (60.9%)
improved after initial therapy and six (26.1%) improved following subsequent
migraine treatment; the remaining three patients (13.0%) did not comply with
their initial treatment regimen, and they showed no improvement. Although no
statistically significant conclusions can be drawn because of the small sample
size, there were trends to suggest that certain demographic, clinical, and
objective-testing characteristics might predict which patients are likely to have
one of these two conditions as opposed to the other. We conclude that a stepwise 
approach to treatment, beginning with therapy for endolymphatic hydrops, is an
appropriate strategy. Also, the fact that no improvement was seen among the three
patients who did not comply suggests that improvement is indeed the result of
treatment rather than simply a function of the passage of time.

PMID: 11775522 [PubMed - indexed for MEDLINE]

3105: Semin Neurol. 2001 Dec;21(4):371-6.

Pearls and pitfalls of headache.

Flippen CC 2nd.

Department of Neurology, UCLA Headache Center, Olive View-UCLA Medical Center,
Sylmar, California 91342-1495, USA.

Headache is one of the most common complaints confronting neurologists. This
article illustrates through case studies both some of the rare and some of the
commonly challenging aspects of diagnosis and management of headache. Each case
is followed by a brief overview of the topic. The reader should have an
appreciation of the importance of historical clues to diagnosis and specific
management for atypical headache entities.

Publication Types: 
    Case Reports
    Review

PMID: 11774052 [PubMed - indexed for MEDLINE]

3106: Expert Opin Investig Drugs. 2001 Oct;10(10):1869-74.

Eletriptan.

Gawel MJ, Grujich NN.

Division of Neurology, Sunnybrook & Women's College Health Sciences Centre,
University of Toronto, Toronto, ON, Canada. marek.gawel@swchsc.on.ca

Eletriptan (Relpax, Pfizer) is one of a group of anti-migraine medications
commonly referred to as 'triptans'. It is a potent serotonin agonist at the
5-HT(1B/1D) receptor and is indicated for the acute treatment of migraine
headaches. Eletriptan is administered orally. It is rapidly absorbed and has a
bioavailability of 50% compared to 14% for sumatriptan. The relatively high
lipophilicity of eletriptan compared to sumatriptan may explain its faster oral
absorption and shorter time to onset of action. Results from comparative studies 
between oral eletriptan and sumatriptan indicate that eletriptan 80 mg was
superior to sumatriptan 100 mg in onset of action, headache response rate, pain
free response rate and relief of associated migraine symptoms at the 1 or 2 h
time intervals. Although there was a modest increase in adverse events with
eletriptan 80 mg than with sumatriptan 100 mg, eletriptan received a high patient
acceptability rating (84%).

Publication Types: 
    Review

PMID: 11772292 [PubMed - indexed for MEDLINE]

3107: Expert Opin Investig Drugs. 2001 Oct;10(10):1831-45.

Advances in pharmacological treatment of migraine.

Diener HC, Limmroth V.

Department of Neurology, University Essen, Hufelandstr. 55, 45122 Essen, Germany.
h.diener@uni-essen.de

Migraine is a paroxysmal disorder with attacks of headache, nausea, vomiting,
photo- and phonophobia and malaise. This review summarises new treatment options 
both for the therapy of the acute attack as well as for migraine prophylaxis.
Analgesics like aspirin or non-steroidal anti-inflammatory drugs (NSAIDs) are
effective in treating migraine attacks. Few controlled trials were performed for 
the use of ergotamine or dihydroergotamine. These trials indicate inferior
efficacy compared with serotonin (5-HT(1B/D)) agonists (triptans). The triptans
(almotriptan, eletriptan, frovatriptan, naratriptan, rizatriptan, sumatriptan and
zolmitriptan), are highly effective. They improve headache as well as nausea,
photo- and phonophobia. The different triptans show only minor differences in
efficacy, headache recurrence and adverse effects. The knowledge of their
different pharmacological profile allows a more specific treatment of the
individual migraine characteristics. Migraine prophylaxis is recommended, when
more than three attacks occur per month, if attacks do not respond to acute
treatment or if side effects of acute treatment are severe. Substances with
proven efficacy include the beta-blockers metoprolol and propranolol, the calcium
channel blocker flunarizine, several 5-HT antagonists and amitriptyline. Recently
anti-epileptic drugs (valproic acid, gabapentin, topiramate) were evaluated for
the prophylaxis of migraine. The use of botulinum toxin is under investigation.

Publication Types: 
    Review

PMID: 11772289 [PubMed - indexed for MEDLINE]

3108: Expert Opin Investig Drugs. 2001 Jun;10(6):1131-8.

Migraine and beyond: cardiovascular therapeutic potential for CGRP modulators.

Doggrell SA.

Doggrell Biomedical Communications, 47 Caronia Crescent, Lynfield, Auckland, New 
Zealand.

CGRP is a potent vasodilator that has been shown to have a physiological and/or
pathological role in neurogenic inflammation, headaches including migraine,
thermal injury, circulatory shock, pregnancy and menopause, hypertension and
heart failure and is known to be cardioprotective. CGRP is also a positive
inotrope and increases heart rate. Clinical trials have shown beneficial effects 
of the vasodilatory action of CGRP in hypertension, angina, heart failure,
Raynaud's disease and venous stasis ulcers. However, the clinical potential of
CGRP is limited as it has to be given by infusion and is quickly broken down.
Oral long acting CGRP-mimetics may have potential in disorders in which CGRP has 
been shown to be beneficial. CGRP-mimetics include capsaicin/vanilloid receptor
agonists and gene transfer of an adenoviral vector that encodes prepro-CGRP. CGRP
inhibitors have therapeutic potential in conditions in which excessive
CGRP-mediated vasodilatation is present; neurogenic inflammation, migraine and
other headaches, thermal injury, circulatory shock and flushing in menopause.
CGRP inhibitors include capsaicin, antagonists at capsaicin/vanilloid receptors, 
civamide, CGRP receptor antagonists and 5-HT1D-receptor agonists. Drugs that are 
5-HT1D-receptor agonists, the 'triptans' are already commonly used in migraine
and the first small molecule CGRP antagonist, BIBN4096BS, is under clinical
investigation for the treatment of migraine.

Publication Types: 
    Review

PMID: 11772240 [PubMed - indexed for MEDLINE]

3109: J Hist Neurosci. 2001 Dec;10(3):253-61.

Aretaeus on migraine and headache.

Koehler PJ, van de Wiel TW.

Dept of Neurology, Atrium Medical Centre, P.O. Box 4446, 6401 CX Heerlen, The
Netherlands. pkoehler@knmg.nl

Aretaeus of Cappadocia's classification of headache has been referred to for many
centuries. Several Latin translations and an English translation (1856) of his
books have been published in the past. We translated the pertinent texts on
headache from the Greek text as published by Hude in 1958. In this paper, we
present an annotated translation preceded by an outline of contemporary knowledge
of headache from Celsus' De Medicina. Although symptomatic headache was most
probably involved in the types of headache identified by Aretaeus and the making 
of retrospective diagnoses is hazardous, the terms heterocrania and cephalea may 
be compared with what today we would call migraine and tension type headache
respectively.

Publication Types: 
    Biography
    Historical Article

Personal Name as Subject: 
    Aretaeus of Cappadocia 
    Celsus A

PMID: 11770192 [PubMed - indexed for MEDLINE]

3110: Clin Ther. 2001 Nov;23(11):1867-75.

Efficacy and tolerability of subcutaneous almotriptan for the treatment of acute 
migraine: a randomized, double-blind, parallel-group, dose-finding study.

Cabarrocas X; Almotriptan Study Group.

Research Center, Almirall Prodesfarma, Barcelona, Spain.
xcabarro@almirall-prodesfarma.com

BACKGROUND: The 5-hydroxytryptamine-receptor agonist almotriptan was found to be 
well tolerated and efficacious when administered orally in clinical trials of
migraine treatment. OBJECTIVE: The primary objective of this study was to assess 
the efficacy and tolerability of 3 different doses of subcutaneous almotriptan in
the treatment of acute migraine attacks. METHODS: This was a Phase II
multicenter, randomized, double-blind, placebo-controlled, parallel-group,
dose-finding study conducted over 7 months at 13 practice-oriented centers and 1 
larger research-focused center. Patients experiencing moderate to severe migraine
with or without aura, as defined by International Headache Society criteria, were
randomly assigned to receive a single subcutaneous dose of almotriptan 2, 6, or
10 mg or placebo. The primary end point, pain relief at 2 hours, was
self-assessed on a 4-point scale (severe, moderate, mild, or no pain). Patients
indicating mild or no pain were considered responders. The analysis was performed
on an intent-to-treat basis. RESULTS: A total of 123 patients were enrolled (23
men, 100 women). Overall, almotriptan 6 and 10 mg were significantly more
effective than placebo (P < 0.05, Fisher exact test). Response rates for the 6-
and 10-mg doses were 96.5% and 90.3%, respectively, compared with 50.0% for
placebo (P < 0.05, Fisher exact test). The proportion of patients with pain
relief at 2 hours was not significantly different between almotriptan 2 mg and
placebo. The response profile for the secondary end points was also better with
almotriptan 6 and 10 mg than with placebo. Administration of almotriptan was well
tolerated; the most frequently observed drug-associated adverse event was
transient local irritation at the injection site. CONCLUSIONS: Almotriptan was
well tolerated and significantly more effective than placebo in relieving
moderate to severe migraine pain when administered as a single 6- or 10-mg
subcutaneous dose.

Publication Types: 
    Clinical Trial
    Clinical Trial, Phase II
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 11768838 [PubMed - indexed for MEDLINE]

3111: Can J Neurol Sci. 2001 Nov;28(4):313-8.

Sumatriptan responsiveness and clinical, psychiatric and psychologic features in 
migraine patients.

Meckling SK, Becker WJ, Rose MS, Dalby JT.

Department of Clinical Neurosciences, University of Calgary, AB, Canada.

OBJECTIVE: To compare sumatriptan responders and nonresponders in a migraine
population with regard to a number of clinical, psychiatric and psychologic
features. METHODS: Patients were drawn from a referral headache clinic
population, and classified as responders or nonresponders. Clinical features were
assessed by a written questionnaire. The lifetime prevalence of several
psychiatric disorders was determined by the National Institute of Mental Health
diagnostic interview schedule and personality factors were measured by the 16
Personality Factors (16PF) Questionnaire. RESULTS: Nonresponders indicated less
influence on their migraine by menstrual factors, had a higher lifetime
prevalence of generalized anxiety, and showed 16PF scores indicating greater
shyness, self-sufficiency and perfectionism. Nonresponders were also more
imaginative and less socially outgoing. CONCLUSION: Although they must be
interpreted with caution due to small sample size and the multiple comparisons
made, our results indicate that there may be differences between sumatriptan
responders and nonresponders with regard to a number of clinical, psychiatric and
psychologic factors. These results suggest that biological differences exist
between the two patient groups which likely account for both the differences in
their responses to sumatriptan and in the clinical features noted above.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 11766775 [PubMed - indexed for MEDLINE]

3112: Hosp Med. 2001 Nov;62(11):687-91.

Modern management of migraine.

Elrington G.

Migraine presents with episodic disabling headache, with additional features that
distinguish it from other headache syndromes: it is not 'just a headache'.
Treatment must be carefully selected, titrated and adjusted according to
individual patient response.

Publication Types: 
    Review

PMID: 11762100 [PubMed - indexed for MEDLINE]

3113: J Med Assoc Thai. 2001 Aug;84(8):1199-203.

The first world report of botulinum A toxin injection for status migrainosus.

Poungvarin N.

Division of Neurology, Department of Medicine, Faculty of Medicine Siriraj
Hospital, Mahidol University, Bangkok, Thailand.

The author reports the first ever documented publication in the world concerning 
the use of botulinum toxin A (BTX-A) injection for status migrainosus. A 58-year 
old man had been suffering from migraine without aura for 20 years. This last
attack (a very severe throbbing headache) started over the left side of his head 
and he had tried several medications (paracetamol, aspirin, ergotamine, mefenamic
acid, and diazepam) during the attack to no vail. Physical examination revealed
an acutely ill patient with an agonizing pain condition. General and neurological
examinations were normal. BTX-A solution was then injected into the Fung Chou
point (classical Chinese acupuncture point for migraine) in the total amount of
25 international unit. Dramatic response was observed within 1 hour of injection 
and status migrainosus was abort within 10 hours. He was headache-free and had no
further attack of migraine for another 2 months.

Publication Types: 
    Case Reports

PMID: 11758858 [PubMed - indexed for MEDLINE]

3114: Neurosci Lett. 2002 Jan 14;317(3):135-8.

Electrophysiological evidence for trigeminal neuron sensitization in patients
with migraine.

Sandrini G, Proietti Cecchini A, Milanov I, Tassorelli C, Buzzi MG, Nappi G.

Laboratory of Pain Psychophysiology, Department of Neurological Sciences,
University Center for Adaptive Disorders and Headache, University of Pavia, Via
Palestro 3, 27100 Pavia, Italy. gsandrin@unipv.it

The electrically elicited corneal reflex is a useful tool for exploring the
trigeminal system in humans and it may provide additional evidence pointing to a 
dysfunction of this system in migrainous patients. Tactile perception, corneal
reflex and pain thresholds were studied in 48 migraine without aura patients
during pain-free periods and compared with those observed in 24 controls.
Twenty-eight of the patients had strictly unilateral headache, while the other 20
had bilateral or side-shifting pain during attacks. Both migraine subgroups
(bilateral and unilateral) showed significantly lower thresholds compared with
controls. The lowest values were observed on the symptomatic side of unilateral
migraine patients. These findings suggest that sensorimotor mechanisms and/or
pain control systems at the trigeminal level are impaired in migraine. The
bilateral location of these abnormalities seems to point to a centrally located
dysfunction.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 11755258 [PubMed - indexed for MEDLINE]

3115: Neurosci Lett. 2002 Jan 11;317(2):111-3.

Apolipoprotein E gene polymorphisms in patients with migraine.

Rainero I, Grimaldi LM, Salani G, Valfrè W, Savi L, Rivoiro C, Gentile S, Pinessi
L.

Neurology III--Headache Center, Department of Neuroscience, University of Torino,
Via Cherasco 15, 10126 Turin, Italy. irainero@molinette.piemonte.it

To investigate the role of apolipoprotein E (APOE) polymorphisms in migraine, we 
analyzed the APOE genotypes of 241 migraine patients and 587 controls. The
results of a Chi-square analysis indicated that APOE alleles were similarly
distributed (chi(2)=2.89, P=0.24) between cases and controls. However, we found a
significant (P<0.001) increase of the varepsilon2-varepsilon4 genotype in the
group of migraine patients. Patients were divided into three subgroups: migraine 
with aura; migraine without aura; and mixed headaches (migraine associated with
tension-type headache). Subgroup analysis showed that the varepsilon2-varepsilon4
genotype was significantly increased only in patients with mixed headaches. The
stratification of patients by APOE status did not reveal significant associations
with the clinical features of the disease. In conclusion, we observed no
significant association between APOE polymorphisms and migraine. The association 
between the APOE varepsilon2-varepsilon4 genotype and the tension-type headache
deserves further evaluation.

Publication Types: 
    Comparative Study

PMID: 11755252 [PubMed - indexed for MEDLINE]

3116: Brain Res Brain Res Rev. 2001 Dec;38(1-2):33-60.

Spreading depression: a review of the clinical relevance.

Gorji A.

Institut für Physiologie, Universität Münster, Robert-Koch-Strasse 27a, D-48149
Münster, Germany. gorjial@uni-muenster.de

Spreading depression (SD), a transient reversible phenomenon with characteristic 
ionic, metabolic and hemodynamic changes, has been known for over 55 years. A
vast number of studies into this mysterious experimental event provides evidence 
for SD involvement in brain pathophysiology. There is sufficient evidence to
admit that SD plays an important role in some clinical disorders including
migraine, cerebrovascular diseases, head injury and transient global amnesia.
However, the exact pathophysiological mechanisms of SD are unknown and further
studies are needed to demonstrate the involvement of SD in these clinical
disorders. The purpose of this review is to collect different evidences and
hypotheses which suggest a link between SD and clinical disorders. Learning more 
about the importance of SD may increase our understanding of SD associated
disorders and improve our fundamental research strategies.

Publication Types: 
    Review

PMID: 11750926 [PubMed - indexed for MEDLINE]

3117: Clin Sci (Lond). 2002 Jan;102(1):39-43.

Prostaglandin F(2alpha) metabolite and F(2)-isoprostane excretion rates in
migraine.

Helmersson J, Mattsson P, Basu S.

Section of Geriatrics, Department of Public Health and Caring Sciences, Faculty
of Medicine, Uppsala University, Box 609, SE-751 25 Uppsala, Sweden.
Johanna.Helmersson@pubcare.uu.se

The pathophysiology theory of migraine postulates a local, neurogenic
inflammation and the possible involvement of oxidative stress. We analysed the
levels of 15-oxo-dihydro-prostaglandin F(2alpha) (a metabolite of prostaglandin
F(2alpha)) and 8-iso-prostaglandin F(2alpha) (a major isoprostane), which are
biomarkers for inflammation and oxidative stress respectively, in urine from 21
patients with migraine, with and without aura. Urine samples from migraine
patients were collected during a migraine attack, and control samples were
collected from the same subjects on a migraine-free morning. The mean basal
levels of 15-oxo-dihydro-prostaglandin F(2alpha) and 8-iso-prostaglandin
F(2alpha) in the morning control urine samples were 0.54+/-0.11 and 0.31+/-0.13
nmol/mmol of creatinine respectively. The mean levels of
15-oxo-dihydro-prostaglandin F(2alpha) and 8-iso-prostaglandin F(2alpha) in the
urine samples collected during the migraine attack in the 21 patients were
0.53+/-0.13 and 0.32+/-0.11 nmol/mmol of creatinine respectively. Thus there were
no differences in the 15-oxo-dihydro-prostaglandin F(2alpha) and
8-iso-prostaglandin F(2alpha) excretion rates during the migraine attack compared
with on the migraine-free day. However, the basal 8-iso-prostaglandin F(2alpha)
excretion levels on the migraine-free day were significantly lower in
pre-menopausal women (0.24+/-0.08 nmol/mmol of creatinine, n=11) compared with
post-menopausal women (0.39+/-0.14 nmol/mmol of creatinine; n=7; P=0.009). In
conclusion, in this study we found no support for the involvement of inflammation
and oxidative stress in migraine pathophysiology. Our results indicate, however, 
a lower level of oxidative stress in pre-menopausal compared with post-menopausal
women.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 11749659 [PubMed - indexed for MEDLINE]

3118: Arch Intern Med. 2001 Nov 26;161(21):2545-53.

Patient treatment preferences and the 5-HT1B/1D agonists.

Ryan RE Jr.

Ryan Headache Center, Department of Otolaryngology, St. Louis University School
of Medicine, St Louis, MO 63017, USA. drrerjr@aol.com

Migraineurs have specific preferences with regard to migraine therapy. In
surveys, they consistently cite several attributes they seek in a migraine
medication: rapid pain relief, complete pain relief, ability to return to normal 
functioning, relief of migraine-associated symptoms, reduction in headache
recurrence, and minimal adverse effects. When prescribing medication for patients
with migraine, physicians should respect patients' treatment preferences and
select drugs that most closely meet patients' needs. As a class, the 5-HT(1B/1D) 
agonists, or triptans, have many of these attributes, including effectively
relieving pain and associated symptoms and allowing patients to return fairly
quickly to their normal activities. However, differences have emerged in the
ability of specific triptans to satisfy patient preferences. Physicians should
consider these differences when prescribing triptans for their patients with
migraine.

Publication Types: 
    Review

PMID: 11718585 [PubMed - indexed for MEDLINE]

3119: Neurology. 2001 Dec 11;57(11):2034-9.

PedMIDAS: development of a questionnaire to assess disability of migraines in
children.

Hershey AD, Powers SW, Vockell AL, LeCates S, Kabbouche MA, Maynard MK.

Division of Neurology, Children's Hospital Medical Center, Cincinatti, OH, USA.
Andrew.Hershey@CHMCC.ORG

BACKGROUND: For adults, disability produced by migraines has been assessed with a
migraine-specific disability tool-MIDAS. The objective of this study was to
develop and validate a similar tool that accurately depicts the disability of
headaches in school-age children and adolescents. METHODS: A six-question tool
(PedMIDAS) was developed and administered to patients attending a tertiary
referral center for pediatric headaches. Internal consistency and test/retest
reliability were assessed. Validity was assessed by correlating scores with
headache frequency, severity, and duration. Changes in the total score in
response to treatment were assessed in a portion of the patients. RESULTS: The
PedMIDAS questionnaire was administered to 441 patients for a total of 724
trials. The mean score at the initial visit was 44.3 +/- 47.9, whereas the
overall mean score was 25.1 +/- 36.5. A 2-week test/retest reliability assessment
for 56 patients confirmed the stability of the instrument with a Pearson
coefficient of 0.80. The correlation of the PedMIDAS score with frequency,
severity, and duration had Pearson's coefficient values of 0.58, 0.27, and 0.23. 
The PedMIDAS score was reduced to 20.0 +/- 32.3 (p < 0.0001) at the first
follow-up assessment with subsequent continued reduction. CONCLUSIONS: The
PedMIDAS questionnaire provided a developmentally sensitive, reliable, and valid 
assessment of the disability of childhood and adolescent headaches. This
questionnaire provides a tool to assess the impact of migraines in children and
to monitor response to treatment. Further research should focus on additional
validation of the PedMIDAS using a larger population and sampling from other
populations (e.g., primary care and community samples).

PMID: 11739822 [PubMed - indexed for MEDLINE]

3120: Cephalalgia. 2001 Oct;21(8):837-41.

Role of factor XIII Val 34 Leu polymorphism in patients with migraine.

Iniesta JA, Corral J, González-Conejero R, Díaz Ortuño A, Martínez Navarro ML,
Vicente V.

Neurology Services, Hospital General Universitario, Murcia, Spain.

At present, it is contradictory to determine if the combination of certain
prothrombotic polymorphisms and migraine increases the risk to develop ischaemic 
cerebrovascular disease. Recently, the common Val34Leu polymorphism of the
A-chain factor XIII gene, associated with variations in factor XIII activity, has
been suggested to play a significant role in the development of arterial and
venous thrombotic disorders. We analysed the prevalence of this polymorphism in
17 patients with coexisting ischaemic cerebrovascular disease and migraine (5
with aura, and 12 without aura), 89 patients with migraine (43 with aura, and 46 
without aura), 116 patients with ischaemic cerebrovascular disease, and 467
healthy Caucasian controls from the South of Spain. Genomic PCR amplification,
using a mutated oligonucleotide, and allele-specific restriction assays were used
for genotyping. The factor XIII Leu 34 variant was present in 47.1; 40.5; 34.9;
and 35.1% of patients with coexisting ischaemic cerebrovascular disease and
migraine, ischaemic cerebrovascular disease, migraine, and control subjects,
respectively. These data suggest that the factor XIII Leu 34 allele does not play
a protective role against these disorders in our population.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 11737010 [PubMed - indexed for MEDLINE]

3121: Cephalalgia. 2001 Oct;21(8):823-9.

Evaluation of the Dutch version of the migraine quality of life instrument
(MSQOL) and its application in headache coping.

Passchier J, Mourik JC, McKenna SP, van den Berg M, Erdman RA.

Department Medical Psychology and Psychotherapy, The Netherlands Institute of
Health Sciences, Erasmus University Rotterdam, The Netherlands.
passchier@mpp.fgg.eur.nl

The Dutch version of the MSQOL was evaluated psychometrically and applied in a
convenience sample of 90 migraine patients from the Dutch Society of Headache
Patients. Internal consistency and test-retest reliability of the Dutch MSQOL
were good (> 0.90) and comparable with those of the original English version. The
measure also had good validity, with its scores associated as expected with
headache intensity, psychological well-being and level of patient functioning.
Respondents who employ more passive methods of coping with their headaches, such 
as 'worrying', 'retreating' and 'resting', had worse quality of life. 'Worrying' 
was particularly associated with diminished quality of life, suggesting that
cognitive interventions might be of benefit to migraineurs who use this method of
coping.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Validation Studies

PMID: 11737008 [PubMed - indexed for MEDLINE]

3122: Cephalalgia. 2001 Oct;21(8):818-22.

Failure of omega-3 polyunsaturated fatty acids in prevention of migraine: a
double-blind study versus placebo.

Pradalier A, Bakouche P, Baudesson G, Delage A, Cornaille-Lafage G, Launay JM,
Biason P.

Service de Médecine Interne IV, Consultation Migraine et Céphalées, Hôpital Louis
Mourier, Colombes, France. pradalier@ginkgo.fr

Omega-3 polyunsaturated fatty acids (OPFA) have beneficial effects on
inflammatory reactions and production of cytokines. They decrease the release of 
5HT by platelets and possess vasorelaxant activity. This led them to be tried in 
the prophylactic treatment of migraine. After 4 weeks of a single-blind placebo
run-in period, patients were randomized and treated in double-blind condition by 
placebo or OPFA 6 g a day for 16 weeks, followed by a 4-week placebo run-out
period. The intention to treat population included 196 patients. Those who
received all four treatment periods included 96 patients taking OPFA and 87
taking placebo. The primary efficacy analysis was the number of migraine attacks 
during the last 4 weeks of treatment. During this period, the mean number of
attacks was 1.20 +/- 1.40 in the OPFA group and 1.26 +/- 1.11 in the placebo
group (NS). The total number of attacks during the 4-month period of the study
was significantly different between groups: 7.05 in the placebo group, 5.95 in
the OPFA group (P = 0.036). Mean intensity, mean duration of the attacks and
rescue medication use, were not significantly different between the two groups.
Except for a significant difference against OPFA for eructations, the tolerance
was satisfying. Despite a run-in placebo period of 1 month, a very strong placebo
effect was observed in this trial: 45% reduction of the attacks between run-in
and 4-month treatment period (55% in the OPFA group, P = 0.058). Finally, this
large study did not confirm two previous studies based on a small number of
patients.

Publication Types: 
    Clinical Trial
    Multicenter Study
    Randomized Controlled Trial

PMID: 11737007 [PubMed - indexed for MEDLINE]

3123: CNS Drugs. 2001;15(12):969-76; discussion 977-8.

Frovatriptan.

Easthope SE, Goa KL.

Adis International Limited, Auckland, New Zealand. demail@adis.co.nz

black triangle Frovatriptan, a new serotonin receptor agonist developed for the
acute treatment of migraine, has high affinity for serotonin 5-HT1B and 5-HT1D
receptor subtypes and is a potent stimulator of contraction in human basilar
arteries. black triangle A long terminal elimination half-life (approximately 26 
hours) is a distinctive pharmacokinetic feature of frovatriptan which appears to 
be independent of dose, age, gender and renal function. black triangle A single
oral dose of frovatriptan 2.5mg was effective in the acute treatment of migraine 
providing meaningful relief within 2 hours to approximately twice as many
recipients as placebo in clinical trials. black triangle Consistent relief of
migraine symptoms was achieved in patients who treated a number of consecutive
attacks with frovatriptan and the incidence of 24-hour migraine recurrence was
reduced. black triangle Frovatriptan was well tolerated in clinical trials, with 
the overall incidence of adverse events occurring with frovatriptan 2.5mg only
slightly higher than that reported with placebo. Mild to moderate fatigue, nausea
and paraesthesia were the most commonly reported drug-related adverse events.

Publication Types: 
    Review

PMID: 11735616 [PubMed - indexed for MEDLINE]

3124: Genomics. 2001 Dec;78(3):150-4.

Migraine with aura susceptibility locus on chromosome 19p13 is distinct from the 
familial hemiplegic migraine locus.

Jones KW, Ehm MG, Pericak-Vance MA, Haines JL, Boyd PR, Peroutka SJ.

Affymetrix, Inc., 3380 Central Expressway, Santa Clara, California 95051, USA.
keith_jones@affymetrix.com

Migraine is a common neurological disease with a major genetic component.
Recently, it has been proposed that a single locus on chromosome 19p13
contributes to the genetic susceptibility of both rare familial hemiplegic
migraine (FHM) and more common types of migraine, migraine with aura and migraine
without aura. We analyzed 16 families for co-segregation of migraine with aura
and chromosome 19p13 markers. Using multipoint model-free linkage analysis, we
obtained a lod score of 4.28 near D19S592. Using an affecteds-only model of
linkage, we observed a lod score of 4.79 near D19S592. We were able to provide
statistical evidence that this locus on chromosome 19p13 is most likely not the
gene CACNA1A, mutations in which cause FHM. These data indicate that chromosome
19p13 contains a locus which contributes to the genetic susceptibility of
migraine with aura that is distinct from the FHM locus.

PMID: 11735221 [PubMed - indexed for MEDLINE]

3125: Genomics. 2001 Dec;78(3):135-49.

Erratum in:
    Genomics 2002 Feb;79(2):271.

Single-nucleotide polymorphism alleles in the insulin receptor gene are
associated with typical migraine.

McCarthy LC, Hosford DA, Riley JH, Bird MI, White NJ, Hewett DR, Peroutka SJ,
Griffiths LR, Boyd PR, Lea RA, Bhatti SM, Hosking LK, Hood CM, Jones KW, Handley 
AR, Rallan R, Lewis KF, Yeo AJ, Williams PM, Priest RC, Khan P, Donnelly C,
Lumsden SM, O'Sullivan J, See CG, Smart DH, Shaw-Hawkins S, Patel J, Langrish TC,
Feniuk W, Knowles RG, Thomas M, Libri V, Montgomery DS, Manasco PK, Xu CF, Dykes 
C, Humphrey PP, Roses AD, Purvis IJ.

GlaxoSmithKline Medicines Research Centre, Gunnels Wood Road, Stevenage SG1 2NY, 
UK. lm93678@gsk.com

We have identified a migraine locus on chromosome 19p13.3/2 using linkage and
association analysis. We isolated 48 single-nucleotide polymorphisms within the
locus, of which we genotyped 24 in a Caucasian population comprising 827
unrelated cases and 765 controls. Five single-nucleotide polymorphisms within the
insulin receptor gene showed significant association with migraine. This
association was independently replicated in a case-control population collected
separately. We used experiments with insulin receptor RNA and protein to
investigate functionality for the migraine-associated single-nucleotide
polymorphisms. We suggest possible functions for the insulin receptor in migraine
pathogenesis.

PMID: 11735220 [PubMed - indexed for MEDLINE]

3126: Arq Neuropsiquiatr. 2001 Dec;59(4):944-7.

Episodic paroxysmal hemicrania with seasonal variation: case report and the
EPH-cluster headache continuum hypothesis.

Veloso GG, Kaup AO, Peres MF, Zukerman E.

Department of Neurology, Federal University of São Paulo, São Paulo, SP, Brazil. 
germanyveloso@hotmail.com

Episodic paroxysmal hemicrania (EPH) is a rare disorder characterized by
frequent, daily attacks of short-lived, unilateral headache with accompanying
ipsilateral autonomic features. EPH has attack periods which last weeks to months
separated by remission intervals lasting months to years, however, a seasonal
variation has never been reported in EPH. We report a new case of EPH with a
clear seasonal pattern: a 32-year-old woman with a right-sided headache for 17
years. Pain occurred with a seasonal variation, with bouts lasting one month
(usually in the first months of the year) and remission periods lasting around 11
months. During these periods she had headache from three to five times per day,
lasting from 15 to 30 minutes, without any particular period preference. There
were no precipitating or aggravating factors. Tearing and conjunctival injection 
accompanied ipsilaterally the pain. Previous treatments provided no pain relief. 
She completely responded to indomethacin 75 mg daily. After three years, the pain
recurred with longer attack duration and was just relieved with prednisone. We
also propose a new hypothesis: the EPH-cluster headache continuum.

Publication Types: 
    Case Reports
    Review

PMID: 11733843 [PubMed - indexed for MEDLINE]

3127: Neurol Sci. 2001 Jun;22(3):275-8.

Migraine and arterial dissection in a young woman.

Buttinelli C, Spalloni A, Fieschi C, Rasura M.

Department of Neurological Sciences, La Sapienza University of Rome, Viale
dell'Università 30, I-00185 Rome, Italy.

Ischemic stroke in young adults is rare (5%-10% of all ischemic strokes) and, in 
absence of other risk factors, may be associated with migraine. We describe the
case of a 34-year-old woman, with a history of migraine without aura, who
presented a sudden onset of headache with Horner's syndrome, and in whom
neuroimaging showed evidence compatible with fibromuscular dysplasia (FMD) and
arterial dissection of the extracranial internal carotid artery (ICA) and the
carotid siphon. In our opinion, in young women with a long history of migraine, a
careful study of the extracranial and intracranial arteries would be useful,
although the cost/benefit ratio does not at present justify such a procedure. Our
aim in the future is, therefore, to study a larger sample of migraine patients in
order to find those patients who are most at risk of arterial dissection and who 
should, consequently, be carefully studied.

Publication Types: 
    Case Reports

PMID: 11731884 [PubMed - indexed for MEDLINE]

3128: Lancet. 2001 Nov 17;358(9294):1668-75.

Comment in:
    Headache. 2002 Oct;42(9):948.    Lancet. 2002 Mar 30;359(9312):1151-2; author reply 1152-3.    Lancet. 2002 Mar 30;359(9312):1151; author reply 1152-3.    Lancet. 2002 Mar 30;359(9312):1152; author reply 1152-3.    Lancet. 2002 Mar 30;359(9312):1152; author reply 1152-3.    Lancet. 2002 Mar 30;359(9312):1152; author reply 1152-3.

Oral triptans (serotonin 5-HT(1B/1D) agonists) in acute migraine treatment: a
meta-analysis of 53 trials.

Ferrari MD, Roon KI, Lipton RB, Goadsby PJ.

Department of Neurology, Leiden University Medical Centre, 2300 RC Leiden,
Albinusdreef 2, 2333 ZA, Leiden, Netherlands. M.D.Ferrari@LUMC.NL

BACKGROUND: The triptans, selective serotonin 5-HT(1B/1D) agonists, are very
effective acute migraine drugs with a well- developed scientific rationale. Seven
different triptans will soon be clinically available, making evidence-based
selection guidelines necessary. Triptan trials have similar designs, facilitating
meta-analysis; this will provide a foundation for using triptans in clinical
practice. METHOD: We asked pharmaceutical companies and the principal
investigators of company-independent trials for raw patient data of all
double-blind, randomised, controlled, clinical trials of oral triptans in
migraine. We calculated summary estimates across studies for important efficacy
and tolerability parameters, and separately summarised direct comparator trials. 
RESULTS: 53 clinical trials (12 unpublished) involving 24089 patients, met the
criteria for inclusion. Mean results for 100 mg sumatriptan were 59% (95% CI
57-60) for 2 h headache response (improvement from moderate or severe to mild or 
no pain); 29% (27-30) for 2 h pain free (improvement to no pain); 20% (18-21) for
sustained pain free (pain free by 2 h and no headache recurrence or use of rescue
medication 2-24 h post dose); and 67% (63-70) for consistency (response in at
least two of three treated attacks); placebo-subtracted proportions for patients 
with at least one adverse event (AE) were 13% (8-18), for at least one central
nervous system AE 6% (3-9), and for at least one chest AE 1.9% (1.0-2.7).
Compared with these data, 10 mg rizatriptan showed better efficacy and
consistency, and similar tolerability; 80 mg eletriptan showed better efficacy,
similar consistency, but lower tolerability; 12.5 mg almotriptan showed similar
efficacy at 2 h but better other results; 2.5 mg naratriptan and 20 mg eletriptan
showed lower efficacy and (the first two) better tolerability; 2.5 mg and 5 mg
zolmitriptan, 40 mg eletriptan, and 5 mg rizatriptan showed very similar results.
The results of the 22 trials that directly compared triptans show the same
overall pattern. We received no data on frovatriptan, but publicly available data
suggest lower efficacy. INTERPRETATION: At marketed doses, all oral triptans were
effective and well tolerated. 10 mg rizatriptan, 80 mg eletriptan, and 12.5 mg
almotriptan provide the highest likelihood of consistent success.

Publication Types: 
    Meta-Analysis
    Research Support, Non-U.S. Gov't

PMID: 11728541 [PubMed - indexed for MEDLINE]

3129: Cranio. 2001 Oct;19(4):269-78.

Migraine and tension-type headache reduction through pericranial muscular
suppression: a preliminary report.

Shankland WE 2nd.

drwes@drshankland.com

Migraine and tension-type headaches have always plagued mankind. In spite of all 
the research dollars spent trying to determine the etiologies of these headaches,
the neurology community still has not established a known cause of migraine and
tension type headaches. This paper describes a study that was conducted for the
U.S. Food and Drug Administration in which the efficacy of the Nociceptive
Trigeminal Inhibition Tension Suppression System was evaluated and proved safe
and efficacious in the reduction of medically diagnosed migraine and tension-type
headache.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial

PMID: 11725851 [PubMed - indexed for MEDLINE]

3130: Neurology. 2001 Nov 27;57(10):1811-7.

Dose finding, placebo-controlled study of oral almotriptan in the acute treatment
of migraine.

Dahlöf C, Tfelt-Hansen P, Massiou H, Fazekas A; Almotriptan Study Group.

Gothenburg Migraine Clinic, Gothenburg, Sweden. carl.dahlof@migraineclinic.se

OBJECTIVE: To assess the efficacy and tolerability of oral almotriptan, a
selective serotonin receptor (5-HT1B/1D) agonist, when used at different doses in
the treatment of acute migraine. METHODS: This was a placebo controlled,
double-blind, parallel-group, dose-finding study. Patients satisfying
International Headache Society criteria for acute migraine were randomized to a
single dose of placebo or oral almotriptan 2, 6.25, 12.5, or 25 mg at the onset
of moderate or severe pain. Patients graded pain intensity on a 4-point verbal
scale from 0 (no pain) to 3 (severe pain) and recorded adverse events. The
primary efficacy variable was headache response at 2 hours. Data were analyzed on
an intent-to-treat basis. RESULTS: Nine hundred and three patients were
randomized, and 742 were included in the evaluation of the efficacy and
tolerability. Headache response at 2 hours was 32.5% with placebo, and 30%,
56.3%, 58.5%, and 66.5% with almotriptan 2, 6.25, 12.5, and 25 mg doses (p < 0.05
for 6.25, 12.5, and 25 mg vs placebo). A dose-dependent decrease in the incidence
of migraine-associated symptoms and the need for escape medication was observed. 
The incidence of adverse events with the almotriptan 2-mg, 6.25-mg, and 12.5-mg
groups was comparable to that with the placebo group. CONCLUSION: Almotriptan
12.5 mg demonstrated the most favorable ratio between efficacy and tolerability, 
offering equivalent efficacy and better tolerability compared with the 25 mg
dose. The minimum effective dose of almotriptan was 6.25 mg.

Publication Types: 
    Clinical Trial
    Clinical Trial, Phase II
    Comparative Study
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 11723269 [PubMed - indexed for MEDLINE]

3131: Neurology. 2001 Nov 27;57(10):1805-11.

Comment in:
    Neurology. 2002 Jul 9;59(1):149-50; author reply 150.    Neurology. 2002 Jul 9;59(1):149; author reply 150.

Ischemic stroke and active migraine.

Milhaud D, Bogousslavsky J, van Melle G, Liot P.

Department of Neurology, CHUV, Lausanne, Switzerland.

OBJECTIVE: To determine the characteristics of acute ischemic stroke (IS) in
patients with active migraine in a prospective stroke registry. METHODS: The
authors studied the characteristics of patients admitted to a population-based
primary-care center with IS and active migraine. The diagnosis of previous
migraine was made based on replies to International Headache Society-based
questions. Patients with migraine were divided into two age groups, one below 45 
years of age and one 45 years or older, and compared by univariate and
multivariate analysis with age-matched control subjects with IS, but without
migraine. RESULTS: Of the 3,502 patients with acute IS, 130 (3.7%) had active
migraine; 66 of these were younger than 45 years and 64 were 45 years or older
(15.8% and 2.1% of the total for the corresponding age group). The proportion of 
women was significantly higher in both groups of patients with migraine (74% and 
63% in the younger and older groups) than in control subjects. In young
migraineurs, the posterior circulation involvement and the presence of patent
foramen ovale were characteristic. In the younger migraine group, nine patients
developed IS during a typical attack of migraine with aura, and 15 during
migraine attack without aura in the absence of any other determined cause. In the
older group, surprisingly, absence of vascular risk factors (previous
hypertension, ischemic heart disease, and cigarette smoking) was characteristic. 
CONCLUSIONS: Migraine is frequent in young patients with IS and infrequent in
older patients with IS. Patients with IS and migraine are mainly women with
stroke features that are age dependent.

PMID: 11723268 [PubMed - indexed for MEDLINE]

3132: J Neurol Neurosurg Psychiatry. 2001 Dec;71(6):747-51.

Hypothalamic involvement in chronic migraine.

Peres MF, Sanchez del Rio M, Seabra ML, Tufik S, Abucham J, Cipolla-Neto J,
Silberstein SD, Zukerman E.

Sao Paulo Headache Center, R Maestro Cardim, 887 01323-001, Sao Paulo SP, Brazil.
marioperes@yahoo.com

OBJECTIVES: Chronic migraine (CM), previously called transformed migraine, is a
frequent headache disorder that affects 2%-3% of the general population.
Analgesic overuse, insomnia, depression, and anxiety are disorders that are often
comorbid with CM. Hypothalamic dysfunction has been implicated in its
pathogenesis, but it has never been studied in patients with CM. The aim was to
analyze hypothalamic involvement in CM by measurement of melatonin, prolactin,
growth hormone, and cortisol nocturnal secretion. METHODS: A total of 338 blood
samples (13/patient) from 17 patients with CM and nine age and sex matched
healthy volunteers were taken. Melatonin, prolactin, growth hormone, and cortisol
concentrations were determined every hour for 12 hours. The presence of comorbid 
disorders was also evaluated. RESULTS: An abnormal pattern of hypothalamic
hormonal secretion was found in CM. This included: (1) a decreased nocturnal
prolactin peak, (2) increased cortisol concentrations, (3) a delayed nocturnal
melatonin peak in patients with CM, and (4) lower melatonin concentrations in
patients with CM with insomnia. Growth hormone secretion did not differ from
controls. CONCLUSION: These results support hypothalamic involvement in CM, shown
by a chronobiologic dysregulation, and a possible hyperdopaminergic state in
patients with CM. Insomnia might be an important variable in the study findings.

PMID: 11723194 [PubMed - indexed for MEDLINE]

3133: Ann Emerg Med. 2001 Dec;38(6):621-7.

Randomized clinical trial of intravenous magnesium sulfate as an adjunctive
medication for emergency department treatment of migraine headache.

Corbo J, Esses D, Bijur PE, Iannaccone R, Gallagher EJ.

Department of Emergency Medicine, Albert Einstein College of Medicine, Bronx, NY,
USA. jillcorbo@aol.com

STUDY OBJECTIVE: We test the hypothesis that intravenous magnesium sulfate is an 
effective adjunctive medication for treatment of acute migraine. METHODS: In this
randomized, double-blind, placebo-controlled trial, adults presenting to 2 urban 
emergency departments with headache meeting International Headache Society
criteria for acute migraine received either 20 mg of intravenous metoclopramide
plus 2 g of intravenous magnesium sulfate or 20 mg of intravenous metoclopramide 
plus a placebo of intravenous saline solution at 15-minute intervals for a
maximum of 3 doses or until pain relief occurred. At 0, 15, 30, and 45 minutes,
patients recorded pain intensity using a standard visual analog scale (VAS). The 
primary study end point was the between-group difference in pain improvement when
initial and final VAS scores were compared. RESULTS: Of 44 patients enrolled (21 
randomized to metoclopramide plus magnesium and 23 to metoclopramide plus
placebo), 42 (95%) were women. Baseline features were comparable in both groups. 
Each group experienced a more than 50-mm improvement in VAS score during the
study. However, this improvement was smaller in the magnesium group for the
primary end point (16-mm difference favoring placebo [95% confidence interval
(CI) -2 to 34 mm]), as was the proportion with normal functional status at their 
final rating (36% absolute difference also favoring placebo [95% CI 7% to 65%]). 
Using a 50% reduction in pain to dichotomize VAS scores, the number needed to
harm with magnesium plus metoclopramide versus metoclopramide alone is 4 patients
(95% CI 2 to 36). CONCLUSION: Although this result was unexpected, our data
suggest that the addition of magnesium to metoclopramide may attenuate the
effectiveness of metoclopramide in relieving migraine. Countertherapeutic
cerebral vasodilatation caused by magnesium is a plausible, although unproven,
explanation for this finding. Because of the preponderance of women in our trial,
these data may not be generalizable to men.

Publication Types: 
    Clinical Trial
    Comparative Study
    Randomized Controlled Trial

PMID: 11719739 [PubMed - indexed for MEDLINE]

3134: Brain Res Bull. 2001 Oct-Nov 1;56(3-4):239-41.

Familial hemiplegic migraine: a ion channel disorder.

Carrera P, Stenirri S, Ferrari M, Battistini S.

I.R.C.C.S. H San Raffaele, Laboratorio Biologia Molecolare Clinica, Milano,
Italy. carrera.paola@hsr.it

At present, little information is available on the genetics of common migraines, 
most likely to be considered a multifactorial disease. Recently, the CACNA1A gene
encoding the brain-specific P/Q type calcium channel alpha(1) subunit, has been
cloned and mutations in this gene, located on chromosome 19p13, have been shown
to be involved in familial hemiplegic migraine (FHM), a rare autosomal dominantly
inherited subtype of migraine with aura. Being part of the migraine spectrum, FHM
represents a good model to study the genetics of more common forms of migraine.
Different classes of mutations within the CACNA1A gene have been associated with 
different diseases, thus identifying a new member among 'channelopathies'.
Variable clinical expression and genetic heterogeneity of FHM will be discussed.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 11719257 [PubMed - indexed for MEDLINE]

3135: Curr Opin Investig Drugs. 2001 Sep;2(9):1261-8.

Development of CGRP antagonists for the treatment of migraine.

Doods H.

Boehringer Ingelheim Pharma KG, Birkendorfer Strasse 65, 88397 Biberach an der
Riss, Germany. henri.doods@bc.boehringer-ingelheim.com

Migraine is one of the most common neurological disorders, involving periodical
attacks of headache and nausea as well as a plethora of other symptoms. Although 
considerable progress has been made, the pathophysiology of migraine is still not
understood. However, several observations point to an involvement of calcitonin
gene-related peptide (CGRP). Migraine headache involves the activation of the
trigeminal system and dilatation of cranial vessels. CGRP is localized to neurons
in the trigeminal ganglia and CGRP levels are increased during a migraine attack,
presumably causing the vasodilation observed. Accordingly, it is conceivable that
inhibition of CGRP-evoked dilatation of the cranial vessels may provide a novel
treatment for migraine headache. The non-peptidic CGRP antagonist BIBN-4096BS
(Boehringer Ingelheim) is presently under clinical investigation to assess the
importance of CGRP in migraine headache and to answer the question of whether the
concept of CGRP antagonists may offer advantages, e.g., higher efficacy, lower
recurrence rate or improved side-effect profile, compared to the currently used
antimigraine drugs.

Publication Types: 
    Review

PMID: 11717813 [PubMed - indexed for MEDLINE]

3136: Curr Opin Investig Drugs. 2001 Sep;2(9):1250-60.

Mutant P/Q-type calcium channel electrophysiology and migraine.

Plomp JJ, van den Maagdenberg AM, Molenaar PC, Frants RR, Ferrari MD.

Department of Neurology, Department of Physiology and Medical Pharmacology,
Leiden University Medical Center, POB 9600, 2300 RC, Leiden, The Netherlands.
j.j.plomp@lumc.nl

The pathophysiological mechanisms of migraine are not yet very well understood.
The gene CACNA1A, coding for the alpha 1A subunit of neuronal P/Q-type Ca2+
channels is mutated in the rare Mendelian inherited variant, familial hemiplegic 
migraine. This finding suggests a role for disturbed neuronal Ca2+ influx and/or 
homeostasis in the pathophysiology of migraine. It has stimulated in vitro
electrophysiological investigations into the function of mutant human and mouse
P/Q-type channels at cell bodies and synapses. A complex picture has emerged from
this work, showing that different CACNA1A mutations lead to different effects on 
Ca2+ channel behavior and that synaptic transmission may become affected. We will
review these studies and discuss the possible implications for the understanding 
of migraine pathophysiology.

Publication Types: 
    Review

PMID: 11717812 [PubMed - indexed for MEDLINE]

3137: Rev Laryngol Otol Rhinol (Bord). 2001;122(2):85-8.

Assessment of migraine-related cochleovestibular symptoms.

Bayazit Y, Yilmaz M, Mumbuç S, Kanlikama M.

Gaziantep University, Faculty of Medicine, Department of Otolaryngology and Head 
and Neck Surgery, Kolejtepe, Gaziantep, Turkey. bayazity@yahoo.com

The objective was to assess the cochleovestibular symptoms in migraine.
Therefore, a questionnaire form was prepared to record the data obtained from 20 
migraineurs. All patients were assessed with audiometry, bithermal caloric
testing and auditory brainstem response testing (ABR) between the migraine
attacks, and 8 of them were also assessed during the attacks. Dizziness (30%) was
the most common symptom that was followed by vertigo (25%) and tinnitus (20%).
All patients had hearing within normal limits. Positional test (Hallpike
maneuver) was positive in 2 (10%). Bithermal caloric testing revealed canal
paresis in 3 (15%) patients. ABR results were normal in 13 patients. Seven
patients (35%) had abnormal ABR results. Four of them (20%) had elongation in the
absolute wave latencies (wave I, III and V) and normal IPLs of wave I-III, III-V 
and I-V. Three (15%) patients had elongation in the absolute wave latencies as
well as in the IPLs of wave I-III, III-V and I-V. In conclusion,
cochleovestibular symptoms can be seen in migraineurs. The test results between
and during attacks are similar. The subjective cochleovestibular symptoms did not
correlate with the objective tests performed (audiometry, ABR and caloric
testing).

Publication Types: 
    Comparative Study

PMID: 11715266 [PubMed - indexed for MEDLINE]

3138: Pain Manag Nurs. 2000 Dec;1(4):139-51.

Predicting disability and quality of life in a community-based sample of women
with migraine headache.

Kolotylo CJ, Broome ME.

Department of Research, University of Alabama at Birmingham, Birmingham, AL, USA.
ckolotylo@aol.com

Migraine is a significant pain problem for almost one third of women in the
United States. Little previous research has been conducted regarding the effects 
of migraine headache on the lives of women migraineurs. The purpose of this
report is to determine the contribution of coping, depressive symptomatology, and
the chronic pain experience on disability and quality of life in women with
migraine. Two hundred and forty-seven women responded to a mailed survey about
migraine headache, the chronic pain experience, coping, depressive
symptomatology, and quality of life. Data were collected with the following: the 
Classification and Diagnostic Criteria for Headache Disorders, Cranial
Neuralgias, and Facial Pain; the McGill Pain Questionnaire; the Chronic Pain
Experience Instrument-Headache; the Coping Strategies Questionnaire; the Center
for Epidemiologic Studies-Depression Scale; the Henry Ford Hospital Disability
Inventory; and the Migraine-Related Quality of Life Questionnaire. Multiple
regression analyses were conducted to determine the amount of variance that could
be explained by selected predictor variables. Women ranged in age from 18 to 66
years and migraineurs reported suffering from migraine from 1 to 54 years. Nearly
half of the migraineurs (41.5%) reported migraine headaches occurring monthly,
and almost a quarter of the sample reported weekly migraines. Migraines were
reported to last for several hours (53.4%). Results indicate that migraine
headache pain was typically severe and throbbing, lasting for hours to days. The 
coping, depressive symptomatology, disability, and quality-of-life variables were
all significantly correlated. Two separate regression analyses that examined
predictor variables and the criterion variables, disability and quality of life, 
showed that a significant amount of both constructs could be explained by the
predictor variables in the model tested. In the first regression analysis,
depressive symptomatology, the chronic pain experience, and migraine headache
pain accounted for 62.9% of the variance in disability. In the second regression 
analysis, 64.8% of the variance in quality of life was accounted for by
depressive symptomatology, migraine headache pain, and the chronic pain
experience. The variance in both outcome variables, disability and quality of
life, was accounted for by similar predictor variables: depressive
symptomatology, the chronic pain experience, and migraine headache pain. Further 
study is needed to determine specific personal and illness-related factors, pain 
characteristics, and coping strategies used that may predict outcomes of migraine
headache such as disability, quality of life, helplessness, and other as yet
unidentified effects of migraine headache.

Publication Types: 
    Research Support, U.S. Gov't, P.H.S.

PMID: 11709867 [PubMed - indexed for MEDLINE]

3139: J Med Chem. 2001 Nov 22;44(24):4031-4.

N-[3-(2-Dimethylaminoethyl)-2-methyl-1H- indol-5-yl]-4-fluorobenzamide: a potent,
selective, and orally active 5-HT(1F) receptor agonist potentially useful for
migraine therapy.

Xu YC, Johnson KW, Phebus LA, Cohen M, Nelson DL, Schenck K, Walker CD, Fritz JE,
Kaldor SW, LeTourneau ME, Murff RE, Zgombick JM, Calligaro DO, Audia JE, Schaus
JM.

Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana 46285, 
USA. Xu_Yao-Chang@Lilly.com

Recent studies have demonstrated that selective 5-HT(1F) receptor agonists
inhibit neurogenic dural inflammation, a model of migraine headache, indicating
that these compounds may be effective therapies for the treatment of migraine
pain. This communication describes the synthesis and discovery of a novel
compound, N-[3-(2-(dimethylamino)ethyl)-2-methyl-1H-indol-5-yl]-4-fluorobenzamide
(4), which possesses high binding affinity and selectivity at the 5-HT(1F)
receptor relative to more than 40 other serotonergic and nonserotonergic
receptors examined.

Publication Types: 
    In Vitro

PMID: 11708905 [PubMed - indexed for MEDLINE]

3140: Ann Neurol. 2001 Nov;50(5):582-7.

Magnetoencephalographic fields from patients with spontaneous and induced
migraine aura.

Bowyer SM, Aurora KS, Moran JE, Tepley N, Welch KM.

Department of Neurology, Henry Ford Health System, Detroit, MI 48202, USA.
susanbo@neurnis.neuro.hfh.edu

We investigate and characterize the magnetoencephalographic waveforms from
patients during spontaneous and visually induced migraine aura. Direct current
neuromagnetic fields were measured during spontaneous onset of migraine auras in 
4 migraine patients, and compared with recordings from 8 migraine-with-aura
patients and 6 normal controls during visual stimulation of the occipital cortex.
Complex direct current magnetoencephalographic shifts, similar in waveform, were 
observed in spontaneous and visually induced migraine patients, but not in
controls. Two-dimensional inverse imaging showed multiple cortical areas
activated in spontaneous and visually induced migraine aura patients. In normal
subjects, activation was only observed in the primary visual cortex. Results
support a spreading, depression-like neuroelectric event occurring during
migraine aura that can arise spontaneously or be visually triggered in widespread
regions of hyperexcitable occipital cortex.

Publication Types: 
    Clinical Trial
    Controlled Clinical Trial
    Research Support, U.S. Gov't, P.H.S.

PMID: 11706963 [PubMed - indexed for MEDLINE]

3141: Vision Res. 2001 Oct;41(23):3063-8.

Visual search in migraine and visual discomfort groups.

Conlon E, Humphreys L.

School of Applied Psychology, Gold Coast Campus, Griffith University, PMB 50 Gold
Coast Mail Centre, Gold Coast 9726, Australia. e.conlon@mailbox.gu.edu.au

Two experiments that investigate automatic and conscious attention among migraine
and visual discomfort groups are reported. The prediction of a heightened sensory
sensitivity producing a processing speed advantage in migraine was tested. In
Experiment 1, an automatic attention task was conducted. There was no effect of
migraine group, but the high visual discomfort group responded significantly more
slowly than the low visual discomfort group when 16 distractors were presented.
In Experiment 2, a conscious visual attention task was conducted. No
processing-speed advantage was found for migraine groups. In all conditions, the 
high visual discomfort group performed significantly more slowly than other
groups. It was concluded that heightened sensory sensitivity could not explain
the processing speed advantage found previously in migraine but may explain the
processing speed disadvantage found for the high visual discomfort group. Results
are discussed in terms of disordered sustained attention in the high visual
discomfort group.

PMID: 11704243 [PubMed - indexed for MEDLINE]

3142: Headache. 2001 Oct;41(9):899-901.

Migraine MLT-down: an unusual presentation of migraine in patients with
aspartame-triggered headaches.

Newman LC, Lipton RB.

The Headache Institute, St. Lukes-Roosevelt Hospital Center, 1000 Tenth Avenue,
Suite 1C10, New York, NY 10019, USA.

Aspartame, an artificial sweetener added to many foods and beverages, may trigger
headaches in susceptible individuals. We report two patients with
aspartame-triggered attacks in whom the use of an aspartame-containing acute
medication (Maxalt-MLT) worsened an ongoing attack of migraine.

Publication Types: 
    Case Reports

PMID: 11703479 [PubMed - indexed for MEDLINE]

3143: Headache. 2001 Oct;41(9):895-8.

Hypoglycemia rebound migraine.

Jacome DE.

Department of Medicine, Franklin Medical Center, Greenfield, Massachusetts, USA.

OBJECTIVE: To describe a patient with specific hypoglycemia rebound migraine.
BACKGROUND: There is an increased prevalence of headache in persons with
diabetes. Although hypoglycemia may precipitate headache in some diabetic (and
nondiabetic) patients, it is not a universal pathogenetic mechanism responsible
for headache in those individuals or in normal fasting subjects. METHODS:
Clinical history, review of past medical records, neurologic examination,
follow-up evaluation, electroencephalogram, and computerized tomography of the
head. RESULTS: A 56-year-old man with unstable diabetes mellitus had recurrent
monthly episodes of profound hypoglycemia for 40 years. These episodes were
followed by severe, global, pulsatile headache after glycemia became normal
subsequent to intravenous infusion of glucose and the patient was no longer
confused and lethargic. He had no headache preceding or throughout the actual
hypoglycemic phase. His neurologic examination was normal when asymptomatic. His 
baseline electroencephalogram was normal, but showed mild slowing of the
background in the immediate posthypoglycemic state. Computerized tomography of
the head demonstrated mild atrophic changes. His severe bouts of hypoglycemia and
migraine were ameliorated by prophylactic treatment with valproic acid.
CONCLUSION: Posthypoglycemic migraine may occur exceptionally in patients with
unstable diabetes as a rebound phenomenon, caused by an unidentified mechanism.

Publication Types: 
    Case Reports

PMID: 11703478 [PubMed - indexed for MEDLINE]

3144: Headache. 2001 Oct;41(9):873-82.

Efficacy and tolerability of subcutaneous sumatriptan for acute migraine: a
comparison between ethnic groups.

Burke-Ramirez P, Asgharnejad M, Webster C, Davis R, Laurenza A.

Department of Medicine, University of Puerto Rico School of Medicine, Box 365067,
San Juan, Puerto Rico 00936-5067.

OBJECTIVE: To evaluate efficacy and tolerability of subcutaneous sumatriptan 6 mg
versus placebo for acute migraine between ethnic groups. BACKGROUND: Patients in 
previous sumatriptan studies have been predominantly Caucasian and the effects of
sumatriptan between different ethnic groups are unknown. METHODS: This was a
multicenter, 3-phase, 12-attack study. Phases I and III (inclinic) were
randomized, double-blind, placebo-controlled, crossover designs. Phase II
(outpatient) was a single-blind design. Sumatriptan was compared to placebo
across 2 groups (non-Caucasian and Caucasian) and individual ethnic subgroups
(black, Hispanic, and others). Headache response, pain-free response, associated 
symptoms, and clinical disability were assessed. Tolerability assessments
included the incidence of adverse events, physical examinations, vital signs,
electrocardiograms, and clinical laboratory data. RESULTS: Two hundred patients
treated at least one migraine attack (150 non-Caucasians: 46 blacks, 68
Hispanics, 36 others). Two hours postdose, significantly more inclinic
sumatriptan-treated patients reported headache response (non-Caucasians, 81%
versus 37% placebo; Caucasians, 87% versus 19% placebo; P<.001) and mild or no
clinical disability, compared with placebo (non-Caucasians, 87% versus 50%
placebo; Caucasians, 90% versus 38% placebo; P<.001). Blacks (80%), Hispanics
(83%), and others (74%) reported similar patterns of headache response at 2
hours. Similar results were reported during the outpatient phase. The incidence
of adverse events following sumatriptan during the inclinic phase was similar
between ethnic groups (non-Caucasian, 75%; Caucasian, 79%) and higher than
placebo (non-Caucasian, 51%; Caucasian, 31%). Overall, adverse events in the
outpatient phase of the study were lower than in the inclinic phase. CONCLUSION: 
Sumatriptan injection is effective and well tolerated in non-Caucasians and
Caucasians for the treatment of acute migraine attacks. Only minor differences in
efficacy or tolerability were observed between blacks, Hispanics, and others.

Publication Types: 
    Clinical Trial
    Clinical Trial, Phase I
    Clinical Trial, Phase II
    Clinical Trial, Phase III
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 11703474 [PubMed - indexed for MEDLINE]

3145: Headache. 2001 Oct;41(9):867-72.

Peripheral levels of inflammatory mediators in migraineurs during headache-free
periods.

Mohammadian P, Hummel T, Arora C, Carpenter T.

Cleveland Chiropractic College, 590 North Vermont Avenue, Los Angeles, CA 90004, 
USA.

OBJECTIVES: The present study investigated the peripheral inflammatory changes of
the trigeminovascular system by measuring the inflammatory mediators leukotriene 
B4 (LTB(4)), prostaglandin E2 (PGE(2)), and thromboxane B2 (TXB(2)) in the nasal 
fluid, as well as saliva, of patients with migraine. BACKGROUND: Migraine has
been hypothesized to be as a result of changes in the peripheral or central
nervous system or both. It is still unclear whether peripheral changes in the
trigeminovascular system are involved in the pathogenesis of migraine. METHODS:
Participants were 18 subjects, 9 patients with migraine and 9 controls, matched
for age and sex. Each subject took part in one experimental session during which 
nasal lavage fluid and saliva samples were collected. These samples were analyzed
by competitive enzyme immunoassay using goat anti-rabbit polyclonal antibody.
RESULTS: With the exception of TXB(2), correlational analyses indicated good
correlations between results obtained using nasal lavage or saliva (LTB(4), r(18)
= 0.91; PGE(2), r(18) = 0.95). When comparing inflammatory mediators measured in 
controls and migraineurs, the LTB(4) level was significantly lower in
migraineurs, while no differences were found for PGE(2) and TXB(2). CONCLUSIONS: 
The study demonstrated that nasal lavage, a noninvasive method, can be easily
used for investigations of pathophysiological mechanisms of migraine. In
addition, the results may indicate that there is no peripheral trigeminal
sensitization in the headache-free period of migraineurs compared with controls
when PGE(2), LTB(4), and TXB(2) in saliva and nasal lavage samples are measured.

PMID: 11703473 [PubMed - indexed for MEDLINE]

3146: Headache. 2001 Oct;41(9):862-6.

Comment in:
    Headache. 2002 Apr;42(4):325-6.

Mixing sumatriptan: a prospective study of stratified care using multiple
formulations.

Kaniecki RG.

University of Pittsburgh Headache Center, 120 Lytton Avenue, Suite 300,
Pittsburgh, PA 15213, USA..

OBJECTIVE: To assess the acceptability, utility, and tolerability of a system of 
stratified care of acute migraine using multiple formulations of sumatriptan.
BACKGROUND: Stratified care matches the treatment of a disease to its level of
severity. Sumatriptan, with its multiple formulations, seems a logical option in 
a stratified care approach. Little data exists on the use of multiple
formulations in a single patient population. DESIGN AND METHODS: A prospective,
open-label, outpatient study recruited patients from a single center during the
period from January 1998 through June 1998. Entry criteria included International
Headache Society migraine diagnostic codes 1.1 or 1.2 and an established response
to sumatriptan tablets or nasal spray. Patients who enrolled were allowed to use 
subcutaneous sumatriptan as either primary or rescue therapy for individual
migraine attacks. RESULTS: Two hundred eighteen (80%) of 273 patients on tablets 
and 40 (85%) of 47 patients on nasal spray enrolled. During a period of 6 months,
61% of the patients on tablets and 85% of the patients using the nasal spray used
at least one subcutaneous dose of sumatriptan. This system was efficacious and
well tolerated. The majority of injections were used as rescue treatments
following a failed oral or nasal dose. Two percent withdrew due to lack of
efficacy, and 6% withdrew due to adverse events; however, 92% professed
satisfaction with subcutaneous sumatriptan as an available tool for migraine
management. CONCLUSION: A system of stratified care using multiple formulations
of sumatriptan is efficacious, well tolerated, and preferable to a program
involving a single form of the drug.

Publication Types: 
    Clinical Trial
    Controlled Clinical Trial

PMID: 11703472 [PubMed - indexed for MEDLINE]

3147: Headache. 2001 Oct;41(9):854-61.

Clinical utility of an instrument assessing migraine disability: the Migraine
Disability Assessment (MIDAS) questionnaire.

Lipton RB, Stewart WF, Sawyer J, Edmeads JG.

Department of Neurology, Epidemiology, and Social Medicine, Montefiore Headache
Unit, Albert Einstein College of Medicine, New York, NY, USA.

OBJECTIVE: We evaluated the agreement between Migraine Disability Assessment
(MIDAS) scores and independent physician judgments about pain, disability, and
treatment needs based on patient medical histories. BACKGROUND: The MIDAS
questionnaire measures headache-related disability as lost time due to headache
from paid work or school, household work, and nonwork activities. METHODS: Twelve
histories from patients with migraine were presented to 49 primary and specialty 
care physicians unaware of the MIDAS scores. Physicians graded each patient for
pain level (mild, moderate, or severe), level of disability (none, mild,
moderate, or severe), and need for medical care (from 0 [lowest] to 100
[highest]). Physicians also identified MIDAS scores they associated with
different degrees of disability and with the urgency to prescribe an effective
treatment during the first consultation. RESULTS: The physicians' perceptions of 
the need for medical care based on medical histories correlated with the MIDAS
score (r =.69). Estimates of pain and disability by physicians were directly
correlated with increasing MIDAS scores. Using the physicians' clinical
judgments, the overall MIDAS score was categorized into four grades of increasing
severity. CONCLUSIONS: Scores on the MIDAS are highly correlated with physician
judgments regarding patients' pain, disability, and need for medical care. These 
findings support the potential utility of the MIDAS questionnaire in clinical
practice.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 11703471 [PubMed - indexed for MEDLINE]

3148: Headache. 2001 Oct;41(9):845-53.

Headache and sferics.

Vaitl D, Propson N, Stark R, Walter B, Schienle A.

Department of Clinical and Physiological Psychology, Justus-Liebig, University of
Giessen, Otto-Behaghel-Strasse 10, D-35394 Giessen, Germany.

Many patients with migraine believe weather is a trigger for their headaches. The
objective of this study was to determine if very low frequency sferics,
pulse-shaped electromagnetic fields originating from atmospheric discharges
(lightning), are precipitating factors. The occurrence of sferics impulses is
characterized by a daily, as well as an annual, periodicity and is thought to be 
associated with various pathological processes. The diaries of 37 women suffering
from migraine and tension-type headaches were analyzed over a period of 6 months 
and correlated with daily sferics activity and other weather phenomena in the
area of Giessen, Germany. From October through December (autumn), sferics
activity was correlated with the occurrence of migraine (r = 0.33, P<.01);
however, there was no correlation in July and August (summer), when the
thunderstorm activity had been very intense. In summer, tension-type headaches
were associated with other weather parameters such as temperature (r = 0.36,
P<.01) and vapor pressure (r = 0.27, P<.05).

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 11703470 [PubMed - indexed for MEDLINE]

3149: Altern Med Rev. 2001 Oct;6(5):488-94.

Treatment of migraine with targeted nutrition focused on improved assimilation
and elimination.

Sensenig J, Johnson M, Staverosky T.

This study was undertaken to assess the impact of three months of targeted
nutritional therapy for migraine on health-related quality of life. The study is 
also intended to lend support to a theory that migraine is caused by an
underlying dysfunction involving assimilation or elimination mechanisms. Forty
people were selected from approximately 120 applications. Fourteen participants
were selected from among those applicants within the authors' practices and 26
from applicants solicited via the Internet. Participants were required to
complete the Medical Outcomes Trust Migraine Specific Quality of Life (MSQ)
Questionnaire. Eighty percent of the study participants experienced significant
and sustained improvements in quality of life during the 90 days of the study.
The study instrument is specifically designed to measure quality of life
improvement and thus does not solicit responses relative to number of migraine
attacks or duration of each migraine. However, it should be noted that
improvement in quality of life is likely due to a reduction in the duration and
frequency of migraine attacks.

PMID: 11703169 [PubMed - indexed for MEDLINE]

3150: Mayo Clin Proc. 2001 Nov;76(11):1093-101.

Comment in:
    Mayo Clin Proc. 2002 Feb;77(2):201.

Cost-effectiveness and cost-benefit of sumatriptan in patients with migraine.

Lofland JH, Kim SS, Batenhorst AS, Johnson NE, Chatterton ML, Cady RK, Kaniecki
R, Nash DB.

Office of Health Policy and Clinical Outcomes, Thomas Jefferson University,
Philadelphia, PA 19107, USA. jennifer.lofland@mail.tju.edu

OBJECTIVE: To investigate the cost-effectiveness and cost-benefit of initiating
sumatriptan therapy in patients with acute migraine who were previously taking
nontriptan drugs. PATIENTS AND METHODS: This is an economic analysis of a
prospective, pretest-posttest, observational 6-month outcomes study of 178
patients with a physician diagnosis of migraine who received their first
prescription for sumatriptan between October 1994 and August 1996 and were
members of a mixed-model managed care organization in western Pennsylvania.
Migraine-related resource use data were obtained from the managed care
organization's medical and pharmacy claims databases. The primary outcome measure
for this economic analysis was the total disability time that patients
experienced because of migraine. Patients reported time missed from work and
usual nonwork activities because of migraine on self-administered questionnaires 
at baseline and at 3 and 6 months after initiation of sumatriptan. RESULTS:
Initiation of sumatriptan resulted in a decrease of 662 migraine-disability-days 
for work and 1236 migraine-disability-days for nonwork activities during the 6
months of the study (decrease from 27.8 to 17.2 days per person), totaling 1898
migraine-disability-days averted with sumatriptan therapy. Migraine-related
medical costs were lower after sumatriptan was initiated ($18,351 vs $26,192),
whereas migraine-related pharmacy costs were lower with prior nontriptan drug
therapy ($22,209 vs $74,861). The overall net cost savings after sumatriptan was 
initiated in these patients was $222,332 ($1249 per patient) with a
benefit-to-cost ratio of $5.67 gained for each health care dollar spent from a
societal perspective. The incremental cost-effectiveness ratio was $25 for each
additional migraine-disability-day averted by using sumatriptan vs nontriptan
drug therapy. Sensitivity analysis showed that changes in medical costs had
little effect on the ratios and that sumatriptan remained cost-beneficial across 
a wide range of patient wages. CONCLUSION: This study showed that initiation of
sumatriptan in patients previously receiving nontriptan therapy was
cost-effective and had an economic benefit for patients, employers, and society. 
Sumatriptan also helped patients and physicians achieve goals recommended by the 
US Headache Consortium by reducing patients' disability and thus improving their 
ability to function at work and nonwork activities.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 11702897 [PubMed - indexed for MEDLINE]

3151: Brain. 2001 Dec;124(Pt 12):2490-502.

Delayed inflammation in rat meninges: implications for migraine pathophysiology.

Reuter U, Bolay H, Jansen-Olesen I, Chiarugi A, Sanchez del Rio M, Letourneau R, 
Theoharides TC, Waeber C, Moskowitz MA.

Stroke and Neurovascular Regulation Laboratory, Massachusetts General Hospital,
Harvard Medical School, Charlestown, Massachusetts 02129, USA.

Nitric oxide (NO) has been implicated in migraine pathogenesis based on the
delayed development of typical migraine headache 4-6 h after infusing the NO
donor nitroglycerin [glyceryl trinitrate (GTN)] to migraineurs. Furthermore,
inhibiting the synthesis of NO by treatment with a NO synthase (NOS) inhibitor
attenuates spontaneous migraine headaches in 67% of subjects. Because NO has been
linked to inflammation and cytokine expression, we investigated the delayed
consequences of brief GTN infusion (30 min) on the development of meningeal
inflammation in a rat model using doses relevant to the human model. We found
dose-dependent Type II NOS [inducible NOS (iNOS)] mRNA upregulation in dura mater
beginning at 2 h and an increase in the corresponding protein expression at 4, 6 
and 10 h after infusion. Type II NOS immunoreactivity was expressed chiefly
within resident meningeal macrophages. Consistent with development of a delayed
inflammatory response, we detected induction of interleukin 1beta in dura mater
at 2 and 6 h and increased interleukin 6 in dural macrophages and in rat
cerebrospinal fluid at 6 h after GTN infusion. Myeloperoxidase-positive cells
were rarely found. Leakage of plasma proteins from dural blood vessels was first 
detected 4 h after GTN infusion, and this was suppressed by administering a
specific Type II NOS inhibitor [L-N(6)-(1-iminoethyl)-lysine (L-NIL)]. In
addition to cytokine induction, macrophage iNOS upregulation and oedema formation
after GTN infusion, dural mast cells exhibited granular changes consistent with
secretion at 4 and 6 h. Because iNOS was expressed in dural macrophages following
topical GTN, and in the spleen after intravenous injection, the data suggest that
the inflammatory response is mediated by direct actions on the dura and does not 
develop secondary to events within the brain. Our findings point to the
importance of new gene expression and cytokine expression as fundamental to the
delayed response following GTN infusion, and support the hypothesis that a
similar response develops in human meninges after GTN challenge.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 11701602 [PubMed - indexed for MEDLINE]

3152: Pharmacoeconomics. 2001;19(9):917-25.

Different approaches to valuing the lost productivity of patients with migraine.

Lofland JH, Locklear JC, Frick KD.

Office of Health Policy and Clinical Outcomes, Thomas Jefferson University,
Philadelphia, Pennsylvania 19107-5099, USA. jennifer.lofland@mail.tju.edu

OBJECTIVE: To calculate and compare the human capital approach (HCA) and friction
cost approach (FCA) methods for estimating the cost of lost productivity of
migraineurs after the initiation of sumatriptan from a US societal perspective.
DESIGN: Secondary, retrospective analysis to a prospective observational study.
SETTING: A mixed-model managed care organisation in western Pennsylvania, USA.
PATIENTS: Patients with migraine using sumatriptan therapy. INTERVENTIONS:
Patient-reported questionnaires collected at baseline, 3 and 6 months after
initiation of sumatriptan therapy. OUTCOME MEASURES: The cost of lost
productivity estimated with the HCA and FCA methods. RESULTS: Of the 178 patients
who completed the study, 51% were full-time employees, 13% were part-time, 18%
were not working and 17% changed work status. Twenty-four percent reported a
clerical or administrative position. From the HCA, the estimated total cost of
lost productivity for 6 months following the initiation of sumatriptan was
$US117905 (1996 values). From the FCA, the six-month estimated total cost of lost
productivity ranged from $US28329 to $US117905 (1996 values). CONCLUSIONS: This
was the first study to retrospectively estimate lost productivity of patients
with migraine using the FCA methodology. Our results demonstrate that depending
on the assumptions and illustrations employed, the FCA can yield lost
productivity estimates that vary greatly as a percentage of the HCA estimate.
Prospective investigations are needed to better determine the components and the 
nature of the lost productivity for chronic episodic diseases such as migraine
headache.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 11700778 [PubMed - indexed for MEDLINE]

3153: Acta Neurol Scand. 2001 Nov;104(5):301-7.

Asymmetric scalp distribution of pattern visual evoked potentials during
interictal phases in migraine.

Logi F, Bonfiglio L, Orlandi G, Bonanni E, Iudice A, Sartucci F.

Department of Neuroscience, Institute of Neurology, University of Pisa, Italy.

The N70 and P100 components of transient pattern visual evoked potentials
(P-VEPs) were measured in migraine patients, with and without aura, and in normal
subjects in order to evaluate their latency, amplitude and occipital scalp
distribution. The aim was to find any typical electrophysiological abnormalities 
in migraine. P-VEP N70 and P100 were analyzed in 59 patients without any known
visual field defect. Mean latency and amplitude values were within normal ranges 
for either N70 and P100 all over the occipital scalp; the only significant
abnormality we found was related to the absolute right-left amplitude ratio
either for N70 and P100 waves, providing an asymmetry in P-VEP scalp
distribution; this finding was detected in 78.9% of patients with aura and 72.5% 
without aura. Our results show that in migraine patients, both P-VEP waves N70
and P100, have an asymmetric topographic distribution, even during interictal
phases, that can be explained by a cortical disturbance in agreement with the
neural hypothesis of headache.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 11696025 [PubMed - indexed for MEDLINE]

3154: Int J Clin Pract. 2001 Oct;55(8):552-6.

Patient satisfaction with rizatriptan versus other triptans: direct head-to-head 
comparisons.

Gerth WC, McCarroll KA, Santanello NC, Vandormael K, Zhang Q, Mannix LK.

Outcomes Research, Merck & Co Inc, 1 Merck Drive, PO Box 100, Whitehouse Station,
NJ 08889, USA.

This study summarises the impact of treatment with rizatriptan 10 mg versus other
5-HT 1B/1D receptor agonists (triptans) on patient satisfaction with medication. 
Rizatriptan is a potent, selective 5-HT1B/1D receptor agonist shown to be fast,
effective and well tolerated in the acute treatment of migraine. We investigated 
patients' overall satisfaction with treatment in studies in which direct
comparisons with other triptans were made. Data from five double-blind,
placebo-controlled trials in which rizatriptan 10 mg was compared with another
triptan were included in the analysis. Rizatriptan 10 mg was compared with
sumatriptan 100 mg in one parallel study (n = 916), sumatriptan 50 mg in two
crossover studies (n = 1599), naratriptan 2.5 mg in one parallel study (n = 502),
and zolmitriptan 2.5 mg in one parallel study (n = 701). Satisfaction was
reported by patients on a seven-point scale ranging from 'completely satisfied,
couldn't be better' to 'completely dissatisfied, couldn't be worse' at 2 hours
after dosing. The percent of patients in the top two 'satisfied' categories
(completely or very satisfied) were analysed. More patients on rizatriptan 10 mg 
were completely or very satisfied compared with sumatriptan 100 mg (33% vs 26%, p
< 0.05), sumatriptan 50 mg (40% vs 35%, p < 0.05), naratriptan 2.5 mg (33% vs
19%, p < 0.01), and zolmitriptan 2.5 mg (38% vs 30%, p < 0.05). In all five
studies more patients treated with rizatriptan 10 mg or other triptans were
completely or very satisfied with treatment than patients receiving placebo (p < 
0.001, except naratriptan vs placebo p = 0.004). The results, combined with the
superior efficacy profile (fast, effective, well tolerated) of rizatriptan 10 mg,
should enhance the treatment of migraine headache and lead to improved
therapeutic intervention in clinical practice.

Publication Types: 
    Comparative Study
    Meta-Analysis
    Research Support, Non-U.S. Gov't

PMID: 11695077 [PubMed - indexed for MEDLINE]

3155: Pain. 2001 Nov;94(2):159-67.

Contingent negative variation in subjects at risk for migraine without aura.

Siniatchkin M, Kropp P, Gerber WD.

Institute of Medical Psychology, University of Kiel, Niemannsweg 147, D-24105
Kiel, Germany. msiniat@gwdg.de

Migraine is a complex disease with a significant genetic background. One possible
strategy to investigate the genetics of migraine is the evaluation of functional 
vulnerability markers or biological elementary endophenotypes in individuals with
the greatest probability of developing the disorder (high-risk design). In this
study the contingent negative variation (CNV) was recorded in 35 high-risk
subjects with a positive family history of migraine without aura (FHP), 35
low-risk individuals without a positive family history (FHN), and 35 migraineurs 
(migraine without aura). FHP subjects and migraine patients differed
significantly from FHN individuals with regard to amplitude and habituation slope
of the early CNV component (initial CNV or iCNV). FHP participants demonstrated
the same iCNV abnormalities and distribution among iCNV characteristics as
migraineurs. The amplitude of the iCNV correlated significantly with the relative
number of subjects suffering from migraine among first- and second-degree
relatives. The higher the density of affected individuals in the family, the more
pronounced were the CNV abnormalities in relatives. This study provides evidence 
that the familial factor contributes to the abnormal amplitude, and to a lesser
degree, habituation of the iCNV, and that the iCNV may be used as a
functional-genetic vulnerability marker in further research of migraine genetics.

PMID: 11690729 [PubMed - indexed for MEDLINE]

3156: Cochrane Database Syst Rev. 2001;(3):CD003224.

Update in:
    Cochrane Database Syst Rev. 2007;(1):CD003224.

Eletriptan for acute migraine.

Smith LA, Oldman AD, McQuay HJ, Moore RA.

ICRF/NHS Centre for Statistics in Medicine, Institute of Health Sciences, Old
Road, Oxford, UK, OX3 7LF. l.smith@icrf.icnet.uk

BACKGROUND: Eletriptan (Relpax) is a new triptan soon to be made available by
prescription for the treatment of acute migraine. Currently five triptans are
available by prescription and more are under development. In light of the many
drugs for treating acute migraine, there is a need for evidence-based assessments
to help determine the relative efficacy and harm of these treatments. OBJECTIVES:
To determine the efficacy of eletriptan for treating a single migraine attack
using the outcomes of headache response and pain-free response at 0.5, 1, 2 and 4
hours, and sustained relief over 24 hours. To express efficacy in terms of
number-needed-to-treat (NNT). To determine the adverse effects of a single dose
of eletriptan and express this in terms of number-needed-to-harm (NNH). To allow 
for the comparison of the efficacy of eletriptan with other migraine treatments
evaluated systematically in the same way. SEARCH STRATEGY: Data from all Phase
III randomised placebo-controlled trials were made available by the manufacturer,
Pfizer Inc. To date, these trials comprise the only data on eletriptan relevant
to this review in a published or unpublished form; thus, searches of electronic
databases for further trials of eletriptan were not conducted. SELECTION
CRITERIA: Trials of eletriptan for acute migraine; randomised allocation to
treatment groups, including a placebo group; double-blind design; International
Headache Society diagnostic criteria for migraine with or without aura; single
migraine attack; single-dose treatment at standard doses; adult population;
baseline pain of moderate or severe intensity using a 4-point standardised rating
scale (0 = no pain, 1 = mild pain, 2 = moderate pain and 3 = severe pain); and
dichotomous or percentage data for at least one of the main efficacy outcomes.
DATA COLLECTION AND ANALYSIS: Trials were scored for quality and data extracted
by two independent reviewers. Dichotomous or percentage data were extracted and
pooled to calculate the relative benefit (RB) or relative risk (RR) and NNTs or
NNHs for a number of outcomes for eletriptan 20 mg, 40 mg and 80 mg. The main
outcomes considered were headache response at 1 and 2 hours, pain-free response
at 2 hours, sustained relief over 24 hours and adverse effects. Minor outcomes
considered were headache response at 0.5 and 4 hours, and pain-free response at
0.5, 1 and 4 hours. MAIN RESULTS: Six trials met the inclusion criteria.
Significant benefit of eletriptan over placebo was shown for eletriptan 20 mg, 40
mg and 80 mg for the primary efficacy outcomes of headache response and pain-free
response at 2 hours. For headache response at 2 hours, the NNTs (with 95%
confidence intervals) were 4.4 (3.4 to 6.2), 2.9 (2.6 to 3.3) and 2.6 (2.4 to
3.0) for eletriptan 20 mg, 40 mg and 80 mg, respectively. For pain-free response 
at 2 hours, the NNTs were 9.9 (6.9 to 18), 4.5 (4.0 to 5.1) and 3.7 (3.4 to 4.2),
for eletriptan 20 mg, 40 and 80 mg, respectively. There was no significant
difference in the incidence of major adverse effects between any dose of
eletriptan and placebo. The incidence of minor adverse effects was significantly 
higher for all eletriptan doses than for placebo, with NNHs of 11 (95% confidence
interval, 6.2 to 39), 7.0 (5.2 to 11) and 3.7 (3.1 to 4.5) for eletriptan 20 mg, 
40 mg and 80 mg, respectively. REVIEWER'S CONCLUSIONS: Eletriptan 20 mg, 40 mg
and 80 mg are effective for the treatment of an acute migraine attack.
Effectiveness is dose-related, with statistically significant differences between
doses for pain-free response and 24-hour outcomes. Eletriptan compares well with 
other triptans available for outcomes measured up to 2 hours and provides
meaningful relief for 24 hours. Taken as a single dose, eletriptan was well
tolerated and caused no major harm. The incidence of minor harm was
dose-dependent, with 80 mg giving significantly more adverse effects than 40 mg.

Publication Types: 
    Review

PMID: 11687056 [PubMed - indexed for MEDLINE]

3157: Cochrane Database Syst Rev. 2001;(3):CD003221.

Update in:
    Cochrane Database Syst Rev. 2007;(1):CD003221.

Rizatriptan for acute migraine.

Oldman AD, Smith LA, McQuay HJ, Moore RA.

62 Campbell Road, Oxford, UK, OX4 3PG. oldman a@ppcuk.com

BACKGROUND: There are a number of different drug treatments for acute migraine,
including currently four triptans, with several more likely to become available
in the future. There is a need for evidence-based information to help determine
the balance of benefit and harm for acute migraine treatment. OBJECTIVES: To
quantitatively assess the efficacy of a single dose of rizatriptan (Maxalt) for
treating a single migraine attack using the outcomes of headache response and
pain-free response at half-an-hour, one hour, two hours, and sustained relief
over 24 hours. To express efficacy in terms of numbers-needed-to-treat (NNTs).
SEARCH STRATEGY: Trials were identified by searching MEDLINE (1966-July 2000),
EMBASE (1980-June 2000), the Cochrane Library (Issue 3, 2000) and the Oxford Pain
Relief Database (1950-1994). Date of last search: July 2000. SELECTION CRITERIA: 
The inclusion criteria were randomised, placebo-controlled trials of rizatriptan 
for acute migraine; double-blind design; International Headache Society
diagnostic criteria for migraine with or without aura; single migraine attack;
single-dose treatment at standard doses; adult population; baseline pain of
moderate or severe intensity using a four-point standardised rating scale;
dichotomous or percentage data for at least one of the main efficacy outcomes;
and full journal publication. DATA COLLECTION AND ANALYSIS: Main outcomes
considered were i) headache response at two hours, ii) headache response at one
hour, iii) pain-free response at two hours, iv) sustained relief over 24 hours,
v) pain-free response at 24 hours and vi) adverse effects. Minor outcomes were
headache response and pain-free response at half-an-hour and four hours, and
pain-free response at one hour. Dichotomous or percentage data were extracted and
used to calculate the relative benefit (RB) and number-needed-to-treat (NNT) for 
each outcome. MAIN RESULTS: Seven trials met our inclusion criteria, with 2626
patients given rizatriptan and 902 given placebo. Significant benefit of
rizatriptan over placebo was shown for both doses of rizatriptan (5 mg and 10 mg)
for all five main efficacy outcomes (ranging from one to 24 hours). A dose
response was seen for the main outcomes. It was not possible to analyse adverse
effects information in a meaningful way. REVIEWER'S CONCLUSIONS: Rizatriptan 5 mg
and 10 mg are effective in treating acute migraine, with a dose-related increase 
in efficacy.

Publication Types: 
    Review

PMID: 11687054 [PubMed - indexed for MEDLINE]

3158: Neuroscience. 2001;106(4):793-800.

The periaqueductal grey matter modulates trigeminovascular input: a role in
migraine?

Knight YE, Goadsby PJ.

Headache Group, Institute of Neurology and The National Hospital for Neurology
and Neurosurgery, Queen Square, WC1N 3BG, London, UK.

The periaqueductal grey (PAG) region of the brainstem is a known modulator of
somatic pain transmission. Migraine is likely to be due to episodic brain
dysfunction in pathways involved in the control of pain and other sensory
modalities, such as light and sound. To investigate the influence of the PAG on
pain transmission from intracranial structures, we examined spinal trigeminal
neuronal activity in response to PAG stimulation in a model of trigeminovascular 
nociception in the cat. Evoked trigeminal neuronal activity in the spinal cord
was reversibly inhibited by stimulation of the PAG. The effect was robust with a 
mean reduction in evoked activity of -61+/-21%. This effect could be seen both
ipsilateral and contralateral to the side of PAG stimulation and was well
localised to the ventrolateral PAG.These data demonstrate that a role of the PAG 
is to inhibit afferent trigeminal nociceptive traffic. Considered with
neurosurgical and human functional imaging studies, these data support the notion
that brainstem dysfunction might lead to disinhibition of trigeminal afferents
and be important in the pain process of migraines.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 11682164 [PubMed - indexed for MEDLINE]

3159: Br Homeopath J. 2001 Oct;90(4):189-97.

Observational study of quality of life in patients with headache, receiving
homeopathic treatment.

Muscari-Tomaioli G, Allegri F, Miali E, Pomposelli R, Tubia P, Targhetta A,
Castellini M, Bellavite P.

Study Group on Non Conventional Medicine of the Medical Association of Venice,
Italy. muscaritomaioli@omeopatia.org

This study describes the results obtained from a prospective observational
research of homeopathic treatment for patients suffering from headache (migraine 
with- and without aura and tension-type headache). Fifty-three patients were
asked to complete the SF-36 questionnaire at the beginning of the treatment and
after 4-6 months. The homeopathic medicine and potency were not pre-defined, but 
were adapted to each single patient according to individualised homeopathic
prescription. Most patients (73.6%) completed the study. There was heterogeneity 
in the answers (patients in very poor health as well as those with only slight
disorders). Analysis of the data according to the concept of 'intention-to-treat'
showed that after therapy, the mean and median scores of all life quality
dimensions rose. More than 60% of the cases experienced an improvement in pain
and the limitations caused by pain, as well as in limitations in social
activities and health in general. All the differences between pre/post post
treatment were statistically highly significant, with the strongest results in
the 'bodily pain' and 'vitality' parameters (P < 0.0001).

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 11680803 [PubMed - indexed for MEDLINE]

3160: Lancet. 2001 Oct 13;358(9289):1230-4.

Comment in:
    Lancet. 2002 Mar 2;359(9308):802.

Selective seratonin 1F (5-HT(1F)) receptor agonist LY334370 for acute migraine: a
randomised controlled trial.

Goldstein DJ, Roon KI, Offen WW, Ramadan NM, Phebus LA, Johnson KW, Schaus JM,
Ferrari MD.

Neuroscience Division, Lilly Research Laboratories, Indianapolis, IN 46285, USA. 
DJGoldstein@Lilly.com

BACKGROUND: Triptans (5-HT(1B/1D) receptor agonists) are effective drugs for
acute migraine, but the side-effect of coronary vasoconstriction restricts their 
use in patients who are at risk of coronary artery disease. We have studied the
efficacy of LY334370, a selective serotonin 1F (5-HT(1F)) receptor agonist with
preclinical efficacy and no vasoconstriction, for migraine relief. METHODS: We
gave LY334370 (20, 60, or 200 mg) or placebo to 99 outpatients with moderate or
severe migraine headaches in a double blind, parallel group study. We measured
efficacy by sustained response, response at 2 h, pain free at 2 h, and sustained 
pain free. FINDINGS: The proportions of patients with defined endpoints for
placebo and LY334370 20, 60, and 200 mg, respectively, were: sustained response, 
two of 26 (8%), three of 22 (14%), 11 of 30 (37%), and 11 of 21 (52%) (dose
response p<0.001); response, five of 26 (19%), four of 22 (18%), 15 of 30 (50%), 
and 15 of 21 (71%) (p<0.001); pain free, one of 26 (4%), none of 22, eight of 30 
(27%), and eight of 21 (38%) (p=0.001); sustained pain free, one of 26 (4%), none
of 22, seven of 30 (23%), and seven of 21 (33%) (p=0.002); recurrence rates, one 
of five (20%), none of four, four of 15 (27%), and three of 15 (20%). More
patients given LY334370 than placebo reported asthenia, somnolence, and
dizziness. INTERPRETATION: Our findings show that LY334370 is effective in
treatment of acute migraine through selective trigeminovascular neuronal
inhibition.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 11675061 [PubMed - indexed for MEDLINE]

3161: J Vestib Res. 2001;11(1):53-65.

Application of multivariate statistics to vestibular testing: discriminating
between Menière's disease and migraine associated dizziness.

Dimitri PS, Wall C 3rd, Oas JG, Rauch SD.

Collaborators: Wall CC 3rd.

Harvard University, Massachusetts Institute of Technology Division of Health
Sciences and Technology, Cambridge, USA.

Menière's disease (MD) and migraine associated dizziness (MAD) are two disorders 
that can have similar symptomatologies, but differ vastly in treatment.
Vestibular testing is sometimes used to help differentiate between these
disorders, but the inefficiency of a human interpreter analyzing a multitude of
variables independently decreases its utility. Our hypothesis was that we could
objectively discriminate between patients with MD and those with MAD using select
variables from the vestibular test battery. Sinusoidal harmonic acceleration test
variables were reduced to three vestibulo-ocular reflex physiologic parameters:
gain, time constant, and asymmetry. A combination of these parameters plus a
measurement of reduced vestibular response from caloric testing allowed us to
achieve a joint classification rate of 91%, independent quadratic classification 
algorithm. Data from posturography were not useful for this type of
differentiation. Overall, our classification function can be used as an unbiased 
assistant to discriminate between MD and MAD and gave us insight into the
pathophysiologic differences between the two disorders.

Publication Types: 
    Research Support, U.S. Gov't, Non-P.H.S.
    Research Support, U.S. Gov't, P.H.S.

PMID: 11673678 [PubMed - indexed for MEDLINE]

3162: Neurology. 2001 Oct 23;57(8):1377-83.

Comment in:
    Neurology. 2002 Sep 10;59(5):787-8; author reply 788.    Neurology. 2002 Sep 10;59(5):787; author reply 788.

Comparison of rizatriptan and other triptans on stringent measures of efficacy.

Adelman JU, Lipton RB, Ferrari MD, Diener HC, McCarroll KA, Vandormael K, Lines
CR.

Headache Wellness Center, Greensboro, NC 27401, USA. jadelman@triad.rr.com

OBJECTIVE: To compare the efficacy of oral rizatriptan 10 mg with oral doses of
sumatriptan, naratriptan, and zolmitriptan on stringent outcome measures.
METHODS: Retrospective analysis of data from five randomized, placebo-controlled,
double-masked clinical trials in which oral rizatriptan was directly compared
with oral sumatriptan 100 mg (n = 772), 50 mg (n = 1116), 25 mg (n = 1183),
naratriptan 2.5 mg (n = 413), and zolmitriptan 2.5 mg (n = 580) for the acute
treatment of a moderate or severe migraine attack. OUTCOME MEASURES: Percentage
of patients pain-free at 2 hours, symptom-free at 2 hours (no pain, nausea,
photophobia, phonophobia, vomiting, or functional disability), 24-hour sustained 
pain-free (no headache at 2 hours, no recurrence, and no additional antimigraine 
medications for 24 hours). RESULTS: More patients taking rizatriptan 10 mg were
pain-free at 2 hours than were patients taking sumatriptan 100 mg (40% vs 33%, p 
= 0.019), sumatriptan 50 mg (40% vs 35%, p = 0.009), sumatriptan 25 mg (38% vs
27%, p < 0.001), naratriptan 2.5 mg (45% vs 21%, p < 0.001), and zolmitriptan 2.5
mg (43% vs 36%, p = 0.041). More patients taking rizatriptan 10 mg were
symptom-free at 2 hours than were patients taking sumatriptan 100 mg (31% vs 22%,
p = 0.002), sumatriptan 50 mg (33% vs 28%, p = 0.003), sumatriptan 25 mg (33% vs 
24%, p < 0.001), naratriptan 2.5 mg (30% vs 11%, p < 0.001), and zolmitriptan 2.5
mg (31% vs 24%, p = 0.042). More patients taking rizatriptan 10 mg had a 24-hour 
sustained pain-free response than did patients taking sumatriptan 100 mg (27% vs 
23%, p = 0.112), sumatriptan 50 mg (30% vs 26%, p = 0.015), sumatriptan 25 mg
(27% vs 20%, p = 0.005), naratriptan 2.5 mg (29% vs 17%, p = 0.004), and
zolmitriptan 2.5 mg (32% vs 24%, p = 0.013). CONCLUSION: Oral rizatriptan 10 mg
was more effective than oral sumatriptan, naratriptan, and zolmitriptan on
stringent outcome measures of pain-free response at 2 hours, symptom-free
response at 2 hours, and 24-hour sustained pain-free response.

Publication Types: 
    Comparative Study
    Meta-Analysis
    Research Support, Non-U.S. Gov't

PMID: 11673575 [PubMed - indexed for MEDLINE]

3163: Brain. 2001 Nov;124(Pt 11):2310-8.

Increased visual after-effects following pattern adaptation in migraine: a lack
of intracortical excitation?

Shepherd AJ.

School of Psychology, Birkbeck College, London, UK.
a.shepaerd@psychology.bbk.ac.uk

Much research on visual function in migraine has examined early aspects of visual
processing, often using detection or discrimination measures and stimuli reported
to trigger an attack, e.g. striped patterns or flickering lights. Differences
between people with and without migraine have been attributed to abnormal
cortical processing in migraine, variously described by interictal
hyperexcitability, heightened responsiveness, a lack of habituation and/or a lack
of intra-cortical inhibition. Here, two experiments are presented that explore a 
uniquely cortical phenomenon, pattern or contrast adaptation, one using the
motion after-effect, one the tilt after-effect. Pattern adaptation reflects
specific interactions between groups of neurones and is therefore ideally suited 
to address proposed models of cortical function in migraine. These models lead to
specific predictions in an adaptation study: there should be smaller effects in
people with migraine than in people without. The results from both adaptation
experiments, however, revealed larger effects in migraine sufferers than in
headache-free control subjects. There were no differences between migraine
subgroups classified according to the presence or absence of aura. These results 
are discussed in terms of models of cortical function in migraine.

Publication Types: 
    Clinical Trial
    Comparative Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 11673331 [PubMed - indexed for MEDLINE]

3164: AJNR Am J Neuroradiol. 2001 Oct;22(9):1795-7.

A case of hemiplegic migraine in childhood: transient unilateral hyperperfusion
revealed by perfusion MR imaging and MR angiography.

Masuzaki M, Utsunomiya H, Yasumoto S, Mitsudome A.

Department of Pediatrics, Fukuoka University School of Medicine, Fukuoka, Japan.

We report on an 8-year-old girl with a typical attack of hemiplegic migraine, in 
whom MR angiography and perfusion MR imaging revealed unilateral dilation of
branches of both the middle and posterior cerebral arteries and hyperperfusion of
the ipsilateral hemisphere, respectively. The findings resolved spontaneously
after the attack. These imaging techniques should be indicated for patients with 
migraine attacks and may play a role in assessing the vascular events in migraine
headache.

Publication Types: 
    Case Reports

PMID: 11673182 [PubMed - indexed for MEDLINE]

3165: J Child Neurol. 2001 Oct;16(10):731-4.

Pediatric migraine prophylaxis with divalproex.

Pakalnis A, Greenberg G, Drake ME Jr, Paolichi J.

Department of Neurology, Ohio State University College of Medicine, Children's
Hospital, Columbus 43205, USA. pakalnisa@pediatrics.ohio-state.edu

We followed 23 patients with pediatric migraine, ranging in age from 7 to 17
years, who were treated with preventive divalproex sodium for migraine
prophylaxis. Patients were evaluated for the presence or absence of comorbid
psychiatric disorders or epilepsy to assess the possible differential effects of 
divalproex therapy. Doses ranged from 3.1 to 32.9 mg/kg/day. Seven patients had
comorbid psychiatric disorders, whereas six patients had epilepsy (three
rolandic, two generalized, and one indeterminate). Fifteen patients had a greater
than 50% reduction in migraine; six patients became headache free. Divalproex
doses used were not statistically different among the three groups. A favorable
response and headache freedom were more likely in patients with migraine alone or
with comorbid epilepsy, and less likely in patients with psychiatric comorbidity.
Divalproex was well tolerated, and no significant side effects were reported. No 
notable changes were noted in behavioral problems, and patients with epilepsy
were well controlled. In our cohort of patients, divalproex was most effective in
patients with migraine alone or comorbid epilepsy.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 11669346 [PubMed - indexed for MEDLINE]

3166: J Neurosci Nurs. 2001 Oct;33(5):270-7, 285.

Efficacy of sumatriptan in the treatment of migraine: a review of the literature.

McAlhany A.

College of Nursing, University of Florida, 1600 SW Archer Road, Gainesville, FL
32610, USA.

Advanced practice nurses treat many patients, including children and adolescents,
with migraine headaches. Management of headache episodes requires a delicate
balance of prophylactic and abortive therapies. Sumatriptan has been used
effectively to treat adult patients with migraine headaches, but its efficacy in 
children has not been established. Results of a literature review provide strong 
evidence supporting the use of sumatriptan in treating adults with migraine
headaches. Some evidence also exists for using sumatriptan to treat migraines in 
pediatric patients. Open prospective studies used small convenience samples, thus
limiting the external validity of the research findings. Two randomized,
double-blind, placebo-controlled, crossover trials found conflicting results for 
the efficacy of sumatriptan in the treatment of pediatric migraine. Further
research is needed to determine its efficacy in children.

Publication Types: 
    Review

PMID: 11668885 [PubMed - indexed for MEDLINE]

3167: J Laryngol Otol. 2001 Oct;115(10):782-7.

Vertigo syndromes and mechanisms in migraine.

Thakar A, Anjaneyulu C, Deka RC.

Department of Otolaryngology and Head Neck Surgery, All India Institute of
Medical Sciences, New Delhi 110029, India. meenaal@ndb.vsnl.net.in

This paper attempts to define and categorize the vertigo associated with
migraine. A retrospective chart review of 344 cases of vertigo identified 19
cases with headaches characteristic of migraine as per strictly defined criteria 
(International Headache Society, 1988). Four distinct types of vertiginous
syndromes were noted. The commonest syndrome (Group I) manifested transient
episodes of imbalance with additional momentary subjective rotary vertigo
worsened by movement. The attacks lasted a few hours and evaluation in the
inter-episode interval demonstrated no vestibular deficit. Group II manifested
transient objective rotatory vertigo of from 10 minutes to a few hours but no
demonstrable permanent vestibular deficit. Group III displayed symptoms and signs
characteristic of benign paroxysmal positional vertigo (BPPV) and Group IV
manifested a permanent unilateral labyrinthine weakness. Causation of vertigo by 
migraine was implied in 10 of 19 cases where the headache and vertigo occurred
simultaneously and in two other cases where the vertigo improved with
anti-migraine prophylactic treatment. Four distinct and characteristic vertigo
syndromes have been noted with migraine. Their spectrum ranges from a transient
reversible dysfunction to a more permanent destruction, and includes involvement 
of both the peripheral and the central vestibular systems.

PMID: 11667987 [PubMed - indexed for MEDLINE]

3168: Life Sci. 2001 Aug 31;69(15):1817-29.

Modulation of in vitro platelet 5-HT release by species of Erythrina and
Cymbopogon.

Rogers KL, Grice ID, Griffiths LR.

Genomics Research Centre and School of Health Science, Griffith University, Gold 
Coast, Queensland, Australia.

Extracts of Australian plants were screened to detect constituents affecting
adenosine di-phosphate (ADP) induced platelet aggregation and
[14C]5-hydroxytryptamine (5-HT) release. Extracts of four tested plants
including, Eremophila gilesii, Erythrina vespertilio, Cymbopogon ambiguus, and
Santalum acuminatum, were found to cause significant inhibition of platelet 5-HT 
release. Inhibition levels ranged from 56-98%, and was not due to the
non-specific effects of protein binding tannins. These extracts, and those we
have previously identified as being active, were examined further to determine if
they affect epinephrine (EPN), arachidonic acid (A.A) or collagen stimulated
platelet aggregation and 5-HT release. Among those extracts investigated, we
found that both the methanolic extract of E. vespertilio and the dichloromethane 
(DCM) extract of C. ambiguus were most potent and caused significant inhibition
of platelet activation induced by EPN, A.A and to a lesser extent by collagen.
Inhibition of ADP induced platelet 5-HT release by both of these extracts, was
dose-dependent, with IC50 values for E. vespertilio and C. ambiguus estimated to 
be 20.4 microl (1.855 mg/ml) and 8.34 microl (0.758 mg/ml), respectively.
Overall, C. ambiguus exhibited most activity and also caused dose-dependent
inhibition of A.A induced platelet activation. These results indicate that
inhibition may occur specifically at a site within the A.A pathway, and suggest
the presence of a cyclo-oxygenase inhibitor. Both E. vespertilio and C. ambiguus 
are reported to be traditional headache treatments, with the present study
providing evidence that they affect 5-HT release.

PMID: 11665843 [PubMed - indexed for MEDLINE]

3169: Arzneimittelforschung. 2001 Sep;51(9):726-32.

Safety profile of almotriptan, a new antimigraine agent. Effects on central
nervous system, renal function and respiratory dynamics.

Gras J, Llupià J, Llenas J, Palacios JM.

Department of Pharmacological Development, Almirall Prodesfarma, Research Center,
Cardener 68-74, 08024-Barcelona, Spain. jgras@almirallprodesfarma.com

Almotriptan (3-[2-(dimethylamino)
ethyl]-5-(pyrrolidin-1-ylsulfonylmethyl)-1H-indole, CAS 154323-57-6) is a new
5-HT1B/1D agonist whose clinical efficacy has been demonstrated in Phase III
clinical trials. This study aimed to evaluate the safety of almotriptan with
respect to the central nervous system, renal function and respiratory dynamics
using preclinical animal models. The results indicate that almotriptan does not
cross the blood-brain barrier, since no effects on/interaction with spontaneous
locomotor activity, hexobarbital-induced sleeping time, caffeine-induced increase
of spontaneous locomotor activity, or hypothermia (caused by stimulation of
central 5-HT1D receptors) was observed following treatment. Almotriptan had a
mild antiemetic effect and a slight, transient diuretic effect in dogs, although 
the latter effect is probably of no clinical relevance. In addition, no effect on
the respiratory system of conscious guinea pigs was observed following
almotriptan treatment. These results indicate that almotriptan has a favourable
safety profile with respect to the central nervous, renal and respiratory
systems.

PMID: 11642004 [PubMed - indexed for MEDLINE]

3170: J AAPOS. 2001 Oct;5(5):307-10.

Magnetic resonance imaging in ophthalmoplegic migraine of children.

O'Hara MA, Anderson RT, Brown D.

Department of Surgery, F. Edward Hébert School of Medicine, Uniformed Services
University of the Health Sciences, Bethesda, Maryland, USA.

PURPOSE: To present 2 children with ophthalmoplegic migraine and characteristic
magnetic resonance imaging (MRI) findings post enhancement with gadopentetate
dimeglumine diethylenetriamine pentaacetic acid (Gd-DTPA). METHODS: Two patients,
ages 3 years and 7 years, underwent MRI during the acute phases of a recurring
oculomotor palsy. MRI was repeated several weeks later as symptoms resolved.
RESULTS: In both cases, enhancement and thickening of the cisternal segment of
the oculomotor nerve were present at initial presentation. Ophthalmoplegia
resolved spontaneously in 1 child and after steroid treatment in the other. Both 
postresolution MRIs demonstrated decrease in enhancement and thickening of the
third nerve. CONCLUSIONS: The enhancing, thickened lesion identified on MRI in
our patients may represent an inflammatory process similar to Tolosa-Hunt
syndrome occurring in the interpeduncular segment of the oculomotor nerve.
Patients with ophthalmoplegic migraine may, therefore, benefit from the use of
steroids. MRI of the brain post enhancement is a useful adjunct in the diagnosis 
and treatment of ophthalmoplegic migraine and should be considered as part of a
workup of ophthalmoplegic migraine in children.

Publication Types: 
    Case Reports

PMID: 11641641 [PubMed - indexed for MEDLINE]

3171: Med Hypotheses. 2001 Oct;57(4):432-4.

Melatonin: a significant contributor to the pathogenesis of migraine.

Toglia JU.

Temple University Health Sciences Center, Philadelphia, Pennsylvania 19141, USA.

It is generally accepted that migraine is caused by a primary biochemical
disorder of the central nervous system involving neurotransmitters, specifically 
serotonin. The pathogenetic mechanism triggered by external and internal stimuli 
is not well explained or understood. This article points to the possibility that 
the pineal gland, a primary source of central serotonin and melatonin,
contributes significantly to migraine attacks. Copyright 2001 Harcourt Publishers
Ltd.

PMID: 11601864 [PubMed - indexed for MEDLINE]

3172: Brain Res Mol Brain Res. 2001 Oct 19;94(1-2):193-6.

Significance of the catechol-O-methyltransferase gene polymorphism in migraine.

Emin Erdal M, Herken H, Yilmaz M, Bayazit YA.

Department of Medical Biology and Genetics, Faculty of Medicine, Mersin
University, Mersin, Turkey.

The objective was to assess the significance of the catechol-o-methyltransferase 
(COMT) enzyme polymorphism in migraine. For this reason, 62 migraineurs and 64
healthy volunteers were included in the study. The analysis of COMT polymorphism 
was performed using PCR. The H/H genotype was more frequent in the control group 
than in the patients group (P=0.032). The homozygous or heterozygous L allele was
over represented in the migraineurs compared with the controls (P=0.013). The L/L
genotype was over represented in the migraineurs who also had a family history of
migraine (P=0.003). There was no relationship between aura and COMT genotypes. In
conclusion, the COMT polymorphism may be of potential pharmacological importance 
regarding the individual differences in the metabolism of catechol drugs in
migraineurs. Although altered catecholamine activity due to polymorphism of COMT 
gene may be one of the mechanisms involved in the pathogenesis of migraine, these
mechanisms are not related to presence or absence of aura.

PMID: 11597779 [PubMed - indexed for MEDLINE]

3173: Pharmacoeconomics. 2001;19(8):819-29.

The cost effectiveness of stratified care in the management of migraine.

Williams P, Dowson AJ, Rapoport AM, Sawyer J.

Genesis Pharma Strategies, Uxbridge, UK.

OBJECTIVE: To examine the cost effectivess of a stratified-care regimen for
patients with migraine--in which patients are stratified by severity of illness, 
and then prescribed differing treatments according to level of severity--compared
with a conventional stepped-care approach. DESIGN AND METHODS: A decision
analytic model was constructed to simulate a controlled clinical trial in which
patients with migraine receiving primary medical care were randomly assigned to
treatment under a stepped-care or a stratified-care regimen. A health service
payer perspective was adopted and the time horizon was 1 year. Data inputs were: 
(i) the frequency and disability of migraine, derived from population-based
studies; (ii) disability level-specific treatment response rates for
over-the-counter analgesics,aspirin/metoclopramide and zolmitriptan as the
representative of high-end therapy obtained from an international consensus
opinion enquiry; and (iii) unit costs of healthcare obtained from UK health
service sources. MAIN OUTCOME MEASURES AND RESULTS: The estimated 1-year direct
healthcare costs per primary care patient with migraine were pound sterling
156.82 for stepped care and sterling pound 151.57 for stratified care. Estimates 
of treatment response rates were 40 and 71% for stepped and stratified care,
respectively. The cost per successfully treated attack was sterling pound 23.43
for stepped care and sterling pound 12.60 for stratified care. Stratified care
remained cost effective when tested in a wide range of one-way sensitivity
analyses, and probabilistic sensitivity analysis showed the cost effectiveness of
stratified care to be significant at the 3% level. Conditional confidence
analysis showed that the level of confidence in the cost effectiveness of
stratified care varied positively with the case mix, i.e. in populations where
the proportion of moderate and severely disabled patients with migraine was
greater than 25%, the cost effectiveness of stratified care remained
statistically significant. CONCLUSION: A stratified-care treatment strategy
(including zolmitriptan as the representative of high-end therapy) is a highly
cost-effective method of managing migraine in the primary care setting compared
with stepped care, delivering improved clinical outcomes at no additional cost.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 11596834 [PubMed - indexed for MEDLINE]

3174: Cephalalgia. 2001 Sep;21(7):781-5.

Human migraine models.

Iversen HK.

Department of Neurology, Glostrup Hospital, University of Copenhagen, Denmark.
hki@dadlnet.dk

The need for experimental models is obvious. In animal models it is possible to
study vascular responses, neurogenic inflammation, c-fos expression etc. However,
the pathophysiology of migraine remains unsolved, why results from animal studies
not directly can be related to the migraine attack, which is a human experience. 
A set-up for investigations of experimental headache and migraine in humans, has 
been evaluated and headache mechanisms explored by using nitroglycerin and other 
headache-inducing agents. Nitric oxide (NO) or other parts of the NO activated
cascade seems to be responsible for the induced headache and migraine.
Perspectives are discussed.

Publication Types: 
    Review

PMID: 11595013 [PubMed - indexed for MEDLINE]

3175: Cephalalgia. 2001 Sep;21(7):778-80.

Genetics of migraine without aura, migraine with aura, migrainous disorder, head 
trauma migraine without aura and tension-type headache.

Russell MB.

Department of Neurology, Gentofte Hospital, University of Copenhagen, Hellerup,
Denmark. mbr@dadlnet.dk

This review is a tribute to Professor Jes Olesen involvement in the genetics of
migraine and tension-type headache as it is coming up to his 60th birthday.

Publication Types: 
    Review

PMID: 11595012 [PubMed - indexed for MEDLINE]

3176: Cephalalgia. 2001 Sep;21(7):757-60.

Cortical spreading depression in migraine.

Lauritzen M.

Department of Clinical Neurophysiology, Glostrup Hospital, Glostrup, Denmark.
marl@glostruphosp.kbhamt.dk

Cortical spreading depression (CSD) is associated with a dramatic failure of
brain ion homeostasis as well as efflux of excitatory amino acids from nerve
cells and increased energy metabolism. There is strong clinical and experimental 
evidence to suggest that CSD is involved in the mechanism of migraine. This paper
will, based on the experience related to the detection of CSD in humans, discuss 
pitfalls and possible strategies for detection of CSD in man. Development of
reliable methods for detection of CSD in humans will determine the extent to
which the large body of experimental findings from animal studies of CSD can be
applied to the investigation and treatment of human brain disease. The paper is
based on the experience that has been gained from two decades of studies of CSD
in relation to clinical neurological diseases.

Publication Types: 
    Review

PMID: 11595007 [PubMed - indexed for MEDLINE]

3177: Cephalalgia. 2001 Sep;21(7):733-7.

Consulting behaviour in migraine and tension-type headache sufferers: a
population survey in Santiago, Chile.

Lavados PM, Tenhamm E.

Neurointensive Care Service, Institute of Neurosurgery, Neurology Service,
Clínica Alemana de Santiago, Chile.

Migraine and tension-type headaches are the most frequent types of headaches in
Santiago. The purpose of this paper is to describe the patterns of health care
utilization in migraine and compare them with tension-type headache sufferers in 
a community-based study of the prevalence of headache in Santiago, Chile. A
two-step questionnaire was administered to an age- and gender-representative
sample of 1540 eligible subjects who were aged 15 years or older. Of these, 1385 
(89.9%) responded. Cases were defined according to the most frequent type of
headache experienced in the last year. Migraine and tension-type headaches were
diagnosed according to a questionnaire-based algorithm constructed using the IHS 
criteria. Consultation rates in migraneurs were significantly (P < 0.01) higher
(63%) than in tension-type headache suffers (39%). Migraneurs were more likely to
be female, younger and less educated, and had more severe attacks than those with
tension-type headache. Female sex, younger age, fewer years of education in
migraneurs and younger age and moderate or severe headache in tension-type
headache sufferers were found to be independently associated with the likelihood 
of ever consulting, respectively. Migraneurs are more likely to consult than
tension-type headache suffers in this population.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 11595001 [PubMed - indexed for MEDLINE]

3178: Cephalalgia. 2001 Sep;21(7):727-32.

Comment in:
    Cephalalgia. 2001 Sep;21(7):711.

Safety and efficacy of PNU-142633, a selective 5-HT1D agonist, in patients with
acute migraine.

Gomez-Mancilla B, Cutler NR, Leibowitz MT, Spierings EL, Klapper JA, Diamond S,
Goldstein J, Smith T, Couch JR, Fleishaker J, Azie N, Blunt DE.

Pharmacia & Upjohn Company, Kalamazoo, MI 491001-0199, USA.
baltazar.gomez-mancilla@am.pnu.com

In this randomized, double-blind, placebo-controlled, parallel-group study,
patients received a single 50-mg oral dose of a 5-HT(1D) agonist, PNU-142633 (n =
34), or matching placebo (n = 35) during an acute migraine attack. No
statistically significant treatment effects were observed at 1 and 2 h after
dosing, even after stratifying by baseline headache intensity. At 1 and 2 h
post-dose, 8.8% and 29.4% of the PNU-142633 group, respectively, and 8.6% and
40.0% of the placebo group, respectively, experienced headache relief; 2.9% and
8.8% of the PNU-142633 group and 0% and 5.7% of the placebo group were free of
headache pain. Adverse events associated with PNU-142633 treatment included chest
pain (two patients) and QTc prolongation (three patients). Results from this
study suggest that anti-migraine efficacy is not mediated solely through the
5-HT(1D) receptor subtype, although this receptor may contribute, at least in
part, to the adverse cardiovascular effects observed with 5-HT agonist
medications.

Publication Types: 
    Clinical Trial
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 11595000 [PubMed - indexed for MEDLINE]

3179: Cephalalgia. 2001 Sep;21(7):712-7.

Corona phenomenon as visual aura symptom in migraine.

Podoll K, Robinson D.

Department of Psychiatry and Psychotherapy, University of Technology Aachen,
Germany.

The visual illusion of a typical corona phenomenon was represented as a visual
migraine aura symptom in six of 562 Migraine Art pictures, whereas another five
pictures illustrated atypical variants of the said illusion. The extra edges of
the corona phenomenon are commonly seen around the perceptual images of objects, 
but in atypical cases they can similarly surround illusory images and both
elementary and complex hallucinatory images. The corona phenomenon is strongly
associated with visual loss and the presence of elementary geometric
hallucinations.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 11594998 [PubMed - indexed for MEDLINE]

3180: Arq Neuropsiquiatr. 2001 Sep;59(3-B):708-11.

Dexamethasone decreases migraine recurrence observed after treatment with a
triptan combined with a nonsteroidal anti-inflammatory drug.

Krymchantowski AV, Barbosa JS.

Headache Center of Rio and Institute of Neurology Deolindo Couto/UFRJ, Rio de
Janeiro, Brasil. abouchkrym@globo.com

BACKGROUND AND OBJECTIVES: Triptans are effective drugs for the acute treatment
of migraine. However, 30-40% of the patients commonly present recurrence before
24 hours therefore requiring another dose. Nonsteroidal anti-inflammatory drugs
(NSAID) such as tolfenamic acid and naproxen sodium combined with sumatriptan
have demonstrated efficacy in reducing recurrence observed with the single use of
this drug. Steroids also have been suggested to treat refractory migraine and
status migranosus. The aim of this study was to evaluate whether patients
presenting frequent recurrence with the combination triptan plus NSAID, would
decrease it with the association of dexamethasone. METHOD: Twenty three patients,
17 women and 6 men with migraine according to IHS criteria were prospectively
studied. All patients presented frequent recurrence (> or= 60%, mean recurrence
rate 74,8%) with the single use of sumatritpan 100 mg or zolmitriptan 2,5 mg or
rizatriptan 10mg in at least 5 consecutive attacks, and didn't present a
reduction of the recurrence rate superior than 20% with the combination of
tolfenamic acid 200 mg or rofecoxib 25 mg in at least 5 other consecutive attacks
(mean recurrence rate 60%). The patients had to treat 6 consecutive moderate or
severe migraine attacks with their usual combination plus 4 mg of dexamathasone
with a maximum of twice a week, and fill out a diary reporting headache
parameters. RESULTS: Twenty patients, 16 women and 4 men completed the study. Of 
those who completed the study, 11 took rizatriptan plus rofecoxib, 4 rizatriptan 
plus tolfenamic acid, 3 zolmitriptan plus rofecoxib, 1 zolmitriptan plus
tolfenamic acid and 1 patient took sumatriptan plus tolfenamic acid, having the
20 patients taken as a third medication, a single tablet of 4 mg of
dexamethasone. All patients took oral formulations and none presented vomiting
after that. Among all 20 patients, one female and one male patient presented
recurrence in 3 out of the 6 attacks (50%) while the remaining 18 patients
revealed recurrence in 1 or 2 treated attacks (mean 23,4%) (p<0,001). CONCLUSION:
We concluded that the judicious use of oral dexamethasone might be useful for a
limited population of migraine patients still presenting recurrence with the
combination of a triptan and a NSAID. Case-control studies and studies with a
randomized double-blind design are necessary to confirm these observations.

PMID: 11593269 [PubMed - indexed for MEDLINE]

3181: Arq Neuropsiquiatr. 2001 Sep;59(3-B):702-7.

Evaluation of headache intensity in migrainous patients with visual handicap
through the tactile analogical scale (TAS).

Piovesan EJ, Lange MC, Kowacs PA, Pacheco C, Werneck LC.

Unidade de Cefaléia, Especialidade de Neurologia, Departamento de Clínica Médica,
Hospital de Clínicas, Universidade Federal do Paraná, Curitiba, PR, Brasil.
piovesan@avalon.sul.com.br

The tactile analogue scale (TAS) was elaborated to be used in blind subjects or
those who can not use the vision during their crises. The objective of this study
was to characterize, from TAS, the architecture of migraine attacks in subjects
with visual disability. For that, 11 migrainous with visual disturb (MVD)
subjects were studied and 22 migrainous subjects with no visual disability as a
control group. All patients fulfilled the criteria for migraine and the patients 
of the group studied showed visual acuteness less than 20/200. To evaluate the
results, the patients of the group MVD were subdivide within two groups,
according to their visual acuteness: subgroup A subjects with subnormal vision
and subgroup B amaurotic ones. In subgroup A measurement 46 attacks with average 
of the migraine attacks of the 56.50 mm, in the subgroup B 45 attacks with
average of the 59.58 mm and in the control group 92 attacks with average of the
49.88 mm. When subgroup B and control group were compared there was a significant
statistic difference (p=0.022). Through these outcomes we can observe that the
migrainous subjects with no visual afference show a higher pain intensity during 
the migraine crises comparing to those subjects with no visual handicap. The
study suggests that, as in other forms of sensibility, the total visual loss can 
also interfere in the nociceptive control of the pain during the migraine
attacks.

PMID: 11593268 [PubMed - indexed for MEDLINE]

3182: Neurology. 2001 Oct 9;57(7):1326-8.

Fibromyalgia is common in patients with transformed migraine.

Peres MF, Young WB, Kaup AO, Zukerman E, Silberstein SD.

Jefferson Headache Center, Department of Neurology, Thomas Jefferson University, 
Philadelphia, PA 19107, USA. marioperes@yahoo.com

Fibromyalgia (FM) and transformed migraine (TM) are common chronic pain
disorders. The authors estimated the prevalence of FM in 101 patients with TM,
and analyzed its relationship to depression, anxiety, and insomnia. FM was
diagnosed in 35.6% of cases. Patients with FM had more insomnia, were older, and 
had headaches that were more incapacitating than patients without FM. Insomnia
and depression predicted FM in patients with TM.

PMID: 11591860 [PubMed - indexed for MEDLINE]

3183: Altern Med Rev. 2001 Aug;6(4):383-9.

The therapeutic potential of melatonin in migraines and other headache types.

Gagnier JJ.

j_gagnier@hotmail.com

A large number of individuals suffer from migraine headaches. Several theories
attempt to explain migraine etiology. One such theory holds that since
environmental stimuli are well known to trigger migraine headaches, the pineal
gland may be involved in migraine etiology. Specifically, a pineal gland
irregularity may be the physical origin of migraine headaches, with subsequent
physiological changes being secondary. Research has found the pineal hormone
melatonin is low in migraine patients. Additionally, several studies found
administering melatonin to migraine sufferers relieved pain and decreased
headache recurrence in some cases. It has been suggested melatonin may play an
important therapeutic role in the treatment of migraines and other types of
headaches, particularly those related to delayed sleep phase syndrome. Current
research supports the hypothesis that migraines are a response to a pineal
circadian irregularity in which the administration of melatonin normalizes this
circadian cycle; i.e., melatonin may play a role in resynchronizing biological
rhythms to lifestyle and subsequently relieve migraines and other forms of
headaches. In addition, research testing the administration of melatonin found it
safe in migraine sufferers, with few or no side effects. However, a larger,
randomized control trial is needed to definitively determine if administration of
melatonin to migraine patients is effective.

Publication Types: 
    Review

PMID: 11578254 [PubMed - indexed for MEDLINE]

3184: Headache. 2001 Sep;41(8):823-5.

Persistent migrainous visual phenomena might be responsive to lamotrigine.

Chen WT, Fuh JL, Lu SR, Wang SJ.

Neurological Institute, Taipei Veterans General Hospital and the Department of
Neurology, National Yang-Ming University School of Medicine, Taipei, Taiwan.

Two patients with migraine reported having experienced persistent auralike visual
phenomena for months to years. All laboratory investigations were normal except
for occipital hypoperfusion on the brain single photon emission computed
tomography. After lamotrigine treatment for 2 weeks, they both had a resolution
of the visual symptoms. Persistent migrainous visual phenomena are potentially
benign and probably a status of spontaneous aura.

Publication Types: 
    Case Reports
    Research Support, U.S. Gov't, Non-P.H.S.

PMID: 11576209 [PubMed - indexed for MEDLINE]

3185: Headache. 2001 Sep;41(8):805-12.

Prevalence of migraine in Croatia: a population-based survey.

Zivadinov R, Willheim K, Jurjevic A, Sepic-Grahovac D, Bucuk M, Zorzon M.

Department of Clinical Medicine and Neurology, University of Trieste, Italy.

OBJECTIVES: The aim of the present study was to estimate the prevalence of
migraine among Croatian adults. This is the first epidemiological study of
migraine in Croatia in which the operational diagnostic criteria of the
International Headache Society have been applied. METHODS: The study population
consisted of all residents (aged 15 to 65 years) of Bakar, County of The Coast
and Gorski Kotar, Croatia. A population-based survey was undertaken using a
"face-to-face, door-to-door" interview METHOD: The participation rate was 73.3%. 
All participants were screened for headache history according to the
International Headache Society criteria. Headache screen positive responders
(65.7%) were interviewed by trained medical students with a structured detailed
interview focused on migraine. RESULTS: A total of 720 lifetime migraineurs were 
identified. The lifetime prevalence of migraine was 22.9% (95% confidence
interval, 20.9 to 25.1) in women, 14.8% (95% confidence interval, 13.1 to 16.8)
in men, and 19% (95% confidence interval, 17.6 to 20.5) in both sexes. The
highest lifetime prevalence of migraine was in women in the age group 40 to 49
years (38.1%). Among 636 active migraineurs, 399 (62.7%) were women and 237
(37.3%) were men; 55.8% had migraine without aura, 35.2% migraine with aura, and 
6.9% migraine both with and without aura. The 1-year prevalence of migraine,
migraine without aura, migraine with aura, and migraine both with and without
aura in women was 18%, 11.3%, 8.6%, and 2.2%, respectively. In men, the 1-year
prevalence of migraine, migraine without aura, migraine with aura, and migraine
both with and without aura was 12.3%, 7.3%, 3%, and 0.7%, respectively.
CONCLUSIONS: The prevalence of migraine in this Croatian population showed rates 
quite similar to those reported in neighboring countries, such as Italy and
France. Further studies are needed to estimate the prevalence rates of migraine
in the total Croatian population.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 11576206 [PubMed - indexed for MEDLINE]

3186: Headache. 2001 Sep;41(8):798-804.

Prevalence and clinical characteristics of headache in medical students in oman.

Deleu D, Khan MA, Humaidan H, Al Mantheri Z, Al Hashami S.

Department of Clinical Pharmacology and Therapeutics, Sultan Qaboos University
and the Neurology Clinic, Sultan Qaboos University Hospital, Muscat, Sultanate of
Oman.

OBJECTIVES: To perform a descriptive epidemiological study of headache in medical
students at Sultan Qaboos University, analyzing prevalence, symptom profile, and 
pattern of health care utilization. BACKGROUND: Headache is one of the most
common complaints in medical practice. To our knowledge, headache has not been
the subject of investigation in medical students in the Arabian Gulf. METHODS:
Lifetime and last-year prevalence of headache was based on a detailed structured 
headache assessment questionnaire. Besides demographic data, headache
characteristics and pattern of health care utilization were evaluated. In
addition, questions were included referring to the use of traditional remedies.
Interviewers included three previously trained final-year medical students. The
evaluation was done per cohort, and the students were guided through the
assessment questionnaire by the interviewers. Migraine and tension-type headache 
were diagnosed according to the criteria of the International Headache Society.
RESULTS: Four hundred three students (95.3%) completed the questionnaire: 151 men
(37.5%) and 252 women (62.5%). The lifetime and last-year prevalence of headache 
was 98.3% and 96.8%, respectively. A positive family history of headache was
found in 57.6% of students. The prevalence rate of migraine and tension-type
headache was found to be the same (12.2%), with a difference in distribution
across sexes: 6.6% of the men and 15.5% of the women had migraine, while 13.9% of
the men and 11.1% of the women suffered from tension-type headache. Only 23.3% of
students sought medical assistance during headache episodes, and 80.3% took
medication: 24.6% took prescribed medication, 72.9% took nonprescription
medication, and only 2.5% took traditional remedies. Acetaminophen (83.1%)
followed by mefenamic acid (24.6%) were the most commonly used drugs.
CONCLUSIONS: The results of this prospective epidemiological study show that
headache is highly prevalent among medical students at this university. The high 
prevalence rate of migraine sufferers in this student population might be due to 
the high female-to-male ratio (1.7:1). It is likely that analgesic use/overuse
also coexists with headache in medical students at Sultan Qaboos University,
since a large majority of them rely on nonprescription medications.

PMID: 11576205 [PubMed - indexed for MEDLINE]

3187: Headache. 2001 Sep;41(8):782-91.

Effects of medication use on health state in postictal migraineurs.

Mulder EJ, Passchier J, Linssen WH, de Geus EJ.

Department of Biological Psychology, Vrije Universiteit, Amsterdam, The
Netherlands.

We investigated whether headache-free patients with migraine report a lower
health state compared with healthy controls, and whether health state is
differently affected during the postattack period after using sumatriptan versus 
habitual nonvasoactive medication. Mood, health state, and personality
questionnaires were administered once during an interictal period and twice
within 30 hours after different migraine attacks treated with sumatriptan or
habitual nonvasoactive medication. Twenty migraineurs without aura, 10
migraineurs with aura, and 30 matched and headache-free controls participated in 
this study. During an interictal period, patients with migraine reported more
problems regarding social activities and pain compared with healthy controls.
During the postictal period, mood (fatigue and emotional state) was negatively
affected by an attack that was treated with habitual medication, whereas health
state (physical pain, social activities, current pain) was similar to the
migraine-free period. Sumatriptan treatment had beneficial effects on aspects of 
health state and mood during the postictal period.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 11576203 [PubMed - indexed for MEDLINE]

3188: Headache. 2001 Sep;41(8):779-81.

Is blood homocysteine elevated in migraine?

Hering-Hanit R, Gadoth N, Yavetz A, Gavendo S, Sela B.

Headache Unit, Sackler Faculty of Medicine, Tel Aviv University, Israel.

OBJECTIVE: To determine total serum homocysteine levels in a large group of
patients with migraine with and without aura. BACKGROUND: Hypercoagulable state
is a known risk factor for stroke in the young. The existence of a
hypercoagulable state has been postulated in migraine and homocysteinemia with
young-onset stroke. To the best of our knowledge, blood homocysteine has not been
studied in a significant number of patients with various forms of migraine.
METHODS: Total serum homocysteine was measured with high-performance liquid
chromatography in 78 patients with migraine and in 126 age- and sex-matched
healthy volunteers. RESULTS: Seventy-eight patients aged 18 to 65 years were
studied: 22 with migraine with aura and 56 with migraine without aura. Only 1 man
had significantly elevated blood homocysteine (38.6 micromol/L), while another
had a borderline elevation (15.8 micromol/L) (reference value for both sexes in
our laboratory is 4 to 14 micromol/L). Both patients suffered from migraine
without aura. CONCLUSIONS: Blood homocysteine is not elevated in migraine.

PMID: 11576202 [PubMed - indexed for MEDLINE]

3189: Headache. 2001 Sep;41(8):774-8.

Valproic acid is effective in migraine prophylaxis at low serum levels: a
prospective open-label study.

Kinze S, Clauss M, Reuter U, Wolf T, Dreier JP, Einhäupl KM, Arnold G.

Department of Neurology, Charité Clinic, Humboldt University of Berlin, Germany.

OBJECTIVE: We evaluated the efficacy of prophylactic valproic acid treatment (6
months) on the frequency of migraine attacks and the number of migraine headache 
days with respect to serum levels. BACKGROUND: Valproic acid, a GABAergic drug,
has been shown to be effective for migraine prophylaxis. Results from several
dose- and serum level-adjusted studies have recommended valproic acid doses
within a range of 500 to 1500 mg per day for migraine prophylaxis. Design and
METHODS: In this prospective open-label study, 52 patients received valproic acid
doses of 300 to 1200 mg per day; 45 patients were treated per protocol. Valproic 
acid serum levels increased linearly in relation to the valproic acid dose and
were between 21 and 107 microg/mL at the end of the treatment period. Patients
were divided into two groups: those with valproic acid serum levels less than 50 
microg/mL (group 1) and those with serum levels greater than 50 microg/mL (group 
2). RESULTS: The frequency of migraine attacks was significantly reduced in group
1 from 3.5 +/- 0.9 to 2.0 +/- 0.9 attacks per month. Migraine headache days also 
decreased (6.4 +/- 3.5 to 4.6 +/- 2.9 days per month). In the high serum level
group, a reduction of migraine attacks from 3.5 +/- 0.9 to 2.8 +/- 1.0 attacks
per month and only a slight decrease in headache days (6.4 +/- 3.5 to 6.1 +/- 2.4
days per month) was observed. The outcome of group 1 (low serum level) was
significantly better than that of group 2 with respect to both parameters
(P<.05). Side effects were generally mild and temporary. CONCLUSIONS: Due to the 
lack of additional benefit from higher valproic acid doses (more than 600 mg per 
day), we recommend daily valproic acid doses of 500 to 600 mg with a target serum
level less than 50 microg/mL for the prophylactic treatment of migraine.

Publication Types: 
    Clinical Trial
    Comparative Study
    Controlled Clinical Trial

PMID: 11576201 [PubMed - indexed for MEDLINE]

3190: Headache. 2001 Sep;41(8):768-73.

Reduction in the intensity of abortive migraine drug use during coumarin therapy.

Rahimtoola H, Egberts AC, Buurma H, Tijssen CC, Leufkens HG.

Department of Pharmacy Practice Research, SIR Institute, Leiden, The Netherlands.

OBJECTIVE: To investigate the impact of coumarin therapy on migraine attack
frequency. BACKGROUND: Sporadic case reports and clinical studies have described 
beneficial effects of coumarin therapy on migraine severity. Design and METHODS: 
A retrospective follow-up study based on a prescription database covering a
population of 450 000 was conducted. All patients using an abortive migraine drug
(ergotamine or sumatriptan) and subsequently treated with either coumarin (index 
group) or low-dose acetylsalicylic acid (control group) were analyzed. The impact
of coumarin and low-dose acetylsalicylic acid on the frequency of migraine
attacks was assessed by measuring the intensity of ergotamine and sumatriptan
use, in defined daily doses per month per patient, before and during coumarin or 
acetylsalicylic acid treatment. In addition, a "therapeutic intensity reduction" 
was determined for each patient. RESULTS: The study population consisted of 92
patients; 35% had been prescribed coumarin and 65% had been prescribed low-dose
acetylsalicylic acid after the initiation of ergotamine or sumatriptan. Two
thirds of the study population was treated with ergotamine. Overall, ergotamine
and sumatriptan use for the coumarin cohort decreased from 6.4 defined daily
doses per month prior to coumarin treatment to 3.0 defined daily doses during
coumarin treatment, compared with a reduction from 5.2 defined daily doses per
month to 4.4 defined daily doses per month for the low-dose acetylsalicylic acid 
cohort (P>.05). The therapeutic intensity of ergotamine and sumatriptan use was
significantly decreased by 40% for the coumarin cohort, compared with 4.7% for
the low-dose acetylsalicylic acid cohort (P=.004). CONCLUSIONS: We observed that 
coumarin treatment was clearly associated with a reduction in the therapeutic
intensity of abortive migraine drug use in comparison with low-dose aspirin
treatment. This suggests that, overall, the coumarin cohort had experienced a
substantial reduction in the frequency of migraine attacks during anticoagulation
treatment. Our findings, as well as those of others, justify a controlled
clinical trial to further establish the effects of coumarin therapy on migraine
severity and its possible role in the prophylactic management of patients
suffering from migraine.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 11576200 [PubMed - indexed for MEDLINE]

3191: Headache. 2001 Sep;41(8):764-7.

Immunological aspects in migraine: increase of IL-10 plasma levels during attack.

Munno I, Marinaro M, Bassi A, Cassiano MA, Causarano V, Centonze V.

Department of Internal Medicine, Immunology, and Infectious Disease, University
of Bari, Italy.

In the present study, 23 patients with migraine without aura were monitored
during a migraine attack. Plasma levels of interleukin (IL)-4, IL-5, IL-10, and
interferon-gamma were measured by enzyme-linked immunosorbent assay techniques.
Interestingly, we observed low to undetectable IL-5 and IL-4 levels, whereas high
IL-10 levels were seen in 52.2% of the patients. Interferon-gamma plasma levels
were undetectable in all patients. After treatment with sumatriptan, 10 patients 
showed a subsequent decrease in IL-10 and an increase in both IL-4 and IL-5
plasma levels. Although these findings are derived from a limited number of
patients, the apparent return to the IL-4 and IL-5 cytokine profile observed
during the interictal period leads us to speculate that a preferential
enhancement of TH2-type cytokine production may contribute to the pathogenesis of
migraine.

PMID: 11576199 [PubMed - indexed for MEDLINE]

3192: Headache. 2001 Sep;41(8):754-63.

Effect of rizatriptan and other triptans on the nausea symptom of migraine: a
post hoc analysis.

Lipton RB, Pascual J, Goadsby PJ, Massiou H, McCarroll KA, Vandormael K, Jiang K,
Lines CR.

Albert Einstein College of Medicine, Bronx, NY, USA.

OBJECTIVE: To compare the effects of oral rizatriptan, sumatriptan, naratriptan, 
and zolmitriptan on the relief and emergence of nausea during a migraine attack. 
METHODS: Data from five randomized, placebo-controlled, double-blind clinical
trials in which oral rizatriptan 10 mg was directly compared with oral
sumatriptan 100 mg (N = 772), 50 mg (N = 1168), 25 mg (N = 1180), naratriptan 2.5
mg (N = 406), or zolmitriptan 2.5 mg (N = 571) for the acute treatment of a
migraine attack were retrospectively analyzed. Migraine was diagnosed according
to International Headache Society criteria. Presence or absence of nausea was
recorded at baseline and at 0.5, 1, 1.5, and 2 hours after dosing. The end points
analyzed were relief of nausea in those who had it at baseline and emergence of
nausea in those who were free of it at baseline. Treatments were compared using
odds ratios estimated from logistic regression models at 2 hours, and averaged
odds ratios for the first 2 hours posttreatment. RESULTS: Approximately 60% of
patients in each treatment group had nausea at baseline. In those patients with
nausea at baseline, significantly more patients treated with rizatriptan 10 mg
were free of nausea at 2 hours compared with sumatriptan 100 mg (66% versus 58%, 
P =.043), sumatriptan 50 mg (68% versus 57%, P =.010), sumatriptan 25 mg (68%
versus 59%, P =.017), and naratriptan 2.5 mg (59% versus 45%, P =.014). Averaging
over the four posttreatment time points in the first 2 hours, significantly more 
patients treated with rizatriptan 10 mg were free of nausea compared with
sumatriptan 100 mg (P =.004), sumatriptan 50 mg (P =.001), and naratriptan 2.5 mg
(P =.015). No significant differences in nausea relief were seen between
rizatriptan 10 mg and zolmitriptan 2.5 mg, either at 2 hours (65% versus 61%, P
=.210) or over the first 2 hours (P =.781). Rates of treatment-emergent nausea at
2 hours ranged from 11% to 18% with placebo, from 5% to 13% with rizatriptan 10
mg, and from 10% to 20% with other comparator triptans. CONCLUSIONS: Oral
rizatriptan 10 mg was more effective than oral sumatriptan and naratriptan at
eliminating nausea within 2 hours in patients who had it at baseline. Rates of
emergent nausea in patients who were free of it at baseline were low, and no
consistent differences were observed between active treatments.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 11576198 [PubMed - indexed for MEDLINE]

3193: Headache. 2001 Sep;41(8):745-53.

Preference comparison of rizatriptan ODT 10-mg and sumatriptan 50-mg tablet in
migraine.

Loder E, Brandes JL, Silberstein S, Skobieranda F, Bohidar N, Wang L, Boyle D,
Kolodny A, Guerra F, Santanello N, Johnson-Pratt L; Rizatriptan Protocol 060
Study Group.

Spaulding Rehabilitation Hospital, Boston, MA, USA.

OBJECTIVE: To compare the proportion of patients who prefer rizatriptan orally
disintegrating tablet (ODT) 10-mg to sumatriptan 50-mg tablet. BACKGROUND:
Migraineurs express treatment preference based on a variety of attributes
including the speed of pain relief and medication formulation. Rizatriptan ODT is
an orally disintegrating formulation of rizatriptan, a selective 5-HT1B/1D
receptor agonist. This study was conducted to determine patient preference
between rizatriptan ODT 10-mg and sumatriptan 50-mg tablet for the acute
treatment of migraine. METHODS: This was a multicenter, randomized, open-label,
two-period crossover study conducted in the United States with 524 enrolled
patients. Patients treated a single moderate or severe headache in each treatment
period. Patients treated one migraine with either rizatriptan ODT 10-mg or
sumatriptan 50-mg tablet, then treated a second migraine with the alternate
therapy. Patients completed diary assessments at baseline, and 30, 45, 60, 90,
and 120 minutes postdose and rated headache severity on a 4-point scale (0 =
none, 1 = mild, 2 = moderate, and 3 = severe). At the final study visit following
treatment of their second migraine, patients expressed preference for one of the 
two study medications by completing an interviewer-administered Global Preference
Question and then responded to a self-administered series of questions to capture
their most important reason for preferring one study medication over the other.
Safety measurements were recorded through standard adverse experience reporting. 
RESULTS: Three hundred eighty-six patients treated two migraine attacks. For
those patients who expressed a preference for either rizatriptan ODT or
sumatriptan (n = 374), the percentage of patients who preferred rizatriptan ODT
10-mg (57%, n = 213) was significantly greater than those who preferred
sumatriptan 50-mg tablet (43%, n = 161) (P<.01). For those patients who treated
two migraine attacks and had drug severity measures for both attacks (n = 384), a
significantly greater percentage of patients reported pain relief after taking
rizatriptan ODT than sumatriptan at the 45- and 60-minute time points (38% versus
29% and 58% versus 49%, respectively) (P<.01). In addition, a significantly
greater percentage of patients taking rizatriptan ODT reported a pain-free status
at the 60- and 120-minute time points (23% versus 17% [P<.05] and 60% versus 52% 
[P<.01], respectively). Both rizatriptan ODT and sumatriptan were well tolerated.
CONCLUSIONS: A significantly greater proportion of patients preferred rizatriptan
ODT 10-mg to sumatriptan 50-mg tablet for the acute treatment of migraine.
Efficacy and safety data are consistent with the preference findings.

Publication Types: 
    Clinical Trial
    Comparative Study
    Multicenter Study
    Randomized Controlled Trial

PMID: 11576197 [PubMed - indexed for MEDLINE]

3194: Arch Intern Med. 2001 Sep 10;161(16):1969-73.

Comment in:
    Arch Intern Med. 2002 Apr 8;162(7):845; author reply 846.

Headache evaluation and treatment by primary care physicians in an emergency
department in the era of triptans.

Maizels M.

Department of Family Practice, Kaiser Permanente, 5601 De Soto Ave, Woodland
Hills, CA 91365-4084, USA. Morris.Maizels@kp.org

BACKGROUND: Despite advances in treatment, patients with migraine have been
underdiagnosed and undertreated. METHODS: Documentation of visits by patients
with headache to an urgent care department staffed by primary care physicians was
reviewed. Patients were also sent a brief headache screen, and those who replied 
were interviewed by telephone. "Repeaters" (patients who made 3 or more visits in
6 months) were excluded from chart review. RESULTS: Over 6 months, 518 patients
made 1004 visits to the emergency department for primary headache complaints: 464
patients (90%) made 1 or 2 visits (total visits, 502). A review of 174 charts
documenting a diagnosis of migraine found that (1) the need for prophylaxis was
determined in only 40 (31%) of the patients who were not already undergoing
prophylaxis and (2) treatment in the emergency department was migraine specific
in 46 patients (26%) or otherwise appropriate in 45 (25%). A review of 90 charts 
documenting nonmigraine diagnoses found that 30 patients (33%) had adequate
history documented to exclude migraine as the diagnosis. Eighty-six patients
(17%) were interviewed. An emergency department diagnosis of migraine (n = 59)
corresponded to a final diagnosis of migraine with (n = 21) or without (n = 18)
medication overuse or chronic daily headache and/or transformed migraine with (n 
= 18) or without (n = 2) medication overuse. Discharge diagnoses that were not
migraine (n = 27) had final diagnoses of migraine with (n = 9) or without (n = 9)
medication overuse or chronic daily headache/transformed migraine with (n = 7) or
without (n = 2) medication overuse. CONCLUSIONS: In this emergency department
population, many patients with migraine, chronic daily headache, or medication
overuse are not accurately diagnosed. The need for prophylaxis is not usually
assessed. Treatment is migraine specific in the minority of patients.
Tension-type headache is rarely an accurate diagnosis in this emergency
department population.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 11525699 [PubMed - indexed for MEDLINE]

3195: J Pediatr Gastroenterol Nutr. 2001 Aug;33(2):149-54.

Abdominal migraine in children with neurofibromatosis type 1: a case series and
review of gastrointestinal involvement in NF1.

Heuschkel R, Kim S, Korf B, Schneider G, Bousvaros A.

Division of Gastroenterology, Children's Hospital, Partners Center for Human
Genetics, Boston, Massachusetts 02115, USA.

BACKGROUND: Symptomatic involvement of the gastrointestinal tract in children
with neurofibromatosis type 1 (NF1) is rare. Most reported complications in
adults are caused by the presence of neurofibromas in the stomach, small bowel,
or mesentery. In contrast, abdominal pain in children with NF1 may be the result 
of nonanatomic causes, such as migraine. There are no previous reports of an
association between abdominal migraine and NF1. METHODS: Children with abdominal 
migraine were identified from a group of children with NF1, all of whom had been 
followed up for a minimum of 3 years. Medical records of cases were reviewed
independently by two authors. MEDLINE was searched via PubMed for all reports of 
children with NF1 and any associated gastrointestinal involvement. RESULTS: Six
children with NF1 and intermittent, episodic, severe abdominal pain are reported.
Investigations for obstructive or inflammatory causes of abdominal pain were
negative. All patients had previously been diagnosed with migraine headaches by a
neurologist. In five of the six patients, propranolol (10-15 mg three times
daily) resulted in relief of their abdominal pain within days of starting
therapy. Our review identified 24 children in the medical literature with
gastrointestinal complications of NF1, mostly secondary to visceral
neurofibromas. In almost all of these cases, clinical examination and simple
radiologic investigations led to the definitive diagnosis. There were no reports 
of abdominal migraine complicating NF1. CONCLUSIONS: Abdominal pain secondary to 
migraine is an unrecognized cause of abdominal pain in children with NF1 and may 
be more common than anatomic causes of abdominal pain in children with NF1. In
children with NF1 and severe recurrent abdominal pain in whom an evaluation for
anatomic lesions is negative, a trial of migraine therapy may be indicated.

Publication Types: 
    Research Support, U.S. Gov't, P.H.S.
    Review

PMID: 11568515 [PubMed - indexed for MEDLINE]

3196: J Manipulative Physiol Ther. 2001 Sep;24(7):457-66.

Efficacy of spinal manipulation for chronic headache: a systematic review.

Bronfort G, Assendelft WJ, Evans R, Haas M, Bouter L.

Department of Research, Wolfe-Harris Center for Clinical Studies, Northwestern
Health Sciences University, Bloomington, MN 55431, USA. gbronfort@nwhealth.edu

BACKGROUND: Chronic headache is a prevalent condition with substantial
socioeconomic impact. Complementary or alternative therapies are increasingly
being used by patients to treat headache pain, and spinal manipulative therapy
(SMT) is among the most common of these. OBJECTIVE: To assess the
efficacy/effectiveness of SMT for chronic headache through a systematic review of
randomized clinical trials. STUDY SELECTION: Randomized clinical trials on
chronic headache (tension, migraine and cervicogenic) were included in the review
if they compared SMT with other interventions or placebo. The trials had to have 
at least 1 patient-rated outcome measure such as pain severity, frequency,
duration, improvement, use of analgesics, disability, or quality of life. Studies
were identified through a comprehensive search of MEDLINE (1966-1998) and EMBASE 
(1974-1998). Additionally, all available data from the Cumulative Index of
Nursing and Allied Health Literature, the Chiropractic Research Archives
Collection, and the Manual, Alternative, and Natural Therapies Information System
were used, as well as material gathered through the citation tracking, and hand
searching of non-indexed chiropractic, osteopathic, and manual medicine journals.
DATA EXTRACTION: Information about outcome measures, interventions and effect
sizes was used to evaluate treatment efficacy. Levels of evidence were determined
by a classification system incorporating study validity and statistical
significance of study results. Two authors independently extracted data and
performed methodological scoring of selected trials. DATA SYNTHESIS: Nine trials 
involving 683 patients with chronic headache were included. The methodological
quality (validity) scores ranged from 21 to 87 (100-point scale). The trials were
too heterogeneous in terms of patient clinical characteristic, control groups,
and outcome measures to warrant statistical pooling. Based on predefined
criteria, there is moderate evidence that SMT has short-term efficacy similar to 
amitriptyline in the prophylactic treatment of chronic tension-type headache and 
migraine. SMT does not appear to improve outcomes when added to soft-tissue
massage for episodic tension-type headache. There is moderate evidence that SMT
is more efficacious than massage for cervicogenic headache. Sensitivity analyses 
showed that the results and the overall study conclusions remained the same even 
when substantial changes in the prespecified assumptions/rules regarding the
evidence determination were applied. CONCLUSIONS: SMT appears to have a better
effect than massage for cervicogenic headache. It also appears that SMT has an
effect comparable to commonly used first-line prophylactic prescription
medications for tension-type headache and migraine headache. This conclusion
rests upon a few trials of adequate methodological quality. Before any firm
conclusions can be drawn, further testing should be done in rigorously designed, 
executed, and analyzed trials with follow-up periods of sufficient length.

Publication Types: 
    Meta-Analysis
    Research Support, Non-U.S. Gov't

PMID: 11562654 [PubMed - indexed for MEDLINE]

3197: Curr Pain Headache Rep. 2001 Oct;5(5):463-6.

What's in a name? tension-type headache versus migraine.

Rothrock JF.

Department of Neurology, University of South Alabama, 3401 Medical Park Drive,
Building 3, Suite 205, Mobile, AL 36693, USA. jrothroc@usamail.usouthal.edu

For years clinicians and researchers have debated the nosology of headache
generally and of "migraine" versus "tension-type headache" in particular, an
exhaustive process that arguably has done little to improve patient management
and clinical outcome. New research data now indicate that the migraine versus
tension-type distinction indeed may possess some clinical use, because patients
with migraine or "mixed" headache syndromes may respond differently to a specific
therapeutic intervention than patients with "pure" tension-type headache. This
variable response to treatment intervention would seem to imply that similarly
distinctive biologies are generating the respective headache syndromes, but to
date we have insufficient evidence to support that conclusion.

Publication Types: 
    Review

PMID: 11560812 [PubMed - indexed for MEDLINE]

3198: Br J Clin Pharmacol. 2001 Sep;52(3):237-43.

The prevention of migraine: a critical review with special emphasis on
beta-adrenoceptor blockers.

Limmroth V, Michel MC.

Department of Neurology, University of Essen, Germany.

Migraine is one of the most frequent neurological disorders affecting up to 15%
of the general population. Many patients require not only management of
individual migraine episodes but also prophylactic treatment. beta-adrenoceptor
blockers, flunarizine and valproic acid have been established as first-line
agents for the prophylaxis of migraine attacks. Among the beta-adrenoceptor
blockers propranolol and metoprolol are best documented and hence deserve
preferential use. On the other hand, it appears that other beta-adrenoceptor
blockers, perhaps with the exception of those with intrinsic sympathomimetic
activity, can be equally effective. Uncertainties regarding the relative merits
of various treatment modalities are largely caused by lack of adherence to
specific requirements for clinical trials on migraine prophylaxis. Therefore,
this article reviews internationally recommended conditions for reliable studies 
on migraine prophylaxis and appraises individual agents in the light of these
criteria.

Publication Types: 
    Review

PMID: 11560555 [PubMed - indexed for MEDLINE]

3199: AJNR Am J Neuroradiol. 2001 Sep;22(8):1550-2.

Migrainous spasm simulating carotid dissection: a pitfall in MR arteriographic
findings.

Iu PP, Lam HS.

Department of Radiology, Kwong Wah Hospital, Kowloon, Hong Kong.

An MR arteriogram obtained in a patient with migraine headaches during prodrome
showed features of carotid dissection. A repeated study conducted within minutes 
demonstrated complete patency. Vascular spasm was proposed to be the cause.
Migraine occurs in more than 10% of the population. The possibility of
misdiagnosing a vascular spasm as carotid dissection is real and should be
guarded against since there are great prognostic and treatment implications.

Publication Types: 
    Case Reports
    Research Support, Non-U.S. Gov't

PMID: 11559503 [PubMed - indexed for MEDLINE]

3200: Pharmacol Toxicol. 2001 Aug;89(2):65-73.

Aspects on the pathophysiology of migraine and cluster headache.

Edvinsson L.

Department of Internal Medicine, Lund University Hospital, S-221 85 Lund, Sweden.
lars.edvinsson@med.lu.se

The specific cause of migraine headache remains unknown. Current theories suggest
that the initiation of a migraine attack involves a primary CNS dysfunction with 
subsequent activation of the trigeminovascular system. Studies in patients have
revealed a clear association between headache and the release of the neuropeptide
calcitonin gene-related peptide, probably from C fibres. In cluster headache and 
in a case of chronic paroxysmal headache there was in addition release of the
parasympathetic neuropeptide vasoactive intestinal peptide, which was associated 
with headache, nasal congestion and rhinorrhea. Triptan administration,
activating the 5-HT(1B/1D) receptors, caused the headache to subside and the
neuropeptide release to normalise. These data suggest the involvement of sensory 
and parasympathetic mechanisms in the pathophysiology of primary headaches.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 11555322 [PubMed - indexed for MEDLINE]

3201: Headache. 2001 Jul-Aug;41(7):710-9.

Evaluation of the impact of migraine and episodic tension-type headache on the
quality of life and performance of a university student population.

Bigal ME, Bigal JM, Betti M, Bordini CA, Speciali JG.

School of Medicine at Ribeirão Preto, University of São Paulo, Brazil.

OBJECTIVE: To determine the prevalence of migraine and episodic tension-type
headache (ETTH) among university students as well as its impact on academic
performance and quality of life. BACKGROUND: Headache is a very common symptom in
clinical practice. The reduced capacities due to migraine can be profound, and
more studies are needed to evaluate, in particular, school performance. Few
studies have been conducted to evaluate the impact of tension-type headache on
work productivity, quality of life, and the impact of headache on school
performance. METHODS: A total of 1022 students were interviewed. Two
questionnaires were utilized, a standard one that permitted a diagnosis of
migraine or ETTH according to the criteria of the International Headache Society 
and a second one consisting of a battery of tests on quality of life. RESULTS: A 
total of 256 students (25%) had migraine and 336 (32.9%) reported ETTH. When in
pain, migraineurs demonstrated a 62.7% decrease in productivity while studying,
compared with a 24.4% decrease in those with ETTH. Fifty percent of migraineurs
tried to study despite the pain, compared with 53.2% of those with ETTH. With
respect to all other items tested, there was a significantly higher impairment in
the presence of migraine than in the presence of ETTH and in the presence of the 
latter compared with a control situation. CONCLUSIONS: The present study confirms
the profound impact of headache on the performance of university students, with
this impact much more evident among migraineurs but also important among students
with ETTH.

PMID: 11554960 [PubMed - indexed for MEDLINE]

3202: Headache. 2001 Jul-Aug;41(7):704-9.

Blood flow velocity and pulsatility index differences in patients with unilateral
migraine.

Chernyshev OY, Vein AM, Mathew NT, Kolosova OA, Kailasam J, Frolov A, Danilov AB,
Meadors L, Gentry P, Alexandrov AV.

Houston (Tex) Headache Clinic, USA.

OBJECTIVE: To evaluate blood flow velocity and pulsatility in unilateral migraine
without aura during the headache-free period using transcranial Doppler (TCD)
sonography. METHODS: Patients with unilateral headache were recruited during the 
headache-free period. Maximum mean flow velocity (MFV) and pulsatility index (PI)
were measured in the middle cerebral (MCA) and basilar arteries. Controls were
headache-free individuals without cerebrovascular disease. RESULTS: Twenty-five
patients with right-sided migraine, 25 patients with left-sided migraine, and 19 
controls were studied. The MCA PI was higher on the right headache side versus
the left headache side (0.97 +/- 0.2 versus 0.86 +/- 0.1 cm/s, P =.02) and versus
controls (0.9 +/- 0.2 cm/s, NS). The basilar artery MFV was higher in patients
with right-sided headache versus left-sided headache (39.5 +/- 5.6 versus 34.7
+/- 8.2 cm/s, P =.02) and versus controls (38.2 +/- 8 cm/s, NS). No decrease in
MFV with age was observed in patients with migraine. CONCLUSIONS: Middle cerebral
artery flow pulsatility and basilar artery velocity are higher in patients with
right-sided migraine compared with left-sided migraineurs, during the
headache-free period. Although these parameters were similar to controls, the
differences found during the headache-free period in migraineurs may indicate
vascular involvement predisposing to the unilateral headache recurrence.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 11554959 [PubMed - indexed for MEDLINE]

3203: Headache. 2001 Jul-Aug;41(7):693-7.

Effectiveness of nasal sumatriptan in 5- to 12-year-old children.

Hershey AD, Powers SW, LeCates S, Bentti AL.

Division of Neurology, Children's Hospital Medical Center, Cincinnati, Ohio
45229-3039, USA.

OBJECTIVE: To assess the tolerability and effectiveness of nasal sumatriptan in
the treatment of migraine in 5- to 12-year-old children. BACKGROUND: Although
headaches are a common disorder and occur in up to 10.6% of children, many of the
new migraine abortive agents have not been well evaluated in this population. It 
has recently been reported that nasal sumatriptan is effective in the treatment
of migraine in adolescents. In younger children, it is yet to be characterized.
In addition, many children have significant amounts of vomiting with their
migraines, limiting their use of oral medications. DESIGN AND METHODS: Children
with headache were evaluated by a child neurologist, child psychologist, and
pediatric nurse practitioner. Clinical and International Headache Society
diagnoses were established for each child. Patients with headaches that were
either unresponsive to oral medications or had significant vomiting were treated 
with nasal sumatriptan. Initial administration and tolerability were performed in
the Headache Center at Cincinnati's Children's Hospital Medical Center. Patients 
or their parents were contacted to assess the overall effectiveness of nasal
sumatriptan after home administration. RESULTS: Ten patients aged between 5 and
12 years (mean, 9.9 years) received either a 5-mg (n = 2) or 20-mg (n = 8) dose
of sumatriptan. All 10 patients had a clinical diagnosis of migraine; 7 met the
International Headache Society criteria for migraine. The mean age of headache
onset was 6.6 years. A total of 57 headaches were treated; 47 (82.5%) responded
to sumatriptan. Of the patients who treated headaches, the mean number of
headaches treated was 5.2, while the mean number of responsive headaches was 4.3.
One patient had no response, 2 patients had a 50% response, and 6 patients had
100% response to the nasal sumatriptan. Three patients reported persistent "bad
taste." CONCLUSIONS: This report demonstrates that nasal sumatriptan may be
effective in aborting migraine in young children (aged 5 to 12 years). It also
suggests that there may be subgroups for which it works well. This information
suggests that double-blind, placebo-controlled studies are necessary to determine
the overall effectiveness of nasal sumatriptan in this age group.

Publication Types: 
    Clinical Trial
    Research Support, Non-U.S. Gov't

PMID: 11554957 [PubMed - indexed for MEDLINE]

3204: Headache. 2001 Jul-Aug;41(7):680-4.

Depression scores following migraine treatment in patients attending a
specialized center for headache and neurology.

Miranda H, Ortiz G, Figueroa S, Pérez CM, Suárez E.

Specialized Headache Management and Neurology Center, San Francisco Hospital, San
Juan, Puerto Rico, USA.

OBJECTIVE: To determine the changes in clinical characteristics and depression
levels among patients following treatment for migraine. BACKGROUND: Epidemiologic
studies have provided consistent evidence regarding an association between
migraine and depression. In Puerto Rico, however, migraine has not yet been
systematically investigated. METHODS: A chart review of 144 Puerto Rican patients
who presented with migraine, diagnosed according to the International Headache
Society criteria, and depression over a 2-year period was performed. The level of
depression, before and after migraine treatment, was evaluated using the Zung
Self-rating Depression Scale. RESULTS: The mean age of patients was 37.0 +/- 14.4
years; 77.1% were women. More than half (52.8%) reported severe headache and
56.9% reported a monthly frequency of five attacks or more. Nearly 9% were using 
antidepressant therapy and 8% were under psychiatric treatment. The mean Zung
index score at baseline was 50.6 +/- 10.9. Following treatment with triptans, the
intensity and frequency of migraine and the Zung index score decreased
significantly (P<.00001). A trend for a greater reduction in Zung index scores
among patients receiving triptan medications for more than a year was
demonstrated (P =.07). CONCLUSIONS: These results indicate that migraine
treatment with triptans appears to be effective in decreasing the headache
frequency and intensity, and depression levels, independent of antidepressant
medication use or psychiatric treatment.

PMID: 11554955 [PubMed - indexed for MEDLINE]

3205: Headache. 2001 Jul-Aug;41(7):665-79.

Efficacy of nonprescription doses of ibuprofen for treating migraine headache. a 
randomized controlled trial.

Codispoti JR, Prior MJ, Fu M, Harte CM, Nelson EB.

Medical Department, McNeil Consumer Healthcare, Fort Washington, PA 19034, USA.

OBJECTIVE: To evaluate the efficacy and safety of ibuprofen, 200 mg and 400 mg,
compared with placebo and each other for the treatment of pain of migraine
headache. BACKGROUND: Migraine headache is a common illness with significant
social and economic impact. DESIGN: Randomized, placebo-controlled, double-blind 
trial of 6 hours' treatment duration. METHODS: Fifteen investigators at 17
private practice and referral centers in the United States participated in this
study of 660 outpatient adults aged 18 to 84 years with migraine headache of
moderate to severe intensity. Each patient was randomly assigned to a single dose
of study medication: ibuprofen 200 mg (n = 216) or 400 mg (n = 223), or placebo
(n = 221). The percentage of patients with a reduction in baseline headache
intensity from severe or moderate to mild or none 2 hours after treatment and the
headache pain intensity difference from baseline at 2 hours were the primary
efficacy measures. Secondary outcomes included other measures of pain relief,
severity differences from baseline for migraine-associated symptoms of nausea,
photophobia, phonophobia, and functional disability, and percentage of patients
with migraine-associated symptoms reduced to none. RESULTS: Significantly (P < or
= .006) more patients treated with ibuprofen, 200 mg or 400 mg, reported mild to 
no pain after 2 hours (41.7% and 40.8%, respectively), compared with those
treated with placebo (28.1%). The mean pain intensity difference from baseline
measured at 2 hours was significantly (P < or = .001) greater for patients
treated with ibuprofen 200 mg or 400 mg (0.68 and 0.65, respectively), compared
with those treated with placebo (0.39). Statistically significant differences in 
favor of both doses of ibuprofen over placebo were observed for mean pain
intensity difference at 1 hour after treatment. In patients with severe baseline 
pain intensity, ibuprofen, 400 mg, was significantly (P < or = .048) superior to 
placebo for the primary efficacy end points, while ibuprofen, 200 mg, was not.
Ibuprofen, 200 mg and 400 mg, were statistically significantly more effective
than placebo for all clinically important secondary pain relief outcomes. Mean
severity changes of migraine-associated symptoms of nausea, photophobia,
phonophobia, and functional disability at 2 and 6 hours were significantly (P <
or = .03) in favor of both doses of ibuprofen over placebo, and results for the
percentage of patients with symptoms reduced to none consistently, although less 
often statistically significant, favored ibuprofen. No statistically significant 
differences in adverse events were found among treatment groups. CONCLUSIONS:
Ibuprofen at doses of 200 mg and 400 mg is an efficacious, cost-effective,
well-tolerated, single-ingredient nonprescription treatment for pain of migraine 
headache. In addition, while not always statistically significant, ibuprofen
provided a beneficial effect on associated symptoms of migraine including nausea,
photophobia, phonophobia, and functional disability.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 11554954 [PubMed - indexed for MEDLINE]

3206: Headache. 2001 Jul-Aug;41(7):646-57.

Prevalence and burden of migraine in the United States: data from the American
Migraine Study II.

Lipton RB, Stewart WF, Diamond S, Diamond ML, Reed M.

Department of Neurology, Albert Einstein College of Medicine, Bronx, NY, USA.

OBJECTIVE: To describe the prevalence, sociodemographic profile, and the burden
of migraine in the United States in 1999 and to compare results with the original
American Migraine Study, a 1989 population-based study employing identical
methods. METHODS: A validated, self-administered questionnaire was mailed to a
sample of 20 000 households in the United States. Each household member with
severe headache was asked to respond to questions about symptoms, frequency, and 
severity of headaches and about headache-related disability. Diagnostic criteria 
for migraine were based on those of the International Headache Society. This
report is restricted to individuals 12 years and older. RESULTS: Of the 43 527
age-eligible individuals, 29 727 responded to the questionnaire for a 68.3%
response rate. The prevalence of migraine was 18.2% among females and 6.5% among 
males. Approximately 23% of households contained at least one member suffering
from migraine. Migraine prevalence was higher in whites than in blacks and was
inversely related to household income. Prevalence increased from aged 12 years to
about aged 40 years and declined thereafter in both sexes. Fifty-three percent of
respondents reported that their severe headaches caused substantial impairment in
activities or required bed rest. Approximately 31% missed at least 1 day of work 
or school in the previous 3 months because of migraine; 51% reported that work or
school productivity was reduced by at least 50%. CONCLUSIONS: Two
methodologically identical national surveys in the United States conducted 10
years apart show that the prevalence and distribution of migraine have remained
stable over the last decade. Migraine-associated disability remains substantial
and pervasive. The number of migraineurs has increased from 23.6 million in 1989 
to 27.9 million in 1999 commensurate with the growth of the population. Migraine 
is an important target for public health interventions because it is highly
prevalent and disabling.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 11554952 [PubMed - indexed for MEDLINE]

3207: Headache. 2001 Jul-Aug;41(7):638-45.

Migraine diagnosis and treatment: results from the American Migraine Study II.

Lipton RB, Diamond S, Reed M, Diamond ML, Stewart WF.

Department of Neurology, Albert Einstein College of Medicine, Bronx, NY, USA.

OBJECTIVE: A population-based survey was conducted in 1999 to describe the
patterns of migraine diagnosis and medication use in a representative sample of
the US population and to compare results with a methodologically identical study 
conducted 10 years earlier. METHODS: A survey mailed to a panel of 20 000 US
households identified 3577 individuals with severe headache meeting a case
definition for migraine based on the International Headache Society (IHS)
criteria. Those with severe headache answered questions regarding physician
diagnosis and use of medications for headache as well as headache-related
disability. RESULTS: A physician diagnosis of migraine was reported by 48% of
survey participants who met IHS criteria for migraine in 1999, compared with 38% 
in 1989. A total of 41% of IHS-defined migraineurs used prescription drugs for
headaches in 1999, compared with 37% in 1989. The proportion of IHS-defined
migraineurs using only over-the-counter medications to treat their headaches was 
57% in 1999, compared with 59% in 1989. In 1999, 37% of diagnosed and 21% of
undiagnosed migraineurs reported 1 to 2 days of activity restriction per episode 
(P<.001); 38% of diagnosed and 24% of undiagnosed migraineurs missed at least 1
day of work or school in the previous 3 months (P<.001); 57% of diagnosed and 45%
of undiagnosed migraineurs experienced at least a 50% reduction in work/school
productivity (P<.001). CONCLUSIONS: Diagnosis of migraine has increased over the 
past decade. Nonetheless, approximately half of migraineurs remain undiagnosed,
and the increased rates of diagnosis of migraine have been accompanied by only a 
modest increase in the proportion using prescription medicines. Migraine
continues to cause significant disability whether or not there has been a
physician diagnosis. Given the availability of effective treatments, public
health initiatives to improve patterns of care are warranted.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 11554951 [PubMed - indexed for MEDLINE]

3208: Headache. 2001 Jul-Aug;41(7):629-37.

Periaqueductal gray matter dysfunction in migraine: cause or the burden of
illness?

Welch KM, Nagesh V, Aurora SK, Gelman N.

Department of Neurology, University of Kansas Medical Center, Kansas City, KS
66160-7300, USA.

OBJECTIVE: The periaqueductal gray matter (PAG) is at the center of a powerful
descending antinociceptive neuronal network. We studied iron homeostasis in the
PAG as an indicator of function in patients with episodic migraine (EM) between
attacks and patients with chronic daily headache (CDH) during headache.
High-resolution magnetic resonance techniques were used to map the transverse
relaxation rates R2, R2*, and R2' in the PAG, red nucleus (RN), and substantia
nigra (SN). R2' is a measure of non-heme iron in tissues. METHODS: Seventeen
patients diagnosed with EM with and without aura, 17 patients diagnosed with CDH 
and medication overuse, and 17 normal adults (N) were imaged with a 3.0-tesla
magnetic resonance imaging system. For each subject, mean values of the
relaxation rates, R2 (1/T2), R2* (1/T2*), and R2' (R2* - R2) were obtained for
the PAG, RN, and SN. R2, R2*, and R2' values of the EM, CDH, and N groups were
compared using analysis of variance, Student t test, and correlation analysis.
RESULTS: In the PAG, there was a significant increase in mean R2' and R2* values 
in both the EM and CDH groups (P<.05) compared with the N group, but no
significant difference in these values was demonstrated between the EM and CDH
groups, or between those with migraine with or without aura in the EM group.
Positive correlations were found for duration of illness with R2' in the EM and
CDH groups. A decrease in mean R2' and R2* values also was observed in the RN and
SN of the CDH group compared with the N and EM groups (P<.05), explained best by 
flow activation due to head pain. CONCLUSIONS: Iron homeostasis in the PAG was
selectively, persistently, and progressively impaired in the EM and CDH groups,
possibly caused by repeated migraine attacks. These results support and emphasize
the role of the PAG as a possible "generator" of migraine attacks, potentially by
dysfunctional control of the trigeminovascular nociceptive system.

Publication Types: 
    Research Support, U.S. Gov't, P.H.S.

PMID: 11554950 [PubMed - indexed for MEDLINE]

3209: Eur J Neurol. 2001 Sep;8(5):441-9.

Familial migraine with and without aura: clinical characteristics and
co-occurrence.

Kallela M, Wessman M, Havanka H, Palotie A, Färkkilä M.

Department of Neurology, University of Helsinki Central Hospital, Haartmaninkatu 
4, 00290 Helsinki, Finland. mikko.kallela@pp.fimnet.fi

Migraine with aura (MwA) and migraine without aura (MwoA) are the two common
forms of migraine. Many migraine patients suffer from both kinds of attacks. In a
questionnaire-based study using the current International Headache Society (IHS) 
criteria we determined the clinical characteristics and occurrence of MwA + MwoA 
in 1000 migraine patients belonging to 210 Finnish migraine families. Nine
hundred and six patients were able to indicate whether they suffered from MwA
(but not MwoA), migraine aura without headache (migraine equivalent) (but not
MwA) or MwA and MwoA. Of these patients, 3.2% had experienced MwoA, 11.1% MwA,
40.6% MwA + MwoA, 23.5% MwoA and 20.3% MwA-like symptoms not meeting the IHS
criteria. The high prevalence of MwA attacks in the families studied supports the
belief that aura has a strong hereditary component. The MwA + MwoA patients had
significantly more severe attacks, more typical headache and more prodromal
symptoms than the MwA and MwoA subjects. Therefore, it is possible that there is 
a continuum with pure MwA at the neural and pure MwoA at the headache end of the 
spectrum, and MwA + MwoA lying in between the two. The MwA + MwoA patients would 
thus be liable to both types of migraine, making their attacks more
characteristic and more severe. This would also explain why the co-occurrence of 
MwA and MwoA is more common in the clinic compared with population based
epidemiological studies. These findings have consequences for future research on 
liability genes for migraine.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 11554907 [PubMed - indexed for MEDLINE]

3210: MedGenMed. 2001 Jun 1;3(3):1.

Long-term efficacy and tolerability of rizatriptan wafers in migraine.

Cady R, Crawford G, Ahrens S, Hairwassers D, Getson A, Visser WH, Lines C;
Rizatriptan-RPD Study Group.

Headache Care Center, Springfield, Missouri, USA.

CONTEXT: Rizatriptan is a selective 5-HT1B/1D receptor agonist for the acute
treatment of migraine. It is available in a unique wafer formulation that
dissolves rapidly in the mouth and can be taken without liquids, thereby offering
patients a very convenient way to take treatment. OBJECTIVE: To investigate the
long-term efficacy of rizatriptan 10-mg and 5-mg wafers in migraineurs. SETTING: 
19 headache clinics in 5 countries. PATIENTS: 458 patients diagnosed with
migraine according to International Headache Society criteria. DESIGN: 6-month,
open-label, extension, which followed a double-blind, placebo-controlled study.
INTERVENTIONS: Patients were randomly assigned to 1 of 3 treatments for moderate 
or severe migraines: rizatriptan 10-mg wafer, rizatriptan 5-mg wafer, or
"standard care" (usual migraine treatment -- eg, nonsteroidal anti-inflammatory
drugs [NSAIDs], analgesics, other triptans). Patients randomized to rizatriptan
were blinded to the dose. MAIN OUTCOME MEASURES: Headache severity (none, mild,
moderate, severe) and adverse events were recorded on a diary card. RESULTS: 181 
patients treated 3393 attacks with rizatriptan 10-mg wafer, 191 treated 3254
attacks with rizatriptan 5-mg wafer, and 86 treated 1582 attacks with standard
care. The median number of treated attacks per patient was 16 for rizatriptan
10-mg wafer, 13 for rizatriptan 5-mg wafer, and 14 for standard care. The median 
patient on rizatriptan 10-mg wafer reported pain relief at 2 hours (reduction of 
headache from moderate or severe at baseline to mild or none) in 82% of attacks, 
vs 73% of attacks for standard care (odds ratio [95% confidence interval] = 1.63 
[1.14, 2.34], P <.01) and 72% of attacks for rizatriptan 5-mg wafer (OR [95% CI] 
= 1.60 [1.23, 2.08], P <.001). The median patient on rizatriptan 10-mg wafer was 
pain free at 2 hours in 46% of attacks, vs 30% of attacks for standard care (OR
[95% CI] = 1.50 [1.06, 2.12], P <.05) and 25% of attacks for rizatriptan 5-mg
wafer (OR [95% CI] = 1.93 [1.50, 2.49], P <.001). All treatments were generally
well tolerated. Compared with standard care, rizatriptan 5-mg wafer was
associated with fewer specific adverse events of asthenia/fatigue, back pain,
nausea, pharyngeal discomfort, upper respiratory infection, and vomiting (P
values <.05), and, compared with rizatriptan 10-mg wafer, fewer overall
drug-related adverse events (P <.05). CONCLUSIONS: Rizatriptan 10-mg wafer was
more effective than standard care and rizatriptan 5-mg wafer for treating
intermittent moderate or severe migraine attacks occurring over periods of up to 
6 months. Rizatriptan wafers were well tolerated.

Publication Types: 
    Clinical Trial
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 11549974 [PubMed - indexed for MEDLINE]

3211: Cephalalgia. 2001 Jul;21(6):680-4.

Comment in:
    Cephalalgia. 2001 Oct;21(8):791-5.

An open preference study with sumatriptan 50 mg and zolmitriptan 2.5 mg in 100
migraine patients.

Pascual J, Muñoz R, Leira R.

Services of Neurology, University Hospital, Santander, Spain. pascualj@unican.es

Understanding factors influencing patients' preference will improve guidance to
make rational choices in expanded symptomatic migraine treatment. The objective
of this open-label, cross-over study was to explore patients' preferences for
sumatriptan 50 mg vs. zolmitriptan 2.5 mg tablets, focusing on factors
influencing this preference. One hundred consecutive migraine patients attending 
our clinics were asked to treat three attacks with each medication and then fill 
out a preference questionnaire. Ninety-four migraineurs completed the trial and
42 (44%, 95% CI 34-58%) reported that they preferred zolmitriptan 2.5 mg over
sumatriptan 50 mg tablets and 27 (29%, 20-38%) preferred sumatriptan 50 mg. The
remaining 25 (27%, 18-36%) did not show any preference. For the initial treatment
of the attacks, there were more patients needing just one tablet of zolmitriptan 
2.5 mg compared with sumatriptan 50 mg (67 vs. 39%). The reasons for preference
among those 69 patients who had shown preference for either of the two triptans
were: a faster onset of action (speed of onset) (73%), a longer duration of the
effects (39%), fewer adverse events (35%) and lower price (13%). Only one-quarter
of the studied migraine population thought that sumatriptan 50 mg and
zolmitriptan 2.5 mg were equivalent, which suggests that most migraine patients
differentiate between triptans. A faster onset of action (speed of onset) was the
most important reason for preference.

Publication Types: 
    Comparative Study

PMID: 11531900 [PubMed - indexed for MEDLINE]

3212: Cephalalgia. 2001 Jul;21(6):672-9.

The efficacy and safety of sc alniditan vs. sc sumatriptan in the acute treatment
of migraine: a randomized, double-blind, placebo-controlled trial.

Diener HC, Tfelt-Hansen P, de Beukelaar F, Ferrari MD, Olesen J, Dahlöf C, Mathew
N; Study Group.

Department of Neurology, University Hospital, University of Essen, Essen,
Germany. h.diener@uni-essen.de

This double-blind, placebo-controlled, parallel-group, multicentre,
multinational, phase-III trial was designed to assess the efficacy and safety of 
a single subcutaneous injection of placebo, 2 doses of alniditan (1.4 mg and 1.8 
mg) and 6 mg of sumatriptan in subjects with acute migraine. A total of 114
investigators from 13 different countries screened 2021 subjects. In total 924
patients were treated with placebo (157), alniditan 1.4 mg (309), alniditan 1.8
mg (141) and sumatriptan 6 mg (317). The lower number of subjects in the
alniditan 1.8 mg group is due to the termination of this trial arm after the
incidence of a serious adverse event and a subsequent protocol amendment. The
number of subjects who were pain free at 2 h (primary endpoint) was: 22 (14.1%)
with placebo, 174 (56.3%) with alniditan 1.4 mg, 87 (61.7%) with alnditan 1.8 mg 
and 209 (65.9%) with sumatriptan 6 mg. Alniditan 1.4 mg was significantly better 
(P < 0.001) than placebo and sumatriptan was significantly better (P = 0.015)
than alniditan 1.4 mg. The number of responders (reduction of headache severity
from moderate or severe headache before treatment to mild or absent at 2 h), was 
59 (37.8%) on placebo, 250 (80.9%) on alniditan 1.4 mg, 120 (85.1%) on alniditan 
1.8 mg, and 276 (87.1%) on sumatriptan. Response was significantly higher (P <
0.001) with alniditan 1.4 mg than with placebo, and significantly lower (P =
0.036) with alniditan 1.4 mg than with sumatriptan. Recurrence rates were: 22
(37.3%) with placebo, 87 (34.8%) with alniditan 1.4 mg, 35 (29.2%) with alniditan
1.8 mg and 108 (39.1%) with sumatriptan. Adverse events occurred in 577/924
(62.4%) subjects, i.e. in 62/157 (39.5%) with placebo, 214/309 (69.3%) with
alniditan 1.4 mg, 91/141 (64.5%) with alniditan 1.8 mg and 210/317 (66.2%) with
sumatriptan 6 mg. Sumatriptan was significantly better than alniditan 1.4 mg for 
pain free at 2 h. The difference, however, was small and clinically not
important. For alniditan, a dose-dependent adverse event relationship was seen.
The safety profile of alniditan 1.4 mg was similar to that of sumatriptan.

Publication Types: 
    Clinical Trial
    Clinical Trial, Phase III
    Comparative Study
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 11531899 [PubMed - indexed for MEDLINE]

3213: Cephalalgia. 2001 Jul;21(6):664-71.

One-year prevalence of migraine in Sweden: a population-based study in adults.

Dahlöf C, Linde M.

Gothenburg Migraine Clinic, Göteborg, Sweden. carl.dahlof@migraineclinic.se

A randomly selected sample of 1668 individuals (782 women and 886 men) aged 18-74
years was interviewed by telephone using a standardized questionnaire including
the International Headache Society (IHS) criteria for migraine. The survey was
performed by SIFO, the national public opinion poll agency. The results obtained 
demonstrate that 21% of the Swedish population had suffered from severe headaches
during the past year. A majority of these headache sufferers (61%) fulfilled the 
IHS-criteria for migraine. The 1-year prevalence of migraine in Sweden was found 
to be 13.2 +/- 1.9% (16.7% among women and 9.5% among men). The prevalence of
migraine in this Swedish population did not differ between the northern, middle
and southern part of Sweden, or between urban and rural areas or different income
groups. Only about half (49%) of the migraineurs had been diagnosed by a
physician. Among the individuals who fulfilled the IHS criteria for migraine the 
mean attack-frequency was 1.3 per month and the mean attack-duration was 19 h. If
the duration of the attack was disregarded as a strict criterion for migraine
(attacks < 4 h and > 72 h were included), the prevalence increased to 17.0 +/-
1.9% without affecting the sex distribution. With this amendment, 92% of those
who considered their headaches to be migraine or migraine-like in fact fulfilled 
the alternative criteria for migraine. However, only 76% of those who believed
that they had migraine or migraine-like headaches fulfilled the strict IHS
criteria for migraine. An extension of the time window from 4 to 72 h may be
reasonable both from a pragmatic and from a rational clinical point of view.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 11531898 [PubMed - indexed for MEDLINE]

3214: Cephalalgia. 2001 Jul;21(6):656-63.

The lack of vasoconstrictor effect of the pineal hormone melatonin in an animal
model predictive of antimigraine activity.

Tom B, De Vries P, Heiligers JP, Willems EW, Scalbert E, Delagrange P, Saxena PR.

Department of Pharmacology, Erasmus University Medical Centre Rotterdam,
Rotterdam, The Netherlands.

The pineal hormone, melatonin, has been implicated in the pathophysiology of
migraine and several studies have demonstrated its vasoconstrictor properties. In
the present study, systemic and carotid haemodynamic effects of melatonin,
administered directly into the carotid artery, were investigated in anaesthetized
pigs. Ten-minute intracarotid infusions of melatonin (1, 10 and 100 microg kg(-1)
min(-1)) produced slight decreases in blood pressure and total carotid and
arteriovenous anastomotic blood flows, but nutrient blood flow was not affected. 
The decrease in carotid blood flow was entirely caused by the hypotension, since 
no changes in vascular conductance values were observed. It is concluded that
melatonin itself is not capable of producing vasoconstriction in the cranial
circulation of anaesthetized pigs. Thus, it appears that melatonin has no
anti-migraine potential via a vasoconstrictor mechanism.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 11531897 [PubMed - indexed for MEDLINE]

3215: Cephalalgia. 2001 Jul;21(6):630-6.

Migraine and haemostasis.

Crassard I, Conard J, Bousser MG.

Service de Neurologie, Hôpital Lariboisière, Paris, France.

Migraine is a risk factor for cerebral infarction in young women. The nature of
the connection between these diseases remains however essentially unknown.
Abnormalities of haemostasis leading to an increased thrombotic risk would
provide a logical link. Platelets, antiphospholipid antibodies and more recently 
congenital thrombophilia have thus successively been implicated. The different
studies concerning these topics have been reviewed. Because of the conflicting
results obtained and because of the numerous methodological shortcomings of many 
of these studies, no definite conclusion can be reached. It is possible that
these 3 factors play a role in the ischemic risk of migraine, but it is as likely
or even more likely that other factors (inside or outside the hemostatic system) 
play a more important role. Further studies are thus deeply needed.

Publication Types: 
    Review

PMID: 11531894 [PubMed - indexed for MEDLINE]

3216: CNS Drugs. 2001;15(8):583-7.

When should triptans be taken during a migraine attack?

Schoenen J.

Department of Neurology, University of Liège, CHR Citadelle, Liège, Belgium.
jschoenen@ulg.ac.be

The common strategy to treat a migraine attack as soon as it begins, made for
classical acute antimigraine treatments such as ergotamine and analgesics, has
not been transposed to the triptans. The recommendation to delay triptan intake
until headache intensity is at least moderate is merely a habit generated by the 
protocol used in triptan trials and a nonvalidated attempt to reduce costs. It is
also favoured by the few studies suggesting that sumatriptan is less effective
when given early in an attack, especially during the aura phase. Recent
retrospective analyses of small numbers of 'protocol violators' in controlled
trials of sumatriptan suggest that the drug is more efficient when taken while
the headache is mild. Pain-free responses and therapeutic gains over aspirin
(acetylsalicylic acid)-metoclopramide or ergotamine-caffeine combinations were
increased under these conditions. The available circumstantial evidence is
reviewed and discussed. Before any conclusion can be drawn and recommendation
made, results are awaited from randomised controlled trials specifically
addressing whether or not triptans are more efficient in mild headache.
Meanwhile, there seems to be no medical reason to withhold treatment of a mild
headache with a triptan as long as triptan intake does not exceed 1 or 2 doses
per week. Most mild headaches in patients with migraine appear indeed to be mild 
migraine attacks, even when the headache characteristics are those of
tension-type headache.

PMID: 11524030 [PubMed - indexed for MEDLINE]

3217: Eur J Neurol. 2001 Jan;8(1):61-6.

Validation of a migraine-specific questionnaire for use in family studies.

Kallela M, Wessman M, Färkkilä M.

Department of Neurology, University of Helsinki, Helsinki, Finland.
mikko.kallela@pp.fimnet.fi

The availability of valid migraine-specific questionnaires is important when
large numbers of migraine patients have to be analysed. The Finnish
Migraine-Specific Questionnaire has been validated in two stages. In the first, a
clinical diagnosis of migraine was reached, using International Headache Society 
criteria, in 100 consecutive patients. Migraine was then diagnosed independently 
on the basis of responses to the Finnish Migraine-Specific Questionnaire. In the 
second stage, responses to 100 questionnaires returned consecutively in a family 
study in progress were analysed, and respondents were contacted by telephone for 
interview and diagnosis of migraine. Contact proved impossible in six cases. The 
sensitivity of the questionnaire for migraine was 0.99 (167 out of 168;
validation stages 1 and 2 combined) and specificity was 0.96 (25 out of 26 cases;
validation stage 2). It also proved possible to differentiate between migraine
with and without aura on the basis of responses to the Finnish Migraine-Specific 
Questionnaire: chance-corrected agreement (Cohen's kappa) was 0.804 in relation
to diagnoses reached on the basis of responses to the Finnish Migraine-Specific
Questionnaire and clinically was 0.858 in relation to diagnoses reached on the
basis of responses to the Finnish Migraine-Specific Questionnaire combined with
the results of the telephone interviews. A value for Cohen's kappa > 0.75
indicates good agreement. Therefore, use of the Finnish Migraine-Specific
Questionnaire in research into migraine genetics is justified.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Validation Studies

PMID: 11509082 [PubMed - indexed for MEDLINE]

3218: Neurosci Lett. 2001 Aug 24;309(2):105-8.

Non-linear electroencephalogram dynamics in patients with spontaneous nocturnal
migraine attacks.

Strenge H, Fritzer G, Göder R, Niederberger U, Gerber WD, Aldenhoff J.

Institute of Medical Psychology, University Kiel, Niemannsweg 147, 24105 Kiel,
Germany. strenge@med-psych.uni-kiel.de

The present study was conducted to examine non-linear electroencephalogram (EEG) 
measures during the development of a spontaneous migraine attack. We investigated
the sleep EEG of five patients with migraine without aura in the pain-free
interval and at the onset of a nocturnal attack. Sleep EEG recordings were
analysed using the method of global dimensional complexity compared to
conventional sleep scoring techniques. We found no divergence between classical
sleep architecture and the estimated dimensional course nor any relevant
short-term changes related to the onset of headache. There was, however, a loss
of dimensional complexity in the first two non-rapid eye movement sleep states in
the migraine night, with statistical significance during the second sleep cycle. 
For the first time, these results provide evidence of a global dimension decrease
that is related to cortical network changes during a migraine attack.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 11502356 [PubMed - indexed for MEDLINE]

3219: J Neurol Sci. 2001 Jul 15;188(1-2):99-101.

Association of the T102C polymorphism of 5-HT2A receptor gene with aura in
migraine.

Erdal ME, Herken H, Yilmaz M, Bayazit YA.

Department of Medical Biology and Genetics, Faculty of Medicine, Mersin
University, Mersin, Turkey.

OBJECTIVE: To find out the significance of the 5-HT2A receptor gene polymorphism 
in migraine. Study design: A PCR study in which 61 migraineurs and 44 healthy
controls were included. METHODS: The T102C polymorphism of the 5-HT2A receptor
gene was studied. The results of the migraineurs and controls were compared. The 
relationship between the gene polymorphism and aura was also assessed. RESULTS:
The representations of the 5-HT2A genotypes were similar in migraineurs and
controls (p>0.05) as well as in the male and female migraineurs (p>0.05). The
family history of migraine did not associate with 5-HT2A receptor gene
polymorphism (p>0.05). There was a significant relationship between the presence 
of C/C genotype and migraine with aura (p=0.02) while C/T and T/T genotypes were 
over represented in the patients with migraine without aura (p<0.01). CONCLUSION:
The T102C polymorphism of the 5-HT2A receptor gene is not directly related to the
increased risk of migraine. The associations between the genotypes of this gene
and aura may suggest that 5-HT2A receptor gene polymorphism may be involved in
determining the subtypes of or accompanying symptoms in the migraine disease.

PMID: 11489292 [PubMed - indexed for MEDLINE]

3220: Ultraschall Med. 2001 Jun;22(3):122-9.

Impaired compliance of the intracranial vessels in complicated childhood
migraine. Demonstration by transcranial Doppler-sonography--a vascular model
approach.

Rupprecht T, Hofbeck M, Wenzel D.

Klinik und Poliklinik für Kinder und Jugendliche, Universität Erlangen.
thomas.rupprecht@kinder.med-uni-erlangen.de

AIM: To increase the diagnostic value of Doppler sonography a uniform lumped
parameter model of pulsatile blood flow in human arteries was derived from the
serial and/or parallel connection of parallel oscillatory circuits. METHODS AND
PATIENTS: In this setting the current (I) in the ohmic resistor (R) represents
the volume flow in the vessel, the voltage (V) the blood pressure. The vessel
compliance corresponds to the capacitance (C), the inductivity (L) represents the
accelerated mass. The flow velocity (v) which is assessable non-invasively is
given by v = I/A, where A is the cross-sectional area of the vessel.
Mathematically, the model represents a two-dimensional Fourier-series of the
input signal by the segments. Thus it seems to be evident that almost all forms
of flow and pressure pulses can be generated. The equations of the model were
solved numerically. Doppler-sonographically measured flow velocities in the
ascending aorta were used as input signal. The parameters for A, R, L and C were 
optimized to gain the measured flow spectrum in the target vessel as model
response. RESULTS: Application in 14 children (aged 3-16 yrs.) with complicated
migraine during a symptom-free interval revealed a significantly lowered cross
sectional area of the middle cerebral artery on the side of the higher flow
velocities. For both middle and posterior cerebral arteries, a decreased vessel
compliance (C) (mean -30%) was found, whereas values for R and L were within
normal limits. CONCLUSION: These findings suggest an altered vascular compliance 
even between attacks. This may contribute to the pathogenesis of migraine through
increased cerebral impedance resulting in impaired cerebral perfusion.

PMID: 11484443 [PubMed - indexed for MEDLINE]

3221: Med Clin North Am. 2001 Jul;85(4):997-1016.

Cluster and related headaches.

Newman LC, Goadsby P, Lipton RB.

Department of Neurology, Albert Einstein College of Medicine, Bronx, New York,
USA.

The disorders described in this article are relatively rare, but probably are
more common than previously thought. Because these disorders cause significant
pain and disability and treatment response differs from that of migraine,
tension-type, and cluster headaches, recognition is essential. Table 1 lists the 
important clinical features of these syndromes and contrasts them with cluster
headache, the disorder for which they are often confused.

Publication Types: 
    Review

PMID: 11480270 [PubMed - indexed for MEDLINE]

3222: Med Clin North Am. 2001 Jul;85(4):971-85.

Evaluation and management of headache in the emergency department.

Ward TN, Levin M, Phillips JM.

Department of Medicine, Dartmouth Medical School, New Hampshire, USA.
Thomas.N.Ward@hitchcock.org

In the ED, correct diagnosis is the necessary foundation on which specific
therapy is based. There is no substitute for obtaining a thorough history and
examining the patient competently. Patients with a past history of primary
headaches, such as migraine, also may be afflicted with (new) secondary
headaches. Although efficiency is desirable from the perspective of ED
management, a thoughtful approach complemented by the judicious selection of
tests is compatible with that goal as well as achieving the desired outcome of
accurate diagnosis and relief of pain. Arrangements for long-term follow-up are
important.

Publication Types: 
    Review

PMID: 11480268 [PubMed - indexed for MEDLINE]

3223: Med Clin North Am. 2001 Jul;85(4):959-70.

Safety and rational use of the triptans.

Tepper SJ.

New England Center for Headache, Stamford, Connecticut, USA. sjtepper@aol.com

The safety of the triptans has been established, with more than 8 million
patients treating greater than 340 million attacks with sumatriptan alone. All
triptans narrow coronary arteries by 10% to 20% at clinical doses and should not 
be administered to patients with coronary or cerebrovascular disease. Some
triptans have the potential for significant drug-drug interactions (sumatriptan, 
rizatriptan, and zomitriptan and monoamine oxidase inhibitors; rizatriptan and
propanolol; zolmitriptan and cimetidine; and eletriptan and CYP3A4 metabolized
medications and p-glycoprotein pump inhibitors). Rational use of triptans should 
be governed by the use of these medications for patients with disability
associated with migraine. Patients with greater than 10 days of at least 50%
disability during 3 months have benefited from treating with triptans as their
first-line treatment for acute attacks. When the decision has been made to treat 
with a triptan, the patient should be instructed to treat early in the attack,
when the pain is at a mild phase. This approach increases the likelihood of
achieving a pain-free response, with fewer adverse events and lower likelihood of
the headache recurring.

Publication Types: 
    Review

PMID: 11480267 [PubMed - indexed for MEDLINE]

3224: Med Clin North Am. 2001 Jul;85(4):943-58, vi-vii.

Mechanism of migraine and action of antimigraine medications.

Spierings EL.

Department of Neurology, Brigham and Women's Hospital, Harvard Medical School,
Boston, Massachusetts, USA. spierings@mediaone.net

Dilation and inflammation of cephalic arteries and intracranial extra cerebral
arteries cause the migraine headache. The migraine-associated symptoms result
from the activation of the sympathetic nervous system caused by the pain. The
migraine aura is caused by the neurophysiological phenomenon of spreading
excitation/depression. The various mechanisms are tied together in the so-called 
"parallel theory" of the pathogenesis of the migraine attack. The abortive
antimigraine medications act by constricting the dilated arteries through
stimulation of the serotonin 1B receptor. The preventive antimigraine medications
act by increasing the tone of the extacranial arteries, inhibiting the mechanism 
of neurogenic inflammation, or inhibiting pain transmission within the central
nervous system.

Publication Types: 
    Review

PMID: 11480266 [PubMed - indexed for MEDLINE]

3225: Med Clin North Am. 2001 Jul;85(4):911-41.

Toward a rational understanding of migraine trigger factors.

Martin VT, Behbehani MM.

Department of Medicine, University of Cincinnati, Ohio, USA.

The typical migraine patient is exposed to a myriad of migraine triggers on a
daily basis. These triggers potentially can act at various sites within the
cerebral vasculature and the central nervous system to promote the development of
migraine headache. The challenge to the physician is in the identification and
avoidance of migraine trigger factors within patients suffering from migraine
headache. Only through a rational approach to migraine trigger factors can
physicians develop an appropriate treatment strategy for migraine patients.

Publication Types: 
    Review

PMID: 11480265 [PubMed - indexed for MEDLINE]

3226: Med Clin North Am. 2001 Jul;85(4):897-909.

The clinical spectrum of migraine.

Blumenthal HJ, Rapoport AM.

Neurological Associates of Tulsa, Inc., Oklahoma, USA. neurotulsa@aol.com

The variable clinical features of migraine and some relationships of migraine
with other headache disorders have been reviewed. Although these views generally 
are shared by most headache specialists, some respected headache investigators
reject the concept of a spectrum of migraine and conclude that the continuum
model is an artifact.

Publication Types: 
    Review

PMID: 11480264 [PubMed - indexed for MEDLINE]

3227: Med Clin North Am. 2001 Jul;85(4):887-95.

Epidemiology and impact of primary headache disorders.

Mannix LK.

LKMannixMD@aol.com

Migraine is a common disorder that remains largely undiagnosed and has a profound
economic impact. In the future, better recognition and treatment can decrease
costs and improve the lives of millions of Americans.

Publication Types: 
    Review

PMID: 11480263 [PubMed - indexed for MEDLINE]

3228: Med Clin North Am. 2001 Jul;85(4):865-85.

Diagnostic testing for headache.

Evans RW.

Department of Neurology, Park Plaza Hospital, Houston, Texas, USA.
rwevans@pol.net

A careful and complete headache history supplemented by a neurologic and general 
physical examination, as appropriate, enables the astute physician to diagnose
most headaches correctly without diagnostic testing. When indications are present
(see Box 1), some headache patients with a normal physical examination require
testing even though the yield may be low. Failure to test may result in
misdiagnosis of potentially serious and life-threatening causes of headaches,
such as brain tumors, chronic meningitis, SAH, and temporal arteritis.

Publication Types: 
    Review

PMID: 11480262 [PubMed - indexed for MEDLINE]

3229: Med Clin North Am. 2001 Jul;85(4):1085-92.

A spectrum of exertional headaches.

Green MW.

Department of Neurology, Columbia University, New York, New York, USA.

Headaches that have an explosive onset with exercise, including sexual activity, 
generally are benign in origin. A subarachnoid hemorrhage, a mass lesion in the
brain, or an anomaly of the posterior fossa must be considered, however. The
mechanisms that produce sexually induced or cough headaches of abrupt onset are
unknown. It is known, however, that a rapid increase in intrathoracic pressure
suddenly reduces right atrial pressure and presumably decreases venous sinus
drainage from the brain. This situation results in a transient increase in
intracranial pressure. Jaw pain that occurs with chewing often is considered to
be TMJ dysfunction when arthritic in quality and if subluxations of the jaw can
be shown on the physical examination. Giant cell arteritis and common or external
carotid artery occlusive disease should be considered when the pain is ischemic
in quality. An anginal equivalent is another possibility. Headaches that worsen
with vigorous exercise are commonly migrainous. When their onset is apoplectic
with exertion (particularly exertion against a closed glottis), the most likely
diagnoses are increased intracranial pressure, a posterior fossa abnormality, or 
benign exertional headaches. Most cardiac induced headaches, but not all, are of 
a more gradual onset. If there are significant risk factors for coronary artery
disease, an exercise stress test is appropriate. A therapeutic trial of
nitroglycerin may help to establish a diagnosis if it improves the headache.
Using antimigraine drugs as a diagnostic test is inappropriate because triptans
and ergots are contraindicated in the presence of coronary artery disease, and a 
positive response is not diagnostic of migraine.

Publication Types: 
    Case Reports

PMID: 11480260 [PubMed - indexed for MEDLINE]

3230: Med Clin North Am. 2001 Jul;85(4):1077-84.

Alternative therapies in headache. Is there a role?

Mauskop A.

New York Headache Center, New York, USA.

Alternative or complementary modes of treatment often lack scientific proof of
efficacy. This is true for many drugs that are used for prophylaxis of headaches 
as well. Many of these complementary modes are inexpensive, harmless, and
possibly effective. Patients can be given a list of options in the following
order of clinician preference: aerobic exercise; isometric neck exercise;
biofeedback; a combination product containing magnesium, riboflavin, and
feverfew; and acupuncture. The patient must decide which of these approaches is
appealing, affordable, and realistically doable.

Publication Types: 
    Review

PMID: 11480259 [PubMed - indexed for MEDLINE]

3231: Med Clin North Am. 2001 Jul;85(4):1055-75.

Behavioral and nonpharmacologic treatments of headache.

Lake AE 3rd.

Michigan Head-Pain and Neurological Institute, Ann Arbor, Michigan, USA.
aelake3rd@aol.com

Cognitive-behavioral analysis and the multiaxial assessment of relevant
behavioral domains (headache frequency and severity, analgesic and abortive use
and misuse, behavioral and stress-related risk factors, comorbid psychiatric
disorders, and degree of overall functional impairment) help set the stage for
CBT of headache disorders. Controlled studies of CBTs for migraine, such as
biofeedback and relaxation therapy, have a prophylactic efficacy of about 50%,
roughly equivalent to propranolol. Cluster headache responds poorly to behavioral
treatment. The persistent overuse of symptomatic medication impedes the
effectiveness of behavioral and prophylactic medical therapies. Behavioral
treatment can help sustain improvement after analgesic withdrawal, however, and
prevent relapse in cases of analgesic overuse. Cognitive factors (e.g., an
enhanced sense of self-efficacy and internal locus of control) appear to be
important mediators of successful behavioral treatment. Patients with CDH are
more likely to overuse symptomatic medication (and in some cases abuse
analgesics), have more psychiatric comorbidity; have more functional impairment
and disability, and are at least as likely to experience stress-related
intensification of headache as patients whose episodic headaches occur less than 
15 days per month. Despite the significance of these behavioral factors, patients
with CDH (particularly those with migrainous features) are less likely to benefit
from behavioral treatment without concomitant prophylactic medication than is the
case for episodic TTH and migraine sufferers. Continuous daily pain may be more
refractory to behavioral treatment as a solo modality than CDH marked by at least
some pain-free days or periods of time. The combination of behavioral therapies
with prophylactic medication creates a synergistic effect, increasing efficacy
beyond either type of treatment alone. Compliance-enhancement techniques,
including behavioral contracts for patients with severe personality disorders,
can increase adherence to behavioral recommendations. CBT has earned an important
place in the comprehensive treatment of patients with episodic migraine/TTH and
severe, treatment-resistant chronic daily headache.

Publication Types: 
    Review

PMID: 11480258 [PubMed - indexed for MEDLINE]

3232: Med Clin North Am. 2001 Jul;85(4):1017-35.

Hormone-related headache.

Silberstein SD.

Jefferson Headache Center and Department of Neurology, Thomas Jefferson
University Hospital, Philadelphia, Pennsylvania, USA.
Stephen.Silberstein@mail.tju.edu

The normal female life cycle is associated with hormonal milestones including
menarche, pregnancy, OC use, menopause, and the use of HRT. Menarche marks the
onset of menses and cyclic changes in hormone levels. Pregnancy is associated
with rising noncyclic levels of sex hormones. Menopause is associated with
declining noncyclic levels. Hormonal OC use during the reproductive years and HRT
in menopause are therapeutic hormonal interventions that alter the levels and
cycling of sex hormones. These events and interventions may cause a change in the
prevalence or intensity of headache. Headaches associated with OC use or
menopausal HRT may be related, in part, to periodic discontinuation of oral sex
hormone preparations. The treatment of migraine associated with changes in sex
hormone levels is difficult, and patients often are refractory to therapy. Based 
on what is known of the pathophysiology of migraine, a logical approach to the
treatment of headaches that are associated with menses, menopause, and OCs using 
abortive and preventive medications and hormonal manipulations has been
presented.

Publication Types: 
    Review

PMID: 11480256 [PubMed - indexed for MEDLINE]

3233: Arch Neurol. 2001 Jul;58(7):1056-8.

Establishing a standard of speed for assessing the efficacy of the
serotonin(1B/1D) agonists (triptans).

Marcus DA.

Department of Anesthesiology, University of Pittsburgh Medical Center, PA, USA.
dawnpainmd@yahoo.com

The current International Headache Society guidelines for migraine clinical
trials recommend assessment of pain relief at 2 hours as a primary end point.
Patients, however, express a clear preference for more rapid pain relief, with
most patients defining rapid relief as occurring within 30 minutes after drug
administration. Thus, consideration should be given to establishing clinical
trial end points that more accurately reflect the preferences of patients with
migraine. In this case, assessment of pain relief at 1 hour would be an
appropriate primary end point. Using speed of relief as a criterion for migraine 
drug selection also is appropriate. The migraine-specific serotonin(1B/1D)
agonists, or triptans, are able to meet this faster relief end point and are
preferred by patients.

Publication Types: 
    Review

PMID: 11448293 [PubMed - indexed for MEDLINE]

3234: Neurol Res. 2001 Jul;23(5):447-56.

Cortical spreading depression and the pathogenesis of brain disorders: a
computational and neural network-based investigation.

Ruppin E, Reggia JA.

Departments of Computer Science and Physiology, Tel-Aviv University, Tel-Aviv,
69978, Israel. ruppin@math.tau.ac.il

This paper reviews our recent studies of the role of cortical spreading
depression (CSD) in the pathogenesis of brain disorders. Our investigation is a
computational one, involving the development and utilization of a complex
neuro-metabolic model of the interactions assumed to occur in the cortex during
the passage of multiple CSD waves. Incorporating these neuro-metabolic changes of
CSD within a neural network model of normoxic cortex produces cortical activation
patterns during the passage of a CSD wave that, projected onto the visual fields,
resemble the visual hallucinations observed during the migraine aura. When focal 
ischemia is simulated with the model, the evoked CSD waves are found to affect
the expansion of the infarction into the ischemic penumbra. Our findings support 
the hypothesis that CSD does play an important pathogenic role in these and other
neurological disorders, and suggest additional experimental studies that may
further substantiate it.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 11474800 [PubMed - indexed for MEDLINE]

3235: Semin Cutan Med Surg. 2001 Jun;20(2):93-100.

Botulinum toxin type A (BOTOX) for treatment of migraine.

Binder WJ, Brin MF, Blitzer A, Pogoda JM.

Department of Head and Neck Surgery, University of California, Los Angeles, USA. 
wjb@doctorbinder.com

An open-label study and 2 double-blind, placebo-controlled studies have provided 
supporting evidence of botulinum toxin type A (BTX-A) as an effective,
well-tolerated treatment for migraine. Observed durations of benefit were
consistent with known properties of BTX-A. Findings suggest that response may
vary by features of preinjection headaches, such as migraine frequency. The
precise mechanism by which BTX-A provides pain relief is hypothesized to be
related not only to acetylcholine inhibition but also to a blocking action on the
parasympathetic nervous system. Additional studies that control factors likely to
be related to response may lead to better understanding of the BTX-A effect on
migraine and an optimal treatment protocol.

Publication Types: 
    Review

PMID: 11474749 [PubMed - indexed for MEDLINE]

3236: Cephalalgia. 2001 Jun;21(5):611-6.

Altered cerebrovascular response pattern in interictal migraine during visual
stimulation.

Bäcker M, Sander D, Hammes MG, Funke D, Deppe M, Conrad B, Tölle TR.

Department of Neurology, Technical University of Munich, Munich, Germany.

A dysbalance of the cerebrovascular response during functional activation of the 
brain has been postulated as a factor in the pathophysiology of migraine. To
determine the dynamic pattern of the cerebrovascular response in migraineurs
compared with a control group, changes of the cerebral perfusion during cerebral 
activation were studied with high temporal resolution by functional transcranial 
Doppler sonography (fTCD). The cerebral blood flow velocity (CBFV) in the right
posterior cerebral artery (PCA) and the left middle cerebral artery (MCA) was
measured simultaneously during visual stimulation in 19 interictal migraineurs
and in 19 age- and sex-matched control subjects. Data were analysed with a
previously validated technique based on automated stimulus-related averaging of
the CBFV. The MCA migraineurs exhibited a steady increase of CBFV during the
stimulation, while normal subjects showed a habituation of the CBFV response. The
lack of habituation in migraineurs was significantly (P < or = 0.05) more
pronounced across patients with a high attack frequency (> or = 4 per month)
compared with migraineurs with a low attack frequency (< 4 per month). In the
PCA, compared with normal subjects, migraineurs showed significantly (P < or =
0.05) stronger CBFV changes at the beginning and after the end of stimulation,
with a slower decline to baseline. Data are in accordance with
electrophysiological findings in migraineurs. It is assumed that a lack of
habituation of the cerebrovascular response in migraineurs might contribute to a 
disturbance of the metabolic homeostasis of the brain that might induce migraine 
attacks.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 11472388 [PubMed - indexed for MEDLINE]

3237: Cephalalgia. 2001 Jun;21(5):596-603.

Patterns of ergotamine and sumatriptan use in the Netherlands from 1991 to 1997.

Rahimtoola H, Egberts AC, Buurma H, Tijssen CC, Leufkens HG.

SIR Institute of Pharmacy Practice Research, Leiden, The Netherlands.
h.rahimtoola@pharm.uu.nl

The objective of this study was to assess usage patterns of ergotamine and
sumatriptan over a period of 6 years, primarily to evaluate the impact that
sumatriptan has had on the prescription of ergotamine. This study used ergotamine
and sumatriptan prescription data representing inhabitants of eight cities in the
Netherlands and covering the period of 1991-1997. The yearly incidence of new
users between 1991 and 1997 was estimated for both drugs as well as for the drug 
of first choice to be prescribed to patients initiating specific abortive
migraine treatment with either ergotamine or sumatriptan. Intra-individual
ergotamine and sumatriptan usage patterns, characterized by single (incidental), 
continuous (rate of retention) or switch use, were examined for five patient
cohorts, each for a follow-up period of 1 year. During the year of sumatriptan
introduction (1991-1992), the overall incidence of new use for both drugs was
highest (5.4 per 1000 inhabitants). Hereafter, a substantial reduction of more
than 50% was observed. From 1992 to 1996, the yearly incidence of ergotamine
first-time use was significantly higher than that of sumatriptan and up to 1996
ergotamine was more than twice as likely than sumatriptan to be prescribed to
patients initiating specific abortive treatment. Hereafter, sumatriptan was as
likely as ergotamine to be prescribed as the drug of first choice, which
coincided with the full reimbursement of sumatriptan tablets. Overall,
neurologists were more likely than general practitioners (GPs), to prescribe
sumatriptan as the drug of first choice. Approximately half of the total study
population were identified as single-time users. This phenomonen occurred more
frequently in the ergotamine cohorts. The sumatriptan cohorts displayed a slight 
yet significant stronger retention rate compared with the ergotamine cohorts. The
overall impact of sumatriptan on ergotamine use in The Netherlands was marginal, 
predominantly due to GP's adherence to migraine treatment guidelines and
reimbursement policies concerning sumatriptan tablets. Overall, incidental use
was relatively high and may reflect the reported difficulties in diagnosing
migraine, lack of patient-doctor consultation, or that anticipated benefits of
the drug were not achieved. Further study is required to clarify these issues.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 11472386 [PubMed - indexed for MEDLINE]

3238: Cephalalgia. 2001 Jun;21(5):584-95.

Diagnosis of migraine: empirical analysis of a large clinical sample of atypical 
migraine (IHS 1.7) patients and proposed revision of the IHS criteria.

Rains JC, Penzien DB, Lipchik GL, Ramadan NM.

Center for Sleep Evaluation, Elliot Hospital, Manchester, NH 03103, USA.
JRains@Elliot-HS.org

The International Headache Society (IHS) diagnostic criteria for headache
improved the accuracy of primary headache diagnoses, including migraine. However,
many migraineurs receive an 'atypical migraine' diagnosis according to the IHS
nosology (IHS 1.7), indicating that they approximate but do not fully meet all
IHS criteria. This study characterized and sub-classified patients with atypical 
migraine. Within a clinical sample of 382 headache sufferers, 83 patients met IHS
criteria for 'atypical migraine'. Patients receiving the IHS 1.7 designation did 
not converge to form a homogeneous group. Rather, distinct and clinically
relevant subgroups were empirically derived (e.g. migraine with atypical pain
parameters, brief migraine, chronic migraine). The results call for revisions of 
the IHS diagnostic criteria for migraine that would minimize the number of
patients receiving an atypical diagnosis. Revisions would include decreasing the 
minimum headache duration criteria from 4 h to 2 h, and developing a
classification for 'chronic migraine' for migraine greater than 15 days per
month. The proposed revision provides a means of diagnosing the daily and
near-daily headache commonly observed in clinical populations.

PMID: 11472385 [PubMed - indexed for MEDLINE]

3239: Cephalalgia. 2001 Jun;21(5):567-72.

Platelet 3H ketanserin binding in migraine.

Shukla R, Khanna VK, Pradeep S, Husain M, Tandon R, Nag D, Dikshit M, Srimal RC, 
Seth PK.

Department of Neurology, K.G.'s Medical College, Lucknow, India.

Platelet 3H ketanserin binding was studied in 33 patients of migraine and 30
healthy controls. The binding characteristics: equilibrium dissociation constant 
(Kd) and maximal number of binding sites (Bmax) determined by Scatchard analysis 
revealed a significant decrease in Kd and no change in Bmax in migraine cases. No
correlation was observed between the Kd and Bmax with the clinical features of
migraine. The findings of the present study show that there is a decreased
affinity of platelet 5-HT2 receptors in migraine.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 11472383 [PubMed - indexed for MEDLINE]

3240: Cephalalgia. 2001 Jun;21(5):558-66.

Clinical presentation of transformed migraine: possible differences among male
and female patients.

Krymchantowski AV, Moreira PF.

Headache Center of Rio and Institute of Neurology Deolindo Couto, Rio de Janeiro,
Brazil. abouchkrym@openlink.com.br

Chronic daily headache (CDH) represents a group of non-paroxysmal headache
disorders that occur on a daily or near-daily basis, for longer than 6 months.
Even though it is a common problem, affecting 30-70% of the patients attending
specialized headache clinics, it is not a well-defined and classified disorder,
resulting in controversies regarding its description and approach. The aim of
this study was to evaluate the clinical presentation of CDH due to transformed
migraine and possibly compare the differences among male and female patients. Two
hundred and seventy-one patients, 217 women and 54 men, ages 16-83 (mean 37.5
years for women and 41.4 for men), fulfilling the proposed criteria for
transformed migraine and selected from a group of 300 consecutive CDH patients
attending a subspecialty headache centre, were studied retrospectively. The most 
observed clinical presentation was pressure or tightening, bilateral
fronto-temporal, moderate non-continuous headache, with a progressive onset. The 
association with nausea and phonophobia was demonstrated in 60% and 32% of the
patients, respectively. The association with photophobia (29.6% male, 44.2%
female, P = 0.05) sleep (77.7% male, 49.8% female, P = 0.0002) and emotional (87%
male, 64.1% female, P = 0.001) disturbances, as well as the occurrence of
intermittent full-blown migraine attacks (81.5% male, 95.4% female, P = 0.001)
was significantly different among male and female patients. Overuse of
symptomatic medications (SM) was observed in 87% of the male and in 83.8% of the 
female patients, with a significant difference concerning the use of more than
one type of SM (male 68% compared with female 91.7%; P = 0.006). We concluded
that TM patients have a clinical presentation compatible with previous
descriptions but suggesting, even though limited by the restricted number of male
patients, different aspects among male and female patients.

Publication Types: 
    Comparative Study

PMID: 11472382 [PubMed - indexed for MEDLINE]

3241: Cephalalgia. 2001 Jun;21(5):549-57.

Migraine and function of the immune system: a meta-analysis of clinical
literature published between 1966 and 1999.

Kemper RH, Meijler WJ, Korf J, Ter Horst GJ.

Department of Psychiatry, Section Biological Psychiatry, University Groningen,
Groningen, The Netherlands.

Mechanisms underlying migraine precipitation are largely unknown. A role of the
immune system in migraine precipitation is a matter of debate because of the
association of atopic disorders and migraine. Recently, it was demonstrated that 
migraineurs benefit from eradication of a Helicobacter pylori infection, which
substantiates a possible role for (sub-clinical) infections in precipitation of
migraine. Since 1966, about 45 clinical investigations have reported on
alterations of immune function in migraine patients, which we present in this
review. Changes of serum levels of complement and immunoglobulins, histamine,
cytokines and immune cells were found in some of these studies but in most cases 
not corroborated by others. Migraineurs suffering from comorbid atopic disorders 
show elevated plasma IgE levels but not patients without a type I
hypersensitivity. Histamine plasma levels are chronically elevated in
migraineurs, and interictally decreased lymphocyte phagocytotic function and
increased plasma tumor necrosis factor alpha (TNFalpha) levels were found, and
may be related to increased infection susceptibility. The cause of this increased
susceptibility is unclear but most likely is a result of chronic stress, a
well-known suppressor of the immune system. Stress relief enhances immune
activity and triggers a burst of circulating vasoactive compounds that function
as mediators of inflammation and potential precipitators of a migraine attack in 
vulnerable subjects. In conclusion, in the clinical literature of the past
decades, there is no clear-cut evidence of an immune dysfunction in migraineurs, 
but we cannot totally exclude the possibility of an altered immune function in
migraineurs. Discrepancies in the literature most likely are caused by the
divergent patterns of sample collection relative to the time of the attack. We
propose stringent definition of sample collection times for future studies of
immune function in migraine patients.

Publication Types: 
    Meta-Analysis
    Research Support, Non-U.S. Gov't

PMID: 11472381 [PubMed - indexed for MEDLINE]

3242: Neurol Clin. 2001 Feb;19(1):1-21.

Topics in migraine management: a survey of headache specialists highlights some
controversies.

Evans RW, Lipton RB.

Department of Neurology, University of Texas Medical School, Houston, USA.
rwevans@pol.net

The authors' Survey of headache specialists highlights a number of controversial 
issues in migraine management including the following: acute treatment, focusing 
on use of triptans, and preventative medications; treatment of migraine with
prolonged aura and basilar migraine; and the use of oral contraceptives in
migraine. Interestingly, the prevalence of migraine among the headache
specialists themselves is much higher than in the general population. Although
triptans have revolutionized the acute treatment of migraine, treatment is still 
problematic for the sizable percentages of patients with an incomplete or no
response and recurrence of headache. Triptans are generally very safe when the
physician, aware of the potential for coronary artery vasoconstriction,
appropriately screens patients before and during their use. Serotonin syndrome as
a complication of triptan use is quite rare. Although there is no definite
evidence of teratogenesis, triptans should not be taken during pregnancy unless
the potential benefit justifies the potential risk to the fetus. Caution is also 
advised when using a triptan during breastfeeding. The United States Headache
Consortium parameters, which consider indications for preventative treatment and 
propose general principles of management, are reviewed. Unfortunately, the
experience of many migraineurs with preventative medications is less than
satisfactory because of side effects or lack of efficacy. Treatment of both
migraine with prolonged aura and basilar migraine is anecdotally based. Many
headache specialists do not use beta blockers for prevention for those with
prolonged aura and basilar migraines because of concerns over the potential
limitation of compensatory vasodilatory capacitance. There are seven case reports
in the literature of an association between stroke and the use of beta blockers
in migraineurs. Prevention using divalproex sodium and verapamil is favored by
many headache specialists. Triptans are contraindicated in the treatment of
patients with hemiplegic or basilar migraine because of concern over the
potential for cerebral vasoconstriction. The frequency of migraine is usually
unchanged with the use of oral contraceptives although, occasionally, migraine
may occur for the first time or increase in frequency. Studies have produced
conflicting results as to whether low-dose estrogen oral contraception increases 
the risk of stroke. Migraine alone increases the risk of stroke, at least in
women under the age of 45 years. Most women with migraine without aura and
migraine with visual aura lasting less than 1 hour can safely use low-dose
estrogen oral contraceptives when there are no other contraindications. Those
with aura symptoms such as hemiparesis or dysphasia or prolonged focal neurologic
symptoms and signs lasting more than 1 hour should avoid starting low-dose
estrogen oral contraceptives and stop the medication if they are already taking
it.

Publication Types: 
    Review

PMID: 11471758 [PubMed - indexed for MEDLINE]

3243: Neurology. 2001 Jul 24;57(2):334-6.

Increased von Willebrand factor in migraine.

Tietjen GE, Al-Qasmi MM, Athanas K, Dafer RM, Khuder SA.

Department of Neurology, Medical College of Ohio, Toledo, USA. gtietjen@mco.edu

The authors determined von Willebrand factor (vWF) in 63 persons with migraine,
11 persons with migraine and prior stroke, and 35 frequency-matched controls.
Additional studies were done in a subset with migraine without aura who were
headache free for >7 days. Migraineurs with prior stroke had significantly higher
vWF antigen (170% versus 106%) and activity (162% versus 108%) than the control
group. vWF antigen (126%) and activity (130%) were also significantly higher in
migraineurs without stroke. Multimers and protease activity were normal in the
interictal subset.

PMID: 11468324 [PubMed - indexed for MEDLINE]

3244: CNS Drugs. 2001;15(2):105-18.

Clinically significant drug interactions with agents specific for migraine
attacks.

Eadie MJ.

Department of Medicine, University of Queensland, Royal Brisbane Hospital,
Australia. M.Eadie@mailbox.uq.edu.au

The drugs which provide specific relief from migraine attacks, the ergopeptides
(ergotamine and dihydroergotamine) and the various 'triptans' (notably
sumatriptan), are often prescribed for persons already taking various migraine
preventative agents, and sometimes drugs for other indications. As a result,
migraine-specific drugs may become involved in drug-drug interactions. The
migraine-specific drugs all act as agonists at certain subclasses of serotonin
(5-hydroxytryptamine; 5-HT) receptor, particularly those of the 5-HT1D subtype,
and produce vasoconstriction through these receptor-mediated mechanisms. The oral
bioavailabilities of these drugs, particularly those of the ergopeptides, are
often incomplete, due to extensive presystemic metabolism. As a result, if
migraine-specific agents are coadministered with drugs with vasoconstrictive
properties, or with drugs which inhibit the metabolism of the migraine-specific
agents, there is a risk of interactions occurring which produce manifestations of
excessive vasoconstriction. This can also occur through pharmacodynamic
mechanisms, as when ergopeptides or triptans are coadministered with methysergide
or propranolol (although a pharmacokinetic element may apply in relation to the
latter interaction), or if one migraine-specific agent is used shortly after
another. When ergopeptide metabolism is inhibited by the presence of macrolide
antibacterials, particularly troleandomycin and erythromycin, the resultant
interaction can produce ergotism, sometimes leading to gangrene. Similar
pharmacokinetic mechanisms, with their vasoconstrictive consequences, probably
apply to combination of the ergopeptides with HIV protease inhibitors (indinavir 
and ritonavir), heparin, cyclosporin or tacrolimus. Inhibition of triptan
metabolism by monoamine oxidase A inhibitors, e.g. moclobemide, may raise
circulating triptan concentrations, although this does not yet seem to have led
to reported clinical problems. Caffeine may cause increased plasma ergotamine
concentrations through an as yet inadequately defined pharmacokinetic
interaction. However, a direct antimigraine effect of caffeine may contribute to 
the claimed increased efficacy of ergotamine-caffeine combinations in relieving
migraine attacks. Serotonin syndromes have been reported as probable
pharmacodynamic consequences of the use of ergots or triptans in persons taking
serotonin reuptake inhibitors. There have been two reports of involuntary
movement disorders when sumatriptan has been used by patients already taking
loxapine. Nearly all the clinically important interactions between the
ergopeptide antimigraine agents and currently marketed drugs are likely to have
already come to notice. In contrast, new interactions involving the triptans are 
likely to be recognised as additional members of this family of drugs, with their
different patterns of metabolism and pharmacokinetics, are marketed.

Publication Types: 
    Review

PMID: 11460889 [PubMed - indexed for MEDLINE]

3245: Neurology. 2001 Jul 10;57(1):130-2.

Comment in:
    Neurology. 2002 Feb 26;58(4):668-9; author reply 669.

Headache characteristics in patients after migrainous stroke.

Linetsky E, Leker RR, Ben-Hur T.

Department of Neurology, The Agnes Ginges Center for Human Neurogenetics,
Hadassah-Hebrew University Hospital, Jerusalem, Israel.

Six patients who fulfilled strictly defined criteria for migrainous cerebral
infarction and in whom other causes of stroke were ruled out were observed. All
had a long-standing history of migraine with aura. In most, stroke was mild with 
good recovery and no recurrence. Headache frequency and severity decreased after 
the stroke. It is hypothesized that the improvement in migraine may be due to
reduced nociceptive transmission as result of loss in vasoreactivity of the
affected cerebral blood vessel.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 11445642 [PubMed - indexed for MEDLINE]

3246: Cephalalgia. 2001 Apr;21(3):230-5.

Comment in:
    Cephalalgia. 2001 Dec;21(10):1002.

Headache caused by drinking cold water is common and related to active migraine.

Mattsson P.

Department of Neuroscience, Neurology, University Hospital, Uppsala, Sweden.
Peter.Mattsson@neurologi.uu.se

The primary aim of this study was to estimate the prevalence of cold-induced
headache and to test if it is associated with migraine. Women attending a
population-based mammography screening programme were asked to participate in the
study. Fifty-one of 669 women (7.6%) experienced a headache after ingesting 150
ml of ice-cold water through a straw. Women who had experienced one or more
migraine attacks in the last year (active migraine) were twice as likely to
experience a headache from ingesting the cold water as women who had never
suffered from migraine. Ninety-five women who had experienced their most recent
migraine attack more than 1 year ago (inactive migraine) were not at increased
risk. The prevalence of active and inactive migraine was 19.4 and 14.2%,
respectively. Headache caused by drinking cold water is common in women. The
results indicate that active migraine facilitates the perception of forehead pain
induced by a cold palatal stimulus.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 11442559 [PubMed - indexed for MEDLINE]

3247: Cephalalgia. 2001 Apr;21(3):224-9.

Quantitative EEG responses to ischaemic arm stress in migraine.

Rainero I, Amanzio M, Vighetti S, Bergamasco B, Pinessi L, Benedetti F.

Neurology II -- Headache Center, Department of Neuroscience, University of Turin 
Medical School, Torino, Italy. irainero@molinette.piemonte.it

Several studies suggest that patients with migraine respond physiologically to
stress differently from controls, yet experimental data are scarce. In order to
evaluate the reactivity to stress in migraine, we recorded the quantitative
electroencephalogram (qEEG) during non-noxious and noxious ischaemic arm stress
in two groups of healthy controls and compared the results with the effects of
non-noxious ischaemic arm stress in a group of patients with migraine. In the
controls, non-noxious mild stress did not produce any qEEG change but noxious
stress induced a significant decrease of the alpha power. By contrast, in
migraine patients the non-noxious mild stress was sufficient to induce a
significant decrease of the alpha power in all brain regions. The results of our 
study show that migraine sufferers display a lower threshold to physical stress
and confirm previous studies indicating that migraine is a disease characterized 
by a state of altered neuronal excitability.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 11442558 [PubMed - indexed for MEDLINE]

3248: Cephalalgia. 2001 Apr;21(3):184-8.

Influence of intense light stimulation on trigeminal and cervical pain perception
thresholds.

Kowacs PA, Piovesan EJ, Werneck LC, Tatsui CE, Lange MC, Ribas LC, da Silva HP.

Neurology Division, Internal Medicine Department, Hospital de Clínicas da
Universidade Federal do Paraná, Curitiba, Brazil.

Thirty-three migraineurs and 23 healthy controls were submitted to pressure
algometry before and after light-induced discomfort was elicited by progressive
light stimulation in a monoblind fashion. Pressure algometries were performed on 
the emergence of the supraorbital, infraorbital, mental and greater occipital
nerves, and over the temporal muscles, always throughout the same sequence and
from right to left. Measurements were carried out before and immediately after
light stimulation and after 10 min of the second algometry. The final result for 
each site measured at each time-point was the mean of the three measurements.
Light stimulation was carried out progressively until light-induced discomfort
was reported, to a maximum of 20,000 lux. A heat-blocking glass protected
patients' eyes. Migraineurs presented significant and persistent drops in pain
perception thresholds after light stimulation, at all sites tested (P = 0.002 to 
< 0.0001). These drops were not seen in controls, in whom, conversely, a less
significant increase was seen on right infraorbital and left temporal muscle
sites. Our results indicate that in migraineurs, light may have a relevant role
in trigeminal and cervical pain perception thresholds.

Publication Types: 
    Clinical Trial
    Research Support, Non-U.S. Gov't

PMID: 11442552 [PubMed - indexed for MEDLINE]

3249: Cephalalgia. 2001 Apr;21(3):175-83.

Comment in:
    Cephalalgia. 2001 Apr;21(3):167-8.

Low-dose aspirin for migraine prophylaxis in women.

Benseñor IM, Cook NR, Lee IM, Chown MJ, Hennekens CH, Buring JE.

Division of Preventive Medicine, Department of Medicine, Brigham and Women's
Hospital and Harvard Medical School, Boston, Massachusetts 02215-1204, USA.

Although migraine is more common among women than men, the only two large,
randomized trials of low-dose aspirin for migraine prophylaxis have been
conducted in men. As part of the Women's Health Study, an ongoing randomized
trial of low-dose aspirin and vitamin E among 39 876 female health professionals 
aged 45 and older, 1001 women with frequent migraine attacks were assigned to 100
mg of aspirin every other day (n = 525) or aspirin placebo (n = 476). Migraine
frequency, as well as severity, duration, and degree of incapacitation, were
assessed by self-report on questionnaires 12 months and 36 months after
randomization, and also by monthly diaries kept before and after randomization.
Women assigned to aspirin reported small and consistent decreases in migraine
frequency (59.6% vs. 56.4% assigned to placebo reporting improvement at 36
months; odds ratio 1.13, 95% confidence interval, 0.86--1.48), as well as
decreases in severity, duration, and migraine-related incapacitation. These
reductions were not, however, statistically significant. These data are
compatible with a small treatment effect of low-dose aspirin in the prophylaxis
of migraine among middle-aged women.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 11442551 [PubMed - indexed for MEDLINE]

3250: Clin Ther. 2001 Jun;23(6):886-900.

Migraine treatment outcomes with rizatriptan in triptan-naive patients: a
naturalistic study.

Solomon S, Frishberg B, Hu XH, Markson L, Berger M.

Montefiore Medical Center, New York, New York, USA.

BACKGROUND: The 5-hydroxytryptamine(1B/1D) agonists, or triptans, are the newest 
class of drugs to become available for the acute treatment of migraine. The class
currently includes sumatriptan, zolmitriptan, naratriptan, and rizatriptan. The
efficacy of rizatriptan in the acute treatment of migraine has been established
against placebo and other oral triptans in controlled comparative trials.
OBJECTIVE: The US Migraine Assessment Protocol (USMAP) collected data on the use 
of rizatriptan in a naturalistic setting reflecting clinical practice. This paper
presents results for patients enrolled in the USMAP study who had never taken a
triptan before the study. METHODS: At enrollment, 216 patients completed a
questionnaire describing their responses to their current nontriptan medications.
They were then given specially packaged samples of 4 standard 10-mg rizatriptan
tablets and 4 orally disintegrating 10-mg rizatriptan tablets (wafers) and were
asked to take a different formulation for each of their next 2 attacks, the
sequence to be at their discretion. Within approximately 24 hours after taking
rizatriptan, patients were to call a toll-free number to report their responses
to rizatriptan using an interactive voice-response system. RESULTS: Within 2
hours after initial dosing of rizatriptan, significantly more patients taking
either the rizatriptan tablet or the rizatriptan wafer reported onset of pain
relief, had become largely symptom free, and were able to resume usual activities
compared with their baseline responses to nontriptans (P < 0.05). In addition,
compared with their baseline responses to nontriptans, significantly more
patients taking either rizatriptan formulation had mild or no pain 2 hours after 
dosing (P < 0.05). More than twice as many patients taking the rizatriptan
tablets or wafers were either somewhat or very satisfied with the medication
compared with their satisfaction with nontriptans (P < 0.05). CONCLUSIONS: In the
naturalistic setting of this study, migraineurs who had not previously taken a
triptan medication reported more rapid relief of pain, more effective pain
relief, and more rapid resumption of normal activities when taking rizatriptan
tablets or wafers than when taking a nontriptan medication. Patients dissatisfied
with their current nontriptan migraine therapy may benefit from treatment with
rizatriptan.

Publication Types: 
    Comparative Study

PMID: 11440288 [PubMed - indexed for MEDLINE]

3251: Clin Ther. 2001 Jun;23(6):772-88; discussion 771.

Current options for the prevention and treatment of migraine.

Adelman JU, Adelman RD.

Headache Wellness Center Greensboro, North Carolina 27401, USA.
jadelman@triad.rr.com

BACKGROUND: Migraine is a common condition affecting approximately 18% of women
and 6% of men in the United States. The goals of managing migraine are 2-fold: to
prevent attacks from occurring and to effectively and rapidly end them when they 
do occur. OBJECTIVE: This article reviews the acute and prophylactic treatment of
migraine. METHODS: Information for inclusion in this review was identified
through a search of MEDLINE from 1995 to the present. Search terms included
migraine, acute treatment, prophylactic treatment, preventive treatment, and
individual drug names. RESULTS: Preventive measures for migraine include
lifestyle changes (eg, avoiding migraine triggers and maintaining regular sleep, 
eating, and work habits) and drug therapy. Beta-blockers, calcium channel
blockers, tricyclic antidepressants, and anticonvulsants are among the more
common drug classes used for migraine prophylaxis, but preventive therapy must be
individualized, taking into account efficacy, potential adverse effects,
co-existing medical conditions, and drug costs. Many medications are available
for the acute treatment of migraine, including over-the-counter analgesics and
prescription drugs. Of the latter, the 5-hydroxytryptamine(1B/1D)-receptor
agonists, or triptans, are the most recently introduced class. Each of the 4
available triptans (sumatriptan, zolmitriptan, naratriptan, and rizatriptan) is
effective in ending a migraine attack, but comparative trials have shown
differences between individual drugs in the time to pain relief and the
percentage of patients who obtain pain relief. CONCLUSIONS: Medications to
prevent or reduce the frequency of migraine tend to be less specific and
effective than medications for the acute treatment of migraine. As a class,
triptans are generally well tolerated and may be considered drugs of choice for
the acute treatment of moderate to severe migraine.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 11440281 [PubMed - indexed for MEDLINE]

3252: N Engl J Med. 2001 Jul 5;345(1):17-24.

Comment in:
    N Engl J Med. 2001 Jul 5;345(1):57-9.

The clinical spectrum of familial hemiplegic migraine associated with mutations
in a neuronal calcium channel.

Ducros A, Denier C, Joutel A, Cecillon M, Lescoat C, Vahedi K, Darcel F, Vicaut
E, Bousser MG, Tournier-Lasserve E.

INSERM E99-21, Faculté de Médecine Lariboisière, Paris, France.
anne.ducros@lrb.ap-hop-paris.fr

BACKGROUND: Familial hemiplegic migraine, an autosomal dominant disorder
characterized by attacks of transient hemiparesis followed by a migraine
headache, is classically divided into pure familial hemiplegic migraine
(affecting 80 percent of families) and familial hemiplegic migraine with
permanent cerebellar signs (affecting 20 percent of families). Mutations in
CACNA1A, which encodes a neuronal calcium channel, are present in 50 percent of
families with hemiplegic migraine, including all those with cerebellar signs. We 
studied the various clinical manifestations associated with mutations in CACNA1A 
in families with hemiplegic migraine with and without cerebellar signs. METHODS: 
CACNA1A was analyzed and nine mutations were detected in 15 of 16 probands of
families affected by hemiplegic migraine and cerebellar signs, in 2 of 3 subjects
with sporadic hemiplegic migraine and cerebellar signs, and in 4 of 12 probands
of families affected by pure hemiplegic migraine. Genotyping of probands and
relatives identified a total of 117 subjects with mutations whose clinical
manifestations were assessed in detail. RESULTS: Eighty-nine percent of the
subjects with mutations had attacks of hemiplegic migraine. One third had severe 
attacks with coma, prolonged hemiplegia, or both, with full recovery. All nine
mutations, including five newly identified ones, were missense mutations. Six
mutations were associated with hemiplegic migraine and cerebellar signs, and 83
percent of the subjects with these six mutations had nystagmus, ataxia, or both. 
Three mutations were associated with pure hemiplegic migraine. CONCLUSIONS:
Hemiplegic migraine in subjects with mutations in CACNA1A has a broad clinical
spectrum. This clinical variability is partially associated with the various
types of mutations.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 11439943 [PubMed - indexed for MEDLINE]

3253: Headache. 2001 Jun;41(6):573-8.

Quality-of-life differences between patients with episodic and transformed
migraine.

Meletiche DM, Lofland JH, Young WB.

Office of Health Policy and Clinical Outcomes, Thomas Jefferson University,
Philadelphia, Pa 19107-5099, USA.

OBJECTIVE: To determine whether there are any differences in health-related
quality of life between patients with migraine and those with transformed
migraine. BACKGROUND: There are no published reports comparing the health-related
quality of life between patients with migraine and patients with transformed
migraine. METHODS: We conducted a retrospective analysis examining the
health-related quality of life of patients with transformed migraine and migraine
seen at a specialty headache clinic. Data collected included the Short Form-36
(SF-36) and the Migraine Disability Assessment questionnaires as well as
demographic information. Both of these forms are part of the initial evaluation
at the headache clinic. A t test with Bonferroni correction was used to test for 
significant differences in the SF-36 domains between the groups. RESULTS: Data
were collected for 90 patients, 46 with transformed migraine and 44 with
migraine. There were no significant differences between groups with respect to
sex, race, or age. Over the last 90 days prior to their first visit, patients
with transformed migraine reported having a headache an average of 69 days
compared with patients with migraine who averaged 18 days with headache (P<.05). 
Compared with patients with migraine, patients with transformed migraine had
statistically (P<.05) and clinically significant (difference >5 points) lower
mean scores on seven of the eight SF-36 domains and both the mental and physical 
summary scores of the SF-36. CONCLUSIONS: The results of this study suggest that 
patients with transformed migraine have a lower health-related quality of life
than patients with migraine. These findings indicate that the headache chronicity
associated with transformed migraine has a significant influence on quality of
life. The results highlight the importance of effective management of headaches
to avoid the progression of migraine to the more disabling transformed migraine.

Publication Types: 
    Comparative Study

PMID: 11437893 [PubMed - indexed for MEDLINE]

3254: Headache. 2001 Jun;41(6):565-72.

Visual cortex excitability in migraine with and without aura.

Mulleners WM, Chronicle EP, Palmer JE, Koehler PJ, Vredeveld JW.

Departments of Neurology, Atrium Medical Center, Heerlen, The Netherlands.

OBJECTIVES: Previous research using transcranial magnetic stimulation has
produced equivocal findings concerning thresholds for the generation of visual
phosphenes in migraine with aura. These studies were methodologically varied and 
did not systematically address cortical excitability in migraine without aura. We
therefore studied magnetophosphene thresholds in both migraine with aura and
migraine without aura compared with headache-free controls. METHODS: Sixteen
subjects with migraine with aura and 12 subjects with migraine without aura were 
studied and compared with 16 sex- and age-matched controls. Using a standardized 
transcranial magnetic stimulation protocol of the occipital cortex, we assessed
the threshold stimulation intensity at which subjects just perceived phosphenes
via a method of alternating course and fine-tuning of stimulator output. RESULTS:
There were no significant differences across groups in the proportion of subjects
seeing phosphenes. However, the mean threshold at which phosphenes were reported 
was significantly lower in both migraine groups (migraine with aura=47%, migraine
without aura=46%) than in controls (66%). Moreover, there was no significant
correlation between individual phosphene threshold and the time interval to the
closest migraine attack. CONCLUSION: Our findings confirm that the occipital
cortex is hyperexcitable in the migraine interictum, both in migraine with and
without aura.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 11437892 [PubMed - indexed for MEDLINE]

3255: Headache. 2001 Jun;41(6):554-8.

Precipitating and aggravating factors of migraine versus tension-type headache.

Spierings EL, Ranke AH, Honkoop PC.

Department of Neurology, Brigham & Women's Hospital and Harvard Medical School,
Boston, Mass, USA.

OBJECTIVE: We conducted the present study to determine whether there are headache
precipitating and aggravating factors that differentiate migraine from
tension-type headache and headache precipitating and aggravating factors that
differentiate tension-type headache from migraine. METHODS: We interviewed 38
patients with migraine and 17 patients with tension-type headache (diagnosed
using International Headache Society criteria) by telephone, using a
questionnaire. The questionnaire inquired about the following precipitating and
aggravating headache factors: (1) physical activity, (2) straining, (3) bending
over, (4) stress/tension, (5) coughing/sneezing, (6) fatigue, (7) reading, (8)
driving, (9) lack of sleep, (10) specific foods/drinks, (11) alcohol, (12) not
eating on time, (13) smoke, (14) smell, (15) light, (16) noise, (17)
menstruation, and (18) weather. RESULTS: The most common precipitating factors
acknowledged by both groups of patients were stress/tension, not eating on time, 
fatigue, and lack of sleep. Weather, smell, smoke, and light were the
precipitating factors that differentiated migraine from tension-type headache.
Excluding those factors that are part of the International Headache Society
migraine diagnosis, the aggravating factors were straining, bending over, and
smell. We found no precipitating or aggravating factors differentiating
tension-type headache from migraine. CONCLUSION: Apparently there are
precipitating and aggravating factors differentiating migraine from tension-type 
headache but not vice versa. It is interesting that three of the
migraine-specific precipitating factors (ie, weather, smell, and smoke) involve
the nose/sinus system, suggesting a greater significance of this system in
headache than is generally considered.

Publication Types: 
    Comparative Study

PMID: 11437890 [PubMed - indexed for MEDLINE]

3256: Headache. 2001 Jun;41(6):546-53.

Behavioral response to headache: a comparison between migraine and tension-type
headache.

Martins IP, Parreira E.

Department of Neurology, Hospital de Santa Maria, Lisbon, Portugal.

OBJECTIVE: To compare patients with migraine and tension-type headache in their
behavior during the attacks and the maneuvers used to relieve the pain.
BACKGROUND: Patients with headache often perform nonpharmacological measures to
relieve the pain, but it is not known if these behaviors vary with the diagnosis,
clinical features, and pathogenesis. METHODS: One hundred consecutive patients
with either migraine (n = 72 ) or tension-type headache (n = 28) were questioned 
(including the use of a checklist) concerning their usual behavior during the
attacks and nonpharmacological maneuvers performed to relieve the pain. The
results of the two types of headache were compared. RESULTS: Patients with
migraine tended to perform more maneuvers than individuals with tension-type
headache (mean, 6.2 versus 3). These maneuvers included pressing and applying
cold stimuli to the painful site, trying to sleep, changing posture, sitting or
reclining in bed (using more pillows than usual to lay down), isolating
themselves, using symptomatic medication, inducing vomiting, changing diet, and
becoming immobile during the attacks. The only measure predominantly reported by 
patients with tension-type headache was scalp massage. However, the benefit
derived from these measures was not significantly different between the two
groups (except for a significantly better response to isolation, local pressure, 
local cold stimulation, and symptomatic medication in migraineurs). CONCLUSIONS: 
The behavior of patients during headache attacks varies with the diagnosis.
Measures that do not always result in pain relief are performed to prevent its
worsening or to improve associated symptoms. These behavioral differences may be 
due to the different pathogenesis of the attacks or to different styles of
dealing with the pain. They can also aid the differential diagnosis between
headaches in doubtful cases.

Publication Types: 
    Comparative Study

PMID: 11437889 [PubMed - indexed for MEDLINE]

3257: Aust Fam Physician. 2001 May;30(5):461-5.

Migraine and hypertension. Is there a relationship?

Prentice D, Heywood J.

Migraine and Hypertension Services, St Vincent's Hospital, Melbourne, Victoria.
prentida@ozemail.com.au

BACKGROUND Migraine and hypertension are common conditions that frequently
coexist. The relastionship between the two is usually coincidental, but some
evidence suggests that poor control of blood pressure may exacerbate the
frequency and severity of migraine. OBJECTIVE To review the relationship between 
migraine, other headaches and blood pressure and to discuss guidelines for
suitable therapy for both conditions when they occur together. DISCUSSION
Establishing the blood pressure should be a routine task in the assessment of all
headache patients. Severe hypertension in the setting of new acute headache may
indicate a serious underlying cause and requires urgent investigation. In
patients with migraine and established hypertension, good control of blood
pressure may be beneficial in controlling their headache. Many of the drugs used 
to treat hypertension may cause headache and some agents used to treat migraine
can exacerbate hypertension and so careful consideration of the therapeutic
options is important.

Publication Types: 
    Review

PMID: 11432020 [PubMed - indexed for MEDLINE]

3258: Pain. 2001 Aug;93(2):185-90.

A comparison of visual analog scale and categorical ratings of headache pain in a
randomized controlled clinical trial with migraine patients.

Lines CR, Vandormael K, Malbecq W.

Merck & Co., Inc., P.O. Box 4, West Point, PA 19486, USA. chris_lines@merck.com

A visual analog scale (VAS) method of assessing headache pain was compared with a
standard categorical four-grade scale (4GS) in a randomized, placebo-controlled, 
double-blind, clinical trial involving 792 treated migraine outpatients who
received oral rizatriptan 5 mg, sumatriptan 50 mg, or placebo for a moderate or
severe headache. The VAS and 4GS were equally useful in demonstrating that the
active drugs were superior to placebo at reducing headache pain, and in showing
that the active drugs were similarly effective. For both rizatriptan and
sumatriptan, slightly larger effect sizes were observed with the 4GS compared
with the VAS. In analyses using data combined across all treatment groups, VAS
and 4GS scores were highly correlated. Use of the VAS imposed additional
administrative burdens. These findings suggest that the 4GS may be the preferred 
scale for assessing headache pain in clinical trials involving adult migraineurs.

Publication Types: 
    Clinical Trial
    Clinical Trial, Phase III
    Comparative Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 11427330 [PubMed - indexed for MEDLINE]

3259: Am J Med Genet. 2001 Jan 8;105(1):110-3.

No evidence for involvement of the human inducible nitric oxide synthase (iNOS)
gene in susceptibility to typical migraine.

Lea RA, Curtain RP, Shepherd AG, Brimage PJ, Griffiths LR.

Genomics Research Centre, School of Health Science, Griffith University, Gold
Coast, Queensland, Australia.

Migraine is a debilitating disorder affecting approximately 12% of Caucasian
populations. The disease has a large genetic component, although at present the
type and number of genes involved is unclear. Candidate gene studies may be
useful strategies for identifying genes involved in complex diseases such as
migraine, especially if the gene being examined contributes only a minor effect
to the overall phenotype. Nitric oxide (NO) is emerging as a key molecule
affecting the pain associated with migraine. Since NO synthase (NOS) enzymes
catalyze the synthesis of NO, the genes that code for these enzymes are good
candidates for migraine molecular genetic analysis. This study investigated the
role of a functionally relevant bi-allelic tetranucleotide polymorphism located
in the promoter region of the human inducible nitric oxide synthase (iNOS) gene
in migraine etiology. A large group of migraine affected individuals (n = 261)
were genotyped and compared with an age- and sex-matched group of unaffected
controls (n = 252). Results of a chi-squared analysis indicated that allele
distributions for both migraine cases and controls were not significantly
different (chi2 = 1.93, P = 0.16). These findings offer no evidence for an
allelic association of the tested iNOS polymorphism with the common forms of the 
disease and therefore do not support a role for this gene in migraine
pathogenesis.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 11424980 [PubMed - indexed for MEDLINE]

3260: Eur J Neurosci. 2001 Jun;13(11):2099-104.

Colocalization of CGRP with 5-HT1B/1D receptors and substance P in trigeminal
ganglion neurons in rats.

Ma QP, Hill R, Sirinathsinghji D.

Department of Pharmacology, Merck Sharp & Dohme Research Laboratories,
Neuroscience Research Centre, Terlings Park, Harlow CM20 2QR, UK.
qingping_ma@merck.com

Vasodilatation in the dura mater has been implicated in migraine pathogenesis.
Anti-migraine triptan drugs block vasodilatation by binding to 5-HT1B/1D
receptors localized on the peripheral sensory terminals and dural blood vessel
smooth muscles. Previous studies suggest that calcitonin gene-related peptide
(CGRP) released from Adelta-fibres plays a more important role than substance P
(SP) released from C-fibres in inducing dural vasodilatation and that one of the 
antimigraine mechanisms of triptan drugs is inhibiting CGRP release. In the
present study, the relationship between CGRP and 5-HT1B/1D receptors, and between
CGRP and SP in the trigeminal ganglion neurons in rats was examined by double
immunohistochemical staining. CGRP, 5-HT1B, 5-HT1D and SP-positive trigeminal
ganglion neurons were all predominantly small and medium-sized. In the trigeminal
ganglia, approximately 50% of CGRP-positive neurons were 5-HT1B positive.
Similarly, approximately 55% of CGRP-positive neurons were 5-HT1D immunoreactive.
Approximately 50% of CGRP-positive neurons were SP-positive, while 93% of
SP-positive neurons were CGRP-positive, suggesting that nearly all SP-positive
neurons also contain CGRP. The fibre types of the 5-HT1B- and 5-HT1D-positive
neurons were further investigated with an antibody against the A-fibre marker
200-kDa neurofilaments (NF200). Approximately 46% of the 5-HT1B-positive and 43% 
of the 5-HT1D-positive trigeminal ganglion neurons were also NF200 positive,
indicating that many A-fibre trigeminal neurons express 5-HT1B or 5-HT1D
receptors. These results support the hypothesis that one important action of
antimigraine drugs is the inhibition of CGRP release and that Adelta-fibres may
play an important role in migraine pathogenesis.

PMID: 11422450 [PubMed - indexed for MEDLINE]

3261: Cephalalgia. 2001 Mar;21(2):140-4.

Treatment of migraine attacks with intranasal alniditan: an open study.

Diener HC, Louis P, Schellens R, De Beukelaar F; Study Group.

Department of Neurology, University of Essen, Hufelandstr. 55, 45122 Essen,
Germany. h.diener@uni-essen.de

In this open phase-II clinical tolerability trial 17 neurologists enrolled a
total of 112 patients and instructed them to administer a maximum of two doses of
intranasal alniditan, a 5-HT1B/D receptor agonist, for the treatment of three
consecutive migraine attacks of moderate to severe intensity. A second dose of
the trial medication was allowed within 1-24 h after the first administration. At
1 h after intranasal administration, 70/103 (68%) patients had responded to
treatment (reduction from severe or moderate headache before treatment to mild or
no headache) after their first migraine attack, 65/94 (69%) after their second
and 52/75 (71%) after their third. In 187/270 (69%) of all attacks, patients were
considered responders at 1 h. The median time to onset of effect was 30 min. The 
migraine headache recurred in 44% (attack 1), 55% (attack 2) and 44% (attack 3)
after 4-5 h. Sixty-eight per cent of the patients reported nasal irritation, 19% 
taste disturbance and 44% throat irritation. Alniditan 2 mg, administered via the
intranasal route, was effective in relieving migraine headaches in over
two-thirds of the patients at 1 h.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 11422097 [PubMed - indexed for MEDLINE]

3262: Cephalalgia. 2001 Mar;21(2):137-9.

Evidence for activation of the coagulation system in migraine with aura.

Hering-Hanit R, Friedman Z, Schlesinger I, Ellis M.

Headache Unit, Department of Neurology, Meir General Hospital, Kfar Saba, Israel.

Migraine with aura has been shown to be an independent risk factor for stroke.
Although the precise mechanism of migraine-related stroke is not known, risk
factors for hypercoagulability have been found in migraineurs. Prothrombin factor
1.2 (F1.2) is a cleavage product of prothrombin. Elevated plasma F1.2 has been
shown to be a sensitive and a specific marker of ongoing thrombin generation, and
thus may serve as an indicator of hypercoagulability. In this study we determined
plasma F1.2 levels in 35 patients with migraine (22 with aura and 13 without
aura) and in 24 healthy age- and sex-matched volunteers. Elevated F1.2 levels
were found in 11 of 22 (50%) patients with migraine with aura (1.25-3.5 nmol/l). 
None of the patients with migraine without aura nor any of the healthy volunteers
had elevated plasma F1.2 levels (normal < 1.1 nmol/l). We conclude that
prothrombin F1.2 levels are elevated in a significant number of patients with
migraine with aura but not in patients with migraine without aura. This finding
suggests that there is activation of the clotting system in certain patients with
migraine with aura.

PMID: 11422096 [PubMed - indexed for MEDLINE]

3263: Cephalalgia. 2001 Mar;21(2):129-36.

Meta-analysis of rizatriptan efficacy in randomized controlled clinical trials.

Ferrari MD, Loder E, McCarroll KA, Lines CR.

Department of Neurology, Leiden University Medical Center, Leiden, The
Netherlands.

Data from seven randomized, placebo-controlled, double-blind phase III clinical
trials were analysed to further evaluate the efficacy of rizatriptan 10 mg (n =
2068) in comparison with placebo (n = 1260) and rizatriptan 5 mg (n = 1486) for
the acute treatment of a migraine attack. Migraine was diagnosed according to
International Headache Society criteria. Headache severity, associated migraine
symptoms and functional disability were measured immediately before dosing and at
0.5, 1, 1.5 and 2 h. Headache recurrence (return of moderate or severe headache
after an initial response) was also recorded. In addition to conventional pain
relief (reduction of moderate or severe headache to mild or none) and pain free
measures, the analysis looked at the elimination of associated migraine symptoms 
and disability in patients who had symptoms or disability at baseline.
Maintenance of pain relief or pain-free status over 24 h was also analysed. At 2 
h, rizatriptan 10 mg was significantly more effective than placebo for pain
relief (71% vs. 38%, P < 0.001), and for elimination of pain, nausea,
photophobia, phonophobia and functional disability. The benefit was maintained
over 24 h; 37% of patients on rizatriptan 10 mg had sustained pain relief vs. 18%
for placebo (P < 0.001). Rizatriptan 10 mg was also more effective than
rizatriptan 5 mg, with a significant superiority at 2 h on all measures except
for elimination of nausea. The benefit was maintained over 24 h; 38% of patients 
on rizatriptan 10 mg had sustained pain relief vs. 32% for rizatriptan 5 mg (P = 
0.001).

Publication Types: 
    Meta-Analysis
    Research Support, Non-U.S. Gov't

PMID: 11422095 [PubMed - indexed for MEDLINE]

3264: Cephalalgia. 2001 Mar;21(2):120-8.

A comparative study of oral acetylsalicyclic acid and metoprolol for the
prophylactic treatment of migraine. A randomized, controlled, double-blind,
parallel group phase III study.

Diener HC, Hartung E, Chrubasik J, Evers S, Schoenen J, Eikermann A, Latta G,
Hauke W; Study Group.

Department of Neurology, University of Essen, Hufelandstr. 55, 45122 Essen,
Germany. h.diener@uni-essen.de

This study was a multinational, multicentre, double-blind, active controlled
phase III trial designed to investigate efficacy and safety of 300 mg
acetylsalicyclic acid (ASA) (n = 135) vs. 200 mg metoprolol (n = 135) in the
prophylaxis of migraine. In total 270 (51 male and 219 female) patients, aged
18-65 years, suffering between two and six migraine attacks per month were
recruited. The main objective was to show equivalence with respect to efficacy,
defined as a 50% reduction in the rate of migraine attacks. A run-in phase was
carried out with placebo for 4 weeks, followed by a 16-week drug phase. In both
treatment groups the median frequency of migraine attacks improved during the
study period, from three to two in the ASA group and from three to one in the
metoprolol group; 45.2% of all metoprolol patients were responders compared with 
29.6% with ASA. Medication-related adverse events were less frequent in the ASA
group (37) than in the metoprolol group (73). The findings from this trial show
that metoprolol is superior to ASA for migraine prophylaxis but has more
side-effects. Acetylsalicylic acid is better tolerated than metoprolol. Using a
strict responder criterion ASA showed a responder rate comparable with the
placebo rate in the literature.

Publication Types: 
    Clinical Trial
    Clinical Trial, Phase III
    Comparative Study
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 11422094 [PubMed - indexed for MEDLINE]

3265: Cephalalgia. 2001 Mar;21(2):110-9.

Alpha1-adrenoceptor subtypes mediating vasoconstriction in the carotid
circulation of anaesthetized pigs: possible avenues for antimigraine drug
development.

Willems EW, Heiligers JP, De Vries P, Kapoor K, Tom B, Villalón CM, Saxena PR.

Department of Pharmacology, Dutch Migraine Research Group and Cardiovascular
Research Institute 'COEUR', Erasmus University Medical Centre Rotterdam, 3000 DR 
Rotterdam, The Netherlands.

It has recently been shown that the alpha-adrenoceptors mediating
vasoconstriction of porcine carotid arteriovenous anastomoses resemble both
alpha1- and alpha2-adrenoceptors, but no attempt was made to identify the
specific subtypes (alpha1A, alpha1B and alpha1D) involved. Therefore, the present
study was designed to elucidate the specific subtype(s) of alpha1-adrenoceptors
involved in the above response, using the alpha1-adrenoceptor agonist
phenylephrine and alpha1-adrenoceptor antagonists 5-methylurapidil (alpha1A),
L-765 314 (alpha1B) and BMY 7378 (alpha1D). Ten-minute intracarotid infusions of 
phenylephrine (1, 3 and 10 microgkg-1.min-1) induced a dose-dependent decrease in
total carotid and arteriovenous anastomotic conductance, accompanied by a small
tachycardia. These carotid vascular effects were abolished by L-765 314 (1000
microgkg-1; i.v.), while these responses were only attenuated by 5-methylurapidil
(1000 microgkg-1; i.v.), and BMY 7378 (1000 microgkg-1; i.v.). Furthermore,
intravenous bolus injections of phenylephrine (3 and 10 microgkg-1) produced a
dose-dependent vasopressor response, which was only affected by 1000 microgkg-1
of 5-methylurapidil, while the other antagonists were ineffective. These results,
coupled to the binding affinities of the above antagonists at the different
alpha1-adrenoceptors, suggest that both alpha1A- and alpha1B-adrenoceptors
mediate constriction of carotid arteriovenous anastomoses in anaesthetized pigs. 
In view of the less ubiquitous nature of alpha1B- compared to
alpha1A-adrenoceptors, the development of potent and selective
alpha1B-adrenoceptor agonists may prove to be important for the treatment of
migraine.

Publication Types: 
    Comparative Study

PMID: 11422093 [PubMed - indexed for MEDLINE]

3266: Cephalalgia. 2001 Mar;21(2):107-9.

Referred pain after painful stimulation of the greater occipital nerve in humans:
evidence of convergence of cervical afferences on trigeminal nuclei.

Piovesan EJ, Kowacs PA, Tatsui CE, Lange MC, Ribas LC, Werneck LC.

Setor de Cefaléias, Especialidade de Neurologia, Departamento de Clínica Médica, 
Hospital de Clínicas da Universidade Federal do Paraná, Curitiba, Paraná, Brazil.
piovesan@avalon.sul.com

Cranial sensory innervation is supplied mainly by the trigeminal nerves and by
the first cervical nerves. Excitatory and inhibitory interactions among those
nerve roots may occur in a mechanism called nociceptive convergence, leading to
loss of somato-sensory spatial specificity. Three volunteers in an experimental
trial had sterile water injected over their greater occipital nerve on one side
of the neck. Pain intensity was evaluated 10, 30 and 120 s after the injection.
Two of the patients reported intense pain. Trigeminal autonomic features,
suggestive of parasympathetic activation, were seen associated with trigeminally 
distributed pain. These data add to and reinforce previous evidence of
convergence of cervical afferents on the trigeminal sensory circuit.

PMID: 11422092 [PubMed - indexed for MEDLINE]

3267: Cephalalgia. 2001 Mar;21(2):102-6.

Lanepitant, an NK-1 antagonist, in migraine prevention.

Goldstein DJ, Offen WW, Klein EG, Phebus LA, Hipskind P, Johnson KW, Ryan RE Jr.

Neuroscience Research, Lilly Research Laboratories, Department of Pharmacology
and Toxicology, Indiana University Medical School, Indianapolis, IN 46285-2033,
USA. DJGoldstein@Lilly.com

Lanepitant, a potent non-peptide neurokinin-1 receptor antagonist, inhibits
neurogenic dural inflammation, and may have a role in migraine therapy. This
study evaluated the effect of lanepitant taken daily for migraine prevention.
Patients with migraine headaches with and without aura by International Headache 
Society classification criteria were enrolled in a 12-week double-blind, parallel
design study comparing the effect of 200 mg qd lanepitant (n = 42) and placebo (n
= 42) on reduction of migraine frequency. The primary outcome measure was
response rate, i.e. the proportion of patients with a 50% reduction in days of
headache. Of the 84 patients enrolled, 90.5% were female. The endpoint response
rate for lanepitant-treated patients (41.0%) was not statistically significantly 
(P = 0.065) greater than that for placebo-treated patients (22.0%). No efficacy
variables differed significantly between treatments, except for response rates at
month 3 (P = 0.045). Higher plasma concentrations were no more effective than
lower concentrations. In this study lanepitant was not effective in preventing
migraine, but was well tolerated. These results do not support a role for NK-1
antagonism in migraine prevention.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 11422091 [PubMed - indexed for MEDLINE]

3268: Cephalalgia. 2001 Mar;21(2):96-101.

Neuropeptide localization in the "migraine generator" region of the human
brainstem.

Tajti J, Uddman R, Edvinsson L.

Department of Neurology, Albert Szent-Györgyi University Medical School, Szeged, 
Hungary.

Evidence from animals and humans suggests that brainstem nuclei such as the raphe
nuclei, the locus coeruleus (LC) and the periaqueductal grey matter (PAG), are
involved in the pathophysiology of migraine. In order to understand possible
neurotransmitters involved we have, by means of indirect immunocytochemistry,
analysed these regions for the occurrence and distribution of calcitonin
gene-related peptide (CGRP), substance P (SP), pituitary adenylate-cyclase
activating peptide (PACAP) and vasoactive intestinal polypeptide (VIP).
CGRP-immunoreactive (-ir) cell bodies, but no fibres, were found to occur in high
numbers, constituting 80% of all nerve cell bodies in the LC. A smaller number of
these nerve cell bodies (40%) in the LC proved to be PACAP-ir. The LC neurones
also stored the vesicular monoamine transporter (VMAT)- and the C-terminal
flanking peptide of neuropeptide Y (C-PON)-ir, illustrating their adrenergic
nature. Double immunostaining revealed that all VMAT-and C-PON-containing
neurones, in addition, stored CGRP. Immunoreactive cell bodies were not seen in
the nucleus raphe magnus (NRM) or PAG. Numerous SP-ir nerve fibres were observed 
in the NRM, the LC and the PAG. Few PACAP-ir nerve fibres were detected in the
PAG and few VIP-ir nerve fibres were seen in the NRM and the PAG.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 11422090 [PubMed - indexed for MEDLINE]

3269: Cephalalgia. 2001 Mar;21(2):90-5.

Intravenous metamizol (Dipyrone) in acute migraine treatment and in episodic
tension-type headache--a placebo-controlled study.

Bigal ME, Bordini CA, Speciali JG.

Department of Neurology, School of Medicine at Ribeirão Preto, São Paulo
University, Av. Bandeirantes 3900, 14049-900 Ribeirão Preto, SP, Brazil.

Acute headache is a very frequent symptom, responsible for significant demand at 
primary care units and emergency rooms. In such sets in Brazil, metamizol is
easily found but, on the other hand, neither ergotics nor triptans are available.
The aim of this study is to compare intravenous metamizol with placebo in the
acute treatment of migraine with aura, migraine without aura and episodic
tension-type headache. Fifty-four migraine with aura patients, 95 migraine
without aura patients and 30 tension-type headache patients were treated with
metamizol. Ninety patients (30 migraine with aura, 30 migraine without aura and
30 tension-type headache patients) received placebo. Pain intensity, nausea,
aura, photo- and phonophobia were investigated at 30 min and 60 min after the
administration of the drug. Significant improvement of pain after 30 min and 60
min post-dosage was achieved from metamizol groups compared with placebo groups. 
Significant improvement of all other symptoms was achieved after 60 min
post-dosage. Side-effects were mild and with small incidence. Metamizol is an
effective, safe and low price drug. It may be regarded as a good alternative drug
for the treatment of common acute primary headaches.

Publication Types: 
    Clinical Trial
    Comparative Study
    Randomized Controlled Trial

PMID: 11422089 [PubMed - indexed for MEDLINE]

3270: Cephalalgia. 2001 Mar;21(2):84-9.

Comment in:
    Cephalalgia. 2001 Mar;21(2):81.

Ophthalmoplegic migraine: a recurrent demyelinating neuropathy?

Lance JW, Zagami AS.

Institute of Neurological Sciences, Prince of Wales Hospital and the Faculty of
Medicine, University of New South Wales, Sydney, Australia. jimlance@bigpond.com

The demonstration by magnetic resonance imaging (MRI) scanning of thickening and 
enhancement of the cisternal part of the oculomotor nerve in patients diagnosed
as "ophthalmoplegic migraine" prompts reconsideration of this uncommon disorder. 
The case histories of five patients, three male and two female, varying in age
from 6 to 30 years, are presented here. Recurrent painful ophthalmoplegia started
in infancy in two cases, childhood in two instances and adult life in one. One
child had his first attacks at 3, 5 and 12 months of age, on each occasion 10
days after an injection of triple vaccine. The possibility of this condition
being a recurrent demyelinating neuropathy is considered and its possible
relationship to migraine explored.

Publication Types: 
    Case Reports

PMID: 11422088 [PubMed - indexed for MEDLINE]

3271: Altern Med Rev. 2001 Jun;6(3):303-10.

An extract of Petasites hybridus is effective in the prophylaxis of migraine.

Grossman W, Schmidramsl H.

Department of Neurology, Municipal Hospital, Munchen-Harlaching, Germany.

OBJECTIVE: Migraine is still an unsolved problem. This clinical trial
investigates the efficacy and tolerance of Petasites hybridus in the prophylaxis 
of migraine. METHODS: A randomized, group-parallel, placebo-controlled,
double-blind clinical study was carried out with a special CO2 extract from the
rhizome of Petasites hybridus. Following a four-week run-in phase, 60 patients
received either the special Petasites hybridus extract Petadolex or placebo at a 
dosage of two capsules (each capsule contains 25 mg) twice daily over 12 weeks.
Outcome variables included the frequency, intensity and duration of migraine
attacks as well as any accompanying symptoms. RESULTS: The frequency of migraine 
attacks decreased by a maximum of 60 percent compared to the baseline. This
reduction in migraine attacks with Petadolex was significant (p < 0.05) compared 
to placebo. No adverse events were reported. Petasites was exceptionally well
tolerated. CONCLUSIONS: The results suggest that migraine patients can benefit
from prophylactic treatment with this special extract. The combination of high
efficacy and excellent tolerance emphasizes the particular value that Petasites
hybridus has for the prophylactic treatment of migraine.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial

PMID: 11410074 [PubMed - indexed for MEDLINE]

3272: Psychiatr Genet. 2001 Mar;11(1):49-52.

The -141C Ins/Del polymorphism of the dopamine D2 receptor gene is not associated
with either migraine or Parkinson's disease.

Maude S, Curtin J, Breen G, Collier D, Russell G, Shaw D, Clair DS.

Department of Mental Health, Medical School, University of Aberdeen, UK.

Abnormalities in dopamine neurotransmission at the dopamine D2 receptor (DRD2)
have been implicated in both migraine and Parkinson's disease. Positive
associations have also been found between polymorphisms within the DRD2 gene and 
both of these conditions. The -141C Ins/Del polymorphism in the DRD2 receptor
gene is a putative functional polymorphism. The purpose of this study was to
determine whether it and any genes in linkage disequilibrium with this marker are
involved in either of these conditions. We have compared the genotype and allele 
frequencies of the -141C Ins/Del polymorphism in 200 migraineurs and 260
Parkinson's disease cases with 464 controls. We have found no association between
the receptor gene and either condition (P = 0.89 and P = 0.56 respectively). Our 
findings do not support the hypothesis that this polymorphism is involved in the 
aetiology of migraine or Parkinson's disease.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 11409701 [PubMed - indexed for MEDLINE]

3273: Ann Neurol. 2001 Jun;49(6):753-60.

Delayed cerebral edema and fatal coma after minor head trauma: role of the
CACNA1A calcium channel subunit gene and relationship with familial hemiplegic
migraine.

Kors EE, Terwindt GM, Vermeulen FL, Fitzsimons RB, Jardine PE, Heywood P, Love S,
van den Maagdenberg AM, Haan J, Frants RR, Ferrari MD.

Department of Neurology, Leiden University Medical Centre, The Netherlands.

Trivial head trauma may be complicated by severe, sometimes even fatal, cerebral 
edema and coma occurring after a lucid interval ("delayed cerebral edema").
Attacks of familial hemiplegic migraine (FHM) can be triggered by minor head
trauma and are sometimes accompanied by coma. Mutations in the CACNA1A calcium
channel subunit gene on chromosome 19 are associated with a wide spectrum of
mutation-specific episodic and chronic neurological disorders, including FHM with
or without coma. We investigated the role of the CACNA1A gene in three subjects
with delayed cerebral edema. Two subjects originated from a family with extreme
FHM, and one subject was the previously asymptomatic daughter of a sporadic
patient with hemiplegic migraine attacks. In all three subjects with delayed
severe edema, we found a C-to-T substitution resulting in the substitution of
serine for lysine at codon 218 (S218L) in the CACNA1A gene. The mutation was
absent in nonaffected family members and 152 control individuals. Haplotype
analysis excluded a common founder for both families. Neuropathological
examination in one subject showed Purkinje cell loss with relative preservation
of granule cells and sparing of the dentate and inferior olivary nuclei. We
conclude that the novel S218L mutation in the CACNA1A calcium channel subunit
gene is involved in FHM and delayed fatal cerebral edema and coma after minor
head trauma. This finding may have important implications for the understanding
and treatment of this dramatic syndrome.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 11409427 [PubMed - indexed for MEDLINE]

3274: J Neurol Sci. 2001 May 1;186(1-2):27-30.

Significance of serotonin transporter gene polymorphism in migraine.

Yilmaz M, Erdal ME, Herken H, Cataloluk O, Barlas O, Bayazit YA.

Department of Neurology, Faculty of Medicine, Gaziantep University, Kolejtepe,
Gaziantep, Turkey

OBJECTIVE: To elucidate significance of the serotonin transporter gene (STG)
polymorphism in migraine, and to address the polymorphic patterns of STG, both in
the migraineurs and healthy people in this country. STUDY DESIGN: A PCR study of 
STG in 52 migraineurs and 80 healthy controls. METHODS: Using the PCR technique, 
STG polymorphism was studied in the DNA obtained from leukocytes of the patients 
and healthy controls. Polymorphism of the two regions (VNTR and 5-HTTLPR) of STG 
was assessed. RESULTS: VNTR STin 2.10 and STin 2.12 alleles were detected in
migraineurs and healthy controls. Both homozygous and heterozygous STin 2.10
allele predominated in the migraine group (p=0.01), while STin 2.12 allele was
more frequent in the healthy controls (p=0.02). There was no relationship between
the migraine type, family history of migraine and STG polymorphism. CONCLUSION:
STin 2.10 and STin 2.12 alleles of VNTR are frequent in this country. While the
presence of STin 2.10 allele increases the risk of migraine, 5-HTTLPR
polymorphism is not associated with this risk.

PMID: 11412868 [PubMed - indexed for MEDLINE]

3275: Arch Neurol. 2001 Jun;58(6):944-50.

Oral almotriptan vs. oral sumatriptan in the abortive treatment of migraine: a
double-blind, randomized, parallel-group, optimum-dose comparison.

Spierings EL, Gomez-Mancilla B, Grosz DE, Rowland CR, Whaley FS, Jirgens KJ.

25 Walnut St, Suite 102, Wellesley Hills, MA 02481-2106, USA.
Spierings@MediaOne.net

BACKGROUND: Almotriptan malate is a novel, selective serotonin(1B/D) agonist, or 
triptan, developed for the abortive treatment of migraine. In double-blind,
placebo-controlled studies, it has been shown to be effective, well tolerated,
and safe. OBJECTIVE: To compare the efficacy, tolerability, and safety of
almotriptan with that of the "standard triptan," sumatriptan succinate. The power
calculation of the study was based on 24-hour headache recurrence, an efficacy
measure in the abortive treatment of migraine, and on the occurrence of adverse
events. SUBJECTS AND METHODS: Subjects, aged between18 and 65 years, with
migraine with or without aura but otherwise healthy, were randomized to take
orally either almotriptan malate, 12.5 mg, or sumatriptan succinate, 50 mg. The
medications were provided in identical-looking capsules to ensure blinding and
were taken for the treatment of moderate or severe headache. Efficacy was
determined in terms of (1) headache relief-a decrease in pain intensity to mild
or no pain; (2) headache freedom-a decrease to no pain; (3) use of rescue
medications, allowed after 2 hours; and (4) headache recurrence-moderate or
severe pain returning within 24 hours after headache relief at 2 hours. Adverse
events were collected for 96 hours after treatment and for safety evaluation,
vital signs, blood tests, and electrocardiograms were performed at the screening 
and exit visits. RESULTS: Seventy-five investigators enrolled 1255 subjects of
whom 1173 were treated (591 with almotriptan and 582 with sumatriptan). At 2
hours, almotriptan treatment provided headache relief in 58.0% of the subjects
and sumatriptan treatment in 57.3%; headache freedom was provided by the
medications in 17.9% and 24.6%, respectively (P =.005). Rescue medications were
taken by 36.7% of the subjects in the almotriptan-treated group and by 33.2% in
the sumatriptan-treated group; headaches returned to moderate or severe intensity
in 27.4% and 24.0%, respectively. Treatment-emergent adverse events occurred in
15.2% of the subjects in the almotriptan-treated group and in 19.4% in the
sumatriptan-treated group (P =.06); treatment-related adverse events occurred in 
9.1% and 15.5% of the subjects, respectively (P =.001), including chest pain,
which occurred in 0.3% and 2.2%, respectively (P =.004). CONCLUSIONS: Almotriptan
and sumatriptan are similarly effective in the abortive treatment of moderate or 
severe migraine headache; they are also similarly well tolerated and safe.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial

PMID: 11405809 [PubMed - indexed for MEDLINE]

3276: Neurosci Lett. 2001 Jun 22;306(1-2):132-4.

Reduced gating of middle-latency auditory evoked potentials (P50) in migraine
patients: another indication of abnormal sensory processing?

Ambrosini A, De Pasqua V, Afra J, Sandor PS, Schoenen J.

Headache Clinics - IRCCS Neuromed via Atinense, 18, I-86077 , Pozzilli (Isernia),
Italy.

Habituation of cortical evoked responses to repetitive stimuli is reduced in
migraine between attacks. To explore another aspect of information processing, we
measured auditory sensory gating. The amplitude of the P50 response to the second
of two homologous stimuli was significantly less reduced in migraineurs than in
healthy volunteers. This lack of auditory sensory gating may be due to a
hypofunction of monoaminergic subcortico-cortical pathways, which is also
supposed to cause the interictal deficit of cortical habituation to repetitive
stimuli.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 11403975 [PubMed - indexed for MEDLINE]

3277: J Endocrinol Invest. 2001 May;24(5):310-4.

Neuroendocrine effects of subcutaneous sumatriptan in patients with migraine.

Rainero I, Valfrè W, Savi L, Gentile S, Pinessi L, Gianotti L, Arvat E, Ghigo E, 
Del Rizzo P, Calvelli P, Limone P.

Neurology III, Headache Center, Department of Neuroscience, University of Turin, 
Italy. irainero@molinette.piemonte.it

We evaluated the sensitivity of 5-HT1D receptors in patients with migraine using 
sumatriptan as a pharmacological probe. The drug inhibits the release of ACTH,
cortisol and prolactin and this effect may be used to explore the function of
serotoninergic systems in vivo. We administered sumatriptan (6 mg sc) and placebo
to 15 migraineurs, during the headache-free period, and to 10 healthy controls.
Blood samples were collected -15, 0, 15, 30, 45, 60 and 90 min after injections. 
Sumatriptan induced a significant (p<0.01) decrease of ACTH, cortisol and
prolactin concentrations both in patients with migraine and in controls. The
neuroendocrine response was not significantly different in the two groups. Our
results suggest that 5-HT1D receptor sensitivity is not altered in migraine.

Publication Types: 
    Clinical Trial
    Controlled Clinical Trial
    Research Support, Non-U.S. Gov't

PMID: 11407649 [PubMed - indexed for MEDLINE]

3278: J R Soc Med. 2001 Jun;94(6):286-7.

A diagnostic sign in migraine?

de Silva RN.

Department of Neurology, Essex Centre for Neurology & Neurosurgery, Oldchurch
Hospital, Romford RM7 0BE, UK.

At the bedside it was noted that, after ocular fundoscopy, patients with migraine
complained more often of an after-image than did non-migraineurs. This phenomenon
was then investigated in consecutive patients attending a general neurology
outpatient clinic. The relative risk for the diagnosis of migraine in patients
reporting an after-image was 2.91 (95% confidence interval 1.96 to 4.34), and the
sensitivity, specificity and positive predictive value of this observation for
the diagnosis of migraine were 0.63, 0.75 and 0.55 respectively. After-images
were equally likely to be reported by migraineurs with and without aura, and by
patients with migraine equivalents. The after-image phenomenon probably reflects 
the heightened sensitivity to visual stimuli of patients with migraine. Although 
a diagnosis of migraine is primarily established by the patient's history, the
presence of an after-image following ocular fundoscopy may support this
diagnosis.

Publication Types: 
    Evaluation Studies

PMID: 11387418 [PubMed - indexed for MEDLINE]

3279: Eur Neurol. 2001;45(4):275-83.

Comparison of preference for rizatriptan 10-mg wafer versus sumatriptan 50-mg
tablet in migraine.

Pascual J, Bussone G, Hernandez JF, Allen C, Vrijens F, Patel K;
Rizatriptan-Sumatriptan Preference Study Group.

Hospital Marqués de Valdecilla, Santander, Spain.

Rizatriptan (MAXALT, a registered trademark of Merck & Co. Inc.) is a selective
5-HT(1B/1D) receptor agonist with rapid oral absorption and early onset of action
in the acute treatment of migraine. This randomized, open-label, crossover
outpatient study assessed the preference of 481 patients for rizatriptan 10-mg
rapidly disintegrating tablets versus sumatriptan (IMIGRAN, a registered
trademark of GlaxoWellcome PLC) 50-mg tablets in the treatment of a single
migraine attack with each therapy. Almost twice as many patients preferred
rizatriptan 10-mg rapidly disintegrating tablet to sumatriptan 50-mg tablet (64.3
vs. 35.7%, p < or = 0.001). Faster relief of headache pain was the most important
reason for the preference, cited by 46.9% of patients preferring rizatriptan and 
43.4% of patients who preferred sumatriptan. Headache relief at 2 h was 75.9%
with rizatriptan and 66.6% with sumatriptan (p < or = 0.001), with rizatriptan
being superior to sumatriptan within 30 min of dosing. Fifty-five percent of
patients were pain free 2 h after rizatriptan, compared with 42.1% treated with
sumatriptan (p < or = 0.001), rizatriptan being superior within 1 h of treatment.
Forty-one percent of patients taking rizatriptan were pain free at 2 h and had no
recurrence or need for additional medication, compared to 32.3% of patients on
sumatriptan. Rizatriptan was also superior to sumatriptan in terms of the
proportions of patients with no nausea, phonophobia or photophobia, and patients 
with normal function 2 h after treatment intake (p < 0.05). More patients were
(completely, very or somewhat) satisfied 2 h after treatment with rizatriptan
(73.3%) than 2 h after treatment with sumatriptan (59.0%) (p < or = 0.001).
Additionally, 2 h after the dose, more patients found rizatriptan to be very
convenient, convenient or somewhat convenient (87.2%) than they did sumatriptan
(76.3%) (p < or = 0.001). Both active treatments were well tolerated. The most
common side effects with rizatriptan and sumatriptan were nausea (6.6 and 6.9% of
patients, respectively), dizziness (6.1 and 5.8%) and somnolence (7.4 and 6.7%). 
Copyright 2001 S. Karger AG, Basel

Publication Types: 
    Clinical Trial
    Comparative Study
    Multicenter Study
    Randomized Controlled Trial

PMID: 11385269 [PubMed - indexed for MEDLINE]

3280: Eur Neurol. 2001;45(4):206-13.

Tolerability and efficacy of almotriptan in the long-term treatment of migraine.

Pascual J, Falk R, Docekal R, Prusinski A, Jelencsik J, Cabarrocas X, Segarra X, 
Luria X, Ferrer P.

Servicio de Neurología, University Hospital, Santander, Spain.
pascualj@medi.unican.es

BACKGROUND: Almotriptan is a highly specific 5-HT(1B/1D) receptor agonist, which 
acts selectively on blood vessels of the brain. Short-term studies have
demonstrated that almotriptan provides rapid, effective and reliable relief of
migraine attacks, while offering excellent tolerability. Purpose: To assess the
long-term tolerability and efficacy of oral almotriptan 12.5 mg administered for 
every migraine attack over a 1-year period. METHODS: A total of 762 patients
treated 13,751 attacks (1-97 per patient); 61.5% of attacks were treated with one
12.5-mg dose, while for 38.5% of attacks, patients took a second dose within 24
h. RESULTS: Three hundred and ninety-one patients (51.3%) experienced a total of 
1,617 adverse events (AEs). The majority (88.6%) of AEs were of mild-to-moderate 
intensity, and only 28.8% of AEs were considered to be related to the study drug.
Only 2 patients experienced serious AEs possibly related to almotriptan, syncope 
and chest pain; both recovered without any sequelae. Patients reported at least 1
AE in 11% of attacks treated. The incidence of AEs decreased during the study.
Only 6 (0.8%) study withdrawals were due to AEs considered to be related to
almotriptan. Tolerability was not compromised in patients taking 2 doses of
almotriptan or in those using migraine prophylactics. Patient age or sex did not 
influence the incidence of AEs. There was no evidence of tachyphylaxis in those
patients completing the study. Pain relief at 2 h after the initial dose was
achieved in 84.2% of moderate/severe attacks. Patients were pain free at 2 h
after dose in 58.2% of all attacks. Older patients (> 40 years) tended to respond
better than younger ones (< 40 years). Efficacy was not modified by use of
migraine prophylactics or hormonal contraceptives. Efficacy measurements were
consistent on treating repeated moderate/severe migraine attacks. CONCLUSION:
This large, open study indicates that the new, specific 5-HT(1B/1D) agonist
almotriptan, at a dose of 12.5 mg, is a well tolerated and effective treatment
for migraine pain when used over a period of up to 1 year. Copyright 2001 S.
Karger AG, Basel

Publication Types: 
    Clinical Trial
    Clinical Trial, Phase III
    Multicenter Study

PMID: 11385257 [PubMed - indexed for MEDLINE]

3281: Headache. 2001 May;41(5):503-8.

Indirect costs of migraine in a public Brazilian hospital.

Bigal ME, Moraes FA, Fernandes LC, Bordini CA, Speciali JG.

Department of Neurology, University of São Paulo, School of Medicine at Ribeirão 
Preto, Brazil.

OBJECTIVES: To evaluate the indirect costs of migraine affecting employees of a
public Brazilian hospital. BACKGROUND: Migraine is a common primary headache
which has a negative influence on the well-being and quality of life, as well as 
the professional life, of affected individuals. METHODS: Our series consisted of 
846 employees with migraine. The Lost Hours Equivalence Index, which considers
both the hours lost due to the absence from work and reduction in productivity,
was used to estimate the number of working hours lost due to migraine. RESULTS:
Of the employees with migraine studied, 91% presented a mean 56.9% loss of
productivity. The mean number of total lost working hours per month due to
migraine was 6.5. The estimated total indirect cost of migraine was R $986 903.77
(US $815 622.54), implicating costs of R $241.30 (US $199.42) per employee per
year. CONCLUSIONS: Based on its impact on life and the resulting costs, migraine 
should be considered a public health problem and thus measures should be adopted 
to reduce its impact on the individual and on society.

PMID: 11380649 [PubMed - indexed for MEDLINE]

3282: Headache. 2001 May;41(5):475-81.

Blood nitrite levels in patients with migraine during headache-free period.

Shukla R, Barthwal MK, Srivastava N, Nag D, Seth PK, Srimal RC, Dikshit M.

Department of Neurology, King George's Medical College, Lucknow, India.

OBJECTIVE: To investigate blood nitrite levels after migraine attacks and to
assess whether or not the change in nitric oxide levels observed during acute
migraine persist after the attacks. BACKGROUND: Involvement of nitric oxide has
been suggested in the initiation of acute migraine. Recent studies have shown
alteration in the platelet response and platelet nitrite levels during migraine
attacks. METHODS: Patients with migraine with aura and patients without aura were
included in the study. The study was conducted on 50 patients with migraine and
90 healthy controls. Blood from the patients was collected at least 7 +/- 0.8
days after the last attack of migraine. Nitrite levels in the polymorphonuclear
leukocytes, platelets, and plasma were estimated. Platelet aggregation response
in some of these patients was also studied. RESULTS: No significant change in the
polymorphonuclear leukocyte, platelet, and plasma nitrite levels in patients with
migraine compared to controls was observed. Patients with migraine with aura had 
significantly lower polymorphonuclear leukocyte nitrite levels compared to those 
without aura (P<.05). In addition, no significant difference in the adenosine
diphosphate-induced platelet aggregation was observed in the migraineurs compared
to the healthy controls. CONCLUSIONS: Results obtained indicate that the platelet
aggregation response and the blood nitrite levels were not altered significantly 
after an attack in the patients with migraine.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 11380645 [PubMed - indexed for MEDLINE]

3283: Headache. 2001 May;41(5):456-64.

Treatment of migraine in Canada with naratriptan: a cost-effectiveness analysis.

Caro JJ, Getsios D, Raggio G, Caro G, Black L.

Caro Research, Boston, Mass; Caro Research, Montreal, Quebec, Canada.

OBJECTIVE: To evaluate the cost-effectiveness of naratriptan for the treatment of
migraine in Canada. BACKGROUND: The substantial disability brought on by
migraine, coupled with the high prevalence of this disorder, leads to substantial
costs. Naratriptan is a newly developed triptan shown to be effective in the
treatment of migraine. METHODS: Monte Carlo modeling techniques were used to
simulate the experience of Canadian migraineurs over the course of 1 year. Data
from a multinational study comparing oral naratriptan 2.5 mg to customary
therapies were used in the cost-effectiveness analysis. RESULTS: Naratriptan
leads to an annual reduction in symptom duration of 225 hours compared to
customary therapy not including other triptans. Reductions in lost productivity
yield savings of Can $390 (1998 Canadian dollars) relative to customary therapy, 
which exceed the increase in drug costs resulting in overall savings of Can $109 
per year. CONCLUSIONS: The use of naratriptan in the treatment of migraine is an 
economically attractive option, leading to savings in overall costs. Increases in
drug costs seem acceptable in light of reductions in symptom duration.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 11380643 [PubMed - indexed for MEDLINE]

3284: Headache. 2001 May;41(5):449-55.

Oral almotriptan in the treatment of migraine: safety and tolerability.

Dodick DW.

Department of Neurology, Mayo Clinic Scottsdale, Ariz.

OBJECTIVE: To summarize safety and tolerability data on orally administered
almotriptan from premarketing clinical trials. BACKGROUND: Almotriptan is a new
5-HT1B/1D receptor agonist similar to sumatriptan in mode of action and
therapeutic efficacy. In addition, the safety and tolerability profile of
almotriptan has been demonstrated in a number of controlled clinical trials.
Sumatriptan is generally safe and well tolerated; however, in controlled clinical
trials, it has been associated with chest symptoms (pressure, warmth, and other
unpleasant sensations) with an incidence of 3% to 5%. DESIGN: Three phase 1
dose-finding and pharmacokinetic studies in healthy men and women volunteers were
reviewed to assess the safety and tolerability of oral almotriptan at single
doses ranging from 2 to 200 mg. The objective of one study was to evaluate
cardiovascular safety. Two phase 2 trials assessed the safety and tolerability of
single doses of 2 to 150 mg in migraine (n=911). Two phase 3 trials assessed the 
safety and tolerability of a single 12.5-mg oral dose after three attacks (n=910)
and repeated doses of 12.5 mg for multiple attacks over the long term (n=747).
All studies were conducted in Europe. Data from the United States is currently
being analyzed and will be published at a later date. RESULTS: In phase 2 and 3
trials comprising more than 2500 patients with migraine and 15 000 attacks,
adverse events were infrequent and mild. The most common events-dizziness, nausea
and vomiting, headache, fatigue, paresthesia, and drowsiness-were reported in
fewer than 3% of patients. At the recommended therapeutic dose of 12.5 mg, the
adverse events profile was not statistically different from placebo. The
incidence of chest symptoms was 0.2% in the phase 3 trials. The long-term safety 
and tolerability profile after treatment of more than 10 000 attacks was similar 
to that following the single-dose studies. In all clinical trials, almotriptan
demonstrated a very favorable adverse event profile, particularly with respect to
nonischemic-related chest symptoms. CONCLUSIONS: Almotriptan was safe and well
tolerated in nearly all adult patients with migraine, with and without aura,
enrolled in these studies. The incidence of chest symptoms in preclinical studies
was substantially lower than that reported for sumatriptan in premarketing
studies, indicating that almotriptan may be better tolerated than sumatriptan at 
clinically anticipated doses. However, any potential difference in cardiovascular
safety between almotriptan and sumatriptan cannot be determined or inferred from 
this data. Cardiovascular risk profiles for all drugs within this class
(triptans) should be considered similar. Only extensive postmarketing data, not
currently available, can potentially change this recommendation.

Publication Types: 
    Meta-Analysis
    Research Support, Non-U.S. Gov't

PMID: 11380642 [PubMed - indexed for MEDLINE]

3285: Acta Neurol Belg. 2001 Mar;101(1):42-6.

New generation anti-epileptics for facial pain and headache.

Delvaux V, Schoenen J.

University Department of Neurology, University of Liège, Liège, Belgium.

The prophylactic management of recurrent head and facial pains may be challenging
because of lack of efficacy and/or bothersome adverse effects of available drug
therapies. New generation antiepileptic drugs offer new perspectives in difficult
cases. We will review the available published data and present our experience
with lamotrigine in various head and facial pains such as migraine, cluster
headache, neuropathic trigeminal pain, atypical facial pain, and chronic
tension-type headache. Twenty-five patients were enrolled and followed for 18
months. The dose was gradually increased in steps of 25 mg up to the effective
dose (mean 250 mg/d). Lamotrigine was most effective in trigeminal neuralgia and 
dysesthesia, but was of little utility in the other head or facial pains.

Publication Types: 
    Clinical Trial
    Review

PMID: 11379275 [PubMed - indexed for MEDLINE]

3286: Neurology. 2001 May 22;56(10):1273-7.

Association between migraine and endothelin type A receptor (ETA -231 A/G) gene
polymorphism.

Tzourio C, El Amrani M, Poirier O, Nicaud V, Bousser MG, Alpérovitch A.

INSERM U 360, Salpêtrière Hospital, Paris, France. tzourio@chups.jussieu.fr

BACKGROUND: Previous studies have described an association between migraine and
endothelin, a potent vasoconstrictor. OBJECTIVE: To test the association between 
migraine and gene polymorphisms of the endothelin system. METHODS: A
population-based study of elderly individuals (n = 1,188) in Nantes (western
France) was conducted. Lifetime migraine was defined according to the
International Headache Society criteria, after an interview with a headache
specialist. Five polymorphisms in genes encoding endothelin 1, endothelin type A 
(ET(A)), and type B receptors were determined in more than 90% of the sample.
RESULTS Migraine was diagnosed in 140 participants (11.9%). The ETA (-231 A/G)
polymorphism was the only polymorphism significantly associated with migraine.
There was a trend of decreasing prevalence of migraine with number of copies of
the G allele (AA genotype: 15.7% of participants with migraine, AG: 9.7%, GG:
2.9%; p < 0.001). Carrying the G allele was associated with a sex- and
age-adjusted odds ratio of 0.50 (95% CI, 0.34 to 0.74). The association was
observed in both sexes and was stronger in participants with a family history of 
severe headaches than in those without. CONCLUSIONS: A variant of the ET(A)
receptor gene modulates the risk for migraine. These results offer new insights
into the pathophysiology of the vascular component of migraine.

PMID: 11376172 [PubMed - indexed for MEDLINE]

3287: Curr Opin Neurol. 2001 Jun;14(3):341-5.

Pharmacological opportunities and pitfalls in the therapy of migraine.

May A, Goadsby PJ.

Department of Neurology, University of Regensburg, Regensburg, Germany.
arne.may@klinik.uni-regensberg.de

The mild vasoconstrictor effects of modern antimigraine drugs, such as serotonin 
(5-HT; 5-hydroxytryptamine)1B/D agonists, have led to a search for
nonvasoconstrictor approaches to therapy. Such approaches have included substance
P (neurokinin I) antagonists, endothelin antagonists and highly specific 5HT1D
agonists. All of these substances are effective in animal models and have no
significant vasoconstrictive effects. However, all of them failed to demonstrate 
any antimigraine effects. Current clinical and experimental evidence therefore
supports the view that isolated peripheral trigeminal nerve inhibition is
insufficient to relieve acute migraine.

Publication Types: 
    Review

PMID: 11371757 [PubMed - indexed for MEDLINE]

3288: Curr Opin Neurol. 2001 Jun;14(3):323-33.

Headache and female hormones: what you need to know.

Silberstein SD.

Thomas Jefferson University Hospital, Jefferson Headache Center, Philadelphia, PA
19107, USA. stephen.silberstein@mail.tju.edu

The normal female lifecycle is associated with hormonal milestones, including
menarche, pregnancy, contraceptive use, menopause, and the use of replacement sex
hormones. Attacks of migraine without aura, but not with aura, are more likely to
occur 2 days before onset and on the first 2 days of menses, but they are not
more severe than those that occur outside the perimenstrual period. Oral
sumatriptan and naratriptan are effective as short-term perimenstrual
prophylaxis. Postdural headache can occur during the postpartum period. The
International Headache Society Task Force assessed the efficacy of treatment of
women who had migraine with combined oral contraceptives and hormone replacement 
therapy, as well as the risk of ischemic stroke associated with their use. There 
is no contraindication to the use of oral contraceptives in women with migraine
in the absence of migraine aura or other risk factors. There is a potentially
increased risk of ischemic stroke in women with migraine who are using combined
oral contraceptives and have additional risk factors that cannot easily be
controlled, including migraine with aura. There is no compelling evidence that
postmenopausal hormone replacement therapy either decreases or increases stroke
risk.

Publication Types: 
    Review

PMID: 11371755 [PubMed - indexed for MEDLINE]

3289: Curr Opin Neurol. 2001 Jun;14(3):315-21.

Nitric oxide in primary headaches.

Thomsen LL, Olesen J.

Department of Neurology, The Lundbeck Institute, Skodsborg, Denmark.
llt@lundbeck.com

The molecular mechanisms that underlie the primary headaches-migraine, cluster
headache and tension-type headache-have not yet been clarified. On the basis of
studies in headache induced by intravenous infusions of glyceryl trinitrate (an
exogenous nitric oxide donor) and histamine (which liberates nitric oxide from
vascular endothelium), it has been suggested that nitric oxide is a likely
candidate responsible molecule. The present review deals with the biology of this
small messenger molecule, and the updated scientific evidence that suggests a key
role for this molecule in primary headaches. This evidence suggests that the
release of nitric oxide from blood vessels, perivascular nerve endings or from
brain tissue is an important molecular trigger mechanism in spontaneous headache 
pain. Pilot trials have shown efficacy of a nitric oxide synthase inhibitor in
both migraine attacks and chronic tension-type headache. These observations
suggest new approaches to the pharmacological treatment of headache.

Publication Types: 
    Review

PMID: 11371754 [PubMed - indexed for MEDLINE]

3290: Pediatrics. 2001 Apr;107(4):E62.

Tolerability and effectiveness of prochlorperazine for intractable migraine in
children.

Kabbouche MA, Vockell AL, LeCates SL, Powers SW, Hershey AD.

Division of Neurology, Cincinnati Children's Hospital Medical Center, Cincinnati,
Ohio 45229-3039, USA.

OBJECTIVE: To study the effectiveness of prochlorperazine in aborting severe,
intractable migraines in children. STUDY DESIGN: Patients for this study were
drawn from the population seen and evaluated in the Headache Center at Cincinnati
Children's Hospital Medical Center. All patients were diagnosed with migraine
headache by both clinical and International Headache Society criteria. The
effectiveness of intravenous prochlorperazine in 20 consecutive patients referred
to the emergency department for severe, prolonged migraines was retrospectively
reviewed. RESULTS: Patients evaluated in this study presented with a mean
headache severity of 8.4 on a 0- to 10-point scale and an average duration of 54 
hours. At 1 hour, 90% of the patients reported feeling better with 50% becoming
pain-free. A 50% or greater reduction in severity occurred in 75% of patients at 
1 hour and in 95% at 3 hours. At 3 hours, 95% of the patients reported feeling
better, and 60% were pain-free. Only 1 patient failed to respond to
prochlorperazine. CONCLUSION: Prochlorperzaine was shown to be highly effective
in aborting intractable migraines in children. It was well tolerated with no
significant side effects. Additional large, double-blinded, randomized,
placebo-controlled studies are needed to further investigate its effectiveness.

Publication Types: 
    Clinical Trial

PMID: 11335783 [PubMed - indexed for MEDLINE]

3291: Med Hypotheses. 2001 Mar;56(3):360-3.

New neural theory of migraine.

Eggers AE.

Department of Neurology, SUNY-Health Science Center at Brooklyn, NY 11203, USA.

Insufficient attention has been given to reports in the literature describing
patients with symptomatic migraine who, in addition to, or instead of, the
well-recognized zones of hypofusion, have zones of hyperperfusion, which can be
interpreted as hypermetabolism due to neuronal activation. A new neural theory of
migraine is proposed in which it is hypothesized that migraine is an electrical
disease of the brain in which abnormally-functioning serotonergic pacemaker cells
in the raphe nuclei inappropriately activate and inhibit wide areas of the brain.
Excessive neuronal activation could cause migraine stroke by excitotoxicity and
could explain the association of migraine with epilepsy. The serotonergic nuclei 
are positioned to mediate stress-induced migraine. Copyright 2001 Harcourt
Publishers Ltd.

PMID: 11359360 [PubMed - indexed for MEDLINE]

3292: Ann Neurol. 2001 May;49(5):668-72.

Subclinical cerebellar impairment in the common types of migraine: a
three-dimensional analysis of reaching movements.

Sándor PS, Mascia A, Seidel L, de Pasqua V, Schoenen J.

Neurology Department, University Hospitals of Zurich, Switzerland.

Mutations in the CACNA1A gene can cause familial hemiplegic migraine (FHM) and/or
cerebellar ataxia CACNA1A codes for the alpha1 subunit of P/Q-Ca2+ channels and
is highly expressed in the cerebellum. Using a pointing paradigm and infrared
optoelectronic tracking system, we found subclinical hypermetria and other subtle
cerebellar signs in the common forms of migraine. These were more pronounced in
migraine with than without aura. Whether this reflects involvement of Ca2+
channel genes in the common types of migraine needs to be investigated by genetic
analyses.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 11357959 [PubMed - indexed for MEDLINE]

3293: J Neurol. 2001 Apr;248 Suppl 1:34-8.

Evidence-based medicine: botulinum toxin A in migraine and tension-type headache.

Göbel H, Heinze A, Heinze-Kuhn K, Jost WH.

Kiel Pain Clinic, Heikendorfer Weg 9-27 D-24149 Kiel, Germany.

The therapeutic effect of botulinum toxin in headache was observed
coincidentally. The rationale for this new indication initially met with a great 
deal of scepticism, because the toxin's mechanism of action, cholinergic
chemodenervation, does not fit the pathophysiological concept of migraine and
other forms of headache. Meanwhile a fair number of studies have been published
which indicate efficacy for botulinum toxin and recommend its use for the
treatment of tension headache and migraine. According to the evidence-based
medicine criteria, grade I evidence has been demonstrated. In addition the use of
botulinum toxin for cluster-headache and secondary headache is discussed. Further
large scale studies will be regarded to demonstrate the long-term efficacy.

Publication Types: 
    Review

PMID: 11357239 [PubMed - indexed for MEDLINE]

3294: Nurse Pract. 2001 Apr;26(4 Suppl):1-11; quiz 12-3.

Managing migraine: strategies for successful patient outcomes.

Moriarty-Sheehan M, Jamieson DG, Russell DD.

Speed Headache Associates, PA, Baltimore, Maryland, USA.

This article highlights information from the 2000 National Conference for Nurse
Practitioners symposium held in Washington, D.C., on November 9, 2000. It was
sponsored by The Nursing Institute of Springhouse Corporation and funded by an
unrestricted educational grant from Merck & Co., Inc. The firsttopic, "Overview
of Migraine: Compelling Effects on Patients and Society," was presented for Dedie
Downey Russell, CNP, ANP/GNP, MS. The second topic, "Understanding
Pathophysiology: Evolving from Traditional to Current Therapeutic Options," was
presented by Dara G. Jamieson, MD. Maureen Moriarty-Sheehan, MS, CRNP, who also
served as chairperson, presented the third topic, "Developing a Management Plan
for Optimal Patient Benefit."

Publication Types: 
    Review

PMID: 11337821 [PubMed - indexed for MEDLINE]

3295: Expert Opin Pharmacother. 2001 Apr;2(4):549-55.

Treatment of status migrainosus.

Marcus DA.

Anesthesiology & Neurology Department, Multidisciplinary Headache Cliniic,
Pittsburgh, PA, USA. dawnpainmd@yahoo.com

Migraine episodes that persist for at least 3 days despite treatment are termed
status migrainosus. Traditionally, these long-lasting migraine episodes were
treated with brief in-patient hospitalisations for iv. medication. The full
duration of disability associated with these episodes includes both the several
days of migraine and the several days of hospital stay. The development of
medications that specifically target the mechanism of migraine, such as
dihydroergotamine and the triptans, has reduced the number of headache episodes
that persist after initial treatment or fail to respond to self-administered
therapy.

Publication Types: 
    Review

PMID: 11336606 [PubMed - indexed for MEDLINE]

3296: Int J Geriatr Psychiatry. 2001 Apr;16(4):430-5.

Validating mini-mental status, cognitive capacity screening and Hamilton
depression scales utilizing subjects with vascular headaches.

Meyer JS, Li YS, Thornby J.

Cerebrovascular Research Laboratories, Bldg. 110, Room 225, Holcombe Boulevard
151A, Houston, TX 77030, USA. jmeyer@bcm.tmc.edu

INTRODUCTION: The Mini-Mental State Examination (MMSE) and Cognitive Capacity
Screening Examination (CCSE) are easily and rapidly administered tests for
quantifying the general cognitive status of young as well as geriatric subjects. 
Likewise, the Hamilton Depression Rating Scale (HDRS) is a brief instrument for
quantifying depression that may confound cognitive test performances. Testing by 
means of all three scales concurrently provides useful information for
longitudinal research among the elderly. OBJECTIVES: To validate the combined
longitudinal use of MMSE, CCSE and HDRS among a specific cohort of normal
subjects with vascular headaches characterized by known well-established
temporary cognitive decline occurring only during temporary intervals with
headache. METHODS: The MMSE, CCSE and HDRS were serially tested at 3-12 monthly
intervals among 196 healthy subjects attending our out-patient headache clinic
who suffered from migraine or cluster headaches. Stability and specificity of
MMSE, CCSE and HDRS were evaluated by comparing consecutive normative scores
during headache-free intervals. Sensitivity of MMSE and CCSE for detecting
temporary cognitive decline were evaluated by comparing scores during headache
and headache-free intervals. RESULTS: CCSE, MMSE and HDRS gave stable
headache-free normative values over intervals of 3-10 years among 182 subjects.
Among 77 subjects during headache intervals, temporary cognitive decline were
confirmed by both CCSE and MMSE (p < 0.0001). When cutoff points for both CCSE
and MMSE normal scores were placed at >/= 27, specificity for detecting
cognitively normal values for CCSE and MMSE when headache-free were 92.2 and
89.6%, respectively (p > 0.05), while sensitivity for detecting cognitively
decline during headache intervals were 83.7 and 49%, respectively (p < 0.001).
Compared with scoring by a single rater, reliability estimates for all three
rating scales were slightly lower when tested by different raters, but these
differences were not significant. CONCLUSIONS: CCSE is reliable and more
sensitive than MMSE for detecting cognitive decline. Copyright 2001 John Wiley & 
Sons, Ltd.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, Non-P.H.S.
    Validation Studies

PMID: 11333433 [PubMed - indexed for MEDLINE]

3297: Int J Clin Pharmacol Ther. 2001 Apr;39(4):144-51.

Alpha-dihydroergocryptine and predictive factors in migraine prophylaxis.

Micieli G, Cavallini A, Marcheselli S, Mailland F, Ambrosoli L, Nappi G.

Headache Center, Department of Neurology, C. Mondino Institute, University of
Pavia, Italy. micieli@mondino.it

OBJECTIVE: A double-blind, crossover study was carried out to compare the
efficacy of alpha-dihydroergocryptine mesylate (10 mg twice daily) vs propranolol
(40 mg twice daily) in the prophylaxis of migraine without aura, and to identify 
possible predictors of therapeutic response by evaluating the symptomatological
profile of individual migraine attacks and the autonomic cardiovascular response 
to noradrenergic and dopaminergic (cold pressor, bromocriptine) tests. PATIENTS
AND METHODS: Forty migraineurs (10 males, 30 females) were randomized according
to a two-period (3-month), two-treatment, crossover design. Efficacy was assessed
using quantitative data recorded in the patient's headache diary. Data were
evaluated using the Wallenstein's method. RESULTS: Both drugs showed a
significant reduction in all the efficacy variables (headache attacks, days with 
headache, analgesic consumption) with no difference between treatments. Neither a
bromocriptine test, nor a cold pressor test nor the symptomatological profile of 
individual migraine attacks differed between the two groups of migraine patients.
Ten patients experienced at least one adverse drug reaction during the first
period of the crossover design, 5 being treated with alpha-dihydroergocryptine
and 5 with propranolol. CONCLUSIONS: It is concluded that
alpha-dihydroergocryptine is an effective medication for migraine prophylaxis.
The biochemical tests and the type of psychological profile cannot be used to
predict drug response.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial

PMID: 11332869 [PubMed - indexed for MEDLINE]

3298: Semin Pediatr Neurol. 2001 Mar;8(1):7-12.

Complicated migraine and migraine variants.

Rothner AD.

Department of Pediatric Neurology, The Cleveland Clinic Foundation, OH 44195,
USA.

Complicated migraine and migraine variants are relatively uncommon forms of
migraine. This article reviews migraines, with special emphasis on diagnosis,
differential diagnoses, and treatment.

Publication Types: 
    Review

PMID: 11332867 [PubMed - indexed for MEDLINE]

3299: Semin Pediatr Neurol. 2001 Mar;8(1):27-33.

Status migrainosus in children and adolescents.

Akhtar ND, Murray MA, Rothner AD.

Department of Pediatric Neurology, The Cleveland Clinic Foundation, OH 44195,
USA.

Data concerning status migrainosus in children and adolescents is sparse. The
varied clinical presentations, diagnostic evaluation, and treatment modalities
are discussed.

Publication Types: 
    Case Reports

PMID: 11332863 [PubMed - indexed for MEDLINE]

3300: Semin Pediatr Neurol. 2001 Mar;8(1):22-6.

Triptans in childhood and adolescence.

Winner P.

Premiere Research Institute, Palm Beach Headache Center, FL, USA.

The triptans are medications that are the most important advance, to date, in the
treatment of migraine. Their use in adolescents is highlighted, including
indications, dosages, benefits, and adverse effects.

Publication Types: 
    Review

PMID: 11332862 [PubMed - indexed for MEDLINE]

3301: Semin Pediatr Neurol. 2001 Mar;8(1):13-21.

Cyclic vomiting syndrome: age-old syndrome and new insights.

Li BU.

Department of Pediatrics, Northwestern University, and Children's Memorial
Hospital, Chicago, IL 60614-3394, USA.

Cyclic vomiting is a variant of migraine that is discussed in depth. The
importance of the diagnostic criteria, differential diagnosis, supportive and
pharmacologic therapies is stressed.

Publication Types: 
    Review

PMID: 11332860 [PubMed - indexed for MEDLINE]

3302: Eur J Neurol. 2001 May;8(3):237-45.

Zolmitriptan versus sumatriptan for the acute oral treatment of migraine: a
randomized, double-blind, international study.

Gruffyd-Jones K, Kies B, Middleton A, Mulder LJ, Røsjø Ø, Millson DS.

Box Surgery, London Road, Box Corsham, Wiltshire, UK.

This randomized, double-blind, parallel-group study compared the efficacy and
tolerability of zolmitriptan (2.5 or 5 mg) and sumatriptan (50 mg) in the acute
oral treatment of up to six moderate-to-severe migraine attacks. The intention to
treat (ITT) population comprised of 1522 patients: 500 treated with zolmitriptan 
2.5 mg (2671 attacks), 514 with zolmitriptan 5 mg (2744 attacks) and 508 with
sumatriptan 50 mg (2693 attacks). Overall, the 2-h headache response rates in
these groups were 62.9, 65.7 and 66.6%, respectively. There were no statistically
significant differences between sumatriptan 50 mg and zolmitriptan 2.5 mg (P =
0.12) or 5 mg (P = 0.80). Approximately 40% of patients in each group reported a 
2-h headache response in > or = 80% of attacks. There were no statistically
significant differences between the groups in the rates of headache response at 1
h (zolmitriptan 2.5 mg 36.9%, zolmitriptan 5 mg 39.5% and sumatriptan 50 mg
38.0%) or 4 h (70.3, 72.9 and 72.2%, respectively) or in the rates of meaningful 
migraine relief at 1, 2 or 4 h or sustained (24-h) pain relief. All treatments
were well tolerated. In conclusion, zolmitriptan (2.5 or 5 mg) proved similarly
efficacious compared with sumatriptan (50 mg), both in terms of response rates
and consistency across attacks.

Publication Types: 
    Clinical Trial
    Comparative Study
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 11328332 [PubMed - indexed for MEDLINE]

3303: Eur J Neurol. 2001 May;8(3):231-5.

Is the genetic liability in multifactorial disorders higher in concordant than
discordant monozygotic twin pairs? A population-based family twin study of
migraine without aura.

Gervil M, Ulrich V, Kaprio J, Russell MB.

Department of Neurology, Glostrup Hospital, University of Copenhagen, DK-2600
Glostrup, Denmark. gervil@dadlnet.dk

Migraine without aura (MO) is a multifactorial disorder. Expression of a disorder
with multifactorial inheritance depends on the genetic liability and on
environmental factors. A high liability is reflected by a high frequency of
affected relatives. We have previously shown that monozygotic (MZ) twin pairs
have a significant higher concordance of MO than dizygotic twin pairs. The
incomplete concordance among MZ twin pairs may be due to a lower genetic
liability among discordant than concordant MZ twin pairs. The present study
analysed the genetic liability in MZ twin pairs concordant and discordant for MO 
by the population-relative risk of MO among parents and siblings. The twin pairs 
were from the population-based Danish Twin Register. First-degree relatives of 29
concordant and 34 discordant MZ twin pairs were blindly telephone interviewed by 
a physician. The participation rate of the eligible first-degree relatives was
96%. The population-relative risk of MO among parents and siblings was 2.73
(2.39-3.06) in concordant and 2.37 (2.03-2.71) in discordant MZ twin pairs. The
relative risk of MO was significantly higher in female first-degree relatives of 
concordant than of discordant MZ male and female twin pairs. An opposite effect
was observed in male first-degree relatives, although this was not significant
for male first-degree relatives of female MZ twin pairs. The present study found 
no statistically significant difference in genetic liability to MO among
concordant and discordant MZ twin pairs. However, a difference in genetic
liability among MZ and DZ twin pairs is anticipated to be small. Thus, it may be 
possible to show the effect in a larger study population or by investigating a
more frequent trait than MO.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 11328331 [PubMed - indexed for MEDLINE]

3304: Clin Pharmacokinet. 2001;40(3):189-205.

Pharmacokinetics and pharmacodynamics of the triptan antimigraine agents: a
comparative review.

Jhee SS, Shiovitz T, Crawford AW, Cutler NR.

California Clinical Trials, Beverly Hills 90211, USA. stan.jhee@cctrials.com

The current approach to antimigraine therapy comprises potent serotonin 5-HT1B/1D
receptor agonists collectively termed triptans. Sumatriptan was the first of
these compounds to be developed, and offered improved efficacy and tolerability
over ergot-derived compounds. The development of sumatriptan was quickly followed
by a number of 'second generation' triptan compounds, characterised by improved
pharmacokinetic properties and/or tolerability profiles. Triptans are believed to
effect migraine relief by binding to serotonin (5-hydroxy-tryptamine) receptors
in the brain, where they act to induce vasoconstriction of extracerebral blood
vessels and also reduce neurogenic inflammation. Although the pharmacological
mechanism of the triptans is similar, their pharmacokinetic properties are
distinct. For example, bioavailability of oral formulations ranges between 14%
(sumatriptan) and 74% (naratriptan), and their elimination half-life ranges from 
2 hours (sumatriptan and rizatriptan) to 25 hours (frovatriptan). Clearly, such
diverse pharmacokinetic properties will influence the effectiveness of the
compounds and favour the prescription of one over another in different patient
populations. This article reviews the pharmacological properties of the triptans 
(time to peak plasma concentration, half-life, bioavailability and receptor
binding) and relates these properties to efficacy and time of onset. It also
considers the effects of concomitant medication, food, age and disease on the
pharmacokinetics of the compounds. In addition, the relative merits, such as
headache recurrence, tolerability and route of administration, are discussed.
Finally, the performance of the triptans is considered in the context of direct
head-to-head comparative trials that have assessed the efficacy profile of the
compounds.

Publication Types: 
    Comparative Study
    Review

PMID: 11327198 [PubMed - indexed for MEDLINE]

3305: J Gend Specif Med. 2001;4(1):64-74.

Gender-specific issues in the treatment of migraine.

Weitzel KW, Strickland JM, Smith KM, Goode JV.

University of Florida College of Pharmacy, Department of Pharmacy Practice, Box
100486, JHMHC, Gainesville, FL 32610-0486, USA. weitzel@cop.ufl.edu

Migraine is approximately three times more common in women than in men. Women
tend to have longer attacks and are more likely than men to experience aura with 
migraine, but both sexes can experience frequent and severe attacks. Treatment
principles for migraine and guidelines for the use of prophylactic and abortive
therapies are generally consistent between males and females. However, due to
hormonal changes induced in the female during menstruation, oral contraceptive
use, pregnancy, and menopause, gender-specific therapeutic strategies are often
necessary when treating migraine in females.

Publication Types: 
    Review

PMID: 11324243 [PubMed - indexed for MEDLINE]

3306: Pain. 2001 May;92(1-2):101-6.

An in vivo rat model to study calcitonin gene related peptide release following
activation of the trigeminal vascular system.

Limmroth V, Katsarava Z, Liedert B, Guehring H, Schmitz K, Diener HC, Michel MC.

Department of Neurology, University of Essen, Essen, Germany.
volker.limmroth@uni-essen.de

Calcitonin gene related peptide (CGRP) released from the C-fibers projecting from
the trigeminal ganglion to the meninges has been suggested to play a crucial role
in the pathophysiology of headache, particularly migraine. In humans it has been 
shown that CGRP is released during migraine-attacks, and this is attenuated by
the administration of typical anti-migraine drugs such as dihydroergotamine or
sumatriptan. We describe a new rat model which allows the study of CGRP release
from the meninges into venous blood following activation of the trigeminal
vascular system. The effects of classical and new anti-migraine drugs such as
acetylsalicylic acid (ASA), sumatriptan and the new high efficacy 5-HT1B/1D
agonist donitriptan
(4-[4-[2-(2-aminoethyl)-1H-indol-5-yloxyl]acetyl]piperazinyl-1-yl]benzonitrile)
were evaluated in comparison with the established model of neurogenic
inflammation in the meninges. Sumatriptan and donitriptan inhibited CGRP release 
as well as neurogenic inflammation. ASA, however, attenuated neurogenic
inflammation, but not CGRP release, confirming the concept of prejunctional
inhibition of CGRP release by 5-HT1B/1D receptors. This new model allows the
further study of prejunctional pharmacology and mechanisms of neuropeptide
release in the trigeminal vascular system, which might be crucial for the further
development of potent, more effective anti-migraine drugs.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 11323131 [PubMed - indexed for MEDLINE]

3307: Neurology. 2001 Apr 24;56(8):1038-43.

Comment in:
    Neurology. 2002 Apr 23;58(8):1316; author reply 1316-7.

Neuromuscular transmission in migraine: a single-fiber EMG study in clinical
subgroups.

Ambrosini A, Maertens de Noordhout A, Schoenen J.

Mediterranean Neurological Institute, IRCCS Neuromed, Pozzilli, Italy.

OBJECTIVE: To search for impairment of neuromuscular transmission by single-fiber
electromyography (SFEMG) in patients with common forms of migraine. BACKGROUND:
P/Q Ca(2+) channels are genetically abnormal in most cases of familial hemiplegic
migraine (International Headache Society [IHS] code 1.2.3) and may be involved in
other types of migraine. Besides in the brain, these channels are found in motor 
nerve endings, where they control stimulation-induced acetylcholine release. If
they are functionally abnormal, the neuromuscular transmission might be impaired.
METHODS: Sixty-two migraineurs (18 without aura, IHS code 1.1; 19 with typical
aura, IHS code 1.2.1; 10 with prolonged aura, IHS code 1.2.2; 15 with and without
aura) and 16 healthy control subjects underwent stimulation SFEMG. Results were
expressed as the mean value of consecutive differences (MCD) and percentage of
single-fiber abnormalities (abnormal jitter or impulse blocking). RESULTS:
Average MCD was comparable in control subjects and migraineurs (17.1 +/- 2.6
versus 17.5 +/- 4.7 microsec). By contrast, single-fiber abnormalities were found
in 17 patients but in none of the control subjects (p = 0.036). Most of these
patients had unilateral sensorimotor symptoms and/or aphasia and/or loss of
balance during the aura. SFEMG abnormalities were significantly correlated with
the occurrence of these clinical features and with a diagnosis of migraine with
prolonged aura. CONCLUSIONS: Stimulation SFEMG shows mild abnormalities of
neuromuscular transmission in a subgroup of migraineurs with aura, characterized 
by clinical features frequently found in human P/Q Ca(2+) channelopathies. These 
abnormalities might thus be due to genetically modified P/Q Ca(2+) channels.

Publication Types: 
    Clinical Trial
    Research Support, Non-U.S. Gov't

PMID: 11320175 [PubMed - indexed for MEDLINE]

3308: Neurology. 2001 Apr 24;56(8):1028-32.

Involvement of the CACNA1A gene containing region on 19p13 in migraine with and
without aura.

Terwindt GM, Ophoff RA, van Eijk R, Vergouwe MN, Haan J, Frants RR, Sandkuijl LA,
Ferrari MD; Dutch Migraine Genetics Research Group.

Department of Neurology, Leiden University Medical Centre, the Netherlands.

OBJECTIVE: To assess the involvement of the 19p13 familial hemiplegic migraine
(FHM) locus in migraine with and without aura. BACKGROUND: Migraine with and
without aura are likely to be polygenetic multifactorial disorders. FHM is a rare
dominantly inherited type of migraine with aura. In about 50% of families, FHM is
caused by mutations in the P/Q-type calcium channel alpha(1A)-subunit (CACNA1A)
gene on chromosome 19p13. The CACNA1A gene is thus a good candidate gene for
"nonhemiplegic" migraine with or without aura. METHODS: The authors performed an 
affected sibpair analysis using flanking and CACNA1A intragenic markers. The
authors assessed the occurrence of shared parental marker alleles among 189
affected siblings from 36 extended families with typical migraine with or without
aura. RESULTS: Sibling pairs with any form of migraine had inherited the same
19p13 CACNA1A-containing region significantly more frequently than expected by
chance (maximum multipoint lod score = 1.22). This result was almost exclusively 
dependent on the increased sharing found in sibling pairs with migraine with aura
(maximum multipoint lod score = 1.41). The locus-specific relative risk for a
sibling (lambda(s)) to suffer from migraine with aura, defined as the increase in
risk of the trait attributable to the 19p13 locus, was lambda(s) = 1.56. When
combining migraine with and without aura, lambda(s) was 1.22. CONCLUSIONS: The
increased allele sharing in the CACNA1A gene region on 19p13 is consistent with
an important involvement of this region in migraine, especially migraine with
aura.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 11320173 [PubMed - indexed for MEDLINE]

3309: Headache. 2001 Apr;41(4):410-3.

Migraine with aura after intracranial endovascular procedures.

Beekman R, Nijssen PC, van Rooij WJ, Wijnalda D.

Departments of Neurology, St. Elisabeth Hospital, Tilburg, The Netherlands;
Radiology, St. Elisabeth Hospital, Tilburg, The Netherlands; Neurosurgery, St.
Elisabeth Hospital, Tilburg, The Netherlands.

OBJECTIVE: To describe three cases of migraine (two with aura) after an
intracranial endovascular procedure. Method.-Retrospective. RESULTS: One patient 
had an attack of migraine with prolonged aura after embolization of a dural
arteriovenous fistula. Another patient had an attack of migraine with aura (and
hemiparesis) after a diagnostic angiogram. The third patient already suffered
from migraine with aura and had a migraine attack after embolization of an
occipital arteriovenous malformation. A quadrantanopia persisted in this patient.
Outcome of the other two patients was good. CONCLUSION: Intracranial endovascular
procedures can induce migraine with aura. We could not identify the underlying
pathophysiological mechanism, but mechanical, chemical, immunological, or
hemodynamic factors could be involved.

Publication Types: 
    Case Reports

PMID: 11318889 [PubMed - indexed for MEDLINE]

3310: Headache. 2001 Apr;41(4):402-9.

Development and validation of the Headache Needs Assessment (HANA) survey.

Cramer JA, Silberstein SD, Winner P.

Department of Neurology, Yale University School of Medicine, New Haven, Conn,
USA.

OBJECTIVE: To develop and validate a brief survey of migraine-related
quality-of-life issues. The Headache Needs Assessment (HANA) questionnaire was
designed to assess two dimensions of the chronic impact of migraine (frequency
and bothersomeness). METHODS: Seven issues related to living with migraine were
posed as ratings of frequency and bothersomeness. Validation studies were
performed in a Web-based survey, a clinical trial responsiveness population, and 
a retest reliability population. Headache characteristics (eg, frequency,
severity, and treatment), demographic information, and the Headache Disability
Inventory were used for external validation. RESULTS: The HANA was completed in
full by 994 adults in the Web survey, with a mean total score of 77.98 +/- 40.49 
(range, 7 to 175). There were no floor or ceiling effects. The HANA met the
standards for validity with internal consistency reliability (Cronbach alpha
=.92, eigenvalue for the single factor = 4.8, and test-retest reliability =
0.77). External validity showed a high correlation between HANA and Headache
Disability Inventory total scores (0.73, P<.0001), and high correlations with
disease and treatment characteristics. CONCLUSIONS: These data demonstrate the
psychometric properties of the HANA. The brief questionnaire may be a useful
screening tool to evaluate the impact of migraine on individuals. The
two-dimensional approach to patient-reported quality of life allows individuals
to weight the impact of both frequency and bothersomeness of chronic migraines on
multiple aspects of daily life.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 11318888 [PubMed - indexed for MEDLINE]

3311: Headache. 2001 Apr;41(4):399-401.

A history of migraine is not a risk factor to develop an ischemic stroke in the
elderly.

Mosek A, Marom R, Korczyn AD, Bornstein N.

Department of Neurology, Sourasky Medical Center, Tel Aviv, Israel.

OBJECTIVE: To assess the prevalence of migraine in elderly patients hospitalized 
with ischemic stroke compared with vascular and nonvascular control groups.
BACKGROUND: Migraine is a disease with a presumed vascular mechanism. While
migraine is a common complaint of young victims of ischemic stroke, it is unclear
whether a current or past history of migraine constitutes a risk factor for
developing an ischemic stroke in the elderly. METHODS: We obtained current and
past headache history from 100 consecutive patients hospitalized with ischemic
stroke (aged 60 years or older) and compared the results with 100 patients
hospitalized due to acute myocardial infarction and 100 hospitalized patients
with no vascular disease. RESULTS: The sex and the age of the patients did not
differ among the groups. The lifetime prevalence of migraine (8% of the patients 
with ischemic stroke, 8% of the nonvascular controls, and 15% of the patients
with acute myocardial infarction) or of all types of headaches (27%, 30%, and
15%, respectively), did not differ significantly between the groups. CONCLUSIONS:
Based on the reported history, elderly migraineurs are not at increased risk to
develop ischemic stroke.

Publication Types: 
    Comparative Study

PMID: 11318887 [PubMed - indexed for MEDLINE]

3312: Headache. 2001 Apr;41(4):391-8.

Comment in:
    Headache. 2002 Apr;42(4):322-3; author reply 323-4.

Comparative study of a combination of isometheptene mucate, dichloralphenazone
with acetaminophen and sumatriptan succinate in the treatment of migraine.

Freitag FG, Cady R, DiSerio F, Elkind A, Gallagher RM, Goldstein J, Klapper JA,
Rapoport AM, Sadowsky C, Saper JR, Smith TR.

Diamond Headache Clinic, Chicago, Ill 60614-1726, USA.

OBJECTIVE: To compare the safety and efficacy of isometheptene mucate,
dichloralphenazone with acetaminophen to sumatriptan succinate for the treatment 
of mild-to-moderate migraine, with or without aura, when taken at the first sign 
of an attack. BACKGROUND: The Food and Drug Administration approved sumatriptan
succinate and the combination of isometheptene mucate, dichloralphenazone with
acetaminophen for the treatment of migraine. As part of the stratified treatment 
of migraine, those patients whose headaches are mild or moderate may benefit from
nontriptan medications. Additionally, early treatment of acute migraine before
the headache has become moderate or severe may improve response to treatment.
METHODS: This was a multicenter, double-blind, randomized, parallel-group study
to assess the safety and efficacy of the combination of isometheptene mucate,
dichloralphenazone with acetaminophen and sumatriptan succinate in the early
stages of a single migraine attack. Patients diagnosed with migraine, with or
without aura, as defined by the International Headache Society diagnostic
criteria were enrolled. RESULTS: One hundred thirty-seven patients were enrolled 
in the study. Data for efficacy were available for 126 patients; safety data were
available for 128 patients. No statistically significant difference between the
two active agents in the patient's response to treatment was demonstrated.
Headache recurrence was not significantly different over the 24-hour evaluation
period for those patients responding in the first 4 hours. In those with headache
recurrence, it was statistically significantly more severe in those patients
treated with sumatriptan succinate. Improvement in functional disability was, in 
general, better among those treated with isometheptene mucate, dichloralphenazone
with acetaminophen. Global analysis of efficacy was similar in the two active
groups. Patients treated with sumatriptan succinate were somewhat more likely to 
have adverse effects than the isometheptene mucate, dichloralphenazone with
acetaminophen group. CONCLUSIONS: Both isometheptene mucate, dichloralphenazone
with acetaminophen and sumatriptan succinate are safe and effective when used
early in the treatment of an acute migraine. Several parameters suggest that
isometheptene mucate, dichloralphenazone with acetaminophen may have a slight
advantage compared with sumatriptan succinate in the early treatment of
mild-to-moderate migraine.

Publication Types: 
    Clinical Trial
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 11318886 [PubMed - indexed for MEDLINE]

3313: Headache. 2001 Apr;41(4):377-84.

Sumatriptan nasal spray and cognitive function during migraine: results of an
open-label study.

Farmer K, Cady R, Bleiberg J, Reeves D, Putnam G, O'Quinn S, Batenhorst A.

Headache Care Center, Springfield, Mo 65804, USA.

OBJECTIVE: To examine measures of cognitive function during acute migraine,
before and after treatment with sumatriptan nasal spray, 20 mg. BACKGROUND:
Migraineurs frequently report symptoms of cognitive impairment during migraine.
The efficacy of sumatriptan for treatment of migraine-related cognitive
impairment is undocumented. METHODS: This open-label, single-attack study of 28
subjects used the Headache Care Center-Automated Neuropsychological Assessment
Metrics, a computerized neuropsychological assessment battery, to measure
cognitive function under three patient conditions: migraine-free, untreated
migraine, and following sumatriptan (primary outcome). Headache response and
pain-free response, percent effectiveness, and clinical disability were measured.
RESULTS: Cognitive function (simple reaction time, sustained
attention/concentration, working memory, visual-spatial processing) and
alertness/fatigue were adversely affected during migraine compared with
migraine-free performance (P<.05), and rapidly restored following sumatriptan
nasal spray, 20 mg (P<.05). Headache and pain-free response were 86% and 68%,
respectively, at 135 minutes postdose. Changes in migraine pain severity,
clinical disability, and percent effectiveness following treatment with
sumatriptan nasal spray, 20 mg, were significantly correlated with cognitive
function measures across all subtests (P<.001). CONCLUSIONS: Sumatriptan nasal
spray, 20 mg, restored migraine-related cognitive function and clinical
disability.

Publication Types: 
    Clinical Trial
    Research Support, Non-U.S. Gov't

PMID: 11318884 [PubMed - indexed for MEDLINE]

3314: Headache. 2001 Apr;41(4):351-6.

Comment in:
    Headache. 2004 Mar;44(3):293-4.

Delivery outcome in women who used drugs for migraine during pregnancy with
special reference to sumatriptan.

Källén B, Lygner PE.

Tornblad Institute, University of Lund, Sweden; Glaxo Wellcome AB, Mölndal,
Sweden.

OBJECTIVE: To evaluate delivery outcome in women who used drugs for migraine
during pregnancy with special reference to sumatriptan. BACKGROUND: The safety of
the use of drugs for migraine during pregnancy is not established. Design and
METHODS: Using the Swedish Medical Birth Registry which contains information on
drug use reported by women at the first antenatal visit, 912 infants (born in 905
deliveries) whose mothers had used drugs for migraine were identified, the
majority of whom (n = 658) had used sumatriptan. RESULTS: These women differed
from the general population of women who had delivered by being older and more
often of first parity, but they had similar smoking habits. Slightly more often, 
the infants were preterm, and they had a birth weight less than 2500 g; neither
of these effects were statistically significant. There seemed to be no difference
between infants exposed to sumatriptan and those exposed to other drugs used for 
migraine. No increase in the rate of congenital malformations was seen.
CONCLUSIONS: The data indicate that use of sumatriptan in early pregnancy does
not result in a large increase in teratogenic risk, but do not rule out the
possibility of a moderate increase in risk for a specific birth defect.

PMID: 11318881 [PubMed - indexed for MEDLINE]

3315: Headache. 2001 Apr;41(4):343-50.

Information about migraine disability influences physicians' perceptions of
illness severity and treatment needs.

Holmes WF, MacGregor EA, Sawyer JP, Lipton RB.

Sherrington Park Medical Practice, Nottingham, City of London, England.

OBJECTIVE: To assess physician-patient communication about headache-related
disability and to evaluate the influence of information about disability on
physicians' perceptions of illness severity and the treatment needs of
migraineurs. BACKGROUND: Evidence suggests that migraine is suboptimally treated 
in clinical practice, partly due to poor communication between physicians and
their patients. METHODS: One hundred five neurologists and primary care
physicians with an interest in headache participated in two interactive surveys, 
one in North America (n=42) and one in Europe (n=63). Each survey focused on the 
evaluation of four videotaped migraine cases. The first case was evaluated twice,
initially after a typical symptom history that centered on diagnosis and then
following a fuller history of migraine disability. Additional questions assessed 
the extent of the collection of migraine disability information in clinical
practice. RESULTS: Physicians reported that they recorded symptoms relating to
diagnosis (eg, pain location/intensity, associated symptoms) rather than
information on headache-related disability. Only about one third of patients
volunteered disability information. When made available to them, physicians rated
information on disability as one of the most important factors in assessing
treatment needs. In particular, when physicians knew the patient's disability
history: (1) the proportion of physicians who rated the patient's illness as
"severe" increased by 128% in North America, 27% in Europe; (2) the proportion of
physicians who recommended immediate treatment increased by 63% in North America,
37% in Europe; and (3) the proportion of patients recommended for a follow-up
visit increased by 15% in North America, 18% in Europe. CONCLUSIONS: Physicians
and patients often fail to discuss headache-related disability during
consultation. This information has a powerful influence on physicians'
perceptions of illness severity, treatment choice, and the need for follow-up.
Tools to improve communication about headache-related disability, such as the
Migraine Disability Assessment questionnaire, may favorably improve migraine
management.

Publication Types: 
    Case Reports
    Research Support, Non-U.S. Gov't

PMID: 11318880 [PubMed - indexed for MEDLINE]

3316: Am J Ther. 2000 May;7(3):185-94.

Degradation kinetics of leucine5-enkephalin by plasma samples from healthy
controls and various patient populations: in vitro drug effects.

Mosnaim AD, Wolf ME, Nguyen TD, Puente J, Freitag F, Diamond S.

Department of Cellular and Molecular Pharmacology, The Chicago Medical School,
North Chicago, Chicago, Illinois 60064, USA.

Incubation of [3H]tyrosine leucine5-enkephalin with platelet-poor human plasma
(final concentration 1 x 10(-8) M; 1:9 ratio to Trizma base buffer, pH 7.4)
resulted in rapid and complete peptide degradation in each of the subjects
studied, with more than 95% of the initial labeled tyrosine consistently
recovered as the free amino acid (< or =30 minutes). Essentially, and
irrespective of the incubation time (1-180 minutes), tyrosine was the only Leu
metabolite formed; we were unable to identify significant amounts (> or =3%) of
any other possible labeled or nonlabeled Leu degradation fragments. Neither
gender (64 men and 20 women; samples tested individually), age (men, 23-70;
women, 25-65 years), nor the subjects' medical condition appeared to make a
significant difference in either the t1/2 of Leu elimination, the initial
velocity of this reaction (x +/- SD, median, minimum and maximum of 12.0 +/- 0.9,
12.0, and 10.6-13.7 minutes; 1.2 +/- 0.3, 1.1, and 0.6-2.0 pg/min, respectively),
or in the Km and Vmax values for aminopeptidase Leu degradation (x +/- SD; 0.81
+/- 0.01 mM and 14.30 +/- 1.17 micromol/L/min, respectively). Subjects were
diagnosed as chronic schizophrenics (n = 15), polydrug abusers including alcohol 
(n = 9) and polydrug abusers excluding alcohol (n = 8), chronic alcoholics (n =
12), and migraineurs (n = 10) during or outside an acute migraine episode; for
comparison we used a group of gender-matched (20 men and 10 women),
age-comparable, drug-free, healthy volunteers. Differences in plasma storage time
or repeated sample freezing and thawing failed to alter significantly any of
these kinetic parameters of Leu metabolism or to change the identity and/or
relative ratio of the products formed. The Leu degradation rate was pH and
temperature dependent (optimum, 7.4 and 37 degrees C, respectively). Leu
degradation was strongly and similarly inhibited by puromycin, bacitracin, and
bestatin (IC50 [+/- SD] of 1.4 +/- 0.2 micromol/L) and to a lesser extent by
various L-tyrosine-containing Leu fragments. The kinetics of this reaction was
not significantly affected by either thiorphan, N-carboxyphenylmethyl leucine, or
any other of a number of monoamine neurotransmitters, substances of abuse,
nonsteroidal anti-inflammatory agents, and miscellaneous compounds tested
(concentration up to 10(-4) mol/L).

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 11317167 [PubMed - indexed for MEDLINE]

3317: Arch Dis Child. 2001 May;84(5):415-8.

The prognosis of childhood abdominal migraine.

Dignan F, Abu-Arafeh I, Russell G.

Department of Child Health, University of Aberdeen, Scotland AB25 2ZD, UK.

AIMS: To determine the clinical course of childhood abdominal migraine, seven to 
10 years after the diagnosis. METHODS: A total of 54 children with abdominal
migraine were studied; 35 were identified from a population survey carried out on
Aberdeen schoolchildren between 1991 and 1993, and 19 from outpatient records of 
children in the same age group who had attended the Royal Aberdeen Children's
Hospital. Controls were 54 children who did not have abdominal pain in childhood,
matched for age and sex, obtained from either the population survey or the
patient administration system. Main outcome measures were presence or resolution 
of abdominal migraine and past or present history of headache fulfilling the
International Headache Society (IHS) criteria for the diagnosis of migraine.
RESULTS: Abdominal migraine had resolved in 31 cases (61%). Seventy per cent of
cases with abdominal migraine were either current (52%) or previous (18%)
sufferers from headaches that fulfilled the IHS criteria for migraine, compared
to 20% of the controls. CONCLUSIONS: These results support the concept of
abdominal migraine as a migraine prodrome, and suggest that our diagnostic
criteria for the condition are robust.

PMID: 11316687 [PubMed - indexed for MEDLINE]

3318: Trends Neurosci. 2001 May;24(5):266-71.

Cortical spreading depression and migraine: new insights from imaging?

James MF, Smith JM, Boniface SJ, Huang CL, Leslie RA.

Neuroscience Research, GlaxoSmithKline, New Frontiers Science Park (North), Third
Avenue, Harlow, Essex, UK, CM19 5AW.

The possibility that spreading depression (SD) of cortical activity, a phenomenon
observed in all vertebrates, causes the aura of migraine remains an open question
in spite of nearly half a century of investigation. SD is also thought to be
associated with the progressive neuronal injury observed during cerebral
ischaemia. Thus, the ability to detect and investigate SD in humans might prove
clinically significant. Animal studies of cortical spreading depression (CSD)
have benefited greatly from the advent of relatively non-invasive imaging
techniques. The use of these new imaging techniques for clinical studies will
accelerate progress in this area of neurobiology.

Publication Types: 
    Review

PMID: 11311378 [PubMed - indexed for MEDLINE]

3319: Acta Anaesthesiol Scand. 2001 May;45(5):649-51.

Computerized tomography-guided epidural blood patch in the treatment of
spontaneous low cerebrospinal fluid pressure headache.

Karst M, Hollenhorst J, Fink M, Conrad I.

Department of Anesthesiology, Pain Clinic, Medical School of Hannover, D-30623
Hannover, Germany. Karst.Matthias@MH-Hannover.De

A 54-year-old woman suffering from migraine for 35 years was referred to the pain
clinic with a changed pattern of headache that had developed over the last 6
weeks. The pain was located in the central forehead region; aggravation in the
prone and immediate relief in the supine position led to the hypothesis of a
spontaneous low cerebrospinal fluid (CSF) pressure headache. Cisternography
revealed a cyst-like formation in the cervico-thoracic region, indicating
cerebrospinal fluid leakage. Magnetic resonance imaging (MRI) myelography
confirmed ventral leakage but failed to locate the exact site. Computerized
tomography (CT)-guided epidural blood patching between T1 and T2 completely
relieved the headache.

Publication Types: 
    Case Reports

PMID: 11309021 [PubMed - indexed for MEDLINE]

3320: Maturitas. 2001 Apr 20;38(2):157-63.

Course of primary headaches during hormone replacement therapy.

Nappi RE, Cagnacci A, Granella F, Piccinini F, Polatti F, Facchinetti F.

Department of Obstetrics and Gynecology, IRCCS S. Matteo, University of Pavia,
Piazzale Golgi 2, 27100, Pavia, Italy. renappi@tin.it

OBJECTIVE: The aim of the present study was to evaluate how hormone replacement
therapy (HRT) could influence the course of primary headaches in postmenopausal
women. METHODS: Fifty patients presenting for clinical evaluation of menopausal
status and suffering from headache were enrolled. The observational period lasted
7 months during which women filled in a diary with the clinical characteristics
of headache attacks (frequency, days with headache, severity) and the analgesic
use (no. of analgesic/month). Climacteric symptoms and both anxiety and
depression were also measured. At the first visit the patients were divided into 
two groups: those suffering from migraine without aura (MwA) and those suffering 
from episodic tension-type headache (ETTH) and separately randomized. After a
month of run-in period, they received two different HRT regimen, either: (1)
transdermal estradiol 50 mcg every 7 days for 28 days plus medroxyprogesterone
acetate (MAP) 10 mg/day from 15th to 28th day, or (2) oral conjugated estrogens
0.625 mg/day for 28 days plus MAP 10 mg/day for the last 14 days. Follow up
evaluations were planned after 1, 3 and 6 months of treatment. RESULTS: While we 
did not observe any significance change regarding headache parameters in ETTH
patients during both transdermal and oral treatment, the course of migraine was
significantly affected by the route of HRT. Both frequency of attacks (F = 8.5; P
< 0.000) and days with headache (F = 6.9; P < 0.000) significantly increased
during HRT in the subgroup assuming oral formulation. On the contrary, no changes
in the same parameters were found in the group taking transdermal treatment.
Moreover, while severity of migraine was unaffected by HRT, analgesic consumption
was significantly increased in the subgroup on oral treatment (F = 6.3; P =
0.001). CONCLUSIONS: HRT significantly affects the course of headache in
postmenopausal migraine sufferers. Indeed, while the clinical pattern of ETTH
remained stable throughout the observational period, patients suffering from MwA 
worsened their symptoms within the first 3 months of treatment. In particular,
the oral route of administration significantly worsened migraine in comparison to
the transdermal route.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial

PMID: 11306204 [PubMed - indexed for MEDLINE]

3321: Brain Res Bull. 2001 Mar 1;54(4):437-41.

Deficient energy metabolism is associated with low free magnesium in the brains
of patients with migraine and cluster headache.

Lodi R, Iotti S, Cortelli P, Pierangeli G, Cevoli S, Clementi V, Soriani S,
Montagna P, Barbiroli B.

Dipartimento di Medicina Clinica e Biotecnologia Applicata D. Campanacci,
Università di Bologna, Bologna, Italy. lodi@med.unibo.it

We used phosphorus magnetic resonance spectroscopy to assess in vivo the brain
cytosolic free magnesium concentration and the free energy released by the
reaction of adenosine triphosphate (ATP) hydrolysis (DeltaG(ATPhyd)), the latter 
being an index of the cell's bioenergetics condition. We studied 78 patients with
migraine in attack-free periods (7 with migraine stroke, 13 with migraine with
prolonged aura, 37 with migraine with typical aura or basilar migraine, and 21
with migraine without aura), and 13 patients with cluster headache. In the
occipital lobes of all subgroups of migraine and in cluster headache patients
cytosolic free [Mg(2+)] as well as the free energy released by the reaction of
ATP hydrolysis were significantly reduced. Among migraine patients, the level of 
free energy released by the reaction of ATP hydrolysis and the cytosolic free
[Mg(2+)] showed a trend in keeping with the severity of clinical phenotype, both 
showing the lowest values in patients with migraine stroke and the highest in
patients with migraine without aura. These results support our current hypothesis
that the reduction in free [Mg(2+)] in tissues with mitochondrial dysfunction is 
secondary to the bioenergetics deficit, and are against a primary role of low
brain cytosolic free [Mg(2+)] in causing the bioenergetics deficit in headache.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 11306197 [PubMed - indexed for MEDLINE]

3322: Cephalalgia. 2000 Dec;20(10):925-30.

A prospective study of migraine with aura attacks in a headache clinic
population.

Cologno D, Torelli P, Cademartiri C, Manzoni GC.

Headache Centre, Institute of Neurology, University of Parma, Italy.
dcologn@tin.it

In order to investigate the prevalence of migraine with aura (MA) attacks
according to the criteria set by the International Headache Society (IHS) for
diagnosis down to the three-digit level of classification, and to determine the
recurrence and possible variability of MA attacks over time, we conducted a
6-15-month-long prospective study on 64 MA patients (42 women and 22 men)
consecutively referred for the first time to the University of Parma Headache
Centre. At the end of the follow-up period, diagnosis was the same as at the
first visit for 80.0% of patients, while it was changed for 20.0%. Throughout the
duration of the study, the average number of attacks for each patient was 5.3 +/-
6.2 (range 0-30). Attacks of migraine with typical aura were the most frequent
(69.1% of patients), but migraine aura without headache (29.1%) and migraine with
prolonged aura (20.0%) were also common; by contrast, basilar migraine and
migraine with acute onset aura were reported only by one patient in either case. 
Migraine aura without headache was statistically significantly more frequent in
males than in females. Our study results suggest that in most cases the frequency
of recurrent MA attacks is relatively low and provide interesting indications
about the prevalence of the different MA subtypes listed in the IHS
classification, albeit in a headache clinic population.

PMID: 11304028 [PubMed - indexed for MEDLINE]

3323: Cephalalgia. 2000 Dec;20(10):907-18.

Nitric oxide metabolites, prostaglandins and trigeminal vasoactive peptides in
internal jugular vein blood during spontaneous migraine attacks.

Sarchielli P, Alberti A, Codini M, Floridi A, Gallai V.

Interuniversity Centre for the Study of Headache and Neurotransmitter Disorders, 
University of Perugia, Italy. neuro@netemedia.net

Despite evidence emerging from the experimental model of nitroglycerin-induced
headache, the endogenous increase in nitric oxide (NO) production during migraine
attacks is only speculative. It has been hypothesized that there is a close
relationship between activation of the L-arginine/NO pathway and production of
certain vasoactive and algogenic prostaglandins during spontaneous migraine
attacks, but this suggestion also needs to be confirmed. In the present study the
levels of nitrites, the stable metabolites of NO, were determined with high
performance liquid chromatography (HPLC) in the internal jugular venous blood of 
five patients affected by migraine without aura examined ictally. These samples
were taken within 30 min, 1, 2, and 4 h from the onset of the attack and at the
end of the ictal period. At the same time, the plasma levels of calcitonin
gene-related peptide (CGRP), neurokinin A (NKA), prostaglandin E2 (PGE2) and 6
keto PGF1alpha, the stable product of PGI2, were assessed with radioimmunoassay
(RIA) kits in the same samples. The levels of the intracellular messengers, cGMP 
and cAMP, were also measured with the RIA method. Nitrite, cGMP, CGRP and NKA
levels reached their highest values at the first hour, then they tended to
decrease progressively and returned, after the end of attacks, to values similar 
or below those detected at the time of catheter insertion (ANOVA, statistical
significance: P<0.001; P<<0.002; P<0.002; P<0.003, respectively). PGE2 and 6 keto
PGF1alpha, as well as cAMP levels also significantly increased at the first hour 
but reached a peak at the 2nd hour and remained in the same range until the 4th
and 6th hours. Then their values tended to decrease after the end of attacks,
becoming lower than those measured immediately after catheter positioning for
internal jugular venous blood drawing (ANOVA: P<0.002, P<0.004, P<0.001,
respectively). Our results support early activation of the L-arginine/NO pathway 
which accompanies the release of vasoactive peptides from trigeminal endings and 
a late rise in the synthesis of prostanoids with algogenic and vasoactive
properties which may intervene in maintaining the headache phase.

PMID: 11304026 [PubMed - indexed for MEDLINE]

3324: Cephalalgia. 2000 Dec;20(10):900-6.

Prevalence of migraine and non-migrainous headache--head-HUNT, a large
population-based study.

Hagen K, Zwart JA, Vatten L, Stovner LJ, Bovim G.

Department of Clinical Neuroscience, Faculty of Medicine, Norwegian University of
Science and Technology, Trondheim. knut.hagen@medisin.ntnu.no

The objective of this study was to estimate the 1-year prevalence of the
following categories of headache; migraine, non-migrainous headache, frequent
headache (>6 days/month), and chronic headache (>14 days/month). Between 1995 and
1997, all 92,566 inhabitants 20 years and older in Nord-Trøndelag county in
Norway were invited to a comprehensive health study. Out of 64,560 participants, 
a total of 51,383 subjects (80%) completed a headache questionnaire. The overall 
age-adjusted 1-year prevalence of headache was 38% (46% in women and 30% in men).
The prevalence of migraine was 12% (16% in women and 8% in men), and for
non-migrainous headache 26% (30% in women and 22% in men). For frequent headache 
(> 6 days per month) and for chronic headache (>14 days per month), the
prevalence was 8% and 2%, respectively. Women had a higher prevalence than men in
all age groups and for all headache categories. Prevalence peaked in the fourth
decade of life for both men and women, except for 'frequent non-migrainous
headache', which was nearly constant across all age groups in both genders. In
accordance with findings in other western countries, we found that headache
suffering, including migraine, was highly prevalent, especially in younger women.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 11304025 [PubMed - indexed for MEDLINE]

3325: Cephalalgia. 2000 Dec;20(10):893-9.

The prevalence of migraine in women aged 40-74 years: a population-based study.

Mattsson P, Svärdsudd K, Lundberg PO, Westerberg CE.

Department of Neuroscience, University Hospital, Uppsala, Sweden.
Peter.Mattsson@neurologi.uu.se

The objective of this study was to investigate the age-dependence of the
prevalence and characteristics of migraine headache and migraine visual aura. A
neurologist interviewed 728 women attending a mammography screening programme.
International Headache Society (IHS) criteria were used. The lifetime prevalence 
of migraine headache was 31.5% and the 1-year prevalence 18.0%. The magnitude of 
the decline of the prevalence of active (one or more attacks in the previous
year) migraine headache was estimated to 50% per decade. The prevalence of active
migraine visual aura was 3.8%. This did not vary by age. Except for the pain
intensity and the presence of nausea, other characteristics and concomitant
symptoms did not change with age. Active migraine headache and migraine visual
aura in middle-aged and older women are common and modified differently by age.
We suggest that the decline of prevalence of active migraine headache with age is
caused by a decrease in pain intensity.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 11304024 [PubMed - indexed for MEDLINE]

3326: Cephalalgia. 2000 Dec;20(10):881-92.

Slow cortical potentials in migraine families.

Siniatchkin M, Kirsch E, Kropp P, Stephani U, Gerber WD.

Institute of Medical Psychology, University of Kiel, Germany.
siniatchkin@med-psych.uni-kiel.de

Amplitude and habituation of event-related potentials are abnormal in migraine.
We investigated 43 migraine and 41 healthy families to evaluate the influences of
age, sex and familial contribution on the variance of amplitude and habituation
of the contingent negative variation (CNV). Analysis of individual differences in
relation to the CNV habituation was performed. The study demonstrated that
habituation of the early CNV component characterizes migraine considerably better
than the CNV amplitudes. Habituation, however, is strongly influenced by age.
Migraine adults and children generally showed reduced habituation. Surprisingly, 
more than 30% of the healthy adults demonstrated a marked loss of habituation.
The reduced CNV habituation represented a high sensitivity but low specificity to
migraine, especially in children. CNV amplitude and habituation parameters
revealed a considerable familial contribution associated with migraine. No
familial influence on either morphology or habituation of the CNV in healthy
families or between healthy members of migraine families was observed. The low
specificity and familial transmission of CNV parameters in members of migraine
families suggest that increased amplitudes and reduced habituation of CNV do not 
constitute a primary risk factor for migraine, but rather represent a
predisposition. Genetic components probably affect variation of the CNV amplitude
and habituation.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 11304023 [PubMed - indexed for MEDLINE]

3327: Cephalalgia. 2000 Dec;20(10):865-80.

Visual contrast processing in migraine.

Shepherd AJ.

School of Psychology, Birkbeck College, London. a.shepherd@psychology.bbk.ac.uk

Some migraine sufferers report certain visual patterns can reliably trigger a
migraine attack, such as high contrast striped patterns or flickering lights.
Differences between people with and without migraine on tasks that involve these 
patterns have been attributed to abnormal cortical processing in migraine,
although the locus and extent of the abnormality remains unclear, as is any
relationship between impairment on various visual tasks. In this study 58
migraine sufferers and 61 control subjects participated in three visual tasks
involving striped patterns. One assessed pattern sensitivity with high contrast
patterns, the second detection thresholds for low contrast patterns and the third
supra-threshold contrast scaling. With each measure, the performance of migraine 
sufferers as a group differed to the performance of non-migraine control
subjects. There were no significant differences between the migraine subgroups
when classified according to the presence or absence of aura. Cross-correlating
the results from the three tasks, however, revealed consistent associations:
impaired or extreme responses on one task were associated with impaired or
extreme responses on the others. There were no overall effects due to migraine
duration, the frequency of migraine attacks or the time since the last attack.
These results are discussed in the context of visually induced migraine, proposed
causes of abnormal cortical function in migraine and the prospects for developing
clinically useful tests of visual function.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 11304022 [PubMed - indexed for MEDLINE]

3328: Pharmacoeconomics. 2001;19(3):231-44.

Workplace productivity. A review of the impact of migraine and its treatment.

Stang P, Cady R, Batenhorst A, Hoffman L.

Galt Associates, Inc., Sterling, Virginia, USA.

Migraine is a common disorder characterised by recurrent episodes of disability. 
Despite the high prevalence of migraine, data have been lacking on its impact in 
a working population. The advent of new therapies has stimulated interest in this
area, and evidence is now available that documents the substantial impact of
migraine on workplace productivity and the likelihood of untreated migraine
leading to unemployment or underemployment for the patient. This paper reviews
current findings of both observational and interventional studies about the
impact of migraine on productivity and employment. When considered in the light
of migraine demographics, the high prevalence of migraine, and its low
consultation and treatment rates, this evidence indicates that improved screening
and treatment for this common condition could have a substantial impact on worker
productivity and on patient well-being.

Publication Types: 
    Review

PMID: 11303412 [PubMed - indexed for MEDLINE]

3329: Microsc Res Tech. 2001 May 1;53(3):193-211.

Functional immunohistochemistry of neuropeptides and nitric oxide synthase in the
nerve fibers of the supratentorial dura mater in an experimental migraine model.

Knyihár-Csillik E, Tajti J, Chadaide Z, Csillik B, Vécsei L.

Department of Neurology, Albert Szent-Györgyi Medical and Pharmaceutical Center, 
University of Szeged, H-6701 Szeged, Hungary. knyihar@nepsy.szote.u-szeged.hu

The supratentorial cerebral dura of the albino rat is equipped with a rich
sensory innervation both in the connective tissue and around blood vessels, which
includes nociceptive axons and their terminals; these display intense calcitonin 
gene-related peptide (CGRP) immunoreactivity. Stereotactic electrical stimulation
of the trigeminal (Gasserian) ganglion, regarded as an experimental migraine
model, caused marked increase and disintegration of club-like perivascular
CGRP-immunopositive nerve endings in the dura mater and induced an apparent
increase in the lengths of CGRP-immunoreactive axons. Intravenous administration 
of sumatriptan or eletriptan, prior to electrical stimulation, prevented
disintegration of perivascular terminals and induced accumulation of CGRP in
terminal and preterminal portions of peripheral sensory axons. Consequently,
immunopositive terminals and varicosities increased in size; accumulation of
axoplasmic organelles resulted in the "hollow" appearence of numerous
varicosities. Since triptans exert their anti-migraine effect by virtue of
agonist action on 5-HT(1D/B) receptors, we suggest that these drugs prevent the
release of CGRP from perivascular nerve terminals in the dura mater by an action 
at 5-HT(1D/B) receptors. Nitroglycerine (NitroPOHL), given subcutaneously to
rats, induces increased beading of nitric oxide synthase (NOS)-immunoreactive
nerve fibers in the supratentorial cerebral dura mater, and an apparent increase 
in the number of NOS-immunoreactive nerve fibers in the dural areas supplied by
the anterior and middle meningeal arteries, and the sinus sagittalis superior.
Structural alterations of nitroxidergic axons innervating blood vessels of the
dura mater support the idea that nitric oxide (NO) is involved in the induction
of headache, a well-known side effect of coronary dilator agents. Copyright 2001 
Wiley-Liss, Inc.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 11301495 [PubMed - indexed for MEDLINE]

3330: Microsc Res Tech. 2001 May 1;53(3):179-87.

Neuroimaging in headache.

Goadsby PJ.

Institute of Neurology, The National Hospital for Neurology and Neurosurgery,
Queen Square, London WC1N 3BG, United Kingdom. peterg@ion.ucl.ac.uk

Neuroimaging of primary headache syndromes, such as cluster headache and
migraine, has begun to provide a glimpse of the neuroanatomical and physiological
basis of the conditions. Although these headache types have been widely described
as vascular, there is now considerable imaging and clinical evidence to suggest
that they are primarily driven from the brain. The shared anatomical and
physiological substrate for both of these clinical problems is the neural
innervation of the cranial circulation. Functional imaging with positron emission
tomography (PET) has shed light on the genesis of both syndromes, documenting
activation in the midbrain and pons in migraine, and in the hypothalamic grey in 
cluster headache. These areas are involved not simply as a response to first
division nociceptive pain impulses but specifically in each syndrome, probably in
some permissive or dysfunctional role. In a recent PET study in cluster headache,
as well as brain activation, tracer pooled in the region of the major basal
arteries. This is likely to be due to vasodilatation of these vessels during the 
acute pain-attack and represents the first convincing activation of neural
vasodilator mechanisms in humans. The author takes the view that the known
physiology and pathophysiology of the systems involved dictate that these
disorders should be collectively regarded as neurovascular headaches to place
emphasis on the interaction between nerves and vessels, which is the underlying
characteristic of these syndromes. Understanding this neurovascular relationship 
facilitates an understanding of the pain mechanisms, while characterising the CNS
dysfunction will ultimately allow us to dissect out the basic pathogenesis of
these disorders. Copyright 2001 Wiley-Liss, Inc.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 11301493 [PubMed - indexed for MEDLINE]

3331: Microsc Res Tech. 2001 May 1;53(3):167-78.

Neurogenic inflammation in the context of migraine.

Williamson DJ, Hargreaves RJ.

Whole Animal Pharmacology, Department of Pharmacology, Merck Sharp and Dohme
Neuroscience Research Centre, Terlings Park, Harlow, Essex, United Kingdom.
david_williamson@merck.com

Despite considerable research into the pathogenesis of idiopathic headaches, such
as migraine, the pathophysiological mechanisms underlying them remain poorly
understood. Although it is well established that the trigeminal nerve becomes
activated during migraine, the consequences of this activation remain
controversial. One theory, based on preclinical observations, is that activation 
of trigeminal sensory fibers leads to a painful neurogenic inflammation within
the meningeal (dural) vasculature mediated by neuropeptide release from
trigeminal sensory fibres and characterized by plasma protein extravasation,
vasodilation, and mast cell degranulation. Effective antimigraine agents such as 
ergots, triptans, opioids, and valproate inhibit preclinical neurogenic dural
extravasation, suggesting that this activity may be a predictor of potential
clinical efficacy of novel agents. However, several clinical trials with other
agents that inhibit this process preclinically have failed to show efficacy in
the acute treatment of migraine in man. Alternatively, it has been proposed that 
painful neurogenic vasodilation of meningeal blood vessels could be a key
component of the inflammatory process during migraine headache. This view is
supported by the observation that jugular plasma levels of the potent
vasodilator, calcitonin gene-related peptide (CGRP) are elevated during the
headache and normalized by successful sumatriptan treatment. Preclinically,
activation of trigeminal sensory fibers evokes a CGRP-mediated neurogenic dural
vasodilation, which is blocked by dihydroergotamine, triptans, and opioids but
unaffected by NK1 receptor antagonists that failed in clinical trials. These
observations suggest that CGRP release with associated neurogenic dural
vasodilation may be important in the generation of migraine pain, a theory that
would ultimately be tested by the clinical testing of a CGRP receptor antagonist.
Copyright 2001 Wiley-Liss, Inc.

Publication Types: 
    Review

PMID: 11301492 [PubMed - indexed for MEDLINE]

3332: Arq Neuropsiquiatr. 2001 Mar;59(1):46-9.

Oral lysine clonixinate in the acute treatment of migraine: a double-blind
placebo-controlled study.

Krymchantowski AV, Barbosa JS, Cheim C, Alves LA.

Headache Center of Rio, Rio de Janeiro, Brazil.

Several oral nonsteroidal anti-inflammatory drugs (NSAIDs) are effective to treat
migraine attacks. Lysine clonixinate (LC) is a NSAID derived from nicotinic acid 
that has proven to be effective in various pain syndromes such as renal colic and
muscular pain. The aim of this double-blind, placebo-controlled study was to
evaluate the efficacy of oral LC compared to placebo in the acute treatment of
migraine. Sixty four patients with the diagnosis of migraine, according to the
IHS criteria, were studied prospectively. Patients received LC or placebo once
the headache reached moderate or severe intensity for 6 consecutive attacks. With
regard to the moderate attacks, LC was superior than placebo after 1, 2 and 4
hours. The consumption of other rescue medications after 4 hours was
significantly higher in the placebo group. With regard to the severe attacks,
there was no difference between the active drug group and the placebo group
concerning headache intensity and consumption of other rescue medications. We
conclude that the NSAID lysine clonixinate is effective in treating moderately
severe migraine attacks. It is not superior than placebo in treating severe
migraine attacks.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial

PMID: 11299430 [PubMed - indexed for MEDLINE]

3333: Cephalalgia. 2001 Feb;21(1):66-70.

Cyclandelate in the prophylaxis of migraine: a placebo-controlled study.

Diener HC, Krupp P, Schmitt T, Steitz G, Milde K, Freytag S.

Department of Neurology, University of Essen, Germany. h.diener@uni-essen.de

The prophylactic action of cyclandelate was investigated in a multicentre,
randomized, placebo-controlled, parallel group study. A 4-week baseline period
was followed by a 4-week placebo phase and a 16-week treatment period with either
1600 mg cyclandelate or placebo. Patients (n = 251) with two to six migraine
attacks/month were randomized. Neither the primary study endpoint (reduction of
migraine days from baseline to the last 28 days) nor most of the secondary
endpoints (reduction in the number of migraine attacks, severity or duration of
attacks, frequency of autonomic disturbances, medication for treatment of
attacks) showed a difference between cyclandelate and placebo. Cyclandelate,
however, was superior to placebo in a global impression of efficacy rated by the 
patients and the treating physicians. Both treatments were well tolerated. In
conclusion, cyclandelate was not superior to placebo in the prophylaxis of
migraine with regard to parameters usually used in migraine prophylaxis trials.

Publication Types: 
    Clinical Trial
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 11298666 [PubMed - indexed for MEDLINE]

3334: Cephalalgia. 2001 Feb;21(1):61-5.

Lack of pharmacokinetic interaction between the antimigraine compound,
almotriptan, and propranolol in healthy volunteers.

Fleishaker JC, Sisson TA, Carel BJ, Azie NE.

Clinical Pharmacology Unit, Pharmacia & Upjohn, Inc., Kalamazoo, MI 49007, USA.

This study was designed to assess the pharmacokinetics of almotriptan, a
5-HT1B/1D agonist, when administered in the presence and absence of propranolol. 
Healthy male (n = 10) and female (n = 2) volunteers received (i) 80 mg
propranolol twice daily for 7 days and 12.5 mg almotriptan on day 7, and (ii)
12.5 mg almotriptan on day 7, according to a two-way crossover design. Plasma and
urinary almotriptan concentrations were measured by high performance liquid
chromatography (HPLC) methods. Treatment effects on pharmacokinetic parameters
were assessed by analysis of variance (ANOVA). Statistically significant
differences between treatments in area under the curve (AUC), clearance, and
half-life were observed (P < 0.03), but these differences were < 7%. Ninety
percent confidence interval analysis of log-transformed pharmacokinetic
parameters showed that the treatments were equivalent. Adverse events were mild
to moderate in intensity, and no treatment effects on vital signs were observed. 
The results show that propranolol has no effect on the pharmacokinetics of
almotriptan. Concomitant administration of the two drugs is well tolerated.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial

PMID: 11298665 [PubMed - indexed for MEDLINE]

3335: Cephalalgia. 2001 Feb;21(1):46-52.

Investigations into migraine pathogenesis: time course for effects of m-CPP,
BW723C86 or glyceryl trinitrate on appearance of Fos-like immunoreactivity in rat
trigeminal nucleus caudalis (TNC).

Martin RS, Martin GR.

Neurobiology Unit, Roche Bioscience, Palo Alto, CA 94304, USA.
renee.martin@roche.com

Clinical and preclinical studies suggest that 5-HT and nitric oxide (NO)
mobilization within the trigeminovascular system is fundamental to the initiation
of migraine attacks., e.g. m-chlorophenylpiperazine (m-CPP) and glyceryl
trinitrate (GTN) induce headache in humans. 5-HT2B receptors are known to mediate
NO-dependent vasorelaxation in peripheral blood vessels, raising the possibility 
that this receptor is implicated in the pathogenesis of the disease. Therefore,
we measured the effects of 5-HT2B agonists (m-CPP or BW723C86) or GTN on
trigeminal nerves by quantifying Fos expression in the rat TNC. m-CPP (0.1 mg/kg,
i.v.) induced time-dependent elevations in Fos-LI in the rat TNC 2 h and 8 h
after injection. In contrast, neither intravenous GTN (0.5 microg/kg per min,
infused 20 min) nor BW723C86 (0.1 mg/kg, i.v.) increased Fos-LI at 2 h or 8 h
after administration. These data are not consistent with the involvement of the
5-HT2B/2C receptors or NO in trigeminovascular activation, and by inference
migraine, and suggest the contribution of some other unidentified pathway.

PMID: 11298663 [PubMed - indexed for MEDLINE]

3336: Cephalalgia. 2001 Feb;21(1):38-45.

Hypofunctionality of Gi proteins as aetiopathogenic mechanism for migraine and
cluster headache.

Galeotti N, Ghelardini C, Zoppi M, Del Bene E, Raimondi L, Beneforti E, Bartolini
A.

Department of Pharmacology, University of Florence, Italy.

The involvement of Gi proteins in the modulation of pain perception has been
widely established, and mutations in G-proteins have already been identified as
the aetiopathological cause of human diseases. The aim of the present study was
to determine whether a deficiency or a hypofunctionality of the Gi proteins
occurred in primary headache. The functionality and the level of expression of Gi
proteins were investigated in lymphocytes from migraine without aura, migraine
with aura and cluster headache sufferers. A reduced capability to inhibit
forskolin-stimulated adenylyl cyclase activity in headache patients was observed.
Migraine patients also showed basal adenosine cAMP levels about four times higher
than controls. The reduced activity of Gi proteins seems not to be related to a
reduction of protein levels since no significant reduction of the Gialpha
subunits was observed. These results indicate Gi protein hypofunctionality as an 
aetiopathogenic mechanism in migraine and cluster headache.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 11298662 [PubMed - indexed for MEDLINE]

3337: Cephalalgia. 2001 Feb;21(1):31-7.

Polysomnographic findings in nights preceding a migraine attack.

Göder R, Fritzer G, Kapsokalyvas A, Kropp P, Niederberger U, Strenge H, Gerber
WD, Aldenhoff JB.

Department of Psychiatry and Psychotherapy and Institute of Medical Psychology,
Christian-Albrechts-University of Kiel, Germany. rgoeder@psychiatry.uni-kiel.de

Sleep recordings were performed in eight patients to analyse sleep alterations
preceding migraine attacks. Polysomnographic recordings from nights before an
attack were compared with nights without following migraine. We analysed standard
sleep parameters and electroencephalogram (EEG) power spectra. The main findings 
preceding migraine attacks were a significant decrease in the number of arousals,
a decrease in rapid eye movement (REM) density, a significant decrease of beta
power in the slow wave sleep, and a decrease of alpha power during the first REM 
period. The results suggest a decrease in cortical activation during sleep
preceding migraine attacks. According to the models of sleep regulation,
alterations in the function of aminergic or cholinergic brainstem nuclei have to 
be discussed.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 11298661 [PubMed - indexed for MEDLINE]

3338: Cephalalgia. 2001 Feb;21(1):12-9.

Sumatriptan: economic evidence for its use in the treatment of migraine, the
Canadian comparative economic analysis.

Caro G, Getsios D, Caro JJ, Raggio G, Burrows M, Black L.

Caro Research, Montreal, QC, Canada.

The objective of this study was to evaluate economic and health effects of
sumatriptan relative to customary therapy in Canada. The relationship between
treatment and functionality was established based on analysis of existing data
from a multinational study. A Monte Carlo model was developed to simulate 1 year 
for each of customary therapy and six sumatriptan formulations. Costs are
expressed in 1998 Canadian dollars. Sumatriptan is expected to reduce the time
spent with migraine symptoms and resulting time lost. Under customary therapy,
the annual cost of lost time is estimated at pound908 ($1973). With sumatriptan, 
these costs ranged from pound406 ($882) with subcutaneous sumatriptan to pound577
($1254) with nasal sumatriptan 10 mg, saving pound331-502 ($719-1091) in the
annual cost of time lost. All these benefits are expected to be obtained at an
additional drug cost ranging from pound869 ($1889) for subcutaneous sumatriptan
to pound278 ($605) for sumatriptan suppository. The cost of sumatriptan treatment
is significantly offset by a substantial reduction of costs associated with time 
lost due to migraine symptoms.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 11298658 [PubMed - indexed for MEDLINE]

3339: Neurology. 2001;56(6 Suppl 1):S35-42.

The role of headache-related disability in migraine management: implications for 
headache treatment guidelines.

Lipton RB, Silberstein SD.

Departments of Neurology, and Epidemiology and Social Medicine, the Albert
Einstein College of Medicine, New York, NY, USA. rlipton@imrinc.com

Recently published US Headache Consortium Guidelines recommend a process of
diagnosis, patient education, and individualized treatment for the management of 
migraine. Clinicians are advised to base their treatment choice on attack
frequency and duration, degree of disability, non-headache symptoms, patient
preference, and prior history of treatment response, using a stratified approach 
to care. In stratified care, initial treatment is individualized based on an
assessment of the patients' medical needs. One approach to stratification uses
the Migraine Disability Assessment (MIDAS) Questionnaire to stratify patients
into groups with different treatment needs based on the degree of
headache-related disability. Stratified care was developed as an alternative to
step-care approaches, which begin patients on nonspecific medication with gradual
escalation until they obtain effective relief. Results from the Disability in
Strategies for Care (DISC) study indicate that stratified care provides superior 
outcomes compared to step-care and that the approach is cost-effective,
supporting the US Headache Consortium GUIDELINES: Stratified care may become the 
approach of choice for managing migraine in clinical practice. This approach
increases the chances of providing appropriate therapy at the patient's initial
consultation, sparing the patient a series of failed therapeutic efforts. The
MIDAS Questionnaire provides a practical tool for helping to implement the
recommendations of the US Headache Consortium GUIDELINES:

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 11294958 [PubMed - indexed for MEDLINE]

3340: Neurology. 2001;56(6 Suppl 1):S29-34.

Potential of the Migraine Disability Assessment (MIDAS) Questionnaire as a public
health initiative and in clinical practice.

Edmeads J, Láinez JM, Brandes JL, Schoenen J, Freitag F.

Department of Medicine, University of Toronto, Ontario, Canada.
John.Edmeads@swchsc.on.ca

Migraine is not always well managed in clinical practice, often being
under-diagnosed and under-treated. As a result, many sufferers never consult a
physician or lapse from care after physician contact. Although most migraine care
is provided by general practitioners, others, including specialists, emergency
room physicians, pharmacists, and alternative practitioners, may also be
involved. A method of standardizing clinical information about migraine is
essential for coordinated, logical, and systematic care. The impact of migraine
on the patient is an important clinical parameter but one that is seldom inquired
about, perhaps because it exhibits such marked variability among and within
individuals. Headache-related disability can be an objective and measurable index
of this impact. The Migraine Disability Assessment (MIDAS) Questionnaire is a
simple and validated instrument with potential for use in clinical practice,
research, and public health. It can improve communication between patients and
health-care professionals regarding the impact of migraine which, in turn, allows
tailoring of the intensity of treatment to the severity of the illness. Changes
in the MIDAS score may serve as an end point in assessing treatment efficacy. In 
populations, MIDAS scores may indicate the burden of migraine in the community
and spark public health initiatives to improve management.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 11294957 [PubMed - indexed for MEDLINE]

3341: Neurology. 2001;56(6 Suppl 1):S20-8.

Development and testing of the Migraine Disability Assessment (MIDAS)
Questionnaire to assess headache-related disability.

Stewart WF, Lipton RB, Dowson AJ, Sawyer J.

Johns Hopkins School of Public Health, Baltimore, MD, USA.

The MIDAS Questionnaire was developed to assess headache-related disability with 
the aim of improving migraine care. Headache sufferers answer five questions,
scoring the number of days, in the past 3 months, of activity limitations due to 
migraine. The internal consistency, test-retest reliability, and validity
(accuracy) of the questionnaire were assessed in separate population-based
studies of migraine sufferers. In addition, the face validity, ease of use, and
clinical utility of the questionnaire were evaluated in a group of 49 physicians 
who independently rated disease severity and need for care in a diverse sample of
migraine case histories. The test-retest Pearson correlation coefficient for the 
total MIDAS score was approximately 0.8. The MIDAS score was valid when compared 
with a reference diary-based measure of disability; the overall correlation
between MIDAS and the diary-based measure was 0.63. The MIDAS score was also
correlated with physicians' assessments of need for medical care (r = 0.69). From
studies completed to date, the MIDAS Questionnaire has been shown to be
internally consistent, highly reliable, valid, and correlates with physicians'
clinical judgment. These features support its suitability for use in clinical
practice. Use of the MIDAS Questionnaire may improve physician-patient
communication about headache-related disability and may favorably influence
health-care delivery for migraine patients.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 11294956 [PubMed - indexed for MEDLINE]

3342: Neurology. 2001;56(6 Suppl 1):S13-9.

Migraine-related disability: impact and implications for sufferers' lives and
clinical issues.

Holmes WF, MacGregor EA, Dodick D.

Sherrington Park Medical Practice, Nottingham, UK. Holmes@mail.com

Migraine is a common, debilitating disorder that imposes a large personal burden 
on sufferers and high economic costs on society. Sufferers have a significant
level of migraine-related disability in all aspects of their daily lives,
including employment, household work, and non-work activities. Despite this
burden of illness, physicians often do not diagnose or treat the illness
effectively. Physicians consider that specific treatment is necessary when
disability information is known but, until recently, no criteria have been
available for assessment of migraine severity. Two studies indicate that
information on disability is an important criterion in assessing migraine
severity and influences physicians in their judgments of illness severity and
treatment needs. However, physicians and patients often do not seek or share
migraine-associated disability, which may contribute to suboptimal management.
Efforts to improve knowledge of headache-related disability in the consultation
have the potential to improve migraine management. An assessment tool that could 
reliably quantify headache-related disability has the potential for grading
migraine severity and improving care.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 11294955 [PubMed - indexed for MEDLINE]

3343: Neurology. 2001;56(6 Suppl 1):S4-12.

The impact of migraine: Epidemiology, risk factors, and co-morbidities.

Breslau N, Rasmussen BK.

Department of Psychiatry, Henry Ford Hospital, Detroit, Michigan 48202, USA.

In Western countries, recent community-based studies of migraine prevalence using
standardized diagnostic criteria give 1-year prevalence estimates of around 10 to
12%. The prevalence of migraine is age- and gender-dependent. Age at onset of
migraine is earlier in boys than in girls. Migraine is two to three times more
common in women than in men, with peak prevalence occurring during mid-life in
both sexes. Current evidence also indicates that migraine prevalence is higher in
Caucasians than in Africans or Asians. In some migraineurs, attacks may be
frequent or prolonged, leading to considerable pain and disability. There has
been much debate over predisposing factors, which are not sufficient by
themselves to cause an attack, as well as precipitants, which immediately precede
the attack. However, convincing data are lacking for most of these. Significant
associations have been reported between migraine and certain psychiatric
disorders, epilepsy, and stroke in women under the age of 45. These findings
demonstrate that migraine is common, has a substantial impact on sufferers, and
may be associated with other disorders.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 11294954 [PubMed - indexed for MEDLINE]

3344: Lancet. 2001 Mar 31;357(9261):1016-7.

Brainstem activation specific to migraine headache.

Bahra A, Matharu MS, Buchel C, Frackowiak RS, Goadsby PJ.

Findings from functional imaging studies have shown activation of the brainstem
during migraine without aura (MWOA) and activation of the hypothalamus during
cluster headache. We assessed a patient with cluster headache and migraine by
positron emission tomography during an active cluster headache after he had taken
1.2 glyceryl trinitate. The patient developed a typical MWOA, during which we saw
activation in the dorsal rostral brainstem. There was no activation in the region
of the hypothalamus. Our findings provide evidence that migraine involves the
brainstem, and show several areas involved in cluster headaches. Our data show
the potential for objective distinction between primary headache syndromes with
functional imaging, in disorders hitherto distinguished on clinical grounds.

Publication Types: 
    Case Reports
    Letter

PMID: 11293599 [PubMed - indexed for MEDLINE]

3345: Clin Ther. 2001 Feb;23(2):284-91.

Economic implications of early treatment of migraine with sumatriptan tablets.

Cady RK, Sheftell F, Lipton RB, Kwong WJ, O'Quinn S.

Headache Care Center, Springfield, Missouri, USA.

BACKGROUND: Early treatment of migraine with sumatriptan 50 mg and 100 mg, while 
pain is mild, has been reported to enhance pain-free response 2 hours and 4 hours
postdose and sustained pain-free response 2 to 24 hours postdose compared with
treatment when pain has become moderate to severe. Early treatment with
sumatriptan 50 mg and 100 mg also resulted in less redosing, which translated to 
a reduction in the mean number of doses used per migraine episode. OBJECTIVE: We 
examined the economic implications of early treatment with sumatriptan 50 mg and 
100 mg while pain is mild versus treatment when pain has become moderate to
severe. METHODS: Using data from retrospective analyses of a dose-ranging
clinical trial of sumatriptan (protocol S2CM09) involving 1003 patients, we
estimated the mean cost per treatment success for a hypothetical population of
1000 migraine patients who received treatment with sumatriptan 50-mg or 100-mg
tablets early while pain was mild versus treatment when pain had become moderate 
to severe. RESULTS: With a conservative estimate of migraine frequency of 1.5
episodes per month, the total cost of early migraine treatment with sumatriptan
50 mg and 100 mg was reduced by $31.68 and $20.16, respectively, per patient per 
year. The average cost per pain-free treatment success was reduced by 32% to 57% 
with sumatriptan 50 mg and 100 mg if migraines were treated while pain was mild
in intensity versus when pain had become moderate to severe. CONCLUSIONS:
Treatment of migraine with sumatriptan 50-mg and 100-mg tablets is effective
regardless of whether pain is mild, moderate, or severe. However, initiating
treatment while pain is mild may be more cost-effective than delaying treatment
until pain has become moderate to severe.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 11293561 [PubMed - indexed for MEDLINE]

3346: Clin Ther. 2001 Feb;23(2):260-71.

Efficacy, tolerability, and patient satisfaction with 50- and 100-mg sumatriptan 
tablets in those initially dissatisfied with the efficacy of 50-mg sumatriptan
tablets.

Savani N, Pfaffenrath V, Rice L, Boswell D, Black L, Jones M; Sumatriptan
SUMB4007 Study Group.

Colne House Surgery, Hertfordshire, United Kingdom.

BACKGROUND: Both 50- and 100-mg sumatriptan tablets are effective and well
tolerated in the acute treatment of migraine. However, given a choice between the
2 doses, many patients in clinical practice and clinical studies prefer the
100-mg dose. OBJECTIVE: This study was designed to assess whether patients
initially dissatisfied with the efficacy of 50-mg sumatriptan tablets would be
satisfied with 100-mg sumatriptan tablets. METHODS: In phase 1 of the study,
triptan-naive patients with migraine (International Headache Society diagnosis)
received open-label treatment of 3 migraine attacks with 50-mg sumatriptan
tablets. At the end of phase 1, those who were dissatisfied with the efficacy but
satisfied with the tolerability of 50-mg sumatriptan tablets entered phase 2 and 
were randomized in a double-blind, parallel-group fashion to receive either 50-
or 100-mg sumatriptan tablets for the treatment of 3 attacks. Patients who were
satisfied with the efficacy or dissatisfied with the tolerability of the 50-mg
tablets in phase 1 were given the option of continuing open-label treatment with 
50-mg sumatriptan tablets in phase 2. The primary end point was the percentage of
patients satisfied with medication at the end of phase 2 double-blind treatment. 
Patient satisfaction with specific medication attributes was assessed using the
Patient Perception of Migraine Questionnaire. RESULTS: Seven hundred twenty-two
patients were enrolled in phase 1 of the study (the intent-to-treat population), 
609 of whom had evaluable satisfaction data at the end of open-label treatment.
Three hundred twenty-six (54%) of these patients were satisfied with 50-mg
sumatriptan tablets, whereas 283 (46%) were not satisfied. Among those who were
dissatisfied, lack of efficacy was cited as the sole reason for dissatisfaction
by 242 (86%). Two hundred thirty-one of those who were dissatisfied with efficacy
only and wished to continue the study were randomized to double-blind treatment
with either 50-mg sumatriptan tablets (n = 123; 82% female, 18% male; mean age,
37.6 years) or 100-mg sumatriptan tablets (n = 108; 86% female, 14% male; mean
age, 36.0 years). The remaining 310 patients elected to continue open-label
treatment with 50-mg sumatriptan tablets. At the end of double-blind treatment,
64 of 101 patients (63%) in the 100-mg group indicated that they were satisfied
with treatment, compared with 55 of 113 (49%) in the 50-mg group (P = 0.031).
Across the 3 attacks treated in the double-blind phase. headache relief 2 hours
postdose was reported by 47% to 53% of patients in the 50-mg group and 45% to 60%
of patients in the 100-mg group. The overall incidence of patients reporting > or
=1 adverse event was 19% (23/123) in the 50-mg group and 22% (24/108) in the
100-mg group. CONCLUSIONS: For most patients, 50 mg is the appropriate starting
dose of sumatriptan tablets. In patients who experience inadequate relief with 50
mg, increasing the dose to 100 mg is an appropriate therapeutic option.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 11293559 [PubMed - indexed for MEDLINE]

3347: Clin Ther. 2001 Feb;23(2):242-51.

Effect of encapsulation on absorption of sumatriptan tablets: data from healthy
volunteers and patients during a migraine.

Fuseau E, Petricoul O, Sabin A, Pereira A, O'Quinn S, Thein S, Leibowitz M,
Purdon H, McNeal S, Salonen R, Metz A, Coates P.

EMF Consulting France, Siret, France.

BACKGROUND: Some comparative trials of selective serotonin 1B/ID-agonists in
migraine have reported -15% lower efficacy for sumatriptan tablets than that
reported in placebo-controlled trials. OBJECTIVE: This study was designed to test
the hypothesis that the encapsulation methods used to mask active drug may delay 
absorption of sumatriptan from dosing to 2 hours after dosing (the traditional
end point in clinical trials of migraine treatment), an effect that may be
enhanced by migraine-associated gastric stasis. METHODS: Two randomized,
open-label, 2-way crossover trials were conducted to evaluate the absorption and 
bioequivalence of conventional 50-mg sumatriptan tablets and encapsulated 50-mg
sumatriptan tablets in supine, fasted, healthy volunteers (Glaxo Wellcome
protocol SUM40270) and supine patients experiencing a migraine (Glaxo Wellcome
protocol SUM40268). Absorption was assessed by calculating the area under the
plasma concentration-time curve from dosing to 2 hours after dosing (AUC2) and
the times to first measurable plasma concentration, 10 ng/mL, 20 ng/mL, and
maximum plasma concentration. Data for the AUC from time zero to infinity and
maximum plasma concentration were used to assess standard bioequivalence, which
is considered to occur when the 90% CIs for the geometric mean treatment ratios
(test/reference) fall between 0.8 and 1.25. RESULTS: Study 1 included 26 healthy 
subjects (73% men, 27% women; mean age, 39.1 years), and study 2 included 30
patients with migraine (67% women, 33% men; mean age, 42.7 years). Sumatriptan
absorption was delayed with the encapsulated tablet compared with the
conventional tablet 0 to 2 hours after dosing, particularly during a migraine.
AUC2 values with encapsulated sumatriptan compared with the conventional tablet
were 21% lower in healthy volunteers (ratio of capsule/tablet, 0.79; 90% CI,
0.588-1.050) and 27% lower in patients experiencing a migraine (ratio of
capsule/tablet, 0.73; 90% CI, 0.519-1.023). Standard bioequivalence was
demonstrated in both healthy volunteers and patients experiencing a migraine.
CONCLUSIONS: Encapsulation delayed absorption of sumatriptan 0 to 2 hours after
dosing, particularly during a migraine. This delay in absorption of the
encapsulated form may account for the lower efficacy of sumatriptan in some
comparative studies.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial

PMID: 11293557 [PubMed - indexed for MEDLINE]

3348: J Child Neurol. 2001 Feb;16(2):71-8.

Preventive therapy in pediatric migraine.

Wasiewski WW.

Mayday Pediatric Headache Center, Lancaster, PA 17601, USA. wwwasiew@lha.org

Preventive therapy for migraine headache includes identification of migraine
precipitants, possible adjustments in lifestyle, appropriate management of acute 
headache, and, when necessary, the use of pharmacologic agents. There are no
well-controlled clinical trials with sufficient patient numbers to support the
use of any agent in the prevention of migraine headache in children. Data on the 
use of amitriptyline and divalproex sodium in open-label studies suggest that
these agents may be efficacious. The mechanism of action for these agents is
unknown but may be related to the 5-hydroxytyptamine-2 (5-HT2) receptor
antagonism or regulation of ion channels. A review of the pertinent literature on
migraine prophylaxis in children is presented. Dosing guidelines are presented
based on the limited data available and clinical experience.

Publication Types: 
    Review

PMID: 11292228 [PubMed - indexed for MEDLINE]

3349: Proc Natl Acad Sci U S A. 2001 Apr 10;98(8):4687-92. Epub 2001 Apr 3.

Mechanisms of migraine aura revealed by functional MRI in human visual cortex.

Hadjikhani N, Sanchez Del Rio M, Wu O, Schwartz D, Bakker D, Fischl B, Kwong KK, 
Cutrer FM, Rosen BR, Tootell RB, Sorensen AG, Moskowitz MA.

Nuclear Magnetic Resonance Center and Stroke and Neurovascular Laboratory,
Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129,
USA.

Cortical spreading depression (CSD) has been suggested to underlie migraine
visual aura. However, it has been challenging to test this hypothesis in human
cerebral cortex. Using high-field functional MRI with near-continuous recording
during visual aura in three subjects, we observed blood oxygenation
level-dependent (BOLD) signal changes that demonstrated at least eight
characteristics of CSD, time-locked to percept/onset of the aura. Initially, a
focal increase in BOLD signal (possibly reflecting vasodilation), developed
within extrastriate cortex (area V3A). This BOLD change progressed contiguously
and slowly (3.5 +/- 1.1 mm/min) over occipital cortex, congruent with the
retinotopy of the visual percept. Following the same retinotopic progression, the
BOLD signal then diminished (possibly reflecting vasoconstriction after the
initial vasodilation), as did the BOLD response to visual activation. During
periods with no visual stimulation, but while the subject was experiencing
scintillations, BOLD signal followed the retinotopic progression of the visual
percept. These data strongly suggest that an electrophysiological event such as
CSD generates the aura in human visual cortex.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 11287655 [PubMed - indexed for MEDLINE]

3350: Neurol Sci. 2000 Oct;21(5):272-8.

Efficacy and tolerability of sumatriptan in the treatment of multiple migraine
attacks.

Bussone G, Manzoni GC, Cortelli P, Roncolato M, Fabbri L, Benassuti C.

C. Besta National Neurological Institute, Milan, Italy.

This cross-over, double blind, randomized, multicentre study evaluated the
consistency of efficacy and safety of oral sumatriptan in 233 migraneurs. The
patients received 50 mg oral sumatriptan or placebo for the treatment of 12
migraine attacks. Within each group of 4 attacks, three were treated with
sumatriptan and one with placebo, according to a randomization list. Over all the
attacks, the efficacy rate was statistically significant for sumatriptan against 
placebo at 2 or 4 hours (2 hours: sumatriptan 60%, PLO 38%, p < 0.001; 4 hours
sumatriptan 79%, PLO 47%, p < 0.001). Oral sumatriptan was similarly effective at
relieving the associated symptoms and at reducing clinical disability in most
attacks. The incidence of adverse events did not differ between treatment groups.
All the events recorded were mild to moderate as intensity and resolved
spontaneously.

Publication Types: 
    Clinical Trial
    Multicenter Study
    Randomized Controlled Trial

PMID: 11286039 [PubMed - indexed for MEDLINE]

3351: Pharmacoeconomics. 2001;19(2):197-206.

The multinational impact of migraine symptoms on healthcare utilisation and work 
loss.

Gerth WC, Carides GW, Dasbach EJ, Visser WH, Santanello NC.

Merck & Co., Inc., Whitehouse Station, New Jersey, USA. william_gerth@merck.com

OBJECTIVE: To compare self-reported healthcare resource utilisation, paid work
loss, unpaid work loss and loss of effectiveness at work due to migraine in a
clinic-based adult migraine population. METHODS: The Migraine Background
Questionnaire (MBQ) was translated and pilot-tested for use in 25 countries. The 
questionnaire was then self-administered by patients at a screening visit for 3
phase III clinical trials of rizatriptan [a selective serotonin
(5-hydroxytryptamine) 5-HT1B/1D receptor agonist] in 23 US and 78 non-US sites.
PARTICIPANTS: Persons 18 to 65 years of age with at least a 6-month history of
moderate to severe migraines prior to the screening visit were surveyed. RESULTS:
A total of 2670 persons (54.7% Europe, 16.5% Latin America, 23.1% North America, 
5.5% other countries) completed the MBQ and had responses which could be
analysed. On average, each patient reported 2.78 doctor visits, 0.53 emergency
room visits and 0.06 hospitalisations related to migraine per year. Patients
self-reported being only 46% effective while on the job with migraine symptoms.
Extrapolation of patient self-reported work and productivity loss for the last 4 
weeks to an annual basis suggested that clinic-based patients with migraine lose 
19.5 workday equivalents (8.3 days due to absenteeism, 11.2 days due to reduced
workday equivalents) due to migraine per year. In the US, the annual employer
cost of this total migraine-related work loss is estimated to be $US3309 (2000
values) per patient with migraine. The levels of self-reported healthcare
resources utilised for migraine and work loss were generally consistent across
geographic regions. CONCLUSIONS: The impact of migraine symptoms on healthcare
resource utilisation and work loss was similar across most measures in Europe,
Latin America, North America and other countries. Total migraine-related work
loss due to absenteeism and reduced workday equivalents accounts for most of the 
economic burden of migraine, regardless of country, in a clinic-based migraine
population.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 11284383 [PubMed - indexed for MEDLINE]

3352: Acad Emerg Med. 2001 Apr;8(4):337-42.

Intranasal lidocaine for the treatment of migraine headache: a randomized,
controlled trial.

Blanda M, Rench T, Gerson LW, Weigand JV.

Department of Emergency Medicine, Northeastern Ohio Universities College of
Medicine, Summa Health System, Akron, OH 44304, USA.

OBJECTIVE: To evaluate the effect of intranasal lidocaine for immediate relief (5
minutes) of migraine headache pain. METHODS: A randomized, double-blind,
placebo-controlled clinical trial at two university-affiliated community teaching
hospitals enrolled patients 18-50 years old with migraine headache as defined by 
the International Headache Society. Patients who were pregnant, lactating, known 
to abuse alcohol or drugs, or allergic to one of the study drugs, those who used 
analgesics within two hours, or those with a first headache were excluded.
Statistical significance was assessed by using chi-square or Fisher's exact test 
for categorical variables and Student's t-test for continuous variables. Patients
rated their pain on a 10-centimeter visual analog scale (VAS) prior to drug
administration and at 5, 10, 15, 20, and 30 minutes after the initial dose.
Medication was either 1 mL of 4% lidocaine or normal saline (placebo)
intranasally in split doses 2 minutes apart and intravenous prochlorperazine.
Medications were packaged so physicians and patients were unaware of the
contents. Successful pain relief was achieved if there was a 50% reduction in
pain score or a score below 2.5 cm on the VAS. RESULTS: Twenty-seven patients
received lidocaine and 22 placebo. No significant difference was observed between
groups in initial pain scores, 8.4 (95% CI = 7.8 to 9.0) lidocaine and 8.6 (95%
CI = 8.0 to 9.2) placebo (p = 0.75). Two of 27 patients (7.4%, 95% CI = 0.8,
24.3) in the lidocaine group and three of 22 patients (13.6%, 95% CI = 2.8 to
34.9) in the placebo group had immediate successful pain relief (p = 0.47), with 
average pain scores of 6.9 (95% CI = 5.9 to 7.8) and 7.0 (95% CI = 5.8 to 8.2),
respectively. No difference in pain relief was detected at subsequent
measurements. CONCLUSION: There was no evidence that intranasal lidocaine
provided rapid relief for migraine headache pain in the emergency department
setting.

Publication Types: 
    Clinical Trial
    Comparative Study
    Multicenter Study
    Randomized Controlled Trial

PMID: 11282668 [PubMed - indexed for MEDLINE]

3353: Expert Opin Investig Drugs. 2001 Apr;10(4):673-8.

Substance P receptor antagonists in the therapy of migraine.

May A, Goadsby PJ.

Department of Neurology, University of Regensburg, 93053 Regensburg, Germany.
arne.may@klinik.uni-regensburg.de

Clinical observations, the vascular component of migraine pain, its pulsating or 
throbbing pain character, have focused attention on the trigeminal innervation of
pain-sensitive intracranial structures, such as the dura mater and large vessels.
These intracranial structures are innervated by the ophthalmic branch of the
trigeminal nerve, which is marked by the presence of vasoactive peptides, such as
substance P and calcitonin gene-related peptide. Substance P is a mediator of the
sterile inflammation of the dura mater, which has been considered to be the
source of migraine pain. Modern antimigraine drugs, such as 5-HT(1B/D) agonists
(triptans), block this dural neurogenic inflammation dose-dependently in an
animal model but their vasoconstrictor effects have led to a search for
non-vasoconstrictor approaches. One such approach has been substance P
(neurokinin-1) antagonists. These are highly effective in animal models of dural 
inflammation and have no significant vasoconstrictive effect. However, several
NK(1) antagonists failed to demonstrate any effect in acute migraine. Current
clinical and experimental evidence therefore supports the view that NK(1)
receptor antagonists may have no significant antimigraine properties.

Publication Types: 
    Review

PMID: 11281817 [PubMed - indexed for MEDLINE]

3354: Compr Ther. 2001 Spring;27(1):65-71.

Menstrual cycle effects on common medical conditions.

Case AM, Reid RL.

Department of Obstetrics and Gynaecology, Royal University Hospital, University
of Saskatchewan, Saskatoon, Saskatchewan, Canada.

Menstrual cycle-related exacerbation of common medical conditions such as
migraine, epilepsy, asthma, irritable bowel syndrome, and diabetes, is a
well-recognized phenomenon. Accurate documentation of symptoms on a menstrual
calendar allows identification of women with cyclic alterations in disease
activity.

Publication Types: 
    Review

PMID: 11280858 [PubMed - indexed for MEDLINE]

3355: Public Health Nutr. 2000 Dec;3(4A):509-14.

The efficacy and safety of feverfew (Tanacetum parthenium L.): an update of a
systematic review.

Ernst E, Pittler MH.

Department of Complementary Medicine, School of Postgraduate Medicine and Health 
Science, University of Exeter, UK. e.ernst@exeter.ac.uk

OBJECTIVE: Feverfew (Tanacetum parthenium L.) is a popular herbal remedy often
advocated for the prevention of migraine. The aims of this systematic review are 
to update the evidence from rigorous clinical trials for or against the efficacy 
of feverfew for migraine prevention and to provide a safety profile of this
herbal remedy. DESIGN: Literature searches were performed using the following
databases: Medline, Embase, Biosis, CISCOM and the Cochrane Library (all from
their inception to December 1999). Only randomized, placebo-controlled,
double-blind trials of feverfew mono-preparations for the prevention of migraine 
in human subjects were included. All articles were read by two independent
reviewers. Data were extracted in a pre-defined, standardized fashion. The
methodological quality of the trials was evaluated by the Jadad score. For the
assessment of safety issues, major reference texts were also consulted. RESULTS: 
Six trials met the inclusion/exclusion criteria. The majority favour feverfew
over placebo. Yet important caveats exist. The data also suggest that feverfew is
associated with only mild and transient adverse effects and few other safety
concerns. CONCLUSIONS: Feverfew is likely to be effective in the prevention of
migraine. There are no major safety problems.

Publication Types: 
    Review

PMID: 11276299 [PubMed - indexed for MEDLINE]

3356: Headache. 2001 Mar;41(3):310-6.

Hemiplegic migraine during pregnancy: unusual magnetic resonance appearance with 
SPECT scan correlation.

Barbour PJ, Castaldo JE, Shoemaker EI.

Department of Medicine, Division of Neurology, Lehigh Valley Hospital, Allentown,
PA 18103, USA.

OBJECTIVE: This article discusses the pathophysiology and implications for
treatment of hemiplegic migraine within a case study presentation. BACKGROUND: We
evaluated a 31-year-old white woman for hemiplegia in her 36th week of pregnancy.
She initially presented with severe headache, dysarthria, lethargy, and
left-sided numbness and weakness. Hemiplegic migraine remains a diagnosis made by
exclusion; neurologic examination of these patients is localizing, but
nonspecific. DESIGN: Magnetic resonance imaging and single photon emission
computed tomography scanning were performed on this patient during an
exacerbation of headache associated with dense hemiplegia. RESULTS: Magnetic
resonance imaging showed a superficial cerebral hemispheric signal abnormality
with enhancement. Single photon emission computed tomography scanning confirmed
hyperperfusion of that hemisphere. CONCLUSIONS: We believe the imaging evidence
in our patient suggests that hemiplegia was caused and sustained by
hyperperfusion. This case lends supportive evidence to a primarily vasodilatory
mechanism and hyperperfusion as an etiology of the paralysis in such headaches
and perhaps migraine with aura.

Publication Types: 
    Case Reports

PMID: 11264693 [PubMed - indexed for MEDLINE]

3357: Headache. 2001 Mar;41(3):303-9.

Opiate use to control bowel motility may induce chronic daily headache in
patients with migraine.

Wilkinson SM, Becker WJ, Heine JA.

University of Calgary, Alberta, Canada.

OBJECTIVES: To investigate whether opiate overuse might cause chronic daily
headache in those with migraine, we studied patients who were taking codeine (or 
other opiates) for control of bowel motility after colectomy for ulcerative
colitis. BACKGROUND: Analgesic overuse is considered by many to be one factor
which can result in the transformation of migraine into a chronic daily headache 
pattern. Most of the evidence for this comes from patients with migraine who are 
taking increasing amounts of analgesia for headache. Many of these patients
revert to an intermittent migraine pattern once the analgesics are stopped.
METHODS: Women who were 1 year postcolectomy for ulcerative colitis were
identified in several colorectal surgery practices in Calgary. They were sent a
questionnaire designed to determine if they had a history of migraine prior to
surgery, if they currently had chronic daily headache, what medications they were
taking to control bowel motility, and what medications they were taking for
headache. RESULTS: Twenty-eight patients who met our inclusion criteria returned 
completed questionnaires. Eight of these exceeded the recommended limits for
opiate use in patients with headache. Eight patients met diagnostic criteria for 
migraine. Two patients had chronic daily headache starting after surgery. Both
used daily opiates beginning after their surgery, and both had a history of
migraine. The other six patients who used opiates daily did not have a history of
migraine and did not have chronic daily headache. All patients with migraine who 
used daily opiates to control bowel motility following surgery developed chronic 
daily headache after surgery. CONCLUSIONS: Patients with migraine who use daily
opiates for any reason are at high risk of developing transformed migraine with
chronic daily headache. This risk appears much lower in patients without a
history of migraine who use opiates for nonpain indications.

Publication Types: 
    Comparative Study

PMID: 11264692 [PubMed - indexed for MEDLINE]

3358: Headache. 2001 Mar;41(3):290-6.

Does relaxation treatment have differential effects on migraine and tension-type 
headache in adolescents?

Fichtel A, Larsson B.

Department of Public Health and Caring Sciences, Section of Caring Sciences,
Uppsala Science Park, Sweden.

The present study evaluated the effects of relaxation treatment in 36 adolescents
aged 13 to 18 years (mean +/- SD, 15.4 +/- 1.55 years) suffering from migraine or
migraine and tension-type headache as compared with a waiting-list condition
group. The subjects rated various characteristics of migraine and tension-type
headache in a diary. Significant reductions were found for total headache sum (P 
<.05) and intensity scores of total headache activity (P <.05) as well as for
migraine intensity (P <.05) for subjects treated with relaxation as compared with
those in the waiting-list condition group. However, no significant differences
between the two groups were found for tension-type headache. Fifty percent of the
adolescents treated with relaxation training attained a clinically significant
improvement, compared with 12% of those in the waiting-list condition. It is
suggested that treatment goals for migraine and migraine occurring with
tension-type headache might be different and that relaxation training also might 
benefit from focusing on specific aspects of the two headache types.

Publication Types: 
    Comparative Study

PMID: 11264690 [PubMed - indexed for MEDLINE]

3359: Headache. 2001 Mar;41(3):285-9.

Prevalence of migraine in patients with systemic lupus erythematosus.

Glanz BI, Venkatesan A, Schur PH, Lew RA, Khoshbin S.

Department of Neurology, Brigham and Women's Hospital, Harvard Medical School,
Boston, MA 02115, USA.

OBJECTIVE: To determine the prevalence of migraine in patients with systemic
lupus erythematosus (SLE), and to examine the relationships between headache type
and other clinical, serologic, and treatment features of the disease. BACKGROUND:
Headaches are common in SLE and are a significant source of patient disability.
The exact prevalence of headaches in patients with SLE is unknown. The
classification of headache syndromes in SLE is also unclear. Previous studies
were based on small numbers of patients and the headache types and criteria to
define headache types varied widely. METHODS: Four hundred fourteen patients
meeting American College of Rheumatology criteria for the diagnosis of SLE were
sent the University of California, San Diego Migraine Questionnaire. Patients who
completed the questionnaire had their medical records reviewed for
constitutional, respiratory, cardiac, vascular, skin, musculoskeletal, other
neuropsychiatric, hematologic, renal, and immunologic manifestations of the
disease. Recent corticosteroid, nonsteroidal anti-inflammatory drug,
antimalarial, and immunosuppressive medications were also recorded. RESULTS: One 
hundred eighty-six patients completed the questionnaire. Sixty-two percent of
patients reported headaches: 39% met diagnostic criteria for migraine and 23% met
criteria for nonmigrainous headache. Of the patients with migraine, 56% met
criteria for migraine without aura and 44% met criteria for migraine with aura.
There were no significant associations between headache type and other clinical, 
serologic, or treatment features of the disease. CONCLUSIONS: There is a high
prevalence of migraine in patients with SLE, and patients should be routinely
evaluated for migraine symptoms.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 11264689 [PubMed - indexed for MEDLINE]

3360: Headache. 2001 Mar;41(3):271-8.

Divalproex in the long-term treatment of chronic daily headache.

Freitag FG, Diamond S, Diamond ML, Urban GJ.

Diamond Headache Clinic, Chicago, IL 60614-1726, USA.

OBJECTIVE: The purpose of this study was to assess the safety and efficacy of
divalproex sodium in the long-term treatment of chronic daily headache.
Correlations between treatment variables were assessed. BACKGROUND: Controlled
and open-label trials of divalproex sodium have previously demonstrated its
efficacy and safety in the treatment of migraine and chronic daily headaches.
These data were primarily short-term and did not examine interaction between
treatment variables. METHODS: Retrospective chart review with data extraction was
conducted from headache diaries of 642 current patients under treatment with
divalproex sodium for chronic daily headaches. One hundred thirty-eight of the
patients were treated with only divalproex sodium. Demographic variables
including age, sex, initial and final body weights, adverse events, dose of
divalproex sodium, duration of treatment, and the ability to differentiate their 
chronic daily headache into its migraine and tension-type headache components
were analyzed. Baseline and end of study headache frequency indices were
obtained. RESULTS: The mean improvement was 47%, with an improvement in migraine 
of about 65%. At least a 50% reduction in headache frequency was reported by 93
of the 138 patients receiving treatment with only divalproex sodium. No
correlation between response and age, sex, duration of treatment, and the
prescribed dose of divalproex sodium was demonstrated. Adverse events occurred in
approximately 35% of the patients. None were severe. Women were more likely to
experience adverse effects than men. Weight gain, however, occurred less commonly
in women (mean, 1.9 lbs) than in men (mean, 7 lbs). Initial body weight and age
did not correlate with the weight change. CONCLUSIONS: Divalproex sodium can be
used for a prolonged period as a sole agent for the successful treatment of
chronic daily headache. Nearly 75% of the patients had at least a 50% reduction
in headache frequency, and adverse effects occurred in approximately one third.
Weight gain was negligible and hepatotoxicity did not occur during treatment
periods of up to 6 years.

PMID: 11264687 [PubMed - indexed for MEDLINE]

3361: Headache. 2001 Mar;41(3):264-70.

Efficacy and tolerability of rizatriptan 10 mg in migraine: experience with 70
527 patient episodes.

Göbel H, Heinze A, Heinze-Kuhn K, Lindner V.

Kiel Pain Clinic, Germany; Department of Neurology, University of Kiel, Germany.

As patients who suffer from migraine need long-term treatment, the safety and
consistent efficacy of such therapy is very important. Concurrent illness and
additional medication can interfere with the treatment chosen for the attacks of 
migraine. The objective of this open-label study was to investigate the efficacy 
and tolerability of rizatriptan, in the treatment of up to three attacks of
migraine, in the clinical setting. From October 1998 to July 1999, 6 174 doctors 
enrolled 33 147 patients into the study (26 644 women, 650 men). The mean age was
42.7 years. We were able to examine standardized migraine diaries relating to 25 
501 patients and 70 537 migrainous episodes. Rizatriptan scored consistently high
on efficacy and showed a consistently rapid onset. There was no evidence of
tolerance to repeated use. An effect was reported within 1 hour of ingestion in
79% of attacks treated. In 27.8% of attacks, remission of headache was complete
at 1 hour. Two hours after ingestion, 74% of attacks had subsided completely.
Repeated administration of rizatriptan was well tolerated, and few adverse
effects were seen. The most common unwanted effects were dizziness, weakness,
fatigue, and nausea. No cardiovascular disturbance was seen. In the clinical
setting, rizatriptan, 10 mg, is an effective and well-tolerated agent for the
treatment of migraine attacks. Particularly noteworthy is the rapid onset of
effect, with swift disappearance of headache. Rizatriptan has a favorable side
effect profile, and, provided contraindications are observed, severe adverse
cardiovascular complications are extremely unlikely.

Publication Types: 
    Clinical Trial

PMID: 11264686 [PubMed - indexed for MEDLINE]

3362: Headache. 2001 Mar;41(3):257-63.

Differentiating the efficacy of 5-HT(1B/1D) agonists.

Sheftell FD, Fox AW, Weeks RE, Tepper SJ.

New England Center for Headache, Stamford, CT 06902, USA.

OBJECTIVE: To examine, for a set of published clinical trials of serotonin
(5-HT(1B/1D)) agonists as acute treatments for migraine, whether transformation
of efficacy data into therapeutic gain (TG) or number needed to treat (NNT) is
useful. BACKGROUND: Pivotal clinical trials of 5-HT(1B/1D) agonists in migraine
use a primary end point of change in pain score from 3 or 2 to 1 or 0. Placebo
response rates among such studies are variable. Meta-analytic comparisons of
5-HT(1B/1D) agonists often employ TG and NNT as efficacy measures. METHODS: Data 
from US product labeling or published sources were converted into TG (TG = active
response rate [%] - placebo response rate [%]) and NNT (NNT = 1/TG). Pivotal
clinical trial data were compared before and after transformation. RESULTS:
Therapeutic gain ranged from 17.5% to 51%. The transformation of TG into NNT
yielded no clinically significant difference in efficacy estimate for the range
of 17.5% to 47% (N = 29 clinical trials). However, NNT and TG had a nonlinear
relationship for some secondary end points. When the relationship between the
standard primary and secondary end points was compared, the correlation of TG
with clinical disability (Pearson coefficient R = 0.93) was stronger than for
NNT. Placebo response rates correlated more strongly with NNT (R = 0.66) than
active response rates (R = 0.42; N = 29 clinical trials), although both TG and
NNT were sensitive to placebo response rate. CONCLUSIONS: Transforming efficacy
rates into TG or NNT adds no new information to placebo-controlled trials. The
variables, TG and NNT, should not be used to compare members of this class of
drugs. Migraine therapies can only be compared using well-designed head-to-head
studies and not by meta-analysis. Broader measures of efficacy should be used to 
describe and compare 5-HT(1B/1D) efficacy.

PMID: 11264685 [PubMed - indexed for MEDLINE]

3363: Headache. 2001 Mar;41(3):248-56.

Naratriptan as short-term prophylaxis of menstrually associated migraine: a
randomized, double-blind, placebo-controlled study.

Newman L, Mannix LK, Landy S, Silberstein S, Lipton RB, Putnam DG, Watson C,
Jöbsis M, Batenhorst A, O'Quinn S.

St. Luke's-Roosevelt Hospital Center, Headache Institute, New York, NY 10019,
USA.

OBJECTIVE: To determine the efficacy of naratriptan 1-mg and 2.5-mg tablets twice
daily compared with placebo as short-term prophylaxis of menstrually associated
migraine. BACKGROUND: Approximately 60% of women with migraine report headaches
associated with their menstrual cycles. Results from an open-label study suggest 
that short-term administration of sumatriptan is useful in the prophylaxis of
menstrually associated migraine. METHODS: A randomized, double-blind, three-arm, 
parallel-group, placebo-controlled study was conducted in women aged 18 years or 
older with a history of migraine with or without aura, as defined by the
International Headache Society, of at least 6 months. Two dose strengths of
naratriptan (1 mg, 2.5 mg) or identical-appearing placebo tablets (1:1:1) were
administered twice daily for 5 days starting 2 days prior to the expected onset
of menses across four perimenstrual periods. End points included the number of
menstrually associated migraines, total migraine days, peak headache severity,
lost work/activity time, migraine-related quality of life, and incidence of
adverse events. RESULTS: Overall, the intent-to-treat population comprised 206
women (naratriptan 1 mg, n = 70; naratriptan 2.5 mg, n = 70, and placebo, n =
66); 171 women treated four perimenstrual periods. Significantly more
perimenstrual periods per subject treated with naratriptan, 1 mg, were
headache-free compared with placebo (50% versus 25%, P =.003). Naratriptan, 1 mg,
significantly reduced the number of menstrually associated migraines (2.0 versus 
4.0, P <.05) and menstrually associated migraine days (4.2 versus 7.0, P <.01)
compared with placebo. More patients treated with naratriptan, 1 mg, were
headache-free across all treated perimenstrual periods compared with placebo (23%
versus 8%). No difference in headache severity was observed in breakthrough
headaches. The incidence and severity of adverse events was similar across
treatment groups. Naratriptan, 2.5 mg, was not statistically superior to placebo 
for any measure. CONCLUSIONS: Naratriptan, 1 mg, with tolerability similar to
placebo, is an effective, short-term, prophylactic treatment for menstrually
associated migraine.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 11264684 [PubMed - indexed for MEDLINE]

3364: High Alt Med Biol. 2000 Fall;1(3):207-11.

Transient high altitude expressive aphasia.

Dietz TE, McKiel VH.

Emergency Department, Providence Hood River Memorial Hospital, OR 97031, USA.
tdietz@high-altitude-medicine.com

Transient focal neurological deficits have been described in sojourners to high
altitude. We present two cases of transient expressive aphasia in
well-acclimatized high altitude climbers. We speculate that this type of
transient focal neurological impairment may represent migraine aura, and we
discuss other reports of transient focal neurological deficit at high altitude.

Publication Types: 
    Case Reports

PMID: 11254230 [PubMed - indexed for MEDLINE]

3365: Can J Neurol Sci. 2001 Feb;28(1):30-41.

Comment in:
    Can J Neurol Sci. 2001 Aug;28(3):272.

A systematic review of the use of triptans in acute migraine.

Gawel MJ, Worthington I, Maggisano A.

Division of Neurology, Sunnybrook & Women's College Health Sciences Centre,
Toronto, ON, Canada.

OBJECTIVE: A systematic review of the literature was undertaken, to consolidate
evidence concerning the efficacy and safety of triptans currently available in
Canada (sumatriptan, rizatriptan, naratriptan, zolmitriptan), and to provide
guidelines for selection of a triptan. METHODS: Data from published, randomized, 
placebo-controlled trials were pooled and a combined number needed to treat (NNT)
and number needed to harm (NNH) was generated for each triptan. Direct
comparative trials of triptans were also examined. RESULTS: The lowest NNT for
headache response/pain-free at one/two hours is observed with subcutaneous
sumatriptan. Among the oral formulations, the lowest NNT is observed with
rizatriptan and the highest NNT with naratriptan. The lowest NNH is observed with
subcutaneous sumatriptan. CONCLUSIONS: Triptans are relatively safe and effective
medications for acute migraine attacks. However, differences among them are
relatively small. Considerations in selecting a triptan include individual
patient response/tolerance, characteristics of the attacks, relief of associated 
symptoms, consistency of response, headache recurrence, delivery systems and
patient preference.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 11252291 [PubMed - indexed for MEDLINE]

3366: Curr Pain Headache Rep. 2001 Apr;5(2):195-9.

Menstrual migraine: diagnosis and treatment.

Lay CL, Mascellino AM.

The Headache Institute, St. Lukes-Roosevelt Hospital Center, New York, NY 10019, 
USA.

Of the nearly 20 million American women suffering with migraine, approximately 12
million experience a worsening of their migraines in association with their
menstrual cycle. Prior to puberty the prevalence of migraine is slightly higher
in boys; however, after puberty there is an emerging female predominance.
Estrogen likely plays an important role in explaining this gender difference;
however, hormones unlikely explain the entire epidemiologic variation. This
article reviews the diagnosis and treatment options for menstrually associated
migraine.

Publication Types: 
    Review

PMID: 11252155 [PubMed - indexed for MEDLINE]

3367: Curr Pain Headache Rep. 2001 Apr;5(2):189-94.

Epidemiology of migraine.

Hamelsky SW, Stewart WF, Lipton RB.

Bristol-Myers Squibb, 1350 Liberty Avenue, Hillside, NJ 07205, USA.
sandra.hamelsky@bms.com

Migraine is a highly prevalent headache disorder that has a substantial impact on
the individual and society. Over the past decade, substantial advances in
research have increased understanding of the pathophysiology, diagnosis,
epidemiology, and treatment of the disorder. This article reviews data on the
epidemiology and impact of migraine. It also highlights the increased awareness
of migraine, citing examples from the popular media and the Internet.

Publication Types: 
    Review

PMID: 11252154 [PubMed - indexed for MEDLINE]

3368: Curr Pain Headache Rep. 2001 Apr;5(2):183-8.

Diagnostic issues in migraine.

Kaniecki RG.

The Headache Center, University of Pittsburgh, PA 15213, USA.

Headache poses diagnostic challenges to the clinician for many reasons. It is an 
extremely common complaint, and may be associated with acute illness or serious
pathology such as brain tumor or cerebral aneurysm. However, the majority of
patients experiencing recurrent headache in the population suffer either from a
variant of tension-type headache or migraine. Because migraine is more likely to 
be disabling, it becomes the most likely diagnosis for any patient presenting
with recurrent headache interfering with function. Although the diagnostic
criteria developed by the International Headache Society in 1998 are useful as a 
guide, migraine may be more readily recognized in a clinical setting by its
consideration at the top of the differential for patients presenting with
recurrent headache. This article reviews the standard diagnostic criteria for
migraine, while also addressing the primary and secondary headache syndromes that
may be considered in a differential diagnosis. The indications and roles for
specific investigative procedures such as neuroimaging are reviewed. Specific
emphasis is placed on the clinical recognition of migraine in the context of an
assortment of headache conditions.

Publication Types: 
    Review

PMID: 11252153 [PubMed - indexed for MEDLINE]

3369: Curr Pain Headache Rep. 2001 Apr;5(2):179-82.

Pathophysiology of migraine headache.

Aurora SK.

Swedish Headache Clinic, Swedish Neurosciences Center, Seattle, WA 98104, USA.

The underlying mechanism of migraine and pain has been unraveled recently with
the advent of neuroimaging. In this article mechanism of migraine aura and the
pain of migraine are discussed. In addition, interictal studies demonstrating
hyperexcitability in migraine are reviewed.

Publication Types: 
    Review

PMID: 11252152 [PubMed - indexed for MEDLINE]

3370: Curr Pain Headache Rep. 2001 Apr;5(2):170-8.

How to pick optimal acute treatment for migraine headache.

Sanchez del Rio M, Silberstein S.

Jefferson Headache Center, Thomas Jefferson University Hospital, Philadelphia, PA
19107, USA.

Drug selection for the acute treatment of migraine is based on comorbid
disorders, coexistent diseases, and the patient's pain profile and specific needs
and expectations. Patients should be instructed to tailor their treatment
strategy to meet their specific needs by varying their medications according to
pain intensity. This will aid in successful headache management, by increasing
compliance and decreasing disability and cost.

Publication Types: 
    Review

PMID: 11252151 [PubMed - indexed for MEDLINE]

3371: Curr Pain Headache Rep. 2001 Apr;5(2):165-9.

Migraine variants.

Solomon S.

Department of Neurology, Albert Einstein College of Medicine, Montefiore Medical 
Center, Bronx, NY 10467, USA. sysol@earthlink.net

The term "migrant variant" is not used in the headache classification of the
International Headache Society (IHS), but it includes those forms of migraine
that are not typical of migraine with or without aura. Headaches that do not
quite fulfill all of the IHS criteria are termed "migrainous disorder." Migraine 
associated with auras arising from unusual sites includes basilar migraine,
retinal migraine, and ophthalmoplegic migraine. Two of the chromosomal sites for 
hemiplegic migraine have been identified. Migraine aura may occur without
headache and an aura may be prolonged. Migrainous infarct has occurred when the
aura lasts more than 1 week or imaging studies are positive and other etiologies 
have been ruled out. If the migraine attack is prolonged beyond 3 days the term
"status migrainousus" is applied.

Publication Types: 
    Review

PMID: 11252150 [PubMed - indexed for MEDLINE]

3372: Curr Pain Headache Rep. 2001 Feb;5(1):67-70.

Migrainous features in cluster headache.

Peatfield R.

Charing Cross Hospital, Fulham Palace Road, London W6 8RF, UK.
rpeatfield@ic.ac.uk

Migraine and cluster headache have been considered entirely separate clinical
syndromes, both in routine clinical practice and in the 1988 International
Headache Society classification. Neurologists seeing large numbers of patients
soon realize, however, that there is a considerable overlap between the two
conditions. Some patients have attacks with the cardinal features of cluster
headache, but also have a few symptoms (especially a visual aura) usually
attributed to migraine. In addition, it is not uncommon for a patient with a
lifetime's history of migraine to experience a typical bout of cluster headache, 
although the reverse is less common. This article reviews the published series of
such patients.

Publication Types: 
    Review

PMID: 11252140 [PubMed - indexed for MEDLINE]

3373: Headache. 2001 Feb;41(2):201-3.

Migrainous aura versus transient ischemic attack in an elderly migraineur.

Evans RW, Tietjen GE.

In older patients with migraine, the distinction between a migrainous aura and a 
transient ischemic episode can be difficult, as this case illustrates.

Publication Types: 
    Case Reports

PMID: 11251707 [PubMed - indexed for MEDLINE]

3374: Headache. 2001 Feb;41(2):193-7.

Daily migraine with visual aura associated with an occipital arteriovenous
malformation.

Spierings EL.

Department of Neurology, Brigham and Women's Hospital, Boston, MA, USA.

A 51-year-old woman with daily attacks of migraine with visual aura is described.
The aura always occurred on the right and the headache always on the left side of
the head, suggesting a structural lesion in the left occipital lobe. The lesion
appeared to be an arteriovenous malformation of which almost full obliteration
resulted in a decrease in frequency of the aura and in intensity of the headache.
Subsequent treatment of borderline hypothyroidism with levothyroxine brought
about a dramatic improvement in frequency of both the aura and the headache. The 
case is discussed in the light of our present understanding of the pathogenesis
of the migraine attack.

Publication Types: 
    Case Reports

PMID: 11251705 [PubMed - indexed for MEDLINE]

3375: Headache. 2001 Feb;41(2):171-7.

Efficacy of intravenous magnesium sulfate in the treatment of acute migraine
attacks.

Demirkaya S, Vural O, Dora B, Topçuoğlu MA.

Gülhane Military Medical Academy Neurology Department, Ankara, Turkey.

OBJECTIVE: To study the efficacy and tolerability of 1 g of intravenous magnesium
sulfate as acute treatment of moderate or severe migraine attacks. BACKGROUND:
Migraine is a common disorder in which not only the pain but also the
accompanying symptoms such as nausea and vomiting reduce activity and
productivity of sufferers. Many drugs used for the treatment of acute migraine
attacks have many side effects, are not well tolerated, are ineffective in some
patients, or cannot be used during pregnancy or in patients with ischemic heart
disease. Magnesium deficiency has been proposed to play a role in the
pathophysiology of migraine, and recently treatment of migraine with magnesium
has gained considerable interest. METHODS: This was a randomized, single-blind,
placebo-controlled trial including 30 patients with moderate or severe migraine
attacks. Fifteen patients received 1 g intravenous magnesium sulfate given over
15 minutes. The next 15 patients received 10 mL of 0.9% saline intravenously.
Those in the placebo group with persisting complaints of pain or nausea and
vomiting after 30 minutes also received 1 g magnesium sulfate intravenously over 
15 minutes. The patients were assessed immediately after treatment, and then 30
minutes and 2 hours later. Intensity of pain, accompanying symptoms, and side
effects were noted. RESULTS: All patients in the treatment group responded to
treatment with magnesium sulfate. The pain disappeared in 13 patients (86.6%); it
was diminished in 2 patients (13.4%); and in all 15 patients (100%), accompanying
symptoms disappeared. In the placebo group, a decrease in pain severity but
persisting nausea, irritability, and photophobia were noted in 1 patient (6.6%). 
Accompanying symptoms disappeared in 3 patients (20%) 30 minutes after placebo
administration. All patients initially receiving placebo were subsequently given 
magnesium sulfate. All of these patients responded to magnesium sulfate. In 14
patients (93.3%), the attack ended; in 1 patient (6.6%), pain intensity
decreased; and in all 15 patients (100%), accompanying symptoms disappeared. Both
the response rate (100% for magnesium sulfate and 7% for placebo) and the
pain-free rate (87% for magnesium sulfate and 0% for placebo) showed that
magnesium sulfate was superior to placebo. Twenty-six patients (86.6%) had mild
side effects which did not necessitate discontinuing treatment during magnesium
sulfate administration. CONCLUSION: Our results show that 1 g intravenous
magnesium sulfate is an efficient, safe, and well-tolerated drug in the treatment
of migraine attacks. It is possible that magnesium sulfate could be used in a
broader spectrum of patients than other drugs commonly used for attack treatment.
In view of these results, the effect of magnesium sulfate in acute migraine
should be examined in large-scale studies.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial

PMID: 11251702 [PubMed - indexed for MEDLINE]

3376: Headache. 2001 Feb;41(2):157-63.

Spontaneous oscillations in cerebral blood flow velocity give evidence of
different autonomic dysfunctions in various types of headache.

Sliwka U, Harscher S, Diehl RR, van Schayck R, Niesen WD, Weiller C.

Department of Neurology, Friedrich-Schiller University, Philosophenweg 3, D-07740
Jena, Germany.

OBJECTIVES: Our objectives were to determine if: (1) patients with migraine have 
B wave abnormalities in comparison to normal controls and patients with chronic
tension headache and (2) patients with chronic tension headache have an imbalance
in autonomic activity that is reflected in differences in Mayer wave activity in 
comparison to normal controls. BACKGROUND: B waves and Mayer waves are
spontaneous oscillations in cerebral blood flow velocity with a frequency of 0.5 
to 3 or 4 to 7 cycles per minute, respectively, and can be measured by
transcranial Doppler sonography. There is experimental evidence that B waves are 
generated by certain brain stem nuclei which modulate the lumen of the small
intracerebral vessels via monoaminergic nerve endings. In contrast, Mayer waves
in cerebral blood flow velocity have no central generator but mirror the Mayer
waves in arterial blood pressure which represent peripheral autonomic activity.
Migraine may be attributed to a neurotransmitter imbalance in brain stem nuclei. 
Dysfunctions of the peripheral autonomic nervous system are known in patients
with chronic tension headache. METHODS: Using bilateral transcranial Doppler
monitoring of the middle cerebral artery B waves and Mayer waves were studied in 
30 patients with migraine without aura, 28 subjects with tension-type headache,
and 30 normal controls. Coefficient of variation as a quantitative parameter for 
amplitude of waves and the mean frequency were calculated from the envelope
curves of the Doppler spectra. RESULTS: The coefficient of variation of B waves
was higher in migrainous patients compared with patients with tension-type
headache and normal controls (P<.05), indicating an increase in activity of brain
stem nuclei in migraine only. Patients with chronic tension headaches had lower
values for Mayer wave activity in comparison with normal controls (P<.05), a sign
of an impairment of sympathetic activity. CONCLUSIONS: Our data support the
dysfunction of the brain stem monoaminergic/serotonergic system in migraine. In
contrast, patients with chronic tension headache have an autonomic dysfunction of
peripheral origin presenting as a decrease of sympathetic activity.

Publication Types: 
    Comparative Study

PMID: 11251700 [PubMed - indexed for MEDLINE]

3377: Headache. 2001 Feb;41(2):150-6.

Development of a brief 24-hour adolescent migraine functioning questionnaire.

Hartmaier SL, DeMuro-Mercon C, Linder S, Winner P, Santanello NC.

Hartmaier and Associates, Austin, TX, USA.

The objective was to develop a brief questionnaire to assess short-term
functioning decrements in adolescents with acute migraine. One hundred
twenty-three potential items were generated by literature review and by
interviewing adolescent migraineurs and migraine specialists. To reduce the
items, 127 adolescents were asked to identify which items affected their daily
functioning in the 24 hours following onset of a migraine, and to rate them on a 
5-point scale from "not very important" to "extremely important." Reduction to an
18-item questionnaire was performed by evaluating subject-perceived importance
(number of times an item was chosen times mean importance score) in combination
with principal components factor analysis. Five domains were identified: (1)
activities, (2) social functioning, (3) cognitive functioning, (4) migraine
headache symptoms, and (5) emotional functioning. Questions regarding school loss
and school performance during a migraine were added to the final questionnaire as
a separate outcome measure. The correlation between the five domains as measured 
by the Spearman correlation coefficient ranged from 0.17 to 0.49 suggesting some,
but minimal, overlap. Cronbach alpha for individual domains ranged from.50 to.84.
The questionnaire was pilot-tested in 12 adolescent migraineurs to determine ease
of administration and comprehension and revised to improve clarity.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 11251699 [PubMed - indexed for MEDLINE]

3378: Headache. 2001 Feb;41(2):142-9.

Recovery cycle of the blink reflex and exteroceptive suppression of temporalis
muscle activity in migraine and tension-type headache.

Aktekin B, Yaltkaya K, Ozkaynak S, Oguz Y.

Department of Neurology, Akdeniz University School of Medicine, Dumlupinar
Bulvari, 07070, Antalya, Turkey.

Brain stem interneuronal excitability can be assessed by recording the recovery
cycle of the blink reflex and exteroceptive suppression of temporalis muscle
activity. Abnormal endogenous pain control mechanisms due to disturbed brain stem
interneuronal activity have been implicated in the pathogenesis of tension-type
headaches. The blink reflex, exteroceptive suppression of temporalis muscle
activity, and the recovery curve of both the R2 component of the blink reflex and
the ES2 component of the exteroceptive suppression of the temporalis muscle
activity were studied in 20 patients with migraine without aura, 32 patients with
tension-type headache, and 20 normal controls. In our study, the blink reflex was
elicited by stimulation of the supraorbital nerve; the exteroceptive suppression 
of the temporalis muscle activity was elicited by applying electrical shocks to
the labial commissure, both on the lower and upper sides. The recovery cycle was 
established by delivering paired shocks at different interstimulus intervals.
Comparisons were made between normal control subjects, patients with migraine
without aura, and patients with tension-type headache. The latency of R1, R2, and
R2', the amplitude and size of the R2 and R2' components of the blink reflex, the
latency and duration of the ES1 and ES2 components, and the recovery curve of the
ES2 component of the temporalis muscle activity did not differ between groups.
However, the recovery curve of the R2 component of the blink reflex diminished in
patients with tension-type headache compared with the other groups. Our findings 
indicate reduced excitability of the brain stem interneurons in patients with
tension-type headache.

Publication Types: 
    Comparative Study

PMID: 11251698 [PubMed - indexed for MEDLINE]

3379: Headache. 2001 Feb;41(2):129-37.

Deficiency of tumor necrosis factor alpha in a subclass of menstrual migraineurs.

Mueller L, Gupta AK, Stein TP.

Department of Family Medicine, University Headache Center, University of Medicine
and Dentistry of New Jersey, Moorestown, NJ 08057, USA.

OBJECTIVE: The objective of this study was to determine whether differences in
urinary proinflammatory cytokines, interleukin-1beta (IL-1beta), interleukin-6
(IL-6), and tumor necrosis factor alpha (TNF-alpha), exist between migraineurs
and nonheadache control subjects, and between nonhormonal migraine and menstrual 
migraine. Any differences noted would expand and clarify a neuroimmune hypothesis
of migraine pathogenesis and lead to future diagnostic markers or therapeutic
options or both for the disorder. BACKGROUND: Current theories of migraine
pathogenesis focus on biochemical abnormalities in the central nervous system
resulting in sterile inflammation of meningeal blood vessels. Vasoactive
substances involved in this process may include substance P, calcitonin
gene-related peptide, neurokinin A, serotonin, and nitric oxide. Immune cell
products, such as histamine, leukotrienes, and cytokines, also have vascular
inflammatory properties. METHODS: A study of proinflammatory cytokines, IL-1beta,
IL-6, and TNF-alpha, was undertaken in menstrual migraineurs. During and outside 
of menses, 24-hour urine samples of 19 women with migraine were taken during a
menstrual migraine, a nonmenstrual migraine, and a headache-free day, and
compared with 24-hour urine samples taken of 10 nonheadache controls during and
outside of menses. RESULTS: A neuroimmune mechanism for migraine was tested with 
expected increases in proinflammatory cytokines tested during a migraine. This
hypothesis was not validated. Mean IL-6 levels were increased in all three
samples of migraineurs versus controls, but did not achieve statistical
significance. No differences were found in IL-1beta levels between samples.
Interestingly, marked differences were found in TNF-alpha values in menstrual
migraineurs. Twelve (63%) of 19 migraineurs had at least one urine sample with
undetectable TNF-alpha levels, whereas none of the 20 samples given by the 10
nonheadache controls in this study had undetectable levels. Thirty-two samples
from men with cluster headache and nonheadache control subjects in prior studies 
had detectable levels. CONCLUSIONS: This deficiency of TNF-alpha levels in women 
with migraine may signal a disordered neuroimmune communication network and
predisposition to migraine.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 11251696 [PubMed - indexed for MEDLINE]

3380: Headache. 2001 Feb;41(2):119-28.

Comment in:
    Headache. 2002 Mar;42(3):235.

Efficacy of gabapentin in migraine prophylaxis.

Mathew NT, Rapoport A, Saper J, Magnus L, Klapper J, Ramadan N, Stacey B, Tepper 
S.

Houston Headache Clinic, 1213 Hermann Drive, Suite 350, Houston, TX 77004, USA.

OBJECTIVE: To compare gabapentin with placebo for use as a prophylactic agent in 
patients with migraine (with or without aura). STUDY DESIGN AND TREATMENT: After 
screening, a 4-week, single-blind, placebo baseline period was followed by a
12-week, double-blind, treatment period. The 12-week treatment period consisted
of a 4-week titration phase and an 8-week stable-dosing phase. During the 4-week 
titration phase, patients were started on one 300-mg capsule of gabapentin or
matching placebo. Patients were titrated weekly from 900 mg/day (end of week 1)
to 2400 mg/day (end of week 4) and had to be receiving a stable dose of study
medication by the end of the titration period. Study medication was to be given
on a three-times-a-day dosing regimen. METHODS: The study hypothesis was defined 
a priori as a lower 4-week migraine rate during the second stabilization period
for the gabapentin-treated patients as compared with the placebo-treated
patients. The analyses were performed with the 4-week migraine rate at baseline
as a covariate and center as a blocking factor. RESULTS: At seven participating
centers, 143 patients with migraine were randomized in a 2:1 ratio and received
either gabapentin (n = 98) or matching placebo (n = 45). Thirty-three patients
(24.1%) discontinued prematurely from the study, including 24 (24.5%) of 98
gabapentin-treated patients and 9 (20.0%) of 45 placebo-treated patients; the
majority of patients discontinued due to adverse events (16 [16.3%] of 98
gabapentin-treated patients; 4 [8.9%] of 45 placebo-treated patients). Patients
included in the analysis were evenly balanced for age, sex, race, weight, and
height. The majority of these patients were white (80 [92.0%] of 87) and women
(72 [82.8%] of 87), with a mean age of approximately 39.4 years and a history of 
migraine episodes for a mean of about 21 years. At the end of the 12-week
treatment phase, the median 4-week migraine rate was 2.7 for the
gabapentin-treated patients maintained on a stable dose of 2400 mg/day and 3.5
for the placebo-treated patients (P =.006), compared with 4.2 and 4.1,
respectively, during the baseline period. Additionally, 26 (46.4%) of 56 patients
receiving a stable dose of 2400 mg/day gabapentin and 5 (16.1%) of 31 patients
receiving placebo showed at least a 50% reduction in the 4-week migraine rate (P 
=.008). The average number of days per 4 weeks with migraine was also
statistically significant and favored gabapentin (P =.006) during stabilization
period 2. The median change in 4-week headache rate was statistically significant
as well (P =.013). The most frequently reported adverse events for both treatment
groups were asthenia, dizziness, somnolence, and infection. Adverse events
determined by the investigator to be associated with study drug resulted in
patient withdrawal in 13 (13.3%) of 98 gabapentin-treated patients and 3 (6.7%)
of 45 placebo-treated patients. Somnolence and dizziness accounted for many of
the premature withdrawals among those taking gabapentin. CONCLUSION: Gabapentin
is an effective prophylactic agent for patients with migraine. In addition,
gabapentin appears generally well tolerated with mild to moderate somnolence and 
dizziness.

Publication Types: 
    Clinical Trial
    Multicenter Study
    Randomized Controlled Trial

PMID: 11251695 [PubMed - indexed for MEDLINE]

3381: Expert Opin Pharmacother. 2000 Mar;1(3):391-404.

Migraine pharmacotherapy with oral triptans: a rational approach to clinical
management.

Millson DS, Tepper SJ, Rapoport AM.

Department of Medicines Management, Keele University, Staffs, ST5 5BG, UK.
d.millson@keele.ac.uk

The recent clinical development of a number of migraine specific 5-HT1B/1D
agonist triptans with enhanced lipophilicity (TELs), relative to the first drug
of this class sumatriptan, and with a range of different metabolic,
pharmacokinetic and receptor affinity profiles, provides the potential for
critically different clinical profiles. Eletriptan, naratriptan, rizatriptan and 
zolmitriptan display both increased stability to first pass metabolic
inactivation by monoamine oxidase (MAO-A) and enhanced lipophilicity (4- to >
120-fold more than sumatriptan), leading to increased oral bioavailability (2- to
5-fold more than the 14% reported for oral sumatriptan). Central penetration and 
increased receptor affinity and selectivity for the neuronal (5-HT1D) receptor
also combine to allow for lower total oral dosing (i.e., unit doses of 15 mg or
less compared with 50-300 mg doses of sumatriptan) and reduced peripheral
exposure to the coronary vasoconstrictor (5-HT1B) receptor. The notable exception
being eletriptan, where an active P-glycoprotein blood-brain barrier efflux
system effectively negates these benefits and requires an 80 mg oral dose.
Differences in the metabolic balance between hepatic P450 (especially CYP 1A2)
and MAO-A inactivation lead to potential drug interactions for all TELs with the 
oral contraceptive pill (OCP), fluvoxamine and the quinilone antibiotics (with
increased triptan levels). An important but complex MAO-A interaction between a
metabolite of propranolol and rizatriptan mandates dosage reduction (to 5 mg) for
rizatriptan in the presence of propranolol treatment. There is also an absolute
contraindication for the concurrent administration of the MAO-A inhibitor
moclobemide and rizatriptan. All the new-marketed TELs have potential clinical
benefits and were well-tolerated relative to sumatriptan. Both rizatriptan (10
mg) and zolmitriptan (2.5 mg and 5 mg) demonstrate at least equivalent efficacy
to sumatriptan 25, 50 and 100 mg, respectively, making them suitable first line
agents for moderate or severe migraine headaches. Rizatriptan has the fastest
onset of effect of the TELs. Naratriptan would appear to have lower recurrent
headache rate than sumatriptan, rizatriptan or zolmitriptan. Therefore, for
headaches of long duration and with a tendency to recur naratriptan may be the
most appropriate treatment. Thus, knowledge of the metabolic, pharmacokinetic and
clinical profiles of the TELs facilitates the selection of a triptan which allows
optimisation of the clinical benefits for individual patients, minimising the
risk of drug interactions and a minimally effective dose to reduce potential
adverse events (AEs).

Publication Types: 
    Review

PMID: 11249525 [PubMed - indexed for MEDLINE]

3382: J Affect Disord. 2001 Mar;63(1-3):35-41.

Long-term medical conditions and major depression in a Canadian population study 
at waves 1 and 2.

Patten SB.

Alberta Heritage Foundation for Medical Research, The University of Calgary,
Calgary, Alberta, Canada T2N 4N1. patten@ucalgary.ca

BACKGROUND: Cross-sectional studies have reported that certain long-term medical 
conditions are associated with major depression. Here, these associations are
explored using a longitudinal analysis. METHODS: Data from the first (1994/95)
and second (1996/97) waves of the Canadian National Population Health Survey
(NPHS) were utilized. The first wave of the NPHS utilized a probability sample of
17626 members of the Canadian population. Members of this cohort were recontacted
by Statistics Canada 2 years later. The Composite International Diagnostic
Interview Short Form for Major Depression was used to identify episodes of major 
depression in both waves of the survey. Subjects free of major depression in the 
year preceding the 1994/95 survey were selected for inclusion in this analysis.
The incidence of new-onset episodes in subjects with and without reported
long-term medical conditions was compared. RESULTS: Individuals suffering from
one or more long-term medical conditions were found to be at increased risk of
major depression. Migraine headaches, sinusitis and back problems were the
conditions most strongly associated with major depression. Having a long-term
medical condition approximately doubled the risk of major depression in this
analysis. LIMITATIONS: The most important limitation of this study was its
reliance on self report data about medical conditions. CONCLUSIONS: A large
proportion of the general population in Canada suffers from long-term medical
conditions. These individuals are at increased risk of major depression. This
study suggests an important role for long-term medical conditions in the etiology
of major depression.

PMID: 11246078 [PubMed - indexed for MEDLINE]

3383: Brain Res Brain Res Rev. 2001 Mar;35(1):20-35.

Receptor systems mediating c-fos expression within trigeminal nucleus caudalis in
animal models of migraine.

Mitsikostas DD, Sanchez del Rio M.

Athens Naval Hospital, Neurology Department, Headache Clinic, 70 Dinokratous
Street, 115 21, Athens, Greece. dmitsikostas@ath.forthnet.gr

In intracranial structures unmyelinated C- and Adelta-fibers of the trigeminal
nerve transmit pain stimuli from meninges to the trigeminal nucleus caudalis
(Sp5C). Peripheral nerve endings surround meningeal vessels (the so-called
trigeminovascular system) and contain vasoactive neuropeptides (calcitonin
gene-related peptide, substance P and neurokinin A). Activation of the
trigeminovascular system promotes a meningeal sterile inflammatory response
through the release of neuropeptides by peripheral endings. Orthodromic
conduction along trigeminovascular fibers transmits information centrally with
induction of immediate early c-fos gene within post-synaptic Sp5C neurons, as a
marker of neuronal activity within central nociceptive pathways. In laboratory
animals the system is activated by either electrical stimulation of the TG,
chemical stimulation of the meninges, electrical or mechanical stimulation of the
superior sagittal sinus or by induction of cortical spreading depression. All
these techniques induce c-fos within Sp5C and are used as a rodent/feline model
of vascular headache in humans. Up-to-date there is evidence that at least ten
receptors (5-HT(1B), 5-HT(1D), 5-HT(lF), 5-HT(2B), NK-1, GABA(A), NMDA, AMPA,
class III metabotropic glutamate receptors, and opioids mu receptors) modulate
c-fos expression within Sp5C. These receptors represent potential targets for
anti-migraine drugs as shown by triptans (5-HT(1B/1D/1F)) and ergot alkaloids
(5-HT(1A1B/1D/1F)). This review discusses the importance of c-fos expression
within Sp5C as a marker of cephalic nociception, the different cephalic pain
models that induce c-fos within Sp5C, the receptors involved and their potential 
role as targets for anti-migraine drugs.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 11245884 [PubMed - indexed for MEDLINE]

3384: J Neurol Sci. 2001 Mar 1;184(2):139-41.

Visual evoked potential changes in migraine. Influence of migraine attack and
aura.

Yilmaz M, Bayazit YA, Erbagci I, Pençe S.

Department of Neurology, Faculty of Medicine, Gaziantep University, Kolejtepe,
Gaziantep, Turkey.

OBJECTIVE: To assess the visual evoked potential (VEP) changes in migraines with 
and without aura. STUDY DESIGN: A clinical study in which the VEP results of 45
migraineurs (study group) and 22 healthy volunteers (control group) were
compared. Of 45 migraineurs, 29 had migraine with aura (MA) and 16 had migraine
without aura (MOA), and they were examined both during and between the migraine
attacks. METHODS: The patients and healthy controls underwent VEP assessment. On 
VEP recording, mono-ocular stimulation was performed by means of the pattern
reversal check board. The latencies of N1, P1 and N2, and the N1--P1 amplitude
were noted. The following comparisons were made between NI, P1 and N2 latencies
and N1--P1 amplitudes of the migraine and control groups; during and between
attack the VEP results of the patients with MA and MOA. RESULTS: The VEP results 
of the migraineurs and healthy controls were similar (P>0.05). The during attack 
results of MA, during and between attack results of MOA, and the results of the
control group were also similar (P>0.05). N2 latency significantly elongated in
patients with MA in the attack free period than it was during the attack
(P=0.01), and was also longer than it was in the control group (P=0.01).
CONCLUSIONS: There is involvement of the visual pathway in MA rather than MOA,
and differentiation between these subtypes of the migraine disease may be
performed on the basis of VEP findings manifesting by the prolongation of the N2 
wave latency. This contention should be confirmed by further studies.

Publication Types: 
    Clinical Trial

PMID: 11239947 [PubMed - indexed for MEDLINE]

3385: Stroke. 2001 Mar;32(3):649-51.

Transtentorial herniation after unilateral infarction of the anterior cerebral
artery.

Leistner S, Boegner F, Marx P, Koennecke HC.

Department of Neurology, Stroke Unit, Universitätsklinikum Benjamin Franklin,
Freie Universität Berlin, Berlin, Germany.

BACKGROUND: Fatal cerebral herniation is a common complication of large
("malignant") middle cerebral artery infarcts but has not been reported in
unilateral anterior cerebral artery (ACA) infarction. CASE DESCRIPTION: We report
a 47-year-old woman who developed an acute left hemiparesis during an attack of
migraine. Cranial CT (CCT) was normal but demonstrated narrow external
cerebrospinal fluid compartments. Transcranial Doppler sonography was compatible 
with occlusion of the right ACA. Systemic thrombolytic therapy with tissue
plasminogen activator was initiated 105 minutes after symptom onset. Follow-up
CCT 24 hours after treatment revealed subtotal ACA infarction with hemorrhagic
conversion. Two days later, the patient suddenly deteriorated with clinical signs
of cerebral herniation, as confirmed by CCT. An extended right hemicraniectomy
was immediately performed. Within 6 months, the patient regained her ability to
walk but remained moderately disabled. CONCLUSIONS: This is the first reported
case of unilateral ACA infarct leading to almost fatal cerebral herniation.
Narrow external cerebrospinal fluid compartments in combination with early
reperfusion, hemorrhagic transformation, and additional dysfunction of the
blood-brain barrier promoted by tissue plasminogen activator and migraine may
have contributed to this unusual course.

Publication Types: 
    Case Reports

PMID: 11239181 [PubMed - indexed for MEDLINE]

3386: Hosp Med. 2001 Feb;62(2):96-100.

Almotriptan: a balanced approach to migraine.

Cull R.

Head Clinic, Western General Hospital, Edinburgh EH4 2XU.

Effective acute treatment of migraine is possible with the 4HT(1B/1D) agonists
(triptans), but their use has been limited in the UK because of concerns about
limited efficacy, recurrence of attacks, adverse events, and cost. Almotriptan
(Almogran, Lundbeck Ltd, Milton Keynes), the most recently available member of
the class, offers some advantages over previously available agents.

Publication Types: 
    Review

PMID: 11236625 [PubMed - indexed for MEDLINE]

3387: J Neurosci Nurs. 2001 Feb;33(1):6-13.

Overview of migraine.

Lin JN.

Cheng Kung University, Tainan, Taiwan. joannie94122@yahoo.com

Migraine, one of the most common incapacitating headaches, afflicts 23 million
adults in the United States. There is a controversy in the literature on the
theoretical perspective of migraine, the efficacy of treatment strategies,
measurement, and correlates. Thus, more research is needed on these issues. A
wide range of treatments is available for migraine. In addition to terminating
migraine headache, appropriate migraine care includes preventing its attacks and 
improving patients' quality of life by administrating pharmacologic preparations 
in conjunction with a variety of alternative methods.

Publication Types: 
    Review

PMID: 11233364 [PubMed - indexed for MEDLINE]

3388: Epileptic Disord. 2000;2 Suppl 1:S37-9.

Migraine and the benign partial epilepsies of childhood: evidence for an
association.

Andermann F.

Montreal Neurological Hospital and Institute, Canada. mida@musica.McGill.ca

There is an increasing body of evidence to suggest that benign rolandic epilepsy 
and benign occipital epilepsy of childhood are frequently associated with
migraine. This however has not been universally recognized. Clearly further
investigation of this association is required. The purpose of this report is to
examine the varied diagnostic criteria for common migraine utilized by
epileptologists and other neurologists, to review clinical migraine epilepsy
relationships, EEG abnormalities in migraine and epilepsy, and the association of
seizures with vascular headache in patients with various forms of epilepsy.
Hopefully, this will stimulate further research into this intriguing association 
of two conditions which though they have different pathophysiology frequently
coexist.

Publication Types: 
    Review

PMID: 11231222 [PubMed - indexed for MEDLINE]

3389: Can Fam Physician. 2001 Feb;47:322-9.

Delivery systems for acute migraine medications.

Worthington I.

Metro Toronto Hospitals Drug Information Service (MetroDIS), Department of
Pharmacy at Sunnybrook. irene.worthington@swchsc.on.ca

OBJECTIVE: To discuss advantages and disadvantages of various routes of
administration and delivery systems for acute migraine medications, and to assist
family physicians in optimizing treatment for individual patients. QUALITY OF
EVIDENCE: A MEDLINE search from January 1966 to October 2000 and a Current
Contents search for the year 1999 to October 2000 were conducted. Randomized
controlled trials were selected, when available. Also included are guidelines
(Canadian), non-blinded trials, systematic reviews, and population-based studies.
MAIN MESSAGE: Selecting an appropriate way to deliver medication is important in 
acute migraine therapy. The parenteral route has advantages, such as rapid onset,
greater efficacy, and the possibility of use during nausea and vomiting.
Disadvantages include local site discomfort, inconvenience, and patients' dislike
of needles. Most patients prefer oral therapy, but gastric stasis and nausea and 
vomiting during a migraine attack might limit its use. The intranasal route
usually provides fairly rapid onset, but side effects, such as disturbances in
taste, can occur. The rectal route is another option, but absorption is sometimes
erratic, rectal irritation can occur, and few migraine medications are available 
in rectal formulation. CONCLUSION: Selection of appropriate medications and
suitable delivery systems for individual patients, based on the characteristics
of their attacks (e.g., severity, speed of progression to severe intensity,
degree of associated symptoms), ease of administration, and patient preference,
will optimize therapy for acute migraine attacks.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 11228033 [PubMed - indexed for MEDLINE]

3390: Pharmacoeconomics. 2000 Dec;18(6):557-66.

Effectiveness of eletriptan in reducing time loss caused by migraine attacks.

Wells NE, Steiner TJ.

Pfizer Central Research, Sandwich, England. Nicholas_Wells@Sandwich.Pfizer.com

BACKGROUND: The growing literature on the economics of migraine and its treatment
generally indicates that the direct healthcare costs of managing the disorder are
relatively low compared with the personal and societal burdens resulting from the
disruption to normal functioning caused by migraine attacks. OBJECTIVE: To
investigate the effectiveness of eletriptan, a new selective serotonin
(5-hydroxytryptamine; 5-HT)5-HTIB/ID agonist, in reducing both the
patient-focused burden of migraine and the amount of work time foregone during a 
single attack. DESIGN: In a phase III, multinational, randomised clinical trial, 
692 patients treated a migraine attack with eletriptan 40 mg or 80 mg, or
placebo. Patients responded to a questionnaire seeking information concerning the
amount of time lost from usual activities during the attack. Time loss
assessments were made 24 hours after the last dose taken and recorded in a diary.
MAIN OUTCOME MEASURES AND RESULTS: Patients receiving either dose of the active
compound were unable to perform their usual activities for a median period of 4
hours compared with 9 hours experienced by those taking placebo. This difference 
was highly statistically significant (p < 0.001). The time saving associated with
eletriptan usage reflected the differences in efficacy findings in the clinical
component of the study. CONCLUSION: In this placebo-controlled trial, eletriptan 
produced a significant reduction in the loss of usual functioning time associated
with a migraine attack. This gain clearly represents a substantial benefit to
patients with migraine irrespective of how it might most appropriately be valued 
in monetary terms. Further methodological progress in this area is warranted.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 11227394 [PubMed - indexed for MEDLINE]

3391: Brain Res Bull. 2001 Jan 1;54(1):83-9.

Sex steroid hormones exert biphasic effects on cytosolic magnesium ions in
cerebral vascular smooth muscle cells: possible relationships to migraine
frequency in premenstrual syndromes and stroke incidence.

Li W, Zheng T, Altura BM, Altura BT.

Department of Physiology and Pharmacology, State University of New York, Health
Science Center at Brooklyn, Brooklyn, NY 11203, USA.

Clinically, it is known that: (1) magnesium (Mg) supplementation relieves
premenstrual problems (e.g., migraine, bloating and edema) occurring in the late 
luteal phase of the menstrual cycle; and (2) migraine syndromes, particularly in 
women, are associated with deficits in brain and serum ionized Mg levels. We
investigated whether concentrations of sex steroid hormones, found in the serum
during the menstrual cycle of women, are associated with changes in the levels of
cytosolic free magnesium ions ([Mg2+]i in single cultured canine cerebral
vascular smooth muscle cells. The resting level of [Mg2+]i in these cells was 645
+/- 89 microM before exposure to sex steroid hormones. Exposure of these vascular
cells to a low concentration of estrogen (10 pg/ml) failed to interfere with the 
levels of [Mg2+]i. However, exposure to estrogen, at concentrations ranging from 
40 to 200 pg/ml, induced significant loss of [Mg2+]i in a concentration-dependent
manner. At a concentration of 200 pg/ml estrogen, the level of [Mg2+]i decreased 
approximately 30% in comparison with controls. Progesterone produced biphasic
effects on the levels of [Mg2+]i, depending on its concentration. Exposure of the
cultured cells to a low concentration of progesterone (0.5 ng/ml) resulted in an 
increased level of [Mg2+]i (from 690 +/- 50 microM to 753 +/- 56 microM, p <
0.05). However, when these cells were exposed to higher concentrations of
progesterone (i.e., from 5.0 to 20 ng/ml), the cellular levels of [Mg2+]i were
decreased significantly. The higher the estrogen or progesterone concentration,
the lower the levels of [Mg2+]i. In contrast, testosterone, a male hormone,
didn't produce any significant alteration in [Mg2+]i levels in these cerebral
vascular smooth muscle cells. These data indicate that low, physiological
concentrations of female sex hormones, estrogen and progesterone, help cerebral
vascular smooth cells sustain normal concentrations of [Mg2+]i, which are
beneficial to vascular function, whereas high levels of estrogen and progesterone
deplete, significantly, [Mg2+]i in cerebral vascular smooth muscle cells,
possibly resulting in cerebrovasospasms and reduced cerebral blood flows related 
to premenstrual syndromes, migraine and stroke risk. Our findings could provide
new insight into the mechanism whereby migraine occurs frequently in the late
luteal phase in the premenstrual syndrome. In addition, our results demonstrate
that female sex steroids but not testosterone (in physiologic concentrations) can
exert direct effects on [Mg2+]i in cerebral vascular cells.

Publication Types: 
    Research Support, U.S. Gov't, P.H.S.

PMID: 11226717 [PubMed - indexed for MEDLINE]

3392: Int J Clin Pract. 2000 Dec;54(10):670-4.

Pharmacology and efficacy of eletriptan for the treatment of migraine attacks.

Diener HC, McHarg A.

Department of Neurology, University of Essen, Hufelandstrasse 55, 45122 Essen,
Germany.

Sumatriptan, a 5-HT 1B/1D agonist, was introduced 10 years ago and was the most
effective therapy for migraine attacks at that time. Eletriptan is a new 5-HT
1B/1D agonist with high potency and selectivity at 5-HT 1B/1D receptors. It is
effective in animal models in which the vascular and neurogenic mechanisms
implicated in migraine were measured. Eletriptan is selective for the
intracranial blood vessels over other extracranial vasculature, in particular
coronary arteries. Eletriptan has a rapid and complete oral absorption and a good
oral bioavailability in migraineurs. In comparative trials 20 mg, 40 mg and 80 mg
eletriptan, 100 mg sumatritpan and placebo were compared for the treatment of
migraine attacks. All three doses of eletriptan were statistically superior to
placebo for headache response and headache-free patients. The 80 mg dose of
eletriptan was also superior to sumatriptan 100 mg. Headache recurrence, defined 
as return of moderate or severe headache within 24 hours of dosing and following 
a headache response at two hours after initial dosing, occurred in 33% of the
patients following 100 mg sumatriptan and in 28%, 34% and 32% after 20 mg, 40 mg 
and 80 mg eletriptan. In another large trial, headache response rates were
significantly higher for both doses of eletriptan (64% for 40 mg and 67% for 80
mg) than for two doses of sumatriptan (50% for 50 mg and 53% for 100 mg).
Eletriptan 40 mg or 80 mg was also superior to ergotamine plus caffeine
(Cafergot). In summary, eletriptan is a highly effective and fast-acting drug for
the treatment of acute migraine attacks.

Publication Types: 
    Comparative Study

PMID: 11221281 [PubMed - indexed for MEDLINE]

3393: Neurology. 2001 Feb 27;56(4):436-41.

Comment in:
    Neurology. 2001 Oct 23;57(8):1522.    Neurology. 2001 Oct 23;57(8):1522.

The interrelations of migraine, vertigo, and migrainous vertigo.

Neuhauser H, Leopold M, von Brevern M, Arnold G, Lempert T.

Neurologische Klinik, Charité, Humboldt-Universität, Berlin, Germany.
hanne.neuhauser@charite.de

OBJECTIVE: To assess the prevalence of migrainous vertigo in patients with
migraine and in patients with vertigo according to explicit diagnostic criteria
that are presented for discussion. METHODS: The authors prospectively evaluated
200 consecutive patients from a dizziness clinic and 200 patients from a migraine
clinic for migrainous vertigo based on the following criteria: 1) recurrent
vestibular symptoms (rotatory/positional vertigo, other illusory self or object
motion, head motion intolerance); 2) migraine according to the criteria of the
International Headache Society (IHS); 3) at least one of the following migrainous
symptoms during at least two vertiginous attacks: migrainous headache,
photophobia, phonophobia, visual or other auras; and 4) other causes ruled out by
appropriate investigations. In addition, the authors compared the prevalence of
migraine according to the IHS criteria in the dizziness clinic group with a sex- 
and age-matched control group of 200 orthopedic patients. RESULTS: The prevalence
of migraine according to the IHS criteria was higher in the dizziness clinic
group (38%) compared with the age- and sex-matched control group (24%, p < 0.01).
The prevalence of migrainous vertigo was 7% in the dizziness clinic group, and 9%
in the migraine clinic group. In 15 of 33 patients with migrainous vertigo,
vertigo was regularly associated with migrainous headache. In 16 patients,
vertigo occurred both with and without headache, and in two patients headache and
vertigo never occurred together. The duration of attacks varied from minutes to
days. CONCLUSION: These results substantiate the epidemiologic association
between migraine and vertigo and indicate that migrainous vertigo affects a
significant proportion of patients both in dizziness and headache clinics.

PMID: 11222783 [PubMed - indexed for MEDLINE]

3394: Invest Ophthalmol Vis Sci. 2001 Mar;42(3):626-33.

Visual dysfunction between migraine events.

McKendrick AM, Vingrys AJ, Badcock DR, Heywood JT.

Department of Optometry and Vision Sciences, University of Melbourne, Victoria
3010, Australia.

PURPOSE. To evaluate interictal visual dysfunction in persons with migraine in
terms of spatiotemporal selectivity and location within the visual pathways.
METHODS. The vision of a group of 15 persons who had experienced migraine with
aura was compared with that of 15 normal age-matched control subjects. A range of
thresholds was measured to evaluate precortical (background modulation, contrast 
thresholds for static, and moving stimuli), area V1 (orientation discrimination
and motion discrimination thresholds), and higher order (global dot motion
thresholds) visual processes. Testing was performed centrally and at 10 degrees
in the superior visual field. For each of the tests, the spatial and temporal
parameters of the stimuli were selected to bias detection toward either
parvocellular or magnocellular visual mechanisms. RESULTS. No defects were found 
for parvocellular processes. Significant (P: < 0.05) losses were apparent with
the temporal background modulation method (16 Hz), orientation discrimination
(0.5 cyc/deg), and global dot motion tasks. CONCLUSIONS. Both cortical and
precortical visual dysfunction were identified in migraine group 7 days after the
headache. This loss was selective for targets with temporal modulation of
approximately 16 Hz.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 11222520 [PubMed - indexed for MEDLINE]

3395: Clin Ther. 2001 Jan;23(1):127-45.

Treatment satisfaction, functional status, and health-related quality of life of 
migraine patients treated with almotriptan or sumatriptan.

Colman SS, Brod MI, Krishnamurthy A, Rowland CR, Jirgens KJ, Gomez-Mancilla B.

The Lewin Group, San Francisco, California 94107, USA. shoshana.colman@lewin.com

BACKGROUND: Patient-reported outcomes, such as treatment satisfaction, functional
status, and health-related quality of life (HRQOL) are essential components of
migraine research. Almotriptan is a new selective serotonin 1B/1D agonist triptan
migraine treatment. OBJECTIVE: The purpose of this double-blind, multicenter,
randomized, parallel-group study was to compare treatment satisfaction,
functional status, and HRQOL of patients treated with oral almotriptan versus
sumatriptan, the leading triptan on the market. METHODS: Migraine patients, aged 
18 to 71 years, took equivalent oral doses of 12.5 mg almotriptan or 50 mg
sumatriptan for the abortive treatment of a migraine headache. Treatment
satisfaction differences between study groups were assessed using a 6-item
measure to determine patients' satisfaction with pain relief and satisfaction
with side effects 48 hours after drug administration. Functional status was
assessed by analyzing the change in patients' ability to perform normal
activities during the course of the migraine. HRQOL was compared between
treatment groups at 24 hours using the Migraine Quality of Life Questionnaire.
End points were assessed using entries from patients' 48-hour diaries. RESULTS: A
total of 1173 patients were treated with almotriptan or sumatriptan. There were
no significant differences between the 2 treatment groups in terms of
satisfaction with pain relief; however, patients in the almotriptan group were
significantly more satisfied (less bothered) with side effects than those
receiving sumatriptan (P = 0.016). Functional status and HRQOL outcomes were not 
significantly different between groups. CONCLUSIONS: In this study, migraine
patients treated with almotriptan were significantly more satisfied with the
side-effect profile of the drug than patients treated with sumatriptan. The
results of this study may help inform practicing physicians and neurologists
about the potential treatment satisfaction advantages of almotriptan.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 11219473 [PubMed - indexed for MEDLINE]

3396: Manag Care Interface. 2001 Jan;14(1):68-72.

Comment in:
    Manag Care Interface. 2001 Jan;14(1):47-8.

Effect of sumatriptan on health care resource use among patients with migraine.

Joish VN, Cady PS.

College of Pharmacy, Idaho StateUniversity, Pocatello, Idaho, U.S.A.
Joish@pharmachy.arizona.edu

Previous investigations examining health care resource utilization in patient
populations have shown patients with migraine to consume significantly higher
health care resources compared with individuals without migraine. The purpose of 
this study was to compare health care resource and narcotic use in migraineurs
prescribed sumatriptan (oral, subcutaneous, or nasal) with those not prescribed
sumatriptan.

PMID: 11214537 [PubMed - indexed for MEDLINE]

3397: J Clin Pharmacol. 2001 Feb;41(2):170-5.

Pharmacokinetics of naratriptan in adolescent subjects with a history of
migraine.

Christensen ML, Eades SK, Fuseau E, Kempsford RD, Phelps SJ, Hak LJ.

Department of Clinical Pharmacy, Pediatric Pharmacology Research Unit, Center for
Pediatric Pharmacokinetics and Therapeutics, University of Tennessee, Memphis
38163, USA.

Naratriptan is a novel 5-HT1 agonist developed to treat acute migraine. The study
objective was to characterize the pharmacokinetics of oral naratriptan in
adolescent migraine patients outside a migraine attack. Subjects received a
single 2.5 mg naratriptan tablet. Serial serum samples for naratriptan
concentrations were collected over 24 hours. Blood pressure, pulse rate, and
12-lead ECG were recorded at baseline and at regular intervals after dosing.
Seven patients--3 males and 4 females, 12 to 16 years of age--received drug and
completed the study. The geometric mean and 95% confidence interval maximum
concentration (Cmax) was 8.0 ng/mL (5.9-10.7), elimination half-life (t1/2) was
4.9 hours (4.5-5.4), area under the concentration-time curve (AUC) was 74.6
ng.h/mL (56.6-98.2), and apparent total clearance (Cl/F) was 558.8 mL/min
(424.3-735.9). The median time to maximal concentration (tmax) was 4 hours, with 
a range of 1.5 to 4. Blood pressure, pulse rate, and ECG parameters did not
change significantly from baseline. No serious adverse events or subject
withdrawal after drug administration occurred. Oral naratriptan pharmacokinetic
parameters in adolescents were similar to values reported in adults. Naratriptan 
doses for adolescents older than 12 years of age would be expected to be similar 
to adult doses.

Publication Types: 
    Clinical Trial
    Controlled Clinical Trial
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 11210397 [PubMed - indexed for MEDLINE]

3398: Cephalalgia. 2000;20 Suppl 2:5-9.

Evidence-based migraine therapy: learning needs and knowledge assessment.

Purdy RA.

Division of Neurology, Dalhousie University and Queen Elizabeth II Health
Sciences Centre, Halifax, Nova Scotia, Canada.

One of the primary goals of continuing medical education (CME) is to enhance the 
learners' performance, and a major goal of evidence-based medicine (EBM) is to
improve knowledge of current best care. This paper overviews the use of a
Learning Needs and Knowledge Assessment tool to highlight the potential learning 
needs and knowledge of neurologists and to focus the issues, interest and
interactions of neurologists in a workshop on EBM migraine therapy. Virtually all
neurologists felt they used evidence-based medicine in their daily practice.
Surprisingly, 50% of neurologists agreed that they were uncertain which triptan
to use. The great majority of neurologists felt that the triptans were not all
equally efficacious. Our survey identified significant knowledge gaps among
neurologists regarding how to appraise the validity of evidence from a randomized
clinical trial, and with regard to what are the most clinically useful measures
of benefit in clinical trials.

Publication Types: 
    Review

PMID: 11206865 [PubMed - indexed for MEDLINE]

3399: Cephalalgia. 2000;20 Suppl 2:33-8.

Comment in:
    Cephalalgia. 2001 Nov;21(9):932-3; author reply 933-4.

Evidence-based analysis of a migraine treatment drug comparison trial.

Gawel M, Wiebe S.

Department of Medicine, Sunnybrook and Women's College Health Sciences Centre,
Toronto, Ontario, Canada.

Patients present with specific problems against a background of their particular 
situation. The applicability of a treatment to a specific case may be difficult
to assess in the light of the information available on that treatment.
Evidence-based medicine is a discipline developed to achieve the best informed
treatment decisions in clinical situations. In this paper, we illustrate a
logical approach to reaching a decision regarding which of two migraine
treatments should be used in a clearly defined patient. The information evaluated
is a comparative trial between sumatriptan (100 mg), rizatriptan (5 and 10 mg)
and placebo. The use of the analytical tools of evidence-based medicine is
demonstrated in this exercise. The example was chosen because this is an area of 
great current interest in the field of neurology.

Publication Types: 
    Comparative Study
    Review

PMID: 11206864 [PubMed - indexed for MEDLINE]

3400: Cephalalgia. 2000;20 Suppl 2:25-32.

Comment in:
    Cephalalgia. 2001 Nov;21(9):932-3; author reply 933-4.

Drug comparisons: why are they so difficult?

Salonen R.

Neurology & Psychiatry Therapeutic Development Group, Glaxo Wellcome, Research
Triangle Park, NC 27709, USA. rs86976@glaxowellcome.com

Comparing therapeutic agents in a drug class can be difficult. This article
examines the ways in which the triptans can be and have been compared and
evaluates the advantages and disadvantages of the approaches. Direct comparative 
trials are clearly the best method for evaluating the triptans, however, there is
a scarcity of this type of data on the currently available compounds. Indirect
comparison such as meta-analysis is a second method of comparing these agents but
only serves as an estimate of relative efficacy or safety based on a comparison
of pooled data derived from a number of different trials for each agent.
Comparison of the data found in the regulatory documents represents another type 
of indirect comparison that can be done so long as the data is presented in a
consistent format across products.

Publication Types: 
    Comparative Study
    Review

PMID: 11206863 [PubMed - indexed for MEDLINE]

3401: Cephalalgia. 2000;20 Suppl 2:14-24.

Acute migraine treatment outcome measures: a clinician's view.

Sheftell FD, Fox AW.

New England Center for Headache, Stamford, CT, USA.

The efficacy of acute therapies for migraine can be measured in many ways.
Traditional endpoints (such as reduction in pain from moderate or severe to mild 
or absent) are used for regulatory purposes, but do not reflect all components of
the migraine syndrome, nor, necessarily, what is most valued by patients and
clinicians. There is also a pharmacokinetic-pharmacodynamic disconnection for
these traditional types of endpoint, suggesting that they teach us little about
how these drugs work. More rigorous, but nonetheless pain-score based, endpoints 
are reviewed. The biases that can attach to measures such as therapeutic gain and
number needed to treat, in the context of migraine therapy, and the limitations
of these measures for use in meta-analysis, are discussed. The clinical
subtleties of these endpoints are numerous: understanding patients' ability to
distinguish between multiple headache types, the best timing of treatment
relative to the start of an attack, and measuring clinical outcome may be
statistically difficult, but yet may also provide more clinical utility than
pain-score analyses. The three therapeutic strategies (Step,
Stepped-within-attack, and Stratified care) are reviewed and the place of
5HT(1B/1D) agonists within them, based on the currently best available evidence, 
is identified. Consideration should be given to more real-life studies, to
measuring drug efficacy after early administration during onset of headache, and 
to greater sophistication in our approach to the necessarily gestalt measures of 
patient satisfaction and treatment preference.

Publication Types: 
    Review

PMID: 11206862 [PubMed - indexed for MEDLINE]

3402: Cephalalgia. 2000;20 Suppl 2:10-3.

The principles of evidence-based medicine.

Wiebe S.

Clinical Neurological Sciences University of Western Ontario, Canada.
swiebe@julian.uwo.ca

Evidence-based medicine (EBM) integrates individual clinical expertise with the
best available external evidence in the care of individual patients. By enabling 
clinicians to directly appraise and apply current clinical research, EBM deals
with the problems of deterioration in clinical performance, information overload,
and lag in application of research findings to clinical practice. Thus, EBM is a 
useful tool to address the problems faced by clinicians attempting to provide
optimum, current care for their patients. The rationale for EBM, its principles
and application, as well as some limitations, are described here.

Publication Types: 
    Review

PMID: 11206861 [PubMed - indexed for MEDLINE]

3403: Cephalalgia. 2000;20 Suppl 2:1-4.

The challenge of evidence-based migraine therapy.

Becker WJ.

Department of Clinical Neurosciences, University of Calgary and the Calgary
Regional Health Authority, Alberta, Canada.

It is important that physicians practise evidence-based medicine. Clinical
experience is important, but there are a number of reasons why clinical
experience can lead to the impression that ineffective treatments are effective. 
There are major educational and research challenges which must be met before
clinicians can practice evidence-based migraine therapy more extensively than at 
present. Treating physicians will need to learn more about the principles of
evidence-based medicine. Researchers will need to produce more and better
clinical trials that address important clinical questions. The results of these
trials will need to be reported clearly, and we need to improve the efficiency
with which these results can be accessed. It is important that the pharmaceutical
industry, clinicians, and academic health centres work together to meet these
challenges.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 11206860 [PubMed - indexed for MEDLINE]

3404: Dev Med Child Neurol. 2001 Jan;43(1):45-51.

Classification criteria and distinction between migraine and tension-type
headache in children.

Rossi LN, Cortinovis I, Menegazzo L, Brunelli G, Bossi A, Macchi M.

Pediatric Department, Institute of Biometry and Medical Statistics, University of
Milan, Italy. livia.rossi@unimi.it

The International Headache Society (IHS) classification system (1988) was
developed primarily for headache disorders in adults and its validity for
paediatric age is currently under discussion; in 1995 Seshia et al. proposed a
revision of the criteria for migraine without aura to make diagnostic criteria
more applicable to children. The purposes of the current study were to: (1)
compare the IHS classification with the Seshia proposal, (2) compare the children
affected by migraine without aura (MO) with the children affected by tension
headache (TH) as defined by Seshia, for characteristics which are not included in
the classification. The patients are a series of 320 children (mean age 9.9, SD
2.6 years; 144 males, 176 females) with recurrent or chronic headaches referred
to a headache clinic in Milan, Italy. Using the Seshia criteria instead of the
IHS criteria a higher number of children were included in the MO category:
bilateral pain and family history of migraine were the most important factors
which allowed a shift of children into this category. However, with the Seshia
classification there was no reduction in the number of unclassifiable children.
The reason why some children could not be classified was a short duration of
attacks; the majority of unclassifiable children were 6 years old or less. No
relevant difference was found between children with MO and children with TH for
the following variables: occurrence of attacks in the afternoon or evening after 
school, reduction of attacks during school holidays, full-time schooling,
after-school activities on school days, disordered daily life. On the contrary
children with MO when compared with those with TH showed a higher number of
precipitating factors and for the following factors a significant difference was 
found: exposure to TV or a computer, sleep deficiency, and strong emotions.
Furthermore, children with MO showed a greater severity of attacks.

Publication Types: 
    Comparative Study
    Validation Studies

PMID: 11201423 [PubMed - indexed for MEDLINE]

3405: Funct Neurol. 2000;15 Suppl 3:9-18.

Experimental models of migraine.

Reuter U, Sanchez del Rio M, Moskowitz MA.

Harvard Medical School, Massachusetts General Hospital, Stroke and Neurovascular 
Regulation Laboratory, 149 13th Street, Rm 6403, Charlestown, MA 02129, USA.

Experimental models have been developed to study various aspects of migraine.
Here we describe the most commonly used models--mostly animal models--which led
to the development of a pathophysiological concept of migraine. We focus on
activation studies of the trigeminovascular system, the sphenopalatine ganglion, 
the superior sagittal sinus, the dura mater as well as blood vessels. The most
common consequences of activation are noted and include protein extravasation,
neuropeptide release, rCBF and diameter changes, c-fos expression and electrical 
neuronal activity. In addition, we briefly summarize the results of cortical
spreading depression studies, as they relate to the human migraine aura. These
models will continue to be useful to elucidate migraine pathophysiology and
explore drug mechanisms.

Publication Types: 
    Review

PMID: 11200808 [PubMed - indexed for MEDLINE]

3406: Funct Neurol. 2000;15 Suppl 3:78-81.

Contingent negative variation as indicator of duration of migraine disease.

Kropp P, Siniatchkin M, Gerber WD.

Institute of Medical Psychology, Centre of Nervous Diseases, University of Kiel, 
Niemannsweg 147, D-24105 Kiel, Germany.

Amplitudes of early wave contingent negative variation (iCNV) reveal significant 
differences between migraine patients and healthy controls, indicating a lack of 
habituation and pronounced attentional functions in migraine patients. CNV
amplitudes were recorded in 20 migraine patients. The CNV amplitudes were Pearson
correlated with the individual duration of the migraine disease. Only iCNV
correlates inversely with the duration (r = -.544). The data show an influence of
duration of migraine disease on iCNV amplitudes. It is suggested that iCNV is an 
indicator of chronicity in persistent migraine.

Publication Types: 
    Clinical Trial
    Research Support, Non-U.S. Gov't

PMID: 11200805 [PubMed - indexed for MEDLINE]

3407: Funct Neurol. 2000;15 Suppl 3:73-7.

Neurophysiological evidence of increased cortical reactivity in migraine.

van Dijk JG.

Dept of Neurology and Clinical Neurophysiology, Leiden University Medical Centre,
PO Box 9600, 2300 RC Leiden, The Netherlands.

Cortical reactivity in migraine can be studied with evoked potentials. The
majority of the evidence shows increased reactivity in migraine, which may be due
to abnormal inhibition. At present, the techniques are not useful for diagnosis. 
Discrepancies between reports may be due to fluctuations in reactivity over time.
Documenting this changing reactivity requires refinement of analysis techniques.

Publication Types: 
    Review

PMID: 11200804 [PubMed - indexed for MEDLINE]

3408: Funct Neurol. 2000;15 Suppl 3:68-72.

From neurophysiology to genetics: cortical information processing in migraine
underlies familial influences--a novel approach.

Sándor PS, Afra J, Proietti Cecchini AP, Albert A, Schoenen J.

Department of Neurology, CHR Citadelle, University of Liège, Belgium.

Migraine patients show impaired cortical information processing between attacks
with deficient habituation of pattern-reversal visual evoked potentials (VEP),
and strong intensity dependence of auditory cortical evoked potentials (IDAP).
This could be a genetic trait as certain genetic patterns are known for evoked
potentials in healthy subjects. VEP-habituation and IDAP were studied in 40
migraine patients, i.e. pairs of 20 parents and their children. We developed a
novel approach based on Monte Carlo statistics to selectively assess vertical
familial influences. Both groups, parents and children, were characterized by
abnormal VEP-habituation and IDAP. However, similarity between related pairs was 
far more pronounced than similarity between unrelated pairs. Assessed with a
novel statistical approach, familial influences proved to be highly significant
in determining cortical information processing in migraineurs, thus supporting
the important role of genetic factors.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 11200803 [PubMed - indexed for MEDLINE]

3409: Funct Neurol. 2000;15 Suppl 3:63-7.

Central and peripheral mechanisms in migraine: a neurophysiological approach.

Jensen R.

Department of Neurology, University of Copenhagen, Glostrup Hospital, DK-2600
Glostrup, Denmark.

The author briefly reviews the main evidence in favour of both central and
peripheral factors supposed to take part in the complex pathomechanisms leading
to the activation of the trigemino-vascular system in the migraine attack.

Publication Types: 
    Review

PMID: 11200802 [PubMed - indexed for MEDLINE]

3410: Funct Neurol. 2000;15 Suppl 3:43-9.

Pharmacology of emesis and gastrointestinal motility: implications for migraine.

De Ponti F.

Department of Pharmacology, University of Bologna, Italy.

This paper outlines the physiopharmacology of emesis and its gastrointestinal
motor correlates in relation to the possible treatment strategies of a migraine
attack. The gastrointestinal motor correlates of vomiting consist of a
stereotyped motor response to diverse stimuli and basically include gastric
relaxation and a series of events (intestinal motor inhibition and disruption of 
slow wave activity) in preparation for the occurrence of a retrograde giant
contraction that propagates orally and empties intestinal contents into the
stomach. These motor correlates always accompany vomiting, but may also appear as
an independent phenomenon. Antidopaminergic agents, such as metoclopramide and
domperidone, have antiemetic/prokinetic properties, block the gastrointestinal
motor correlates of vomiting and may speed up absorption of antimigraine agents. 
The use of 5-HT4 receptor agonists may be an alternative strategy to achieve
prokinesia during a migraine attack, although this issue still needs to be fully 
addressed by controlled studies. Sumatriptan was found to induce gastric
relaxation and delay gastric emptying, but the impact of these effects during a
migraine attack remains to be determined.

Publication Types: 
    Review

PMID: 11200800 [PubMed - indexed for MEDLINE]

3411: Funct Neurol. 2000;15 Suppl 3:36-42.

The search for novel migraine therapies: experimental models.

Parsons AA, Bingham S.

Neurosciences Research, SmithKline Beecham Pharmaceuticals, New Frontiers Science
Park North, 3rd Avenue, Harlow, Essex CM19 5AW, UK.

The identification and development of the potent 5-HT1B/1D agonist, sumatriptan
has resulted in new therapeutic opportunities for the treatment of migraine and a
number of chemically novel agents with a similar mechanism of action have been
identified. Whilst these agents are optimised to enhance the therapeutic effect
of sumatriptan, development of mechanistically novel therapies may provide new
directions for the care of migraine sufferers. To develop new treatment
paradigms, novel chemical entities should be evaluated in animal models which are
predictive of therapeutic efficacy e.g.: in animal models where sumatriptan has
shown activity, or the pathophysiological processes involved in the disease must 
be targeted. Therefore, investigation of mechanisms underlying cortical activity 
and its involvement in the activation of trigeminal vascular pathways may allow
better understanding of the disease and result in the identification of new
non-triptan-like therapies.

Publication Types: 
    Review

PMID: 11200799 [PubMed - indexed for MEDLINE]

3412: Funct Neurol. 2000;15 Suppl 3:211-8.

The relevance and application of disease management and pharmacoeconomics to
migraine.

Wells NE.

Department of Outcomes Research, Pfizer Central Research, Europe.

Disease management is a comprehensive approach to improving the outcomes for
patients suffering from chronic disease. It has frequently been applied to
diseases like diabetes and asthma but, to date, has not widely been regarded as
particularly relevant to migraine. Yet a number of factors suggest that this view
might usefully be reconsidered, notably the dissatisfaction with migraine control
expressed by many patients and the inconsistencies in treatment patterns observed
across clinical practice. Another factor is the growing range of therapeutic
options available to manage the disorder. In this latter respect, decision-making
must not only be governed by individual patient needs, but also by considerations
of clinical cost effectiveness. Pharmacoeconomic analysis can play a useful role 
in determining the relative value for money offered by different treatments and
is increasingly being applied in migraine. It is clear, however, that full
realisation of its potential contribution requires progress to be made in a
number of key areas, perhaps most importantly agreement on the definition of
successful treatment.

Publication Types: 
    Review

PMID: 11200794 [PubMed - indexed for MEDLINE]

3413: Funct Neurol. 2000;15 Suppl 3:202-7.

NSAIDs: behind the mechanisms of action.

Tulunay FC.

Department of Pharmacology and Clinical Pharmacology and Headache Research
Center, Medical School of Ankara University, Ankara, Turkey.

Non-steroidal anti-inflammatory drugs (NSAIDs) are a heterogeneous group of
compounds. These heterogeneous agents have a similar therapeutic action for the
treatment of pain, fever and inflammation. The major mechanism of action of
NSAIDs is the inhibition of cyclooxygenase (COX), the enzyme catalysing the
synthesis of prostaglandins (PGs). Appropriate and effective treatment for
migraine depends upon an accurate diagnosis. The goals of treatment are
amelioration of the symptoms of an acute attack and prevention of further
attacks.

Publication Types: 
    Review

PMID: 11200793 [PubMed - indexed for MEDLINE]

3414: Funct Neurol. 2000;15 Suppl 3:196-201.

The effectiveness of combined oral lysine acetylsalicylate and metoclopramide
(Migpriv) in the treatment of migraine attacks. Comparison with placebo and oral 
sumatriptan.

Tfelt-Hansen P.

Department of Neurology, Glostrup Hospital, University of Copenhagen, Glostrup,
DK-2600 Glostrup, Denmark.

In two, double-blind, randomised, clinical, trials (RCTs), oral lysine
acetylsalicylate (1620 mg, equivalent to 900 mg aspirin) combined with
metoclopramide (10 mg) (LAS + MTC) was compared with placebo, and with oral
sumatriptan (100 mg) in one of these RCTs. In both RCTs the LAS + MTC combination
was superior to placebo with therapeutic gains (percentage relief after active
treatment minus percentage relief after placebo) of 30% and 31% for the first
treated attack. These therapeutic gains are in the same range as those found for 
100 mg oral sumatriptan, and in the comparative RCT the LAS + MTC combination was
quite comparable to 100 mg sumatriptan, with success rates for the first attack
of 57% and 53%, respectively.

Publication Types: 
    Clinical Trial
    Comparative Study
    Randomized Controlled Trial
    Review

PMID: 11200792 [PubMed - indexed for MEDLINE]

3415: Funct Neurol. 2000;15 Suppl 3:192-5.

New methods for evaluating acute treatments in migraine.

Buzzi MG, Fabbri L.

IRCCS Neuromed, Via Atinense 18, 86077 Pozzilli, IS, Italy.

The crescendo of activities in the field of migraine therapy, has led to the
emergence of a class of molecules, the triptans, that are similar in terms of
their activity on serotonin receptors, but which actually differ from one
another, as each one has its own peculiar clinical profile. A careful examination
of their clinical activity and their validation with objective methods may
promote the wise use of each drug, make room for new products, and allow patients
to make their own choices.

Publication Types: 
    Review

PMID: 11200791 [PubMed - indexed for MEDLINE]

3416: Funct Neurol. 2000;15 Suppl 3:182-91.

Rational migraine management: optimising treatment with the triptans.

Millson DS.

Keele University, ST5 5BG, UK.

In the last two years, a number of 5-HT1B/1D agonist triptans with enhanced
lipophilicity (TELs) relative to the first drug of this class, sumatriptan, have 
been approved for marketing in most countries of the world (naratriptan,
rizatriptan and zolmitriptan). In addition, at least three others are in advanced
stage of clinical development (almotriptan, eletriptan, and frovatriptan). This
paper sets out to review the recent data with the aim of identifying: 1) What are
the critical differences between the TELs and sumatriptan? 2) How do the
currently licensed TELs compare? 3) Is it possible to provide a rational approach
to migraine therapy based on objective differences in the clinical profile of
these new drugs? Recent randomised controlled and comparator data were reviewed, 
including the independent FDA assessment of rizatriptan. Critical differences for
the new TELs (naratriptan, rizatriptan and zolmitriptan) which may lead to more
rational migraine management: Both rizatriptan (10 mg) and zolmitriptan (2.5 mg
and 5.0 mg) have demonstrated superior efficacy to sumatriptan 100 mg, and 25 and
50 mg respectively. Therefore, for first line use either rizatriptan or
zolmitriptan would be appropriate for moderate and severe headache. Rizatriptan
has a more rapid onset of action than sumatriptan 100 mg. Both rizatriptan and
zolmitriptan have a more rapid onset of action than naratriptan. Therefore, for a
rapid onset of action either rizatriptan or zolmitriptan would be appropriate.
Naratriptan would appear to have a lower recurrent headache rate than
sumatriptan, rizatriptan or zolmitriptan. However, 24-hour efficacy rates for
zolmitriptan 2.5 mg were significantly greater than for sumatriptan 25 mg and 50 
mg and were not significantly different from naratriptan. Therefore, for
headaches of long duration and with a tendency to recur (e.g. menstrual
headaches) either naratriptan or zolmitriptan would be appropriate. Naratriptan
has lower reported adverse event rates comparable with placebo. This would
support the use of naratriptan 2.5 mg in patients who have demonstrated poor
tolerance to the "triptan type" adverse events.

Publication Types: 
    Review

PMID: 11200789 [PubMed - indexed for MEDLINE]

3417: Funct Neurol. 2000;15 Suppl 3:171-81.

Dopamine involvement in the migraine attack.

Fanciullacci M, Alessandri M, Del Rosso A.

Department of Internal Medicine, Headache Centre, University of Florence, Italy.

Clinical evidence and recent genetic findings seem to indicate an involvement of 
dopamine in the pathophysiology of the migraine attack. Prodromal symptomatology 
(mood changes, yawning, drowsiness, food craving), accompanying symptoms (nausea,
vomiting, hypotension) and postdromal symptoms (mood changes, drowsiness,
tiredness) may be related to dopaminergic activation. The dopaminergic system
could also play a role in the headache phase, either by taking part in
nociception mechanisms, or by regulating cerebral blood flow. A body of
pharmacological findings seems to support this involvement. Migraine patients,
between attacks, show a higher responsiveness to acute administration of
dopaminergic agents. Apomorphine administration induces in migraineurs more yawns
as well other dopaminergic symptoms e.g. nausea, vomiting, dizziness. Migraine
has been associated with hypotension and, occasionally, with syncope.
Bromocriptine causes severe orthostatic syndrome in migraine patients. Both
piribedil and apomorphine markedly increase cerebral blood flow of migraine
patients, thus indicating enhanced responsiveness of dopamine receptors which are
involved in cerebral blood flow regulation. Interictal dopaminergic
hypersensitivity has also been demonstrated by means of neuroendocrine tests.
Altered dopaminergic control of prolactin secretion exists in migrainous women.
L-deprenyl, a MAO-B inhibitor, is significantly more effective in reducing
prolactin levels in migraineurs than in controls. Taken together, these findings 
support the view that hypersensitivity of peripheral and central dopaminergic
receptors is a specific migraine trait. Finally, a high density of lymphocytic D5
receptors has been found in migraine sufferers, thus suggesting their
upregulation. Therefore, the hypothesis that dopaminergic activation is a primary
pathophysiological component in certain subtypes of migraine, namely those
characterised by marked dopaminergic symptomatology, has been advanced. From this
perspective, a blockade of dopaminergic hyperresponsive receptors can be
considered as a rationale for the therapy of migraine.

Publication Types: 
    Review

PMID: 11200788 [PubMed - indexed for MEDLINE]

3418: Funct Neurol. 2000;15 Suppl 3:163-70.

Dopaminergic hypersensitivity in migraine: clinical and genetic evidence.

Del Zompo M.

Headache Center, B.B. Brodie, Department of Neurosciences, University of
Cagliari, Via Porcell 4, 09124 Cagliari, Italy.

Migraine is a common disorder characterized by recurrent pain attacks of
mild-severe intensity associated with autonomic and occasionally neurological
symptoms. The migraine attack is a complex process that involves both central and
peripheral structures. Various pathogenetic hypotheses have been proposed but the
pathophysiology of the disease is still unknown. The study of the pathophysiology
of migraine includes the investigation of neurotransmitter systems and their
potential role in the development of the attack. Several studies performed since 
the '60s have demonstrated the key role of serotonin. The theory whereby
hypersensitivity of the dopaminergic system may be involved in the pathogenesis
of migraine has been supported by various authors on the basis of clinical,
pharmacological and recent genic evidence. Recent neurophysiological studies
performed using new techniques have led to a correlation of migraine with central
nervous system disorders characterized by an altered neuronal excitability.
Migraine seems to be characterized by a low threshold of neuronal excitability
which is in turn regulated by genetic factors involving the dopaminergic system. 
A genetically determined hypersensitivity of the dopaminergic system may be
involved in the onset of the migraine attack.

Publication Types: 
    Review

PMID: 11200787 [PubMed - indexed for MEDLINE]

3419: Funct Neurol. 2000;15 Suppl 3:157-62.

Central and peripheral mechanisms of migraine.

Sanchez del Rio M, Reuter U, Moskowitz MA.

Stroke & Neurovascular Regulation Laboratory, Department of Neurology,
Massachusetts General Hospital, Harvard Medical School, 149 13th Street,
CNY-6403, Charlestown, MA 20129, USA.

Central (cortex and upper brainstem) and peripheral (trigeminovascular)
mechanisms are involved in the pathophysiology of migraine. We propose that
unknown migraine triggers initiate depolarization of cortical neurons followed
concomitantly by a transient increase in blood flow. This transient hyperemia
spreads at a rate of 3-6 mm/min followed by hypoperfusion which is more
long-lasting. Through unknown mechanisms (probably chemical), we hypothesize that
this wave activates or sensitizes trigeminovascular axons which is a consequence 
of neuropeptide release and neurogenic inflammation. Orthodromic conduction along
trigeminovascular fibers transmits information centrally via the trigeminal
caudalis and other brainstem nuclei to higher cortical structures for
registration and modulation of nociceptive information.

Publication Types: 
    Review

PMID: 11200786 [PubMed - indexed for MEDLINE]

3420: Funct Neurol. 2000;15 Suppl 3:143-53.

Migraine associated with menstruation.

MacGregor A.

City of London Migraine Clinic and St Bartholomew's Hospital, London, UK.

Many women report increased frequency of migraine in association with
menstruation. The term 'menstrual' migraine is often used despite lack of an
agreed definition. The International Headache Society has classified most
headaches but not 'menstrual' migraine. A proposed definition is based on the
finding that the prevalence of migraine increases on day 1 +/- 2 of the menstrual
cycle. Attacks occurring at this time of the cycle are typically without aura.
Effective acute therapy is the mainstay of management for menstrual and
non-menstrual attacks although there is some evidence that attacks linked to
menstruation are less responsive to treatment compared with migraine at other
times of the cycle. If several attacks occur throughout the cycle, standard
prophylactic agents should be used. Women with exclusive 'menstrual' migraine may
benefit from perimenstrual prophylaxis but this should only be instigated once
the association between migraine and menstruation has been confirmed with
prospective records kept for a minimum of three cycles. NSAIDs are the treatment 
of choice in reducing migraine associated with menorrhagia and/or dysmenorrhoea, 
otherwise perimenstrual oestrogen supplements using percutaneous or transdermal
oestrogens are recommended. Combined oral contraceptives are useful for women
requiring contraception although there is a tendency for attacks to occur during 
the pill-free interval. If these are contraindicated, depot progestogen is an
alternative as it also inhibits ovulation and can improve migraine, provided
amenorrhoea is achieved. Oral progestogen-only contraception has little place in 
the management of 'menstrual' migraine as it does not inhibit ovulation and is
often associated with a disrupted menstrual cycle. Some women consulting with
menstrual migraine are menopausal and may be considering hormone replacement
therapy. Studies suggest that non-oral routes of delivery of oestrogen, which
provide stable levels, are more likely to improve migraine than oral oestrogens, 
which produce variable day-to-day levels. Too low a dose of oestrogen is
ineffective at controlling symptoms but too high a dose, particularly if coupled 
with surges of endogenous oestrogen, can trigger migraine aura. Once the route
and dose has been optimised, continuous oestrogens can control migraine as well
as menopausal symptoms. Additional progestogen, necessary for unhysterectomised
women, can exacerbate migraine. To minimise this, progesterone derivatives or
non-oral routes of delivery are recommended, with continuous regimens used where 
possible.

Publication Types: 
    Review

PMID: 11200785 [PubMed - indexed for MEDLINE]

3421: Funct Neurol. 2000;15 Suppl 3:137-42.

Hypothalamic resetting at puberty and the sexual dimorphism of migraine.

Facchinetti F, Sgarbi L, Piccinini F.

Department of Gynaecology, Obstetrics and Paediatric Sciences, University of
Modena and Reggio Emilia, Modena, Italy.

It is well known that migraine is far more represented in females than in males. 
However, this gender-related difference is present only during reproductive life 
since in prepubertal children, migraine prevalence figures are independent of
sex. Thus, transition to puberty accounts for changes which render females more
susceptible to migraine attacks. In females, the main driver of the hormonal
events allowing sexual maturation is the pulsatile secretion of hypothalamic LHRH
modulated by opioid activity. Clinical reports suggest that migraine attacks
could be prevented by the abolition of this neurohormonal secretion. On the other
hand, several clinical and experimental observations have focused on
neuroendocrine systems (opiatergic, serotonergic, adrenergic) as participating in
the constitution of the so-called "migraine trait", the biological predisposition
in patients that would explain their sensitivity to migraine triggers. Such
neuroendocrine secretions are mainly dependent upon hypothalamic activity where a
sexual dimorphic nucleus has been discovered in the preoptic area. We suggest
that the sexual dimorphism of migraine should be sought in hypothalamic networks 
related to LHRH secretion.

Publication Types: 
    Review

PMID: 11200784 [PubMed - indexed for MEDLINE]

3422: J Child Neurol. 2000 Dec;15(12):826-7.

Severe migraine associated with coarctation of aorta: complete recovery following
balloon dilation.

Shahar E, Borenstein A, Filk D.

Child Neurology Unit, Rambam Medical Center, Haifa, Israel.
e_shahar@rambam.health.gov.il

We report on a rare association of severe migraine headaches associated with
coarctation of aorta that completely resolved following dilation of the
constricted aorta. A 6-year-old girl presented with severe pounding headaches
accompanied with recurrent vomiting, associated with photophobia and phonophobia.
She experienced frequent awakenings with severe headaches and vomiting. The
described excruciating, prolonged, and practically persistent headaches were not 
relieved by analgesics and ergotamines. Neurologic assessment and brain computed 
tomography were both normal. A systolic murmur at the third right intercostal
space prompted a cardiac echocardiogram, which demonstrated coarctation of the
ascending aorta beyond the orifice of the left common carotid artery.
Catheterization revealed a systolic gradient of 54 mm Hg, and the constricted
lumen of the aorta was then dilated by a balloon. The excruciating vascular
headaches and associated symptoms had abated instantaneously following this
procedure. To the best of our knowledge, this is the first report associating
severe migraine headaches in a child with coarctation of the aorta. Given
complete recovery following balloon dilation of the aorta, cardiac echocardiogram
should be added to the diagnostic battery of children with severe unresponsive
migraine.

Publication Types: 
    Case Reports

PMID: 11198503 [PubMed - indexed for MEDLINE]

3423: Ann Neurol. 2001 Jan;49(1):7-13.

Comment in:
    Ann Neurol. 2001 Jan;49(1):4-6.

Is there a correlation between spreading depression, neurogenic inflammation, and
nociception that might cause migraine headache?

Ebersberger A, Schaible HG, Averbeck B, Richter F.

Department of Physiology, University of Jena, Germany.

The time course of propagation of scotoma and blood flow changes during migraine 
aura parallels the phenomenon of cortical spreading depression (CSD). It was
proposed that CSD generates a sterile neurogenic inflammation in the meninges,
which may then lead to the activation or sensitization of nociceptors, thus
generating headache. We performed rat experiments in which the effect of CSD on
plasma extravasation in the dura mater and on neuronal activity in deep laminae
of the trigeminal nucleus was assessed in vivo. CSD did not alter dural plasma
extravasation measured by means of bovine serum albumin-coupled flourescein (n = 
17 rats) compared to the CSD-free contralateral side. In an in vitro model, the
application of KCl to the dura at concentrations extracellularly found during CSD
did not alter the release of calcitonin gene-related peptide and prostaglandin E2
from the dura. In 33 rats, neither single CSDs nor a series of CSDs altered
ongoing neuronal activity or mechanical and/or thermal sensitivity of the deeply 
located neurons to stimulation of their receptive fields in the dura mater. These
results are at variance with data that showed increased c-Fos labeling in
superficial laminae of the trigeminal nucleus following CSD. They do not suggest 
that CSD initiates migraine headache via neurogenic inflammation.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 11198299 [PubMed - indexed for MEDLINE]

3424: Postgrad Med. 2001 Jan;109(1):49-54, 57-60.

A fresh look at migraine therapy. New treatments promise improved management.

Diamond S.

Diamond Headache Clinic and Diamond Inpatient Headache Unit, Columbus Hospital,
Chicago, USA. macf48@aol.com

Successful management of migraine headaches involves identifying and avoiding
headache triggers and using appropriate abortive therapy once a headache is
recognized. Pain relief measures include over-the-counter analgesics, parenteral 
NSAID therapy when needed, and use of antiemetics and cold packs. Narcotic
analgesics are best used only as a "last resort" measure. Prophylactic therapy
should be considered for patients who have more than two acute migraine attacks
each month or whose daily activities are seriously compromised by headaches. For 
the patient in whom status migrainosus threatens well-being, hospitalization and 
more intensive therapy may be needed.

Publication Types: 
    Review

PMID: 11198258 [PubMed - indexed for MEDLINE]

3425: Postgrad Med. 2001 Jan;109(1):38-40, 43-5.

Migraine's impact today. Burden of illness, patterns of care.

Lipton RB, Stewart WF, Reed M, Diamond S.

Albert Einstein College of Medicine of Yeshiva University, Bronx, New York, USA.

Migraine is a common disorder that causes severe headaches and associated nausea,
photophobia, phonophobia, and temporary disability. Though the pain and other
symptoms of migraine can be effectively managed, the condition remains
underdiagnosed and undertreated. In this article, Drs Lipton, Stewart, Reed, and 
Diamond consider the scope and distribution of the migraine problem and the
current patterns of care in the United States.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 11198257 [PubMed - indexed for MEDLINE]

3426: Clin Ther. 2000 Dec;22(12):1533-46.

One-year tolerability and efficacy of sumatriptan nasal spray in adolescents with
migraine: results of a multicenter, open-label study.

Rothner AD, Winner P, Nett R, Asgharnejad M, Laurenza A, Austin R, Peykamian M.

The Cleveland Clinic, Cleveland, Ohio 44195, USA. rothned@ccf.org

OBJECTIVE: The objective of this study was to determine the 1-year tolerability
and efficacy of sumatriptan nasal spray (NS) at doses of 5, 10, and 20 mg for the
treatment of acute migraine in adolescents. METHODS: This was a prospective,
multicenter, open-label, 1-year, multiple-attack study. Adolescents (aged 12-17
years) with a > or =6-month history of migraine with or without aura, 2 to 8
moderate or severe migraines per month, and a typical migraine duration of > or
=4 hours were eligible for participation. After initial treatment with
sumatriptan 10 mg, the dose could be adjusted down to 5 mg or up to 20 mg at the 
investigator's discretion to optimize tolerability or efficacy. Patients could
treat an unlimited number of moderate or severe migraine attacks, provided there 
was a 24-hour headache-free period between treated attacks and a 2-hour period
between doses of sumatriptan NS. A second dose of sumatriptan NS was available
for headache recurrence 2 to 24 hours after initial treatment; no more than 2
doses could be used within a 24-hour period. Adverse events, vital signs,
electrocardiographic and physical findings, and laboratory variables were
assessed. Headache response (reduction of moderate/severe predose pain to mild/no
pain) and pain-free response (reduction of moderate/severe predose pain to no
pain) were reported by patients 2 hours after dosing. RESULTS: A total of 437
patients treated > or =1 migraine; 3272 total attacks were treated, with 3675
drug exposures (mean, 1.1 dose/attack). Patients had a mean age of 14.1 years,
91% were white, and 53% were female. Seven patients used the 5-mg dose;
meaningful conclusions concerning this dose could not be made. Drug-related
adverse events were reported in 33% of attacks with the 10-mg dose and 31% with
the 20-mg dose; most were related to taste disturbance. Adverse events did not
increase with a second dose or over time. Four percent (16/437) of patients
withdrew due to drug-related adverse events. One serious adverse event, a
facial-nerve ischemic event (10-mg dose), was considered drug related. No
drug-related changes in vital signs or electrocardiographic findings were
observed. Headache response 2 hours after dosing was reported by 76% of patients 
taking the 10-mg dose and 72% of those taking the 20-mg dose. Pain-free response 
2 hours after dosing was reported by 43% and 40% of patients in the 10- and 20-mg
groups, respectively. Conclusions: Based on these results, sumatriptan NS at
doses of 10 and 20 mg was well tolerated and effective in the 1-year treatment of
multiple migraine attacks in adolescents.

Publication Types: 
    Clinical Trial
    Multicenter Study

PMID: 11192144 [PubMed - indexed for MEDLINE]

3427: Curr Med Res Opin. 2000;16(3):190-7.

Comparison of a fixed combination of domperidone and paracetamol (Domperamol)
with sumatriptan 50 mg in moderate to severe migraine: a randomised UK primary
care study.

Dowson A, Ball K, Haworth D.

Kings Headache Service, Kings College Hospital, Denmark Hill, London SE5 9RS.

Migraine is a common and debilitating condition routinely managed in primary
care. A number of treatment options--both acute and prophylactic--are currently
available but may differ in terms of efficacy, tolerability and cost. The aim of 
this study was to compare the effectiveness and tolerability of a fixed
combination of domperidone and paracetamol (Domperamol; Servier), which has
anti-nauseant and anti-emetic activity, with sumatriptan 50 mg in moderate to
severe migraine. To do this, 120 patients were recruited from 23 primary care
practices throughout the UK and were enrolled into the six-month trial. Patients 
were randomised at entry to one of the comparator regimens (used to treat their
first migraine attack) and then crossed over to the alternative treatment for
their second attack. Detailed diary cards were completed for each attack using a 
scale of pain severity. At two hours and four hours post-dose, the two treatments
showed comparable efficacy (< or = 15% difference) in relieving headache and
reducing nausea and vomiting. Both were well tolerated and there were no serious 
adverse effects. In the management of migraine patients typically seen in routine
general practice, this trial showed that the effects of Domperamol and
sumatriptan 50 mg were broadly comparable. Since Domperamol is considerably less 
expensive than sumatriptan (and other triptans), a first-line role for this agent
appears appropriate.

Publication Types: 
    Clinical Trial
    Comparative Study
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 11191009 [PubMed - indexed for MEDLINE]

3428: Epilepsia. 2001 Jan;42(1):62-6.

Visual symptoms in epilepsy and migraine: localization and patterns.

Muranaka H, Fujita H, Goto A, Osari SI, Kimura Y.

Department of Pediatrics, Hirosaki University School of Medicine, Zaifu-cho 5,
Hirosaki 036-8562, Japan. muranaka@cc.hirosaki-u.ac.jp

PURPOSE: To clarify differences in the localization of visual symptom patterns in
epilepsy and migraine, we analyzed patient-generated illustrations of visual
symptoms. METHODS: Patients were asked to draw their visual symptoms from memory 
using marker pens of 12 colors. All patients illustrated their symptoms on a
template sheet representing the binocular visual field. We analyzed a total of 67
illustrations from 54 patients aged 6-40 years: 28 with epilepsy, 23 with
migraine, and 3 with migraine-epilepsy syndrome. RESULTS: With respect to
positive visual manifestations, those of epileptic patients were predominantly
centrally localized (20 of 24, 83%), whereas those of migraine patients were
predominantly peripherally localized (10 of 13, 77%) (p < 0.0001). With respect
to negative visual symptoms, those in epilepsy were commonly diffuse (10 of 14,
71%) compared with those in migraine, which were peripheral (9 of 12, 75%) (p <
0.05). CONCLUSIONS: Results of this study suggest that the localization of visual
symptoms differs between epilepsy and migraine.

Publication Types: 
    Comparative Study

PMID: 11207786 [PubMed - indexed for MEDLINE]

3429: Pain. 2001 Feb 15;90(3):227-31.

Modulation of neuronal activity in the nucleus raphé magnus by the
5-HT(1)-receptor agonist naratriptan in rat.

Ellrich J, Messlinger K, Chiang CY, Hu JW.

Institute of Physiology and Experimental Pathophysiology,
Friedrich-Alexander-University, Universitätsstrasse 17, D-91054 Erlangen,
Germany. ellrich@pharmakologie.uni-erlangen.de

Modulatory effects of the new antimigraine drug naratriptan, a
5-HT(1)-receptor-agonist, on neurons of the nucleus raphé magnus were examined in
rat by extracellular recordings. In the nucleus raphé magnus neuronal activity
decreased in on-cells and increased in off-cells after intravenous administration
of naratriptan. The modulatory effects of naratriptan were similar to the
well-known effects of morphine on neurons in the nucleus raphé magnus. The
results of this study suggest central actions of naratriptan and may point to an 
involvement of the endogenous pain control system in the antinociceptive effects 
of the 5-HT(1)-receptor-agonist.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 11207394 [PubMed - indexed for MEDLINE]

3430: J Pediatr. 2001 Feb;138(2):176-80.

Comment in:
    J Pediatr. 2001 Feb;138(2):156-8.

Comorbidity of other pains in schoolchildren with migraine or nonmigrainous
headache.

Anttila P, Metsähonkala L, Mikkelsson M, Helenius H, Sillanpää M.

Departments of Child Neurology and Biostatistics, University of Turku, Turku,
Finland.

OBJECTIVE: To compare the occurrence of pain other than headache in prepubertal
children with migraine and those with nonmigrainous headache. STUDY DESIGN: An
unselected population-based prospective follow-up study on the occurrence of
headache in school-aged children was carried out in 1290 children aged 8 to 9
years. The children (n = 725) who reported headache during the preceding 6 months
were sent a more detailed questionnaire concerning the occurrence of pain other
than headaches; 622 children (86%) returned an acceptably completed second
questionnaire. Of them, 53 (8.5%) had migraine. Nonmigrainous headache was found 
in 460 children (74%). RESULTS: Children with migraine reported neck-shoulder
pain, abdominal pain, back pain, and otalgia significantly more often than those 
with nonmigrainous headache. The median of the sum of other pains in children
with migraine was significantly higher than that in children with nonmigrainous
headache. The sum of other pains correlated positively with the frequency of
nonmigrainous headache episodes (r =.40; 95% CI.31-.47), but there was no
correlation between the sum of other pains and frequency of migraine attacks (r =
-0.09; 95% CI -0.36-0.20). CONCLUSION: Children with migraine are more likely to 
report types of pain other than headaches, regardless of the frequency of
attacks. Children with frequent nonmigrainous headaches also report higher
frequencies of other types of pain.

PMID: 11174613 [PubMed - indexed for MEDLINE]

3431: Eur J Pharmacol. 2001 Feb 9;413(1):1-10.

The impact of pharmacogenetics for migraine.

Ophoff RA, van den Maagdenberg AM, Roon KI, Ferrari MD, Frants RR.

MGC-Department of Human and Clinical Genetics, Leiden University Medical Center, 
Wassenaarseweg 72, 2333 AL Leiden, Netherlands.

Migraine is a paroxysmal neurological disorder affecting up to 12% of males and
24% of females in the general population. As migraine has been demonstrated to
have a strong, but complex, genetic component, pharmacogenetics bears great
promise in providing new targets for drug development and optimization of
individual specific therapy. Better, preferably prophylactic, treatment of
migraine patients is desired because the drugs now used are not effective in all 
patients, allow recurrence of the headache in a high percentage of patients and
sometimes have severe adverse side-effects. With the recent identification of the
brain-specific P/Q-type Ca(2+)channel gene CACNA1A as a pivotal player in the
pathogenesis of migraine, the first step has been taken to identify primary
biochemical pathways leading to migraine. The work on migraine can also have
implications for the increasing number of additional neurological episodic
disorders having the common denominator of channelopathy.

Publication Types: 
    Review

PMID: 11173058 [PubMed - indexed for MEDLINE]

3432: Clin Sci (Lond). 2001 Feb;100(2):215-20.

Comment in:
    Clin Sci (Lond). 2005 Apr;108(4):365-7.

Relationship between migraine and cardiac and pulmonary right-to-left shunts.

Wilmshurst P, Nightingale S.

Royal Shrewsbury Hospital, Mytton Oak Road, Shrewsbury SY3 8XQ, U.K.

A relationship between migraine with aura and the presence of right-to-left
shunts has been reported in two studies. Right-to-left shunts are also associated
with some forms of decompression illness. While conducting research in divers
with decompression illness, it was our impression that divers with a large shunt 
often had a history of migraine with aura in everyday life and after dives.
Therefore we routinely asked all divers about migraine symptoms. The medical
records of the last 200 individuals referred for investigation of decompression
illness were reviewed to determine the association between right-to-left shunts
and migraine aura after diving, and migraine in daily life unconnected with
diving. Migraine with aura in daily life unconnected with diving occurred
significantly more frequently in individuals who had a large shunt which was
present at rest (38 of 80; 47.5%) compared with those who had a shunt which was
smaller or only seen after a Valsalva manoeuvre (four of 40; 10%) or those with
no shunt (11 of 80; 13.8%) (P<0.001). Hemiplegic migraine occurred in 10 divers, 
each of whom had a shunt that was present at rest; in eight of these cases the
shunt was large. The prevalence of migraine without aura was similar in all
groups. Post-dive migraine aura was significantly more frequent in individuals
who had a large shunt present at rest (21 of 80; 26.3%) compared with those who
had a shunt that was smaller or only seen after a Valsalva manoeuvre (five of 40;
12.5%) or no shunt (one of 80; 1.3%) (P<0.001). Thus individuals with a large
right-to-left shunt have an increased prevalence of migraine with aura in daily
life unconnected with diving, and they also have an increased incidence of
migraine aura after dives, but only when the dives liberate venous bubbles. These
data suggest the possibility that, in some individuals, right-to-left shunts have
a role in the aetiology of migraine with aura. The observations suggest that
paradoxical gas embolism may precipitate migraine with aura.

PMID: 11171291 [PubMed - indexed for MEDLINE]

3433: Headache. 2001 Jan;41(1):99-101.

Subarachnoid hemorrhage or migraine?

Evans RW, Davidoff RA.

The differential diagnosis of "the worst headache of my life" is illustrated by
the following history.

Publication Types: 
    Case Reports

PMID: 11168612 [PubMed - indexed for MEDLINE]

3434: Headache. 2001 Jan;41(1):97-8.

Migraine versus multiple sclerosis.

Evans RW, Rolak LA.

A headache associated with focal neurological signs and symptoms is always a
clinical dilemma.

Publication Types: 
    Case Reports

PMID: 11168611 [PubMed - indexed for MEDLINE]

3435: Headache. 2001 Jan;41(1):92-6.

Successful use of propranolol in migraine associated with electroconvulsive
therapy.

Hawken ER, Delva NJ, Lawson JS.

Kingston Psychiatric Hospital and the Department of Psychiatry, Queen's
University, Kingston, Ontario K7L 3J7, Canada.

To date, there have been no reports on the use of propranolol in
electroconvulsive therapy (ECT)-induced migraine; we describe a 32-year-old woman
who was successfully treated with propranolol for this condition. Over a course
of ECT, the patient developed increasingly severe migraine which was refractory
to treatment with acetaminophen, codeine, and naproxen. Sumatriptan did not
relieve the headache and aggravated the nausea. Successful migraine relief was
achieved with a combination of propranolol and naproxen, administered before and 
after ECT. Propranolol reduced blood pressure and decreased the heart rate,
measured before and immediately after ECT. Propranolol, possibly in combination
with naproxen, may be useful in both acute and prophylactic treatment of post-ECT
migraine.

Publication Types: 
    Case Reports

PMID: 11168610 [PubMed - indexed for MEDLINE]

3436: Headache. 2001 Jan;41(1):88-91.

Migraine-associated vomiting and asystole in a child.

Buchhalter JR, Berland G, Konkol R, Silka M.

Division of Pediatric Neurology, Oregon Health Sciences University, Portland, OR,
USA.

A variety of symptoms that accompany migraine in the child and adult are mediated
by the autonomic nervous system. Significant effects on cardiac rhythm are
uncommon, but can be life threatening. We describe a 3-year-old girl in whom
migraine-associated vomiting precipitated cardiac asystole which was effectively 
treated with a cardiac pacemaker.

Publication Types: 
    Case Reports

PMID: 11168609 [PubMed - indexed for MEDLINE]

3437: Headache. 2001 Jan;41(1):84-7.

Migraine with aura after administration of sublingual nitroglycerin tablets.

Bánk J.

Kenézy Teaching Hospital, Neurology Department, Debrecen, Bartók Béla u.3, 4031
Hungary.

As a nitric oxide donor, nitroglycerin can trigger migraine in migraineurs. The
headache is not characteristically accompanied by an aura. A patient with no
personal or family history of migraine reported the development of a typical
visual aura and a throbbing headache while using nitroglycerin for angina
pectoris. The possible mechanisms are discussed.

Publication Types: 
    Case Reports

PMID: 11168608 [PubMed - indexed for MEDLINE]

3438: Headache. 2001 Jan;41(1):72-8.

Interictal and postictal contingent negative variation in migraine without aura.

Mulder EJ, Linssen WH, Passchier J, de Geus EJ.

Department of Biological Psychology, Vrije Universiteit, De Boelelaan 1111, 1081 
HV, Amsterdam, The Netherlands.

Cortical hyperexcitability is thought to explain the more enhanced contingent
negative variation (CNV) amplitudes and impaired CNV habituation that have been
found during the interictal period in migraine without aura. These CNV
characteristics have been shown to normalize to the level of healthy controls
during an attack. This study aimed to replicate the interictal findings, and
additionally examine whether migraineurs show reduced CNV amplitudes during the
postattack period. Of 12 patients with migraine without aura and their sex- and
age-matched healthy controls, CNV characteristics were recorded once in an
interictal period, once during the postattack period within 30 hours after an
attack that was treated with sumatriptan, and once after an attack that was
treated with habitual nonvasoactive medication (counterbalanced). The present
results did not confirm the enhanced CNV early and late wave amplitudes or
impaired habituation, and cortical hyperexcitability that have previously been
reported in the interictal period in patients with migraine without aura. During 
the postattack period, a decrease in CNV early and late amplitudes was found but 
only after sumatriptan use. This reduction in CNV amplitudes was most prominent
over the frontal cortex and could reflect cortical hypoexcitability, possibly
related to a suppression of central catecholaminergic activity by sumatriptan.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 11168606 [PubMed - indexed for MEDLINE]

3439: Headache. 2001 Jan;41(1):63-71.

Aminergic tone correlates of migraine and tension-type headache: a study using
the tridimensional personality questionnaire.

Di Piero V, Bruti G, Venturi P, Talamonti F, Biondi M, Di Legge S, Lenzi GL.

Centro Interuniversitario per lo Studio delle Cefalee e dei Disordini
Neurotrasmettitoriali del Sistema Nervoso, Rome, Italy.

BACKGROUND: Aminergic neurotransmitter activity has been studied in many
neuropsychiatric diseases by means of a self-administered questionnaire proposed 
by Cloninger. Given that central aminergic modulation plays a major role in the
pathophysiology of primary headaches, we investigated the personality dimensions 
related to aminergic neurotransmitter activity in patients with migraine and
tension-type headache. METHODS: From a consecutive series of 230 patients, we
selected those presenting with migraine and tension-type headache according to
the International Headache Society criteria. All patients were assessed by means 
of the Cloninger 100-item self-report Tridimensional Personality Questionnaire
and a depression scale. The four dimensions of personality are novelty seeking
(dopaminergic), harm avoidance (serotonergic), reward dependence (noradrenergic),
and persistence (glutaminergic). RESULTS: One hundred twenty-one patients
presenting with migraine and 42 with tension-type headache were recruited. The
results indicate significantly higher harm avoidance scores (P<.001) in both
patients with migraine and those with tension-type headache than in controls.
Furthermore, patients with migraine had a significantly low score in the novelty 
seeking dimension (P<.001). When we compared only the two groups of patients with
headache, we found that the persistence dimension alone was significantly higher 
in patients with migraine than in those with tension-type headache (P<.05). No
differences were observed either in the overall scores of the other personality
dimensions or in the depression scale scores. CONCLUSIONS: The Tridimensional
Personality Questionnaire results support a role of the serotonergic system in
both migraine and tension-type headache pathophysiology. A dysfunction of
dopaminergic and glutaminergic tone seems to be a specific feature of migraine.

Publication Types: 
    Comparative Study

PMID: 11168605 [PubMed - indexed for MEDLINE]

3440: Headache. 2001 Jan;41(1):57-62.

Long-term efficacy and safety of oral almotriptan: interim analysis of a 1-year
open study.

Cabarrocas X, Esbri R, Peris F, Ferrer P.

Medical Department/Clinical Research, Laboratorios Almirall, SA, E-08024
Barcelona, Spain.

OBJECTIVE: To assess the long-term tolerability and safety of a single, oral
12.5-mg dose of almotriptan and its efficacy in alleviating pain associated with 
consecutive migraine episodes occurring during a 12-month period. BACKGROUND:
While sumatriptan appears to be effective for treatment of migraine, the drug has
several properties that limit its use. Almotriptan, a new selective 5-HT1B/1D
agonist, may be better tolerated over the long term. METHODS: This 1-year study
was conducted on 806 adults between the ages of 18 and 65 years suffering from
migraine, either with or without aura. The patients met the criteria for study as
outlined by the International Headache Society and were instructed on drug use.
Oral almotriptan 12.5 mg was used to treat the attack of any pain severity and a 
second dose was permitted in case of relapse of pain during the first 24 hours.
Rescue medication was provided. Efficacy and tolerability were assessed by a
combination of patient reporting and clinical visit evaluations. RESULTS:
Overall, almotriptan was well tolerated. At 2 hours, 81% of attacks were
relieved; 56% of the subjects were entirely free of pain. These efficacy data are
similar for the first as well as the last attack studied. At analysis, 534
patients had treated their migraines for at least 6 months. About half of all
patients experienced at least one adverse event, with 87% of the events being
mild or moderate in nature. The most frequent adverse events were back pain
(7.23% of patients), bronchitis (5.76%), and influenzalike symptoms (5.62%).
Seventy-one percent of the adverse events were not related to almotriptan use.
CONCLUSIONS: Almotriptan at an oral dose of 12.5 mg is safe antimigraine
treatment. The safety profile results are similar to those obtained in other
controlled triptan clinical studies. Almotriptan is efficacious in
moderate-to-severe migraine pain and can be used repeatedly in recurrent
episodes. The long-term safety data will be reanalyzed when full data become
available.

Publication Types: 
    Clinical Trial
    Research Support, Non-U.S. Gov't

PMID: 11168604 [PubMed - indexed for MEDLINE]

3441: Headache. 2001 Jan;41(1):49-56.

Migraine and masticatory muscle volume, bite force, and craniofacial morphology.

Lamey PJ, Burnett CA, Fartash L, Clifford TJ, McGovern JM.

School of Clinical Dentistry, The Queen's University of Belfast, The Royal Group 
of Hospitals, Grosvenor Road, Belfast BT12 6BP, Northern Ireland, UK.

The purpose of this investigation was to compare the masticatory muscle volume,
bite force, and craniofacial morphology of migrainous subjects with age- and
sex-matched controls. Ten adult dentate migraineurs were matched with 10 dentate 
age- and sex-matched controls. The groups consisted of nine women and one man
(mean age, 43 years; range, 29 to 51 years). Volumetric analysis of the masseter 
and medial pterygoid muscles was performed using magnetic resonance imaging.
Craniofacial morphology was analyzed from standard cephalometric radiographs
using 30 angular and linear variables. Recordings of bite force were made using a
strain gauge transducer. There was a significant difference in the volume of both
masseter and medial pterygoid muscles between the two subject groups (P<.0001),
with the muscles of the migraineurs nearly 70% larger. The migraineurs recorded
significantly higher maximal bite forces (P<.0001) than did the controls. No
significant differences for any craniofacial morphological measurement were
demonstrated between the two groups. It was concluded that the migraineurs had
larger masseter and medial pterygoid muscle volumes, and greater bite forces than
the controls, which could not be explained by any change in craniofacial
morphology.

Publication Types: 
    Comparative Study

PMID: 11168603 [PubMed - indexed for MEDLINE]

3442: Headache. 2001 Jan;41(1):40-8.

Perceived scintillation rate of migraine aura.

Crotogino J, Feindel A, Wilkinson F.

Department of Psychology, McGill University, 1205 Dr. Penfield Avenue, Montreal, 
Quebec H3A 1B1, Canada.

OBJECTIVE: To measure the perceived rate of flicker (temporal frequency) observed
during visual auras. BACKGROUND: The flickering or scintillating quality of aura 
elements is a commonly described characteristic of visual migraine auras.
Hypotheses about the neural mechanisms involved in aura have rarely taken this
feature into account, perhaps because of a lack of quantitative data on this
aspect of the aura. While a rate of 10 Hertz had been suggested in the
literature, estimates have been speculative due to the difficulty of judging
temporal frequencies subjectively. METHODS: Eleven participants were given
portable devices that contained an adjustable light-emitting diode with which to 
match the flickering of their auras. Observers were asked to make flicker matches
at two time points so that rate change during aura progression could be analyzed.
RESULTS: Data were obtained for 36 aura episodes. The mean rate of flicker across
individuals was 17.8 Hertz. Rates varied widely between individuals, but were
more consistent across multiple episodes in the same observer. Rate of flicker
did not appear to relate to aura side or type, or to individual characteristics
such as migraine history. When episodes were analyzed for change in flicker rate 
over time, patterns of increase (n = 7), decrease (n = 4), and no change (n = 22)
were all observed. CONCLUSIONS: When measured with an objective task, aura
scintillation rates were found to be somewhat higher than previous anecdotal
observations had suggested. These data are discussed in the context of two
competing hypotheses concerning the neural mechanism underlying the flicker
percept during migraine aura.

Publication Types: 
    Clinical Trial
    Controlled Clinical Trial
    Research Support, Non-U.S. Gov't

PMID: 11168602 [PubMed - indexed for MEDLINE]

3443: Headache. 2001 Jan;41(1):31-9.

Self-reported photophobic symptoms in migraineurs and controls are reliable and
predict diagnostic category accurately.

Mulleners WM, Aurora SK, Chronicle EP, Stewart R, Gopal S, Koehler PJ.

Department of Neurology, Atrium Medical Center, PO Box 4446, 6401 CX Heerlen, The
Netherlands.

OBJECTIVES: To assess the reliability of self-reported photophobia across
different patient populations and to examine how visual stress thresholds and
photophobic symptoms may be predictive of diagnosis. BACKGROUND: Relatively
little is known about interictal photophobia in migraine. In particular, the
variability of photophobia across different patient groups has not previously
been studied, and a pathophysiological hypothesis to account for the symptoms is 
not agreed upon. METHODS AND RESULTS: Study 1 compared 99 self-selected Dutch
patients and 101 headache-free controls using survey methods. Patients both with 
and without aura were significantly more likely to report symptoms, such as the
wearing of sunglasses in normal daylight, consistent with interictal photophobia.
Study 2 replicated these findings in a series of consecutive referrals to a
headache clinic in the United States. Study 3 used a specially designed
laboratory test to examine the threshold for visual stress in those patients who 
had participated in study 2. Visual stress thresholds were significantly lower in
patients than in controls. A discriminant function analysis of data from both
studies 2 and 3 showed that diagnostic category (migraine; control) could be
predicted from photophobic symptoms and visual stress thresholds at a level
significantly better than chance. CONCLUSIONS: We suggest that interictal
photophobia is common in migraine and similar across different patient
populations. One pathophysiological hypothesis is that interictal photophobia is 
associated with cortical hypersensitivity to stimulation. The predictive validity
of interictal photophobic symptoms suggests that clinical diagnosis may be aided 
by questioning the patient about light sensitivity in the period between attacks.

Publication Types: 
    Clinical Trial
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 11168601 [PubMed - indexed for MEDLINE]

3444: Headache. 2001 Jan;41(1):1-10.

Childhood headache, stress in adolescence, and primary headache in young
adulthood: a longitudinal cohort study.

Waldie KE.

Dunedin Multidisciplinary Health and Development Research Unit, Department of
Preventive and Social Medicine, Dunedin School of Medicine, University of Otago, 
PO Box 913, Dunedin, New Zealand.

OBJECTIVES: To determine the association between childhood history of headache,
adolescent stress, and headache syndromes (determined by International Headache
Society criteria) in young adulthood. BACKGROUND: The association between stress 
and tension-type headache has recently been challenged. Little is known about
stress and other headache subtypes, particularly among young people from the
general population. DESIGN: Members of the longitudinal Dunedin Multidisciplinary
Health and Development Study participated in this study. Study members were asked
about headache characteristics/symptoms at aged 26 (96% of the living cohort),
and historical records were examined to ascertain headache history (younger than 
12 years) and the reporting of stressful life events at aged 15 years. RESULTS:
Study members with childhood headache were significantly more likely to report
adolescent stress than those without headache. High-intensity stress during mid
adolescence increased the likelihood of migraine diagnosis. In those with
combined headache (migraine as well as tension-type headache), this relation held
only for those with a history of headache. Stress associated with bodily changes 
during mid adolescence was the only significant predictor of tension-type
headache. CONCLUSIONS: Childhood headaches are related to the appraisal of life
events reported during mid adolescence. Childhood headaches also appear to confer
a specific risk for the development of combined headache. There was little
evidence for a prospective relation between stress in mid adolescence and
tension-type headache in young adulthood, supporting claims that proximal (rather
than distal) stress is associated with this disorder.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 11168598 [PubMed - indexed for MEDLINE]

3445: Cephalalgia. 2000 Nov;20(9):830-4.

Work and productivity loss in the rizatriptan multiple attack study.

Dasbach EJ, Carides GW, Gerth WC, Santanello NC, Pigeon JG, Kramer.

Merck & Co, Inc, Blue Bell, PA 19422, USA. erik_dasbach@merck.com

The objective of this study was to measure the self-reported effect of acute
migraine and its treatment on paid work and productivity loss. Patients
self-administered a questionnaire in which the impact of a recent migraine on
paid work and productivity activities was assessed. We included the questionnaire
in a randomized, double-blind, placebo-controlled, crossover, out-patient study
designed to examine the safety and efficacy of rizatriptan (5-HT1B/1D receptor
agonist) 10 mg p.o. in patients treating four separate migraine attacks. A total 
of 407 patients, aged 18-65 years, suffering from moderate to severe migrainous
headaches was studied. Patients receiving rizatriptan compared with placebo
reported 0.7 fewer hours (P < 0.01) of paid worked missed due to absenteeism, 0.4
fewer hours (P < 0.05) of productive time lost on the job, and 1.1 fewer total
hours (P < 0.01) of work loss per migraine attack. Rizatriptan compared with
placebo significantly reduced migraine-related work loss associated with
absenteeism and decreased effectiveness on the job.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 11167913 [PubMed - indexed for MEDLINE]

3446: Cephalalgia. 2000 Nov;20(9):821-5.

Possible risk factors and precipitants for migraine with aura in discordant
twin-pairs: a population-based study.

Ulrich V, Olesen J, Gervil M, Russell MB.

Department of Neurology, Glostrup Hospital, University of Copenhagen, Denmark.
ulrich@post1.tele.dk

The aim of the present study was to detect possible risk factors in migraine with
aura (MA) by analysis of discordant twin-pairs. In a recent population-based twin
study we established that environmental factors account for approximately 50% of 
the variation in liability to MA. A cohort of 5,360 same-gender twin-pairs from
the general population was screened for migraine. All twin-pairs with possible
migraine were interviewed by a physician. A questionnaire provided information
about living conditions and lifestyle. Of the 169 discordant twin-pairs 51 were
monozygotic and 118 were dizygotic twin-pairs. Several putative risk
factors-schooling, education, marital status, smoking status and alcohol
consumption-showed no association with MA. The presence of migraine without aura 
or tension-type headache did not increase the risk of MA. Stress and mental
tension, and bright light precipitated attacks of MA in, respectively, 44% and
28% of the twins.

PMID: 11167911 [PubMed - indexed for MEDLINE]

3447: Cephalalgia. 2000 Nov;20(9):804-20.

Visual, long-latency auditory and brainstem auditory evoked potentials in
migraine: relation to pattern size, stimulus intensity, sound and light
discomfort thresholds and pre-attack state.

Sand T, Vingen JV.

Department of Clinical Neurosciences, Trondheim University Hospital, Norwegian
University of Science and Technology. trond.sand@medisin.ntnu.no

We aimed to estimate primary sensory evoked potential (EP) amplitude,
amplitude-intensity functions and habituation in migraine patients compared with 
healthy control subjects and to investigate the possible relation to check size, 
sound and light discomfort thresholds, and the time to the next attack.
Amplitudes of cortical visual evoked potentials (VEP, check size 8' and 33'),
cortical long latency auditory evoked potential (AEP NIP1; 40, 55 and 70 dB SL
tones) and brainstem auditory evoked potential (BAEP wave IV-V; 40, 55 and 65 dB 
SL clicks) were recorded and analysed in a blind and balanced design. The
difference between the response to the first and the second half of the stimulus 
sequence was used as a measure of habituation. Twenty-one migraine patients (16
women and five men, mean age 39.3 years, six with aura, 15 without aura) and 22
sex- and age-matched healthy control subjects were studied (18 women and four
men, mean age 39.5 years). Low sound discomfort threshold correlated
significantly with low levels of BAEP wave IV-V amplitude habituation (r = -0.30,
P = 0.05). VEP an AEP amplitudes, habituation, and amplitude-intensity function
(ASF) slopes did not differ between groups when ANOVA main factors were
considered. Control group VEP habituation was found for small check stimuli (P = 
0.04), while potentiation was observed for medium sized checks (P = 0.02). The
eight migraine patients who experienced headache within 24 h after the test
tended to have increased BAEP wave IV-V ASF slopes (P = 0.08). This subgroup did 
also have a significant VEP habituation to small checks (P = 0.04). No
correlation was found between different modalities. These results suggest that:
(i) VEP habituation/potentiation state and brainstem activatio state may depend
on the attack-interval cycle in migraine; (ii) VEP habituation/ potentiation may 
depend on spatial stimulus frequency; (iii) phonophobia (and possibly
photophobia) may depend more on subcortical (brainstem) function than on cortical
mechanisms; (iv) low cortical preactivation in migraine could not be confirmed;
(v) EP habituation and ASF analysis may reflect sensory modality-specific, not
generalized, central nervous system states in migraine and healthy control
subjects.

PMID: 11167910 [PubMed - indexed for MEDLINE]

3448: Cephalalgia. 2000 Oct;20(8):738-9.

Migraine-like headache in bacterial meningitis.

Lampl C, Yazdi K, Buzath A, Klingler D.

Department of Neurology, Psychiatry and Pain Clinic, General Hospital Linz,
Austria. christian.lampl@akh.linz.at

The effect of sumatriptan has not been previously described in the treatment of
the headache of meningitis, although this headache has similarities to migraine. 
This study presents the clinical features of two patients who had fulminant
bacterial meningitis with migraine-like headache and who experienced no
improvement in headache intensity after administration of sumatriptan 6 mg s.c.
On these grounds the lack of response of this type of headache to sumatriptan is 
discussed.

Publication Types: 
    Case Reports

PMID: 11167904 [PubMed - indexed for MEDLINE]

3449: Cephalalgia. 2000 Oct;20(8):732-7.

Are triptans with enhanced lipophilicity used for the acute treatment of migraine
associated with an increased consulting rate for depressive illness?

Millson D, Frischer M, Croft P, Goadsby PJ.

Primary Care Sciences Research Centre, Keele University, London, UK.
d.millson@keele.ac.uk

1997, sumatriptan-treated migraineurs had significantly higher depression PCRs
(22.3%) compared with non-triptan users (19.3%), a difference of 6.4% (95%
confidence interval (CI) 4.6-8.4%, P < 0.001). In the year (April 1997 to March
1998) following the launch of the TELs, depression PCRs were significantly higher
among patients using these compounds compared with sumatriptan-treated patients
(5.1%, CI 1.8-12.0%, P < 0.05). However, after taking account of prior depression
(odds ratio (OR) 6.45, 95% CI 3.63-11.43), TELs were not significantly associated
with depression (OR 0.27, 95% CI 0.03-2.13). Furthermore, rates of newly
diagnosed depression after treatment were similar in the two triptan groups
(sumatriptan 4.2%; TELs 3.9%). Although, the TELs are being prescribed to
patients with higher pre-existing rates of depression, they are not associated
with subsequently increased consulting for depressive illness compared with
patients taking sumatriptan. This study highlights the potential to use GPRD to
test targeted hypotheses exploring pharmacovigilance issues for patients using
new medicines.

Publication Types: 
    Comparative Study

PMID: 11167903 [PubMed - indexed for MEDLINE]

3450: Cephalalgia. 2000 Oct;20(8):724-31.

Assessing the onset of relief of a treatment for migraine.

Laska EM, Siegel C.

Statistical Sciences & Epidemiology Division, The Nathan S. Kline Institute for
Psychiatric Research, Orangeburg, New York 10962, USA. laska@nki.rfmh.org

It is common for clinical trials designed to compare treatments for migraine to
incorporate a component for estimating onset. Our objective is to describe a
stopwatch method for collecting data on time to meaningful relief and a
conceptual framework for describing and analysing the results. The survival
distribution of onset is modelled in two parts: the probability that onset does
not occur, and the survival distribution conditional on its occurrence. Using
data from a clinical trial comparing an active treatment and placebo, we
illustrate the method and find that the distributions of onset among those with
onset do not differ, but the probabilities that onset occurs are substantially
different. We illustrate how the model can be used to help determine how long
patients without onset should wait before further intervention, how patients
interpret the phrase meaningful relief, and how baseline clinical characteristics
affect the onset.

Publication Types: 
    Clinical Trial
    Clinical Trial, Phase III
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 11167902 [PubMed - indexed for MEDLINE]

3451: Cephalalgia. 2000 Oct;20(8):720-3.

Comment in:
    Cephalalgia. 2001 Jul;21(6):706-7.

Dopamine and migraine: does Parkinson's disease modify migraine course?

Barbanti P, Fabbrini G, Vanacore N, Rum A, Lenzi GL, Meco G, Cerbo R.

Department of Neurosciences, University La Sapienza, Rome, Italy.
piero.barbanti@uniroma1.it

As brainstem mechanisms and dopaminergic neurotransmission are involved in
migraine pathophysiology, we decided to investigate the course of migraine in
Parkinson's disease (PD), the paradigm of brainstem dopaminergic disease. We
screened 237 consecutive PD out-patients by direct interview to assess the
prevalence of lifetime and current migraine. Moreover, we compared the course of 
migraine in PD patients with that of otherwise healthy age- (+/- 3 years) and
sex-paired migraine controls in a cross-sectional study. PD patients showed a
lifetime migraine prevalence of 27.8% and a current migraine prevalence of 13.1%.
A positive family history of migraine was less frequent in PD patients than in
controls. The frequency of current migraine was significantly lower in PD
patients than in controls (47.0% vs. 68.2%; odds ratio = 0.41, 95% confidence
interval = 0.19-0.89). Approximately two-thirds of PD patients reported an
improvement in or remission of migraine after PD onset. Effects of menopause on
migraine course were similar in patients and controls. These findings suggest
that PD might somehow shorten the clinical course of migraine. Possible
explanations include a prolonged prophylactic effect by chronic dopaminergic
therapy or a positive effect of PD pathophysiology, namely nigral degeneration,
on migraine mechanisms.

PMID: 11167901 [PubMed - indexed for MEDLINE]

3452: Cephalalgia. 2000 Oct;20(8):714-9.

Habituation of visual and intensity dependence of auditory evoked cortical
potentials tends to normalize just before and during the migraine attack.

Judit A, Sándor PS, Schoenen J.

Department of Neurology, Semmelweis University of Medicine, Budapest, Hungary.

Between attacks, migraine with (MO) or without aura (MA) patients show deficient 
habituation of pattern-reversal visual evoked potentials (PR-VEP) and a strong
intensity dependence of auditory evoked cortical potentials (IDAP). Clinical
observations of migraine prodromes and previously published electrophysiological 
studies suggest that cortical information processing may vary in close temporal
relationship to the attack. We studied PR-VEP and IDAP just before (11 MO pts),
during (23 MO, 3 MA), 1 day following (27 MO, 1 MA) and 2 days following (14 MO) 
a migraine attack. The results were compared with a large group of MO patients
recorded at a distance of at least 3 days from an attack (n = 66 for IDAP; n = 39
for VEP). Patients recorded the day before the attack had on average an
habituation of -13.6+/-20.5% (mean +/- SD) between the 5th and 1st block of 100
averaged VEP responses and a flat (0.38+/-1.06 microV/10 dB) amplitude-stimulus
intensity function (ASF) slope of the auditory evoked cortical potential. Both
values were significantly different from those obtained in the attack interval
(P=0.003; P=0.020). During the attack, VEP habituation was less pronounced
(-0.17+/-26.2%) and ASF slopes remained flat (0.32+/-1.44 microV/10 dB; P=0.002
compared to interval). During the 2 days following the attack, VEP habituation
was replaced by potentiation (+0.09+/-29.1% the 1st day; 19.5+/-45.7% the 2nd
day) and ASF slopes increased markedly (0.87+/-1.39 and 1.14+/-1.12 microV/10
dB). The normalization of evoked cortical responses just before and during the
attack, might reflect an increase in the cortical preactivation level due to
enhanced activity in raphe-cortical serotonergic pathways.

PMID: 11167900 [PubMed - indexed for MEDLINE]

3453: Cephalalgia. 2000 Oct;20(8):708-13.

The influence of pattern interference on performance in migraine and visual
discomfort groups.

Conlon E, Hine T.

School of Applied Psychology, Griffith University, Brisbane, Australia.
e.conlon@mailbox.gu.edu.au

Performance in migraine with and without visual aura, non-specific headache and
headache-free control groups was measured using a visual search task. Data from
groups with high and low visual discomfort were also gathered. No pattern, 2
c/deg, 15 c/deg and a grey field were used in different background conditions.
Presentation of patterned backgrounds slowed performance for all groups with the 
2 c/deg pattern producing greatest interference. Performance of headache groups
did not differ from that of the control group in any condition. The high visual
discomfort group responded significantly more slowly than other groups with the 2
c/deg background. It was concluded that the presence of visual discomfort,
reported on an everyday basis was a better indicator of heightened sensory
sensitivity than the occurrence of migraine with or without aura.

Publication Types: 
    Comparative Study

PMID: 11167899 [PubMed - indexed for MEDLINE]

3454: Cephalalgia. 2000 Oct;20(8):701-7.

Migraine with aura and reproductive life events: a case control study.

Granella F, Sances G, Pucci E, Nappi RE, Ghiotto N, Napp G.

University Centre for Adaptive Disorders and Headache (UCADH), Institute of
Neurology, University of Parma, Italy. granella@unipr.it

The course of migraine without aura (MO) is greatly influenced by the events of
female reproductive life. Much less is known about migraine with aura (MA). The
aim of this study was to evaluate the relationship between MA and the milestones 
of reproductive life. A retrospective case control study was carried out on 100
women affected by migraine with typical aura (cases) and 200 age-matched women
with MO (controls). Premenstrual syndrome was found to be much more common among 
the patients with MA (odds ratio (OR) 6.0; confidence interval (CI) 3.1-11.6).
Menstrually triggered migraine was more frequently encountered among MO than
among MA patients (MA 15.0%; MO 53.5%; OR 0.1; CI 0.1-0.3). In both forms of
migraine, pregnancy had a favourable effect; however, a lower percentage of MA
(43.6%) than MO patients (76.8%; OR 0.2; CI 0.1-0.5) showed improvement or
remission. The use of oral contraceptives worsened migraine in MA more frequently
than in MO patients (MA 56.4%; MO 25.3%; OR 3.8; CI 1.6-9.3). The course of MA
seems to be influenced by female reproductive life events, but in a different way
with respect to MO.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 11167898 [PubMed - indexed for MEDLINE]

3455: Cephalalgia. 2000 Oct;20(8):696-700.

Comment in:
    Cephalalgia. 2000 Oct;20(8):685.

Alternating hemiplegia of childhood: no mutations in the familial hemiplegic
migraine CACNA1A gene.

Haan J, Kors EE, Terwindt GM, Vermeulen FL, Vergouwe MN, van den Maagdenberg AM, 
Gill DS, Pascual J, Ophoff RA, Frants RR, Ferrari.

Department of Neurology, Leiden University Medical Centre, The Netherlands.

INTRODUCTION: Alternating hemiplegia of childhood (AHC) is a rare disorder mainly
characterized by attacks of hemiplegia and mental retardation. It has been often 
associated with migraine. The CACNA1A gene on chromosome 19 is involved in
familial hemiplegic migraine and other episodic cerebral disorders, but also with
progressive neuronal damage. METHODS: We performed mutation analysis in this gene
in four AHC patients, using single strand conformation polymorphism analysis.
RESULTS: We found nine polymorphisms, but no mutations in any of the 47 exons.
CONCLUSIONS: Other cerebral ion channel genes remain candidate genes for AHC.

Publication Types: 
    Case Reports
    Research Support, Non-U.S. Gov't

PMID: 11167897 [PubMed - indexed for MEDLINE]

3456: Cephalalgia. 2000 Oct;20(8):687-95.

Erratum in:
    Cephalalgia 2001 Mar;21(2):164-5.

Comment in:
    Cephalalgia. 2001 Oct;21(8):855-6.

Tolerability of sumatriptan: clinical trials and post-marketing experience.

Welch KM, Mathew NT, Stone P, Rosamond W, Saiers J, Gutterman D.

University of Kansas School of Medicine, Kansas City, Kansas, USA.

Through December 1998, sumatriptan had been used to treat more than 236 million
migraine attacks world-wide. In clinical trials alone, more than 88000 migraine
patients had treated more than 300000 migraine attacks with sumatriptan, and 2000
normal healthy volunteers had been exposed to the drug. This paper describes the 
safety and tolerability profile of sumatriptan in three sections: adverse events 
reported in clinical trials, special issues, and spontaneous post-marketing
reports of adverse reactions. Data from the extensive clinical trials programme
coupled with information from nearly 10 years of experience in clinical practice 
demonstrate that sumatriptan is generally well-tolerated, with an acceptable
benefit-risk ratio when used properly. Significant cardiovascular and
cerebrovascular events are rare but have been observed. This fact highlights the 
need for careful patient selection and vigilant adherence to the prescribing
recommendations for sumatriptan. The wealth of clinical trials and post-marketing
information for sumatriptan may be useful in guiding prescribing decisions for
members of this class of drugs.

Publication Types: 
    Review

PMID: 11167896 [PubMed - indexed for MEDLINE]

3457: J Neurol Sci. 2001 Jan 15;183(1):43-6.

An MR study of tissue damage in the cervical cord of patients with migraine.

Rovaris M, Bozzali M, Rocca MA, Colombo B, Filippi M.

Neuroimaging Research Unit, Department of Neuroscience, Scientific Institute
Ospedale San Raffaele, Milan, Italy.

Hyperintense abnormalities on T2-weighted magnetic resonance (MR) scans of the
brain from patients with migraine are a relatively frequent finding and may
represent a diagnostic challenge. We studied the cervical cord of patients with
migraine using T2-weighted and magnetization transfer (MT) scans to assess
whether the study of macro- and microscopic tissue damage in the cervical cord of
these patients may have some diagnostic utility. T2-weighted and MT scans of the 
cervical cord and dual-echo scans of the brain were acquired from 16 patients
with migraine and 17 sex- and age-matched healthy volunteers. Cervical cord MT
ratio (MTR) histograms were obtained from all subjects and the relative peak
height, the peak position, and the average MTR measured. Five migraine patients
(31%) had hyperintense lesions in the brain. Neither healthy controls nor
patients with migraine had any abnormalities on cervical cord MR scans. There was
no difference for any of the cord MTR histogram-derived metrics between patients 
with migraine and healthy controls. No MTR histogram-derived measures from
migraine patients were 2 standard deviations below the mean values from controls.
Patients with migraine do not have MR or MT abnormalities in the cervical cord.
MR scanning of the cervical cord in patients with migraine and hyperintense brain
lesions of unknown etiology may be a useful investigation to facilitate the
diagnostic workout.

PMID: 11166793 [PubMed - indexed for MEDLINE]

3458: Eur J Pharmacol. 2001 Jan 12;411(3):289-99.

Mechanisms of blockade by the novel migraine prophylactic agent, dotarizine, of
various brain and peripheral vessel contractility.

Ruiz-Nuño A, Villarroya M, Cano-Abad M, Rosado A, Balfagón G, López MG, García
AG.

Departamento de Farmacología, Facultad de Medicina, Instituto Teófilo Hernando,
Universidad Autónoma de Madrid, Arzobispo Morcillo 4, 28029 Madrid, Spain.

The novel antimigraineur, dotarizine, inhibited 5-HT (5 hydroxytryptamine)-evoked
contractions of rabbit vertebral, aorta, femoral and mesenteric arteries, with
IC(50)s of 1.35, 1.40, 0.52 and 1.09 microM, respectively. Flunarizine had little
effect on these contractions, while ketanserin was more potent (IC(50)s of 0.17
microM for vertebral, 0.22 microM for aorta, 0.05 microM for femoral and 0.03
microM for mesenteric arteries). At 10 microM, dotarizine caused 40% blockade of 
K(+)-evoked contractions of rabbit aorta, and 70% inhibition of 5-HT-evoked
responses; these values were 30% and 20% for 10 microM flunarizine. Contractions 
of rabbit aorta elicited by noradrenaline, angiotensin II or prostaglandin
F(2alpha) were not affected by 10 microM dotarizine or flunarizine. Ketanserin
shifted to the right, in parallel, the concentration-response curves for 5-HT in 
rabbit aorta; however, dotarizine caused a non-competitive type of blockade,
increasing the maximum 5-HT contraction at 30 nM and decreasing it at 3 and 30
microM. K(+)-evoked contractions of rabbit aorta were halved by 3 microM
dotarizine in a voltage-independent manner; flunarizine caused a delayed-type,
non-reversible post-drug blockade, and exhibited some voltage-dependence.
Blockade by nifedipine was voltage-dependent and fully reversible. Ca(2+)-evoked 
contractions of depolarised bovine middle cerebral arteries were blocked by 1--3 
microM dotarizine in a non-surmountable manner. Contraction of these vessels
evoked by electrical stimulation was blocked 50% and 70% by 1 and 3 microM
dotarizine, respectively. Dotarizine (1--3 microM) also inhibited to a similar
extent the K(+)-evoked [(3)H]noradrenaline release from cultured rat sympathetic 
neurones. These data suggest that the mechanism of blockade by dotarizine of
cerebral vessels contractility has three components: (i) presynaptic inhibition
of noradrenaline release; (ii) blockade of postsynaptic vascular 5-HT receptors; 
(iii) blockade of Ca(2+)entry into the vascular smooth muscle cell cytosol. The
compound does not affect the vascular receptors for noradrenaline, angiotensin II
or prostaglandin F(2alpha).

Publication Types: 
    In Vitro
    Research Support, Non-U.S. Gov't

PMID: 11164387 [PubMed - indexed for MEDLINE]

3459: Neurology. 2001 Jan 23;56(2):178-83.

Suppression of perception in migraine: evidence for reduced inhibition in the
visual cortex.

Mulleners WM, Chronicle EP, Palmer JE, Koehler PJ, Vredeveld JW.

Department of Psychology, Lancaster University, Lancaster, UK.
W.Mulleners@freeler.nl

BACKGROUND: Results from transcranial magnetic stimulation (TMS) studies of
visual cortex have confirmed visual cortical hyperexcitability in patients with
migraine. It has been speculated that this may be due to deficient intracortical 
inhibitory tone. However, the TMS induction of phosphenes relies on the reporting
of a subjective experience, and may thus be subject to bias. METHODS: Seven
migraineurs with visual aura and seven sex- and age-matched controls were
studied. Fifty-four different three-letter combinations were briefly displayed
and followed by a magnetic pulse at 40, 70, 100, 130, 160, and 190 msec. Subjects
were required to report as many letters as they thought they had recognized.
RESULTS: In the migraine group, the mean proportion of correctly identified
letters was significantly higher at 100 msec, as was the proportion of trials
with two or three letters correctly reported. The time window in which perceptual
suppression could be introduced was narrower in migraineurs compared to controls.
CONCLUSION: These findings suggest that inhibitory systems are activated to a
lesser extent by TMS pulses in patients. This observation is in agreement with
the hypothesized deficiency of intracortical inhibition of the visual cortex, at 
least in migraineurs with aura.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 11160952 [PubMed - indexed for MEDLINE]

3460: Invest Ophthalmol Vis Sci. 2000 Apr;41(5):1239-47.

Visual field losses in subjects with migraine headaches.

McKendrick AM, Vingrys AJ, Badcock DR, Heywood JT.

Discoveries in Sight, Devers Eye Institute, Legacy Clinical Research and
Technology Center, Portland, Oregon, USA.

PURPOSE: To characterize the visual fields of subjects with migraine headaches
using static and temporal modulation perimetry. METHODS: Sixteen subjects with
migraines (15 with aura, 1 without) and 15 nonheadache controls were tested.
Perimetry was conducted 7 days after the offset of a headache with both static
and temporally modulated targets using the Medmont M-600 automated perimeter
(Medmont Pty Ltd., Camberwell, Victoria, Australia). Flicker thresholds were
measured using the autoflicker test, which varies flicker rate with eccentricity.
A subset of four subjects with migraines (3 with aura, 1 without) had the
temporal tuning characteristics of their loss evaluated using fixed temporal
frequencies (4, 6, 9, 12, and 16 Hz). RESULTS: Field losses were identified with 
temporal modulation perimetry in 11 of 16 migraine subjects. The majority of
these losses occurred in the presence of normal static thresholds (8/11). The
deficits displayed temporal tuning, being greatest for higher temporal
frequencies (> or =9 Hz). None of the subjects revealed deficits typical of
cortical lesions. The migraine-without-aura subject displayed a selective loss to
temporally modulated stimuli, which was consistent with the aura group. This
defect altered over time, decreasing for 30 to 40 days but remaining, to a
smaller extent, for up to 75 days after the headache event. CONCLUSIONS: Visual
dysfunction that is selective for temporally modulated targets occurs in migraine
subjects. The migrainous pattern of dysfunction shares some features with that
identified in early stages of glaucoma and raises the possibility for a common
precortical vascular involvement in these two conditions.

PMID: 10752965 [PubMed - indexed for MEDLINE]

3461: Drugs. 2000 Dec;60(6):1259-87.

Triptans in migraine: a comparative review of pharmacology, pharmacokinetics and 
efficacy.

Tfelt-Hansen P, De Vries P, Saxena PR.

Department of Neurology, Glostrup Hospital, University of Copenhagen, Denmark.
tfelt@inet.uni2.dk

Triptans are a new class of compounds developed for the treatment of migraine
attacks. The first of the class, sumatriptan, and the newer triptans
(zolmitriptan, naratriptan, rizatriptan, eletriptan, almotriptan and
frovatriptan) display high agonist activity at mainly the serotonin 5-HT1B and
5-HT1D receptor subtypes. As expected for a class of compounds developed for
affinity at a specific receptor, there are minor pharmacodynamic differences
between the triptans. Sumatriptan has a low oral bioavailability (14%) and all
the newer triptans have an improved oral bioavailability and for one,
risatriptan, the rate of absorption is faster. The half-lives of naratriptan,
eletriptan and, in particular, frovatriptan (26 to 30h) are longer than that of
sumatriptan (2h). These pharmacokinetic improvements of the newer triptans so far
seem to have only resulted in minor differences in their efficacy in migraine.
Double-blind, randomised clinical trials (RCTs) comparing the different triptans 
and triptans with other medication should ideally be the basis for judging their 
place in migraine therapy. In only 15 of the 83 reported RCTs were 2 triptans
compared, and in 11 trials triptans were compared with other drugs. Therefore, in
all placebo-controlled randomised clinical trials, the relative efficacy of the
triptans was also judged by calculating the therapeutic gain (i.e. percentage
response for active minus percentage response for placebo). The mean therapeutic 
gain with subcutaneous sumatriptan 6mg (51%) was more than that for all other
dosage forms of triptans (oral sumatriptan 100mg 32%; oral sumatriptan 50mg 29%: 
intranasal sumatriptan 20mg 30%; rectal sumatriptan 25mg 31%; oral zolmitriptan
2.5mg 32%; oral rizatriptan 10mg 37%; oral eletriptan 40mg 37%; oral almotriptan 
12.5mg 26%). Compared with oral sumatriptan 100mg (32%), the mean therapeutic
gain was higher with oral eletriptan 80mg (42%) but lower with oral naratriptan
2.5mg (22%) or oral frovatriptan 2.5mg (16%). The few direct comparative
randomised clinical trials with oral triptans reveal the same picture. Recurrence
of headache within 24 hours after an initial successful response occurs in 30 to 
40% of sumatriptan-treated patients. Apart from naratriptan, which has a tendency
towards less recurrence, there appears to be no consistent difference in
recurrence rates between the newer triptans and sumatriptan. Rizatriptan with its
shorter time to maximum concentration (tmax) tended to produce a quicker onset of
headache relief than sumatriptan and zolmitriptan. The place of triptans compared
with non-triptan drugs in migraine therapy remains to be established and further 
RCTs are required.

Publication Types: 
    Comparative Study
    Review

PMID: 11152011 [PubMed - indexed for MEDLINE]

3462: Fam Pract. 2001 Feb;18(1):101-6.

New avenues in treatment of paediatric migraine: a review of the literature.

Pakalnis A.

Section of Neurology, Columbus Children's Hospital, 700 Children's Drive,
Columbus, OH 43206, USA.

BACKGROUND: Headaches are a common problem in paediatric practice. Recurrent
headaches can be a significant source of stress for patient and parents, and
disruptive regarding school obligations and parental work responsibilities. Most 
treatment interventions are developed from research data extrapolated from adult 
studies, with resultant concerns of safety and efficacy when utilizing these
therapeutic conclusions in children. METHODS: This paper incorporates current
treatment strategies in paediatric migraine utilizing a Medline search of English
language studies from January 1988 to December 1999, with a literature search
referencing the terms of paediatrics, migraines, headaches, therapy and
treatment. Reference sections of the articles were reviewed for pertinent
information prior to January 1988. Articles were evaluated systematically to
formulate concise terms for diagnosis of paediatric migraine and applicability to
clinical treatment studies. Particular emphasis was placed on newer options with 
relevance in adult treatment such as triptans and anti-epileptic drugs, and their
benefit in therapy of paediatric migraine. Non-pharmacological options were also 
subjected to organized review to determine relevance in treatment of paediatric
migraine. RESULTS: The review of the literature indicates that although migraine 
in childhood and adolescence appears to be increasing in prevalence, few clinical
studies are available, with most current treatment recommendations utilizing data
from adult studies. CONCLUSION: Further headache treatment studies in the
paediatric population are necessary in order to ascertain safety and efficacy of 
pharmaco-therapeutics in these children. Also, much current interest in treatment
in adults with recurrent headaches involves non-pharmacological areas-dietary
modification and stress management. Application of these avenues especially
warrants further clarification with regard to relevance in paediatric migraine
treatment.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 11145638 [PubMed - indexed for MEDLINE]

3463: BMJ. 2001 Jan 6;322(7277):19-22.

Prophylactic treatment of migraine with angiotensin converting enzyme inhibitor
(lisinopril): randomised, placebo controlled, crossover study.

Schrader H, Stovner LJ, Helde G, Sand T, Bovim G.

Norwegian University of Science and Technology, Department of Neurology, 7006
Trondheim, Norway. harald.schrader@medisin.ntnu.no
harald.schrader@medisin.ntnu.no

OBJECTIVE: To determine the efficacy of an angiotensin converting enzyme
inhibitor in the prophylaxis of migraine. DESIGN: Double blind, placebo
controlled, crossover study. SETTING: Neurological outpatient clinic.
PARTICIPANTS: Sixty patients aged 19-59 years with migraine with two to six
episodes a month. INTERVENTIONS: Treatment period of 12 weeks with one 10 mg
lisinopril tablet once daily for one week then two 10 mg lisinopril tablets once 
daily for 11 weeks, followed by a two week wash out period. Second treatment
period of one placebo tablet once daily for one week and then two placebo tablets
for 11 weeks. Thirty participants followed this schedule, and 30 received placebo
followed by lisinopril. MAIN OUTCOME MEASURES: Primary end points: number of
hours with headache, number of days with headache, number of days with migraine. 
Secondary end points: headache severity index, use of drugs for symptomatic
relief, quality of life and number of days taken as sick leave, acceptability of 
treatment. RESULTS: In the 47 participants with complete data, hours with
headache, days with headache, days with migraine, and headache severity index
were significantly reduced by 20% (95% confidence interval 5% to 36%), 17% (5% to
30%), 21% (9% to 34%), and 20% (3% to 37%), respectively, with lisinopril
compared with placebo. Days with migraine were reduced by at least 50% in 14
participants for active treatment versus placebo and 17 patients for active
treatment versus run-in period. Days with migraine were fewer by at least 50% in 
14 participants for active treatment versus placebo. Intention to treat analysis 
of data from 55 patients supported the differences in favour of lisinopril for
the primary end points. CONCLUSION: The angiotensin converting enzyme inhibitor, 
lisinopril, has a clinically important prophylactic effect in migraine.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 11141144 [PubMed - indexed for MEDLINE]

3464: Bull Exp Biol Med. 2000 Jul;130(7):633-5.

Effects of calcium antagonists on serotonin-dependent aggregation and serotonin
transport in platelets of patients with migraine.

Pukhal'skaya TG, Kolosova OA, Men'shikov MY, Vein AM.

Institute of Pharmacology, Russian Academy of Medical Sciences, Moscow.

Flunarizine and cinnarizine (IC50 6.8x10(-6) and 2.8x10(-5) M, respectively)
inhibited 3H-serotonin uptake by platelets. In higher doses, they blocked
serotonin-induced platelet aggregation and stimulated 3H-serotonin release from
these cells. Imipramine did not affect serotonin-releasing effects of
preparations. In all patients cinnarizine was more potent in inhibiting serotonin
uptake, and in half of the patients cinnarizine displayed higher activity as an
inductor of serotonin release.

PMID: 11140571 [PubMed - indexed for MEDLINE]

3465: Rev Neurol (Paris). 2000;156 Suppl 4:4S30-41.

Sex hormones and headache.

Silberstein SD.

Jefferson Headache Center, Thomas Jefferson University Hospital, Philadelphia,
Pennsylvania. Stephen.Silberstein@mail.tju.edu

The normal female life cycle is associated with a number of hormonal milestones: 
menarche, pregnancy, contraceptive use, menopause, and the use of replacement sex
hormones. Menarche marks the onset of menses and cyclic changes in hormone
levels. Pregnancy is associated with rising noncyclic levels of sex hormones, and
menopause with declining noncyclic levels. Hormonal contraceptive use during the 
reproductive years and hormone replacement in menopause are therapeutic hormonal 
interventions that alter the levels and cycling of sex hormones. These events and
interventions may cause a change in the prevalence or intensity of headache. The 
menstrual cycle is the result of a carefully orchestrated sequence of
interactions between the hypothalamus, pituitary, ovary, and endometrium, with
the sex hormones acting as modulators and effectors at each level. Estrogen and
progestins have potent effects on central serotonergic and opioid neurons,
modulating both neuronal activity and receptor density. The primary trigger of
Menstrually-related migraine (MM) appears to be the withdrawal of estrogen rather
than the maintenance of sustained high or low estrogen levels. However, changes
in the sustained estrogen levels with pregnancy (increased) and menopause
(decreased) appear to affect headaches. Headaches associated with OC use or
menopausal hormonal replacement therapy may be related, in part, to periodic
discontinuation of oral sex hormone preparations. The treatment of migraine
associated with changes in sex hormone levels is frequently difficult and the
patients are often refractory to therapy. Based on what is known of the
pathophysiology of migraine, we have attempted to provide a logical approach to
the treatment of headaches that are associated with menses, menopause, and OCs
using abortive and preventive medications and hormonal manipulations.
Considerable evidence suggests a link between estrogen and progesterone, the
female sex hormones, and migraine. (Silberstein and Merriam, 1997; Lipton and
Stewart, 1993; Epstein et al., 1975; Goldstein and Chen, 1982; Selby and Lance,
1960) Although no gender difference is apparent in prepubertal children, with
migraine occurring equally in 4p. 100 of boys and girls, (Goldstein and Chen,
1982, Waters and O'Connor, 1971) migraine occurs more frequently in adult women
(18p. 100) than in men (6p. 100). (Lipton and Stewart, 1993) Migraine develops
most frequently in the second decade, with the peak incidence occurring with
adolescence. (Selby and Lance, 1960; Epstein et al., 1975) Menstrually-related
migraine (MM) begins at menarche in 33p. 100 of affected women (Epstein et al. , 
1975). MM occurs mainly at the time of menses in many migrainous women, and
exclusively with menses (true menstrual migraine [TMM]) in some (Epstein et al., 
1975). Menstrual migraine can be associated with other somatic complaints arising
before and often persisting into menses, such as nausea, backache, breast
tenderness, and cramps and like them appears to be the result of falling sex
hormone levels (Silberstein and Merriam, 1997; American Psychiatric Association, 
1994). In addition, premenstrual migraine can be associated with premenstrual
dysphoric disorder (PDD), also called "premenstrual syndrome" (PMS), which is
distinct from the physical symptoms of the perimenstrual period and is probably
not directly driven by declining progesterone levels (Mortola, 1998). Migraine
occurring during (rather than prior to) menstruation is usually not associated
with PMS (Silberstein and Merriam, 1997). Migraine may worsen during the first
trimester of pregnancy and, although many women become headache-free during the
last two trimesters, 25p. 100 have no change in their migraine (Silberstein,
1997). MM typically improves with pregnancy, perhaps due to sustained high
estrogen levels (Silberstein, 1997). Hormonal replacement with estrogens can
exacerbate migraine and oral contraceptives (OCs) can change its character and
frequency

Publication Types: 
    Review

PMID: 11139745 [PubMed - indexed for MEDLINE]

3466: Headache. 2000 Nov-Dec;40(10):853-5.

Chronic paroxysmal hemicrania-like headaches in a child: response to a headache
diary.

Klassen BD, Dooley JM.

Division of Neurology, Department of Medicine, Dalhousie University, Halifax,
Nova Scotia, Canada.

Chronic paroxysmal hemicrania and cluster headache are both characterized by
recurrent, severe, unilateral headaches accompanied by symptoms and signs of
autonomic dysfunction. They are differentiated by the frequency, duration, and
medication responsiveness of the headaches. Both occur in childhood, although
such reports are rare. A 6-year-old boy presented with chronic paroxysmal
hemicrania-like headaches. Through the use of a headache diary, his headaches
were found to follow stressful events and resolved shortly after the introduction
of the diary. Precipitation of chronic paroxysmal hemicrania-like headaches by
stress has not been previously reported. We recommend the use of a headache diary
as both an aid to diagnosis and an initial nonpharmacological therapeutic
intervention for children with such headaches.

Publication Types: 
    Case Reports

PMID: 11135033 [PubMed - indexed for MEDLINE]

3467: Headache. 2000 Nov-Dec;40(10):836-9.

Comment in:
    Headache. 2002 Mar;42(3):236-7; author reply 235-6.

Chronic Helicobacter pylori infection and migraine: a case-control study.

Pinessi L, Savi L, Pellicano R, Rainero I, Valfrè W, Gentile S, Cossotto D,
Rizzetto M, Ponzetto A.

Neurology III-Headache Center, Department of Neuroscience, University of Turin,
Italy.

OBJECTIVE: To determine whether chronic Helicobacter pylori infection is a risk
factor for migraine. BACKGROUND: Preliminary studies have shown a high prevalence
of Helicobacter pylori infection in patients with primary headaches. METHODS: One
hundred three consecutive patients with migraine were enrolled in the study and
compared with a group of 103 matched controls. Helicobacter pylori infection was 
diagnosed by means of both (13)C-urea breath test and serology. RESULTS: Of
patients with migraine, 30.1% were positive for Helicobacter pylori, compared
with 31.1% of controls (P = NS). The odds ratio for migraine associated with
chronic Helicobacter pylori infection was 0.96 (95% confidence interval, 0.51 to 
1.80). Demographic, clinical, and psychological characteristics of Helicobacter
pylori-positive migraineurs were compared with those of migrainous patients
without infection. Helicobacter pylori-positive patients had a significantly
(P<.05) lower incidence of food sensitivity than Helicobacter pylori-negative
patients. No significant difference was found in any other feature examined.
CONCLUSIONS: Our study suggests that chronic Helicobacter pylori infection is not
more frequent in patients with migraine than in controls and that infection does 
not modify clinical features of the disease.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 11135029 [PubMed - indexed for MEDLINE]

3468: Headache. 2000 Nov-Dec;40(10):824-9.

Migraine, as compared to other headaches, is worse during midnight-sun summer
than during polar night. A questionnaire study in an Arctic population.

Salvesen R, Bekkelund SI.

Department of Neurology, University of Tromsø, Bodø, Norway.

OBJECTIVE: To investigate potential seasonal variation of migraine and other
headaches in an Arctic population where light conditions are extreme during both 
winter and summer. BACKGROUND: Due to the immense seasonal variation in sunlight,
focus on seasonal migraine variation in a population living in an Arctic area is 
interesting even from a theoretical point of view. METHODS: Northern Norway
comprises the three Norwegian counties north of the Arctic Circle. There are
three neurology centers in this region, which provide service for approximately
half a million people. During a 2-year period, 1403 patients (0.3% of the
population) were referred to these centers for a specialist assessment of their
headache. A questionnaire was mailed to all these patients; the questionnaire
included questions on headache characteristics to make it possible to identify
migraine according to the International Headache Society criteria. Questions on
seasonal variation of headache were also included. RESULTS: One thousand
fifty-two patients (75%) returned the questionnaire. Nineteen percent reported
that their headaches clearly did vary with season; 11% experienced more headache 
during polar night, while 7% had more symptoms during midnight sun season. When
the migraine and nonmigraine groups were compared, significant differences were
demonstrated. Patients with nonmigrainous headache were more likely to have
increased headaches during the dark winter season, while patients with migraine
experienced more headache during the summer (P =.002). CONCLUSIONS: Patients with
migraine were more likely to have headache during the bright Arctic summer
season, and this distinguishes migraine from other headaches in this study. This 
observation may pertain to the increased light sensitivity and recently
demonstrated cortical hyperexcitability in patients with migraine, and may
perhaps suggest a role of the hypothalamus and/or melatonin secretion in migraine
pathophysiology.

Publication Types: 
    Comparative Study

PMID: 11135027 [PubMed - indexed for MEDLINE]

3469: Headache. 2000 Nov-Dec;40(10):813-7.

Masseter and temporalis muscle EMG levels and bite force in migraineurs.

Burnett CA, Fartash L, Murray B, Lamey PJ.

School of Clinical Dentistry, The Queen's University of Belfast, Northern
Ireland, UK.

The purpose of this study was to compare absolute and proportional
electromyography (EMG) levels in the masseter and temporalis muscles during
performance of a variety of oral functions for migraineurs and age- and
sex-matched controls. Both groups consisted of nine women and one man, with a
mean age of 43 years (range, 29 to 51 years). Absolute resting EMG levels and
those levels during swallowing and speech were not significantly different
between the groups, but the levels of the group with migraine were significantly 
higher during maximum voluntary effort contractions on the anterior teeth and on 
the posterior teeth for both muscles. When expressed as a percentage of those
levels obtained at maximal posterior contraction (ie, proportional levels), no
difference in functional activity was demonstrated between groups. It was
concluded that the two groups studied had similar levels of EMG activity in the
masseter and temporalis muscles during the normal oral functions investigated,
but that the group with migraine had higher levels of absolute EMG activity
during anterior and posterior maximum voluntary contractions. Furthermore, the
group with migraine demonstrated higher levels of anterior and posterior bite
force, although not correlated with EMG levels.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 11135025 [PubMed - indexed for MEDLINE]

3470: Headache. 2000 Nov-Dec;40(10):809-12.

Comment in:
    Headache. 2001 Oct;41(9):917-8.

Effect of withdrawal of misused medication on sleep disturbances in migraine
sufferers with chronic daily headache.

Hering-Hanit R, Yavetz A, Dagan Y.

Headache Unit, Department of Neurology, Meir General Hospital, Sapir Medical
Center, Kfar Saba, Israel.

OBJECTIVES: To evaluate the sleep pattern of migraineurs with chronic daily
headache and to determine whether and to what degree it is improved by withdrawal
of medication, and to reconfirm relief of headache by withdrawal of medications
in migraineurs with chronic daily headache due to medication misuse. BACKGROUND: 
Misuse of ergotamine and analgesics by migraineurs is one of the causes of
chronic daily headache. The latter is alleviated or abolished in these patients
by abrupt withdrawal of the misused medication. In common with patients with
chronic daily headache, migraineurs frequently complain of insomnia, usually
verifiable by polysomnography. METHODS: Twenty-six women with migraine, aged 18
to 49 years, with chronic daily headache due to medication misuse, voluntarily
discontinued ergotamine and analgesics, and were followed at monthly intervals
for 3 months. In 25 subjects, polysomnography was performed before withdrawal of 
medication and 3 months after withdrawal. All subjects filled out a standard
sleep questionnaire on those two occasions and a daily self-assessment
questionnaire focused on headaches. RESULTS: After 3 months, a significant
decrease in mean headache frequency (P<.001) and intensity (P<.001) was
demonstrated. Polysomnography performed 3 months after medication withdrawal
showed significant improvement in total sleep time (P<.05), sleep efficiency
(P<.05), and number of arousals (P<.001). The score of the sleep questionnaire
was also significantly improved (P<.01). CONCLUSIONS: In migraineurs with chronic
daily headache due to medication misuse, withdrawal of the misused medications
alleviates the associated sleep disturbance along with diminution in frequency
and intensity of chronic daily headache.

PMID: 11135024 [PubMed - indexed for MEDLINE]

3471: Headache. 2000 Nov-Dec;40(10):792-7.

Comment in:
    Headache. 2001 Oct;41(9):918-22.

Treatment of mild headache in disabled migraine sufferers: results of the
Spectrum Study.

Cady RK, Lipton RB, Hall C, Stewart WF, O'Quinn S, Gutterman D.

Headache Care Center, Springfield, MO 65804, USA.

OBJECTIVE: To evaluate the effectiveness of sumatriptan, 50-mg tablets, versus
placebo for early intervention while head pain was mild in patients with
disabling migraine. METHODS: A post hoc analysis was performed in a subgroup of
patients from a large, randomized, placebo-controlled study of patients with
disabling headache who treated while pain was mild. Pain-free response 2 and 4
hours postdose, headache recurrence, and safety were examined. Significance tests
were performed only for the first-treated attacks. RESULTS: Twenty-six patients
with disabling headache treated 46 mild and 166 moderate or severe headaches. For
the first-treated headaches while pain was mild, pain-free rates were
significantly higher for sumatriptan than placebo 4 hours postdose (78% versus
0%, P =.02), but not 2 hours postdose (52% versus 0%, P =.22). Across all
headaches treated while pain was mild, pain-free responses were higher for
sumatriptan than placebo 4 hours (85% versus 17%) and 2 hours (50% versus 0%)
postdose compared with placebo. When the same patients treated headaches while
pain was moderate or severe, pain-free rates were lower than that reported for
treatment during mild pain. There was a trend toward lower headache recurrence in
headaches treated while pain was mild compared with moderate or severe pain (13% 
versus 18%). No drug-related adverse events were reported in the headaches
treated while pain was mild. CONCLUSIONS: Patients with disabling migraine may
benefit from early intervention with sumatriptan, 50 mg, while pain is mild.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 11135022 [PubMed - indexed for MEDLINE]

3472: Headache. 2000 Nov-Dec;40(10):783-91.

Comment in:
    Headache. 2001 Oct;41(9):918-22.

2000 Wolfe Award. Sumatriptan for the range of headaches in migraine sufferers:
results of the Spectrum Study.

Lipton RB, Stewart WF, Cady R, Hall C, O'Quinn S, Kuhn T, Gutterman D.

Albert Einstein Medical College and Montefiore Headache Unit, New York, NY, USA.

BACKGROUND: Migraineurs experience a spectrum of headaches: migraine, migrainous,
and episodic tension-type as defined by the International Headache Society (IHS).
OBJECTIVE: To evaluate the effectiveness of sumatriptan, 50-mg tablets, in
treating the spectrum of headaches in IHS-diagnosed migraineurs. DESIGN/METHODS: 
Migraineurs with severe disability (Headache Impact Questionnaire score 250 or
greater) were enrolled in a randomized, double-blind, placebo-controlled,
crossover study. Patients treated up to 10 headaches with sumatriptan, 50 mg, or 
placebo (4:1). Headache features, recorded prior to treatment, were used to
classify each headache using IHS criteria. Headache response (moderate or severe 
pain reduced to mild or no pain) and pain-free response were recorded at 2 and 4 
hours postdose (primary endpoint). Because patients treated multiple attacks,
statistical methods controlling for within-subject correlation were used.
RESULTS: Two hundred forty-nine migraineurs treated 1576 moderate or severe
headaches: migraine (n = 1110), migrainous (n = 103), and tension-type (n = 363).
Sumatriptan was superior to placebo for headache response 4 hours postdose
(primary endpoint) across all headache types (migraine, 66% versus 48%; P<.001;
migrainous, 71% versus 39%; P<.01; tension-type, 78% versus 50%, P<.001).
Sumatriptan was also superior to placebo for pain-free response 4 hours postdose 
for migraine (41% versus 24%, P<.001) and tension-type headaches (56% versus 36%,
P =.001). Sumatriptan provided superior pain-free response 2 hours postdose for
migraine (18% versus 7%, P<.0001) and tension-type headache (28% versus 14%, P
=.0005) compared with placebo. CONCLUSION: Sumatriptan, 50-mg tablets, are
effective for the full spectrum of headaches experienced by patients with
disabling migraine due to a sumatriptan-responsive mechanism.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 11135021 [PubMed - indexed for MEDLINE]

3473: Eur J Pharmacol. 2000 Dec 20;410(1):53-9.

Cardiovascular safety profile of almotriptan, a new indolic derivative for the
treatment of migraine.

Gras J, Cardelús I, Llenas J, Palacios JM.

Pharmacological Development Department, Almirall Prodesfarma, Research Center,
Cardener 68-74, 08024-, Barcelona, Spain. jgras@almirallprodesfarma.com

Almotriptan is a new 5-HT(1B/1D) receptor agonist effective for treating acute
migraine attacks with or without aura. As 3-5% of patients treated with
sumatriptan experience chest symptoms thought to be of cardiac origin, we
investigated the cardiovascular safety profile of almotriptan in comparison with 
that of sumatriptan in six animal models. Almotriptan did not modify blood
pressure or heart rate in conscious telemetered normotensive Wistar rats (p.o.), 
in anaesthetised beagle dogs (i.v.), or in conscious beagle dogs (i.v.), and only
produced transient increases when administered (s.c.) to telemetered cynomolgus
monkeys. Almotriptan did not consistently affect the duration of the
electrocardiogram (ECG) intervals in anaesthetised beagle dogs even when the drug
was administered into the coronary artery, nor was ECG morphology altered in
telemetered cynomolgus monkeys. In contrast, sumatriptan i.v. consistently
increased mean blood pressure and heart rate in conscious beagle dogs. Finally,
almotriptan did not modify coronary blood flow at a dose of up to 0.3 mg/kg i.v. 
in conscious beagle dogs. Thus, almotriptan has a favourable cardiovascular
safety profile.

Publication Types: 
    Comparative Study

PMID: 11134656 [PubMed - indexed for MEDLINE]

3474: Eur J Pharmacol. 2000 Dec 20;410(1):43-51.

Functional profile of almotriptan in animal models predictive of antimigraine
activity.

Gras J, Bou J, Llenas J, Fernández AG, Palacios JM.

Pharmacological Development Department, Almirall Prodesfarma, Research Center,
Cardener 68-74, 08024-, Barcelona, Spain. jgras@almirallprodesfarma.com

Almotriptan is a new 5-HT(1B/1D) receptor agonist whose clinical efficacy for the
treatment of migraine attacks has been demonstrated in Phase III clinical trials.
We now compare the functional profile of almotriptan (assessed using animal
models) with that of sumatriptan. Almotriptan selectively increased carotid
vascular resistance in anaesthetised cats after intravenous or intraduodenal
administration (ED(100)=11 microg/kg, i.v.; ED(50)=339 microg/kg, i. d.) and in
anaesthetised beagle dogs following intravenous administration (ED(50)=116
microg/kg). A study in anaesthetised cats also demonstrated that almotriptan acts
by selectively increasing the resistance of the carotid arteriovenous anastomoses
without adversely affecting brain irrigation. In addition, almotriptan inhibited 
meningeal extravasation produced by electrical stimulation of the trigeminal
ganglion in anaesthetised guinea pigs in the dose range of 0.3-3 mg/kg, i.v. In
conclusion, almotriptan is both a selective constrictor affecting intracranial
blood vessels and an inhibitor of neurogenically evoked plasma protein
extravasation of the dura mater.

Publication Types: 
    Comparative Study

PMID: 11134655 [PubMed - indexed for MEDLINE]

3475: Eur J Pharmacol. 2000 Dec 20;410(1):33-41.

Pharmacological characterization of almotriptan: an indolic 5-HT receptor agonist
for the treatment of migraine.

Bou J, Domènech T, Puig J, Heredia A, Gras J, Fernández-Forner D, Beleta J,
Palacios JM.

Almirall Prodesfarma, Research Center, Cardener 68-74, 08024, Barcelona, Spain.

Almotriptan (3-[2-(dimethylamino)ethyl]-5-(pyrrolidin-1-ylsulfonylmethyl
)-1H-indo le) has been studied in several models predictive of activity and
selectivity at 5-HT receptors. Almotriptan showed low nanomolar affinity for the 
5-HT(1B) and 5-HT(1D) receptors in several species, including the human, while
affinity for 5-HT receptors other than 5-HT(1B/1D) was clearly less. Affinity for
5-HT(7) and 5-HT(1A) receptors was approximately 40 and 60 times lower than that 
for 5-HT(1B/1D) receptors, respectively. Almotriptan did not exhibit significant 
affinity for several non-5-HT receptors studied up to 100 microM. Almotriptan
inhibited forskolin-stimulated cyclic AMP accumulation in HeLa cells transfected 
with 5-HT(1B) or 5-HT(1D) human receptors. In this model, almotriptan had the
same efficacy as serotonin and an affinity in the low nanomolar range. It induced
vasoconstriction in several vessels in which it was compared with sumatriptan. In
isolated dog saphenous veins, almotriptan elicited concentration-dependent
contractions with an EC(50) of 394 nM. In both these systems, almotriptan behaved
as a full agonist. Infusion of almotriptan into the porcine meningeal vasculature
induced vasoconstriction. In contrast, in the pig renal and rabbit mesenteric
arteries, it had a very low maximal efficacy even at 100 microM, with similar
results obtained in the rabbit renal artery. The results suggest that almotriptan
is a potent and selective 5-HT(1B/1D) receptor agonist, with selectivity for the 
cranial vasculature as compared with peripheral vessels.

Publication Types: 
    Comparative Study

PMID: 11134654 [PubMed - indexed for MEDLINE]

3476: Med Hypotheses. 2001 Jan;56(1):91-4.

Hypothesized treatment for migraines using low doses of tryptophan, niacin,
calcium, caffeine, and acetylsalicylic acid.

Gedye A.

The author hypothesized that existing agents known to influence serotonin blood
level, vascular tone, and inflammatory reactions might terminate migraines. The
author presented the rationale for using five different agents therapeutically
and avoiding two other agents during a migraine. The proposed treatment is to use
low doses of tryptophan, niacin, calcium, caffeine, and acetylsalicylic acid
(ASA) soon after migraine symptoms are noticed and to avoid during a migraine
high-potassium food and magnesium supplements. Preliminary results from 12
migraine patients indicated that 9 of 12 (75%) had significant benefit from this 
approach. Using these five agents together is a novel combination and a new idea 
for treating migraines.

PMID: 11133261 [PubMed - indexed for MEDLINE]

3477: Cephalalgia. 2000 Sep;20(7):663-7.

Acetylsalicylic acid effervescent 1000 mg (Aspirin) in acute migraine attacks; a 
multicentre, randomized, double-blind, single-dose, placebo-controlled parallel
group study.

Lange R, Schwarz JA, Hohn M.

Bayer AG, BG Consumer Care, Medical Department, Leverkusen, Germany.
ralph.lange.rl@bayer-ag.de

In this multicentre, randomized, double-blind, single-dose study a total of 374
patients generally suffering from migraine attacks suitable for treatment with
non-prescription drugs, received either oral acetylsalicylic acid effervescent
1000 mg (ASAE) or effervescent placebo for the treatment of an acute migraine
attack. Of the 343 patients fulfilling the criteria for efficacy analysis 169
patients took acetylsalicylic acid and 174 placebo. Response rates (reduction of 
headache severity from severe or moderate to mild or no pain at 2 h after
administration) were 55.0% for acetylsalicylic acid and 36.8% for placebo (P <
0.001). Twenty-nine percent of patients in the active treatment group were
pain-free after 2 h compared with 16.7% in the placebo group (P = 0.007). No
headache recurred within 24 h post-dose in 84.6% of patients in the active group 
and in 85.1% of patients in the placebo group. Effervescent placebo reduced
nausea and vomiting to the same degree as the active drug. Adverse events of
acetylsalicylic acid (8.3%) were generally mild or moderate and comparable to
those of placebo (2.9%). This study shows that oral ASAE is safe and effective
for the treatment of acute migraine attacks.

Publication Types: 
    Clinical Trial
    Multicenter Study
    Randomized Controlled Trial

PMID: 11128825 [PubMed - indexed for MEDLINE]

3478: Cephalalgia. 2000 Sep;20(7):621-31.

Olfactory and trigeminal event-related potentials in migraine.

Grosser K, Oelkers R, Hummel T, Geisslinger G, Brune K, Kobal G, Lötsch J.

Department of Experimental and Clinical Pharmacology and Toxicology, University
of Erlangen Nürnberg, Erlangen, Germany.

BACKGROUND: Trigeminal/neuronal hyperexcitability and spreading depression
activating the trigemino-vascular system are discussed in
migraine-pathophysiology. This study investigated trigeminal and olfactory
event-related potentials in migraineurs. METHODS: Nasal chemosensitivity was
assessed in 19 female migraineurs with or without aura > 72 h before or after an 
attack and in 19 healthy females employing event-related cortical potentials
(ERPs) after specific trigeminal stimulation of nasal nociceptors with short
pulses of CO2, and specific olfactory stimulation with H2S. Odour thresholds and 
odour identification performance were also tested. RESULTS: Migraineurs exhibited
greater responses to trigeminal stimulation, indicated by significantly larger
ERP amplitudes N1. In contrast, olfactory ERP amplitudes P1N1 were significantly 
smaller in migraineurs. A leave-one-out classification procedure on the basis of 
these two parameters assigned 76.3% cases correctly. The olfactory ERP amplitude 
discriminated better between groups than trigeminal ERPs (71.1 vs. 68.4% correct 
classification). CONCLUSIONS: Our data suggest trigeminal hyperexcitability in
migraineurs. A general increase of nasal chemosensitivity is not supported
because of smaller olfactory ERP amplitudes in migraineurs. Olfactory ERPs
discriminate better than trigeminal ERPs between migraineurs and controls,
emphasizing the significance of the olfactory system in migraine.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 11128819 [PubMed - indexed for MEDLINE]

3479: Cephalalgia. 2000 Sep;20(7):617-20.

Migraine without aura and migrainous disorder in children; International Headache
Society (IHS) and revised IHS criteria.

Cano A, Palomeras E, Alfonso S, Ortega D, Sanz P, Fossas P.

Department of Neurology, Hospital de Mataró, Barcelona, Spain. 26821acg@comb.es

The widely used criteria of the IHS to define migraine without aura in children
are highly specific but show poor sensitivity, with a large percentage of
headaches being classified as migrainous disorder (MD). The objective of this
study was to assess how many headache patients in a series of children met the
diagnostic criteria of the IHS for migraine without aura or MD and to determine
the changes required to convert the greatest number of MD into migraine without
aura, without affecting classification of the remaining headache types. A
prospective study was undertaken of 131 patients under 15 years old referred to
our centre for headache. Patients were classified according to the IHS criteria
and according to a modification of these criteria consisting of: (1) reduction of
minimum time required for classification into migraine without aura from 2 h to 1
h; (2) acceptance of bifrontal location in addition to hemicranial; (3)
acceptance of either phonophobia or photophobia as valid criteria instead of
requiring presence of both. Using the IHS criteria, 51 (39%) children were
diagnosed as having migraine without aura and 26 (20%) as having MD. According to
our revised IHS criteria, 68 (52%) were diagnosed as migraine without aura and
nine (7%) as MD. When the three modified criteria were applied, three tension
headaches and one unclassifiable headache changed category. When only reduced
duration and bifrontal location were applied, none of the headaches other than MD
changed category. Application of two modifications to the IHS criteria--reduction
in duration of headache to 1 h and acceptance of bifrontal location--increased
sensitivity without reducing specificity in classifying migraine without aura in 
children.

PMID: 11128818 [PubMed - indexed for MEDLINE]

3480: Cephalalgia. 2000 Sep;20(7):611-6.

Migrainous disorder and headache of the tension-type not fulfilling the criteria:
a follow-up study in children and adolescents.

Zebenholzer K, Wöber C, Kienbacher C, Wöber-Bingöl C.

Department of Neuropsychiatry of Childhood and Adolescence, University of Vienna,
Austria. Karin.Zebenholzer@univie.ac.at

In this follow-up study in children and adolescents with recurrent headaches
classified as migrainous disorder (IHS 1.7) and headache of the tension-type not 
fulfilling the criteria (IHS 2.3), 28.6% were headache-free and 71.4% still had
headaches 2-5 years after the first examination. The majority remained in the
same one-digit IHS diagnosis, whereas 20% changed from migraine to tension-type
headache or vice versa. The number of IHS criteria fulfilled increased
significantly from the first to the second examination. The reason for diagnosing
IHS 1.7 and IHS 2.3 most often was a short headache duration or headache
characteristics not meeting the criteria. By reducing the minimum headache
duration to 1 h, 11 of 58 patients could be diagnosed as migraine without aura.
There was a remarkable overlap in the diagnostic criteria for migraine without
aura and tension-type headache. In IHS 1.7 and IHS 2.3 this overlap exceeded 80%,
with a trend to decrease at the second examination.

PMID: 11128817 [PubMed - indexed for MEDLINE]

3481: Compr Ther. 2000 Winter;26(4):263-8.

A practical approach to migraine headache.

Mendizabal JE.

University of South Alabama Medical Center, 2451 Fillingim Street, Suite 10-1,
Mobile, AL 36617, USA.

Headache is a common problem in primary care practice. Migraine accounts for the 
vast majority of patients seeking treatment for their headaches. The ability to
simplify the evaluation and treatment of these patients translates into patient's
relief and increased productivity.

Publication Types: 
    Review

PMID: 11126097 [PubMed - indexed for MEDLINE]

3482: Acta Neurol Scand. 2000 Dec;102(6):354-8.

Valproic acid in prophylaxis of refractory migraine.

Erdemoglu AK, Ozbakir S.

Kirikkale University, Faculty of Medicine, Department of Neurology, Turkey.
ake@anet.net.tr

OBJECTIVE: The efficacy and safety of valproic acid were assessed as a
prophylactic agent in migraine patients who previously derived no significant
benefit from conventional prophylactic medications for migraine. PATIENTS AND
METHODS: One hundred and twenty patients aged 23-58 years with the diagnosis of
migraine without aura. Response to therapy was determined by using a headache
calendar detailing the frequency and severity of attacks. Reduction of 50% or
greater in the frequency or severity of headache was considered as improvement.
RESULTS: Improvement was observed in headache frequency within 67% of patients.
Headache severity had been improved in 60% of patients. The mean average dosage
of valproic acid was 1,250 mg daily. Most of the side effects are mild and
tolerable. CONCLUSION: These results suggest that valproic acid is effective and 
safe in the treatment of refractory migraine headache.

Publication Types: 
    Clinical Trial

PMID: 11125749 [PubMed - indexed for MEDLINE]

3483: Arch Dis Child. 2001 Jan;84(1):55-57.

The prognosis of cyclical vomiting syndrome.

Dignan F, Symon DN, AbuArafeh I, Russell G.

Department of Child Health, University of Aberdeen, Aberdeen AB25 2ZD, UK.

AIMS: The medium term prognosis of cyclical vomiting syndrome (CVS) was studied
to determine the proportion of affected individuals who had gone on to develop
headaches fulfilling the International Headache Society criteria for migraine.
METHODS: Twenty six (76%) of 34 CVS sufferers identified from the authors'
clinical records were traced, and all agreed to participate. Each child was
matched to a control, and telephone interviews were conducted using a
standardised questionnaire. RESULTS: Thirteen (50%) of the subjects had
continuing CVS and/or migraine headaches while the remainder were currently
asymptomatic. The prevalence of past or present migraine headaches in subjects
(46%) was significantly higher than in the control population (12%). CONCLUSION: 
Results support the concept that CVS is closely related to migraine.

PMID: 11124785 [PubMed - indexed for MEDLINE]

3484: Eur J Med Res. 2000 Nov 30;5(11):473-83.

Evidence for neuronal dysfunction in migraine: concurrence between specific qEEG 
findings and clinical drug response--a retrospective analysis-.

Vonderheid-Guth B, Todorova A, Wedekind W, Dimpfel W.

Pro Science Private Research Clinic GmbH, Kurt-Schumacher-Str. 9, D-35440 Linden,
Germany. vonderheid@proscience.de

OBJECTIVE: The aim of this analysis was to verify objective correlates of the
clinical improvement of migraine in patients by means of quantitative
topographical EEG (qEEG). METHODS: Overall 40 migraine-outpatients participated
in this retrospective analysis of prophylactic migraine treatment over 3-8 months
with 1600 to 2000 mg cyclandelate daily. In all patients qEEG was recorded and
analysed using the Fast Fourier Transformation and the determination of the
Abberation Index (AI = the statistical probability of belonging to a qEEG
reference group of healthy people, n = 500). RESULTS: A clinical response (> 50% 
reduction of migraine attack frequency and duration) was observed in 77.5% (n =
31). The number and duration of migraine attacks per month (median values) were
reduced in a highly significant manner. In this observation 75% of all patients
investigated showed a pathological positive Aberration Index at a single
electrode or a cluster of neighbouring brain sites. This consisted in a power
increase in theta, alpha and/or beta1 activity, and 73.3% of them had also a
corresponding negative AI-focus (power decrease). In 15 patients EEG aberrations 
(positive AI clusters) within one frequency band were found, whereas 15 patients 
showed aberrations in more than one frequency. Positive AI s were mainly found in
fronto-temporal and occipital brain areas with one single topographical
difference between the patients with and without aura. CONCLUSIONS: Positive AI
values were the main electrophysiological findings in these migraine patients.
This was supported by the highly significant decrease of the median amount of the
positive AI after clinically successful treatment with cyclandelate. Twenty four 
out of thirty patients with positive AI foci showed concurrence between
qEEG-changes and clinical response. Patients with positive AI foci involving the 
lower or middle frequencies (theta and/or alpha 1) seemed to show a better
clinical response (84.6%) than those with AI foci with participation of only
faster frequencies (alpha 2 and/or beta 1; 54.5%). A controlled study is needed
to confirm these observations.

PMID: 11121368 [PubMed - indexed for MEDLINE]

3485: Am J Med Genet. 2000 Dec 4;96(6):762-4.

The homozygous C677T mutation in the methylenetetrahydrofolate reductase gene is 
a genetic risk factor for migraine.

Kowa H, Yasui K, Takeshima T, Urakami K, Sakai F, Nakashima K.

Division of Neurology, Institute of Neurological Sciences, Faculty of Medicine,
Tottori University, Yonago, Japan. norkowa@grape.med.tottori-u.ac.jp

Increased homocysteine levels are associated with various pathological conditions
in humans, including stroke and cardiovascular disorders. Homocysteine acts as an
excitatory amino acid in vivo and may influence the threshold of migraine
headache. Frosst et al. [1995] reported an association between the homozygous
C677T mutation in the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene and
serum homocysteine levels. This study was designed to determine the prevalence of
the MTHFR mutation in Japanese patients with migraine and tension-type headache
(TH). Seventy-four patients with migraine headaches (22 with aura and 52 without 
aura), 47 with THs, and 261 normal controls were recruited. Genotyping of MTHFR
C677T polymorphism was performed by polymerase chain reaction-restriction
fragment length polymorphism. We detected that the incidence of the homozygous
transition (T/T) in migraine sufferers (20.3%) was significantly higher than that
in controls (9.6%). Moreover, the frequency of the T/T genotype in individuals
with migraine headaches with aura was remarkably high (40.9%). The MTHFR T allele
was more frequent in the migraine group than in the control group. Our results
support the conclusion that the MTHFR gene, causing mild hyperhomocysteinemia may
be a genetic risk factor for migraine. Am. J. Med. Genet. (Neuropsychiatr.
Genet.) 96:762-764, 2000. Copyright 2000 Wiley-Liss, Inc.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 11121176 [PubMed - indexed for MEDLINE]

3486: Clin Ther. 2000 Nov;22(11):1346-56.

Health care utilization by migraine patients: a 1998 Medicaid population study.

Joish VN, Cady PS, Shaw JW.

College of Pharmacy, University of Arizona, Tucson 85721-0207, USA.
joish@pharmacy.arizona.edu

BACKGROUND: In the last decade, a number of studies have documented the economic 
impact of migraine headaches on society. Although previous research has shown
that patients with migraine headache consume a greater amount of health care
resources than those without migraine, the economic impact of this condition on a
Medicaid population has not been assessed. OBJECTIVE: The purpose of this study
was to compare the health care resource utilization of-patients with and without 
migraine headache in the Idaho Medicaid population. METHODS: Idaho Medicaid
claims from 1998 were reviewed to identify cases and controls. Four controls,
matched for age, sex, race, and residence, were obtained for each case. Physician
services, hospital services, emergency room services, and prescription use were
compared between the 2 groups. Multivariate analyses were performed to determine 
differences between the 2 groups after controlling for potential confounders.
RESULTS: Eighty percent of the cases were female, and 94% of the patients were
white. Patients with migraine headache had statistically significantly higher
health care resource consumption than matched controls (P < 0.05). Total log
costs for prescription use, physician services, and hospital services were
significantly higher (P < 0.001) in the migraine group even after controlling for
migraine-associated comorbid conditions and demographic variables. CONCLUSIONS:
Total health care costs for migraine patients were 1.6 times higher than for
matched controls. The results of this study suggest that migraine is a
significant economic burden to the Medicaid program.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 11117659 [PubMed - indexed for MEDLINE]

3487: Otolaryngol Head Neck Surg. 2000 Dec;123(6):669-76.

Botulinum toxin type A (BOTOX) for treatment of migraine headaches: an open-label
study.

Binder WJ, Brin MF, Blitzer A, Schoenrock LD, Pogoda JM.

University of California, USA.

OBJECTIVE: The object of this clinical experience was to evaluate the correlation
between pericranial botulinum toxin type A (BOTOX, Allergan Corp, Irvine, CA)
administration and alleviation of migraine headache symptoms. Study Design and
Setting: A nonrandomized, open-label study was performed at 4 different test
sites. The subjects consisted of 106 patients, predominantly female, who either
(1) initially sought BOTOX treatment for hyperfunctional facial lines or other
dystonias with concomitant headache disorders, or (2) were candidates for BOTOX
treatment specifically for headaches. Headaches were classified as true migraine,
possible migraine, or nonmigraine, based on baseline headache characteristics and
International Headache Society criteria. BOTOX was injected into the glabellar,
temporal, frontal, and/or suboccipital regions of the head and neck. Main outcome
measures were determined by severity and duration of response. The degrees of
response were classified as: (1) complete (symptom elimination), (2) partial > or
=50% reduction in headache frequency or severity), and (3) no response [neither
(1) nor (2)]. Duration of response was measured in months for the prophylactic
group. RESULTS: Among 77 true migraine subjects treated prophylactically, 51%
(95% confidence interval, 39% to 62%) reported complete response with a mean (SD)
response duration of 4.1 (2.6) months; 38% reported partial response with a mean 
(SD) response duration of 2.7 (1.2) months. Overall improvement was independent
of baseline headache characteristics. Seventy percent (95% confidence interval,
35% to 93%) of 10 true migraine patients treated acutely reported complete
response with improvement 1 to 2 hours after treatment. No adverse effects were
reported. CONCLUSIONS: BOTOX was found to be a safe and effective therapy for
both acute and prophylactic treatment of migraine headaches. Further research is 
needed to explore and develop the complete potential for the neuroinhibitory
effects of botulinum toxin.

Publication Types: 
    Clinical Trial
    Multicenter Study

PMID: 11112955 [PubMed - indexed for MEDLINE]

3488: Arch Intern Med. 2000 Dec 11-25;160(22):3486-92.

Efficacy and safety of acetaminophen in the treatment of migraine: results of a
randomized, double-blind, placebo-controlled, population-based study.

Lipton RB, Baggish JS, Stewart WF, Codispoti JR, Fu M.

Department of Neurology, Albert Einstein College of Medicine of Yeshiva
University, 1300 Morris Park Ave, Bronx, NY 10461, USA. rlipton@imrinc.com

BACKGROUND: Although most persons with migraine treat their headaches with
over-the-counter medication, systematic data on the safety and efficacy of widely
used treatment, including acetaminophen, are sparse. METHODS: This is a
randomized, double-blind, placebo-controlled study comparing oral acetaminophen, 
1000 mg (two 500-mg Extra Strength Tylenol tablets), with identical placebo in
the treatment of a single acute migraine attack. Eligible subjects met
International Headache Society diagnostic criteria for migraine with or without
aura. Patients who usually required bed rest with their headaches or who vomited 
more than 20% of the time were excluded. MAIN OUTCOME MEASURES: The percentage of
subjects who, at 2 hours after dosing, experienced a change in baseline pain
intensity from severe or moderate pain to mild or no pain (headache response);
and pain intensity difference from baseline at the 2-hour postmedication
assessment. RESULTS: The headache response rate 2 hours after dosing was 57.8% in
the acetaminophen group and 38.7% in the placebo group (P =.002). Pain-free rates
at 2 hours were 22.4% in the acetaminophen group and 11.3% in the placebo group
(P =.01). The mean pain intensity difference from baseline 2 hours after dosing
was 1.08 in the acetaminophen group and 0.73 in the placebo group (P<.001). At 2 
hours, other migraine headache characteristics, such as functional disability (P 
=.002), photophobia (P =.02), and phonophobia (P =.08), were significantly
improved after treatment with acetaminophen vs placebo. CONCLUSIONS:
Acetaminophen was highly effective for treating pain, functional disability,
photophobia, and phonophobia in a population-based sample of persons with
migraine, excluding the most disabled persons with migraine. The drug also had an
excellent safety profile and was well tolerated. Arch Intern Med.
2000;160:3486-3492.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 11112243 [PubMed - indexed for MEDLINE]

3489: Health Care Women Int. 2000 Apr-May;21(3):203-18.

Exploration of migraine pain, disability, depressive symptomatology, and coping: 
a pilot study.

Kolotylo CJ, Broome ME.

School of Nursing, University of Wisconsin-Milwaukee, USA. Ckolotylo@aol.com

As many as 29% of women suffer from migraine headache, yet it remains a poorly
understood phenomenon. Our purpose in conducting this pilot study was to
determine the relationships among migraine pain, disability, depressive
symptomatology, and coping in women. A convenience sample of 34 women was
recruited from university and workplace populations. Nineteen women met the
International Headache Society criteria for migraine, while 15 women served as a 
nonmigraine comparison group. Participants completed eight instruments measuring 
migraine pain, disability, depressive symptomatology, and coping. The two groups 
of women were not significantly different on demographic variables. Migraineurs
scored significantly higher for pain characteristics, disability, depressive
symptomatology, and total coping scores.

Publication Types: 
    Research Support, U.S. Gov't, P.H.S.

PMID: 11111466 [PubMed - indexed for MEDLINE]

3490: Pain. 2000 Oct;88(1):41-52.

Validity of the Migraine Disability Assessment (MIDAS) score in comparison to a
diary-based measure in a population sample of migraine sufferers.

Stewart WF, Lipton RB, Kolodner KB, Sawyer J, Lee C, Liberman JN.

Department of Epidemiology, The Johns Hopkins School of Hygiene and Public
Health, Baltimore, MD 21205, USA.

The Migraine Disability Assessment (MIDAS) questionnaire is a brief,
self-administered questionnaire designed to quantify headache-related disability 
over a 3 month period. The MIDAS score has been shown to have moderately high
test-retest reliability in headache sufferers and is correlated with clinical
judgment regarding the need for medical care. The aim of the study was to examine
the validity of the MIDAS score, and the five items comprising the score,
compared to data from a 90 day daily diary used, in part, to record acute
disability from headache. In a population-based sample, 144 clinically diagnosed 
migraine headache sufferers were enrolled in a 90 day diary study and completed
the MIDAS questionnaire at the end of the study. The daily diary was used to
record detailed information on headache features as well as activity limitations 
in work, household chores, and non-work activities (social, family and leisure
activities). The MIDAS score was the sum of missed work or school days, missed
household chores days, missed non-work activity days, and days at work or school 
plus days of household chores where productivity was reduced by half or more in
the last 3 months. Validity was assessed by comparing MIDAS items and the MIDAS
score with equivalent measures derived from the diary. The MIDAS items for missed
days of work or school (mean 0.96, median 0) and for missed days of household
work (mean 3.64, median 2.0) were similar to the corresponding diary-based
estimates of missed work or school (mean 1.23, median 0) and of missed household 
work (mean 3.93, median 2.01). Values for missed days of non-work activities
(MIDAS mean 2.6 and median 1 versus diary mean 2.22 and median 0.95) were also
similar. Responses to MIDAS questions about number of days where productivity was
reduced by half or more in work (mean 3.77, median 2.00) and in household work
(mean 3.92, median 2.00) significantly overestimated the corresponding
diary-based measures for work (mean 2.94, median 1.06) and household work (mean
2.22, median 0.98). Nonetheless, the overall MIDAS score (mean 14.53, median 9.0)
was not significantly different form the reference diary-based measure (mean
13.5, median 8.4). The correlation between the MIDAS summary score and an
equivalent diary score was 0.63. The group estimate of the MIDAS score was found 
to be a valid estimate of a rigorous diary-based measure of disability. The mean 
and median values for the MIDAS score in a population-based sample of migraine
cases were similar to equivalent diary measures. The correlation between the two 
measures was in the low moderate range, but expected given that two very
different methods of data collection were compared.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't
    Validation Studies

PMID: 11098098 [PubMed - indexed for MEDLINE]

3491: Neurology. 2000 Nov 28;55(10):1517-23.

Menstrual cycle and headache in a population sample of migraineurs.

Stewart WF, Lipton RB, Chee E, Sawyer J, Silberstein SD.

Department of Epidemiology, The Johns Hopkins School of Hygiene and Public
Health, Baltimore, MD 21205, USA.

BACKGROUND: Migraine is three times more common in women than men. There is a
clinical impression that migraines are more common and severe around the time of 
menses. OBJECTIVES: To determine 1) the distribution of headache attacks by day
of the menstrual cycle in women with migraine, 2) if the excess occurrence varies
by headache type, and 3) if headache features differ by time in the menstrual
cycle. METHODS: In a population-based sample, 81 menstruating women with
clinically diagnosed migraine were enrolled in a 98-day diary study and completed
a total of 7219 diary days. The daily diary was used to record the occurrence of 
menses, headache days, and, on days with headache, associated headache features
(i.e., symptoms, quality-of-pain, attack duration, pain intensity, and disability
at work, household work, and nonwork activities). RESULTS: An excess risk of
headache occurred perimenstrually and was highest on days 0 and 1 of the cycle
(day 0 being the first day of menses). A significantly elevated risk of headache 
on days 0 and 1 was observed for migraine without aura (OR 2.04; 95% CI 1.49,
2.81) and for tension-type headache (OR 1.67; 95% CI 1.24, 2.25). Elevated risks 
were also observed in the 2 days before onset of menses for migraine without aura
(OR 1.80; 95% CI 1.40, 2.30). A significantly lower risk was observed around the 
time of ovulation for all headaches (OR 0.44; 95% CI 0.27, 0.72). Few significant
differences were observed in headache features (i.e., pain intensity, disability 
score, symptom score, headache duration) by day of the cycle overall or by
headache type. Pain intensity was slightly greater for migraine headaches during 
the first 2 days of menses. CONCLUSIONS: Attacks of migraine without aura, but
not migraine with aura, were more likely to occur 2 days before onset of menses
and on the first 2 days of menses. This study does not support the clinical
notion that headaches, regardless of type, are more severe during the
perimenstrual period compared to other times in the cycle. Although migraine
headaches are significantly more painful during the first 2 days of menses,
differences are small.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 11094107 [PubMed - indexed for MEDLINE]

3492: Neurology. 2000 Nov 28;55(10):1511-6.

Within-patient consistency of response of rizatriptan for treating migraine.

Dahlöf CG, Lipton RB, McCarroll KA, Kramer MS, Lines CR, Ferrari MD.

Gothenburg Migraine Clinic, Sweden.

OBJECTIVE: To determine the within-patient consistency of response for
rizatriptan, a 5-HT(1B/1D) receptor agonist for the acute treatment of migraine. 
METHODS: Post hoc analysis was performed on data from a randomized, double-blind,
placebo-controlled clinical trial. Four hundred seventy-three patients with
migraine diagnosed according to the criteria of the International Headache
Society were randomly assigned to one of five sequence groups in which each
patient was scheduled to treat four separate moderate or severe migraine attacks.
Patients in four groups received 10 mg of rizatriptan for three of four attacks
and placebo for the remaining attack; patients in the fifth group received 10 mg 
of rizatriptan for all four attacks. Headache severity, functional disability,
and associated migraine symptoms were measured immediately before dosing and at
regular intervals up to 4 hours after the dose. The analysis was based on
efficacy at 2 hours after dosing, the last time point before escape medications
were allowed. The percentages of patients who responded in a specified number of 
attacks after treatment with rizatriptan were calculated. The analysis was
descriptive, and no formal statistical testing was performed. RESULTS: Of the
evaluable patients who treated three migraine attacks with 10 mg of rizatriptan
(with an additional interspersed placebo-treated attack in most patients), 216 of
252 (86%) had pain relief (reduction of pain to mild or none), 122 of 252 (48%)
were pain free, 211 of 250 (84%) had no nausea, 163 of 251 (65%) had no
photophobia, 182 of 252 (72%) had no phonophobia, 136 of 249 (55%) had no
functional disability, and 233 of 252 (92%) had no need for escape medications at
2 hours after dosing in at least two of three attacks. CONCLUSION: The response
to 10 mg of oral rizatriptan within individual patients was consistent over three
attacks on a range of measures.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 11094106 [PubMed - indexed for MEDLINE]

3493: Headache. 2000 Oct;40(9):755-7.

Use of intravenous valproate sodium in status migraine.

Norton J.

Department of Psychiatry, University of Mississippi College of Medicine, Jackson 
39216, USA.

Patients with migraines have typically been given one group of medications for
abortive treatment and another for preventative. In the acute situation when the 
patient has severe nausea it is difficult to administer medications. Intravenous 
medications would avoid this problem but are limited to the opiates and
dihydroergotamine. The following cases demonstrate the acute treatment of
migraine with intravenous valproic acid (Depacon). The oral form of valproic acid
has been used as a prophylactic agent, but the intravenous form may provide an
alternative for abortive care as well. The ease of administration and lack of
side effects are also important considerations. Double-blind studies will help
clarify the situation.

Publication Types: 
    Case Reports

PMID: 11091297 [PubMed - indexed for MEDLINE]

3494: Headache. 2000 Oct;40(9):745-7.

Roller coaster migraine: an underreported injury?

McBeath JG, Nanda A.

Head and Neck Pain Program, Willis-Knighton Medical Center, Shreveport, LA, USA.

A 28-year-old woman presented with severe headache, sleep problems, memory
problems, and irritability 2 months after a violent roller coaster ride. She was 
diagnosed with posttraumatic migraine, and intravenous dihydroergotamine resolved
her symptoms. Imaging studies, electroencephalogram, and visual and auditory
evoked responses were normal. Imipramine, divalproex sodium, and propranolol were
prescribed to prevent the headaches from recurring and dihydroergotamine nasal
spray was prescribed for breakthrough headaches. We consider the many short but
significant brain insults delivered during the roller coaster ride a critical
factor in triggering this instance of posttraumatic migraine, which while
unmanaged was a source of significant disability for the patient.

Publication Types: 
    Case Reports

PMID: 11091294 [PubMed - indexed for MEDLINE]

3495: Headache. 2000 Oct;40(9):720-3.

Intravenous valproate sodium (depacon) aborts migraine rapidly: a preliminary
report.

Mathew NT, Kailasam J, Meadors L, Chernyschev O, Gentry P.

Houston (Tex) Headache Clinic 77004, USA.

OBJECTIVE: This study was designed to investigate the efficacy and safety of
intravenous valproate in the treatment of acute migraine attacks. BACKGROUND:
Numerous studies have shown oral valproate therapy to be effective in preventing 
migraine. To date, no published studies have explored the use of valproate in the
acute treatment of migraine. DESIGN/METHODS: After obtaining written informed
consent, 61 patients presenting to a clinic with acute migraine were infused with
300 mg of intravenous valproate sodium. Sixty-six attacks were treated. The time 
at the beginning of infusion; the time at the end of infusion; the time to onset 
of relief of headache, nausea, and other associated symptoms; the time to
meaningful relief; and the time to complete relief were recorded. Patient's
pulse, blood pressure, and respiration were monitored. Adverse events were
recorded. RESULTS: Mean time to onset of relief was 8 minutes, mean time to
meaningful relief was 16 minutes, and mean time to complete relief was 25
minutes. A reduction in pain from severe or moderate to mild or no pain in 30
minutes was reported in 37 of 66 attacks; in 11 attacks, a reduction of more than
50% in headache severity in 30 minutes was reported. Thus, 48 (73%) of 66 attacks
had significant improvement. After treatment with valproate, headache severity
was significantly decreased (P<.0001); nausea, disability, and photophobia
decreased; and patients became more alert. No serious adverse events were
reported. CONCLUSION: Intravenous valproate appears to be safe and effective for 
the acute treatment of migraine. Double-blind, placebo-controlled studies to
further investigate the use of this agent in acute treatment of migraine attacks 
are warranted.

Publication Types: 
    Clinical Trial

PMID: 11091289 [PubMed - indexed for MEDLINE]

3496: Headache. 2000 Oct;40(9):715-9.

Does migraine headache affect cognitive function in the elderly? Report from the 
Maastricht Aging Study (MAAS).

Jelicic M, van Boxtel MP, Houx PJ, Jolles J.

Department of Psychiatry and Neuropsychology, Maastricht Brain and Behavior
Institute and European Graduate School of Neuroscience, Maastricht University,
The Netherlands.

The aim of this study was to examine two aspects of cognitive
functioning-information processing speed and memory-in both young/middle-aged and
older subjects with and without migraine, using data from a large
population-based sample. We found that, although age had a large effect on
processing speed and memory, migraine did not influence cognitive performance. In
addition, there was no significant interaction between age and migraine on
processing speed and memory. Our results suggest that, in the general population,
migraine does not seriously affect cognitive functioning in young/middle-aged or 
older adults.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 11091288 [PubMed - indexed for MEDLINE]

3497: Lancet. 2000 Nov 11;356(9242):1648-51.

Effect on migraine of closure of cardiac right-to-left shunts to prevent
recurrence of decompression illness or stroke or for haemodynamic reasons.

Wilmshurst PT, Nightingale S, Walsh KP, Morrison WL.

Department of Cardiology, Royal Shrewsbury Hospital, UK.

BACKGROUND: A relation between migraine with aura and cardiac right-to-left
shunts has been reported. Right-to-left shunts are also associated with stroke
and certain forms of decompression illness. We investigated the effect of closure
of right-to-left shunts on migraine symptoms. METHODS: A consultant neurologist, 
who was unaware of information about residual shunt, undertook a structured
interview with individuals who had had transcatheter closure of an atrial septal 
defect or patent foramen ovale to assess how the procedure affected migraine
symptoms. FINDINGS: 37 of 40 consecutive patients who had had a closure procedure
(to permit resumption of diving after decompression illness in 29, after stroke
when paradoxical thromboembolism was suspected in four, or to close a large
atrial septal defect in four) could be contacted. 21 (57%) had a history of
migraine before the procedure (with aura in 16, without aura in five). 11
individuals had fortification spectra in the period immediately after closure.
During long-term follow-up, no migraine symptoms were reported by seven
individuals who had previously had migraine with aura and three who had
previously had migraine without aura. Eight others who had had migraine with aura
before closure reported improvement in frequency and severity of migraines. Three
(one migraine with aura, two migraine without aura) reported no alteration in
migraine episodes. INTERPRETATION: These observations suggest a causal
association between right-to-left shunts and migraine with aura. There may be a
subgroup of patients who have severe migraine associated with a large
right-to-left shunt in whom closure of the atrial defect may improve or abolish
migraine.

PMID: 11089825 [PubMed - indexed for MEDLINE]

3498: Neurology. 2000;55(9 Suppl 2):S46-52.

Management of migraine: an algorithmic approach.

Silberstein SD, Goadsby PJ, Lipton RB.

Jefferson Headache Center, Thomas Jefferson University Hospital, Philadelphia, PA
19107, USA.

Good management of migraine requires that the patient participate actively in
decisions regarding therapeutic intervention. Most patients, when carefully
informed, will engage in a wellness program that includes regular exercise and
rest, good nutrition, and avoidance of headache triggers. Acute treatment is
probably most likely to be beneficial if it is started early in the migraine
attack. Headache severity and associated features, such as nausea, vomiting, or
previous treatment responses, can guide selection of medication for acute
treatment. Simple analgesics or nonsteroidal anti-inflammatory drugs, with or
without antiemetics, are usually the first line of treatment and are effective
for some attacks. Combination analgesics or ergotamine preparations represent
second-line therapies for patients with infrequent attacks. For patients unlikely
to respond to simpler treatments, 5-HT1B/1D receptor agonists or
dihydroergotamine offer the best chance for relief. Narcotic analgesics may be
needed when other antimigraine drugs prove ineffective, but must be prescribed
judiciously. Patients with 3 or more days of headache-related disability per
month, or with headaches refractory to acute treatment, are candidates for
preventive therapy. Coexisting disease can contribute to decisions on
prophylaxis. In many cases, a single agent may be used to treat both migraine and
a coexisting disorder. beta-blockers are most often used for preventive therapy. 
Other options include divalproex, antidepressants, calcium-channel antagonists,
serotonin antagonists, and riboflavin.

Publication Types: 
    Review

PMID: 11089519 [PubMed - indexed for MEDLINE]

3499: Neurology. 2000;55(9 Suppl 2):S36-45.

Functional neuroimaging: enhanced understanding of migraine pathophysiology.

Cutrer FM, O'Donnell A, Sanchez del Rio M.

Partners Headache Center, Department of Neurology, Massachusetts General
Hospital, Boston, 02129, USA.

Research into migraine pathophysiology has been hampered by the episodic nature
and unpredictable onset of migraine attacks. Recently, newer imaging techniques
have been providing noninvasive methods of studying metabolism and hemodynamics
in the brains of migraineurs during and between acute attacks. 133Xe blood flow
techniques, transcranial Doppler, and SPECT have all been employed to investigate
hemodynamic changes during migraine aura. PET has been useful in the study of
migraine without aura, with findings of increased blood flow related to pain in
cortical areas and in the medial brainstem. Currently, three functional MRI
imaging techniques are being used in migraine research. Diffusion-weighted
imaging has shown normal findings in measures of the ability of neurons to
maintain osmotic gradients. Studies using perfusion-weighted imaging have shown
alterations in relative cerebral blood flow (CBF), relative cerebral blood
volume, and mean transit time during migraine visual aura. The blood oxygen
level-dependent technique can supply information related to neuronal activation
during acute migraine aura. MRS has been used with mixed success to look for
evidence of abnormal energy metabolism in the brains of migraineurs.
Magnetoencephalography studies support the presence of a spreading
depression-like phenomenon in migraine with aura. Two groups have used
transcranial magnetic stimulation to assess whether neurons in the occipital
cortex are hyperexcitable, predisposing patients to develop aura symptoms.
Despite conflicting findings, migraine with visual aura appears to be generally
associated with transient decreases in regional CBF.

Publication Types: 
    Review

PMID: 11089518 [PubMed - indexed for MEDLINE]

3500: Neurology. 2000;55(9 Suppl 2):S29-35.

Impact of migraine and migraine therapy on productivity and quality of life.

Solomon GD, Santanello N.

Merck Research Laboratories, West Point, PA 19486, USA.

Migraine is an expensive disorder in terms of lost productivity and its
deleterious impact on health-related quality of life (QOL). In addition to lost
wages and productivity due to absenteeism, many patients with migraine also
experience reduced productivity while at work and disruption of their family,
social, and leisure activities. Even a migraine of moderate intensity can impair 
function and productivity, which emphasizes the importance of therapy that
achieves complete, as opposed to partial, pain relief. Rapid onset of complete
relief with abatement of migraine-associated symptoms has been reported to be
most relevant for patient QOL and satisfaction with migraine therapy. Several
instruments have been developed for measuring health-related QOL. Both general
and migraine-specific instruments have been useful in assessing the impact of
migraine and migraine therapy on health-related QOL; migraine-specific
instruments may be more sensitive in measuring the effects of pharmacologic
intervention. Compared with placebo, rizatriptan improved productivity in
migraine patients. Compared with usual care, rizatriptan had favorable effects on
all five domains of the 24-Hour Migraine Quality of Life questionnaire.

Publication Types: 
    Review

PMID: 11089517 [PubMed - indexed for MEDLINE]

3501: Neurology. 2000;55(9 Suppl 2):S25-8.

Rizatriptan versus usual care in long-term treatment of migraine.

Silberstein SD.

Jefferson Headache Center, Thomas Jefferson University Hospital, Philadelphia, PA
19107, USA.

Because of the recurrent nature of migraine, a major concern with pharmacologic
therapy is whether it will remain effective, safe, and tolerable over the long
term. The development of sumatriptan offered an improvement in migraine therapy, 
although concerns remain about chest symptoms associated with this class of
drugs. In early clinical trials, rizatriptan was shown to have good
bioavailability and favorable effects on quality of life. Long-term extension
trials ran for up to 12 months and compared rizatriptan with "usual care" (i.e., 
medications used for acute therapy). These studies showed that the 10-mg
rizatriptan dose was consistently superior to usual care with regard to pain
relief and complete pain relief (pain-free). Side effects were generally mild and
transient in all treatment groups. Nausea, dizziness, and somnolence were the
most commonly reported adverse effects.

Publication Types: 
    Comparative Study

PMID: 11089516 [PubMed - indexed for MEDLINE]

3502: Neurology. 2000;55(9 Suppl 2):S19-24.

Oral therapy for migraine: comparisons between rizatriptan and sumatriptan. A
review of four randomized, double-blind clinical trials.

Tfelt-Hansen P, Ryan RE Jr.

Department of Neurology, Glostrup Hospital, University of Copenhagen, Denmark.

The introduction in 1991 of sumatriptan succinate, the first approved 5-HT1B/1D
receptor agonist, represented a significant advance in the treatment of acute
migraine. The approval of three additional 5-HT receptor agonists, including
rizatriptan, has further expanded the options for migraine treatment. Four
randomized clinical trials have compared the effects of oral sumatriptan with
those of oral rizatriptan. Forty mg rizatriptan was more effective than 100 mg
sumatriptan but was associated with a high incidence of adverse events. Five mg
rizatriptan was comparable to 50 mg sumatriptan. In two trials, rizatriptan 10
mg, the recommended dose in most countries, had a more rapid onset of action than
50 mg (p<0.05) and 100 mg sumatriptan (p=0.075). In addition, 10 mg rizatriptan
resulted in more patients being pain-free after 2 hours than 100 mg sumatriptan
(p<0.05), and resulted in fewer drug-related adverse events than sumatriptan.

Publication Types: 
    Comparative Study

PMID: 11089515 [PubMed - indexed for MEDLINE]

3503: Neurology. 2000;55(9 Suppl 2):S15-8.

The use of rizatriptan in the treatment of acute, multiple migraine attacks.

Saper JR.

Michigan Head Pain and Neurological Institute, Ann Arbor, MI 48104, USA.

Therapy for migraine can be classified as preventive or acute. Preventive therapy
is intended to reduce the frequency of headache, whereas the goal of acute
migraine therapy is to optimize the patient's ability to function by reversing,
aborting, or reducing pain and migraine-associated symptoms. Rizatriptan is a
new, selective 5-HT1B/1D receptor agonist that is effective for treatment of
migraine. Clinical studies of this drug have demonstrated its efficacy, safety,
and tolerability when used as therapy for acute attacks on multiple occasions.

Publication Types: 
    Review

PMID: 11089514 [PubMed - indexed for MEDLINE]

3504: Neurology. 2000;55(9 Suppl 2):S8-14.

Mechanisms of action of serotonin 5-HT1B/D agonists: insights into migraine
pathophysiology using rizatriptan.

Goadsby PJ, Hargreaves RJ.

Institute of Neurology, London, UK.

Current theories on the etiology of migraine headache suggest that it is a
neurovascular disorder (i.e., vascular change secondary to neural activation),
with a primary CNS dysfunction giving rise to headache pain as a result of local 
intracranial vasodilatation and release of sensory neuropeptides from nerve
endings in an activated trigeminal system. The serotonin 5-HT1B/1D agonists,
known as the triptans, represent a major advance in the treatment of acute
migraine. This article describes their mechanisms of action. The development of
5-HT1B/1D agonist drugs, such as rizatriptan, and the study of their pharmacology
have enhanced our understanding of the mechanisms involved in the pathophysiology
of migraine.

Publication Types: 
    Review

PMID: 11089513 [PubMed - indexed for MEDLINE]

3505: Neurology. 2000;55(9 Suppl 2):S3-7.

Methodologic issues in acute migraine clinical trials.

Lipton RB.

Department of Neurology, Epidemiology, and Social Medicine, Albert Einstein
College of Medicine, Bronx, NY 10468, USA.

Migraine is a common chronic condition with an ever-expanding therapeutic
armamentarium. As new migraine therapies are investigated, the methodology of
clinical trials has become increasingly important. Clinical trials should provide
clinicians and patients with the information they need to assess the efficacy,
safety, and comparative benefits of current and emerging therapies. The study
design (e.g., crossover, parallel group) and methods, including determination of 
appropriate dosing, are key. The selection of primary efficacy end points is
another critical factor. There is increasing evidence that complete pain relief
powerfully predicts patient satisfaction with treatment and quality of life.
Secondary end points, such as relief of migraine-associated symptoms, need for
use of escape medication, and quality of life measurements, should also be
carefully considered.

Publication Types: 
    Review

PMID: 11089512 [PubMed - indexed for MEDLINE]

3506: JAMA. 2000 Nov 22-29;284(20):2599-605.

Comment in:
    JAMA. 2000 Nov 22-29;284(20):2640-1.    JAMA. 2001 Feb 28;285(8):1014-5.    JAMA. 2001 Feb 28;285(8):1014; author reply 1014-5.

Stratified care vs step care strategies for migraine: the Disability in
Strategies of Care (DISC) Study: A randomized trial.

Lipton RB, Stewart WF, Stone AM, Láinez MJ, Sawyer JP; Disability in Strategies
of Care Study group.

Innovative Medical Research Inc, 1200 High Ridge Rd, Stamford, CT 06905, USA.
rlipton@imrinc.com

CONTEXT: Various guidelines recommend different strategies for selecting and
sequencing acute treatments for migraine. In step care, treatment is escalated
after first-line medications fail. In stratified care, initial treatment is based
on measurement of the severity of illness or other factors. These strategies for 
migraine have not been rigorously evaluated. OBJECTIVE: To compare the clinical
benefits of 3 strategies: stratified care, step care within attacks, and step
care across attacks, among patients with migraine. DESIGN AND SETTING:
Randomized, controlled, parallel-group clinical trial conducted by the Disability
in Strategies Study group from December 1997 to March 1999 in 88 clinical centers
in 13 countries. PATIENTS: A total of 835 adult migraine patients with a Migraine
Disability Assessment Scale (MIDAS) grade of II, III, or IV were analyzed as the 
efficacy population; the safety analysis included 930 patients. INTERVENTIONS:
Patients were randomly assigned to receive (1) stratified care (n = 279), in
which patients with MIDAS grade II treated up to 6 attacks with aspirin, 800 to
1000 mg, plus metoclopramide, 10 mg, and patients with MIDAS grade III and IV
treated up to 6 attacks with zolmitriptan, 2.5 mg; (2) step care across attacks
(n = 271), in which initial treatment was with aspirin, 800 to 1000 mg, plus
metoclopramide, 10 mg. Patients not responding in at least 2 of the first 3
attacks switched to zolmitriptan, 2.5 mg, to treat the remaining 3 attacks; and
(3) step care within attacks (n = 285), in which initial treatment for all
attacks was with aspirin, 800 to 1000 mg, plus metoclopramide, 20 mg. Patients
not responding to treatment after 2 hours in each attack escalated treatment to
zolmitriptan, 2.5 mg. MAIN OUTCOME MEASURES: Headache response, achieved if pain 
intensity was reduced from severe or moderate at baseline to mild or no pain at 2
hours; and disability time per treated attack at 4 hours for all 6 attacks,
compared among the 3 groups. RESULTS: Headache response at 2 hours was
significantly greater across 6 attacks in the stratified care treatment group
(52.7%) than in either the step care across attacks group (40.6%; P<.001) or the 
step care within attacks group (36.4%; P<.001). Disability time (6 attacks) was
significantly lower in the stratified care group (mean area under the curve
[AUC], 185.0 mm. h) than in the step care across attacks group (mean AUC, 209.4
mm. h; P<.001) or the step care within attacks group (mean AUC, 199.7 mm. h;
P<.001). The incidence of adverse events was higher in the stratified care group 
(321 events) vs both step care groups (159 events in across-attack group; 217 in 
within-attack group), although most events were of mild-to-moderate intensity.
CONCLUSION: Our results indicate that as a treatment strategy, stratified care
provides significantly better clinical outcomes than step care strategies within 
or across attacks as measured by headache response and disability time. JAMA.
2000;284:2599-2605.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 11086366 [PubMed - indexed for MEDLINE]

3507: Neurogenetics. 2000 Sep;3(1):35-40.

Evidence for allelic association of the dopamine beta-hydroxylase gene (DBH) with
susceptibility to typical migraine.

Lea RA, Dohy A, Jordan K, Quinlan S, Brimage PJ, Griffiths LR.

Genomics Research Centre, School of Health Sciences, Griffith University,
Queensland, Australia. L.Griffiths@mailbox.gu.edu.au

Migraine is a debilitating neurological disorder characterized by recurrent
attacks of severe headache. The disorder is highly prevalent, affecting
approximately 12% of Caucasian populations. It is well known that migraine has a 
strong genetic component, although the type and number of genes involved is not
yet clear. However, the calcium channel gene, CACNA1A, on chromosome 19 contains 
mutations responsible for familial hemiplegic migraine, a rare and severe subtype
of migraine. There is also evidence to suggest that serotonin- and
dopamine-related genes may be involved in the pathogenesis of migraine. This
study employed a linkage and association approach to investigate
neurotransmitter-related migraine candidate genes. Polymorphisms within the
dopamine beta-hydroxylase (DBH) gene, serotonin transporter gene (SERT), and
dopamine receptor gene (DRD2) were tested in 177 unrelated Caucasian migraineurs 
and 182 control individuals. In addition, an independent sample of 82 families
affected with migraine was examined. Unrelated case-control association analysis 
of a DBH intragenic dinucleotide polymorphism indicated altered allelic
distribution between migraine and control groups (chi2 = 16.53, P=0.019).
Furthermore, the transmission/disequilibrium test, which was implemented on the
family data, also indicated distortion of allele transmission for the same DBH
marker (chi2 = 4.44, P=0.035). Together, these results provide evidence for
allelic association of the DBH gene with typical migraine susceptibility
(Fisher's combined P value =0.006) and indicate that further research into the
role of the DBH gene in the etiology of migraine is warranted.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 11085595 [PubMed - indexed for MEDLINE]

3508: Pharmacotherapy. 2000 Nov;20(11):1356-64.

Cost-benefit analysis of sumatriptan tablets versus usual therapy for treatment
of migraine.

Biddle AK, Shih YC, Kwong WJ.

Department of Health Policy and Administration, School of Public Health,
University of North Carolina, Chapel Hill 27599-7400, USA.

We performed a systematic assessment of the costs and benefits of sumatriptan and
usual therapy for migraine from society's perspective. A decision tree was
constructed with probability estimates based on data from an open-label clinical 
trial assessing the economic and human impacts of sumatriptan and usual therapy
on nursing personnel. Direct medical care costs including costs for drug,
physician, and emergency room visits were considered. Benefits were estimated
using the human capital approach based on the national average of weekly earnings
and productivity loss estimated from a migraine clinical trial. The net benefits 
of sumatriptan and usual therapy for the treatment of a single migraine attack
were estimated to be $50 and $20, respectively. The annual incremental net
benefit of sumatriptan over usual therapy was estimated to be $114-540/patient.
The price difference was offset by benefits of sumatriptan in reducing use of
health care resources and productivity loss.

PMID: 11079284 [PubMed - indexed for MEDLINE]

3509: Cephalalgia. 2000 Jul;20(6):597-602.

Intranasal civamide for the acute treatment of migraine headache.

Diamond S, Freitag F, Phillips SB, Bernstein JE, Saper JR.

Diamond Headache Clinic, Chicago, IL 60614-1726, USA.

The objective of this study was to investigate the safety and efficacy of
intranasal civamide for the acute treatment of migraine headache with or without 
aura. Civamide is a vanilloid receptor agonist and neuronal calcium channel
blocker that inhibits the neuronal release of excitatory neurotransmitters (e.g. 
calcitonin gene-related peptide (CGRP) and substance P (SP)) and depletes the
neurones of the trigeminal plexus of their neurotransmitter content. Applied
intranasally, the release of neurotransmitters to meningeal and dural blood
vessels should be decreased, along with the resultant vasodilatation, plasma
extravasation, and histamine/serotonin release. Subsequent migraine headache pain
may also be diminished. Thirty-four patients were enrolled into a double-blind
study of intranasal civamide, and randomized to receive a single dose of either
20 microg or 150 microg of civamide, for the treatment of a single migraine
headache, with or without aura, of moderate to severe pain. At 2 h post-dose,
55.6% of patients treated with either dose had a decrease in pain severity, with 
22.2% of patients being pain-free. At 4 h post-dose, 72.7% of patients treated
with either dose had a decrease in pain severity, with 33.0% of patients being
pain-free. Adverse events were similar for both dosages, with 91.2% of patients
experiencing nasal burning and 44.1% of patients experiencing lacrimation. No
systemic side-effects were observed. Based upon the results of this study,
intranasal civamide may be effective in the acute treatment of migraine headache.
Given civamide's proposed mechanism of action, intranasal civamide should be
substantially more effective for prophylaxis than acute treatment of migraine. A 
study evaluating its efficacy in prophylaxis of migraine is currently planned.

Publication Types: 
    Clinical Trial
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 11075845 [PubMed - indexed for MEDLINE]

3510: Cephalalgia. 2000 Jul;20(6):588-96.

Consistent efficacy and tolerability of almotriptan in the acute treatment of
multiple migraine attacks: results of a large, randomized, double-blind,
placebo-controlled study.

Pascual J, Falk RM, Piessens F, Prusinski A, Docekal P, Robert M, Ferrer P, Luria
X, Segarra R, Zayas JM.

Servicio de Neurología, University Hospital, Santander, Spain.
pascualj@medi.unican.es

In this double-blind study, the efficacy and tolerability of a single dose of
almotriptan (6.25 or 12.5 mg) was compared with placebo in the treatment of three
consecutive migraine attacks of moderate or severe intensity. Of 1013 randomized 
patients, 722 evaluable patients completed the study. The total number of attacks
relieved (severe or moderate pain reduced to mild or no pain) at 2 h post-dose
was significantly higher (P < 0.001) after treatment with almotriptan 6.25 or
12.5 mg compared with placebo (60% and 70% vs. 38%, respectively). Moreover, a
consistent response was achieved across and within patients for almotriptan 6.25 
or 12.5 mg compared with placebo (pain relief in at least two out of three
attacks within 2 h for 64% and 75% vs. 36%, respectively) and less than one-third
of the patients relapsed within 24 h. Almotriptan was well tolerated with no
significant differences between the almotriptan and placebo treatment groups in
the percentage of patients reporting adverse events. Overall, the 12.5-mg dose
was associated with the most favourable efficacy/tolerability ratio and is,
therefore, the recommended dose.

Publication Types: 
    Case Reports
    Clinical Trial
    Multicenter Study
    Randomized Controlled Trial

PMID: 11075844 [PubMed - indexed for MEDLINE]

3511: Cephalalgia. 2000 Jul;20(6):580-4.

Migraine attacks and sleep in children.

Aaltonen K, Hämäläinen ML, Hoppu K.

Hospital for Children and Adolescents, Department of Clinical Pharmacology,
University of Helsinki, Finland. kati.aaltonen@fimnet.fi

Falling asleep as a means of ending migraine attack was studied in 133
4-16-year-old children in out-patient settings. Children registered 999 migraine 
attacks in headache diaries using a visual analogue scale (VAS) in 409 attacks
and a five-face scale in 590 attacks. The distribution of maximal pain intensity 
was similar on both scales; on VAS 88% assigned grades between 63 and 100, and on
the face scale 93% assigned grades of 4 or 5. Children fell asleep during 33% of 
the attacks (n = 329), in 64% of these within the first hour (n = 209). Of the
children, 68% (n = 91) had fallen asleep at least once during an attack. Falling 
asleep was more common in children under 8 years of age than in older children.
In those under 8 years, 62% (95% confidence interval (CI) 49-75%) of attacks were
resolved by sleep, in those aged 8-12 years 34% (26-41%), and in children >12
years 24% (15-33%) (ANOVA, P<0.0001). Pain was relieved without sleep in 43% (n =
431) of attacks, in 38% of these (n = 383) within the first 4 h. The data on
migraine resolution were missing for 24% (n = 239) of the attacks, most often
because the attack exceeded the 5-h observation period. This study confirms that 
migraine attacks in children are extremely painful and often resolve during an
interval of sleep in children under 8 years of age.

PMID: 11075842 [PubMed - indexed for MEDLINE]

3512: Cephalalgia. 2000 Jul;20(6):573-9.

Natural history of migraine in childhood.

Hernandez-Latorre MA, Roig M.

Child Neurology Unit, Hospital de Niños de Barcelona, Spain.

Epidemiological studies have shown that 3-7% of the paediatric population suffer 
from migraine. Despite this high prevalence little has been published about the
natural history of migraine or of its prognosis. The objectives of this study
were: (i) to outline the natural history of migraine in childhood; and (ii) to
identify early predictors of an unfavourable clinical evolution. A prospective,
longitudinal, 10-year follow-up study was conducted of the clinical evolution of 
181 paediatric patients with migraine. Data analysis was performed by statistical
significance and logistic regression tests. In our study 24.3% of children with
migraine had their onset before age 6 years and another 57% between 6 and 10
years of age. A positive family history of migraine was recorded in 77.5%.
Eighty-eight percent of patients followed a favourable clinical course. The
remaining 12% of patients had to be placed on prophylactic treatment owing to the
increasing of their headache. Of all parameters investigated, the age of onset
was the only statistically significant predictor of an unfavourable clinical
evolution. We conclude: (i) most patients with migraine headache starting in
childhood do not require prophylactic treatment; (ii) the earlier the disease
begins the more likely is an unfavourable clinical course; (iii) genetic factors 
play an important role in the phenotypic expression of the disease; (iv) our
study suggests the existence, at least, of two different populations among
childhood migraine patients.

PMID: 11075841 [PubMed - indexed for MEDLINE]

3513: Cephalalgia. 2000 Jul;20(6):566-72.

Prevalence of migraine in Taipei, Taiwan: a population-based survey.

Wang SJ, Fuh JL, Young YH, Lu SR, Shia BC.

The Neurological Institute, Taipei Veterans General Hospital, and Department of
Neurology and National Yang-Ming University School of Medicine, Taiwan.
sjwang@vghtpe.gov.tw

We conducted the first population-based migraine survey in Taipei, Taiwan, using 
a validated questionnaire administered by interviewers during the period from
August 1997 to June 1998. Our target population comprised all individuals (age > 
or = 15 years) in 1400 randomly selected households. Migraine diagnoses were made
according to the classification criteria of migraine without aura proposed by the
International Headache Society, 1988, except that attacks with a duration of
between 2 h and 4 h were also included. Of the 4434 eligible subjects in the 1211
respondent households, 3377 (76%) completed the questionnaire. After adjustment
for age and sex distribution according to the population structure, the
prevalence of migraine was 9.1% (F/M 14.4%/4.5%). Fifty-four percent of the
subjects with migraine had consulted a physician about their headaches in the
past year. However, only 18% of them reported that their migraine had been
diagnosed by physicians. This study found that Taipei residents have the highest 
migraine prevalence of all Chinese populations studied, although it is still in
the low range of prevalence compared with the results from Western countries.

Publication Types: 
    Comparative Study
    Research Support, U.S. Gov't, Non-P.H.S.
    Validation Studies

PMID: 11075840 [PubMed - indexed for MEDLINE]

3514: Cephalalgia. 2000 Jul;20(6):561-5.

Association between Helicobacter pylori cytotoxic type I CagA-positive strains
and migraine with aura.

Gasbarrini A, Gabrielli M, Fiore G, Candelli M, Bartolozzi F, De Luca A,
Cremonini F, Franceschi F, Di Campli C, Armuzzi A, Ojetti V, Serricchio M, Pola
R, Gasbarrini G, Giacovazzo M, Pola P.

Angiology Department, Catholic University, Rome, Italy. angiologia@rm.unicatt.it

Recent studies have suggested an association between Helicobacter pylori
infection and migraine. However, various strains of the bacterium are present,
some endowed with greater pathogenicity. In particular, H. pylori type I
CagA-positive strains induce a higher release of proinflammatory substances by
the gastric mucosa that could trigger systemic vasospasms. The aim of the present
study was to assess the prevalence of H. pylori CagA-positive strains in subjects
with migraine. One hundred and seventy-five patients affected by migraine (49
with aura, 126 without aura) were consecutively enrolled and matched for sex,
age, social background and geographical origin with 152 controls. Helicobacter
pylori infection was assessed through 13C-urea breath test. Specific serological 
IgG against CagA were detected through ELISA. The prevalence of H. pylori
infection was similar in migraine patients and in controls (40% vs. 39%,
respectively). Among migraine patients, prevalence of infection was not related
to presence or absence of aura (45% vs. 37%, respectively). However, among
infected subjects, a significantly higher prevalence of CagA-positive strains was
observed in patients affected by migraine with aura when compared with those
affected by migraine without aura (41% vs. 19%, P < 0.01) and with controls (41% 
vs. 17%, P < 0.01). CagA-positive H. pylori strains were found to be strongly
associated with migraine with aura. A higher inflammatory response of the gastric
mucosa to more virulent strains could release substances that may act as triggers
of vasospasm in peculiar cerebral arterial districts, probably implicated in the 
'aura' phenomenon.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 11075839 [PubMed - indexed for MEDLINE]

3515: Cephalalgia. 2000 Jul;20(6):554-60.

Determinants of patient satisfaction with migraine therapy.

Davies GM, Santanello N, Lipton R.

Merck Research Laboratories, West Point, PA 19486-0004, USA.
glenn_davies@merck.com

Determinants of patient satisfaction with migraine treatment are not well
understood. The objective of this study was to evaluate which treatment outcomes 
influence patient satisfaction with treatment. Analyses were performed on data
from 1506 migraineurs from two clinical trials of rizatriptan for treatment of
migraine. Satisfaction with treatment was assessed 2 h after initial treatment
and prior to use of rescue therapy. Over 90% of patients who were pain-free at 2 
h were at least somewhat satisfied with treatment compared with <10% of patients 
with moderate or severe pain. Only 60-70% of patients with mild pain at 2 h
experienced some level of satisfaction with treatment. For patients with mild
pain at 2 h, results showed subjects who reported severe pain at baseline,
absence of associated symptoms at 2 h and pain relief within the first 90 min had
at least a 76% probability of being at least somewhat satisfied. This probability
decreased with the presence of associated symptoms, slower pain relief and
moderate baseline pain intensity. Fast, complete pain relief is one important
factor in determining short-term patient satisfaction with treatment.

Publication Types: 
    Comparative Study

PMID: 11075838 [PubMed - indexed for MEDLINE]

3516: Cephalalgia. 2000 Jul;20(6):546-53.

Repetitive cortical spreading depression in a gyrencephalic feline brain:
inhibition by the novel benzoylamino-benzopyran SB-220453.

Smith MI, Read SJ, Chan WN, Thompson M, Hunter AJ, Upton N, Parsons AA.

Department of Neuroscience Research, SmithKline Beecham Pharmaceuticals, Harlow, 
UK.

Transient cortical depolarization is implicated in the pathology of migraine.
SB-220453 is a potent anti-convulsant which inhibits neurogenic inflammation and 
cortical spreading depression (SD)-evoked nitric oxide release via a novel but
unknown mechanism. This study further investigates the effects of SB-220453 on
generation and propagation of repetitive SD in the anaesthetized cat. Vehicle or 
SB-220453 1, 3 or 10 mg/kg was administered intraperitoneally 90 min prior to
induction of SD in the suprasylvian gyrus (SG). Changes in d.c. potential were
recorded in the SG and the adjacent marginal gyrus (MG). In vehicle-treated
animals (n = 7), a brief exposure (6 min) to KCl induced a median (25-75% range) 
number of five (four to six) and three (two to four) depolarizations over a
duration of 55 min (32-59 min) and 51 min (34-58 min) in the SG and MG,
respectively. SB-220453 produced dose-related inhibition of the number of events 
and period of repetitive SD activity. SB-220453 also reduced SD-induced
repetitive pial vasodilatation but had no effect on resting haemodynamics.
However, when SD events were observed in the presence of SB-220453, it had no
effect on metabolic coupling. These results show that SB-220453 produces marked
inhibition of repetitive SD in the anaesthetized cat. SB-220453 may therefore
have therapeutic potential in treatment of SD-like activity in migraine.

PMID: 11075837 [PubMed - indexed for MEDLINE]

3517: Cephalalgia. 2000 Jul;20(6):533-7.

Different effects of GABAergic anticonvulsants on 4-aminopyridine-induced
spontaneous GABAergic hyperpolarizations of hippocampal pyramidal
cells--implication for their potency in migraine therapy.

Leniger T, Wiemann M, Bingmann D, Hufnagel A, Bonnet U.

Department of Neurology, University of Essen, Germany.
tobias.leniger@uni-essen.de

Clinical studies indicate anti-migrane efficacy of the probably GABAergic
anticonvulsants valproate and gabapentin. For the GABAergic anticonvulsants
vigabatrin and tiagabine, studies about antimigrane efficacy are missing. The aim
of this study was to test the GABAergic potency of these drugs in vitro before
further clinical studies. Intracellular recordings were obtained from hippocampal
pyramidal cells. Spontaneous GABAergic hyperpolarizations (SGH) elicited by 75
microM 4-aminopyridine were used to test the effect of these drugs on
GABA-dependent potentials. Tiagabine (0.1 mM) prolonged the duration of SGH.
Furthermore, monophasic SGH turned over into triphasic typical GABAergic membrane
potential fluctuations within 20 min. In contrast, valproate, gabapentin, and
vigabatrin failed to affect SGH up to 60 min of application. The reason for the
fast action of tiagabine on SGH may be caused by a faster increase of synaptic
GABA levels compared with other drugs. As migraine therapy benefits from an
augmentation of GABA activity, we recommend clinical studies of tiagabine as a
fast-acting agent in migraine attacks.

Publication Types: 
    Comparative Study

PMID: 11075835 [PubMed - indexed for MEDLINE]

3518: Cephalalgia. 2000 Jul;20(6):525-32.

Cortical hyperexcitability is cortical under-inhibition: evidence from a novel
functional test of migraine patients.

Palmer JE, Chronicle EP, Rolan P, Mulleners WM.

Department of Psychology, Lancaster University, UK.

Recent studies of the visual cortex in patients with migraine have generally
concluded that migraine (particularly migraine with aura) is associated with a
state of functional cortical hyperexcitability. The mechanisms giving rise to
this hyperexcitability have hitherto been unclear. This paper reports two studies
that used a novel investigative technique, derived from basic research in vision 
science, to examine specific deficits of inhibitory processing in primary visual 
cortex. The technique is termed the metacontrast test, and it examines visual
masking under highly specified conditions. In Study 1, 12 migraine with aura
patients (MA), 12 age-matched migraine without aura patients (MO) and 12 age- and
sex-matched headache-free control subjects (C) were compared using the
metacontrast test. MA patients were significantly less susceptible to visual
masking in the metacontrast test than both MO and C groups: this result is highly
consistent with a deficit in cortical inhibitory processing in MA patients. Study
2 examined MA patients taking a variety of migraine prophylactics, again using
the metacontrast test. Test results normalized in those MA patients taking sodium
valproate, but not in those taking other prophylactics. Sodium valproate is a
GABA-A agonist that is known to cross the blood-brain barrier: GABA-ergic
networks act as the primary inhibitory mechanism in visual cortex. Taken
together, the results of these studies argue that cortical hyperexcitability, at 
least in MA patients, is likely to be a result of deficient intracortical
inhibitory processes.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 11075834 [PubMed - indexed for MEDLINE]

3519: Arch Neurol. 2000 Nov;57(11):1631-4.

Can migraine damage the inner ear?

Lee H, Lopez I, Ishiyama A, Baloh RW.

Department of Neurology, Box 951769, UCLA School of Medicine, Los Angeles, CA
90095-1769, USA.

BACKGROUND: Auditory and vestibular symptoms and signs are common in patients
with migraine, yet little is known about the pathogenesis of these symptoms and
signs. OBJECTIVE: To perform clinicopathological correlation in a patient with
migraine, sudden deafness, and delayed endolymphatic hydrops. METHODS: A patient 
with long-standing migraine with aura developed sudden hearing loss in the left
ear at the age of 50 years and Ménière disease on the right side at age 73. At
age 76, he had a flurry of sudden drop attacks typical of otolithic crisis. He
died of unrelated causes at age 81. The brain and temporal bones were removed
approximately 24 hours after death. The cochlea and vestibular end organs were
dissected after the surrounding bone was carefully removed. RESULTS: The brain
and cerebrovasculature were normal. The left cochlea showed prominent fibrosis
consistent with an old infarction. The right inner ear showed hydrops, with
relatively good preservation of the hair cells in the cochlea, saccular macule,
and cristae of the semicircular canals. However, the utricular macule was denuded
of hair cells. CONCLUSIONS: The sudden left-sided deafness likely resulted from
ischemia, possibly due to migraine-associated vasospasm. Presumably, the right
ear suffered only minimal damage when the patient was 50 years old, but this
damage later led to the development of delayed endolymphatic hydrops on the
right. Otolithic crises are thought to result from pressure changes across the
utricular macule. We speculate that loss of hair cells in the utricular macule
resulted from a collapse of the utricular membrane onto the macule.

Publication Types: 
    Case Reports
    Research Support, U.S. Gov't, P.H.S.

PMID: 11074796 [PubMed - indexed for MEDLINE]

3520: Pathol Biol (Paris). 2000 Sep;48(7):648-57.

Nitric oxide mechanisms in migraine.

Olesen J, Jansen-Olesen I.

Department of Neurology, Glostrup Hospital, University of Copenhagen, Denmark.

The molecular mechanisms of migraine pain have not yet been clarified. Neurogenic
inflammation and a subsequent plasma extravasation in the dura mater have been
suggested as causative factors. However, monoamine and peptide neurotransmitters 
involved in neurogenic inflammation do not cause significant head pain. Based on 
our previous studies of headache induced by i.v. infusions of glyceryl trinitrate
(exogenous nitric oxide [NO] donor) and histamine (which liberates NO from the
vascular endothelium), it is suggested that NO is a more likely candidate
molecule. The present review examines the biology of this small messenger
molecule, and the scientific evidence suggesting that it may play a key role in
migraine headache. It is hypothesized that the release of NO from blood vessels, 
perivascular nerve endings or from brain tissue is a molecular mechanism which
triggers spontaneous migraine pain. Furthermore, it has been shown that this
hypothesis is supported by the recent findings that i.v. infusion of the NO
synthase (NOS) inhibitor is effective in the acute treatment of migraine attacks.
These novel observations indicate possible new approaches to the pharmacological 
treatment of migraine.

Publication Types: 
    Review

PMID: 11072643 [PubMed - indexed for MEDLINE]

3521: J Am Osteopath Assoc. 2000 Sep;100(9 Suppl):S1-7.

Treatment of acute migraine attacks.

Weintraub JR.

Michigan Head-Pain & Neurological Institute, Ann Arbor 48104-5199, USA.
mhniinfo@aol.com

Migraine headaches are a common medical problem that physicians frequently
encounter in their practice. They can be disabling, leading to the individual's
suffering if not treated appropriately and quickly. There is a variety of
medications and treatment approaches that can be used to relieve pain and any
associated symptoms. New medications have become available in recent years to
aggressively treat migraine headaches. Called "triptans," these medications have 
been designed to specifically treat an acute migraine attack and can be effective
if used early and properly. Many medications are also available to treat symptoms
associated with migraines. Patient education, along with nonpharmacologic
approaches, is an element of effective treatment. Biofeedback, relaxation, and
physical techniques can be effective adjunctive options. Although nonprescription
medications can be helpful initially, more specific treatment is often required. 
Opioids, phenothiazines, ergotamine, and the triptans are generally used in
patients with difficult migraines. The newer agents, the triptans, offer new hope
in aggressively treating this painful condition that often has an impact on
individuals and their families.

Publication Types: 
    Review

PMID: 11070658 [PubMed - indexed for MEDLINE]

3522: Int J Clin Pract. 2000 Sep;54(7):466-9.

Zolmitriptan provides effective migraine relief in adolescents.

Linder SL, Dowson AJ.

Dallas Pediatric Neurology Associates, Texas, USA.

Data from a subgroup of adolescents (12-17 years) entered into a one-year
open-label phase of a large international study were analysed to evaluate
response rates and tolerability of zolmitriptan for the acute treatment of
migraine. In the open-label phase of this study, the first two migraine attacks
were treated with zolmitriptan 2.5 mg and subsequent attacks with zolmitriptan
2.5 mg or 5 mg, at the patient's discretion, for up to 12 months. Two-hour
headache and pain-free responses were evaluated and adverse events were recorded.
Thirty-eight adolescents treated 276 migraine attacks of any intensity. The
overall headache response at 2 hours was 80% (88% and 70% with zolmitriptan 2.5
mg and 5 mg, respectively), and the pain-free response was 66% (76% and 52% for
zolmitriptan 2.5 mg and 5 mg, respectively). Response rates were independent of
whether or not migraine was associated with aura or menses. During prolonged use,
patients learned to adjust the dose of zolmitriptan to effectively manage their
migraine. Treatment was well tolerated. In conclusion, preliminary data indicate 
that zolmitriptan is effective in the acute treatment of migraine in adolescents 
and is well tolerated.

Publication Types: 
    Clinical Trial
    Multicenter Study

PMID: 11070573 [PubMed - indexed for MEDLINE]

3523: Eur J Neurosci. 2000 Nov;12(11):3991-4002.

Effects of eletriptan on the peptidergic innervation of the cerebral dura mater
and trigeminal ganglion, and on the expression of c-fos and c-jun in the
trigeminal complex of the rat in an experimental migraine model.

Knyihár-Csillik E, Tajti J, Csillik AE, Chadaide Z, Mihály A, Vécsei L.

Department of Clinical Neurology, Szeged University, Semmelweis utca 6, H-6701
Szeged, Hungary. knyihar@nepsy.szote.u-szeged.hu

Nociceptive axons and terminals in the supratentorial cerebral dura mater display
an intense calcitonin gene-related peptide (CGRP) immunoreactivity. In an
experimental migraine model, it has been shown that electrical stimulation of the
rat trigeminal ganglion induced an increase in the lengths of CGRP-immunoreactive
axons, increased size and number of pleomorphic axonal varicosities in the dura
mater, and an increased number of c-jun and c-fos protein-expressing nerve cells 
in the trigeminal complex. We demonstrate the effect of the highly specific and
moderately lipophilic serotonin agonist eletriptan (Pfizer) which prevents the
effects of electrical stimulation in the dura mater. Eletriptan also affected the
caudal trigeminal complex; it markedly reduced the numbers of the
oncoprotein-expressing cells, mainly after stimulation and to some extent also in
nonstimulated animals. Eletriptan also affected expression of CGRP in perikarya
of trigeminal ganglion cells, insofar as the number of small nerve cells
exhibiting a compact CGRP immunoreaction was decreased to one quarter of the
original value. In all these respects, eletriptan acted in a similar way to
sumatriptan, with the notable exception that eletriptan also blocked the
stimulation-induced effects in the nucleus caudalis trigemini and the upper
cervical spinal cord (trigeminal complex), whereas sumatriptan did not. It is
concluded that eletriptan, acting on perikarya and both the peripheral and the
central axon terminals of primary sensory neurons, exerts its antimigraine effect
by an agonist action on 5-HT1B/1D receptors throughout the entire trigeminal
system, probably by passing the blood-brain-barrier because of its lipophilic
character.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 11069595 [PubMed - indexed for MEDLINE]

3524: J Child Neurol. 2000 Oct;15(10):694-6.

Vertebral artery dissection and migraine headaches in children.

Lotze TE, Paolicchi J.

Department of Pediatric Neurology, Columbus Children's Hospital, Ohio 43205, USA.

Strokes of the posterior circulation are uncommon in childhood. In
vertebrobasilar insults, vertebral artery dissection remains a rare diagnosis. We
report the case of an 8-year-old boy with a history of migraine headaches who
presented with acute cerebellar signs and agitation following multiple
infarctions of bilateral cerebellar hemispheres. Vertebral angiography
demonstrated dissection of the left vertebral artery with occlusion of the
basilar artery just distal to its origin. Risk factors for vertebral artery
dissection are reviewed, with emphasis on association with migraine headaches. A 
review of imaging studies for the diagnosis of dissection is also presented. This
case demonstrates the importance of considering arterial wall dissection in
pediatric patients with a history of atypical migraines associated with new
neurologic findings.

Publication Types: 
    Case Reports

PMID: 11063085 [PubMed - indexed for MEDLINE]

3525: Pediatrics. 2000 Nov;106(5):989-97.

Comment in:
    Pediatrics. 2001 Sep;108(3):817.

A randomized, double-blind, placebo-controlled study of sumatriptan nasal spray
in the treatment of acute migraine in adolescents.

Winner P, Rothner AD, Saper J, Nett R, Asgharnejad M, Laurenza A, Austin R,
Peykamian M.

Palm Beach Headache Center, West Palm Beach, Florida, USA. pwinner777@aol.com

OBJECTIVE: To compare the efficacy and tolerability of sumatriptan nasal spray
(NS; 5 mg, 10 mg, and 20 mg) with placebo for the treatment of acute migraine in 
adolescents. METHODS: A randomized, double-blind, placebo-controlled,
single-attack study was conducted in 653 US adolescents (12-17 years of age).
Patients with at least a 6-month history of migraine, who met International
Headache Society criteria for migraine (with or without aura) were eligible for
participation. Headache relief 2 hours postdose, complete relief, presence or
absence of associated symptoms, headache recurrence, and use of rescue
medications were recorded. The primary efficacy endpoint was headache relief 2
hours postdose sumatriptan NS (20 mg) versus placebo. Safety and tolerability
were assessed by examining adverse events, changes in electrocardiograms, vital
signs, physical examinations, and clinical laboratory tests. RESULTS: Headache
relief 1 hour postdose was significantly greater for patients using 10 mg (56%)
and 20 mg (56%) of sumatriptan NS compared with placebo (41%). Headache relief 2 
hours postdose was significantly greater for patients using 5 mg of sumatriptan
NS (66%) compared with placebo (53%), and approached statistical significance for
20 mg (63%) compared with placebo (53%). Complete relief 2 hours postdose was
significantly greater for patients using 20 mg of sumatriptan NS compared with
placebo (36% vs 25%, respectively). Each dose of sumatriptan (5 mg, 10 mg, and 20
mg) was superior to placebo with respect to the cumulative percentages of
patients first reporting headache relief within 2 hours of dosing (Kaplan-Meier).
The sumatriptan 20-mg dose was superior to placebo with respect to the cumulative
percentages of patients first reporting complete relief within 2 hours of dosing 
(Kaplan-Meier). Photophobia and phonophobia were significantly reduced 2 hours
postdose for sumatriptan NS (20 mg), compared with placebo (36% vs 48% and 25% vs
44%, respectively). Taste disturbance was the most commonly reported adverse
event (2%, 19%, 30%, and 26% for placebo, 5 mg, 10 mg, and 20 mg, respectively). 
No drug-related serious adverse events or clinically relevant changes in
laboratory parameters, electrocardiograms, or vital signs were reported.
CONCLUSIONS: Sumatriptan NS is effective and well-tolerated for the treatment of 
acute migraine in adolescents, with the 20-mg dose providing the best overall
efficacy and tolerability profiles.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 11061765 [PubMed - indexed for MEDLINE]

3526: Clin Pharmacol Ther. 2000 Oct;68(4):418-26.

Vascular effects of 5-HT1B/1D-receptor agonists in patients with migraine
headaches.

de Hoon JN, Willigers JM, Troost J, Struijker-Boudier HA, Van Bortel LM.

Department of Pharmacology and Toxicology, Cardiovascular Research Institute
Maastricht, The Netherlands.

OBJECTIVES: Second-generation triptans are believed to have fewer cardiovascular 
effects than sumatriptan. This was investigated in vivo by comparing the vascular
effects of equipotent therapeutic dosages of selective 5-HT1B/1D-receptor
agonists. METHODS: Sixteen patients with migraine headaches completed a
double-blind, placebo-controlled, four-way crossover study. With ultrasonography 
and applanation tonometry used 1.5 hours after the oral intake of sumatriptan (50
mg), rizatriptan (10 mg), zolmitriptan (2.5 mg), or placebo arterial vessel wall 
properties, blood flow and pressure waveforms were measured in common carotid,
brachial, and temporal arteries. At the brachial artery, flow-induced
vasodilation (an endothelium-dependent process) was evaluated, and blood
pressures were recorded. RESULTS: Mean arterial pressure, 91 +/- 2 mm Hg after
placebo, increased (P < .05) by 4% to 6% after administration of each triptan.
Each active treatment decreased (P < .001) both brachial and carotid artery
diameter. Isobaric compliance of the brachial artery, 0.077 +/- 0.010 mm2/kPa
after placebo, decreased (P < .01) by 11% +/- 8%, 11% +/- 11%, and 23% +/- 7%
after administration of sumatriptan, rizatriptan, and zolmitriptan, respectively.
Isobaric compliance of the carotid artery was 1.31 +/- 0.10 mm2/kPa after placebo
(no change). Zolmitriptan was the only triptan that decreased temporal artery
diameter significantly (by 12% +/- 3%, P < .001). The resistance of the temporal 
artery vascular bed increased after administration of sumatriptan (by 26% +/-
11%, P < .05) and zolmitriptan (by 40% +/- 9%, P = .001). Flow-induced
vasodilation was unaffected. CONCLUSIONS: Selective 5-HT1B/1D-receptor agonists
induce vasoconstriction and decrease compliance of conduit arteries. These
effects are more pronounced at muscular (temporal, brachial) compared with
elastic (carotid) arteries. Resistance is only increased at the temporal artery
vascular bed, suggesting cranioselectivity for resistance vessels. Endothelial
function is not differently affected by any of the triptans tested.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 11061582 [PubMed - indexed for MEDLINE]

3527: Neurology. 2000 Oct 10;55(7):1040-2.

CACNA1A gene de novo mutation causing hemiplegic migraine, coma, and cerebellar
atrophy.

Vahedi K, Denier C, Ducros A, Bousson V, Levy C, Chabriat H, Haguenau M,
Tournier-Lasserve E, Bousser MG.

Service de Neurologie, Hôpital Lariboisière, Paris, France. vahedi@ccr.jussieu.fr

Familial hemiplegic migraine is caused by CACNA1A missense mutations in 50% of
families, including all families with cerebellar ataxia. A patient with healthy
parents, who experienced prolonged attacks of migraine with hemiplegia, coma, and
seizures, is reported. The patient also had mental retardation, permanent
cerebellar ataxia with cerebellar atrophy, and right-sided brain atrophy. This
patient carried a de novo Tyr 1385 Cys mutation in the CACNA1A gene and
illustrates a novel phenotype associated with CACNA1A mutations.

PMID: 11061267 [PubMed - indexed for MEDLINE]

3528: J Altern Complement Med. 2000 Oct;6(5):391-403.

Clinical evidence of subcutaneous CO2 insufflations: a systematic review.

Brockow T, Hausner T, Dillner A, Resch KL.

Research Institute for Spa Therapies and Health Resort Science, Bad Elster,
Germany. brockow.thomas@medkur.de

OBJECTIVE: To evaluate the evidence of clinical effectiveness of subcutaneous CO2
insufflations (SCIs). STUDY LOCATION: The entire databases of MEDLINE, EMBASE
Excerpta Medica (Field: Rehabilitation and Physical Medicine) and the Cochrane
Library were screened for data up to August 1999. In addition, other potentially 
relevant journals were handsearched and references were checked. STUDY SELECTION:
Uncontrolled observational trials (UCOTs) with sample sizes of at least n = 100, 
and controlled clinical trials (CCTs) and randomized controlled trials (RCTs)
were included. Outcomes had to be patient-centered. English-, Czechoslovakian-,
and German-language papers were considered. DATA ANALYSIS: For all study types, a
criteria-based analysis was performed. For controlled trials only, quality was
quantitatively assessed with the Jadad and Maastricht Scales. RESULTS: Thirteen
studies (5 RCTs, 2 CCTs, and 6 UCOTs) were included. Mean scores on the Jadad and
Maastricht Scales were 2 (Maximum 5) and 37 (Maximum 100), respectively. SCIs
were found to be effective in addition to standard physical therapy in
"peripheral arterial occlusive disease" (2 RCTs) and "stable angina pectoris" (1 
RCT) and superior to sham needling for migraine headaches (1 RCT). There were no 
differences among SCIs and CO2 gas baths (1 RCT) or combined interventions,
including SCIs (2 CCTs). All 6 UCOTs showed marked longitudinal effects.
CONCLUSIONS: The low number and quality of the available studies precludes firm
conclusions on the clinical effectiveness of SCIs.

Publication Types: 
    Review

PMID: 11059501 [PubMed - indexed for MEDLINE]

3529: J Psychosom Res. 2000 Jul;49(1):69-75.

Anger, depression, and coping interactions in headache activity and adjustment: a
controlled study.

Materazzo F, Cathcart S, Pritchard D.

Pain Management Unit, Flinders Medical Center, Bedford Park, South Australia
5042, Australia. felicity.materazzo@fmc.sa.gov.au

OBJECTIVE: To determine if individuals in the general community with chronic
headache or migraine differ in terms of anger, depression, and coping strategies 
and from headache-free individuals in terms of anger and depression. METHOD: A
community sample comprising 16 chronic tension-type headache (CTH), 28 migraine
headache (MH), and 38 headache-free control subjects (CNT) were compared on
measures of anger, depression, and use of various coping strategies. Affective
and coping measures, recorded during a headache-free period, were regressed on
headache activity measured in a daily diary over the following 2 weeks.
Relationships between anger, depression, and coping were also examined in each of
the headache groups. RESULTS: The MH subjects were found to use less effective
coping strategies than controls and CTH, while the CTH group had higher levels on
depression and various anger scales compared to controls and MH. Direct positive 
relationships were observed between suppressed anger and depression in the MH
group, and between trait anger and depression in the CTH group. Anger and coping 
were predictive of headache activity in the following 2 weeks for both MH and CTH
groups, while depression and coping, compared to coping only, were predictive of 
lifestyle interference from head pain in MH and CTH, respectively. CONCLUSION:
The results support a relationship between affective and coping factors in
headache activity and adjustment.

PMID: 11053606 [PubMed - indexed for MEDLINE]

3530: Clin Ther. 2000 Sep;22(9):1035-48.

Effect of early intervention with sumatriptan on migraine pain: retrospective
analyses of data from three clinical trials.

Cady RK, Sheftell F, Lipton RB, O'Quinn S, Jones M, Putnam DG, Crisp A, Metz A,
McNeal S.

Headache Care Center, Springfield, Missouri, USA.

OBJECTIVE: This study assessed the efficacy of sumatriptan 50- and 100-mg tablets
in the treatment of migraine attacks while the pain is mild rather than
moderate/severe. BACKGROUND: Results from The Spectrum Study suggested that early
treatment of migraine attacks with sumatriptan 50-mg tablets while the pain is
mild might enhance pain-free response and reduce headache recurrence. METHODS:
Retrospective analyses of headaches treated during mild pain were performed using
data from 3 studies of sumatriptan tablets (protocols S2CM09, S2BT25, and
S2BT26). Our primary interest was pain-free response 2 and 4 hours after dosing; 
secondary interests were use of a second dose of medication, clinical disability 
(as measured on a 4-point disability scale), migraine-associated symptoms,
meaningful pain relief (patient defined), time to meaningful relief, sustained
pain-free response, and proportion of attacks in which pain had worsened 2 and 4 
hours after dosing, all of which were compared in headaches treated during mild
versus moderate/severe pain. RESULTS: In S2CM09, 92 patients treated 118
headaches during mild pain. Rates of pain-free response were higher 2 hours after
dosing with sumatriptan 50 mg (51%) or 100 mg (67%; P < 0.05) compared with
placebo (28%), and were higher with early treatment of mild pain compared with
treatment of moderate/severe pain at 2 hours (sumatriptan 50 mg: mild pain, 51%; 
moderate/severe pain, 31%; P < 0.05; sumatriptan 100 mg: mild pain, 67%;
moderate/severe pain, 36%) and 4 hours (50 mg: 75% vs 56%; 100 mg: 90% vs 61%; P 
< 0.05). Early intervention also resulted in less redosing than when
moderate/severe pain was treated (50 mg: 21% vs 32%; 100 mg: 20% vs 29%). More
attacks treated early with sumatriptan 50 or 100 mg were associated with normal
function 4 hours after dosing compared with placebo (70% and 93% vs 46%,
respectively). Sustained pain-free response rates 2 to 24 hours after early
dosing with sumatriptan 50 or 100 mg were also higher (34% and 53%, respectively)
compared with treatment of moderate/severe pain (19% and 24%, respectively).
Early treatment with sumatriptan 100 mg produced significantly higher pain-free
rates at 2 hours after dosing (P < 0.001) than did ergotamine plus caffeine
(S2BT25: 69% vs 34%, respectively) or aspirin plus metoclopramide (S2BT26: 73% vs
25%, respectively). CONCLUSIONS: Sumatriptan 50- and 100-mg tablets are effective
whether pain is mild or moderate/severe. However, treatment with sumatriptan
while pain is mild provides high pain-free response rates while reducing the need
for redosing, benefits not seen with ergotamine plus caffeine or aspirin plus
metoclopramide.

Publication Types: 
    Clinical Trial
    Meta-Analysis

PMID: 11048903 [PubMed - indexed for MEDLINE]

3531: Neuroreport. 2000 Sep 28;11(14):3071-5.

Systemic nitroglycerin increases nNOS levels in rat trigeminal nucleus caudalis.

Pardutz A, Krizbai I, Multon S, Vecsei L, Schoenen J.

Department of Neurology, University of Szeged, Hungary.

Systemic administration of nitroglycerin, a nitric oxide donor, triggers in
migraineurs a delayed attack of unknown mechanisms. Subcutaneous nitroglycerin
(10 mg/kg) produced a significant increase of nitric oxide synthase (NOS)- and
c-fos-immunoreactive neurons in the cervical part of trigeminal nucleus caudalis 
in rats after 4 h. This effect was not observed in the thoracic dorsal horn.
Similar increase of NOS and c-fos was obtained in the brain stem after a somatic 
nociceptive stimulus, i.e. on the side of the formalin injection in the lip.
Nitric oxide is thus able to increase NOS availability in second order
nociceptive trigeminal neurons, which may be relevant for central sensitization
and the understanding of its effect in migraine.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 11043526 [PubMed - indexed for MEDLINE]

3532: Int J Clin Lab Res. 2000;30(2):109-11.

Lack of association between antiphospholipid antibodies and migraine in children.

Verrotti A, Cieri F, Pelliccia P, Morgese G, Chiarelli F.

Department of Pediatrics, University of Chieti, Italy.

Anticardiolipin antibodies are found frequently in those suffering from migraine,
but it is not clear if this association is real or coincidental. Moreover, there 
are no data on the prevalence of anticardiolipin antibodies in children. In this 
study, 40 patients were divided into two groups according to the type of
migraine: group I included 22 cases (15 females and 7 males, mean age+/-SD
13.7+/-8.9 years) suffering from migraine with and without aura; group II
consisted of 18 children (10 females and 8 males, age 14.7+/-6.9 years) having
migraine with prolonged aura or migrainous infarction, also called complicated
migraine. We studied two groups of children as controls: a group of 35 children
(25 females and 10 males, mean age 13.9+/-7.1 years) with juvenile chronic
arthritis (group III) and a group of 40 healthy sex- and age-matched children who
did not suffer from migraine or any other neurological disease (group IV). No
statistically significant differences in levels of anticardiolipin antibodies
were found between group I and II and controls. Our data demonstrate that, in
children with migraine, anticardiolipin antibodies are not more frequent than in 
healthy controls, and suggest that anticardiolipin antibodies are not implicated 
in the pathogenesis of migraine.

PMID: 11043505 [PubMed - indexed for MEDLINE]

3533: J Tradit Chin Med. 2000 Sep;20(3):231-40.

Comparison of pharmacological treatment versus acupuncture treatment for migraine
without aura--analysis of socio-medical parameters.

Liguori A, Petti F, Bangrazi A, Camaioni D, Guccione G, Pitari GM, Bianchi A,
Nicoletti WE.

Istituto Paracelso, Italian Center for Non Conventional Medicines, Rome, Italy.

This study was carried out in 120 patients affected by migraine without aura,
treated in 4 public health centers and randomly divided into acupuncture group
(AG) and conventional drug therapy group (CDTG). The evaluation of clinical
results was made 6 and 12 months after the beginning of treatment and was worked 
out as well according to socio-medical parameters. Acupuncture was applied to the
following points: Touwei (ST 8), Xuanlu (GB 5), Fengchi (GB 20), Dazhui (GV 14), 
Lieque (LU 7), treated with the reducing method. In AG, the figure scoring the
entity and frequency of migraine attacks drops from 9,823 before treatment to
1,990 6 months after and 1,590 12 months after; while in CDTG, it drops from
8,405 before treatment to 3,927 6 months after and 3,084 12 months after. In AG, 
the total absence from work amounted to 1,120 working days/year, with a total
cost (private + social costs) of 186,677,000 Italian liras. In CDTG, the absence 
from work amounted to 1,404 working days/year, with a total cost of 266,614,000
Italian liras. If we consider that in Italy the patients affected by migraine
without aura are around 800,000, and that acupuncture therapy is able to save
1,332,000 Italian liras on the total average cost supported for every single
patient, the application of acupuncture in the treatment of migraine without aura
would allow a saving of the health expenses in Italy of over 1,000 billion liras.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial

PMID: 11038990 [PubMed - indexed for MEDLINE]

3534: Cephalalgia. 2000 Jun;20(5):479-85.

Migraine prevalence in adolescents aged 13-15: a student population-based study
in Taiwan.

Lu SR, Fuh JL, Juang KD, Wang SJ.

Neurological Institute, Taipei Veterans General Hospital and Department of
Neurology, National Yang-Ming University School of Medicine, Taiwan.

To estimate the lifetime migraine prevalence in school adolescents aged 13-15 in 
Taiwan, we conducted a self-administered questionnaire survey in four sampled
public junior high schools. Migraine was diagnosed according to the diagnostic
criteria of the International Headache Society. A total of 4064 students (1983
boys, 2081 girls) completed the questionnaire (response rate 91.6%). The lifetime
prevalence of migraine was 6.8%. It was significantly higher in girls than boys
(7.8% vs. 5.7%) and increased with age in both sexes. Students with migraine were
more likely to be absent from school because of their headaches than those with
non-migraine headaches (30% vs. 14%, odds ratio (OR) 2.7). They were also more
likely to use painkillers for their headaches than their non-migraine headache
peers (72% vs. 40%, OR 4.0). These results suggest that migraine is a common
disorder of adolescents in Taiwan and its impact on the quality of life can not
be ignored.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 11037745 [PubMed - indexed for MEDLINE]

3535: Cephalalgia. 2000 Jun;20(5):475-8.

Memory disturbances in migraine with and without aura: a strategy problem?

Le Pira F, Zappalà G, Giuffrida S, Lo Bartolo ML, Reggio E, Morana R, Lanaia F.

Institute of Neurological Sciences, University of Catania, Italy.
lepira@mbox.unict.it

Cognitive defects in migraine have been reported by several authors. These
findings however, are controversial. In this study we carried out an
investigation on 14 patients with migraine with aura and 16 with migraine without
aura according to the International Headache Society criteria. They were
submitted to a comprehensive battery of neuropsychological tests. The patients
were compared with a control group not significantly different as to age, sex and
education. Migraine subjects showed impaired neuropsychological performances only
on some cognitive tests. Both groups of patients did worse than the control group
on visuo-spatial memory tasks, while only migraineurs without aura showed
significantly impaired verbal memory performances. The memory defects, both on
visuo-spatial and on verbal cognitive tasks, could depend on an impaired recall
mechanism. These memory difficulties seem related to strategically and
organizationally defective aspects of learning.

PMID: 11037744 [PubMed - indexed for MEDLINE]

3536: Cephalalgia. 2000 Jun;20(5):470-4.

Tolerability and efficacy of naratriptan tablets in the acute treatment of
migraine attacks for 1 year. Naratriptan Long-Term Study Group.

Heywood J, Bomhof MA, Pradalier A, Thaventhiran L, Winter P, Hassani H.

Department of Neurology, Austin & Repatriation Medical Centre, Heidelberg,
Victoria, Australia.

OBJECTIVE AND DESIGN: This open-label study was conducted to evaluate the
tolerability and efficacy of the 5HT1 agonist naratriptan with repeated use in
the acute treatment of migraine attacks for 1 year. Four hundred and seventeen
(417) migraine patients treated 15,301 migraine attacks over the course of the
study. RESULTS: The results show that 84% of attacks treated with a single 2.5 mg
dose of naratriptan were not associated with the occurrence of an adverse event. 
The percentage of attacks associated with an adverse event did not increase with 
number of doses used to treat a given attack (1 vs. 2) or duration of use (0-6
months vs. > 6-12 months). The only adverse events experienced in > 2% of attacks
throughout the 1-year study were nausea (3% of attacks), hyposalivation (2% of
attacks), and drowsiness/sleepiness (2% of attacks). Headache relief 4 h
post-dose was reported in a median 70% of moderate or severe attacks and a median
86% of mild attacks treated with naratriptan tablets 2.5 mg. The percentages of
patients reporting headache relief did not diminish as a function of increased
duration of treatment (0-6 months vs. > 6-12 months) or frequency of use (for >
36 vs. < 36 attacks). The mean number of tablets taken per attack was 1.2. A
second naratriptan 2.5 mg tablet was taken for headache recurrence in a mean 16% 
(median 8%) of attacks. CONCLUSION: The results of this study demonstrate that
naratriptan tablets 2.5 mg taken for acute migraine attacks over a 1-year period 
are well-tolerated and effective.

PMID: 11037743 [PubMed - indexed for MEDLINE]

3537: Cephalalgia. 2000 Jun;20(5):455-61.

Comparison of rizatriptan 10 mg vs. zolmitriptan 2.5 mg in the acute treatment of
migraine. Rizatriptan-Zolmitriptan Study Group.

Pascual J, Vega P, Diener HC, Allen C, Vrijens F, Patel K.

University Hospital Marqués de Valdecilla, Santander, Spain.

The efficacy and tolerability of rizatriptan (MAXALT) and zolmitriptan (ZOMIG)
were compared in a randomized, double-blind, double-dummy, stratified (on prior
use of rizatriptan and/or zolmitriptan), placebo-controlled, single attack study 
in 766 patients. Rizatriptan tended to provide freedom from pain sooner than
zolmitriptan (hazard ratio 1.26, P = 0.075), acting within 60 min following
dosing. More patients were pain free at 2 h on rizatriptan than on zolmitriptan
(43.2% vs. 35.6%, P=0.041), while headache relief at 2 h was similar (70.5% vs.
66.8%). At 2 h, fewer patients on rizatriptan had symptoms of photophobia (35.6% 
vs. 43.5%, P = 0.029) and nausea (25.2% vs. 32.5%, P=0.046), and more patients on
rizatriptan had normal function (45.4% vs. 37.0%, P=0.025) than zolmitriptan.
Headache recurred in 28% of patients taking rizatriptan, 29% taking zolmitriptan 
and 26% taking placebo. Both active treatments were effective compared to placebo
and were well tolerated. The most common side-effects with rizatriptan were
asthenia/fatigue, somnolence and dizziness, while the most common side-effects
with zolmitriptan were asthenia/fatigue and dizziness.

Publication Types: 
    Clinical Trial
    Comparative Study
    Randomized Controlled Trial

PMID: 11037741 [PubMed - indexed for MEDLINE]

3538: Intern Med. 2000 Oct;39(10):852-5.

Alternate numbness in the upper extremities as the initial symptom of basilar
migraine: an electrophysiological evaluation using EEG power topography.

Hirata K, Kubo J, Arai M, Suga T, Tanaka H, Yamazaki K.

Department of Neurology, Dokkyo University School of Medicine, Mibu, Tochigi.

A case of basilar migraine (BM) with alternate numbness as the initial symptom is
described. The patient's chief complaint was alternate numbness in the right and 
left upper extremities. After angiography the patient fell into a drowsy state,
followed by excitation, and finally confusion. The EEG power topography showed
slow alpha, theta and delta power in the right occipital area, and alternatively 
in the right and left parietal area. These findings suggest that the cause of BM 
is not only based on a vasoconstriction mechanism, but also cortical spreading
depression. BM should be suspected as a cause of sensory symptoms.

Publication Types: 
    Case Reports

PMID: 11030214 [PubMed - indexed for MEDLINE]

3539: J Clin Neurosci. 2000 Nov;7(6):495-9.

The postconcussion syndrome after mild head trauma part II: is migraine
underdiagnosed?

Margulies S.

Johns Hopkins University, MD, USA. lsmarg@erols.com

The evidence for post-traumatic migraine as the cause of the postconcussion
syndrome in a proportion of patients is reviewed. Conclusion: patients suffering 
recurrent post-traumatic headaches or other elements of the postconcussion
syndrome should be treated for migraine. Copyright 2000 Harcourt Publishers Ltd.

Publication Types: 
    Review

PMID: 11029228 [PubMed - indexed for MEDLINE]

3540: Neurol India. 2000 Sep;48(3):223-6.

A double blind controlled study of propranolol and cyproheptadine in migraine
prophylaxis.

Rao BS, Das DG, Taraknath VR, Sarma Y.

Departments of Neurosurgery, Clinical Pharmacology and Neurology, Guntur Medical 
College, Guntur, Andhra Pradesh, 522001, India.

Role of propranolol and cyproheptadine in the prophylaxis of migraine was studied
in a controlled double blind trial. Two hundred fifty-nine patients were divided 
into four groups. Each group was either given a placebo, cyproheptadine,
propranolol or a combination of the latter two drugs. The patients were followed 
for a period of three months. Significant relief in frequency, duration and
severity from migranous attacks was seen in all drug treated groups over placebo.
Significant correlation in response was seen in frequency, duration and severity 
in all the groups which received drugs. Statistically more significant relief was
seen in cyproheptadine and propranolol treated group as compared to individual
drug treated groups. In cyproheptadine and propranolol treated groups, the
dropout rate was lower and associated symptoms were better relieved than in other
groups. The study shows efficacy of combination of cyproheptadine and propranolol
in migraine prophylaxis.

Publication Types: 
    Clinical Trial
    Controlled Clinical Trial

PMID: 11025624 [PubMed - indexed for MEDLINE]

3541: Int J Clin Pharmacol Ther. 2000 Sep;38(9):430-5.

An extract of Petasites hybridus is effective in the prophylaxis of migraine.

Grossmann M, Schmidramsl H.

Department of Neurology, Municipal Hospital, München-Harlaching, Germany.

OBJECTIVE: Migraine is still an unsolved problem. This clinical trial
investigates the efficacy and tolerance of Petasites hydridus in the prophylaxis 
of migraine. METHODS: A randomized, group-parallel, placebo-controlled,
double-blind clinical study was carried out with a special CO2 extract from the
rhizome of Petasites hybridus. Following a 4-week run-in phase, 60 patients
received either the special Petasites hybridus extract petadolex or placebo at a 
dosage of 2 capsules (each capsule contains 25 mg) twice daily over 12 weeks.
Outcome variables included the frequency, intensity and duration of migraine
attacks as well as any accompanying symptoms. RESULTS: The frequency of migraine 
attacks decreased by a maximum of 60% compared to the baseline. This reduction in
migraine attacks with petadolex was significant (p < 0.05) compared to placebo.
No adverse events were reported. Petasites was exceptionally well tolerated.
CONCLUSIONS: The results suggest that migraine patients can benefit from
prophylactic treatment with this special extract. The combination of high
efficacy and excellent tolerance emphasizes the particular value that Petasites
hydridus has for the prophylactic treatment of migraine.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial

PMID: 11020030 [PubMed - indexed for MEDLINE]

3542: Arch Gen Psychiatry. 2000 Oct;57(10):945-50.

Mental disorders and the incidence of migraine headaches in a community sample:
results from the Baltimore Epidemiologic Catchment area follow-up study.

Swartz KL, Pratt LA, Armenian HK, Lee LC, Eaton WW.

Department of Psychiatry, The Johns Hopkins Hospital, 600 N Wolfe St, Meyer
3-181, Baltimore, MD 21287-7381. kswartz@mail.jhmi.edu

BACKGROUND: The cross-sectional relation between migraine headaches and affective
disorders has been demonstrated in studies of clinical and community populations.
Few studies have investigated the prospective relation between psychiatric
disorders and migraine headaches. METHODS: A prospective follow-up of the
Baltimore, Md, cohort of the Epidemiologic Catchment Area Study assessed
psychopathologic features in 1981 and again between 1993 and 1996. Interviews
included a history of headaches at baseline and self-reported assessment of
migraine headaches at follow-up. Risk estimates for incident migraine headaches
by 1981 demographic variables and psychopathologic features were calculated. The 
cross-sectional association between prevalent migraine and lifetime psychiatric
diagnoses was estimated. RESULTS: In the at-risk population of 1343, there were
118 incident cases of migraine headaches. The age- and sex-specific incident
rates of migraine headaches followed the expected patterns, with younger age and 
female sex identified as risk factors. In cross-sectional analyses, major
depression (odds ratio, 3.14; 95% confidence interval, 2.03-4. 84) and panic
disorder (odds ratio, 5.09; 95% confidence interval, 2. 65-9.79) had the
strongest associations, and alcohol and other substance abuse were not
associated. In logistic regression models including age, sex, and psychiatric
illness in 1981, only phobia was predictive of incident migraines (odds ratio,
1.70; 95% confidence interval, 1.11-2.58). Affective disorders were not
predictive of incident migraine headaches. Including a history of tricyclic
antidepressant use did not change the results. CONCLUSIONS: There is a strong
cross-sectional relation between affective disorders and migraine headaches in
this cohort. However, there is no association between antecedent affective
disorders and incident migraine headaches in this population-based prospective
study.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 11015812 [PubMed - indexed for MEDLINE]

3543: Schweiz Med Wochenschr. 2000 Aug 19;130(33):1152-6.

Manifold manifestations of ergotism.

Payne B, Sasse B, Franzen D, Hailemariam S, Gemsenjäger E.

Division of Surgery, Spital Zollikerberg, Zurich.

Vasospastic side effects leading to organic manifestations are rare in ergotamine
therapy. To our knowledge, combinations of more than two signs of ergotism have
rarely been described in the literature so far. We present a 65-year-old male
patient who as a consequence of severe migraine had developed ergotamine abuse.
He was admitted to our hospital after one week of increasing abdominal pain.
During laparotomy, necrotic areas of the small intestine and the sigmoid colon
were resected, which on histopathologic examination revealed severe hypertrophy
of the smooth musculature of mesenteric arteries, resulting from chronic
vasospasms. Postoperatively, the patient developed ischaemia of the limbs which
was confirmed by angiography. Before death, the patient also showed ischaemic
signs in the acrae and necrosis of the tongue.

Publication Types: 
    Case Reports

PMID: 11005105 [PubMed - indexed for MEDLINE]

3544: Postgrad Med. 2000 Sep 1;108(3):121-8; quiz 26.

Providing relief from headache pain. Current options for acute and prophylactic
therapy.

Ward TN.

Dartmouth Medical School, Hanover, New Hampshire, USA.
Thomas.N.Ward@Hitchcock.org

The sometimes debilitating pain of migraine and other types of primary headache
can be difficult to control with acute drug therapy alone. Often patients need
both acute and prophylactic treatment to keep headache pain at bay. Dr Ward
discusses the current treatment options for migraine with and without aura,
tension-type headache, and cluster headache. He also provides practical pointers 
for use of the various formulations of specific drugs, including the newer
"triptan" medications.

Publication Types: 
    Review

PMID: 11004939 [PubMed - indexed for MEDLINE]

3545: Cephalalgia. 2000 May;20(4):244-51.

Head-HUNT: validity and reliability of a headache questionnaire in a large
population-based study in Norway.

Hagen K, Zwart JA, Vatten L, Stovner LJ, Bovim G.

Department of Clinical Neuroscience, Norwegian University of Science and
Technology, Trondheim. knut.hagen@medisin.ntnu.no

We have assessed the validity and reliability of a self-administered headache
questionnaire used in the 'Nord-Trøndelag Health Survey 1995-97 (HUNT)' in
Norway, by blindly comparing questionnaire-based headache diagnoses with those
made in a clinical interview of a sample of the participants. Restrictive
questionnaire-based diagnostic criteria for migraine, assessed according to
modified criteria of the International Headache Society, performed excellently in
selecting 'definite' migraine patients (100% positive predictive value). The best
agreement concerning migraine diagnoses was achieved by using a liberal set of
criteria (kappa 0.59). Similar agreement was found evaluating patient status as
headache sufferers, and as sufferers from frequent headaches (>6 days per month) 
(kappa 0.57 and 0.50, respectively). The kappa values of non-migrainous headache 
and chronic headache (> 14 days per month) were 0.43 and 0.44, respectively. The 
results suggest that our self-administered questionnaire may be suitable in
identifying a population with 'definite' migraine, and the questionnaire is an
acceptable instrument in determining the prevalence in Nord-Trøndelag of headache
sufferers, migraine, non-migrainous headache, and frequent or chronic headache
sufferers.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 10999674 [PubMed - indexed for MEDLINE]

3546: Cephalalgia. 2000 May;20(4):233-43.

Evaluation of a novel solubilized formulation of ibuprofen in the treatment of
migraine headache: a randomized, double-blind, placebo-controlled, dose-ranging
study.

Kellstein DE, Lipton RB, Geetha R, Koronkiewicz K, Evans FT, Stewart WF, Wilkes
K, Furey SA, Subramanian T, Cooper SA.

Clinical Research Department, Whitehall-Robins Healthcare, Madison, NJ 07940,
USA. kellstd@ahp.com

A total of 729 migraine sufferers with moderate to severe baseline pain evaluated
a single 200, 400 or 600 mg dose of a new liquigel formulation of ibuprofen over 
8 h. Ibuprofen liquigels were significantly superior to placebo for cumulative
headache response (pain reduced to mild or none) from 0.5 (600 mg) or 1 h (200
and 400 mg) to 8 h. At 2 h, respective headache response rates for ibuprofen 200,
400 and 600 mg and placebo were 64%, 72%, 72% and 50%. All three doses were also 
significantly superior to placebo for 2-h pain-free (25%, 28%, 29% and 13%,
respectively) and for proportions with mild or no limitation of activity (2-8 h).
Ibuprofen liquigels were generally superior to placebo for reducing photophobia, 
phonophobia, or nausea (1-4 h) and for global evaluation. All doses were well
tolerated. These data demonstrate that ibuprofen liquigels relieve the pain,
ancillary symptoms, and limitation of activity, of migraine.

Publication Types: 
    Clinical Trial
    Multicenter Study
    Randomized Controlled Trial

PMID: 10999673 [PubMed - indexed for MEDLINE]

3547: Cephalalgia. 2000 May;20(4):228-32.

Illusory splitting as visual aura symptom in migraine.

Podoll K, Robinson D.

Department of Psychiatry and Psychotherapy, University of Technology Aachen,
Germany.

Illusory splitting was illustrated as a visual migraine aura symptom in six of
562 Migraine Art pictures. In this type of illusion, objects or persons appear to
be split, along fracture lines of varying form and orientation, into two or more 
parts that may be displaced and separated from each other. The illusion is
strongly associated with the presence of elementary geometric hallucinations.
Phenomenological similarities and differences of illusory splitting to the visual
perceptual disturbances of fragmentation and mosaic illusion are discussed.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 10999672 [PubMed - indexed for MEDLINE]

3548: Cephalalgia. 2000 May;20(4):223-7.

Effects of subcutaneous sumatriptan on plasma growth hormone concentrations in
migraine patients.

Pinessi L, Rainero I, Savi L, Valfrè W, Limone P, Calvelli P, Del Rizzo P,
Gianotti L, Taliano M, Ghigo E, Arvat E.

Neurology III-Headache Centre, Department of Neuroscience, University of Turin,
Italy. Pinessi@galeno.medfarm.unito.it

The purpose of this study was to assess the sensitivity of 5-HT1D receptors in
migraine using sumatriptan as a pharmacological probe. The drug stimulates the
release of growth hormone (GH) and this effect may be used to explore the
function of cerebral serotonergic systems in vivo. We administered sumatriptan
and placebo to 15 migraineurs and to 10 controls. Blood samples were collected
-15, 0, 15, 30, 45, 60 and 90 min after injection. Placebo had no effect on
hormone concentrations. Sumatriptan induced a significant (P<0.01) increase in GH
concentrations both in migraine patients and healthy controls. The GH increase
was not significantly different in the two groups. Our results suggest that
cerebral serotonergic functions mediated by 5-HT1D receptors are not altered in
migraine. Sumatriptan overuse could lead to adverse effects mediated by its
neuroendocrine activity.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 10999671 [PubMed - indexed for MEDLINE]

3549: Cephalalgia. 2000 Apr;20(3):190-9.

Migraine and stroke in young women.

Tzourio C, Kittner SJ, Bousser MG, Alpérovitch A.

INSERM U360 Recherches Epidémiologiques en Neurologie et Psychopathologie,
Hôpital de la Salpêtrière, Paris, France.

In this paper we review the evidence that migraine is associated with ischaemic
stroke in young women, emphasizing potential biases, factors that may influence
the association, potential mechanisms, and potential public health impact.
Consistency of case-control findings from several countries and supporting
evidence from prospective data suggest that the association is not an artifact of
study design or execution, although, due to methodological limitations, none of
the studies mentioned can be considered definite proof of the association.
However, it is less clear whether migraine without aura is associated with stroke
or whether the association is restricted to migraine with aura. Similarly, there 
are few data examining the magnitude of the association among nonusers of oral
contraceptives compared with those who use low oestrogen oral contraceptives. As 
a consequence, there is a lack of data concurrently stratifying both by the
presence vs. the absence of aura and by the use of low oestrogen oral
contraceptives vs. non-use of oral contraceptives. Moreover, there is still no
convincing evidence on the mechanisms that would be implied and on the groups of 
migraineurs really at risk of ischaemic stroke. Despite the considerable advances
in our understanding of the relationship between migraine and stroke, there are
many gaps in the data needed for public health recommendations.

Publication Types: 
    Review

PMID: 10997773 [PubMed - indexed for MEDLINE]

3550: J Neurol Neurosurg Psychiatry. 2000 Oct;69(4):507-11.

Long term decline of P100 amplitude in migraine with aura.

Khalil NM, Legg NJ, Anderson DJ.

Department of Neurology, Imperial College School of Medicine, Hammersmith
Hospital Campus, Du Cane Road, London W12 0NN, UK.

OBJECTIVES: To investigate visual function in migraine using visual evoked
potentials. METHODS: Electroretinograms (ERGs) and visual evoked potentials
(VEPs) to single flash (SF) and pattern reversal (PR) stimuli were studied in 92 
migraine subjects and 62 controls. RESULTS: In subjects with migraine, ERGs to
single flash were normal. Mean latencies of the P1 and P2 waves in the SFVEP were
increased at the occiput by 6% and 4% respectively, but normal at the vertex.
Mean latency of the P100 wave in the PRVEP was increased by 5%. These increases
were not related to the presence or absence of an aura or to the duration of
migraine. P100 amplitude showed a more complex abnormality. It was increased in
migraine without aura by 23% compared with controls, regardless of duration of
migraine. In migraine with aura it was similarly increased, by 23%, in cases of
short duration, but in addition it showed a sharp decline with duration. In cases
with a duration of 30 or more years it was 36% less than in cases of short
duration, and 21% less than in controls. CONCLUSIONS: Subjects with migraine have
constitutionally prolonged VEP latencies and increased P100 amplitude, but the
latter declines to below normal in cases with a long history of migraine with
aura. This decline may reflect subtle neuronal damage within the visual system
from repeated transient ischaemia experienced during the aura. Future
electrophysiological and other studies will need to be controlled for duration of
migraine history.

PMID: 10990512 [PubMed - indexed for MEDLINE]

3551: Arch Neurol. 2000 Sep;57(9):1363-5.

Hemiplegic migraine induced by exertion.

Razavi M, Razavi B, Fattal D, Afifi A, Adams HP Jr.

Department of Neurology, University of Iowa Hospitals and Clinics, 200 Hawkins
Dr, Iowa City, IA 52242, USA. Mehrdad-razavi@uiowa.edu

BACKGROUND: It is known that exertion can aggravate migraine headache. However,
the relationship between exertion and migraine aura is unknown. OBJECTIVE: To
study the relationship between exertion and migraine aura. DESIGN: Case report.
SETTING: Tertiary care hospital. PATIENT: A 67-year-old man presented with
recurrent attacks of exertion-induced hemiplegic migraine. Since the hemiparetic 
attacks were exertion induced, they were initially ascribed to recurrent
transient ischemic attacks. However, the clinical picture, normal findings on
cerebral angiography and neuroimaging (during the period of hemiparesis), lack of
response to treatment with antiplatelets and anticoagulants, and successful
treatment with verapamil suggested that the hemiparesis was not due to ischemia, 
but was indeed a migraine aura. We suggest that exertion induced the aura of
hemiparesis by lowering the threshold for the development of cortical spreading
depression. Even though our patient had no family history of hemiplegic migraine,
a mutation in an ion channel gene (eg, the CACNA1A gene on chromosome 19) might
account for his episodic attacks. CONCLUSION: Migraine aura should be included in
the differential diagnosis of exertion-induced focal neurologic deficit.

Publication Types: 
    Case Reports

PMID: 10987906 [PubMed - indexed for MEDLINE]

3552: West J Med. 2000 Sep;173(3):189-93.

Migraine: pharmacotherapy in the emergency department.

Kelly AM.

Department of Emergency Medicine, Western Hospital, Footscray 3011, Australia.
Anne-Maree.Kelly@nwhcn.org.au

Migraine can be a disabling condition for the sufferer. For the small number of
patients for whom home therapy fails and who seek treatment in an emergency
department, several therapeutic options are available. I review the evidence
regarding the effectiveness and safety of the following therapies: the
phenothiazines, lignocaine (lidocaine), ketorolac, the ergot alkaloids,
metoclopramide hydrochloride, the "triptans," haloperidol, pethidine (meperidine 
hydrochloride), and magnesium sulfate. Based on available evidence, the most
effective agents seem to be prochlorperazine, chlorpromazine and sumatriptan,
each of which has achieved greater than 70% efficacy in several studies.

Publication Types: 
    Review

PMID: 10986188 [PubMed - indexed for MEDLINE]

3553: Med Hypotheses. 2000 Sep;55(3):195-8.

Glucosamine for migraine prophylaxis?

Russell AL, McCarty MF.

Brampton Pain Clinic, Bramalea, Ontario, Canada.

Following a fortuitous observation that migraine headaches ceased in a patient
receiving glucosamine therapy for osteoarthritis, a further ten patients with
migraine or migraine-like vascular headaches, refractory to established
preventive or abortive therapies, have been treated with daily oral glucosamine. 
After a lag of 4-6 weeks, a substantial reduction in headache frequency and/or
intensity has been noted; in some cases, the benefit appears to be
dose-dependent. Since glucosamine can be a rate-limiting precursor for
mucopolysaccharide synthesis, it is germane to note previous reports that heparin
and pentosan polysulfate may have migraine-preventive activity. There is reason
to suspect that mast cells are central mediators of the neurogenic inflammation
associated with migraine and cluster headaches. The heparin produced by mast
cells may function to provide feedback down-regulation of mast cell activation,
and exerts a range of other anti-inflammatory effects. We postulate that
supplemental glucosamine can boost mast cell heparin synthesis - perhaps
correcting a functional heparin deficiency - thereby preventing or ameliorating
the neurogenic inflammation that mediates pain in vascular headache. Whether or
not this idea has validity, a controlled study of glucosamine for migraine
prophylaxis appears to be warranted.

PMID: 10985908 [PubMed - indexed for MEDLINE]

3554: Laryngoscope. 2000 Sep;110(9):1528-34.

Physical therapy for migraine-related vestibulopathy and vestibular dysfunction
with history of migraine.

Whitney SL, Wrisley DM, Brown KE, Furman JM.

Department of Otolaryngology, School of Medicine, University of Pittsburgh,
Pennsylvania, USA. whitney@pitt.edu

OBJECTIVES/HYPOTHESIS: To assess the efficacy of physical therapy for patients
with a diagnosis of migraine-related vestibulopathy (MRV) or vestibular
dysfunction with a history of migraine headache. STUDY DESIGN: Retrospective case
series METHODS: Thirty-nine patients were identified through a retrospective
chart review, 14 with a diagnosis of MRV and 25 with migraine headache. The
patients were treated with a custom-designed physical therapy exercise program
for a mean of 4.9 visits over a mean duration of 4 months. Patients completed the
Dizziness Handicap Inventory (DHI), the Activities-Specific Balance Confidence
Scale (ABC), and the Dynamic Gait Index (DGI), reported the number of falls they 
had experienced in the past 4 weeks, and rated the severity of their dizziness on
an analogue scale of 0 to 100 at initial evaluation and at discharge. RESULTS:
Significant differences were seen before and after therapy in each of the outcome
measures used. The average decrease in DHI score was 12 points (P < .01). ABC
scores increased an average of 14 points (P < .01). Subjects increased their DGI 
scores an average of 4 points (P < .01). The number of patients reporting more
than one fall decreased by 78% at discharge. (P < .05). Baseline symptoms of
dizziness decreased an average of 11 points (P < .05). CONCLUSIONS: Patients with
MRV and migraine headache demonstrated improvement in physical performance
measures and self-perceived abilities after vestibular physical therapy.

PMID: 10983955 [PubMed - indexed for MEDLINE]

3555: Hum Genet. 2000 Jul;107(1):18-23.

Familial typical migraine: significant linkage and localization of a gene to
Xq24-28.

Nyholt DR, Curtain RP, Griffiths LR.

Laboratory of Statistical Genetics, Rockefeller University, New York, NY 10021,
USA.

In a previous study we found evidence for an X-linked genetic component for
familial typical migraine in two large Australian white pedigrees, designated MF7
and MF14. Significant excess allele sharing was indicated by nonparametric
linkage (NPL) analysis using GENEHUNTER (P=0.031 and P=0.012, respectively), with
a combined analysis of the two pedigrees showing further increased evidence for
linkage, producing a maximum NPL score of 2.87 (P=0.011 ) at DXS 1123 on Xq27.
The present study was aimed at refining the localization of the migraine
X-chromosomal component by typing additional markers, performing haplotype
analysis and applying a more powerful technique in the analysis of linkage data
from these two pedigrees. Results from the haplotype analyses, coupled with
linkage analyses that produced a peak GENEHUNTER-PLUS LOD* score of 2.388
(P=0.0005), provide compelling evidence for the presence of a migraine
susceptibility locus on chromosome Xq24-28.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 10982029 [PubMed - indexed for MEDLINE]

3556: Neurology. 2000 Sep 12;55(5):629-35.

Comment in:
    Neurology. 2000 Sep 12;55(5):610-1.

Migraine, quality of life, and depression: a population-based case-control study.

Lipton RB, Hamelsky SW, Kolodner KB, Steiner TJ, Stewart WF.

Departments of Neurology, Epidemiology, and Social Medicine (Dr. Lipton), Albert 
Einstein College of Medicine, Bronx, NY, USA. rlipton@imrinc.com

OBJECTIVE: This study reports on the influence of migraine and comorbid
depression on health-related quality of life (HRQoL) in a population-based sample
of subjects with migraine and nonmigraine controls. METHODS: Two population-based
studies of similar design were conducted in the United States and United Kingdom.
A clinically validated, computer-assisted telephone interview was used to
identify individuals with migraine, as defined by the International Headache
Society, and a nonmigraine control group. During follow-up interviews, 389
migraine cases (246 US, 143 UK) and 379 nonmigraine controls (242 US, 137 UK)
completed the Short Form (SF)-12, a generic HRQoL measure, and the Primary Care
Evaluation of Mental Disorders, a mental health screening tool. The SF-12
measures HRQoL in two domains: a mental health component score (MCS-12) and a
physical health component score (PCS-12). RESULTS: In the United States and
United Kingdom, subjects with migraine had lower scores (p < 0.001) on both the
MCS-12 and PCS-12 than their nonmigraine counterparts. Significant differences
were maintained after controlling for gender, age, and education. Migraine and
depression were highly comorbid (adjusted prevalence ratio 2.7, 95% CI 2.1 to 3. 
5). After adjusting for gender, age, and education, both depression and migraine 
remained significantly and independently associated with decreased MCS-12 and
PCS-12 scores. HRQoL was significantly associated with attack frequency (for
MCS-12 and PCS-12) and disability (MCS-12). CONCLUSIONS: Subjects with migraine
selected from the general population have lower HRQoL as measured by the SF-12
compared with nonmigraine controls. Further, migraine and depression are highly
comorbid and each exerts a significant and independent influence on HRQoL.

Publication Types: 
    Clinical Trial
    Research Support, Non-U.S. Gov't

PMID: 10980724 [PubMed - indexed for MEDLINE]

3557: Neurology. 2000 Sep 12;55(5):624-9.

Comment in:
    Neurology. 2000 Sep 12;55(5):610-1.

The impact of migraine on quality of life in the general population: the GEM
study.

Terwindt GM, Ferrari MD, Tijhuis M, Groenen SM, Picavet HS, Launer LJ.

Department of Neurology, Leiden University Medical Centre, The Netherlands.

OBJECTIVE: To assess health-related quality of life (HRQOL) in migraineurs in the
general population. DESIGN: Cross-sectional study within the context of a
population-based study monitoring health characteristics of the Dutch adult
population in two municipalities representative of the general population in the 
Netherlands. Migraine was assessed in a multistaged procedure that included a
semistructured clinical interview by telephone. Final diagnosis met 1988
International Headache Society criteria. HRQOL was measured with the
self-administered RAND 36-item Health Survey (RAND-36), including physical
functioning, social functioning, role limitations, and physical perception. HRQOL
of migraineurs was compared with that of nonmigraineurs. To compare and study the
effect of comorbidity, the authors also identified subjects with asthma or
chronic musculoskeletal pain. There were 5998 people with complete data, 620 of
whom had migraine in the last year. RESULTS: Compared with nonmigraineurs,
significantly more migraineurs had asthma (OR = 1.6; 95% CI 1.1, 2.4) or chronic 
musculoskeletal pain (OR = 1.7; 95% CI 1.5, 2.1). Migraineurs reported diminished
functioning and well-being on all eight domains as compared with nonmigraineurs. 
HRQOL was inversely related to attack frequency (p < 0.0002). Migraineurs had a
poorer HRQOL than did those reporting asthma, except for dimensions concerning
physical functioning and general health perception, but they had a better HRQOL
than did subjects with chronic musculoskeletal pain. Comorbidity of asthma or
chronic musculoskeletal pain in migraine further reduced HRQOL. CONCLUSIONS:
Migraineurs report more asthma and chronic musculoskeletal pain. Compared with
nonmigraineurs and to others with chronic conditions, migraineurs report
compromised physical, mental, and social functioning, particularly those with a
high frequency of attack.

Publication Types: 
    Clinical Trial
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 10980723 [PubMed - indexed for MEDLINE]

3558: Clin Ther. 2000 Aug;22(8):981-9.

Comparison of naratriptan and sumatriptan in recurrence-prone migraine patients. 
Naratriptan International Recurrence Study Group.

Göbel H, Winter P, Boswell D, Crisp A, Becker W, Hauge T, Mihout B, Niewold J,
Tørring J.

Klinik fur Neurologie der University Kiel, Germany.

OBJECTIVE: This randomized, double-blind, crossover study was undertaken to
compare the incidence of headache recurrence after treatment with naratriptan or 
sumatriptan in migraine patients with a history of frequent headache recurrence
(recurrence in > or =50% of successfully treated attacks). BACKGROUND: Although
the selective 5-hydroxytryptamine, (5-HT1) agonist sumatriptan is effective and
well tolerated for acute treatment of migraine in most patients, headache
recurrence within 24 hours of initial successful treatment with sumatriptan and
other medications has been reported in approximately 35% of patients. The novel
5-HT1 agonist naratriptan possesses pharmacologic and pharmacokinetic
characteristics that may address the issue of headache recurrence. METHODS: Men
and women aged 18 to 65 years with a > or =1-year history of migraine with or
without aura were randomly assigned to treat 1 moderate or severe migraine attack
in a nonclinical setting with one 2.5-mg naratriptan tablet and 1 attack with one
100-mg sumatriptan tablet. A pain-free interval of > or =24 hours was required
between attacks. At 4 hours, patients not using rescue medication and
experiencing headache recurrence could take a second, identical dose of study
medication to treat recurrence. No more than 2 tablets of study medication were
permitted in any 24-hour period. RESULTS: A total of 253 patients treated > or =1
migrane attack and were included in the safety analysis; the 225 patients who
treated both attacks were included in the efficacy analysis. Of the 164
naratriptan-treated and 181 sumatriptan-treated patients experiencing headache
relief after > or =1 attack, headache recurrence 4 to 24 hours after treatment
was reported by 74 naratriptan-treated patients (45%) and 101 sumatriptan-treated
patients (57%; not statistically significant). (One naratriptan- and 3
sumatriptan-treated patients who experienced headache relief did not record
recurrence status and were not included in the denominator for the percentage
calculation.) In a subset of patients experiencing headache relief after 2
attacks, headache recurrence 4 to 24 hours after initial dosing was reported by
55 naratriptan- and 77 sumatriptan-treated patients (41% and 57%, respectively; P
= 0.005). The overall incidence of adverse events was 22% after treatment with
naratriptan and 33% after treatment with sumatriptan. This incidence did not
increase after use of a second dose of naratriptan (20%) or sumatriptan (31%).
CONCLUSION: These data suggest that naratriptan is a long-acting and
well-tolerated addition to currently available medications for the treatment of
acute migraine.

Publication Types: 
    Clinical Trial
    Comparative Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 10972634 [PubMed - indexed for MEDLINE]

3559: Clin Ther. 2000 Aug;22(8):970-80.

Efficacy of naratriptan tablets in the acute treatment of migraine: a
dose-ranging study. Naratriptan S2WB2004 Study Group.

Havanka H, Dahlöf C, Pop PH, Diener HC, Winter P, Whitehouse H, Hassani H.

Lansi-Pohjan Keskussairaala, Neurologian Poliklinikka, Kemi, Finland.

OBJECTIVE: This study sought to compare the efficacy of several doses of
naratriptan tablets with that of sumatriptan tablets and placebo in the acute
treatment of a single migraine attack. METHODS: This was a randomized,
double-blind, placebo-controlled, parallel-group, dose-ranging study. Patients
received either naratriptan tablets (1, 2.5, 5, 7.5, or 10 mg), sumatriptan
tablets (100 mg), or placebo. RESULTS: A total of 643 patients took part in the
study. Two hours after dosing, headache relief was reported by significantly more
patients treated with any dose of naratriptan (52%-69%) or sumatriptan (60%) than
with placebo (31%) (P < 0.05). Four hours after dosing, headache relief was
reported by significantly more patients treated with any dose of naratriptan
(63%-80%) or sumatriptan (80%) than with placebo (39%) and by significantly more 
patients treated with sumatriptan 100 mg (80%) than with naratriptan 1 mg (64%), 
2.5 mg (63%), or 5 mg (65%) (P < 0.05). Twenty-four-hour overall efficacy
(headache relief maintained through 24 hours postdose with no worsening, no use
of rescue medication, and no recurrence) was reported by more patients treated
with any dose of naratriptan (39%-58%) or sumatriptan (44%) than with placebo
(22%). Headache recurrence was reported in 17% to 32% of naratriptan-treated
patients, 44% of sumatriptan-treated patients, and 36% of placebo recipients. The
overall incidence of adverse events was similar in patients treated with
naratriptan 1 mg (20%), naratriptan 2.5 mg (21%), and placebo (23%). For
naratriptan 5, 7.5, and 10 mg, the incidence of adverse events was 32%, 37%, and 
35%, respectively, and for sumatriptan 100 mg it was 26%. CONCLUSIONS: Our
results suggest that the 2.5-mg dose of naratriptan tablets offers the optimal
efficacy-to-tolerability ratio at the dose range between 1 and 10 mg. Although
naratriptan 2.5 mg was less effective than sumatriptan 100 mg at 4 hours after
dosing, the 2 medications showed similar efficacy at 24 hours.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 10972633 [PubMed - indexed for MEDLINE]

3560: Headache. 2000 Sep;40(8):677-81.

Case reports: postpartum cerebral angiopathy in a patient with chronic migraine
with aura.

Modi M, Modi G.

Department of Radiology and the Neurology Unit, Department of Medicine, the Chris
Hani Baragwanath Hospital and the Faculty of Health Sciences, University of the
Witwatersrand, Johannesburg, South Africa.

A 25-year-old woman with a history of chronic severe migraine with aura presented
in an apoplectic state 1 week after the delivery of her third child. She
developed a severe headache and within hours lapsed into a coma. A CT scan of the
brain showed cerebral edema and an occipital hemorrhage. A four-vessel angiogram 
showed diffuse arterial narrowing of all the intracranial vessels with segmental 
narrowing of the suprasellar portion of the internal carotid arteries
bilaterally. She had no risk factors for stroke or vasculitis. Her pregnancy and 
delivery were uneventful with no preeclampsia or eclampsia. Apart from
ergometrine at the time of the delivery, no vasoconstrictor drugs were used. She 
recovered spontaneously. Serial CT scans of the brain demonstrated resolution of 
the edema and hemorrhage with the development of cortical and watershed infarcts.
A repeat cerebral angiogram was normal. She was, therefore, diagnosed as having
suffered from postpartum cerebral angiopathy, a form of reversible cerebral
vasoconstriction, called the Call or Call-Fleming syndrome. The relationship
between migraine and postpartum angiopathy in the development of reversible
cerebral vasoconstriction is discussed.

Publication Types: 
    Case Reports

PMID: 10971665 [PubMed - indexed for MEDLINE]

3561: Headache. 2000 Sep;40(8):672-6.

The efficacy of divalproex sodium in the prophylactic treatment of children with 
migraine.

Caruso JM, Brown WD, Exil G, Gascon GG.

St. Jude Children's Research Hospital, Memphis, TN, USA.

OBJECTIVE: To determine the beneficial use of divalproex sodium as a prophylactic
treatment for migraine in children. BACKGROUND: Previous studies for treatment of
migraine in adults have shown a greater than 50% reduction in migraine attack
frequencies. Few data exist, however, regarding the efficacy and safety of
divalproex sodium use in children with migraine. METHODS: We studied the
incidence of headache relief in our patients with migraine aged 16 years and
younger treated with divalproex sodium prophylactically at our institution from
July 1996 to December 1998 to determine medication dosage used, concomitant
headache medications, and possible adverse effects. RESULTS: A total of 42
patients, ranging in age from 7 to 16 years (mean age, 11.3 years), were treated 
with divalproex sodium for headache. All had a history of migraine with or
without aura. Baseline headache frequency during a minimum 6-month period was one
to four headaches per month. Divalproex sodium dosage ranged from 15 mg/kg/day to
45 mg/kg/day. Of the 42 patients, 34 (80.9%) successfully discontinued their
abortive medications. After 4 months' treatment, 50% headache reduction was seen 
in 78.5% of patients, 75% reduction in 14.2% of patients, and 9. 5% of patients
became headache-free. CONCLUSION: These results indicate divalproex sodium to be 
an effective and well-tolerated treatment for the prophylaxis of migraine in
children.

Publication Types: 
    Clinical Trial

PMID: 10971664 [PubMed - indexed for MEDLINE]

3562: Headache. 2000 Sep;40(8):662-71.

Assessing the impact of migraine on health-related quality of life: An additional
use of the quality of well-being scale-self-administered.

Sieber WJ, David KM, Adams JE, Kaplan RM, Ganiats TG.

University of California, San Diego Health Outcomes Assessment Program, San
Diego, CA, USA.

OBJECTIVES: To compare the interviewer-administered Quality of Well-being Scale
(QWB) with a self-administered form (QWB-SA) for patients with migraine, and to
compare the health status of migraineurs to other medical populations.
BACKGROUND: With the increasing need to document the cost-effectiveness of
treatment for migraine, limitations with both the Medical Outcomes Study Short
Form-36 items and the QWB have been an impediment to research using
cost-effectiveness as an outcome. Demonstrating the sensitivity of an alternative
instrument which addresses these limitations would facilitate cost-effectiveness 
analyses on treatments for migraine. METHODS: Eighty-nine adults (87% women)
known to suffer from migraine were asked to complete both the
interviewer-administered QWB and the self-administered version (QWB-SA) on three 
occasions. The first occasion was on a day when no migraine was experienced in
the previous 7 days. The second and third assessments were completed within 48
hours of the onset of a migraine. RESULTS: While both the QWB and the QWB-SA
successfully distinguished migraine from nonmigraine days, more migraines were
reported on the QWB-SA. Overall, both instruments showed similar patterns of
patient dysfunction during a migraine attack. Each component of the QWB-SA
successfully distinguished migraine from nonmigraine days, and the QWB-SA showed 
a linear sensitivity to pain intensity and disability during a migraine episode. 
Both instruments are able to detect a migraine's effect on multiple domains of
quality of life. Study participants scored significantly lower on the QWB-SA
during a migraine episode than several comparison medical populations.
CONCLUSIONS: The QWB and the QWB-SA appear to have sensitivity to migraine
severity, and the ability to quantitate an effect in multiple quality-of-life
domains. Both measures can be used to calculate quality-adjusted life-years, thus
facilitating cost-effectiveness and health policy work in this important clinical
area.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 10971663 [PubMed - indexed for MEDLINE]

3563: Headache. 2000 Sep;40(8):657-61.

A pilot study to measure cognitive efficiency during migraine.

Farmer K, Cady R, Bleiberg J, Reeves D.

Headache Care Center, Springfield, MO 65804, USA.

BACKGROUND AND OBJECTIVES: The measurement of cognitive efficiency during
migraine has produced conflicting results primarily due to the types of tests
used. The objectives of this pilot study were two-fold: to measure cognitive
efficiency during migraine, compared to a migraine-free period, and to evaluate
the effects of therapy with a 5-HT1 agonist (sumatriptan injection, 6 mg) on the 
cognitive efficiency of migraineurs during a migraine. METHOD: The Headache Care 
Center-Automated Neuropsychological Assessment Metrics was administered to 10
migraineurs, three times without a migraine, once during a migraine, and three
times after administration of sumatriptan injection (6 mg). RESULTS: The results 
demonstrated a significant drop in cognitive efficiency during migraine and
recovery 15 minutes after therapeutic injection. CONCLUSIONS: This pilot study is
the first to document a significant drop in cognitive functioning during migraine
and recovery after administration of a migraine-specific medication.

PMID: 10971662 [PubMed - indexed for MEDLINE]

3564: Headache. 2000 Sep;40(8):638-46.

Reversible cognitive decline accompanies migraine and cluster headaches.

Meyer JS, Thornby J, Crawford K, Rauch GM.

Cerebrovascular Research, Baylor College of Medicine, Houston, TX, USA.

Vascular headaches, including migraine, cluster, and migrainous transformation to
chronic daily headaches, are disabling. During and shortly after headache
intervals, difficulties are reported in concentration, comprehension, and
communication, not accounted for by nausea, photophobia, or sonophobia. These
interfere with interpersonal relations and performance at work with economic
loss. The hypothesis tested and reported here is that cognitive impairments
comprise an important part of vascular headache diatheses. One hundred ninety-six
otherwise normative subjects suffering from migraine or cluster, but not
tension-type, headaches (136 women, 63 men; mean age, 46 years) participated in
an outpatient prospective trial. One hundred thirty-three patients had migraine
without aura, 39 migraine with aura, 11 periodic cluster (by IHS criteria), and
13 had migrainous transformation into chronic daily headaches. Neuropsychological
testing was compared with and without headaches, by combined Mini-Mental Status
Examination (MMSE), Cognitive Capacity Screening Examination (CCSE), and Hamilton
Depression Rating Scale (HDRS). During headache intervals, significant decline
was measured in both CCSE and MMSE scores (P <. 001) without HDRS change in all
types of vascular headache and independent of headache severity, which often
improved, or associated physical symptoms. Cognitive decline was promptly
relieved by serotonin agonists and sleep. Disorders of cerebral serotoninergic
projection systems appear to cause these reversible cognitive impairments.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, Non-P.H.S.

PMID: 10971660 [PubMed - indexed for MEDLINE]

3565: Headache. 2000 Sep;40(8):629-32.

The utility of neuroimaging in the evaluation of children with migraine or
chronic daily headache who have normal neurological examinations.

Lewis DW, Dorbad D.

Departments of Pediatrics and Neurology, Children's Hospital of the King's
Daughters, Eastern Virginia Medical School, Norfolk, VA 23510, USA.

OBJECTIVES: To assess the utility of neuroimaging in the evaluation of children
presenting with two of the most common forms of headache, migraine and chronic
daily headache, and to determine the utility and pathological yield of
neuroimaging in specific headache syndromes in children whose neurological
examinations are normal. METHODS: We retrospectively reviewed the medical records
of patients coded for headache (ICD 784) in the Pediatric Neurology Clinic at
Children's Hospital of the King's Daughters between 1997 and 1999. The age range 
considered was between 6 and 18 years. The study focused on the two most common
types of headache, uncomplicated migraine and chronic daily headache. Only
patients with normal physical and neurological examinations were considered in
this analysis. RESULTS: Three hundred two patients were coded for headache within
the defined age group. One hundred seven (35.4%) patients fulfilled IHS-R
criteria as having uncomplicated migraine with a normal examination, and 30
(9.9%) patients fulfilled criteria for chronic daily headache. Twenty-nine (9.6%)
patients presented with migrainelike symptoms, and 6 (2.0%) presented with
chronic daily symptoms, but had neurological abnormalities present on
examination. The remainder of the patients with headache had the following
etiologies: 50 (16.6%) with secondary headache, 22 (7.3%) with complicated
migraine, 20 (6.6%) with posttraumatic headache, 13 (4.3%) with seizure-related
headache, 11 (3.6%) with brain tumors, 10 (3.3%) with tension-type headache, and 
4 (1.3%) with pseudotumor cerebri. Of the 107 patients with migraine, 42 (39.3%) 
received CT scans; 2 (4.8%) of which were considered "abnormal." One of the
abnormalities was an arachnoid cyst and the other was a dilated Virchow-Robin
space. Twelve (11.2%) patients with migraine received an MRI, 2 (16.7%) of which 
were considered abnormal. Both of the abnormal findings were Chiari type I
malformations. Of the 30 patients with chronic daily headache, 17 (56.7%)
received CT scans, 3 (17.6%) of which were considered abnormal. The abnormalities
consisted of a maxillary opacification, a mucous retention cyst, and an occult
vascular malformation. Eight (26.7%) of the patients with chronic daily headache 
had an MRI, 2 (25.0%) of which were abnormal. One of the abnormalities was a
Chiari I malformation, and the other was an occult vascular malformation.
CONCLUSION: The yield of neuroimaging in children with uncomplicated migraine and
normal neurological examination was 3.7%. The yield in children with chronic
daily headache and normal neurological examination was higher at 16.6%. The
abnormalities discovered included arachnoid cysts, Chiari I malformations, sinus 
disease, occult vascular malformations and "dilated Virchow-Robin spaces." While 
none of the neuroimaging findings were apparent clinically, their discovery did
not influence the diagnosis, management, or outcome of the patients. None of the 
abnormalities necessitated surgical intervention or were associated with the
headache presentation. Therefore, neuroimaging is not warranted in children and
adolescents with defined clinical headache syndrome diagnoses whose neurological 
examinations are normal.

PMID: 10971658 [PubMed - indexed for MEDLINE]

3566: Eur J Neurol. 2000 Jul;7(4):405-11.

Glyceryl trinitrate induced headache in migraineurs - relation to attack
frequency.

Christiansen I, Daugaard D, Lykke Thomsen L, Olesen J.

Department of Neurology, Glostrup Hospital, University of Copenhagen, Denmark.

Glyceryl trinitrate, a prodrug of nitric oxide, induces a mild to moderate
headache in healthy subjects, whilst migraineurs develop a more severe headache, 
resembling spontaneous migraine attacks. In order to investigate whether this
increased nitric oxide sensitivity depends upon the frequency of spontaneously
occurring migraine attacks, intravenous infusion of glyceryl trinitrate (0.5
microg/kg/min) was given to 15 migraine patients with rare attacks (</=4
attacks/year) of migraine without aura. Fourteen age-matched migraine patients
with frequent attacks of migraine without aura (>/=12 attacks/year) and 14
healthy subjects served as controls. No significant difference between the
migraine groups for any of several parameters was detected, although the trend
was always towards more headaches in frequent migraineurs. Both migraineurs with 
frequent and rare attacks experienced a headache that was significantly more
severe, longer lasting, and fulfilled the diagnostic criteria for migraine
without aura more often, compared to the healthy subjects (P = 0.0001).
Conclusively, supersensitivity to glyceryl trinitrate in migraineurs seems to be 
related to a basic - probably genetically determined - pathophysiological
mechanism involving nitric oxide, and not to the environmental influences, which 
to a large extent determine the expression of migraine.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 10971600 [PubMed - indexed for MEDLINE]

3567: Optom Vis Sci. 2000 Aug;77(8):402-11.

The prevalence and symptoms of migraine in a consecutive series of patients
attending an optometric practice.

Gutteridge IF, Cole BL.

Department of Optometry and Vision Sciences, University of Melbourne, Parkville, 
Victoria, Australia.

The purpose of the investigation was to determine the prevalence of migraine in
optometric practice and to document the variety of presentation. One thousand
consecutively presenting patients of a suburban optometric practice were asked
questions to establish whether they experience migraine or have experienced it in
the past. Those with a history of migraine were asked further questions to
establish the type of migraine and to document the variety of the symptoms they
experienced. Eleven percent of male and 23% of female patients currently had
migraine or had experienced it in the past. When corrected for the age
distribution of the population of the state from which the sample was drawn, it
is estimated that the general population prevalence of migraine is 9.5% for men
and 19.7% for women. Half of the sample of migraineurs had not experienced a
migraine within the last 12 months. A third had a known family history of
migraine. Nearly half had not had a formal medical diagnosis of their migraine
but only 7 had attended for optometric examination because of their migraine
symptoms. Four of these patients had single migraine-like episodes and three had 
migraine equivalents (acephalic migraine, experiencing the visual aura without
headache). Optometrists must be thoroughly familiar with migraine and its varied 
presentation because of its high prevalence, the explanatory value in offering a 
formal diagnosis of migraine, and the risk that headache or visual aura may be
wrongly ascribed to migraine when there is some more sinister cause of the
symptoms.

Publication Types: 
    Comparative Study

PMID: 10966066 [PubMed - indexed for MEDLINE]

3568: Neuropediatrics. 2000 Jun;31(3):145-7.

Swelling of the third nerve in a child with transient oculomotor paresis: a
possible cause of ophthalmoplegic migraine.

Ramelli GP, Vella S, Lövblad K, Remonda L, Vassella F.

Department of Pediatrics, Ospedale San Giovanni, Bellinzona, Switzerland.
gpramelli.osg@eoc.ch

Transient oculomotor nerve palsy is rarely observed in childhood and mostly is
recognized to be a migraine equivalent. We report an 8-year old girl who
presented with recurrent attacks of transient oculomotor paresis. The clinical
profile of the patient suggested transient dysfunction in the context of an
ophthalmoplegic migraine. A CT scan was normal, but MRI demonstrated a swollen
right oculomotor nerve.

Publication Types: 
    Case Reports
    Review

PMID: 10963102 [PubMed - indexed for MEDLINE]

3569: Cephalalgia. 2000 Mar;20(2):122-6.

Prevention of migraine during prodrome with naratriptan.

Luciani R, Carter D, Mannix L, Hemphill M, Diamond M, Cady R.

Albuquerque Clinic for Pain, Stress and Health Rehabilitation, New Mexico, USA.

OBJECTIVE: To determine the role of naratriptan in preventing migraine headache
when administered during prodrome. PROCEDURES: Baseline phase: patients recorded 
prodrome symptoms and time of onset, time when patient knew that headache was
inevitable, time of onset and severity of headache. Treatment phase: patients
given naratriptan 2.5 mg to take at the time they knew headache was inevitable.
Patients recorded prodrome symptoms and time of onset, time they knew headache
was inevitable, time naratriptan administered, time of onset and severity of any 
headache. Patients treated three prodromes separated by at least 48 h. FINDINGS: 
Twenty patients completed both phases. During baseline phase, 59 prodromes were
reported and all were followed by headache. Severity of headache: 5% mild, 51%
moderate, 44% severe. During treatment phase, 63 prodromes were reported. Of
these, 38/63 (60%) were not followed by headache. Among headaches that occurred, 
the majority occurred within 2 h of naratriptan administration, suggesting that
naratriptan is more effective in preventing headache if taken early in prodrome. 
Severity of 25 headaches: 44% mild, 24% moderate, 32% severe. CONCLUSIONS:
Naratriptan 2.5 mg appears to prevent migraine headache when given early in
prodrome. If headache occurs, severity appears to be reduced.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 10961768 [PubMed - indexed for MEDLINE]

3570: Cephalalgia. 2000 Mar;20(2):107-13.

Comment in:
    Cephalalgia. 2000 Oct;20(8):748.

Prednisone as initial treatment of analgesic-induced daily headache.

Krymchantowski AV, Barbosa JS.

Headache Center of Rio/Institute of Neurology Deolindo Couto, Rio de Janeiro,
Brazil. abouchkrym@openlink.com.br

The majority of the patients who seek medical care in tertiary headache centres
present with transformed migraine, and convert to daily headache, as a result of 
excessive intake of symptomatic medications (SM). This study aimed to analyse the
possibility of using a short course of oral prednisone for detoxifying patients
with chronic daily headache due to medication overuse in an out-patient setting. 
Four hundred patients with headache occurring more than 28 days per month for
longer than 6 months were studied (mean baseline frequency of 0.96). Symptomatic 
medications were stopped suddenly and prednisone was initiated in tapering doses 
during 6 days, followed by the introduction of preventive treatment. Withdrawal
symptoms and the frequency, intensity and duration of the headache, as well as
the consumption of rescue medications, were analysed during the first 16 and 30
days of withdrawal. Eighty-five percent of the patients experienced a reduction
in headache frequency and no patients presented severe attacks during the first 6
days. With regard to the following 10 days, 46% of the patients experienced at
least 2 days without headache and 58% less intense attacks. Most of the patients 
noticed attacks with longer duration. After the 30-day period there was a
significant decrease in headache frequency (mean 0.83, P<0.001), and no patients 
returned to overuse of SM. This study demonstrates that it is possible to
detoxify patients suffering from rebound headaches, using oral prednisone during 
the first days of withdrawal, in an out-patient setting.

PMID: 10961766 [PubMed - indexed for MEDLINE]

3571: Cephalalgia. 2000 Mar;20(2):100-6.

Linked activation of nitric oxide synthase and cyclooxygenase in peripheral
monocytes of asymptomatic migraine without aura patients.

Stirparo G, Zicari A, Favilla M, Lipari M, Martelletti P.

Institute of Biomedical Technologies, CNR, University La Sapienza, Rome, Italy.

Many reports indicate that nitric oxide (NO) could be involved in migraine
without aura (MWA), an extremely diffuse clinical event. Since monocyte may be a 
relevant source of NO, we analysed monocyte activation in MWA patients, in a
period in which they were free of symptoms. NO basal production by MWA peripheral
monocytes was significantly higher than in healthy subjects (91.25+/-8.6
microM/10(6) cells vs. 22.6+/-3.2 microM/106 cells). Interestingly, even the
release of prostaglandin E2 (PGE2), was higher in MWA patients than in healthy
subjects (3137+/-320 pg/10(6) cells vs. 1531+/-220 pg/10(6) cells). The
incubation of monocytes from healthy subjects and MWA patients with
N-nitro-L-arginine methyl ester caused a marked decrease of both NO and PGE2
release. We hypothesise that NOS and cyclooxygenase pathways in monocytes are
linked and are, in MWA patients, up-regulated, even in a symptoms-free period. NO
and PGE2 hyperproduction could therefore be involved in the neurovascular
modifications leading to migraine attacks.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 10961765 [PubMed - indexed for MEDLINE]

3572: Cephalalgia. 2000 Mar;20(2):74-84.

Visual contrast gain control in migraine: measures of visual cortical
excitability and inhibition.

McColl SL, Wilkinson F.

Department of Psychology, McGill University, Montreal, Quebec, Canada.
fran@hebb.psych.mcgill.ca

The present study examined the extent to which migraineurs demonstrate interictal
visual cortical hyperexcitability as a result of poor inhibitory control in the
visual system. We employed a well-established psychophysical measure of
inhibition, visual contrast gain control. The task involved detecting a briefly
presented target that was superimposed on a highly excitable high contrast
masking pattern. The strength of inhibition was assessed by comparing target
detection thresholds with and without the operation of gain controls. Migraineurs
with and without aura (n=25, n=22, respectively) were compared with those with no
history of migraine (n=25). Our results do not indicate a loss of inhibition in
migraine; the strength of inhibitory feedback contrast gain controls was similar 
between migraineurs and controls. We did however, find a statistically greater
masking effect in migraineurs compared with controls in the zero delay condition,
suggesting cortical hyperexcitability in migraine. Possible mechanisms of
cortical hyperexcitability are discussed in light of the results.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 10961762 [PubMed - indexed for MEDLINE]

3573: Brain. 2000 Sep;123 ( Pt 9):1830-7.

Nitric oxide-induced headache in patients with chronic tension-type headache.

Ashina M, Bendtsen L, Jensen R, Olesen J.

Department of Neurology, Glostrup Hospital, University of Copenhagen, DK-2600
Glostrup, Copenhagen, Denmark. ashina@dadlnet.dk

An experimental model of headache offers unique possibilities to study the
mechanisms responsible for head pain. Using the glyceryl trinitrate [GTN; nitric 
oxide (NO) donor] model of experimental headache, we studied the intensity,
quality and time profile of headache after infusion of GTN in 16 patients with
chronic tension-type headache and in 16 healthy controls. Subjects were
randomized to receive intravenous infusion of GTN (0.5 microg/kg per minute for
20 min) or placebo on two headache-free days separated by at least 1 week.
Headache intensity was measured on a 10-point verbal rating scale during 2 h of
observation and for the next 10 h after discharge from hospital. The primary
endpoints were the difference between the area under the curve (AUC-intensities x
duration) for headache recorded on the day of GTN treatment and on the day of
placebo treatment in patients, and in patients and controls on the days of GTN
treatment. In patients, the AUC on a GTN day [2221 (1572-3704); median with
quartiles in parentheses], was significantly greater than on a placebo day [730
(60-1678), P: = 0. 008]. On the GTN day, the AUC in patients [2221 (1572-3704)]
was significantly higher than in controls [43 (0-972), P: = 0.0001]. In patients,
peak pain intensity occurred 8 h after infusion of GTN, whereas in controls it
occurred 20 min after the start of infusion. The present study demonstrates that 
an NO-induced biphasic response with an immediate and a delayed headache is
common to chronic tension-type headache and migraine. Furthermore, the NO-induced
delayed headache has the characteristics of the primary headache disorder. This
suggests that NO contributes to the mechanisms of several types of primary
headaches and that NO-related central sensitization may be an important common
denominator in the pain mechanisms of primary headaches.

Publication Types: 
    Clinical Trial
    Research Support, Non-U.S. Gov't

PMID: 10960046 [PubMed - indexed for MEDLINE]

3574: Adv Pediatr. 2000;47:161-97.

Childhood migraine.

Turk WR.

Mayo Medical School, Jacksonville, Fla., USA.

Migraines are a common and often undiagnosed and undertreated problem in children
of all ages. Migraine symptoms can vary dramatically in terms of character and
severity, from brief self-limited headaches to prolonged events with complex
neurologic and systemic symptoms. Identification of migraines requires an index
of suspicion in any child with acute recurrent headaches or neurologic symptoms. 
Diagnosis remains predominately based on the patient's history of symptoms and
supported by a positive family history. Neurodiagnostic tests are often
unnecessary and of value predominately to exclude nonmigraine disorders that may 
present with similar symptoms. A number of recent advances in our understanding
of the pathophysiology and genetics of migraines have occurred, and continued
progress in these exciting areas of investigation is anticipated. Identification 
of genetic markers in individuals with FHM is potentially the first step in
discovery of genetic markers that may be useful in other migraine syndromes and
may lead to the development of new therapeutic interventions. The movement from a
vascular to integrated neurovascular pathogenesis for migraine headaches is
already being translated into the study of new pharmacologic treatments, such as 
nitric oxide inhibitors and continued development of 5-HT1 agonist (triptans)
medications. Although not currently approved for use in children, triptans are
being widely evaluated in clinical trials. As additional triptans and new dosage 
formulations are developed and approved, it is anticipated that the treatment of 
migraine headaches in children may change significantly in the next several
years.

Publication Types: 
    Review

PMID: 10959443 [PubMed - indexed for MEDLINE]

3575: Adv Pediatr. 2000;47:117-60.

Cyclic vomiting syndrome: evolution in our understanding of a brain-gut disorder.

Li BU, Balint JP.

Ohio State University, USA.

Cyclic vomiting syndrome (CVS) remains a mysterious disorder despite our
increasing knowledge since its classic description by Gee in 1882. Its hallmark
feature of recurrent, explosive bouts of vomiting punctuating periods of normal
health causes substantial medical morbidity (50% of patients require intravenous 
therapy), as well as significant time lost from school (20 school absences per
year) and work. Limited epidemiologic data indicate that CVS may occur more
commonly than previously thought, affecting as many as 1.9% of school-aged
children. Besides the relentless vomiting, the child usually has pallor (87%),
lethargy (91%), anorexia (74%), nausea (72%), and abdominal pain (80%). There is 
evidence of clinical and physiologic overlap among CVS, abdominal migraine, and
migraine headaches. We propose revised criteria for abdominal migraine that
include pain as the predominant and consistent symptom, lack of abnormal
screening tests, and in retrospect, either subsequent development of migraines or
positive response to antimigraine medication. Besides migraines, other etiologic 
possibilities include mitochondrial DNA mutations, ion channelopathies, excessive
hypothalamic-pituitary-adrenal axis activation, and heightened autonomic
reactivity. The differential diagnosis includes idiopathic CVS (88%);
gastrointestinal disorders (7%), including serious surgical disorders (e.g.,
malrotation); and extraintestinal disorders (5%), including serious surgical
(brain stem neoplasm) and metabolic disorders (e.g., fatty acid oxidation
disorder). Within the idiopathic group, there may be migraine, Sato's
neuroendocrine, mitochondrial, and other subgroups. Treatment includes avoidance 
of triggers, prophylactic medication, supportive care, abortive medication, and
family support. In the future, investigation into mitochondrial DNA mutations,
ion channel defects, corticotropin-releasing factor, and serotonin and tachykinin
receptor physiology and pharmacology may help discover the etiology and
pathogenesis of this disorder.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.
    Review

PMID: 10959442 [PubMed - indexed for MEDLINE]

3576: Clin Ter. 2000 May-Jun;151(3):145-8.

Gabapentin in the prophylaxis of migraine: a double-blind randomized
placebo-controlled study.

Di Trapani G, Mei D, Marra C, Mazza S, Capuano A.

Institute of Neurology, Catholic University, Rome, Italy.
gditrapani@rm.unicatt.it

OBJECTIVE: Gabapentin is an antiepileptic drug of new generation that increases
brain GABA levels. We report the results of a three-month randomised double-blind
placebo-controlled study on the effects of gabapentin in the prophylaxis of
patients with migraine meeting the IHS criteria. PATIENTS AND METHODS: We treated
63 patients suffering from migraine with or without aura. Patients treated their 
attack at home using symptomatic drugs and clinical assessment was recorded on a 
diary. After a washout of 8 week from any other prophylactic treatment, all
patients were treated with 1200 mg/day of gabapentin; this is our therapeutic
plan: 400 mg/day from 1st to 3rd day, 800 mg/day from 4th to 6th day and 1200
mg/day from 7th day. RESULTS: No patients withdrew, gabapentin was well
tolerated; adverse events (somnolence, dizziness, tremor, fatigue and ataxia)
generally were transient and mild to moderate in severity and in 13 patients
(27%) only occurred. At the end of treatment, in such case, we reported a
significative reduction of frequency and intensity of migraine in 30 patients
treated with gabapentin. DISCUSSION: Our observations indicate that gabapentin is
well tolerated by patients and that reduces headache frequency and use of
symptomatic drugs in both groups. Gabapentin shows to have an effective
therapeutic action in the prophylactic treatment of migraine.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial

PMID: 10958046 [PubMed - indexed for MEDLINE]

3577: Int J Clin Pract. 2000 Jun;54(5):281-6.

A clinical comparison of sumatriptan nasal spray and dihydroergotamine nasal
spray in the acute treatment of migraine.

Boureau F, Kappos L, Schoenen J, Esperanca P, Ashford E.

Centre de traitement de la douleur, Paris, France.

A multinational, multicentre, randomised, double-blind, double-dummy, crossover
study (368 patients treating two attacks) was conducted to compare the efficacy
and tolerability of sumatriptan nasal spray (20 mg) with dihydroergotamine (DHE) 
nasal spray (1 mg plus optional 1 mg). At the primary efficacy time point of 60
minutes after dosing, significantly more patients obtained headache relief
(change from moderate or severe to none or mild) after treatment with sumatriptan
than with DHE (53% sumatriptan, 41% DHE, p < 0.001). Significantly more patients 
reported relief of nausea after sumatriptan than after DHE at 60 minutes (64%
sumatriptan, 49% DHE, p = 0.006). A significant difference between the two
treatments was first observed at 45 minutes with respect to both headache relief 
(38% sumatriptan, 31% DHE, p = 0.037) and relief of nausea (55% sumatriptan, 40% 
DHE, p = 0.014). There were no significant differences between the two treatments
for other measures of efficacy. Both treatments were well tolerated, with only
10% of patients in each group reporting one or more adverse events. The most
frequently reported adverse event after sumatriptan was a bad or bitter taste,
which was reported by 5% of patients. After DHE, 4% of patients reported symptoms
of the nasal cavity/sinuses and 3% reported nausea and/or vomiting as adverse
events. It is concluded that sumatriptan nasal spray is superior to DHE nasal
spray in the relief of pain and nausea associated with acute migraine headache.

Publication Types: 
    Clinical Trial
    Multicenter Study
    Randomized Controlled Trial

PMID: 10954953 [PubMed - indexed for MEDLINE]

3578: Plast Reconstr Surg. 2000 Aug;106(2):429-34; discussion 435-7.

Comment in:
    Plast Reconstr Surg. 2005 Jul;116(1):335; author reply 335-6.

Corrugator supercilii muscle resection and migraine headaches.

Guyuron B, Varghai A, Michelow BJ, Thomas T, Davis J.

Case Western Reserve University, Cleveland, Ohio, USA.

This study was conducted to determine whether there is an association between the
removal of the corrugator supercilii muscle and the elimination or significant
improvement of migraine headaches. Questionnaires were sent to 314 consecutive
patients who had undergone corrugator supercilii muscle resection during
endoscopic, transpalpebral, or open forehead rejuvenation procedures. The
patients were queried as to whether they had a history of migraine headaches and,
if so, whether the headaches significantly improved or disappeared after surgery.
If the answer was affirmative, then the patients were further questioned about
the duration of the improvement or cessation of the headaches and the
relationship to the timing of the surgery. After an initial evaluation of the
completed questionnaires, a telephone interview was conducted to confirm the
initial answers and to obtain further information necessary to ensure that the
patients had a proper diagnosis based on the International Headache Society
criteria for migraine headaches. The charts of the patients who had migraine
headaches were studied to ascertain and classify the type of surgery they had
undergone. Patient demographics were reviewed, and the results were statistically
analyzed. Of the 314 patients, 265 (84.4 percent) either responded to the
questionnaire, were interviewed, or both responded to the questionnaire and were 
interviewed. Of this group, 16 patients were excluded because of the provision of
insufficient information to meet the International Headache Society criteria, the
presence of organic problems, and other exclusions mandated by study design.
Thirty-nine (15.7 percent) of the remaining 249 patients had migraine headaches
that fulfilled the Society criteria. Thirty-one of the 39 (79.5 percent) with
preoperative migraine noted elimination or improvement in migraine headaches
immediately after surgery (p < 0.0001; McNemar), and the benefits lasted over a
mean follow-up period of 47 months. When the respondents with a positive history 
of migraine headaches were further divided, 16 patients (p < 0.0001; McNemar)
noticed improvement over a mean follow-up period of 47 months, and 15 (p <
0.0001; McNemar) experienced total elimination of their migraine headaches over a
mean follow-up period of 46.5 months. When divided by migraine headache type, 29 
patients (74 percent) had nonaura migraine headaches. Of these patients, the
headaches disappeared in 11 patients, improved in 13 patients, and did not change
in five patients (p < 0.0001). Ten patients experienced aura-type headaches,
which disappeared or improved in seven of the patients and did not change in
three of the patients (p < 0.0001). This study proves for the first time that
there is indeed a strong correlation between the removal of the corrugator
supercilii muscle and the elimination or significant improvement of migraine
headaches.

PMID: 10946944 [PubMed - indexed for MEDLINE]

3579: Semin Neurol. 2000;20(2):195-200.

Migraine in the athlete.

Lane JC.

The Head Pain Center, Englewood, Colorado 80110, USA.

Migraine in the athlete may occur secondary to effort, prolonged exertion, or
trauma or as a posttraumatic event. The chemistry is probably akin to that of
spontaneous migraine. The purpose of this discussion is to outline the
differential diagnosis of the athlete presenting with headache. Appropriate
treatment can enhance athletic performance and enable the migraineur to
participate in athletic endeavors.

Publication Types: 
    Review

PMID: 10946739 [PubMed - indexed for MEDLINE]

3580: Mayo Clin Proc. 2000 Aug;75(8):782-9.

Comment in:
    Mayo Clin Proc. 2000 Aug;75(8):780-1.

Effectiveness of sumatriptan in reducing productivity loss due to migraine:
results of a randomized, double-blind, placebo-controlled clinical trial.

Schulman EA, Cady RK, Henry D, Batenhorst AS, Putnam DG, Watson CB, O'Quinn SO.

Center for Headache Management, Springfield, Pa., USA.

OBJECTIVE: To determine the effect of sumatriptan on migraine-related workplace
productivity loss. PATIENTS AND METHODS: In this randomized, double-blind,
placebo-controlled, parallel-group trial, adult migraineurs self-injected 6 mg of
sumatriptan or matching placebo to treat a moderate or severe migraine within the
first 4 hours of a minimum of an 8-hour work shift. Outcome measures included
productivity loss and number of patients returning to normal work performance 2
hours after injection and across the work shift, time to return to normal work
performance, and time to headache relief. RESULTS: A total of 206 patients
underwent screening, 140 (safety population) of whom returned for clinic
treatment. Of these 140 patients, 119 received migraine treatment in the
workplace (intent-to-treat population), 116 of whom comprised the study
population. Of these 116 patients, 76 self-administered sumatriptan, and 40
self-administered placebo. Sumatriptan treatment tended to reduce median
productivity loss 2 hours after injection compared with placebo (25.2 vs 29.9
minutes, respectively; P = .14). Significant reductions in productivity loss were
obtained across the work shift after sumatriptan treatment compared with placebo 
(36.8 vs 72.6 minutes, respectively; P = .001). Significantly more
sumatriptan-treated patients vs placebo-treated patients experienced shorter
return to normal work performance at 2 hours (53/76 [70%] vs 12/40 [30%],
respectively) and across the work shift (64/76 [84%] vs 23/40 [58%],
respectively; P < .001). Significantly more sumatriptan-treated patients
experienced headache relief 1 hour after injection compared with placebo-treated 
patients (48/76 [63%] vs 13/40 [33%], respectively; P = .004). CONCLUSION: Across
an 8-hour work shift, sumatriptan was superior to placebo in reducing
productivity loss due to migraine.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 10943230 [PubMed - indexed for MEDLINE]

3581: Headache. 2000 Jul-Aug;40(7):592-4.

Olfactory hallucinations during migraine in an adolescent with an MRI temporal
lobe lesion.

McAbee G, Sagan A, Winter L.

Department of Pediatrics (Neurology) University of Medicine & Dentistry of New
Jersey, School of Osteopathic Medicine, Stratford, NJ 08084, USA.

OBJECTIVE: To report the first example of an abnormal magnetic resonance imaging 
(MRI) test in a patient with migraine and olfactory hallucinations and to provide
additional evidence for a possible role of the temporal lobe in migraine.
BACKGROUND: The relationship between the temporal lobe and migraine with or
without hallucinations is unclear and continues to evolve. Clinical and
functional neuroimaging studies (positron emission tomography/single photon
emission computed tomography) have lent support to the possibility of a
relationship. Anatomical neuroimaging with computed tomography has previously
been normal. METHODS: The history and findings of an adolescent with migraine and
olfactory hallucinations is reported. RESULTS: Brain MRI demonstrated a mass in
the temporal lobe. CONCLUSIONS: Magnetic resonance imaging should be considered
in patients with olfactory hallucinations and migraine. In addition, the role of 
the temporal lobe in migraine warrants further study.

Publication Types: 
    Case Reports

PMID: 10940099 [PubMed - indexed for MEDLINE]

3582: Headache. 2000 Jul-Aug;40(7):587-91.

Cardiac risk factors and the use of triptans: a survey study.

Young WB, Mannix L, Adelman JU, Shechter AL.

Jefferson Headache Center, Thomas Jefferson University Hospital, Philadelphia, PA
19107, USA.

OBJECTIVE: To describe current practice in triptan use. BACKGROUND: Triptans are 
effective migraine treatments that cause chest symptoms in some patients. True
cardiac ischemia is rare. Design.-Headache specialists and family practitioners
completed questionnaires regarding the times when triptans are contraindicated,
obtaining electrocardiograms (ECGs), and giving the first dose in the office.
RESULTS: Sixty-five headache specialists and 67 family practitioners responded.
Headache specialists saw an average of 36.3 patients with headache per week.
Family practitioners saw an average of 7.2. Family practitioners and headache
specialists had similar opinions regarding the age at which triptans were
contraindicated with various numbers of risk factors. Sixty-one percent of
headache specialists and 50% of family practitioners would not use a triptan at
any age for patients with more than three risk factors (P = NS). Ten percent of
headache specialists obtained an ECG for all patients being prescribed triptans, 
while no family practitioners did (P =. 008). Ten percent of both family
practitioners and headache specialists never obtained an ECG, even with multiple 
cardiac risk factors. Headache specialists obtained ECGs more often than family
practitioners (P <.002 for one to three risk factors). Family practitioners were 
more likely to give the first dose of the triptan in the office regardless of
cardiovascular risk (58% versus 20%, P <. 001). Forty-five percent of headache
specialists and 2% of family practitioners never gave the first dose in the
office (P <.001). Family practitioners gave the first dose in the office more
readily than headache specialists in patients with no risk factors (P =.001), but
not for one or more risk factors. CONCLUSIONS: No consensus exists among family
practitioners or headache specialists about when to avoid using a triptan due to 
excessive cardiac risk factors, when to obtain an ECG prior to using a triptan,
and when to give the first dose of a triptan in the office. Headache specialists 
are more likely to obtain ECGs, whereas family practitioners are more likely to
give the first dose of a triptan in the office.

Publication Types: 
    Comparative Study

PMID: 10940098 [PubMed - indexed for MEDLINE]

3583: Headache. 2000 Jul-Aug;40(7):572-80.

Venlafaxine extended release (XR) for the prophylaxis of migraine and
tension-type headache: A retrospective study in a clinical setting.

Adelman LC, Adelman JU, Von Seggern R, Mannix LK.

Headache Wellness Center, Greensboro, NC 27403, USA.

OBJECTIVE: To assess the efficacy of extended-release venlafaxine in the
prophylaxis of migraine and chronic tension-type headache. BACKGROUND:
Venlafaxine, a structurally novel antidepressant, is a selective
serotonin-norepinephrine reuptake inhibitor. This study is the first to test the 
effects of extended-release venlafaxine on headaches. METHODS: Patients were
evaluated on a retrospective basis. Fifty-six patients with chronic tension-type 
headache and 114 patients with migraine were prescribed extended-release
venlafaxine. Nearly all the study subjects had been resistant to several previous
preventive medications. Patients took venlafaxine for an average of 6 months with
a median dose of 150 mg (range, 37.5 to 300 mg). RESULTS: The mean frequency of
headaches in the group with chronic tension-type headache fell from 24.0 to 15.2 
per month (P <.0001). The group with migraine showed a reduction from 16.1 to
11.1 headaches per month (P <.0001). The medicine was well tolerated.
CONCLUSIONS: This trial indicates that extended-release venlafaxine has potential
in headache prophylaxis based on its efficacy and safety profile. We recommend a 
double-blind, placebo-controlled study to further assess the role of
extended-release venlafaxine in headache prevention.

Publication Types: 
    Clinical Trial
    Research Support, Non-U.S. Gov't

PMID: 10940096 [PubMed - indexed for MEDLINE]

3584: Headache. 2000 Jul-Aug;40(7):568-71.

Assessing the relative incidence of mitochondrial DNA A3243G in migraine without 
aura with maternal inheritance.

Di Gennaro G, Buzzi MG, Ciccarelli O, Santorelli FM, Pierelli F, Fortini D,
D'Onofrio M, Costa A, Nappi G, Casali C.

IRCCS Neuromed, Pozzilli, Italy.

OBJECTIVE: To determine whether patients with migraine without aura with maternal
"inheritance" are affected by a monosymptomatic form of the MELAS syndrome
(mitochondrial encephalomyopathy, lactic acidosis, and strokelike episodes) or
carry the most common mitochondrial DNA (mtDNA) mutation associated with MELAS,
namely the A3243G transition in the transfer RNA (tRNA)Leu(UUR) gene. BACKGROUND:
The association between migraine and abnormal mitochondrial function has been
suggested on clinical, biochemical, and neuroradiological grounds. Migraine
attacks with vomiting and cerebral infarctions, most often in the posterior
cerebral regions, which are reminiscent of complicated migraine, are typical
features of MELAS. The observation that migrainous patients have affected mothers
more often than affected fathers suggests a possible role for maternally
transmitted genetic factors. METHODS: We studied 25 patients with migraine with
aura whose mothers were also affected. A sensitive polymerase chain reaction
restriction fragment length polymorphism analysis was used to detect mutated
genomes. CONCLUSIONS: We failed to detect the MELAS mutation, but migraine may
still be associated with point mutations of mtDNA other than A3243G or with
as-yet-unidentified nuclear DNA factors related to mitochondrial function.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 10940095 [PubMed - indexed for MEDLINE]

3585: Headache. 2000 Jul-Aug;40(7):550-60.

Further development and testing of the migraine-specific quality of life (MSQOL) 
measure.

Patrick DL, Hurst BC, Hughes J.

Department of Health Services, University of Washington, Seattle, WA 98195-7660, 
USA.

OBJECTIVE: To evaluate the longitudinal performance of the migraine-specific
quality of life (MSQOL) instrument. METHODS: Psychometric tests evaluated data
obtained from 1383 migraineurs who completed the 20-item MSQOL questionnaire
during a noncomparative, long-term, observational study of zolmitriptan (Zomig), 
5 mg, for the acute treatment of migraine attacks of any intensity. RESULTS:
There was a relationship between a history of a high frequency of migraine
attacks and low baseline MSQOL scores, indicating a lower quality of life.
Principal components analyses confirmed three domains and an overall score.
Cronbach alpha coefficients for the overall score (.93) indicated high internal
consistency. Responsiveness analysis over 180 days of treatment indicated a
significantly greater improvement in MSQOL scores (P <.05) in treatment
responders compared with nonresponders. The average effect size (0.25) and Guyatt
responsiveness statistic (0.46) for the MSQOL instrument exceeded those for the
eight domains of the Medical Outcomes Study Short Form Health Survey (MOS SF-36) 
(-0.05 to 0.14 and 0.01 to 0.12, respectively). Change from baseline for
responders in MSQOL total score was 4.7 to 5.4 compared with 1.1 to 2.7 for
nonresponders. CONCLUSIONS: Cumulative evidence for the MSQOL instrument meets
established criteria for validity, consistency, and reproducibility and shows
moderate responsiveness to treatment. This instrument fulfils the need for an
MSQOL measure to be used as an adjuvant measure in the assessment of long-term
outcomes of therapy.

Publication Types: 
    Evaluation Studies
    Research Support, Non-U.S. Gov't

PMID: 10940093 [PubMed - indexed for MEDLINE]

3586: Headache. 2000 Jul-Aug;40(7):539-49.

Effectiveness of amitriptyline in the prophylactic management of childhood
headaches.

Hershey AD, Powers SW, Bentti AL, Degrauw TJ.

Divisions of Neurology, Children's Hospital Medical Center, Cincinnati, Ohio
45229-3039, USA.

OBJECTIVE: To study the effectiveness of a standardized dose of amitriptyline, 1 
mg/kg, for childhood headaches. BACKGROUND: Amitriptyline has been shown to be
effective for the prophylaxis of migraine in adults. Studies in children,
however, have been quite limited. In adults, the suggested effective dose range
is 10 to 150 mg. In children, a standardized dosage is often not used, resulting 
in a dosage range in clinical practice that often varies from a very low dose to 
a dose equivalent to that used in adults. METHODS: Children with more than three 
headaches per month were treated with amitriptyline, slowly increasing the dose
to 1 mg/kg per day. The frequency, severity, and duration of their headaches were
initially evaluated and subsequently measured at each follow-up evaluation. Two
hundred seventy-nine children had headaches occurring frequently enough to
indicate prophylactic treatment. Of these children, 192 (68.8%) were treated with
amitriptyline. The average age at presentation was 12.0 (+/- 3.0) years. The
ratio of boys to girls was 1:1.74. The average frequency of headaches was 17.1
(+/- 10.1) days per month. The average severity was 6.84 (+/- 1.67) on a 10-point
pain scale. The average duration was 11.5 (+/- 15.0) hours. The most frequent
diagnoses using International Headache Society criteria were migraine (60.6%),
migraine with aura (7.9%), and tension-type headache (10.4%). Of these children, 
146 have been seen for at least one follow-up examination, occurring on average
67.3 (+/- 32.3) days after beginning prophylactic treatment. RESULTS: A total of 
84.2% of the children reported an overall perception of being better, while 11.6%
reported being the same. The frequency of headaches improved to 9.2 (+/- 10.0)
days per month. The average severity was reduced to 5.1 (+/- 2.1), and the
average duration was reduced to 6.3 (+/- 11.1) hours. If daily or continuous
headaches were excluded, the improvements were more marked. Minimal side effects 
were reported from these children and their families. Long-term evaluation (156
to 415 days) showed continued sustained improvement. CONCLUSIONS: Amitriptyline
is an effective prophylactic medication for children with frequent headaches. A
standardized dosing regimen results in a significant number of children
responding with minimal side effects. The children are able to tolerate this
dosing scheme and demonstrate good adherence to a dosing schedule of once a day.

Publication Types: 
    Clinical Trial

PMID: 10940092 [PubMed - indexed for MEDLINE]

3587: Headache. 2000 Jul-Aug;40(7):521-7.

Comparative tolerability of oral 5-HT1B/1D agonists.

Fox AW.

EBD Group Inc, Carlsbad, California 92009, USA.

OBJECTIVES: To compare the relative tolerability of 5-HT1B/1D agonists and to
investigate the relationships (if any) among systemic exposure, lipophilicity,
and clinical tolerability for 5-HT1B/1D agonists. METHODS: Post hoc correlations 
were sought among the following variables: absolute dose (= administered dose x
oral bioavailability), Cmax, LogDpH7.4 (LogD), frequencies of all, neurological
and dizziness/somnolence/drowsiness adverse events, adjusted for corresponding
placebo-associated frequencies. RESULTS: For effective doses of all drugs with
available data, absolute dose-response relationships exist for adverse event
frequencies. The overall rank order of the frequency of adverse events was as
follows: naratriptan < sumatriptan = rizatriptan < zolmitriptan. With the
exception of eletriptan, 5-HT1B/1D agonists exhibit correlations between absolute
dose, Cmax (R = 0.97), and LogD (R = 0. 71). For neurological and
dizziness/somnolence/drowsiness adverse event frequencies, the overall rank order
was sumatriptan < naratriptan < rizatriptan < zolmitriptan. Neither LogD nor
absolute dose size predicted adverse event frequencies. CONCLUSIONS: Triptans may
be distinguished in terms of their tolerability. Effectiveness, absolute dose
size, and lipophilicity are related for the 5-HT1B/1D agonists considered here,
except eletriptan. Adverse event frequencies cannot be predicted from in vitro
measures of lipophilicity, in vivo estimates of absolute bioavailability, dose
size, or any combination of these variables. Since these drugs are all agonists
at 5-HT1B/1D receptors in the low nanomolar range, but differ in their
tolerability profiles, adverse effects are not likely to be mediated through
5-HT1B/1D receptors. Drugs of this class must be studied individually and on a
reasonably large scale in clinical development programs.

Publication Types: 
    Comparative Study

PMID: 10940090 [PubMed - indexed for MEDLINE]

3588: Headache. 2000 Jul-Aug;40(7):513-20.

Naratriptan efficacy in migraineurs who respond poorly to oral sumatriptan.

Stark S, Spierings EL, McNeal S, Putnam GP, Bolden-Watson CP, O'Quinn S.

Innovative Clinical Research Center, Alexandria, VA, USA.

OBJECTIVES: To determine whether 347 patients would respond to a 50-mg oral dose 
of sumatriptan, even though they considered themselves poor responders to this
acute therapy for migraine, and to investigate whether oral naratriptan can be an
effective acute therapy for migraine in the subset of patients who did not
respond to sumatriptan under double-blind, well-controlled conditions.
BACKGROUND: Although most migraineurs respond to sumatriptan, there remains a
need for an effective alternative for those who do not respond. Naratriptan is a 
more potent and more lipophilic member of this class of agent and could prove
beneficial in such patients. This is the first well-controlled study to assess
the value of another 5-HT1B/1D agonist in this difficult patient subset. METHODS:
This study comprised two migraine attacks. The first (attack 1) was a
single-blind assessment of the efficacy of sumatriptan (50 mg orally) in patients
with a history of poor response to the drug. The second (attack 2) was a
randomized, parallel group, double-blind, placebo-controlled trial of naratriptan
(2.5 mg orally) in nonresponders to oral sumatriptan. RESULTS: Attack 1: About
two thirds of this selected migraine population did not respond to sumatriptan.
Attack 2: Naratriptan was statistically superior to placebo for headache relief
at 2 hours and 4 hours, as well as for most other features of migraine attacks.
These data suggest an intrinsic efficacy of naratriptan in this patient subset
and not a coincidental response. No unexpected tolerability issues arose.
CONCLUSIONS: Naratriptan is an alternative therapy for migraineurs who respond
poorly to oral sumatriptan. No response to one "triptan" does not necessarily
predict no response to them all.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 10940089 [PubMed - indexed for MEDLINE]

3589: Platelets. 2000 Jun;11(4):222-5.

Platelet arachidonate cascade of migraineurs in the interictal phase.

Mezei Z, Kis B, Gecse A, Tajti J, Boda B, Telegdy G, Vécsei L.

Department of Pathophysiology, Albert Szent-Györgyi Medical University, Szeged,
Hungary. mezei@patph.szote.u-szeged.hu

Morphological and functional alterations of platelets in migraineurs may be
linked to the development of migraine. We examined the eicosanoid synthesis of
platelets of untreated female migraineurs in a headache-free period and compared 
it to that of age- and blood group-matched healthy female volunteers. In the
platelets of headache-free migraineurs significantly less amounts of
anti-aggregatory prostaglandin D2 and prostacyclin, as well as of
12-L-hydroxy-5,8,10-heptadecatrienoic acid (a potent endogenous inducer of
endothelial prostacyclin production) were produced, while the synthesis of
platelet aggregatory thromboxane did not differ when compared to that of healthy 
women. These results suggest that the platelet eicosanoids of migraineurs in the 
headache-free period might promote the development of cellular, vascular and
neurological events inducing headache.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 10938901 [PubMed - indexed for MEDLINE]

3590: Acta Neurol Belg. 2000 Jun;100(2):96-102.

The three responses of the blink reflex in adult and juvenile migraine.

de Tommaso M, Guido M, Libro G, Sciruicchio V, Puca F.

Interuniversity Center for the Study of Headache and Neurotransmitter Disorders
of the Central Nervous System, Perugia, Italy.

Recent theories about migraine pathogenesis have emphasized the role of the
trigeminal system in the pathogenesis of migraine attacks (Moskowitz, 1997). The 
blink reflex (BR) could be a suitable method to evaluate the trigeminal system in
migraine, as it is generally elicited by stimulation of the trigeminal ophthalmic
division (Kimura et al., 1967), involved in migraine attacks. Sixty one adult and
15 juvenile migraine without aura subjects were selected, in order to evaluate
the BR features, including the subjective perceptive and pain thresholds and the 
R1, R2 and R3 components intensity thresholds and amplitudes. The
electrophysiological procedure was carried out during the pain free phase. The
findings were compared with those of 28 healthy controls, 18 adults and 10
children. In both adult and juvenile migraine sufferers an early appearance of
the R3 response at almost the R2 threshold was observed in comparison with
age-matched controls. Unfortunately, the anatomic and physiologic organization of
the R3 component is uncertain: its early onset could suggest a dysfunction of the
inhibitory control system on the trigeminal networks, which may predispose to
migraine attacks.

PMID: 10934561 [PubMed - indexed for MEDLINE]

3591: Seizure. 2000 Jul;9(5):344-6.

Familial adult onset myoclonic epilepsy associated with migraine.

Saka E, Saygi S.

Department of Neurology, Hacettepe University Hospitals, Ankara, Turkey.

We report a new type of migraine associated epileptic syndrome in a family: adult
onset myoclonic epilepsy with benign course and migraine. Affected members of the
family had myoclonic and rare generalised tonic-clonic seizures. Most of the
patients, but not all, had a history of migraine. Also, some cases of the family 
had only migraine. This family will be discussed because of two distinct
features. Firstly, in this family a different type of epilepsy, adult onset
myoclonic epilepsy was diagnosed that has not been classified in the ILAE 1989,
classification(s), but was similar to that previously reported in Japanese
families. Secondly, in most of the cases migraine was associated with the
epilepsy. Copyright 2000 BEA Trading Ltd.

Publication Types: 
    Case Reports

PMID: 10933990 [PubMed - indexed for MEDLINE]

3592: J Neurosurg. 2000 Aug;93(2):224-8.

Headaches in patients with radiosurgically treated occipital arteriovenous
malformations.

Kurita H, Ueki K, Shin M, Kawamoto S, Sasaki T, Tago M, Kirino T.

Department of Neurosurgery, Graduate School of Medicine, University of Tokyo,
Japan. hkurita-tky@umin.ac.jp

OBJECT: The goal of this study was to determine the prevalence, characteristics, 
and radiosurgical outcomes of headaches associated with occipital arteriovenous
malformations (AVMs). METHODS: The authors reviewed the medical records of 37
consecutive patients with occipital AVMs who had been treated by radiosurgery to 
identify the radiological features of the AVMs before and after treatment and the
clinical features and outcomes of headaches described in accordance with the
criteria of the International Headache Society (IHS). Thirty-six patients (97.3%)
were followed for a mean period of 46.6 months. The median volume of the AVMs was
1.9 cm3, to which a mean radiation dose of 21.6 Gy was delivered. In the entire
study group, periodic headaches were found in 17 patients (45.9%), of whom seven 
(18.9%) suffered from migraines with the characteristic visual aura. Migraine was
predominantly found in patients with right-sided (p = 0.038) or laterally located
(p = 0.025) AVMs. Factors associated with a higher incidence of any type of
headache included larger nidus volume (p = 0.02), tortuous change of feeding
artery (p = 0.036), and cortical drainage with reflux in the superior sagittal
sinus (p = 0.032). The actuarial rate of angiographic obliteration was 71.6% at 3
years. Headaches resolved or improved in 12 (70.6%) of 17 patients, including six
(85.7%) of seven with migraine. The outcome of headache closely correlated with
the obliteration results of the AVM (p = 0.002). CONCLUSIONS: A portion of
occipital AVMs do cause headaches that satisfy the current IHS criteria for
migraine, and the prevalence varies by the topography of the lesion. Radiosurgery
can resolve headaches in the majority of treated patients.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 10930007 [PubMed - indexed for MEDLINE]

3593: Arch Fam Med. 2000 Aug;9(8):753-8.

Evaluation of migraineurs' preferences for naratriptan over conventional
first-line agents.

Powers C, Szeto S, Pangtay D, Bort T, Cervi M, Cady R.

Headache Care Center, Springfield, MO 65804, USA.

OBJECTIVE: To assess patient satisfaction with and preference for naratriptan
hydrochloride therapy over previous "nontriptan" therapy for migraines. DESIGN
AND SETTING: Open-label study conducted at 15 primary care clinics. PATIENTS: One
hundred forty-three adults meeting International Headache Society diagnostic
criteria for migraine who were not using triptans as first-line therapy for
migraines were enrolled; 115 completed the study. INTERVENTION AND OUTCOME
ASSESSMENTS: At baseline, satisfaction with current migraine therapy was
assessed. Patients were provided with naratriptan hydrochloride, 2.5 mg, to treat
3 migraines and diaries to record headache symptoms and response to treatment.
After treating 3 migraines, satisfaction with naratriptan therapy and preference 
for either previous or naratriptan therapy were assessed. RESULTS: Eighty-nine
(62%) of 143 patients had previous exposure to triptans, with lack of prescribing
(55%) as the primary reason for not continuing their use as first-line therapy.
Medications used for first-line therapy included simple analgesics (59%),
combination products (46%), and narcotics (13%). After treating 3 migraines with 
naratriptan, satisfaction with migraine therapy increased from 47% to 75%.
Sixty-three percent of patients preferred naratriptan therapy over their previous
nontriptan therapy, 27% preferred their previous therapy, and 10% had no
preference. The main reasons for preference for naratriptan therapy were
"relieves pain effectively" (86%) and "restores ability to function/perform task"
(81%). CONCLUSION: Naratriptan for first-line migraine therapy was preferred by
most patients over previous nontriptan therapy.

Publication Types: 
    Clinical Trial
    Multicenter Study
    Research Support, Non-U.S. Gov't

PMID: 10927717 [PubMed - indexed for MEDLINE]

3594: Funct Neurol. 2000 Apr-Jun;15(2):87-93.

Migraine as a complex disease: heterogeneity, comorbidity and genotype-phenotype 
interactions.

Nappi G, Costa A, Tassorelli C, Santorelli FM.

IRCCS C. Mondino Institute of Neurology, Pavia, Italy.

Migraine is a chronic illness interspersed with acute signs and symptoms which is
currently defined, according to IHS criteria, in terms of "attacks". However,
this should not lead us to ignore a critical point emerging from the simple
observation of patients, i.e. the variability of the combinations in which the
disease manifests itself in the same individual and especially in different
individuals. This heterogeneity underpins both migraine "as attacks" (e.g.
presence/absence of aura, different pain severity) and migraine "as a disease"
(e.g. different onset, occurrence, association with other diseases, evolution,
outcome). Genetic determinants are certainly at the basis of some migraine forms,
and the role of genetics is now increasing due to the better phenotypical
characterization rendered possible by the 1988 criteria. In most cases, however, 
migraine occurs as multifactorial inherited character. The level of complexity is
further increased by the effect of "modifying" genes (such as those encoding for 
dopamine receptors), by comorbidity (the non coincidental association with other 
neurological diseases), and by the fact that the expression of comorbidity varies
over time (phenotypical heterochronia). The clinical-descriptive approach allows 
only a partial understanding of migraine, the nature of which is more complex and
heterogeneous than previously thought.

Publication Types: 
    Review

PMID: 10916720 [PubMed - indexed for MEDLINE]

3595: J Accid Emerg Med. 2000 Jul;17(4):241-5.

Migraine: pharmacotherapy in the emergency department.

Kelly AM.

Department of Emergency Medicine, Western Hospital, Footscray, Australia.
Anne-Maree.Kelly@nwhcn.org.au

Migraine can be a disabling condition for the sufferer. For the small number of
patients who fail home therapy and seek treatment in an emergency department,
there are a number of therapeutic options. This paper reviews the evidence
regarding the effectiveness and safety of the following therapies: the
phenothiazines, lignocaine (lidocaine), ketorolac, the ergot alkaloids,
metoclopramide, the "triptans", haloperidol, pethidine and magnesium. Based on
available evidence, the most effective agents seem to be prochlorperazine,
chlorpromazine and sumatriptan, each of which have achieved greater then 70%
efficacy in a number of studies.

PMID: 10921808 [PubMed - indexed for MEDLINE]

3596: Arq Neuropsiquiatr. 2000 Jun;58(2B):428-30.

Naproxen sodium decreases migraine recurrence when administered with sumatriptan.

Krymchantowski AV.

Headache Center of Rio de Janeiro, Brasil. abouchkrym@openlink.com.br

Forty to 78% of the patients using sumatriptan for the acute treatment of
migraine may present recurrence at least occasionally. The concomitant use of a
NSAID (nonsteroidal anti-inflammatory drug) has been recommended to decrease the 
recurrence rate. Sixty seven patients that treated successfully 8 migraine
attacks with 100 mg of sumatritpan PO and presented recurrence in at least 5
attacks were studied prospectively. The patients received 100 mg of sumatriptan
and 550 mg of naproxen sodium PO to treat 4 consecutive moderate or severe
migraine attacks. The recurrence rate, once at least 62.5% (5 out of 8 attacks), 
decreased to 14.2% (38 out of 268 attacks) with the combination of compounds
(p<0.0001). We then studied two groups of 13 patients made randomicaly from the
67 initially evaluated, that were given sumatriptan 100 mg plus naproxen sodium
550 mg or placebo, in a double-blind design, to treat 3 other consecutive
migraine attacks. Each group of patients treated 39 attacks. The recurrence among
the patients taking sumatriptan plus placebo was 59% (23 out of 39 attacks) and
the recurrence presented by the group taking sumatriptan plus naproxen was 25.5% 
(10 out of 39 attacks) (p<0.0003). We concluded that the combination of
sumatriptan plus naproxen sodium decreases significantly migraine recurrence
presented by patients taking sumatriptan alone.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial

PMID: 10920403 [PubMed - indexed for MEDLINE]

3597: Ophthalmology. 2000 Aug;107(8):1476-8.

Recurrent isolated ptosis in presumed ophthalmoplegic migraine of childhood.

Stidham DB, Butler IJ.

Department of Ophthalmology and Visual Science, The University of Texas-Houston
Medical School, Houston, Texas, USA.

PURPOSE: To report a rare case of isolated, recurrent unilateral eyelid ptosis as
the sole manifestation of ophthalmoplegic migraine in a healthy young girl.
DESIGN: Single observational case report with review of the literature. TESTING: 
Serologic evaluation, electromyographic, nerve conduction and Tensilon testing,
magnetic resonance and computerized tomographic imaging, and magnetic resonance
angiography were performed. MAIN OUTCOME MEASURES: Four-year descriptive history 
of recurrent eyelid ptosis. RESULTS: Between 1994 and 1998, seven discrete
episodes of right upper eyelid ptosis without ophthalmoplegia or pupil
abnormality occurred. On each occasion, spontaneous resolution occurred over a
period of 6 to 10 weeks. Extensive clinical and laboratory evaluation, including 
testing for myasthenia gravis and magnetic resonance cerebral angiography, was
unremarkable. CONCLUSIONS: Recurrent isolated ptosis is a rare manifestation of
presumed ophthalmoplegic migraine in childhood. As far as we are aware, this has 
not been previously reported.

Publication Types: 
    Case Reports
    Research Support, U.S. Gov't, P.H.S.

PMID: 10919893 [PubMed - indexed for MEDLINE]

3598: Am J Otol. 2000 Jul;21(4):559-67.

Isolated directional preponderance of caloric nystagmus: I. Clinical
significance.

Halmagyi GM, Cremer PD, Anderson J, Murofushi T, Curthoys IS.

Neurology Department, Royal Prince Alfred Hospital, NSW, Sydney, Australia.

OBJECTIVES: To determine the clinical significance of an isolated directional
preponderance (DP) on bithermal caloric testing. An isolated caloric DP was
defined as a DP, calculated according to the standard Jongkees formula, of > or =
40%, with a spontaneous nystagmus (SN) in darkness of < or = 2 degrees/s and a
canal paresis (unilateral weakness) of < or = 25%. STUDY DESIGN: A retrospective 
analysis of all 15,542 bithermal caloric tests performed in the authors'
department in the previous 10 years to identify all tests with an isolated DP of 
> or = 40%. This was followed by a review of the clinical data on the 144
patients identified with such a result and then by a telephone or postal
follow-up study of these patients. The study group eventually comprised 114
patients; these were patients in whom a clinical diagnosis could be made at the
time the caloric test was done, or who responded to requests for follow-up
information. The 34 patients in whom a clinical diagnosis could not be made at
the time of the caloric test, and who did not respond to requests for follow-up
information, were excluded. STUDY SETTING: A balance disorders clinic in a
tertiary referral hospital. INTERVENTION: All patients underwent standard
bithermal caloric testing. Some of the patients also underwent rotational
testing. OUTCOME MEASURES: A clinical diagnosis for the cause of the isolated DP,
made either at the time of the caloric test or on the basis of information
supplied at follow-up by the patient or by the referring physician. RESULTS: Of
114 patients, 39 had benign paroxysmal positioning vertigo, 14 had Ménière's
disease, and 5 had migrainous vertigo. Five patients had central nervous system
(CNS) disorders, and this was clinically apparent at the time of the caloric test
in 4, so that only 1 patient with an isolated DP developed evidence of a CNS
disorder after the caloric test was done. In the other 54 patients, no definite
diagnosis could be made, but 41 of these 54 were either completely well or much
better at follow-up. CONCLUSIONS: An isolated DP on caloric testing is usually a 
transient, benign disorder. About half the patients with an isolated DP have
either Ménière's disease or benign paroxysmal positioning vertigo; in most of the
other half, no definite diagnosis is made but most of these patients will do
well. Only approximately 5% have a CNS lesion and in almost all this is apparent 
at the time the caloric test is done. In a relapsing-remitting peripheral
vestibular disorder such as benign paroxysmal positioning vertigo or Ménière's
disease, the mechanism of an isolated DP could be enhanced dynamic gain of
ipsilesional medial vestibular nucleus neurons, perhaps as a result of
intermittent hyperfunction of primary semicircular canal vestibular afferents.
The authors postulate that an isolated DP reflects a gain asymmetry between
neurons in the medial vestibular nucleus on either side, caused either by
increased sensitivity on one side or by reduced sensitivity on the other, perhaps
as an adaptive change in response to abnormal input. In an accompanying article, 
the authors implement a realistic neural network model in which it is possible to
simulate an isolated DP by adjusting the dynamic sensitivity of type 1 medial
vestibular nucleus neurons on one side or of type 2 medial vestibular nucleus
neurons on the other.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 10912703 [PubMed - indexed for MEDLINE]

3599: Geriatrics. 2000 Jul;55(7):70-4.

Migraine in older patients: a case report and management strategies.

Rankin LM, Bruhl M.

University of Iowa, Des Moines, USA.

Older patients can suffer from various forms of migraine. These patients should
be educated regarding triggers and considered for prophylactic and acute
treatments for frequent episodes. Practitioners should keep in mind the unique
challenges of treating migraine in older persons and first search for other
serious yet treatable causes for headache in these patients.

Publication Types: 
    Case Reports

PMID: 10909408 [PubMed - indexed for MEDLINE]

3600: Obstet Gynecol. 2000 Aug;96(2):237-42.

Rizatriptan in the treatment of menstrual migraine.

Silberstein SD, Massiou H, Le Jeunne C, Johnson-Pratt L, McCarroll KA, Lines CR.

Jefferson Headache Center, Thomas Jefferson University Hospital, Philadelphia,
Pennsylvania, USA.

OBJECTIVE: To determine the efficacy of oral rizatriptan 10 mg and 5 mg for
treating menstrually associated migraine attacks. METHODS: Data from two large
clinical trials with identical designs were included in a retrospective analysis.
The studies were randomized, double-masked, placebo-controlled, incomplete block,
two-period, crossover designs. Women with migraines were randomly assigned to one
of five treatment sequences for the treatment of two migraine attacks. Only data 
from the first attack in women with migraines who were treated with rizatriptan
or placebo were included in the analysis. A menstrually associated attack was
defined as one that occurred within 3 days before or after the onset of the last 
menstrual period. RESULTS: In the subgroup of 335 women with menstrually
associated migraine, rizatriptan was effective compared with placebo. At 2 hours 
after dosing, 68% of 139 women taking rizatriptan 10 mg and 70% of 115 women
taking rizatriptan 5 mg with a menstrually associated migraine had pain relief
compared with 44% of 81 patients taking placebo (P <.05). In all women,
rizatriptan was as effective in treating menstrual as well as nonmenstrual
migraine: 68% of 139 patients taking rizatriptan 10 mg with a menstrually
associated migraine had pain relief at 2 hours after dosing compared with 69% of 
393 patients with nonmenstrually associated attacks (test of menstrual
association = nonsignificant; the analysis had 80% power to detect a difference
of six percentage points between groups). Similar results were found for
rizatriptan 5 mg (menstrual = 70%, nonmenstrual = 66%; not statistically
significant). CONCLUSION: Rizatriptan is effective in the treatment of
menstrually associated migraine attacks.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 10908770 [PubMed - indexed for MEDLINE]

3601: Cochrane Database Syst Rev. 2000;(3):CD002286.

Update in:
    Cochrane Database Syst Rev. 2004;(1):CD002286.

Feverfew for preventing migraine.

Pittler MH, Vogler BK, Ernst E.

Department of Complementary Medicine, School of Postgraduate Medicine & Health
Sciences, University of Exeter, United Kingdom, 25 Victoria Park Road, Exeter,
Devon, UK, EX2 4NT. M.H.Pittler@exeter.ac.uk

BACKGROUND: Feverfew (Tanacetum parthenium L.) is a popular herbal remedy for
migraine. OBJECTIVES: To systematically review the evidence for or against the
efficacy of feverfew versus placebo for the prevention of migraine. SEARCH
STRATEGY: Electronic literature searches were performed using the databases
CISCOM (Research Council for Complementary Medicine, London, UK), MEDLINE,
EMBASE, Biosis and the Cochrane Library (each from its inception to April 1998). 
Manufacturers were contacted and the bibliographies of identified articles
checked for further trials. SELECTION CRITERIA: Randomised, placebo-controlled,
double-blind trials assessing the efficacy of feverfew for preventing migraine
were included. No restrictions regarding the language of publication were
imposed. DATA COLLECTION AND ANALYSIS: Data on patients, interventions, methods, 
outcomes and results were extracted in a pre-defined, standardised manner.
Methodological quality was evaluated using the scoring system developed by Jadad 
and colleagues. Both data extraction and the assessment of methodological quality
were performed independently by two reviewers. MAIN RESULTS: Four trials met the 
inclusion criteria. The majority of these trials suggested beneficial effects of 
feverfew compared with placebo. However, the trial with the highest
methodological quality, which was also among the largest, found no significant
difference between feverfew and placebo. REVIEWER'S CONCLUSIONS: The efficacy of 
feverfew for the prevention of migraine has not been established beyond
reasonable doubt.

Publication Types: 
    Review

PMID: 10908545 [PubMed - indexed for MEDLINE]

3602: Brain. 2000 Aug;123 ( Pt 8):1703-9.

The development of cutaneous allodynia during a migraine attack clinical evidence
for the sequential recruitment of spinal and supraspinal nociceptive neurons in
migraine.

Burstein R, Cutrer MF, Yarnitsky D.

Department of Anesthesia and Critical Care, Harvard Medical School, Boston, MA
02115, USA. rburstei@caregroup.harvard.edu

Recently, we showed that most migraine patients exhibit cutaneous allodynia
inside and outside their pain-referred areas when examined during a fully
developed migraine attack. In this report, we studied the way in which cutaneous 
allodynia develops by measuring the pain thresholds in the head and forearms
bilaterally at several time points during a migraine attack in a 42-year-old
male. Prior to the headache, he experienced visual, sensory, motor and speech
aura. During the headache, he experienced photo-, phono- and odour-phobia, nausea
and vomiting, worsening of the headache by coughing or moving his head, and
cutaneous pain when shaving, combing his hair or touching his scalp. Comparisons 
between his pain thresholds in the absence of migraine and at 1, 2 and 4 h after 
the onset of migraine revealed the following. (i) After 1 h, mechanical and cold 
allodynia started to develop in the ipsilateral head but not in any other site.
(ii) After 2 h, this allodynia increased on the ipsilateral head and spread to
the contralateral head and ipsilateral forearm. (iii) After 4 h, heat allodynia
was also detected while mechanical and cold allodynia continued to increase.
These clinical observations suggest the following sequence of events along the
trigeminovascular pain pathway of this patient. (i) A few minutes after the
initial activation of his peripheral nociceptors, they became sensitized; this
sensitization can mediate the symptoms of intracranial hypersensitivity. (ii) The
barrage of impulses that came from the peripheral nociceptors activated
second-order neurons and initiated their sensitization; this sensitization can
mediate the development of cutaneous allodynia on the ipsilateral head. (iii) The
barrage of impulses that came from the sensitized second-order neurons activated 
and eventually sensitized third-order neurons; this sensitization can mediate the
development of cutaneous allodynia on the contralateral head and ipsilateral
forearm at the 2-h point, over 1 h after the appearance of allodynia on the
ipsilateral head. This interpretation calls for an early use of anti-migraine
drugs that target peripheral nociceptors, before the development of central
sensitization. If central sensitization develops, the therapeutic rationale is to
suppress it. Because currently available drugs that aim to suppress central
sensitization are ineffective, this study stresses the need to develop them for
the treatment of migraine.

Publication Types: 
    Case Reports
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 10908199 [PubMed - indexed for MEDLINE]

3603: Neurosci Lett. 2000 Jul 28;289(1):57-60.

Zolmitriptan reverses blink reflex changes induced during the migraine attack in 
humans.

de Tommaso M, Guido M, Libro G, Sciruicchio V, Puca F.

Interuniversity Center for the Study of Headache and Neurotransmitter Disorders
of the Central Nervous System, Perugia, Roma, Sassari, Bari, Napoli, Firenze,
Italy. ipnobari@cimedoc.uniba.it

The question about the 5-hydroxytryptamine (5-HT)(1B-1D) receptors agonists, if
the clinical efficacy in migraine attacks is linked with the action at the
central level or at the peripheral one, is still unresolved. We evaluated the
effects of zolmitriptan and sumatriptan on blink reflex in thirty migraine
without aura patients during the attacks in order to assess the central action on
the trigeminal system. Both drugs were effective in reducing headache severity
compared to placebo. In the migraine attack an increased area of the R3 component
on the pain side was observed; it was suppressed by zolmitriptan, which confirmed
its action on the central trigeminal circuits, though the clinical relevance of
this effect could be questioned.

PMID: 10899408 [PubMed - indexed for MEDLINE]

3604: Neurology. 2000 Jul 12;55(1):141-3.

Survey of migraineurs referred to headache specialists: care, satisfaction, and
outcomes.

Hu XH, O'Donnell F, Kunkel RS, Gerard G, Markson LE, Berger ML.

Outcomes Research & Management, US Human Health, Merck & Co., Inc., West Point,
PA, USA.

The authors report a survey of 281 migraineurs recently referred to headache
specialists by primary care physicians. Compared with care before referral,
specialists spent substantially more time with patients and were more likely to
ask patients to take a prophylactic drug and to keep a headache diary, to discuss
migraine triggers, and to prescribe 5-hydroxytryptamine1B/1D agonists (triptans).
After referral, patients reported improved satisfaction with care and significant
decreases in frequency, duration, and severity of attacks.

PMID: 10891927 [PubMed - indexed for MEDLINE]

3605: Neurology. 2000 Jul 12;55(1):139-41.

Aura in some patients with familial hemiplegic migraine can be stopped by
intranasal ketamine.

Kaube H, Herzog J, Käufer T, Dichgans M, Diener HC.

Institute of Neurology, The National Hospital for Neurology and Neurosurgery,
Queen Square, London, UK.

Migraine aura is probably caused by cortical-spreading depression. No treatment
for acute and severe migraine aura has been described previously. The effect of
ketamine (25 mg intranasally) was studied in 11 patients with severe, disabling
auras resulting from familial hemiplegic migraine. In five patients ketamine
reproducibly reduced the severity and duration of the neurologic deficits,
whereas in the remaining six patients no beneficial effect was seen. Ketamine
offers, for the first time, a possible treatment option for severe and prolonged 
aura.

PMID: 10891926 [PubMed - indexed for MEDLINE]

3606: Neurology. 2000 Jul 12;55(1):136-9.

The serotonergic agent m-chlorophenylpiperazine induces migraine attacks: A
controlled study.

Leone M, Attanasio A, Croci D, Filippini G, D'Amico D, Grazzi L, Nespolo A,
Bussone G.

Istituto Nazionale Neurologico Carlo Besta, Milan, Italy.

In a double-blind study versus placebo, the serotonergic agent
m-chlorophenylpiperazine (mCPP) was administered to 20 healthy control subjects
and 19 migraineurs to investigate the ability of mCPP (0.5 mg/kg) to induce
typical migraine attacks. In the following 24 hours there were more migraines
after mCPP than after placebo in both groups. These findings are consistent with 
involvement of 5HT2B,2C,1A receptor subtypes in the pathophysiology of migraine.

Publication Types: 
    Clinical Trial
    Controlled Clinical Trial

PMID: 10891925 [PubMed - indexed for MEDLINE]

3607: Neurology. 2000 Jul 12;55(1):95-9.

Effect of naratriptan on myocardial blood flow and coronary vasodilator reserve
in migraineurs.

Gnecchi-Ruscone T, Bernard X, Pierre P, Anderson D, Legg N, Enahoro H, Winter PD,
Crisp A, Melin JA, Camici PG.

MRC Cyclotron Unit and Department of Neurology, Imperial College School of
Medicine, Hammersmith Hospital, London, UK.

BACKGROUND: Migraine drugs can produce adverse cardiac effects. The authors have 
demonstrated previously that ergotamine can lead to a significant reduction of
hyperemic myocardial blood flow, but little is known about the effect of the
newer serotonin analogues. Coronary artery constriction caused by serotonin or
its analogues is mediated mainly by 5HT2 receptors. The selective 5HT1B/1D
agonist naratriptan has no significant activity at 5HT2 receptors; however, like 
all 5HT1B/1D agonists developed for the acute treatment of migraine, naratriptan 
could potentially constrict coronary arteries by activation of 5HT1B receptors.
METHODS: The effects on myocardial blood flow of subcutaneous naratriptan 1.5 mg 
compared with placebo were assessed under resting and hyperemic conditions with
PET using oxygen-15 labeled water during two separate visits. This study was a
randomized, double-blind, placebo-controlled crossover trial in 34 migraine
subjects with no evidence of ischemic heart disease, studied outside a migraine
attack. RESULTS: Naratriptan did not differ significantly from placebo in its
effects on resting myocardial blood flow, but did evoke a small, significant fall
in hyperemic myocardial blood flow (-13% versus placebo) and an increase in
hyperemic coronary resistance (+19% versus placebo) without any signs or symptoms
suggestive of myocardial ischemia. Naratriptan did not significantly affect the
coronary vasodilator reserve (hyperemic/resting blood flow) compared with
placebo. CONCLUSIONS: These results show that at therapeutic doses, naratriptan
exerts only a minor effect on myocardial blood flow, coronary vasodilator
reserve, or coronary resistance among subjects with no evidence of ischemic heart
disease. These results should not be extrapolated to patients with coronary
artery disease, in whom all 5HT1 agonists for migraine are contraindicated.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial

PMID: 10891912 [PubMed - indexed for MEDLINE]

3608: Pediatr Emerg Care. 2000 Jun;16(3):196-201; quiz 203.

Emergency department management of pediatric migraine.

Bulloch B, Tenenbein M.

Department of Pediatrics, Winnipeg Children's Hospital, Manitoba, Canada.

Migraine is a common pediatric emergency department problem. Since its
pathophysiology is unclear and possibly multifactorial, a single treatment
strategy is unlikely to be successful for all patients. A specific treatment that
has been successful for a particular patient should be strongly considered.
Otherwise, it is best to start with simple therapies such as acetaminophen,
aspirin, or an NSAID if not already tried at home. For patients requiring more
specific therapy, reasonable choices would be dihydroergotamine or a dopamine
antagonist such as prochlorperazine. There are several newer agents studied in
adults with examples being sumatriptan and naratriptan. These probably have a
role in the adolescent and should be considered in the younger age group when
other therapies have failed. When the headache has been prolonged, dexamethasone 
may be useful in decreasing inflammation and relieving pain. As illustrated in
many of the above studies, monotherapy is often inadequate in achieving complete 
relief of headache pain in all patients. Most of the drugs discussed here address
only one of the three etiologies thought to be involved in migraine pathogenesis,
namely; the dopaminergic system. the serotonin system or inflammation.
Presumably, therapy directed toward more than one of these etiologies at the same
time may be more effective (11).

Publication Types: 
    Review

PMID: 10888462 [PubMed - indexed for MEDLINE]

3609: J Clin Pharmacol. 2000 Jul;40(7):687-700.

Comment in:
    J Clin Pharmacol. 2002 Nov;42(11):1281-2; author reply 1282-3.

Current and emerging second-generation triptans in acute migraine therapy: a
comparative review.

Deleu D, Hanssens Y.

Department of Clinical Pharmacology, College of Medicine, Sultan Qaboos
University Hospital, Sultanate of Oman.

Sterile neurogenic inflammation within cephalic tissue, involving vasodilation
and plasma protein extravasation, has been proposed as a pathophysiological
mechanism in acute migraine. The action of 5-hydroxytryptamine (5-HT1B/1D)
agonists--so-called triptans--on receptors located in meningeal arteries (5-HT1B)
and trigeminovascular fiber endings (5-HT1D) has an inhibitory effect on this
neurogenic inflammation. Recently, a series of second-generation 5-HT1B/1D
agonists (almotriptan, eletriptan, frovatriptan, naratriptan, rizatriptan, and
zolmitriptan) have been developed and are reviewed in this article. Their in
vitro pharmacological properties, pharmacokinetics, clinical efficacy, drug
interactions, and adverse effects are evaluated and compared to the golden
standard in the treatment of acute migraine, sumatriptan.

Publication Types: 
    Comparative Study
    Review

PMID: 10883409 [PubMed - indexed for MEDLINE]

3610: Acta Neurol Scand. 2000 Jun;101(6):413-6.

Macrosomatognosia and microsomatognosia in migraine art.

Robinson D, Podoll K.

Department of Psychiatry and Psychotherapy, University of Technology, Aachen,
Germany.

OBJECTIVES: To study macrosomatognosia and microsomatognosia occurring as
migraine aura symptoms. MATERIAL AND METHODS: Topological distribution of these
body schema disturbances were assessed in a collection of 562 pictures submitted 
as entries to the 4 national Migraine Art competitions. RESULTS: The said
symptoms were illustrated by 18 artists. Macrosomatognosia was encountered more
frequently than microsomatognosia and applied more often to single parts of the
body, whereas microsomatognosia mostly affected the entire body. In partial
macrosomatognosia, the head and upper extremities were the body parts most
frequently involved, paralleling the extension of their representation in the
sensory maps of the human brain. CONCLUSIONS: The conscious perceptual
experiences of whole body macro- and microsomatognosia argue in favour of the
existence of an integrative neuronal network mediating whole body perception.
Partial macro- and microsomatognosia suggest a reversible modification of
cerebral maps of somatosensation during the migraine aura.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 10877160 [PubMed - indexed for MEDLINE]

3611: Semin Neurol. 2000;20(1):145-9.

Random comments: neurologists and neuro-ophthalmology; the "ocular motor" system;
and update on ophthalmoplegic migraine.

Daroff RB.

Department of Neurology, University Hospitals of Cleveland, OH 44106-5015, USA.

In this brief commentary, I recount the entry of neurologists into the field of
neuro-ophthalmology, which was previously regarded as exclusively within the
purview of ophthalmology. I then quickly describe the difference between
"oculomotor" and "ocular motor," before summarizing "ophthalmoplegic migraine," a
rare condition with a rich history that engendered a heated debate among
legendary neurological luminaries in 1946.

Publication Types: 
    Historical Article
    Portraits

PMID: 10874784 [PubMed - indexed for MEDLINE]

3612: Curr Opin Neurol. 2000 Jun;13(3):273-6.

Migraine: imaging the aura.

Aurora SK, Welch KM.

Neurophysiology Laboratory, Henry Ford Hospital, Detroit, Michigan 48202, USA.
sheaur@neuro.hfh.edu

We currently conceive of a migraine attack as originating in the brain. Triggers 
of an attack initiate a depolarizing neuroelectric and metabolic event likened to
the spreading depression of Leao. This event activates the headache and
associated features of the attack by mechanisms that remain to be determined, but
appear to involve either peripheral trigeminovascular or brainstem pathways, or
both. The excitability of cell membranes, perhaps partly genetically determined, 
is the brain's susceptibility to attacks. Factors that increase or decrease
neuronal excitability constitute the threshold for triggering attacks. Using a
model of visual stress-induced migraine or by studying spontaneous attacks and
applying advanced imaging and neurophysiological methods, results have been
obtained that support spreading neuronal inhibition as the basis of aura. This
neuroelectric event is accompanied by hyperoxia of the brain, possibly associated
with vasodilation. Evidence has also been obtained that the spreading cortical
event can activate the subcortical centers possibly involved in nociception and
associated symptoms of the migraine attack. Susceptibility to migraine attacks
appears to be related to brain hyperexcitability. These newer techniques of
functional neuroimaging have confirmed the primary neural basis of the migraine
attack with secondary vascular changes, reconciling previous theories into a
neurovascular mechanism.

Publication Types: 
    Review

PMID: 10871250 [PubMed - indexed for MEDLINE]

3613: Brain Res. 2000 Jul 7;870(1-2):44-53.

Sumatriptan modifies cortical free radical release during cortical spreading
depression. A novel antimigraine action for sumatriptan?

Read SJ, Parsons AA.

Neuroscience Research, SmithKline Beecham Pharmaceuticals, Third Avenue, Harlow, 
CM19 5AW, Essex, UK.

Increases in concentration of brain NO are proposed to initiate and mediate
migraine headache. Triggered by focal depolarisation, spreading depression (SD)
represents a suitable mechanism for eliciting widespread release of nitric oxide.
The current study examines the effect of sumatriptan, a 5-HT(1B/1D) agonist and
effective antimigraine therapy, on free radical release (nitric oxide and
superoxide) in SD in the simple and complex cortices of the rat and cat.
Following initiation of SD, sumatriptan pretreatment (300 microg kg(-1) i.v., 15 
min prior to SD) modulated all phases of nitric oxide release associated with
each SD in both cats and rats. As a result, superoxide levels were observed to
significantly (ANOVA, post hoc LSD) increase versus vehicle treated animals
(saline 1 ml kg(-1) i.v. 15 min prior to SD) during specific phases of each SD
depolarisation. Averaged over all SD depolarisations, mean peak SD nitric oxide
levels per depolarisation were 0.73+/-0.23 microM (n=29) in cats, and 0.42+/-0.09
microM (n=34) in rats. Sumatriptan significantly (Students t-test, P<0.05, two
tailed hypothesis, P<0.05) modulated this increase in cortical nitric oxide
concentrations to 0.32+/-0.06 microM (n=25) and 0. 22+/-0.07 microM (n=37) in
cats and rats. Sumatriptan appears to decrease the amplitude of nitric oxide
release but enhances extracellular superoxide concentrations in both
lissencephalic and gyrencephalic cortices during SD.

PMID: 10869500 [PubMed - indexed for MEDLINE]

3614: Bioorg Med Chem Lett. 2000 May 1;10(9):903-5.

5-Thienyltryptamine derivatives as serotonin 5-HT1B/1D receptor agonists:
potential treatments for migraine.

Meng CQ, Rakhit S, Lee DK, Kamboj R, McCallum KL, Mazzocco L, Dyne K, Slassi A.

NPS Allelix Corp., Mississauga, Ontario, Canada. cmeng@atherogenics.com

A series of 5-(2- or 3-thienyl)tryptamine derivatives (9) has been synthesized
and shown to be potent and selective 5-HT1D versus 5-HT1B receptor agonists and, 
therefore, potential treatments for migraine.

PMID: 10853656 [PubMed - indexed for MEDLINE]

3615: Headache. 2000 Jun;40(6):487-90.

Comment in:
    Headache. 2001 Mar;41(3):326-8.

Migraine-associated seizure: a case of reversible MRI abnormalities and
persistent nondominant hemisphere syndrome.

Friedenberg S, Dodick DW.

Department of Neurology, Mayo Clinic Scottsdale, AZ 85259, USA.

The complex relationship between migraine and epilepsy is highlighted by the
occurrence of a seizure during a migraine attack without aura. This phenomenon,
referred to as migralepsy, suggests an inherent overlap in the underlying
pathophysiology of these events. We report the case of a patient who had a
generalized seizure, persistent nondominant hemisphere syndrome, and reversible
magnetic resonance imaging abnormalities during a prolonged migraine attack
without aura.

Publication Types: 
    Case Reports

PMID: 10849047 [PubMed - indexed for MEDLINE]

3616: Headache. 2000 Jun;40(6):483-6.

LASH: a syndrome of long-lasting autonomic symptoms with hemicrania (A new
indomethacin- responsive headache).

Rozen TD.

Thomas Jefferson University Hospital/Jefferson Headache Center, Philadelphia, PA 
19107, USA.

A patient presented with a unique, stereotypical, episodic headache disorder
marked by long-lasting autonomic symptoms with associated hemicrania (LASH). The 
autonomic symptoms clearly overshadowed the headache as the major component of
the syndrome. Indomethacin controlled both the autonomic symptoms and the
headache, suggesting that this is a new type of indomethacin-responsive headache.
It may also complete the indomethacin-responsive headache spectrum.

Publication Types: 
    Case Reports

PMID: 10849046 [PubMed - indexed for MEDLINE]

3617: Headache. 2000 Jun;40(6):473-9.

Prevalence of migraine, tension-type headache, and other headaches in Hong Kong.

Cheung RT.

Division of Neurology, University Department of Medicine, The University of Hong 
Kong, Queen Mary Hospital, Pokfulam.

OBJECTIVE: To assess the prevalence of migraine and other headaches in Hong Kong 
in 1998. BACKGROUND: A community-based prevalence survey of headache was carried 
out from July 1992 to March 1993, and the prevalence rates were 1% for migraine, 
2% for tension-type headache, and 1% for other headaches. A similar survey was
carried out in May and June 1998 to interview individuals aged 15 years or older.
Recurrent headache was defined as having two or more headaches unrelated either
to influenza or a common cold within the past 12 months. METHODS: Respondents
with recurrent headache were offered a personal interview for clinical
validation. Of 3156 randomly selected individuals, 1436 responded. RESULTS:
Headache was due to influenza or a common cold in 270 (18.8%) respondents;
recurrent headache affected 533 (37.1%) respondents. The overall prevalence rates
were 4.7% for migraine, 26.9% for tension-type headache, and 5.5% for other
headaches. Clinical validation was available for 72 respondents. After adjustment
for possible misclassification, the estimated prevalence rates became 12.5% for
migraine, 18.7% for tension-type headache, and 6.0% for other headaches. There
was a female preponderance for all types of headache with a peak in the 25- to
34-year-age group for tension-type headache. CONCLUSIONS: All types of headache
were more common in the 1998 study, and the prevalence rates were closer to those
of Western communities.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 10849044 [PubMed - indexed for MEDLINE]

3618: Headache. 2000 Jun;40(6):464-5.

Treatment of nonresponders to oral sumatriptan with zolmitriptan and rizatriptan:
a comparative open trial.

Mathew NT, Kailasam J, Gentry P, Chernyshev O.

Houston, Headache Clinic, TX 77004, USA.

In order to study the effect of zolmitriptan and rizatriptan in oral sumatriptan 
nonresponders (defined as lack of response in three or more of five attacks), 56 
patients were studied in an open trial in a crossover fashion. Both zolmitriptan,
5 mg, and rizatriptan, 10 mg, were effective in the majority of sumatriptan
nonresponders. The response to rizatriptan, 10 mg, appeared to be better than to 
zolmitriptan, 5 mg. Approximately 19% of sumatriptan nonresponders remained
nonresponders to both zolmitriptan and rizatriptan.

Publication Types: 
    Clinical Trial
    Comparative Study
    Controlled Clinical Trial

PMID: 10849042 [PubMed - indexed for MEDLINE]

3619: Headache. 2000 Jun;40(6):457-63.

Cosinor analysis of heart rate variability in ambulatory migraineurs.

Tabata M, Takeshima T, Burioka N, Nomura T, Ishizaki K, Mori N, Kowa H, Nakashima
K.

Division of Neurology, Institute of Neurological Sciences, Tottori University
Faculty of Medicine, Yonago, Japan.

OBJECTIVE: To clarify whether the circadian rhythm of heart rate variability
parameters can be identified in patients with migraine during a headache-free
period and to identify any specific pattern of the circadian rhythm of heart rate
variability, using time-domain and spectral analysis and cosinor rhythm analysis 
of heart rate variability during normal daily activity. METHODS: Forty-eight-hour
Holter electrocardiograms were recorded for 27 patients with migraine during
headache-free periods and 24 healthy controls during free activity. The circadian
rhythms of heart rate fluctuation parameters, that is, mean interval, standard
deviation, root-mean-square successive differences (RMSSD), %RR50, and low (0.
020 to 0.150 Hz) and high frequency (0.150 to 0.400 Hz) heart rate fluctuations
were analyzed with the group mean cosinor method. RESULTS: The group mean cosinor
analysis and the acrophase-amplitude analysis demonstrated significant
differences in circadian rhythm in SD, RMSSD, %RR50, and high frequency between
the group with migraine and controls. The amplitudes of SD, RMSSD, %RR50, and
high frequency in the group with migraine were smaller than those in controls,
which implied parasympathetic hypofunction in migraineurs. There were no
significant differences in the MESOR (midline estimating statistic of rhythms) of
the analyzed heart rate parameters except for low frequency. The MESOR of low
frequency in the migraineurs was significantly smaller than that in the controls.
CONCLUSIONS: Patients with migraine have hypofunction in the parasympathetic
nervous system during normal daily activity in the headache-free period.

PMID: 10849041 [PubMed - indexed for MEDLINE]

3620: Headache. 2000 Jun;40(6):445-50.

Comment in:
    Headache. 2001 Jun;41(6):606.    Headache. 2001 Jun;41(6):607.

Botulinum toxin type A as a migraine preventive treatment. For the BOTOX Migraine
Clinical Research Group.

Silberstein S, Mathew N, Saper J, Jenkins S.

Thomas Jefferson University School of Medicine, Philadelphia, PA, USA.

OBJECTIVE: To assess the safety and efficacy of botulinum toxin type A (BOTOX;
Allergan, Inc) in the prevention of migraine. BACKGROUND: Current migraine
preventive therapies are often unsatisfactory because of their limited efficacy, 
adverse effects, and drug interactions. Botulinum toxin type A injections often
reduce the pain associated with conditions such as cervical dystonia, achalasia, 
rectal fissures, and myofascial pain syndrome. An open-label, noncontrolled study
of botulinum toxin type A suggested benefits for patients with migraine. DESIGN
AND METHODS: This was a double-blind, vehicle-controlled study of 123 subjects
with a history of two to eight moderate-to-severe migraine attacks per month,
with or without aura. Participants were randomized to receive single
administrations of vehicle or botulinum toxin type A, 25 U or 75 U, injected into
multiple sites of pericranial muscles at the same visit. During a 1-month
baseline period and for 3 months following injection, subjects kept daily diaries
in which they recorded migraine frequency, migraine severity, and the occurrence 
of migraine-associated symptoms. RESULTS: Compared with vehicle treatment,
subjects in the 25-U botulinum toxin type A treatment group showed significantly 
fewer migraine attacks per month, a reduced maximum severity of migraines, a
reduced number of days using acute migraine medications, and reduced incidence of
migraine-associated vomiting. Both the 25-U and 75-U botulinum toxin type A
groups were significantly better than the vehicle group on subject global
assessment. Botulinum toxin A treatment was well tolerated, with only the 75-U
treatment group exhibiting a significantly higher rate of treatment-related
adverse events than vehicle. CONCLUSIONS: Pericranial injection of botulinum
toxin type A, 25 U, was found to be a safe treatment that significantly reduced
migraine frequency, migraine severity, acute medication usage, and associated
vomiting.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 10849039 [PubMed - indexed for MEDLINE]

3621: Headache. 2000 May;40(5):389-92.

Comment in:
    Headache. 2001 Jan;41(1):102.

Daily migraine with aura: a new migraine variant.

Merims D, Kuritzky A.

Department of Neurology, Rabin Medical Center, Petach-Tikva, Israel.

The frequency of migraine attacks is not used as a diagnostic criterion, however,
it is a very important factor in the evaluation of migraine severity and its
treatment. Several studies report the frequency of migraine attacks using the
International Headache Society criteria. No investigator, however, has reported
daily migraine attacks. In the current report, we present five patients whose
headaches transformed from episodic migraine to daily migraine with aura. To the 
best of our knowledge, this is the first description of this variant of migraine.
The symptoms in all the patients described comply strictly with the International
Headache Society criteria for the diagnosis of migraine with typical aura. An
interesting additional observation concerns the beneficial effect of phenytoin, a
drug that has not proved to be effective in migraine but showed some efficacy in 
our patients.

Publication Types: 
    Case Reports

PMID: 10849034 [PubMed - indexed for MEDLINE]

3622: Headache. 2000 May;40(5):384-8.

Influence of disease duration on visual evoked potentials in migraineurs.

Yücesan C, Sener O, Mutluer N.

Ankara University Faculty of Medicine, Department of Neurology, Turkey.

OBJECTIVE: To determine the possible influence of the duration of migraine on
pattern-reversal visual evoked potentials. METHODS: An investigation was
conducted in 49 patients with migraine without aura according to the
International Headache Society criteria. Twenty-two of these patients had had
migraine for 2 years or less (group 1), and the other 27 patients had had the
disease for 10 years or more (group 2). The control group consisted of 17 healthy
subjects. RESULTS: Comparison of the mean P100 latency and amplitude showed no
significant difference among the groups. There was, however, a good negative
correlation between age and latency (r = -0.59, P =.003) in group 1, but no such 
correlation was observed for group 2 or the control group. CONCLUSIONS: It was
concluded that the duration of migraine has no influence on pattern-reversal
visual evoked potentials and that the pathogenesis of early- and late-onset
migraine may be different.

Publication Types: 
    Clinical Trial
    Controlled Clinical Trial

PMID: 10849033 [PubMed - indexed for MEDLINE]

3623: Headache. 2000 May;40(5):377-83.

Behavioral self-management in an inpatient headache treatment unit: increasing
adherence and relationship to changes in affective distress.

Hoodin F, Brines BJ, Lake AE 3rd, Wilson J, Saper JR.

Head Pain Treatment Unit at Chelsea Community Hospital, Michigan, USA.

OBJECTIVE: To evaluate prospectively the contribution of a psychological
self-management program to the amelioration of headache-related distress of
patients with intractable migraine treated in a comprehensive, multidisciplinary,
inpatient program. BACKGROUND: Previous research has shown the effectiveness of
this overall inpatient program but did not examine the relationships between the 
use of relaxation and other headache-related behavioral factors. METHODS: Data
from 221 admissions to a Commission on Accreditation of Rehabilitation
Facilities-accredited, nationally recognized, inpatient treatment unit were
analyzed for the current study. On admission and on discharge (average length of 
stay, 12.9 days), subjects completed a 7-day retrospective, self-report
questionnaire assessing health behavior compliance and emotional factors. The
intervention consisted of intensive medical therapy in addition to
cognitive-behavioral treatment delivered in a group setting. RESULTS: Adherence
increased significantly for relaxation practice and life-style modifications of
diet, exercise, and sleep regulation for headache prevention (P<.00001). Beck
Depression Inventory scores decreased significantly (P<.00001), and a greater
decrease in depression by the end of the program was reported by subjects who
practiced relaxation most compared with those who practiced relaxation least.
CONCLUSIONS: Low baseline adherence rates for health behavior increased
significantly during the final week of inpatient treatment. Behavioral
self-management variables, not headache reduction, were significantly associated 
with patients' reduction in affective distress.

PMID: 10849032 [PubMed - indexed for MEDLINE]

3624: Headache. 2000 May;40(5):371-2.

Rizatriptan tablet versus wafer: patient preference.

Adelman JU, Mannix LK, Von Seggern RL.

Headache Wellness Center, Greensboro, NC 27403, USA.

After taking both conventional oral rizatriptan tablets and oral disintegrating
rizatriptan tablets in the treatment of migraine with or without aura, patients
were permitted to select their formulation preference. All adult patients who had
requested continuation of rizatriptan during a 6-month period were included in
the study. Of the 367 patients studied, 188 selected the oral disintegrating
tablet, while 179 preferred the conventional tablet. Although individual patients
had strong preferences for one preparation over the other, no group preference
was found.

Publication Types: 
    Comparative Study

PMID: 10849030 [PubMed - indexed for MEDLINE]

3625: Clin Electroencephalogr. 2000 Apr;31(2):83-7.

Investigation of the cerebral response to flicker stimulation in patients with
headache.

Chorlton P, Kane N.

Grey Walter Department of Neurophysiology, Frenchay Hospital, Bristol, U.K.

Migraine affects 10% of the population, yet there is no proven diagnostic test.
To date the most promising neurophysiological diagnostic technique has been the
analysis of cerebral responses to photic stimulation or flicker (the "H"
response). This test has proved to be sensitive in patients with "classic"
migraine, but has not been re-evaluated since the introduction of the 1988
International Headache Society (IHS) classification system. In 33 migraineurs, we
found that the "H" response was sensitive (86.4%) and specific (97.5%) in those
with migraine defined according to IHS Committee as type 1.2.1 (typical aura) and
type 1.1 (without aura), but not in basilar migraine (1.2.4).

PMID: 10840630 [PubMed - indexed for MEDLINE]

3626: Clin Electroencephalogr. 2000 Apr;31(2):76-82.

Electroclinical features in children and adolescents with epilepsy and/or
migraine, and occipital epileptiform EEG abnormalities.

Brinciotti M, Di Sabato ML, Matricardi M, Guidetti V.

Dipartimento di Scienze Neurologiche e Psichiatriche dell'Età Evolutiva,
University La Sapienza, Rome, Italy.

This study attempted to better define clinical and EEG features for differential 
diagnosis between epilepsy and migraine in children with occipital epileptiform
EEG abnormalities. We studied 126 children (57 males, 69 females; age 4-18 years)
suffering from epilepsy (63), migraine (43) or both (20). Patients were selected 
because of the presence of epileptiform abnormalities in the occipital regions on
their EEG at rest. Differences among groups were statistically analyzed (Pearson 
chi square; ANOVA) for sex, age at onset of seizures and migrainous attacks,
family history, ictal signs and symptoms, EEG at rest (unilateral vs bilateral
distribution of epileptiform abnormalities), and EEG during Hyperventilation (HV)
and Intermittent Photic Stimulation (IPS). Significant differences were found in 
family history, ictal signs and symptoms, EEG at rest and during activation
tests. A family history of epilepsy, visual symptoms such as colored
hallucinations and micro/macropsias, frequently associated with clinical signs in
the visual system (eye deviation, nystagmus), unilateral EEG abnormalities, and
abnormal response to IPS were closely related to diagnosis of epilepsy. On the
other hand, a family history of migraine, visual symptoms such as amaurosis and
scotomata, without evident clinical signs, bilateral EEG abnormalities, and no
changes during IPS were significantly related to migraine. In conclusion, these
clinical and EEG differences should be considered in the differential diagnosis
between epilepsy and migraine in children with occipital epileptiform EEG
abnormalities.

PMID: 10840629 [PubMed - indexed for MEDLINE]

3627: Pediatr Clin North Am. 2000 Jun;47(3):617-31.

Migraine and headache in childhood and adolescence.

Annequin D, Tourniaire B, Massiou H.

Pediatric Pain Clinic, Unité fonctionnelle d'analgésie pédiatrique, Hôpital
d'enfants Armand Tousseau, Paris, France.

Headache is one of the most common physical complaints of children and adults.
The authors have provided definitions of headache, a classification system,
diagnostic evaluations appropriate for children, and treatment options for
patients with acute and chronic headache. Also, this article has emphasized the
importance of diagnosing and treating migraine headache, a painful malady that is
extensively underestimated and misdiagnosed in the pediatric population and one
that can be treated acutely and when appropriate prophylactically with great
success. Lack of a specific biologic marker, specific investigation, or brain
imaging reduce these clinical entities too often to a psychological illness.
Nonpharmacologic treatments are pivotal to manage chronic headaches. Migraine
therapy, if administered early and through the appropriate route, could provide
important and rapid relief.

Publication Types: 
    Review

PMID: 10835994 [PubMed - indexed for MEDLINE]

3628: Appl Psychophysiol Biofeedback. 2000 Mar;25(1):13-32.

Self-regulation of slow cortical potentials in children with migraine: an
exploratory study.

Siniatchkin M, Hierundar A, Kropp P, Kuhnert R, Gerber WD, Stephani U.

Department of Medical Psychology, Neurological Clinic of Kiel University,
Germany. siniatchkin@med-psych.uni-kiel.de

Migraine patients are characterized by increased amplitudes of slow cortical
potentials (SCPs), representing pronounced excitability of cortical networks. The
present study investigated the efficiency of biofeedback training of SCPs in
young migraineurs. Ten children suffering from migraine without aura participated
in 10 feedback sessions. They were compared with 10 healthy children for
regulation abilities of cortical negativity and with 10 migraineurs from the
waiting list for clinical efficacy. During the first two sessions, the migraine
children were characterised by lacking ability to control cortical negativity,
especially during transfer trials, compared with healthy controls. However, there
was no difference following 10 sessions of training. Feedback training was
accompanied by significant reduction of cortical excitability. This was probably 
responsible for the clinical efficacy of the training; a significant reduction of
days with migraine and other headache parameters was observed. It is suggested
that normalization of the threshold regulation of cortical excitability during
feedback training may result in clinical improvement.

Publication Types: 
    Clinical Trial
    Research Support, Non-U.S. Gov't

PMID: 10832507 [PubMed - indexed for MEDLINE]

3629: Can J Neurol Sci. 2000 May;27(2):111-5.

Are the triptans for migraine therapy worth the cost?

Becker WJ.

Department of Clinical Neurosciences, Faculty of Medicine, University of Calgary,
Alberta, Canada.

The triptans represent a major advance in migraine therapy but their cost per
dose greatly exceeds that of many older treatments. There is evidence that for a 
significant proportion of migraine patients these new drugs can show a positive
cost benefit and also improve quality of life. Cost benefit would be expected to 
be greatest in patients with more severe migraine attacks.

Publication Types: 
    Review

PMID: 10830342 [PubMed - indexed for MEDLINE]

3630: Clin Neurophysiol. 2000 Jun;111(6):1124-9.

Comparison of visual and auditory evoked cortical potentials in migraine patients
between attacks.

Afra J, Proietti Cecchini A, Sándor PS, Schoenen J.

Department of Neurology Semmelweis University of Medicine, Budapest, Hungary.

OBJECTIVE: As both habituation of pattern reversal visual evoked potentials
(PR-VEP) (Schoenen J, Wang W, Albert A, Delwaide PJ. Potentiation instead of
habituation characterizes visual evoked potentials in migraine patients between
attacks. Eur J Neurol 1995;2:115-122) and intensity dependence of auditory evoked
cortical potentials (IDAP) (Wang W, Timsit-Berthier M, Schoenen J. Intensity
dependence of auditory evoked potentials in migraine: an indication of cortical
potentiation and low serotonergic neurotransmission? Neurology 1996;46:1404-1409)
were found abnormal in migraine between attacks, we have searched for
intraindividual correlations between both tests in 59 migraine patients (22 with 
aura [MA], 37 without aura [MO]) and in 23 healthy volunteers (HV). METHODS:
Amplitude change of the PR-VEP N1-P1 was measured between the 1st and 5th block
of 50 sequential averagings during continuous stimulation at 3.1 Hz. IDAP was
computed from N1-P2 amplitudes of 100 averagings during stimulations at 40, 50,
60 and 70 dB SL. Amplitude-stimulus intensity function (ASF) slopes and amplitude
changes between 40 and 70 dB were calculated. MO and MA differed from HV in
PR-VEP amplitude change (P=0.007) and IDAP slope (P = 0.0004). RESULTS: There was
no significant correlation between VEP amplitude changes and IDAP slopes, nor
between the latter two and attack frequency or disease duration. A negative
correlation was found between the amplitude of the first block of averaged
responses and potentiation of VEP in all subject groups (P = 0.03) as well as
between the amplitude of the auditory evoked potential, at 40 dB, and the
percentage of amplitude increase between 40 and 70 dB in MO (P = 0.004) and MA (P
= 0.007). ASF slopes and 40 dB amplitudes were significantly correlated only in
the MA group (P = 0.002). These results confirm the interictal deficit of
habituation in cortical processing of repetitive visual and auditory information 
in migraine. Since there is no intraindividual correlation between the cortical
responses to these sensory modalities they are complementary tools for the study 
of migraine and may help to identify subgroups of patients with distinct
pathophysiological mechanisms. CONCLUSIONS: The strong negative correlation
between the initial amplitude of evoked potentials and their amplitude increase
during subsequent averaging confirms that the response potentiation in migraine
is likely to be due to a reduced preactivation level of sensory cortices.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 10825720 [PubMed - indexed for MEDLINE]

3631: Neurochem Int. 2000 Oct;37(4):363-8.

Peripheral-type benzodiazepine receptors in human blood cells of patients
affected by migraine without aura.

Pavese N, Giannaccini G, Betti L, Ferrari S, Bonanni E, Bonuccelli U, Murri L,
Lucacchini A.

Dipartimento di Neuroscience, Sezione di Neurologia, Pisa, Italy.

The kinetic parameters at equilibrium of peripheral benzodiazepine receptors in
platelets, lymphocytes and granulocytes of 15 patients affected by migraine
without aura were tested using [3H]PK 11195, a specific radioligand for this
receptor and compared with the same number of healthy controls: a statistically
significant increase (platelets 212%, lymphocytes 203%, granulocytes 171%, as
absolute percentage) in the maximal number of binding sites (B(max)) in all three
patient samples, compared with healthy controls was detected; on the contrary,
the values of the dissociation constant (K(d)) at equilibrium do not show any
statistically significant variations between the two groups. These data further
confirm the presence of peripheral biochemical alterations in migraine without
aura. As peripheral benzodiazepine receptors appear to be involved in the
regulation of the mitochondrial respiratory chain, the observed increase in
B(max) might be related to the mitochondrial anomalies found in migraine
disorders.

PMID: 10825576 [PubMed - indexed for MEDLINE]

3632: Cephalalgia. 2000 Feb;20(1):57-66.

Orientation discrimination thresholds in migraine: a measure of visual cortical
inhibition.

Wilkinson F, Crotogino J.

Department of Psychology, McGill University, Montreal, Que, Canada.
fran@hebb.psych.mcgill.ca

Orientation discrimination is a visual task dependent on inhibitory mechanisms in
the visual cortex. In this study, orientation discrimination thresholds for bar
and grating patterns were measured at two visual field locations in subjects with
migraine with (n = 20) and without aura (n = 20) and in migraine-free control
subjects (n = 20). No statistically significant differences were found between
migraine groups and the control group on either task at foveal or peripheral
visual field locations. No significant correlations were found between
psychophysical thresholds and age, total lifetime auras or total lifetime
migraine episodes. However, a trend was seen toward slightly impaired performance
on the two foveal tasks in a subgroup of subjects with the highest total lifetime
aura count. Thus we have found no convincing evidence that impaired cortical
inhibitory mechanisms are a predisposing characteristic in migraine, but cannot
rule out the possibility that cortical inhibitory mechanisms may be adversely
affected by repeated visual auras.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 10817448 [PubMed - indexed for MEDLINE]

3633: Cephalalgia. 2000 Feb;20(1):45-50.

Motor cortex excitability in patients with migraine with aura and hemiplegic
migraine.

Werhahn KJ, Wiseman K, Herzog J, Förderreuther S, Dichgans M, Straube A.

Department of Neurology, University of Munich, Germany.

We studied the excitability of the motor cortex using transcranial magnetic
stimulation (TMS) in 12 patients with migraine with aura (MA) and nine patients
with familial hemiplegic migraine (FHM). Motor thresholds at rest, the duration
of the cortical and peripheral silent period and intracortical inhibition and
facilitation using paired-pulse TMS at intervals of 2 to 15 ms were measured with
patients free of attacks for at least 48 h. In contrast to previous reports we
could not find any significant differences between patient groups and compared to
controls (n=17) in the parameters tested. The results suggest that there are no
interictal changes of excitability of the motor cortex in migraine. This study
does not support the concept of general cortical hyperexcitability in migraine
secondary to a genetic predisposition or a structural alteration of inhibitory
interneurones in the cortex due to repeated parenchymal insults during attacks.

PMID: 10817446 [PubMed - indexed for MEDLINE]

3634: Cephalalgia. 2000 Feb;20(1):39-44.

Effects of the anti-migraine drug sumatriptan on muscle energy metabolism:
relationship to side-effects.

Boska MD, Welch KM, Schultz L, Nelson J.

Henry Ford Hospital NMR Research Laboratory, Henry Ford Health Sciences Center,
Detroit, MI, USA. boskam@neurnis.neuro.hfh.edu

Sumatriptan succinate (Imitrex) is a 5-HT (5-hydroxytryptamine) agonist used for 
relief of migraine symptoms. Some individuals experience short-lived
side-effects, including heaviness of the limbs, chest heaviness and muscle aches 
and pains. The effects of this drug on skeletal muscle energy metabolism were
studied during short submaximal isometric exercises. We studied ATP flux from
anaerobic glycolysis (An Gly), the creatine kinase reaction (CK) and oxidative
phosphorylation (Ox Phos) using 31P nuclear magnetic resonance spectroscopy (31P 
MRS) kinetic data collected during exercise. It was found that side-effects
induced acutely by injection of 6 mg sumatriptan succinate s.c. were associated
with reduced oxygen storage in peripheral skeletal muscle 5-20 min after
injection as demonstrated by a transient reduction in mitochondrial function at
end-exercise. These results suggest that mild vasoconstriction in peripheral
skeletal muscle is associated with the action of sumatriptan and is likely to be 
the source of the side-effects experienced by some users. Migraine with aura
patients were more susceptible to this effect than migraine without aura
patients.

Publication Types: 
    Clinical Trial
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 10817445 [PubMed - indexed for MEDLINE]

3635: Cephalalgia. 2000 Feb;20(1):30-8.

Comparison of the efficacy of zolmitriptan and sumatriptan: issues in migraine
trial design.

Geraud G, Olesen J, Pfaffenrath V, Tfelt-Hansen P, Zupping R, Diener HC, Sweet R.

Service de Neurologie, CHU de Rangueil, Toulouse, France.
geraud.g@chu-toulouse.fr

In this international, multicentre, double-blind, placebo-controlled, single
attack study, 'triptan naive' migraine patients were randomized in an 8:8:1 ratio
to receive zolmitriptan 5 mg, sumatriptan 100 mg or placebo. The all-treated
analysis included 1058 patients who took study medication. The primary endpoint, 
complete headache response, was reported by 39%, 38% and 32% of patients treated 
with zolmitriptan, sumatriptan and placebo, respectively, with no significant
difference between treatment groups. In patients with moderate headache at
baseline, complete response was significantly greater following zolmitriptan than
after placebo (48% vs. 27%; P=0.01); there was no significant difference between 
sumatriptan and placebo groups (40% vs. 27%). In patients with severe baseline
headache (where a greater reduction in headache intensity is required for a
headache response), there was no significant difference between any groups in
complete headache response rates. For secondary endpoints, active treatment
groups were significantly superior to placebo for: 1-, 2- and 4-h headache
response (e.g. 2-h headache response rates: zolmitriptan 59%; sumatriptan 61%;
placebo 44%; P < 0.01 vs. placebo); pain-free response rates at 2 and 4 h;
alleviation of nausea and vomiting; use of escape medication and restoration of
normal activity. The incidence of adverse events was similar between zolmitriptan
and sumatriptan groups but was slightly lower in the placebo group. The lack of
difference between active treatments and placebo for complete response probably
reflects the high placebo response obtained, which is probably a result of
deficiencies in trial design. For example, the randomization ratio may result in 
high expectation of active treatment. Thus, while ethically patient exposure to
placebo should be minimized, this must be balanced against the scientific
rationale underpinning study design.

Publication Types: 
    Clinical Trial
    Comparative Study
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 10817444 [PubMed - indexed for MEDLINE]

3636: Cephalalgia. 2000 Feb;20(1):20-9.

Are the periodic changes of neurophysiological parameters during the pain-free
interval in migraine related to abnormal orienting activity?

Siniatchkin M, Gerber WD, Kropp P, Voznesenskaya T, Vein AM.

I.M. Sechenov Moscow Medical Academy, Russian Autonomic Pathology Center, Russian
Headache Center. siniatchkin@med-psych.uni-kiel.de

OBJECTIVE AND METHODS: Migraine patients are characterized by increased amplitude
and reduced habituation of contingent negative variation (CNV). Furthermore, the 
CNV underlies periodic changes during the pain-free interval, being maximal
before attack. The periodicity of CNV is related to periodic changes in
habituation, probably due to variation of orienting activity during the pain-free
interval. CNV and orienting response (OR) were studied in 20 females suffering
from migraine without aura and in 12 matched healthy females. The
neurophysiological recordings in the group of patients were performed 1-4 days
before and 4 days after a migraine attack. The amplitudes and habituation of
early and late components and total CNV were calculated. The OR was assessed
using the habituation of the skin conductance response (SCR) and alpha blocking
(AB). The non-parametric tests were employed for statistical analysis. RESULTS:
There were no differences between the two groups for habituation of all CNV
components and of SCR following an attack. However, the habituation of AB was
significantly reduced in migraine. Before attack we observed a significantly
reduced habituation of the early and total CNV and of the AB compared to controls
and recordings performed after an attack. The habituation of the late component
and of SCR remained unchanged. CONCLUSIONS: The abnormal habituation could be
explained by the periodic changes of physiological parameters during the
pain-free interval. The impaired habituation of early CNV in migraine is
associated with increased orienting activity seen only in the central component
(AB) of OR.

PMID: 10817443 [PubMed - indexed for MEDLINE]

3637: Cephalalgia. 2000 Feb;20(1):15-9.

Migraine patients show an increased density of dopamine D3 and D4 receptors on
lymphocytes.

Barbanti P, Fabbrini G, Ricci A, Pascali MP, Bronzetti E, Amenta F, Lenzi GL,
Cerbo R.

Department of Neuroscience, University La Sapienza, Rome, Italy. pbrbanti@tin.it

Recent studies have revealed peculiar functional and genetic features of dopamine
receptors in migraine. As peripheral blood lymphocytes (PBL) may represent a tool
for peripheral detection of neuroreceptors, we compared the expression of
dopamine D3 (DRD3) and D4 (DRD4) receptors on PBL in migraine patients and in
healthy controls using radioligand binding assay techniques in the presence of
antidopamine D2-like receptor antibodies. The dopamine D2-like receptor agonist
[3H]7-OH-DPAT was used as a radioligand. An increased density of both DRD3
(P=0.0006) and DRD4 (P=0.002) on PBL was observed in migraineurs compared with
controls. This up-regulation might reflect central and/or peripheral dopamine
receptor hypersensitivity due to hypofunction of the dopaminergic system. These
findings support the view that dopamine D2-like receptors are involved in the
determination of the so-called migraine trait, which may help to elucidate
several clinical features of the disease.

PMID: 10817442 [PubMed - indexed for MEDLINE]

3638: Cephalalgia. 2000 Feb;20(1):3-14.

Molecular genetics of migraine headaches: a review.

Montagna P.

Institute of Clinical Neurology, University of Bologna Medical School, Italy.
pmontagn@kaiser.alma.unibo.it

Following the recent discovery of neural calcium channel mutations in familial
hemiplegic migraine, genetic linkage and association studies have been performed 
world-wide in an effort to unveil the genetic basis of the more common types of
migraine too. Mutations in neural calcium channels, mitochondrial DNA, serotonin 
receptors and transporter, dopamine receptors and genetic prothrombotic risk
factors have been especially investigated and are discussed here. No unambiguous 
conclusions have, however, been reached. FHM remains an isolated success story in
the quest for the genetic basis of migraine.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Review

PMID: 10817441 [PubMed - indexed for MEDLINE]

3639: Arch Neurol. 2000 May;57(5):745-6.

Idiopathic stabbing headache associated with monocular visual loss.

Ammache Z, Graber M, Davis P.

Department of Neurology, University of Iowa, Iowa City 52242, USA.
zammache@blue.weeg.uiowa.edu

BACKGROUND: Idiopathic stabbing headache, which is a brief, sharp, severe jabbing
pain that is confined to the head, responds well to treatment with indomethacin
sodium. It may occur as a primary entity but more likely is associated with other
types of headache, including migraine. SETTING: Emergency department of a
teaching hospital. PATIENT: A 27-year-old man presented to the emergency
department with stabbing, sharp pain in the right temporal area associated with
complete of loss vision in his right eye. The patient had a history of migraine
with aura since 1995. RESULT: The patient was treated with oxygen inhalation and 
indomethacin, with complete resolution of his symptoms. CONCLUSION: A case of
idiopathic stabbing headache associated with monocular visual loss was relieved
by oxygen and indomethacin therapy.

Publication Types: 
    Case Reports

PMID: 10815143 [PubMed - indexed for MEDLINE]

3640: Ann Neurol. 2000 May;47(5):648-51.

Serum elastase activity is elevated in migraine.

Tzourio C, El Amrani M, Robert L, Alpérovitch A.

INSERM U360, Hôpital de la Salpêtrière, Paris, France.

Migraine has been associated with diseases considered to be related to
extracellular matrix disorders--in particular, cervical artery dissection. In
this population-based study, we found a highly significant association between
migraine and the activity of serum elastase, a metalloendopeptidase degrading
specific elastin-type amino acid sequences. Such enzymes are involved in matrix
degradation. This association was seen in both sexes and was stronger for
migraine with aura. These findings could help in the understanding of why
patients with migraine are at higher risk of stroke. Further study is needed to
establish whether extracellular matrix abnormalities play a broader role in the
pathophysiology of migraine.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 10805337 [PubMed - indexed for MEDLINE]

3641: Ann Neurol. 2000 May;47(5):614-24.

An association between migraine and cutaneous allodynia.

Burstein R, Yarnitsky D, Goor-Aryeh I, Ransil BJ, Bajwa ZH.

Department of Anesthesia and Critical Care, Beth Israel Deaconess Medical Center,
Harvard Medical School, Boston, MA, USA.

Recent animal studies on the mechanism of migraine show that intracranial pain is
accompanied by increased periorbital skin sensitivity. These findings suggest
that the pathophysiology of migraine involves not only irritation of meningeal
perivascular pain fibers but also a transient increase in the responsiveness (ie,
sensitization) of central pain neurons that process information arising from
intracranial structures and skin. The purpose of this study was to determine
whether the increased skin sensitivity observed in animal also develops in humans
during migraine attacks. Repeated measurements of mechanical and thermal pain
thresholds of periorbital and forearm skin areas in the absence of, and during,
migraine attacks enabled us to determine the occurrence of cutaneous allodynia
during migraine. Cutaneous allodynia is pain resulting from a nonnoxious stimulus
to normal skin. In 79% of the patients, migraine was associated with cutaneous
allodynia as defined, and in 21% of the patients it was not. The cutaneous
allodynia occurred either solely within the referred pain area on the ipsilateral
head, or within and outside the ipsilateral head. Cutaneous allodynia in certain 
well-defined regions of the skin during migraine is an as yet unreported
neurological finding that points to hyperexcitability of a specific central pain 
pathway that subserves intracranial sensation.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 10805332 [PubMed - indexed for MEDLINE]

3642: Neurology. 2000 May 9;54(9):1869-71.

Migraine with aura and white matter abnormalities: Notch3 mutation.

Ceroni M, Poloni TE, Tonietti S, Fabozzi D, Uggetti C, Frediani F, Simonetti F,
Malaspina A, Alimonti D, Celano M, Ferrari M, Carrera P.

Istituto Neurologico IRCCS C. Mondino, Pavia, Italy. mceroni@unipv.it

The authors report on an Italian family with eight affected members who show
autosomal dominant migraine with prolonged visual, sensory, motor, and aphasic
aura. These symptoms are associated with white matter abnormalities on brain MRI.
All living affected members carry a Notch3 mutation (Arg153Cys) previously
reported in cerebral autosomal dominant arteriopathy with subcortical infarcts
and leukoencephalopathy (CADASIL). White matter abnormalities occur in a variable
percentage of the general migraine population; CADASIL should be suspected in
migraineurs with prolonged atypical aura and white matter abnormalities.

Publication Types: 
    Case Reports

PMID: 10802804 [PubMed - indexed for MEDLINE]

3643: Eur J Med Res. 2000 Apr 19;5(4):176-82.

Treatment of menstrual migraine with prostaglandin synthesis inhibitor mefenamic 
acid: double-blind study with placebo.

Al-Waili NS.

Dubai Specialized Medical Center and Medical Research Laboratories, Dubai, United
Arab Emirates. waili2000@hotmail.com

The therapeutic effect of mefenamic acid, prostaglandin synthesis inhibitor, on
pain of acute menstrual migraine and at the following days during menstrual
bleeding period was studied and compared with placebo. 24 patients, 18 to 35
years old, with menstrual migraine were entered for study. They had regular
menstrual cycles and they had been diagnosed as experiencing menstrual migraine
without aura for more than one year. The patients were treated for 2 consecutive 
menstrual cycles, one cycle with 500 mg mefenamic acid and one cycle with
placebo. Each drug was given at beginning of complaint and similar dose was
repeated 8 hourly at following days during the menstrual bleeding period (Total
dosage used 1500 mg per day). The use of medication was double blind. Pain
intensity was rated by means of a 4 points scale and functional disability was
rated from 0 to 3. Results showed that 79.16% of the patients showed significant 
pain relief with mefenamic acid as compared to 16.6% with placebo. The mean pain 
score of the mefenamic acid treated attacks decreased significantly from 2.46 +/-
0.5 to 0.62 +/- 1.0 at 2hr postdose. 83.3% of patients treated with mefenamic
acid was able to function with or without little effort whereas 12.4% restored
their activities with placebo. All the patients (100%) who showed significant
initial responses to placebo experienced headache recurrence as compared to 26.3%
with mefenamic acid. When considering mean pain scores, percentage of patients
with pain free at 2h postdose, percentage of patients required rescue treatment, 
percentage of patients with headache recurrence and percentages of patients
restored full activities, mefenamic acid is significantly superior to placebo in 
treatment of acute menstrual migraine. It might be concluded that mefenamic acid 
is safe and effective for treatment of acute menstrual migraine.

Publication Types: 
    Clinical Trial
    Controlled Clinical Trial

PMID: 10799353 [PubMed - indexed for MEDLINE]

3644: Clin Exp Allergy. 2000 May;30(5):739-43.

Why do some dietary migraine patients claim they get headaches from placebos?

Strong FC 3rd.

Departamento de Ciência de Alimentos, Faculdade de Engenharia de Alimentos,
Universidade Estadual de Campinas, SP, Brasil.

BACKGROUND: In six double-blind studies involving 182 tests of dietary migraine
patients sensitive to tyramine and beta-phenylethylamine, 18% reported headaches 
from placebos which were all concealed in gelatin capsules. OBJECTIVE: The
purpose of this research was to test a hypothesis: gelatin is partially
hydrolysed animal protein; (partially) hydrolysed vegetable protein (PHVP) is
known to cause migraine; perhaps the gelatin caused some of the headaches.
METHOD: The author tested this hypothesis on himself because he suffers from
dietary migraine. He proved this in a double-blind test with tyramine
hydrochloride (TYH). The amount required for the test was so small (1 mg) that it
was tasteless and capsules were unnecessary. The author then undertook tests with
a capsule, PHVP, monosodium glutamate (MSG) aspartame (a dipeptide) and TYH,
adjusting quantities to give a moderate headache. Samples were mixed with foods
to simulate normal eating: the capsule with potato chips, aspartame with orange
juice and the rest with cottage cheese or ricotta cheese. Times were measured
from ingestion (1) to start of the headache and (2) to maximum headache
intensity. Each experiment was repeated three times. The headaches were relieved 
with caffeine. RESULTS: Of eight double-blind test samples, the author identified
correctly the two placebos and five of the six samples containing tyramine.
Quantities giving moderate headaches were: 1 gelatin capsule, 400 mg MSG, 118 mg 
PHVP, 4.0 mg aspartame and 1.0 mg TYH. Typical times for the three repetitions of
the two time periods were 8, 9 and 11 and 17, 19 and 22 min. CONCLUSIONS:
Capsules may give headaches to dietary migraine patients that are similar to
those from foods. This would explain some of the headaches of patients from
placebos. The double-blind test and the repeatability of the time measurements
demonstrated the validity of the experiments.

PMID: 10792367 [PubMed - indexed for MEDLINE]

3645: J Neurol. 2000 Mar;247(3):183-8.

Placebo effect in the acute treatment of migraine: subcutaneous placebos are
better than oral placebos.

de Craen AJ, Tijssen JG, de Gans J, Kleijnen J.

Department of Clinical Epidemiology and Biostatistics, Academic Medical Centre,
University of Amsterdam, The Netherlands. CRAEN@LUMC.NL

We carried out a meta-analysis of 22 trials to determine the comparative placebo 
effect of (a) subcutaneous vs. oral and (b) in-hospital vs. at-home
administration in the treatment of migraine. The headache relief rates were
combined from the placebo arms of these randomised clinical trials assessing the 
value of sumatriptan in acute treatment of migraine. The main outcome measure was
the proportion of patients reclassified from severe or moderate headache severity
to no or mild headache severity 2 h after the beginning of treatment. In the oral
regimen 222 of 865 patients (25.7%) reported no or mild headache severity after 2
h, compared to 279 of 862 patients (32.4%) of those receiving subcutaneous
placebo (6.7% difference; 95% CI 2.4-11.0%). Adjusting for treatment setting and 
severity of headache at baseline did not change the observed difference. After
placebo treatment at home 285 of 1,054 patients (27.0%) reported no or mild
headache severity after 2 h, compared to 216 of 673 patients (32.1%) among those 
receiving placebo in hospital (5.1 % difference; 95% CI 0.6-9.5%). When adjusted 
for route of administration and severity of headache at baseline, the difference 
in relief rates between home and hospital setting disappeared. These findings
indicate that subcutaneous administration enhances the placebo effect of acute
treatment of migraine. Future trials of antimigraine drugs assessing the relative
efficacy of various routes of administration should use a double-dummy technique.
The interpreting of placebo-controlled trial results must therefore consider that
the effect in the drug arm of the trial depends in part on the route of
administration.

Publication Types: 
    Meta-Analysis

PMID: 10787112 [PubMed - indexed for MEDLINE]

3646: J Neurol Sci. 2000 Apr 1;175(1):13-6.

Regional differences of cerebrovascular reactivity effected by calcium channel
blocker - dotarizine.

Kuridze N, Czernicki Z, Jarus-Dziedzic K, Jurkiewicz J, Cervos-Navarro J.

Department of Neurosurgery, Medical Research Center, Polish Academy of Sciences, 
Warsaw, Poland.

Dotarizine, a novel antimigraine prophylactic drug, is chemically related to
Diphenylbutylpiperazines, which are known to have Ca(2+)-antagonistic,
alpha-adrenolytic and antihistaminic properties. Additionally, Dotarizine
exhibits strong 5-HT2 receptor-specific antiserotoninergic properties. The
vasostabilizing effect of Dotarizine on cerebrovascular reactivity during
different ventilation conditions was demonstrated in various in vitro and in vivo
studies. In the presented study, the effect of chronic oral administration of the
drug on vascular reactions of different areas of cerebral vessels following
hyperventilation was investigated. The experiments were carried out on two groups
of experimental animals (rabbits). In the first group (6) 25 mg/kg of Dotarizine 
dissolved in 0.25% agar was administered orally for 5 days twice daily. The
control group of animals (6) was fed with agar of the same concentration
according to the same time schedule. During the experiment, 15 min
hyperventilation was performed and blood flow velocity (BFV) in the middle
cerebral artery (MCA) and the basilar artery (BA) was recorded using Transcranial
Doppler apparatus (TCD) before and after hyperventilation state. The obtained
results revealed a strong antivasoconstrictive effect of Dotarizine on cerebral
vessels reactivity during hyperventilation. In the control experimental group,
the 15 min hyperventilation caused a decrease in the mean BFV in MCA and BA by 36
and 14%, respectively, and in the drug-treated group under the same ventilation
conditions the decrease of the mean BFV in BA was only 6% and even a slight
increase (8% as compared with control values) of BFV in MCA was observed.
Comparison of the pulsatility index (PI) values demonstrated a significant
decrease of vascular resistance in MCA in the Dotarizine-treated group of animals
(P<0.1). From the obtained results it can be concluded that chronic oral
administration of a novel compound (Dotarizine) diminishes the vasoconstrictive
effect of hyperventilation on cerebral vessels in rabbits. The influence of this 
drug demonstrates regional differences in the cerebrovascular reactivity and it
appears to change the vascular resistance in the small arteries of the
cerebrovascular system. Thus, it can be recommended as a good prophylactic
antimigraine compound due its vasostabilizing properties.

PMID: 10785251 [PubMed - indexed for MEDLINE]

3647: Jpn Circ J. 2000 Apr;64(4):239-42.

Prevalence of migraine and Raynaud's phenomenon in Japanese patients with
vasospastic angina.

Nakamura Y, Shinozaki N, Hirasawa M, Kato R, Shiraishi K, Kida H, Usuda K,
Ishikawa T.

Department of Cardiology, Kanazawa National Hospital, Japan. nakay@po.incl.ne.jp

The prevalence of migraine and Raynaud's phenomenon in Japanese patients with
vasospastic angina (group I) were compared with those in 2 control groups: one
with effort angina (group II) and the other group without known ischemic heart
disease (group III). There were no significant differences among the 3 groups
with respect to age and sex. The prevalence of migraine in group I was 23 of 100,
as compared with 4 of 100 in group II (p<0.01) and 11 of 100 in group III
(p<0.05). The prevalence of Raynaud's phenomenon in group I was 9 of 100, as
compared with 3 of 100 in group II and 4 of 100 in group III. Thus, in Japan, the
prevalence of migraine in patients with vasospastic angina was higher than those 
in the 2 control groups, whereas the prevalence of Raynaud's phenomenon did not
differ significantly among the 3 groups. The prevalence of Raynaud's phenomenon
in Japanese patients with vasospastic angina was different from that reported
from North America, although the prevalence of migraine was the same. This may be
partially explained by racial differences.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 10783043 [PubMed - indexed for MEDLINE]

3648: Pain. 2000 May;86(1-2):139-49.

Towards an objective quantitative assessment of daily functioning in migraine: a 
feasibility study.

Tulen JH, Stronks DL, Bussmann JB, Pepplinkhuizen L, Passchier J.

Department of Psychiatry, University Hospital Rotterdam-Dijkzigt and Erasmus
University Rotterdam, Netherlands. tulen@psy.fgg.eur.nl

Migraine is a chronic disabling disorder, with migraine episodes significantly
reducing quality of life and leading to impaired functioning (physically,
socially, emotionally) both at home and at work. We explored whether ambulatory
accelerometry can be used as an objective method to quantify the behavioral
aspects of migraine-related disability. Four body mounted uni-axial
piezo-resistive accelerometers were used to quantify the time spent in different 
body postures (lying, sitting, standing), physical activities (walking, cycling) 
and a general index of body motility during eight migraine attacks and subsequent
recovery periods of six patients in their habitual environment. The migraine
attacks and recovery periods could be monitored after about 1 h, which was the
time required for the investigator to travel to the patient and for the sensors
to be attached. In order to quantify the influence of a migraine episode on daily
activities, we also performed measurements during a headache-free baseline period
of the same patients. Overall, the procedures functioned well, indicating that
ambulatory accelerometry measurements before, during and after a migraine attack 
are feasible to perform. Furthermore, our quantitative data revealed that
migraine always influenced behavior by reducing overall body motility and that,
dependent upon the severity of the attack, the effectiveness of acute treatment
and the time of day, the time spent in various body positions, dynamic
activities, and the number of postural transitions were affected. This
feasibility study showed that ambulatory accelerometry can provide the objective 
behavioral effect parameters for the evaluation of migraine and its treatment on 
daily functioning in the habitual environment of migraine patients.

Publication Types: 
    Clinical Trial
    Research Support, Non-U.S. Gov't

PMID: 10779671 [PubMed - indexed for MEDLINE]

3649: Pain. 2000 May;86(1-2):133-8.

Evidence for increased plasma levels of calcitonin gene-related peptide in
migraine outside of attacks.

Ashina M, Bendtsen L, Jensen R, Schifter S, Olesen J.

Department of Neurology, Glostrup Hospital, University of Copenhagen, DK-2600
Glostrup, Denmark. ashina@dadlnet.dk

Although calcitonin gene-related peptide (CGRP) has been shown to be elevated in 
jugular venous blood of adult migraineurs during acute migraine attacks, it
remains unknown whether CGRP is increased outside of attacks in jugular or
cubital venous blood. The aim of the present study was to compare interictal
plasma levels of CGRP in adult migraine patients and in healthy controls. Twenty 
patients with a diagnosis of migraine with or without aura and 20 healthy
controls were included. In blood from the cubital vein, CGRP levels were
significantly higher in patients (75+/-8 pmol/l (mean+/-SEM)) than in controls
(49+/-3 pmol/l) (P=0.005). The subgroup of patients suffering exclusively from
migraine without aura (n=14) also had significantly higher levels of CGRP
(82+/-10 pmol/l) than controls (n=20; 49+/-3 pmol/l) (P=0.001). The findings
could not be explained by confounding factors such as age, sex or use of
contraceptive pills. We therefore conclude that CGRP is increased in cubital
venous blood of migraineurs outside of attack. It is hypothesized that this
finding may reflect a long-lasting or permanent abnormal neurogenic vascular
control in patients with migraine.

Publication Types: 
    Clinical Trial
    Research Support, Non-U.S. Gov't

PMID: 10779670 [PubMed - indexed for MEDLINE]

3650: Ann Otol Rhinol Laryngol. 2000 Apr;109(4):377-80.

Comment in:
    Ann Otol Rhinol Laryngol. 2000 Dec;109(12 Pt 1):1176.

Migraine and benign positional vertigo.

Ishiyama A, Jacobson KM, Baloh RW.

Division of Head and Neck Surgery, UCLA School of Medicine, Los Angeles,
California, USA.

Because inner ear symptoms are common in patients with migraine, we questioned
whether benign positional vertigo (BPV) is more common in patients with migraine 
than in the general population. We reviewed the records of 247 patients seen in
our neurotology clinic over the past 5 years with a confirmed diagnosis of BPV.
Each patient had the typical history of BPV, and in each case the characteristic 
torsional vertical positioning nystagmus was identified. All were interviewed
regarding migraine symptoms by means of standard International Headache Society
criteria. Migraine was 3 times more common in patients with BPV of unknown cause 
than in those with BPV secondary to trauma or surgical procedures. Most patients 
were cured with the particle repositioning maneuver, regardless of the cause.
Presumably, patients with migraine suffer recurrent damage to the inner ear (due 
to vasospasm or some other mechanism) that predisposes them to recurrent bouts of
BPV.

Publication Types: 
    Research Support, U.S. Gov't, P.H.S.

PMID: 10778892 [PubMed - indexed for MEDLINE]

3651: Med J Aust. 2000 Feb 21;172(4):157-9.

Intravenous lignocaine infusions for severe chronic daily headache.

Hand PJ, Stark RJ.

Department of Neurology, Alfred Hospital, Melbourne, VIC.

OBJECTIVES: To determine the safety and efficacy of intravenous lignocaine
infusion in patients with severe chronic daily headache (CDH). DESIGN:
Retrospective survey of consecutive patients. PARTICIPANTS: 19 patients, 18 with 
rebound headache and three with status migrainosus. Two patients had both
conditions at different times. SETTING: Neurology unit in a major metropolitan
teaching hospital, 1994-1998. MAIN OUTCOME MEASURES: Adverse events; headache
resolution; long term efficacy. RESULTS: The 19 patients (16 women) received 27
lignocaine infusions. Seven minor adverse events were noted during four
infusions. Twenty-two infusions were given for analgesic rebound headache in 18
patients, with headache resolution in 82% of infusions (17 of the 18 patients
responded at least once). Four patients obtained lasting relief, six returned to 
their regular manageable pattern of migraine (in two of these patients CDH
recurred after six months), four were lost to follow-up, and in four there was no
long term benefit. Five infusions were given for status migrainosus in three
patients, with four of these infusions successfully relieving the headache.
CONCLUSIONS: Intravenous lignocaine appears to be useful in the management of
severe intractable CDH and status migrainosus.

PMID: 10772585 [PubMed - indexed for MEDLINE]

3652: Clin Chim Acta. 2000 May;295(1-2):63-75.

Free and total magnesium in lymphocytes of migraine patients - effect of
magnesium-rich mineral water intake.

Thomas J, Millot JM, Sebille S, Delabroise AM, Thomas E, Manfait M, Arnaud MJ.

Centre d'Exploration et de Traitement des Migraines et Céphalées, Vittel, France.

Dietary surveys performed in Western countries show magnesium intakes lower than 
the recommended dietary allowances, suggesting a large prevalence of magnesium
deficiency. Low brain magnesium as well as impaired magnesium metabolism have
also been reported in various diseases such as migraine. To detect these
deficiencies, a non-invasive and sensitive test assessing magnesium status is
needed. Because magnesium is an intracellular cation, either total or ionized
magnesium (Mg(2+)) of blood cells were suggested as the most adequate tests.
Total magnesium levels in plasma, erythrocytes and lymphocytes and Mg(2+) in
lymphocytes were analyzed in a group of 29 migraine patients and 18 control
subjects. Results show significantly lower concentrations of total magnesium in
erythrocytes (50.7+/-4.7 vs. 53.5+/-2.9 mg/l; P<0.01) and of Mg(2+) in
lymphocytes (12.0+/-3.5 vs. 14.2+/-3.8 mg/l; P<0.05) in migraine patients as
compared to controls. While a significant difference of mean values was noted
between migraine patients and controls, an overlap of individual values was
observed. These analyses were repeated on migraine patients before and after a
2-week intake of a mineral water containing 110 mg/l magnesium, and a significant
increase in all intracellular magnesium concentrations with no effect on plasma
magnesium was observed. These increased intracellular magnesium concentrations
demonstrate the bioavailability of magnesium from this mineral water. Among the
analyzed parameters, Mg(2+) in lymphocytes appears to be the most sensitive index
of magnesium deficiency with a 15% decrease in migraine patients when compared to
controls and a 16% increase after 2 weeks of a magnesium-rich mineral water
intake.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 10767394 [PubMed - indexed for MEDLINE]

3653: J Neurol Neurosurg Psychiatry. 2000 May;68(5):609-14.

A new family with paroxysmal exercise induced dystonia and migraine: a clinical
and genetic study.

Münchau A, Valente EM, Shahidi GA, Eunson LH, Hanna MG, Quinn NP, Schapira AH,
Wood NW, Bhatia KP.

Department of Clinical Neurology, Institute of Neurology, Queen Square,
University College London, London WC1N 3BG, UK.

OBJECTIVE: To characterise the phenotype of a family with paroxysmal exercise
induced dystonia (PED) and migraine and establish whether it is linked to the
paroxysmal non-kinesigenic dyskinesia (PNKD) locus on chromosome 2q33-35, the
familial hemiplegic migraine (FHM) locus on chromosome 19p, or the familial
infantile convulsions and paroxysmal choreoathetosis (ICCA syndrome) locus on
chromosome 16. METHODS: A family, comprising 30 members, was investigated.
Fourteen family members in two generations including three spouses were examined.
Haplotypes were reconstructed for all the available family members by typing
several microsatellite markers spanning the PNKD, FHM, and ICCA loci.
Additionally, the four exons containing the known FHM mutations were sequenced.
RESULTS: Of 14 members examined four were definitely affected and one member was 
affected by history. The transmission pattern in this family was autosomal
dominant with reduced penetrance. Mean age of onset in affected members was 12
(range 9-15 years). Male to female ratio was 3:1. Attacks of PED in affected
members were predominantly dystonic and lasted between 15 and 30 minutes. They
were consistently precipitated by walking but could also occur after other
exercise. Generalisation did not occur. Three of the affected members in the
family also had migraine without aura. Linkage of the disease to the PNKD, FHM,
or ICCA loci was excluded as no common haplotype was shared by all the affected
members for each locus. In addition, direct DNA sequential analysis of the FHM
gene (CACNL1A4) ruled out all known FHM point mutations. CONCLUSIONS: This family
presented with the classic phenotype of PED and is not linked to the PNKD, FHM,
or ICCA loci. A new gene, possibly coding for an ion channel, is likely to be the
underlying cause of the disease.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 10766892 [PubMed - indexed for MEDLINE]

3654: Eur Neurol. 2000;43(3):133-6.

Angiotensin-converting enzyme gene deletion polymorphism determines an increase
in frequency of migraine attacks in patients suffering from migraine without
aura.

Paterna S, Di Pasquale P, D'Angelo A, Seidita G, Tuttolomondo A, Cardinale A,
Maniscalchi T, Follone G, Giubilato A, Tarantello M, Licata G.

Department of Internal Medicine, University of Palermo, Italy.

Many authors have reported an association between the angiotensin-converting
enzyme (ACE)-D allele and coronary heart disease and other cardiovascular
diseases. The mechanism underlying the positive associations between the ACE-D
alleles and diseases are not yet clear. Previous reports showed an association
between migraine without aura and ACE-D allele polymorphism. The study is aimed
to evaluate if the DD genotype could also be associated with the frequency and
duration of migraine without aura. In 302 patients suffering from migraine
without aura (at least for 1 year), with no history of cardiovascular diseases
and major risk factors for ischemic events, the genotypes of the ACE gene, plasma
ACE activity, and the frequency (weekly) and duration of migraine attacks were
evaluated. No drugs were given before (4 weeks) and during the study. The same
evaluations were performed in 201 subjects without migraine. The molecular
biologist and the physician evaluating the patient data were blinded to the
clinical history and ACE-DD gene determination. Genotypes were determined by
polymerase chain reaction amplification. Plasma ACE activity was performed by the
HPLC method. The groups were similar for sex, age and smoking habit (migraines:
302 patients (200 F/102 M), mean age 37.8 +/- 8.2 years; control: 201 subjects
(127 F/74 M), mean age 37.5 +/- 9.3 years). Patients with migraine without aura
showed higher incidence of the ACE-DD gene (48.34%) than control subjects
(37.32%), p < 0.05. The frequency of migraine (average attacks per week) was
higher in patients with DD (2.11 +/- 1.9) than in patients with ID (1.54 +/- 1.
44), p < 0.05. No difference in duration of migraine attacks (hours per week) was
observed. Plasma ACE activity was increased in patients with the ACE-DD gene. Our
data suggest that ACE-DD gene polymorphism could have an important role in
determining migraine attacks and the frequency of these attacks. Further data are
needed through further studies, especially on the biomolecular level. Copyright
2000 S. Karger AG, Basel

PMID: 10765051 [PubMed - indexed for MEDLINE]

3655: Headache. 2000 Apr;40(4):324-7.

Transient global amnesia, migraine, thalamic infarct, dihydroergotamine, and
sumatriptan.

Pradalier A, Lutz G, Vincent D.

Service de M¿edecine Interne IV-Centre Migraine et C¿ephal¿ees, Hôpital Louis
Mourier, Colombes, France.

This case report describes an episode of transient global amnesia that occurred
during a migraine attack, which had been treated with vasoconstrictors. Magnetic 
resonance imaging showed a small lesion with an ischemic appearance in the right 
thalamus.

Publication Types: 
    Case Reports

PMID: 10759939 [PubMed - indexed for MEDLINE]

3656: Headache. 2000 Apr;40(4):282-91.

The migraine ACE model: evaluating the impact on time lost and medical resource
Use.

Caro JJ, Caro G, Getsios D, Raggio G, Burrows M, Black L.

Caro Research, Boston, Mass; Caro Research, Montreal, Quebec, Canada.

OBJECTIVE: To describe the Migraine Adaptive Cost-Effectiveness Model in the
context of an analysis of a simulated population of Canadian patients with
migraine. BACKGROUND: The high prevalence of migraine and its substantial impact 
on patients' ability to function normally present a significant economic burden
to society. In light of the recent availability of improved pharmaceutical
treatments, a model was developed to assess their economic impact. METHODS: The
Migraine Adaptive Cost-Effectiveness Model incorporates the costs of time lost
from both work and nonwork activities, as well as medical resource and medication
use. Using Monte Carlo techniques, the model simulates the experience of a
population of patients with migraine over the course of 1 year. As an example,
analyses of a Canadian population were carried out using data from a
multinational trial, surveys, national statistics, and the available literature. 
RESULTS: Using customary therapy, mean productivity losses (amounting to 84 hours
of paid work time, 48 hours of unpaid work time, and 113 hours of leisure time
lost) were estimated to cost $1949 (in 1997 Canadian dollars) per patient, with
medical expenditures adding an average of $280 to the cost of illness.
CONCLUSIONS: With customary treatment patterns, the costs of migraine associated 
with reduced functional capacity are substantial. The migraine model represents a
flexible tool for the economic evaluation of different migraine treatments in
various populations.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 10759932 [PubMed - indexed for MEDLINE]

3657: Headache. 2000 Apr;40(4):267-75.

Hyposerotonin-induced nitric oxide supersensitivity in the cerebral
microcirculation.

Srikiatkhachorn A, Anuntasethakul T, Maneesri S, Phansuwan-Pujito P, Patumraj S, 
Kasantikul V.

Departments of Physiology, Faculty of Medicine, Chulalongkorn University,
Bangkok, Thailand.

OBJECTIVE: To investigate the relationship between hyposerotonin and cranial
microvascular responses to nitric oxide (NO). BACKGROUND: Although the mechanism 
underlying NO supersensitivity in migraine is still unclear, an alteration of the
serotonin system is a possible explanation. METHODS: Wistar rats were divided
into control and hyposerotonin groups. Serotonin was depleted by intraperitoneal 
injection with 300 mg/kg of para-chlorophenylalanine (PCPA), a tryptophan
hydroxylase inhibitor. Three days after PCPA pretreatment, the animals were
prepared for assessment of their NO-induced vasomotor response using glyceryl
trinitrate (GTN: 8 to 10 mg/kg, intravenously) as an NO donor. Pial circulation
was visualized by the intravital fluorescein videomicroscopic technique. Images
of vessels at 0, 5, 15, 30, and 60 minutes post GTN infusion were digitized and
measured. At the end of monitoring, the rat brains were removed for
ultrastructural study of the brain microvessels. RESULTS: Infusion of GTN
produced dose-dependent pial arteriolar dilatation. This vasodilator effect was
significantly increased in the PCPA-treated groups, especially at 30 and 60
minutes. The percentage change from baseline diameter at 30 minutes after the
8-mg/kg GTN infusion was 42.6 +/- 3.1 for the hyposerotonin group and 16.8 +/-
2.9 for the control group (P<.001). Electron microscopic study revealed that
exposure to the NO donor produced considerable changes in cerebral microvessels, 
characterized by focal ballooning of endothelial cells, increased microvillous
formation, and increased endothelial pinocytosis. These anatomical changes were
significantly more prominent in the hyposerotonin group. CONCLUSIONS: A
hyposerotoninergic condition can facilitate the NO-induced physiological and
pathological responses in meningeal and cerebral microvessels and, therefore, is 
a possible explanation for the supersensitivity to NO observed in patients with
migraine.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 10759930 [PubMed - indexed for MEDLINE]

3658: Headache. 2000 Mar;40(3):248-51.

Valproate prophylaxis for migraine induced by selective serotonin reuptake
inhibitors.

Delva NJ, Horgan SA, Hawken ER.

Department of Psychiatry, Queen's University, and the Kingston Psychiatric
Hospital, Kingston, Ontario, Canada.

We report the successful use of valproate in a 44-year-old woman with migraine
induced by selective serotonin reuptake inhibitors. Valproate should be
considered for those patients who develop serious migraine for the first time, or
worsening of previous migraine, after the initiation of treatment with selective 
serotonin reuptake inhibitors and for whom continued treatment with this class of
drugs is important.

Publication Types: 
    Case Reports

PMID: 10759929 [PubMed - indexed for MEDLINE]

3659: Headache. 2000 Mar;40(3):224-30.

Intravenous propofol: unique effectiveness in treating intractable migraine.

Krusz JC, Scott V, Belanger J.

Anodyne Paincare, Dallas, TX 75231-4308, USA.

OBJECTIVE: To report the unique effectiveness of propofol, an intravenous
anesthetic agent, in treating refractory migraines and other headaches in the
setting of an outpatient headache center. BACKGROUND: We initially observed the
dramatic abolition of ongoing migraine in patients (n=6) being treated with
propofol in preparation for epidural and other nerve blocks in the headache and
pain clinic. The reduction of headache severity was virtually 100%. We decided to
treat an additional cohort of patients with intravenous propofol in the headache 
clinic; these patients had intractable migraines that were refractory to the
usual abortive treatments. Subanesthetic doses of propofol were employed in this 
study. This is the first known report of the utility of this agent specifically
for the treatment of intractable headache. METHODS: Seventy-seven patients were
treated for intractable headache in the clinic with intravenous propofol, for
both migraine and nonmigrainous headache refractory to the usual methods of
abortive treatment. RESULTS: The average reduction in headache intensity was
95.4% after an average of 20 to 30 minutes of intravenous propofol treatment,
using a patient-rated visual analog scale of 0 to 10. Sixty-three of 77 patients 
reported complete abolition of their headache. The average dose of propofol was
110 mg, which is well within the usual range of preanesthetic doses and is
clearly subanesthetic. Moreover, only three of the treated patients reported a
return of the headache on the day following treatment. The neuropharmacology of
propofol and the putative multiple mechanisms of action upon various
neurotransmitter systems in the brain, particularly gamma aminobutyric acid A
receptor subtypes, are discussed to explain the results in our patients.
CONCLUSIONS: The use of intravenous propofol may represent a new, rapid, and
highly effective form of abortive headache treatment in the headache clinic or
emergency room setting and may offer an alternative to other treatment modalities
for acute migraine and other severe intractable headaches. The effectiveness of
propofol raises many new questions about the pathophysiology of migraine and
other headaches.

PMID: 10759925 [PubMed - indexed for MEDLINE]

3660: Headache. 2000 Mar;40(3):216-23.

Incidence of medically recognized migraine: A 1989-1990 study in Olmsted County, 
Minnesota.

Rozen TD, Swanson JW, Stang PE, McDonnell SK, Rocca WA.

Department of Neurology, Mayo Clinic and Mayo Foundation, Rochester, MN 55905,
USA.

OBJECTIVE: To investigate the incidence of medically recognized migraine in
Olmsted County, Minnesota, during the years 1989 to 1990. METHODS: We used the
records-linkage system of the Rochester Epidemiology Project to identify all
subjects who sought medical attention for their headache and had their initial
visit for migraine within the study period. Incident cases were classified using 
specified criteria. RESULTS: From 9837 records screened, we found 713 incident
cases. The average annual incidence rate (new cases per 100 000 person-years) was
343.0 in both sexes combined, 481.6 in women, and 194.4 in men. In women,
incidence rates were low at the extremes of age and higher among those aged
between 10 and 49 years, with a striking peak at the age of 20 to 29 years.
Migraine without aura was the most common type of migraine in women. Men had a
more constant risk of migraine throughout life with a lesser peak at the age of
10 to 19 years, and they were equally affected by all types of migraine. Women
had consistently higher incidence rates than men at all ages, and there were
strikingly higher incidence rates of migraine without aura in women than in men. 
CONCLUSIONS: Although our incidence rates were restricted to medically recognized
cases of migraine, we confirmed previously reported epidemiological patterns.

Publication Types: 
    Research Support, Non-U.S. Gov't
    Research Support, U.S. Gov't, P.H.S.

PMID: 10759924 [PubMed - indexed for MEDLINE]

3661: Headache. 2000 Mar;40(3):204-15.

Validity and reliability of the migraine-specific quality of life questionnaire
(MSQ Version 2.1).

Martin BC, Pathak DS, Sharfman MI, Adelman JU, Taylor F, Kwong WJ, Jhingran P.

College of Pharmacy, University of Georgia, Athens 30602, USA.

OBJECTIVE: To assess the scaling properties, reliability, and validity of the
revised Migraine-Specific Quality of Life Questionnaire (MSQ) (Version 2.1)
BACKGROUND: The MSQ is a disease-specific, quality-of-life instrument with three 
hypothesized scales that has been developed, tested, and revised. METHODS: The
study used a multicenter, nondrug, prospective, parallel group,
quasi-experimental design. Patients with migraine were recruited at outpatient
headache specialty practices and were administered the MSQ, the Medical Outcomes 
Study 36-Item Short Form Health Survey (SF-36), and migraine symptom
questionnaires at baseline, 4 weeks, and 12 weeks. Internal consistency (Cronbach
alpha) and 4-week test-retest reproducibility (intraclass correlation
coefficients) were estimated to assess reliability. Construct validity was
assessed using an adaptation of the Campbell and Fiske multitrait-multimethod
approach and by correlating MSQ scores with symptom measures. RESULTS: A total of
267 subjects enrolled in the trial. The criteria for summated rating scales were 
all met. The internal consistency coefficients ranged from 0.86 to 0.96, and the 
intraclass correlation coefficients ranged from 0.57 to 0.63 across the three
dimensions. As anticipated, the MSQ dimensions had low-to-modest correlations
with the two component scores of the SF-36 and were modestly to moderately
correlated with migraine symptoms. CONCLUSIONS: The MSQ is a reliable instrument 
in the assessment of quality of life for patients with migraine with items that
can be summed without weights. The MSQ has demonstrated evidence of construct
validity.

Publication Types: 
    Multicenter Study
    Research Support, Non-U.S. Gov't

PMID: 10759923 [PubMed - indexed for MEDLINE]

3662: Headache. 2000 Mar;40(3):194-9.

The wavelength of light causing photophobia in migraine and tension-type headache
between attacks.

Main A, Vlachonikolis I, Dowson A.

European Institute of Health and Medical Sciences, University of Surrey,
Guildford, Surrey; Kings Headache Service, London, England.

OBJECTIVE: To ascertain the wavelength of light that patients with migraine and
tension-type headache find uncomfortable between attacks. BACKGROUND: Photophobia
is an abnormal perceptual sensitivity to light experienced by most patients with 
headache during and, also, between attacks. METHODS: We examined the discomfort
threshold to light of low, medium, and high wavelengths in a group of patients
with migraine (n=21), patients with tension-type headache (n=19), and healthy
controls (n=21). RESULTS: The results indicate that the migraine group had
significantly lower discomfort thresholds at the low (P=.001) and high (P=.031)
wavelengths compared with both the tension-type headache and control groups; the 
latter two groups had similar average discomfort levels at these two wavelengths.
With the medium wavelength, the control group had significantly higher discomfort
thresholds than the migraine (P=.002) and tension-type headache (P=.031) groups; 
the latter two groups had similar discomfort levels at this wavelength. With
unfiltered (white) light, the migraine group had the lowest discomfort threshold 
and the control group the highest (P=.026), whereas the tension-type headache
group had an intermediate discomfort threshold. CONCLUSIONS: There were
significant differences between migraineurs, patients with tension-type headache,
and healthy controls in the wavelengths that are uncomfortable between attacks.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 10759921 [PubMed - indexed for MEDLINE]

3663: Headache. 2000 Mar;40(3):189-93.

Predictability of exogenous hormone effect on subgroups of migraineurs.

Mueller L.

University of Medicine & Dentistry of New Jersey-School of Osteopathic Medicine, 
Moorestown.

OBJECTIVE: To evaluate whether self-reported past migraine response to
reproductive life events (menses, pregnancy, menopause) alters the likelihood of 
worsening of migraine with exogenous hormone use. METHODS: A retrospective study 
was conducted on 451 female patients at the University Headache Center who had a 
diagnosis of migraine with or without aura. RESULTS: The majority of migraineurs 
recalled no change in headaches with oral contraceptive use or hormone
replacement therapy (67.2% and 77%, respectively). Worsening of migraines with
oral contraceptive use was associated with a menstrual trigger, worsening during 
pregnancy, and a diagnosis of migraine without aura. Worsening with hormone
replacement therapy was associated with worsening during prior oral contraceptive
use, improvement during pregnancy, worsening during menopause, and a diagnosis of
migraine without aura. CONCLUSIONS: Prospective studies are needed to confirm
these associations.

PMID: 10759920 [PubMed - indexed for MEDLINE]

3664: Headache. 2000 Feb;40(2):170-2.

Comment in:
    Headache. 2000 Oct;40(9):767-8.

Acquired transient stuttering during a migraine attack.

Perino M, Famularo G, Tarroni P.

Departments of Emergency Medicine, San Camillo Hospital, Rome, Italy.

Stuttering is an abnormality in the fluency of speech, which is characterized by 
interruption of the normal rhythm due to involuntary repetition and prolongation,
or arrest, of uttered letters or syllables. The aphasic syndrome and dysarthria
can be associated with classic migraine, but, to our knowledge, no study has so
far described stuttering as the only neurological symptom accompanying an attack.

Publication Types: 
    Case Reports

PMID: 10759918 [PubMed - indexed for MEDLINE]

3665: Headache. 2000 Feb;40(2):164-9.

Hungarian migraine epidemiology.

Bánk J, Márton S.

Kenezy Gyula Teaching Hospital, Neurology Unit, Hungary.

OBJECTIVE: A population-based epidemiological survey of migraine without aura and
migraine with aura completed by mailed questionnaire in Hungary. The diagnosis
and classification of migraine was according to the criteria of the International
Headache Society. METHODS: The validity of the self-administered headache
questionnaire was evaluated by a neurologist using clinical interviews. The study
population was a random sample of 2000 men and women aged between 15 and 80
years. The questionnaire was completed by 813 of 1910 people (392 men and 421
women), providing a 42.6% participation rate. RESULTS: Sixty-seven percent of
these people experienced some kind of headache during their lives. The 1-year
prevalence of migraine without aura was 7.6% (the female/male ratio was 3:1),
while the 1-year prevalence of migraine with aura was 2% (female/male ratio was
2:1). Most migraineurs experienced headache attacks 1 to 4 times monthly, which
lasted 24 hours. The most characteristic accompanying signs were nausea and
phonophobia. Stress, sleep deprivation, hot weather, and fasting were the most
common precipitating factors of a migraine attack. In the migraine with aura
group, the most common aura was a visual disturbance. Only 43% of migraineurs had
ever consulted a physician for headache, and only 15% of patients had missed work
or school because of a migraine attack in the previous year. Most of the patients
suffering from migraine without aura were between 20 and 40 years old, while
migraineurs with aura were over 40 years old. According to this investigation,
the prevalence of migraine was not lower than in Western countries.

PMID: 10759917 [PubMed - indexed for MEDLINE]

3666: Headache. 2000 Feb;40(2):158-63.

Montelukast in the prophylaxis of migraine: a potential role for leukotriene
modifiers.

Sheftell F, Rapoport A, Weeks R, Walker B, Gammerman I, Baskin S.

New England Center for Headache, Stamford, CT 06902, USA.

OBJECTIVE: Clinical observation of a decrease in migraine frequency in patients
with comorbid asthma taking montelukast, a specific D4 leukotriene receptor
antagonist, or zafirlukast, another leukotriene receptor antagonist, prompted us 
to explore a possible role for leukotriene modifiers in the treatment of
migraine. (A further prompt was a pharmacist colleague's observation that a
number of patients on these agents reported a decreased sensitivity to perfume
triggers and improvement in migraine.) BACKGROUND: Nonsteroidal anti-inflammatory
agents have been used widely in the treatment of migraine. Another class of
anti-inflammatory agents, known as leukotriene modifiers, have not been studied
to date with regard to their possible role in the treatment of migraine. The name
"leukotriene is derived both from the parent molecule, which was originally
isolated from leukocytes, and from its three double-bond carbon backbone or
triene structure. Both prostaglandins and leukotrienes are derived from the
metabolism of arachidonic acid, with prostaglandins coming off the cyclooxygenase
pathway and leukotrienes derived via the enzyme 5-lipoxygenase. Both
prostaglandins and leukotrienes mediate inflammatory responses. The latter have
been studied with regard to their role in the pathophysiology of asthma. METHODS:
A prospective, open-label study evaluating the efficacy of montelukast, 10 mg or 
20 mg, in the prophylaxis of migraine in 17 patients is presented in this paper. 
All 17 patients completed the study that consisted of a 2-month baseline run-in
period and a 3-month treatment phase. RESULTS: Montelukast was extremely well
tolerated, and no adverse events were reported by any of the patients.
Fifty-three percent showed a reduction of greater than 50% (P<.025) in the
frequency of severe attacks, with 41% showing a reduction of greater than 60%.
Responders, including modest responders, rated the drug as excellent.
CONCLUSIONS: We conclude, given the limitations of an open-label study design and
the small sample size, that montelukast shows potential as an effective,
well-tolerated prophylactic agent in migraine. Double-blinded, placebo-controlled
studies are warranted. In addition, the leukotrienes, as suggested previously in 
the literature, may play a role in the pathogenesis of migraine.

Publication Types: 
    Clinical Trial

PMID: 10759916 [PubMed - indexed for MEDLINE]

3667: Headache. 2000 Feb;40(2):152-7.

Genetic and environmental factors associated with migraine in schoolchildren.

Bener A, Uduman SA, Qassimi EM, Khalaily G, Sztriha L, Kilpelainen H, Obineche E.

Department of Community Medicine, Faculty of Medicine & Health Sciences, UAE
University, Al-Ain, United Arab Emirates.

OBJECTIVE: The aim of this study was to find the prevalence of migraine and
headache in schoolchildren in the United Arab Emirates and to determine the
genetic and environmental factors associated with these conditions. METHODS: A
cross-sectional population study was performed from October 1995 to June 1996.
Subjects were selected by a multistage stratified sampling procedure. Data were
collected by screening questionnaires followed by clinical interviews. Twelve
primary schools and 1400 schoolchildren of United Arab Emirates nationality
resident in the Al Ain City, Dubai, and Sharjah emirates were recruited for this 
study. A total of 1159 (82.7%) schoolchildren gave their consent to the study.
RESULTS: The estimated prevalence rates for headache and migraine were 36.9% and 
13.7%, respectively. The prevalence of headache is increased with age, the
highest prevalence being in 13-year-old children (17.5%). Of the 159 children who
fulfilled the diagnostic criteria for migraine, 76 were boys whose mean age (+/- 
SD) was 10.3 years +/- 2. 8 years, and 83 were girls (mean age 9.9 +/- 2.5
years). Of the children who had migraine, 20 (12.6%) had migraine without aura,
and 13 (8.2%) had migraine with aura. The most common migraine symptoms in
schoolchildren had been aggravated by physical activity (47.2%) and a positive
family history of migraine (46.5%). The most common illnesses were infectious
illnesses (41.5%). There was a strong relationship between migraine and the
timing of examinations (46.5%). The most common environmental exposure for
migraine was found to be playing on a computer (45.9%), followed by loud noise
(41.5%), and a hot climate (37.1%). In familial occurrence of headache among
immediate relatives, the most frequently affected relative was the mother
(17.6%). CONCLUSION:.-Headache and migraine are common in childhood and may be
influenced by social, familial, environmental, and psychological factors.

PMID: 10759915 [PubMed - indexed for MEDLINE]

3668: Headache. 2000 Feb;40(2):129-36.

Decision making in migraine patients taking sumatriptan: an exploratory study.

Ivers H, McGrath PJ, Purdy RA, Hennigar AW, Campbell MA.

School of Psychology, Laval University, Quebec City, Quebec, Canada.

Until recently, much of the medical and psychological literature has examined and
conceptualized the taking of medication from the viewpoint of adherence to or
compliance with recommendations from health professionals. However, some authors 
have argued that medication taking is mostly determined by patient decision
making. In order to investigate the factors and processes influencing the
patient's decision to take or not take abortive therapy for migraines, 20
migraineurs (according to International Headache Society criteria) were asked,
using a semistandardized interview, what factors influenced their decision to
take or not take sumatriptan when they had a migraine. Qualitative analysis
revealed a 2-stage decision-making process. First, the patient collects
information from interoceptive and environmental cues (symptom monitoring) to
predict whether the headache that is beginning will become a migraine. Then, if
the patient decides it is a migraine, he or she weighs various factors to decide 
whether to take sumatriptan. These results are consistent with the current
cognitive psychology literature on decision-making processes and could lead to
significant improvements in understanding the process by which patients make
decisions about taking sumatriptan and, ultimately, could lead to better patient 
education and more effective headache control. They also open a whole new field
in the empirical investigation of medication-taking behavior.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 10759912 [PubMed - indexed for MEDLINE]

3669: Headache. 2000 Feb;40(2):119-28.

Comment in:
    Headache. 2001 Mar;41(3):321-3.

A comparative trial of zolmitriptan and sumatriptan for the acute oral treatment 
of migraine.

Gallagher RM, Dennish G, Spierings EL, Chitra R.

University of Medicine & Dentistry of New Jersey, Headache Center, Moorestown, NJ
08057, USA.

OBJECTIVE: This randomized, double-blind, parallel group multicenter study
compared response rates and tolerability of zolmitriptan with sumatriptan in the 
acute treatment of migraine. METHODS: A sample consisting of 1445 outpatients
with an established diagnosis of migraine was randomized to zolmitriptan, 2.5 mg 
or 5 mg, or sumatriptan, 25 mg or 50 mg. Patients took 1 tablet for
moderate/severe migraine and a second identical tablet, if necessary, for
recurrent headache of moderate/severe intensity 4 to 24 hours after the initial
dose. Up to six attacks were treated during a 6-month period. The primary outcome
measure was headache response 2 hours after the initial dose. Secondary end
points included 1-hour and 4-hour headache response and pain relief over 24
hours. RESULTS: A headache response at 2 hours was noted in 67.1% of patients
taking zolmitriptan, 2.5 mg, and 64.8% of those taking zolmitriptan, 5 mg, versus
59.6% of patients taking sumatriptan, 25 mg, and 63.8% of those taking
sumatriptan, 50 mg. At 2 and 4 hours, the differences between zolmitriptan, 2.5
mg, and sumatriptan, 25 mg, were statistically significant (odds ratio=1.49 and
1.67, respectively; both P<.001). Statistically significant differences between
zolmitriptan, 2.5 mg, and sumatriptan, 50 mg, were seen at 2 and 4 hours post
dose (odds ratio=1.21 and 1.23, respectively; both P<.05). At 1 hour post dose,
the headache response rate for zolmitriptan, 2. 5 mg, was numerically higher than
response rates for sumatriptan, 25 mg and 50mg (odds ratio=1.16, odds ratio=1.06,
though they failed to reach statistical significance; P=.061, P=.461
respectively). Differences between zolmitriptan, 5 mg, and sumatriptan, 25 mg,
were statistically significant at 1, 2, and 4 hours (odds ratio=1.43, 1. 46, and 
1.78, respectively; all P<.001) and at 1 and 4 hours versus sumatriptan, 50 mg
(odds ratio=1.28, P=.002; odds ratio=1.29, P=.012, respectively). Although not
statistically significant at 2 hours, more patients responded to zolmitriptan, 5 
mg, than to sumatriptan, 50 mg (odds ratio=1.16, P=.064). Patients receiving
zolmitriptan, 2. 5 mg or 5 mg, achieved more pain relief over 24 hours than
patients receiving sumatriptan, 25 mg (odds ratio=1.47, and 1.54 respectively,
both P<.001) or sumatriptan, 50 mg (odds ratio=1.17, P=.021; odds ratio=1.22,
P=.005, respectively). All treatments were well tolerated. CONCLUSIONS:
Zolmitriptan, 2.5 mg and 5 mg, was at least as effective as sumatriptan, 25 mg or
50 mg, for all parameters studied. Zolmitriptan, 2.5 mg, was significantly more
effective than sumatriptan, 50 mg, in terms of headache response at 2 and 4
hours. Patients taking zolmitriptan were significantly more likely to have pain
relief over 24 hours than those taking sumatriptan.

Publication Types: 
    Clinical Trial
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 10759911 [PubMed - indexed for MEDLINE]

3670: Headache. 2000 Feb;40(2):103-10.

Low migraine headache recurrence with naratriptan: clinical parameters related to
recurrence.

Sheftell F, O'Quinn S, Watson C, Pait D, Winter P.

New England Center for Headache, Stamford, CT 06902, USA.

OBJECTIVE: To evaluate clinical parameters that may affect the incidence of
headache recurrence or the time to headache recurrence, or both, in migraineurs
treated with naratriptan, 2.5-mg tablets. BACKGROUND: The incidence of headache
recurrence within 24 hours of treatment with naratriptan, 2.5-mg tablets
(17%-28%), is lower than that reported for other currently available selective
serotonin agonists. Identifying clinical parameters that influence headache
recurrence may further reduce the incidence of headache recurrence or prolong the
time to recurrence, or both, for naratriptan-treated patients. METHODS: We
examined the effects of three clinical parameters (predose pain severity,
headache duration prior to treatment, and relief status 4 hours post dose) on the
incidence of and time to headache recurrence across four placebo-controlled
naratriptan clinical trials. The impact of these parameters on headache
recurrence was examined individually and in combination. RESULTS: Predose pain
severity had no effect on the incidence of headache recurrence (overall 23%;
moderate 22%, severe 23%). The median time to recurrence was longer for patients 
with moderate pain before treatment compared with patients with severe pain
before treatment (14.5 hours versus 9.3 hours, respectively). Overall time to
headache recurrence was 11.8 hours. Patients with headache recurrence reported a 
longer time until they treated the headache compared with patients without
headache recurrence (median, 145 minutes versus 97.5 minutes). Patients who
treated headache pain within 3 hours of onset had a lower incidence of headache
recurrence (20%) than patients who treated their headache more than 3 hours after
onset (28%). Patients with no pain 4 hours post dose had a lower incidence of and
a longer time to headache recurrence compared with patients with mild pain 4
hours post dose (17% versus 32%; median, 17.8 hours versus 8.1 hours,
respectively). The interaction of all three clinical parameters was significant
in predicting headache recurrence. CONCLUSIONS: The overall incidence of headache
recurrence is low after naratriptan, 2.5 mg, compared with other currently
available selective serotonin agonists. Predose pain severity, time to treatment,
and 4-hour relief status appear related to the incidence of or time to headache
recurrence, or both. Treating less severe migraine attacks, treating earlier
within an attack, and obtaining complete relief post dose may enhance the low
incidence of headache recurrence and achieve longer times to recurrence with
naratriptan, 2.5 mg.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 10759909 [PubMed - indexed for MEDLINE]

3671: Headache. 2000 Jan;40(1):54-6.

Simultaneous occurrence of ipsilateral cluster headache and chronic paroxysmal
hemicrania: a case report.

Centonze V, Bassi A, Causarano V, Dalfino L, Centonze A, Albano O.

Headache Unit, 1st Institute of Internal Medicine, University of Bari, Italy.

A 42-year-old man came to our headache unit in October 1995 complaining of
recurrent attacks of headache, which had begun in February 1991. Chronic cluster 
headache was diagnosed, and he was given verapamil, 360 mg per day. The attacks
ceased in the following months and verapamil was stopped in March 1996. In May
1997, a recurrence of the attacks required the readministration of verapamil, 360
mg per day. The attacks decreased (one to three per week), but after 2 months the
patient reported a worsening in his condition due to the appearance of shorter
attacks, which were diagnosed as chronic paroxysmal hemicrania. The
administration of indomethacin, 225 mg per day, resulted in the disappearance of 
the short attacks. The concomitant occurrence of attacks of cluster headache and 
chronic paroxysmal hemicrania suggests the presence of shared factors in the
pathophysiology of the two forms of headache. This hypothesis is supported by
previous reports in the literature.

Publication Types: 
    Case Reports

PMID: 10759906 [PubMed - indexed for MEDLINE]

3672: Headache. 2000 Jan;40(1):52-3.

Migraine with prolonged aura.

Bento MS, Esperança P.

Unidade de Neurologia e Neurofisiologia, Hospital de São José, Lisboa, Portugal.

We present the case of a 29-year-old man with a long history of migraine with
aura, in whom migraine with prolonged aura was induced after the sudden
withdrawal of prophylactic therapy.

Publication Types: 
    Case Reports

PMID: 10759905 [PubMed - indexed for MEDLINE]

3673: Headache. 2000 Jan;40(1):45-7.

Comment in:
    Headache. 2001 Jun;41(6):609-11.

Patients with acenocoumarol treatment and migraine.

Morales-Asín F, Iñiguez C, Cornudella R, Mauri JA, Espada F, Mostacero EE.

Servicio de Neurología, Hospital Clínico Universitario, Zaragoza, Spain.

OBJECTIVE: The aim of our study was to investigate the possible effect of
acenocoumarol, which is indicated for nonneurological disease, on headache.
BACKGROUND: It has been suggested that anticoagulation can have beneficial
effects in the control of migraine attacks. METHODS: Four hundred randomized
patients on oral anticoagulant therapy were asked to complete a questionnaire
regarding their headaches. RESULTS: Headache was present before or during oral
anticoagulation in 166 (66 migraineurs and 100 nonmigraineurs) of 326
respondents. The major finding was that oral anticoagulation produced improvement
in 63% of patients with migraine versus 38% of patients with nonmigranous
headache. Improvement was related to the severity of migraine but not to age.
CONCLUSIONS: Oral anticoagulant therapy can improve migraine. The way in which
anticoagulant therapy acts on migraine is unknown, but potential mechanisms
include its effect on platelet aggregability and pharmacological effects such as 
suppression of enhanced nitric oxide.

Publication Types: 
    Comparative Study

PMID: 10759903 [PubMed - indexed for MEDLINE]

3674: Headache. 2000 Jan;40(1):36-40.

Influence of colors on habituation of visual evoked potentials in patients with
migraine with aura and in healthy volunteers.

Afra J, Ambrosini A, Genicot R, Albert A, Schoenen J.

Department of Neurology, Semmelweis University of Medicine, Budapest, Hungary.

OBJECTIVE: To investigate whether colored glasses influence the habituation of
visual evoked potentials. BACKGROUND: We have previously shown that during
pattern-reversal stimulations lasting 2 minutes the amplitude of the visual
evoked potential increases in migraine with and without aura between attacks,
whereas it decreases in healthy volunteers. Red light was found to increase
visually evoked EEG fast activity only in children with migraine with aura.
Wearing rose-tinted glasses for 4 months decreased attack frequency in parallel
with a reduction of the visually evoked EEG fast activity. METHODS: We compared
the change in amplitude of the visual evoked potential using five different
tinted glasses in 12 patients with migraine with aura and in 10 healthy
volunteers. During continuous stimulation at 3.1 Hz, five blocks of 50 responses 
were sequentially averaged using red, yellow, green, blue, and grey glasses and
without glasses in a random order and analyzed in terms of latencies and N1-P1
amplitudes. Amplitude changes were calculated for each block by comparison with
the first block in every condition and analyzed statistically using Zerbe's
method. RESULTS: In healthy volunteers, the visual evoked potential amplitude
increased with red glasses compared to without glasses (P = .05) or with green
glasses (P = .03). In patients with migraine with aura, no significant difference
was detected using colored glasses. Our findings in healthy volunteers are in
line with earlier reports of increased excitability of the human visual cortex
when exposed to red light. The lack of such a pattern in patients with migraine
with aura suggests that the visual cortex is interictally hypoexcitable rather
than hyperexcitable, which is consistent with studies of transcranial magnetic
stimulation.

Publication Types: 
    Comparative Study

PMID: 10759901 [PubMed - indexed for MEDLINE]

3675: Headache. 2000 Jan;40(1):30-5.

Prophylactic treatment of migraine with beta-blockers and riboflavin:
differential effects on the intensity dependence of auditory evoked cortical
potentials.

Sándor PS, Afra J, Ambrosini A, Schoenen J.

Neurology Department, CHR Citadelle, University of Liège, Belgium.

OBJECTIVE: To investigate the influence of different pharmacological treatments
on the intensity dependence of auditory evoked cortical potentials in
migraineurs. BACKGROUND: Between attacks, patients with migraine show
abnormalities in cortical information processing and decreased brain
mitochondrial energy reserve. Both are most probably relevant for migraine
pathogenesis, and they could be differentially modified by prophylactic drug
therapy. Design.-The intensity dependence of the auditory evoked cortical
potentials is, on average, increased in migraine. We have studied this intensity 
dependence in 26 patients before and after a 4-month period of prophylaxis with
beta-blockers (n = 11, all migraine without aura; metoprolol or bisoprolol) or
riboflavin (n = 15, migraine without aura: 13, migraine with aura: 2). Recordings
were performed at least 3 days before or after an attack. RESULTS: After the
treatment with beta-blockers, the intensity dependence of the auditory evoked
cortical potentials was significantly decreased (before: 1.66+/-1.02 microV/10
dB; after: 0.79+/-1.06 microV/10 dB, P=.02). The decrease in intensity dependence
was correlated significantly with clinical improvement (r = .69, P = .02). There 
was no change in intensity dependence after riboflavin treatment (before:
1.80+/-0.81 microV/10 dB; after: 1.56+/-0.83 microV/10 dB, P = .39), although the
majority of patients showed improvement. CONCLUSIONS: These results confirm that 
beta-blockers and riboflavin act on two distinct pathophysiological mechanisms.
Combining both treatments might enhance their efficacy without increasing central
nervous system side effects.

Publication Types: 
    Comparative Study

PMID: 10759900 [PubMed - indexed for MEDLINE]

3676: Headache. 2000 Jan;40(1):20-4.

Comment in:
    Headache. 2000 Nov-Dec;40(10):860-1.    Headache. 2001 Feb;41(2):206-7.

Pregnancy outcome following prescription for sumatriptan.

Olesen C, Steffensen FH, Sorensen HT, Nielsen GL, Olsen J.

Danish Epidemiology Science Centre at the Department of Epidemiology and Social
Medicine, University of Aarhus, Aarhus C.

BACKGROUND: Some 2.5% of fertile Danish women use sumatriptan, and the drug is
also taken during pregnancy. Although sumatriptan reacts selectively in brain
vessels, the possibility of reactions with placental blood flow and uterotonic
activity cannot be ruled out. The aim of our study was to examine the association
between sumatriptan exposure during pregnancy and the risk of preterm delivery
and low birth weight. METHODS: Data from the Pharmaco-Epidemiological
Prescription Database of North Jutland county regarding all women who had given
birth in the county of North Jutland from 1991 to 1996 were linked to the Danish 
Medical Birth Registry. Women who were exposed to sumatriptan during pregnancy
were identified (n = 34), and using logistic regression models their pregnancy
outcome was compared with two groups of pregnant women: (1) healthy women (n = 15
955) and (2) migraine controls (n = 89), defined as migraine patients who did not
redeem prescriptions for migraine treatment during pregnancy. RESULTS: The risk
of preterm delivery was elevated among women exposed to sumatriptan compared with
migraine controls (odds ratio [OR] 6.3, 95% confidence interval [CI] 1.2-32.0)
and healthy women (OR 3.3, 95% CI 1.3-8.5). The odds ratio for having a newborn
with a low birth weight was increased (OR 3.0, 95% CI 1.3-7.0) for all migraine
patients who delivered at term (n=115) compared with the outcome of healthy
pregnancies. CONCLUSIONS: We found that sumatriptan exposure during pregnancy was
associated with an increased risk of preterm delivery and low birth weight. These
findings may be due to drug exposure, but they may also reflect the impact of
disease severity rather than the treatment itself, or confounding, or chance.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 10759898 [PubMed - indexed for MEDLINE]

3677: Headache. 2000 Jan;40(1):17-9.

An analysis of the "carry-over effect" following successful short-term treatment 
of transformed migraine with divalproex sodium.

Rothrock JF, Mendizabal JE.

University of South Alabama Headache Center, Mobile, Alabama 36617, USA.

OBJECTIVE: To determine whether successful short-term prophylactic treatment of
transformed migraine may be followed by a continued respite from headaches once
the treatment has been discontinued ("carry-over effect"). BACKGROUND: The
optimal duration of prophylactic treatment for pervasive headache and for
migraine, in particular, is unknown. METHODS: We prospectively evaluated a series
of patients with transformed migraine, all of whom were managed according to a
uniform treatment protocol involving prophylactic therapy with divalproex sodium 
for a period not exceeding 12 weeks. All patients reporting a positive treatment 
response were followed for at least 2 months after the discontinuation of
divalproex sodium, and the incidence of the carry-over effect in that group was
assessed. RESULTS: A short-term carry-over effect occurred in 12 (60%) of 20
patients, but more sustained relief occurred in only 8 (40%). CONCLUSIONS: The
successful short-term treatment of transformed migraine with divalproex sodium
will often produce a short-term carry-over effect, but this response will be
sustained only in a minority of patients.

PMID: 10759897 [PubMed - indexed for MEDLINE]

3678: Eur J Clin Invest. 2000 Apr;30(4):367-71.

Cytochrome P450 2D6 and glutathione S-transferase M1 genotypes and migraine.

Mattsson P, Bjelfman C, Lundberg PO, Rane A.

University Hospital, Uppsala, Sweden. Peter.Mattsson@neurologi.uu.se

BACKGROUND: Migraine is thought to be a disease of the brain and
trigeminovascular system. Migraine patients often claim that stress, food, and
beverages trigger their attacks. Chemical substances in these foodstuffs with the
property of triggering migraine attacks have not yet been characterised.
Cytochrome P450 2D6 (CYP2D6) and glutathione S-transferase M1 (GSTM1) are thought
to be present in the brain. They metabolise numerous environmental compounds. The
genes exhibit genetic polymorphism that is associated with altered enzyme
activity. The aim of this study was to determine if the genotypes of these two
enzymes are associated with migraine. MATERIALS AND METHODS: The study included
100 female patients and 245 female controls from the general population. Genomic 
DNA was isolated from whole blood. Allele specific PCR methods were used to
identify the normal CYP2D6*1 allele and the mutated CYP2D6*3 and CYP2D6*4
alleles. Initially all samples were genotyped only for GSTM1 plus (+) and GSTM1
null (-) variants. All samples positive for GSTM1 were further analysed for the
presence of allelic variants GSTM1*A and GSTM1*B. RESULTS: None of the CYP2D6 and
GSTM1 genotypes was associated with migraine. We observed an odds ratio (OR) for 
the poor metaboliser genotype of CYP2D6 of 1.4 (95% CI = 0.5-3.6) and for the
GSTM1 null genotype of 1.0 (95% CI = 0.6-1.5). CONCLUSION: The results of this
study indicate that deficient metabolism because of mutated CYP2D6 alleles or
GSTM1 allele variants is not important in the aetiology of migraine.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 10759887 [PubMed - indexed for MEDLINE]

3679: Allergol Immunopathol (Madr). 2000 Jan-Feb;28(1):15-7.

Parental history of migraine and bronchial asthma in children.

Gürkan F, Ece A, Haspolat K, Dikici B.

Dicle Univ, Cocuk Servisi, Diyarbakir, Turquía. fuatgurkan@hotmail. com

BACKGROUND: a possible association between migraine and various allergic
disorders have been reported. It was aimed in this study to inquire the
association between bronchial asthma in children and parental history of
migraine. METHODS AND RESULTS: parental history of allergic diseases and migraine
were inquired among 140 asthmatic children (91 males, 49 females) and 110 age and
sex matched control subjects who had not any allergic or hypersensitivity
disorders, followed-up at Pediatric outpatient clinics of Dicle University
Hospital. While 13 of 140 asthmatic children (9.3%) had parental history of
migraine, 2 of 110 control subjects (1.8%) had parental migraine history.
Difference between asthmatic and control subjects was significant (OR: 5.5, 95%
Cl: 1.3-25.0). Children who had parental history of migraine also had
significantly more frequent parental history of asthma, eczema and particularly
allergic rhinitis (p=0.007). CONCLUSIONS: our results suggest that children are
at increased risk of asthma if their parents have a history of migraine. Migraine
in one generation and asthma in the next lead to the conclusion that the two
disorders may have a relationship to a common denominator.

PMID: 10757853 [PubMed - indexed for MEDLINE]

3680: J Biol Chem. 2000 Mar 31;275(13):9239-43.

Three new familial hemiplegic migraine mutants affect P/Q-type Ca(2+) channel
kinetics.

Kraus RL, Sinnegger MJ, Koschak A, Glossmann H, Stenirri S, Carrera P, Striessnig
J.

Institut für Biochemische Pharmakologie, Peter-Mayr-Strasse 1, Innsbruck A-6020, 
Austria.

Missense mutations in the pore-forming human alpha(1A) subunit of neuronal
P/Q-type Ca(2+) channels are associated with familial hemiplegic migraine. We
studied the functional consequences on P/Q-type Ca(2+) channel function of three 
recently identified mutations, R583Q, D715E, and V1457L after introduction into
rabbit alpha(1A) and expression in Xenopus laevis oocytes. The potential for
half-maximal channel activation of Ba(2+) inward currents was shifted by > 9 mV
to more negative potentials in all three mutants. The potential for half-maximal 
channel inactivation was shifted by > 7 mV in the same direction in R583Q and
D715E. Biexponential current inactivation during 3-s test pulses was
significantly faster in D715E and slower in V1457L than in wild type. Mutations
R583Q and V1457L delayed the time course of recovery from channel inactivation.
The decrease of peak current through R583Q (30.2%) and D715E (30. 1%) but not
V1457L (18.7%) was more pronounced during 1-Hz trains of 15 100-ms pulses than in
wild type (18.2%). Our data demonstrate that the mutations R583Q, D715E, and
V1457L, like the previously reported mutations T666M, V714A, and I1819L, affect
P/Q-type Ca(2+) channel gating. We therefore propose that altered channel gating 
represents a common pathophysiological mechanism in familial hemiplegic migraine.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 10734061 [PubMed - indexed for MEDLINE]

3681: J Manipulative Physiol Ther. 2000 Feb;23(2):91-5.

Comment in:
    J Manipulative Physiol Ther. 2001 Feb;24(2):143.    J Manipulative Physiol Ther. 2001 Feb;24(2):143-4.

A randomized controlled trial of chiropractic spinal manipulative therapy for
migraine.

Tuchin PJ, Pollard H, Bonello R.

Department of Chiropractic, Macquarie University, New South Wales, Australia.

OBJECTIVE: To assess the efficacy of chiropractic spinal manipulative therapy
(SMT) in the treatment of migraine. DESIGN: A randomized controlled trial of 6
months' duration. The trial consisted of 3 stages: 2 months of data collection
(before treatment), 2 months of treatment, and a further 2 months of data
collection (after treatment). Comparison of outcomes to the initial baseline
factors was made at the end of the 6 months for both an SMT group and a control
group. Setting: Chiropractic Research Center of Macquarie University.
PARTICIPANTS: One hundred twenty-seven volunteers between the ages of 10 and 70
years were recruited through media advertising. The diagnosis of migraine was
made on the basis of the International Headache Society standard, with a minimum 
of at least one migraine per month. INTERVENTIONS: Two months of chiropractic SMT
(diversified technique) at vertebral fixations determined by the practitioner
(maximum of 16 treatments). MAIN OUTCOME MEASURES: Participants completed
standard headache diaries during the entire trial noting the frequency, intensity
(visual analogue score), duration, disability, associated symptoms, and use of
medication for each migraine episode. RESULTS: The average response of the
treatment group (n = 83) showed statistically significant improvement in migraine
frequency (P < .005), duration (P < .01), disability (P < .05), and medication
use (P< .001) when compared with the control group (n = 40). Four persons failed 
to complete the trial because of a variety of causes, including change in
residence, a motor vehicle accident, and increased migraine frequency. Expressed 
in other terms, 22% of participants reported more than a 90% reduction of
migraines as a consequence of the 2 months of SMT. Approximately 50% more
participants reported significant improvement in the morbidity of each episode.
CONCLUSION: The results of this study support previous results showing that some 
people report significant improvement in migraines after chiropractic SMT. A high
percentage (>80%) of participants reported stress as a major factor for their
migraines. It appears probable that chiropractic care has an effect on the
physical conditions related to stress and that in these people the effects of the
migraine are reduced.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial

PMID: 10714533 [PubMed - indexed for MEDLINE]

3682: Eur J Neurosci. 2000 Feb;12(2):767-70.

Does the migraine aura reflect cortical organization?

Dahlem MA, Engelmann R, Löwel S, Müller SC.

Otto-von-Guericke-Universität Magdeburg, Institut für Experimentelle Physik,
Abteilung Biophysik, Universitätsplatz 2, D-39016 Magdeburg, Germany.
dahlem@physik.uni-magdeburg.de

Individuals suffering from classical migraine report an astonishing diversity of 
migraine auras. A frequently reported symptom is a visual hallucination known as 
fortification illusion (FI). Here we demonstrate that the typical zig-zag pattern
of the FI can be reproduced using experimental data of orientation maps of the
primary visual cortex (V1) assuming that a continuous excitation front propagates
across V1. We put forward a model in which the cortical neurons within this
excitation wave are activated sufficiently to contribute to conscious perception.
It is shown that the discontinuous repetitive nature of the zig-zag pattern of
the FI can reflect the specific layout of visual cortical orientation maps.
Additionally, dynamic features of the FI are predicted based on our model.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 10712657 [PubMed - indexed for MEDLINE]

3683: Br Homeopath J. 2000 Jan;89(1):4-7.

Comment in:
    Br Homeopath J. 2000 Jan;89(1):1-2.

Homeopathic treatment of migraine: a double blind, placebo controlled trial of 68
patients [see comment]

Straumsheim P, Borchgrevink C, Mowinckel P, Kierulf H, Hafslund O.

Arena Medisinske Senter, Sognsveien, Oslo, Norway.

To evaluate the efficacy of homeopathy in preventing migraine attacks and
accompanying symptoms, a randomised, double-blind, placebo-controlled clinical
trial was conducted. There was a one-month registration period without treatment,
followed by four months individualised homeopathic treatment or identical
placebo. Patients were stratified for common or classical migraine. Seventy-three
patients were randomised, 68 completed the trial. Baseline values were similar in
the two groups. Both the homeopathy and placebo groups had reduction in attack
frequency, pain intensity and drug consumption, with a statistically
non-significant difference favouring homeopathy. Migraine diaries showed no
difference between groups. The neurologists' trial evaluation showed a
statistically significant reduction in attack frequency in the homeopathy group
(P= 0.04) and non-statistically significant trends in favour of homeopathy for
pain intensity and overall evaluation. Further research, with improved trial
design, on the possible role of homeopathy in migraine prophylaxis is justified.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 10703903 [PubMed - indexed for MEDLINE]

3684: Nurse Pract. 2000 Feb;25(2):17-8, 21-4, 27-8 passim; quiz 40-1.

Caring for the woman with migraine headaches.

Moloney MF, Matthews KB, Scharbo-Dehaan M, Strickland OL.

Emory University, Atlanta, Ga., USA.

Approximately 16% of American women experience migraine headaches. These
debilitating headaches cause lost time from family, social activities, and work. 
Although migraines are thought to be a result of shifting menstrual and
perimenopausal hormones, a physiologic connection has not been well established. 
Despite the lack of certainty regarding migraine cause, several theories have
been postulated and a significant amount of literature has been published
addressing the management of premenstrual migraines. Fewer articles have been
published regarding the management of perimenopausal migraines, which are treated
somewhat differently. This article approaches both premenstrual and
perimenopausal migraine headaches from a chronic disease perspective, focusing on
self-care and the use of prescription and nonprescription therapies. Implications
for practice and future research are also discussed.

Publication Types: 
    Case Reports
    Review

PMID: 10703023 [PubMed - indexed for MEDLINE]

3685: Pain. 2000 Mar;85(1-2):247-54.

Intensity dependence of auditory evoked cortical potentials in migraine families.

Siniatchkin M, Kropp P, Neumann M, Gerber W, Stephani U.

Institute of Medical Psychology, University of Kiel, Niemannsweg 147, D-24105,
Kiel, Germany. siniatchkin@med.psych.uni-kiel.de

Intensity dependence of auditory evoked cortical potentials is abnormal in
migraine. This study investigated intensity dependence in migraine and healthy
families using group comparisons and analysis of individual differences.
Migraineurs were characterized by a steeper amplitude/stimulus function slope and
more pronounced difference between the amplitudes of N1-P2 on the more and the
less intensive tones than healthy age matched subjects. Apart from migraine, the 
age of the participants was an important predictive variable of intensity
dependence. Analysis of individual differences revealed low sensitivity and
moderate specificity of intensity dependence for migraine. Familial prevalence of
intensity dependence among first-degree relatives in migraine families was equal 
to that in healthy families. These findings support the assumption that
high-intensity dependence reflects a functional CNS trait which is more
pronounced and prevalent in migraine, but may also be found in healthy
individuals and in other neuropsychiatric disorders. Increased intensity
dependence is only one of several factors contributing to the risk for this form 
of headache.

Publication Types: 
    Clinical Trial
    Research Support, Non-U.S. Gov't

PMID: 10692625 [PubMed - indexed for MEDLINE]

3686: Neurology. 2000 Feb 22;54(4):1005-7.

mtDNA A3243G MELAS mutation is not associated with multigenerational female
migraine.

Buzzi MG, Di Gennaro G, D'Onofrio M, Ciccarelli O, Santorelli FM, Fortini D,
Nappi G, Nicoletti F, Casali C.

IRCCS Neuromed, Pozzilli, Italy.

The authors searched for mitochondrial DNA (mtDNA) A3243G mutation in peripheral 
blood leukocytes from female migraine patients with pure matrilinear history of
migraine along two or three generations. The current study was designed to
exclude any male transmission of the disease. The mutation was absent in all
patients. We conclude that mtDNA A3243G mutation does not contribute to the
pathogenesis of pure matrilinear multigenerational migraine with or without aura.

PMID: 10691007 [PubMed - indexed for MEDLINE]

3687: Forensic Sci Int. 2000 Jan 10;107(1-3):233-7.

Incorporation of propyphenazone in beard hair of a migraine patient.

Yegles M, Wenning R.

Division Toxicologie, CRP-Santé, Centre Universitaire, Luxembourg. yegles@cu.lu

The incorporation of propyphenazone in beard hair after consumption of this
substance present in the analgesic Migraine-Kranit (Codali) was investigated.
Because of a migraine attack a volunteer took four tablets of Migraine-Kranit
(one tablet contains 150 mg propyphenazone) the first day and two tablets the
second day. Shaved beard hair was collected 48, 72, 96 and 120 h after the first 
consumption of the analgesic drug. These hair specimens were washed (acetone and 
water), pulverized and then incubated during 2 h in a thioglycolic solution.
After solid-phase extraction on C18 columns, propyphenazone was assayed in these 
extracts by GC/MS operating in selected ion monitoring mode (m/z 230, 215).
Diazepam-d5 was used as an internal standard. In hair specimen 1 (48 h after
consumption) the highest concentration was found (170 pg/mg hair). In hair
specimen 2 (72 h) and 3 (96 h) the concentration were significantly lower (44 and
18 pg/mg, respectively). After 120 h no propyphenazone could be detected (limit
of detection: 5 pg/mg hair). These results show that propyphenazone was already
in beard hear 2 days after consumption, whereas no more presence could be shown
after 120 h. As the time period of 2 days is too short to allow entrapment into
the hair matrix from bloodstream and growing of hair out of the follicle, our
results suggest that incorporation of propyphenazone may be mainly due to
excretion in sweat and subsequent incorporation into the hair.

PMID: 10689575 [PubMed - indexed for MEDLINE]

3688: Eur Neurol. 2000;43(2):102-6.

An epidemiological study to assess migraine prevalence in a sample of Italian
population presenting to their GPs.

Roncolato M, Fabbri L, Recchia G, Cavazzuti L, Visona G, Brignoli O, Medea G.

Medical Department, GlaxoWellcome, Verona, Italy. mar2799@glaxowellcome.co.uk

This multicentre, observational, cross-sectional study was conducted to determine
migraine prevalence in a sample of population presenting to their GPs. The study 
covered all the patients who visited the GPs practice, for any reason, on 5
consecutive days of 2 different weeks. A total of 71,588 patients were
interviewed by 902 GPs. The prevalence of migraine in this sample was 11.6%.
Copyright 2000 S. Karger AG, Basel.

Publication Types: 
    Multicenter Study

PMID: 10686468 [PubMed - indexed for MEDLINE]

3689: J Neurol Sci. 2000 Feb 15;173(2):140-6.

Migraine, but not subarachnoid hemorrhage, is associated with differentially
increased NPY-like immunoreactivity in the CSF.

Valenzuela RF, Donoso MV, Mellado PA, Huidobro-Toro JP.

Departamento de Neurología, Facultad de Medicina, Pontificia Universidad Católica
de Chile, Marcoleta 367, Santiago, Chile. neuro@med.puc.cl

To test whether migraine and subarachnoid hemorrhage (SAH) are associated with
increased sympathetic tone, we compared the neuropeptide Y-like (NPY-LI) and
chromogranin A-like immunoreactivities (LI) of cerebrospinal fluid (CSF) from
migraneurs and SAH patients with those from control subjects. Increased
sympathetic tone was expected to produce higher co-release of these co-stored
peptides and concordant changes in their CSF levels. In addition, we investigated
a possible disturbed nitric oxide homeostasis by measuring CSF nitrites (NO).
More than 70% of CSF NPY-LI corresponded to the chromatographic peak (HPLC) for
the intact molecule in all three groups. Migraneurs had 64% higher CSF NPY-LI,
but no significant difference in CSF chromogranin A-LI, as compared to controls. 
In contrast, SAH patients had 74% less CSF chromogranin A-LI and a trend to lower
NPY-LI, as compared to controls. No differences in CSF NO were detected among
groups. These results argue against an increased sympathetic tone in patients
with either migraine or SAH, and suggest that the higher CSF NPY-LI of migraneurs
probably originates from central neurons. Furthermore, our findings in SAH
patients argue in favor of a decreased sympathetic tone; this could be a
homeostatic response to counterbalance vasoconstriction mediated by other
mechanisms.

Publication Types: 
    Comparative Study
    Research Support, Non-U.S. Gov't

PMID: 10675658 [PubMed - indexed for MEDLINE]

3690: Nurs Clin North Am. 2000 Mar;35(1):137-46.

Pediatric febrile seizures and childhood headaches in primary care.

Reinhold J, Bentti AL.

Pediatric Nurse Practitioner, Division of Neurology, Children's Hospital Medical 
Center, Cincinnati, Ohio 45229-3039, USA.

Febrile seizures and migraine headaches in children are two of the most common
neurological diagnoses seen by primary care practitioners. It is essential that a
knowledge base be developed to better care for this population. This article
reviews pediatric febrile seizures, including management and treatment
recommendations and childhood headaches, with an emphasis on migraine headaches. 
Diagnosis, management, and referral criteria are also reviewed.

Publication Types: 
    Review

PMID: 10673570 [PubMed - indexed for MEDLINE]

3691: Neurosci Lett. 2000 Jan 21;279(1):1-4.

Migraine in childhood--are periodically occurring migraine attacks related to
dynamic changes of cortical information processing?

Siniatchkin M, Kropp P, Gerber WD, Stephani U.

Institute of Medical Psychology, Center of Nervous Diseases, University of Kiel, 
Germany. siniatchkin@med-psych.uni-kiel.de

Amplitudes and habituation of contingent negative variation (CNV) were analyzed
in relation to spontaneously occurring migraine attacks in ten children suffering
from migraine without aura. Recording took place during feedback training and
instrumental conditioning of slow brain potentials. Both the amplitude of the
early CNV component and its habituation deficit increase during the 5 days prior 
to a migraine attack, with maximum abnormalities the day before the ictal
episode. Abrupt reduction of the amplitude and normalization of the CNV
habituation were observed during the attack. This study provides evidence for
neurophysiological periodicity in young migraineurs and emphasizes that the time 
relative to the migraine attacks must be considered in studies of juvenile
migraine during the headache-free period.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 10670773 [PubMed - indexed for MEDLINE]

3692: Ann Pharmacother. 2000 Jan;34(1):39-43.

The effect of intravenous verapamil on cerebral hemodynamics in a migraine
patient with hemiplegia.

Ng TM, Kohli A, Fagan SC, Mohamed AE, Geiszt G.

Department of Pharmacy Practice, Wayne State University, Detroit, MI, USA.

OBJECTIVE: To describe the use of intravenous verapamil in a migraine patient
with hemiplegia to reverse the symptomatology and hemodynamics of the middle
cerebral artery as determined by transcranial Doppler. CASE SUMMARY: A
31-year-old white woman was admitted with an acute exacerbation of migraine with 
hemiplegia. A transcranial Doppler showed an increased flow velocity through the 
middle cerebral artery consistent with a migrainous process. The patient was
treated with verapamil 5 mg iv and the hemiplegia gradually resolved. A
transcranial Doppler indicated that the flow velocity through the middle cerebral
artery was decreased after verapamil administration, indicating reversal of the
vasospasm. DISCUSSION: Transcranial Doppler has not been previously used to
determine the effect of intravenous verapamil on the migrainous process.
Intravenous verapamil reversed the altered hemodynamics of the middle cerebral
artery as determined by transcranial Doppler. This finding correlated with the
gradual resolution of hemiplegia. Whether both subjective and objective findings 
in this patient can be attributed to the reversal of the cerebral artery
hemodynamics is not known. CONCLUSIONS: Intravenous verapamil appears to reverse 
the vasospasm that may be associated with a migrainous process. Whether this
effect is solely responsible for clinical improvement is not known. Verapamil may
be a consideration for the treatment of intractable migraine, especially when
there is evidence of spasm of the major cerebral arteries.

Publication Types: 
    Case Reports

PMID: 10669185 [PubMed - indexed for MEDLINE]

3693: Neurology. 2000 Jan 25;54(2):510-2.

Decreased hemispheric water mobility in hemiplegic migraine related to mutation
of CACNA1A gene.

Chabriat H, Vahedi K, Clark CA, Poupon C, Ducros A, Denier C, Le Bihan D, Bousser
MG.

Service de Neurologie Hôpital Lariboisière, Paris France.

We report a reversible reduction of water diffusion in the brain during a
prolonged attack of hemiplegic migraine. The patient had a sporadic mutation of
the CACNA1A gene. The diffusion changes were observed in the contralateral
hemisphere 3 and 5 weeks after the onset of hemiplegia. These results suggest the
occurrence of hemispheric cytotoxic edema during severe attacks of hemiplegic
aura. The mechanisms underlying such ultrastructural modifications are unknown
but an abnormal release of excitatory amino acids can be hypothesized.

Publication Types: 
    Case Reports

PMID: 10668728 [PubMed - indexed for MEDLINE]

3694: Neurology. 2000 Jan 25;54(2):507-9.

A magnetization transfer imaging study of the brain in patients with migraine.

Rocca MA, Colombo B, Pratesi A, Comi G, Filippi M.

Department of Neuroscience, Scientific Institute Ospedale San Raffaele,
University of Milan, Italy.

The authors evaluated the magnetization transfer ratio (MTR) of T2 lesions,
normal-appearing white matter (NAWM), and brain from 39 migraineurs, 17 healthy
volunteers, and 22 patients with MS. Migraineurs had NAWM and brain MTR values
similar to those of normal subjects but significantly higher than those of MS
patients. Average lesion MTR values also were significantly lower in MS patients 
than in migraineurs. In patients with migraine, other etiologies should be
considered in the presence of tissue damage beyond that seen on T2-weighted
scans.

PMID: 10668727 [PubMed - indexed for MEDLINE]

3695: Neurology. 2000 Jan 25;54(2):314-9.

Chronic daily headache in Chinese elderly: prevalence, risk factors, and biannual
follow-up.

Wang SJ, Fuh JL, Lu SR, Liu CY, Hsu LC, Wang PN, Liu HC.

Neurological Institute, Veterans General Hospital-Taipei, and Department of
Neurology, Taiwan. sjwang@vghtpe.gov.tw

OBJECTIVE: To investigate the prevalence, risk factors, and prognosis of chronic 
daily headache (CDH) in a population of elderly Chinese subjects. METHODS: A
community-based survey of registered residents > or =65 years old (n = 2,003) in 
two townships of Kinmen Island in 1993. A neurologist used a structured
questionnaire and clinical interview to make the diagnosis of headache. Subjects 
who had headaches > or =15 days/month for > or =6 months in the previous year
were considered to have CDH. CDH was further classified into chronic tension-type
headache (CTTH), CDH with migrainous features (CDH/MF), and other CDH.
Person-to-person biannual follow-up of the subjects with CDH was done in June
1995 and August 1997. RESULTS: A total of 1,533 people (77%) participated in our 
prevalence study. Sixty subjects (3.9%) fulfilled the criteria for CDH, with a
higher prevalence in women (F/M: 5.6%/1.8%, p < 0.001). Of these subjects, 42
(70%) had CTTH, 15 (25%) had CDH/MF, and 3 (5%) had other CDH. Only 23% of those 
with CDH had consulted physicians for their headaches in the previous year.
Multivariate logistic regression revealed the significant risk factors for CDH to
be analgesic overuse (OR = 79), a history of migraine (OR = 6.6), and a Geriatric
Depression Scale-Short Form score of > or =8 (OR = 2.6). The follow-up results in
1995 and 1997 showed that about two-thirds of the subjects still had CDH.
Analgesic overuse (relative risk = 1.6) in 1993 was a significant predictor of
persistent CDH at follow-up. CONCLUSIONS: A total of 3.9% of this elderly
population had CDH, with CTTH being the most common subtype. Almost two-thirds of
those with CDH had persistent frequent headaches at follow-up. Analgesic overuse 
was a significant predictor of a poor outcome.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 10668689 [PubMed - indexed for MEDLINE]

3696: Neurology. 2000 Jan 25;54(2):308-13.

Headache and major depression: is the association specific to migraine?

Breslau N, Schultz LR, Stewart WF, Lipton RB, Lucia VC, Welch KM.

Department of Psychiatry, Henry Ford Health System, Detroit, MI 48202-3450, USA. 
nbresla1@hfhs.org

OBJECTIVE: To examine the relationship between migraine and major depression, by 
estimating the risk for first-onset major depression associated with prior
migraine and the risk for first migraine associated with prior major depression. 
We also examined the extent to which comorbidity with major depression is
specific to migraine or is observed in other severe headaches. METHODS:
Representative samples of persons 25 to 55 years of age with migraine or other
severe headaches (i.e., disabling headaches without migraine features) and
controls with no history of severe headaches were identified by a telephone
survey and later interviewed in person to ascertain history of common psychiatric
disorders. RESULTS: Lifetime prevalence of major depression was approximately
three times higher in persons with migraine and in persons with severe headaches 
compared with controls. Significant bidirectional relationships were observed
between major depression and migraine, with migraine predicting first-onset
depression and depression predicting first-onset migraine. In contrast, persons
with severe headaches had a higher incidence of first-onset major depression
(hazard ratio = 3.6), but major depression did not predict a significantly
increased incidence of other severe headaches (hazard ratio = 1.6). CONCLUSIONS: 
The contrasting results regarding the relationship of major depression with
migraine versus other severe headaches suggest that different causes may underlie
the co-occurrence of major depression in persons with migraine compared with
persons with other severe headaches.

Publication Types: 
    Research Support, U.S. Gov't, P.H.S.

PMID: 10668688 [PubMed - indexed for MEDLINE]

3697: Neurology. 2000 Jan 25;54(2):302-7.

Comment in:
    Neurology. 2000 Jan 25;54(2):280-1.

Chinook winds and migraine headache.

Cooke LJ, Rose MS, Becker WJ.

Department of Clinical Neurosciences Faculty of Medicine, University of Calgary, 
Alberta, Canada.

OBJECTIVE: To determine the effects of chinook weather conditions on probability 
of migraine headache onset. BACKGROUND: Many migraineurs believe weather to be a 
trigger factor for their headaches; however, there is little supportive evidence 
in the literature. Migraineurs in the southern part of the Canadian province of
Alberta frequently report that chinooks, warm westerly winds specific to the
region, trigger their headaches. METHOD: Weather data from Environment Canada
were used to designate each calendar day during the study period as a chinook,
prechinook, or nonchinook day. Headache data were collected from 75 patient
diaries from the University of Calgary Headache Research Clinic. Individual and
multiple logistic regression models were used to determine if the weather
conditions affected the probability of migraine onset. Results: The probability
of migraine onset was increased on both prechinook days (odds ratio 1.24; 95% CI 
1.08 to 1.42) and on days with chinook winds (1.19; 1.02 to 1.39) compared with
nonchinook days. Analysis of chinook wind velocities revealed that for chinook
days, the relative risk of migraine onset was increased only on high-wind chinook
days (velocity > 38 km/h) (odds ratio 1.41; 95% CI 1.06 to 1.88). A subset of
individuals was sensitive to high-wind chinook days, and another subset was only 
sensitive to prechinook days. Only two patients were sensitive to both weather
conditions, and the majority of patients was not sensitive to either. Neither
weather condition had a protective effect. Increasing age was associated with
high-wind chinook sensitivity (p = 0.009) but not prechinook sensitivity (p =
0.389). CONCLUSIONS: Both prechinook and high-wind chinook days increase the
probability of migraine onset in a subset of migraineurs. Because few subjects
were found to be sensitive to both weather types, the mechanisms for these
weather effects may be independent. This is supported by the presence of an age
interaction for high-wind chinook days but not for prechinooks day.

PMID: 10668687 [PubMed - indexed for MEDLINE]

3698: Ann Neurol. 2000 Feb;47(2):238-41.

No acute antimigraine efficacy of CP-122,288, a highly potent inhibitor of
neurogenic inflammation: results of two randomized, double-blind,
placebo-controlled clinical trials.

Roon KI, Olesen J, Diener HC, Ellis P, Hettiarachchi J, Poole PH, Christianssen
I, Kleinermans D, Kok JG, Ferrari MD.

Department of Neurology, Leiden University Medical Centre, The Netherlands.

CP-122,288 is a highly potent inhibitor of neurogenic plasma extravasation in
animal models at doses without vasoconstrictor effect. We evaluated the acute
antimigraine efficacy of intravenous and oral CP-122,288 in two double-blind
studies. In a crossover design, patients randomly received 31.25 microg of
CP-122,288 intravenously, placebo, or both. In the oral study, patients received 
placebo or one of four doses of CP-122,288 between 3.125 and 312.5 microg, using 
a novel "up and down" design for randomization. Both studies were stopped
prematurely when target efficacy could not be achieved. Responder rates were 29% 
for CP-122,288 versus 30% for placebo (difference, -1%; 95% CI, -24-22%;
intravenous study) and an overall rate of 25% for CP-122,288 versus 0% for
placebo (difference, 25%; 95% CI; 10-40%; oral study). CP-122,288 was not
clinically effective at doses and plasma concentrations in excess of those
required to inhibit neurogenic plasma extravasation in animals. Neurogenic plasma
extravasation is unlikely to play a crucial role in the pathophysiology of
migraine headache.

Publication Types: 
    Clinical Trial
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 10665496 [PubMed - indexed for MEDLINE]

3699: Neuroepidemiology. 2000 Jan-Feb;19(1):13-9.

The relationship of migraine and stroke.

Tietjen GE.

Division of Neurology, Medical College of Ohio, Toledo 43614, USA.
gtietjen@mco.edu

Migraine, a common disorder of uncertain pathogenesis, is linked to ischemia in a
variety of ways. In some cases the relationship is coincidental. In others,
migraine may be causally related to stroke, although the mechanism of migrainous 
stroke, if not due to arterial dissection, is unclear. In young women, additional
risk factors for stroke such as cigarette smoking, use of combined oral
contraceptives and anticardiolipin antibody immunoreactivity may potentiate
migraine, especially migraine with aura, as a stroke risk factor. The complexity 
of the relationship is highlighted in certain genetic conditions such as cerebral
autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy
and mitochondrial encephalopathy with lactic acidosis and stroke in which
migraine and stroke are both prominent clinical features.

Publication Types: 
    Review

PMID: 10654284 [PubMed - indexed for MEDLINE]

3700: Am J Ophthalmol. 2000 Jan;129(1):102-4.

Migraine and tension headache in high-pressure and normal-pressure glaucoma.

Cursiefen C, Wisse M, Cursiefen S, Jünemann A, Martus P, Korth M.

Department of Ophthalmology and the Institute of Medical Informatics, Biometry
and Epidemiology, University of Erlangen-Nürnberg, Erlangen, Germany.
claus.cursiefen@augen.med.uni-erlangen.de

PURPOSE: To analyze the association of normal-pressure glaucoma and migraine.
METHODS: In a prospective study, 154 patients with glaucoma (56 normal-pressure
subgroup and 98 high-pressure glaucoma subgroup), 55 patients with ocular
hypertension, and 75 control subjects were analyzed by means of a standardized
questionnaire based on International Headache Society criteria. RESULTS:
According to the questionnaire, 46 patients (17%) were classified as suffering
from migraine and 20 (7%) from tension headache (episodic and chronic). The
prevalence of headache, migraine, and tension headache did not vary significantly
among control subjects, patients with ocular hypertension, and patients with
glaucoma, but migraine was significantly more common in patients with
normal-pressure glaucoma (28%) compared with control subjects (12%; P<.05) and
patients with high-pressure glaucoma (10%; P<.01). CONCLUSION: The results
suggest an association of normal-pressure glaucoma and migraine and a potential, 
common vascular etiology of both diseases.

Publication Types: 
    Research Support, Non-U.S. Gov't

PMID: 10653426 [PubMed - indexed for MEDLINE]

3701: Am Fam Physician. 2000 Jan 1;61(1):180-6.

Newer intranasal migraine medications.

Logemann CD, Rankin LM.

Iowa Lutheran Hospital Family Practice Residency, Des Moines, USA.

Two new intranasal migraine medications, sumatriptan and dihydroergotamine
mesylate, may offer specific advantages for patients who are seeking alternatives
to various oral or parenteral migraine abortive therapies. Placebo-controlled
clinical studies demonstrate that both intranasal forms are effective in
relieving migraine headache pain, but published clinical trial information
comparing these two intranasal medications with current abortive therapies is
lacking. Both agents are generally well tolerated by patients, with the exception
of mild, local adverse reactions of the nose and throat.

Publication Types: 
    Review

PMID: 10643958 [PubMed - indexed for MEDLINE]

3702: Rapid Commun Mass Spectrom. 2000;14(3):168-72.

Determination of antimigraine compounds rizatriptan, zolmitriptan, naratriptan
and sumatriptan in human serum by liquid chromatography/electrospray tandem mass 
spectrometry.

Vishwanathan K, Bartlett MG, Stewart JT.

Dept. of Pharmaceutical and Biomedical Sciences, College of Pharmacy, The
University of Georgia, Athens, GA 30602-2352, USA.

Development of a rapid, sensitive and selective method for the determination of
antimigraine drugs from human serum is essential for understanding the
pharmacokinetics of these drugs when administered concurrently. Solid phase
extraction (SPE) using Oasis HLB was used to extract the drugs (sumatriptan,
naratriptan, zolmitriptan and rizatriptan) and the internal standard bufotenine
from serum. A method based on liquid chromatography/tandem mass spectrometry
(LC/MS/MS) was developed and validated to simultaneously quantitate these
antimigraine drugs from human serum. The precursor and major product ions of the 
analytes were monitored on a triple quadrupole mass spectrometer with positive
ion electrospray ionization (ESI) in the multiple reaction monitoring (MRM) mode.
The base peak in all the analytes is formed by alpha cleavage associated with
protonation of the secondary amine. Mechanisms for the formation of the
collision-induced dissociation products of these antimigraine compounds are
proposed. Linear calibration curves were generated from 1-100 ng/mL with all
coefficients of determination greater than 0.99. The inter- and intraday
precision (%RSD) were less than 9.3% and accuracy (%error) was less than 9.8% for
all components. The limits of detection (LOD) for the method were 250 pg/mL for
sumatriptan and 100 pg/mL for the remaining analytes based on a signal-to-noise
ratio of 3. Copyright 2000 John Wiley & Sons, Ltd.

PMID: 10637423 [PubMed - indexed for MEDLINE]

3703: Neurology. 2000 Jan 11;54(1):156-63.

Comment in:
    Neurology. 2000 Sep 12;55(5):735-6.    Neurology. 2000 Sep 12;55(5):735; author reply 736.

Eletriptan in acute migraine: a double-blind, placebo-controlled comparison to
sumatriptan. Eletriptan Steering Committee.

Goadsby PJ, Ferrari MD, Olesen J, Stovner LJ, Senard JM, Jackson NC, Poole PH.

Institute of Neurology, The National Hospital for Neurology and Neurosurgery,
London, UK. peterg@brain.ion.ucl.ac.uk

OBJECTIVE: To compare the efficacy, safety, and tolerability of oral eletriptan
(20 mg, 40 mg, and 80 mg) with that of oral sumatriptan (100 mg) and placebo for 
the acute treatment of migraine. BACKGROUND: Eletriptan is a potent and selective
agonist at human recombinant 5HT1B/1D receptors, with efficacy in animal models
that predict antimigraine activity. In healthy volunteers, the pharmacokinetics
of eletriptan are characterized by linear and rapid oral absorption. METHODS:
Randomized, double-blind, parallel-group study conducted in 857 outpatients with 
a diagnosis of migraine according to the International Headache Society (IHS)
criteria. Of these, 692 took study medication for one acute migraine attack and
provided on-drug efficacy data. Subjects received either placebo, 100 mg of
sumatriptan or 20 mg, 40 mg, or 80 mg of eletriptan for the treatment of an acute
migraine attack. The primary endpoint was the percentage of patients with a
headache response (improvement in pain intensity from moderate or severe to mild 
or none) at 2 hours after treatment. RESULTS: At the primary endpoint (2 hours
after dosing), headache response rates were 24% (30/126) for placebo; 55%
(63/115) for sumatriptan, 100 mg; 54% (70/129) for eletriptan, 20 mg; 65%
(76/117) for eletriptan, 40 mg; and 77% (91/118) for eletriptan, 80 mg. There was
a difference compared with placebo (p<0.001) for all doses of eletriptan, and at 
2 hours there was a difference between sumatriptan, 100 mg, and eletriptan, 80 mg
(p<0.001). Headache-free rates at 2 hours were superior to placebo (6%; p<0.001) 
for both the 80-mg dose of eletriptan (37%) and the 40-mg dose (29%), with the
80-mg dose also being superior to 100 mg of sumatriptan (23%; p<0.05). Eletriptan
and sumatriptan were well tolerated, and the majority of adverse events were mild
or moderate in intensity and transient. CONCLUSION: In this placebo-controlled
trial, eletriptan, at selected doses, demonstrated superior efficacy, onset of
action and patient acceptability in the acute treatment of migraine when compared
with oral sumatriptan and placebo.

Publication Types: 
    Clinical Trial
    Comparative Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

PMID: 10636142 [PubMed - indexed for MEDLINE]

3704: Brain. 2000 Jan;123 ( Pt 1):9-18.

Ergotamine in the acute treatment of migraine: a review and European consensus.

Tfelt-Hansen P, Saxena PR, Dahlöf C, Pascual J, Láinez M, Henry P, Diener H,
Schoenen J, Ferrari MD, Goadsby PJ.

Department of Neurology, Glostrup Hospital, Copenhagen, Denmark. The

Ergotamine has been used in clinical practice for the acute treatment of migraine
for over 50 years, but there has been little agreement on its place in clinical
practice. An expert group from Europe reviewed the pre-clinical and clinical data
on ergotamine as it relates to the treatment of migraine. From this review,
specific suggestions for the patient groups and appropriate use of ergotamine
have been agreed. In essence, ergotamine, from a medical perspective, is the drug
of choice in a limited number of migraine sufferers who have infrequent or long
duration headaches and are likely to comply with dosing restrictions. For most
migraine sufferers requiring a specific anti-migraine treatment, a triptan is
generally a better option from both an efficacy and side-effect perspective.

Publication Types: 
    Consensus Development Conference
    Review

PMID: 10611116 [PubMed - indexed for MEDLINE]
